___Acta Universitatis Medicinalis Anhui

Exploring the therapeutic effect of total timosaponin on central precocious puberty model rats based on the RFRP-3/GPR147 signaling pathway

Zhang Kai; Zhang Xuerong; Chen Ziqin; Wang Gehuan; Jiang Xingyanying

DOI: 专辑：医药卫生科技

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Abstract:
Objective To explore the molecular mechanism of the therapeutic effect of total timosaponin on central precocious puberty (CPP) rats based on the RF-amide-related Peptide 3 (RFRP-3)/G protein-coupled receptor 147 (GPR147) signaling pathway. Methods Twenty-six day-old female SD rats were randomly assigned into a control group, a model group, an RFRP-3 up-regulated group (1.5 mg/kg), a total timosaponin group (200 mg/kg), a total timosaponin+empty load group, and a total timosaponin+RFRP-3 knockdown group, with 12 rats in each group. A CPP rat model was prepared by subcutaneous injection of N-methyl-DL-aspartic acid (NMA) (40 mg/kg). After modeling and administration, the opening time of the rat’s vulva and the first estrus interval daily were observed. Administration was stopped when the first estrus interval appeared in the model group. The day of vaginal opening and the time of the first estrus interval of rats were recorded in each group of rats. The wet masses of both ovaries and uterus were measured, and the ovarian and uterine indices were calculated; HE staining was used to observe the morphological changes of rat ovarian and uterine tissues, the number of corpus luteum in the ovaries and the thickness of the uterine wall were determined; ELISA method was applied to detect levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E 2); RT-qPCR was used to detect the mRNA expression of hypothalamic gonadotropin-releasing hormone (GnRH), KISS-1, GPR54, RFRP-3, and GPR147. Results Compared with the control group, the day of vaginal opening and the time of the first estrus interval of rats in the model group were advanced ( P<0.05), the ovarian index and uterine index, number of ovarian corpus luteum and uterine wall thickness, serum LH, FSH, E 2 levels, and the GnRH, KISS-1, and GPR54 mRNA expression levels in the hypothalamus increased ( P<0.05), while the RFRP-3 and GPR147 mRNA expression levels decreased ( P<0.05). Compared with the model group, the day of vaginal opening and the time of the first estrus interval of rats in the RFRP-3 up-regulated group and the total timosaponin group were delayed ( P<0.05), the ovarian index and uterine index, number of ovarian corpus luteum and uterine wall thickness, serum LH, FSH, E 2 levels, and the GnRH, KISS-1, and GPR54 mRNA expression levels in the hypothalamus decreased ( P<0.05), while the RFRP-3 and GPR147 mRNA expression levels increased ( P<0.05). Knocking down RFRP-3 could prominently weaken the delaying effect of total timosaponin on the development of precocious puberty in CPP rats ( P<0.05). Conclusion Total timosaponin may inhibit the release of GnRH and premature activation of the hypothalamic pituitary gonadal axis by activating the RFRP-3/GPR147 signaling pathway, thereby alleviating the degree of precocious puberty development in CPP model rats.

PRMT5 promotes angiogenesis in colorectal cancer via the JAK2/STAT3 signaling pathway

Zhang Wen; Geng Yongyong; Tu Xijiang; Yao Qianhui; Guo Wenlong; Yao Bogang; Sun Xuling

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the effect of protein arginine methyltransferase 5 (PRMT5) on the angiogenesis of colorectal cancer (CRC) through the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. MethodsThe expression and prognostic value of PRMT5 in CRC tissues were analyzed based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 105 pairs of cancer tissues and matched adjacent non-tumor tissues were collected from CRC patients, and PRMT5 expression was detected by immunohistochemistry (IHC); Western blot was used to detect the PRMT5 protein level in normal colonic epithelial cells (FHC) and CRC cell lines (including RKO, SW480). SW48 and LoVo cells were divided into negative control (NC) group and PRMT5 knockdown interference group. After the stable knockdown cell models were successfully constructed, the effects of conditioned medium on the proliferation, cell cycle, migration and tube formation abilities of human umbilical vein endothelial cells (HUVECs) were detected; The correlation between PRMT5 and vascular endothelial growth factor A (VEGFA) was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Gene set enrichment analysis (GSEA) and cytoplasm-nucleus separation assay were performed to verify the regulatory pathway. ResultsPRMT5 was highly expressed in CRC tissues and cell lines, which was significantly correlated with poor prognosis and pathological characteristics of patients (all P < 0.05); PRMT5 knockdown could significantly inhibit the angiogenesis-related abilities of HUVECs (all P < 0.05) and down-regulate the expression of VEGFA (all P < 0.01). GSEA results indicated that PRMT5 expression was significantly associated with the activation of JAK2/STAT3 signaling pathway (all P < 0.001). PRMT5 knockdown could inhibit the activation of JAK2/STAT3, the nuclear translocation of STAT3 and the protein level of phosphorylated STAT3 (p-STAT3) in the nucleus, thus inhibiting the expression of VEGFA. Conclusion PRMT5 is highly expressed in CRC tissues and indicates poor prognosis of patients. It promotes the nuclear translocation and transcriptional activity of STAT3 by activating the JAK2/STAT3 pathway and drives the expression of VEGFA to promote tumor angiogenesis.

Relationship between EDNRA gene polymorphisms and congenital bilateral absence of the vas deferens in the male Han Chinese population

Peng Yuwan1, He Xiaojin2 , Yang Xiaoyu3, Wang Jing4, Wang Binbin 4, Tang Dongdong5, Wei Zhaolian5, Cao Yunxia5

DOI: 专辑：医药卫生科技

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The change of EPA1-ROS-NLRP1 signaling in CUMS-induced depression model mice

Tian Shuxiang; Liu Mengqing; Yang Han; Niu Mingguang; Yin Yanyan

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the expression changes of the Endophilin A1 (EPA1)-ROS-NLRP1 signaling pathway in chronic unpredictable mild stress (CUMS)-induced depression model mice. MethodsC57BL/6 mice were randomly divided into control group and CUMS model group. The model mice received 42 days of CUMS stress exposure, after which behavioral changes were assessed through monitoring body weight, sucrose preference test, forced swim test, tail suspension test, open field test, and elevated plus-maze test. Hematoxylin-Eosin and Nissl staining were used to observe neuronal damage in hippocampal CA1 and CA3 regions. Calcium ion (Ca²⁺) assay kit was used to detect Ca²⁺ levels in the hippocampus. Immunofluorescence was used to detect colocalization of EPA1 and NLRP1 as well as ROS changes in the hippocampus. Transmission electron microscopy was used to observe mitochondrial structure in hippocampal neurons. The expression levels of calcium-activated neutral protease 1 (Calpain 1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), NLRP1 inflammasome, downstream inflammatory proteins, and synapse-associated proteins in the hippocampus of mice was detected by using Western blot. Results Compared with the control group, mice in the CUMS model group exhibited depressive-like behavior and hippocampal neuronal damage. The levels of NLRP1 and EPA1 significantly increased in the hippocampus, and both were co-expressed in the cytoplasm and membrane of hippocampal neurons in the CUMS group mice（ P<0.01）. Ca²⁺ concentration was elevated（ P<0.01）, and the protein levels of Calpain 1 and NOX2 were upregulated（ P<0.01）. The average fluorescence intensity of ROS significantly increased, accompanied by structural damage to neuronal mitochondria（ P<0.01）; The levels of NLRP1 and its downstream inflammatory proteins significantly increased ( P<0.01), while the expression levels of synapse-associated proteins significantly decreased ( P<0.01). Conclusion EPA1 exhibits abnormal expression changes in CUMS-induced depression model mice, which may be closely associated with ROS generation, NLRP1 inflammasome activation, and the regulation of synaptic protein expression.

Research on the role of 7-dehydrocholesterol reductase in promoting the proliferation, migration, and invasion of lung adenocarcinoma cells

Tang Jing; Qiu Ping; Chen Renjie; Liu Yaqing; Liu Hui; Liu Yu; Chen Liwen

DOI: 专辑：医药卫生科技

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Abstract:
ObjectiveTo investigate the effects of 7-dehydrocholesterol reductase (DHCR7) in promoting proliferation, migration, and invasion of lung adenocarcinoma cells and the underlying signaling mechanisms. Methods The expression level of DHCR7 in lung adenocarcinoma and its prognosis were analyzed by using public databases. DHCR7 protein expression levels in the lung adenocarcinoma cell lines H1299 and A549 were assessed by Western blot, using the normal lung epithelial cell line BEAS-2B as a control. Small interfering RNA (siRNA) was used to knock down DHCR7 expression in H1299 and A549 cells. Assays including colony formation, CCK-8, wound healing, and Transwell experiments were conducted to assess the proliferation, migration, and invasion of the knockdown cells. Next, Western blot was employed to assess the phosphorylation levels of key signaling molecules in the Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3),Mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) (p-AKT, p-STAT3, p-ERK). ResultsBioinformatics results indicated that both DHCR7 mRNA and protein were highly expressed in lung adenocarcinoma compared with normal tissues adjacent to cancer. Furthermore, higher DHCR7 mRNA level was associated with poor prognosis ( P< 0.001). The expression levels of DHCR7 were significantly higher in both H1299 and A549 cells than that in BEAS-2B cells ( P< 0.05, P< 0.01). Compared with si-Control, the proliferation, migration, and invasion abilities of si- DHCR7 H1299 and A549 cells significantly decreased. Among the phosphorylated signaling molecules detected, p-ERK was significantly downregulated ( P< 0.000 1, P< 0.01) whereas p-AKT and p-STAT3 levels were not significantly changed. ConclusionDHCR7 has prominent effects in promoting the proliferation, migration, and invasion of lung adenocarcinoma cells, and the underlying mechanisms are related to the MAPK/ERK signaling pathway.

Research progress of macrophage-related microRNA in rheumatoid arthritis

Jiang Qijiang; Luo Chenggen; Chen Yanjuan; Tian Mei; Chen Yong

DOI: 专辑：医药卫生科技

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Risk factors and altered functional connectivity of brain networks in end-stage renal disease complicated with frailty

Sun Zhaohua, Li Dashan, Feng Nan, Chen Zilian, Zhang Pei, Wu Yonggui

DOI: 医药卫生科技

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Effects of VEGFA genetic polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors

Liu Zhengyue1, Meng Lingjia1, Yan An1, Li Miao1, 2, Wang Shumei1

DOI: 专辑：医药卫生科技

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Abstract:
Objective To explore the effects of Vascular Endothelial Growth Factor A (VEGFA)rs2010963 and rs3025039 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors. Methods A total of 104 pediatric patients with brain tumors receiving standardized chemotherapy were enrolled. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used for VEGFA rs2010963 and rs3025039 genotyping. The χ² test was applied to analyze the association between genotypes and chemotherapy_related toxicities.Cox proportional hazards regression was used to evaluate the correlations of clinicopathological characteristics and genotypes with the progression_free survival (PFS). In addition, bioinformatic analyses were conducted to investigate the regulatory factors potentially affected by the two SNP loci. Results The VEGFA expression in brain tumors (5.17±1.81) was significantly higher than that in normal tissues (4.33±1.56, P<0.001). Patients with high VEGFA expression had significantly worse overall survival than patients with low VEGFA expression (P<0.001). Among the 104 children with brain tumors included, the rs2010963 CC, CG, and GG genotypes accounted for 14.42%, 55.77%, and 29.81%, respectively. The frequencies of C and G alleles were 42.31% and 57.69%, respectively. The rs3025039 CC, CT, and TT genotypes accounted for 70.19%, 25.96%, and 3.85%, respectively. The frequencies of C and T alleles were 83.17% and 16.83%, respectively. The children with the rs3025039 CC genotype had significantly higher incidences of thrombocytopenia (46.58%) and gastrointestinal toxicity (56.16%), and significantly lower incidences of coagulation disorders (4.11%) than CT genotype carriers (22.22%, 33.33%, and 50.00%, respectively, P<0.05). They had significantly lower incidences of dyslipidemia (2.74%) than TT genotype carriers (14.82%, P<0.05). The tumor type and the rs2010963 genotype were significantly associated with PFS (P<0.05) in univariable and multivariable Cox regression analysis. Bioinformatic analysis indicated that the rs2010963 and rs3025039 polymorphisms regulated VEGFA expression by affecting the binding of transcription factors and miRNAs to their target gene sequences, respectively. Conclusion The VEGFA rs3025039 CC genotype significantly affects the risk of thrombocytopenia, gastrointestinal toxicity, coagulation disorders, and hyperlipidemia, while the rs2010963 CG genotype significantly affects the risk of brain tumor progression.

CDH18 promotes proliferation and migration of cervical cancer cellsviathe Wnt/β-catenin signaling pathway

Zhang Xuechen; Dong Yangliu; Zhao Bo; Xia Zongyi; Dong Zhaocheng; Zhe Xiangyi; Pan Zhenzhen; Pan Zemin

DOI: 专辑：医药卫生科技

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Association study ofSLC7A11gene polymorphisms withhelicobacter pyloriinfection and non-cardia gastric cancer

Wang Linli; Gao Fang; Dong Wenjie; Chu Ning; Jia Yanbin

DOI: 专辑：医药卫生科技

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Research on the relationship between social support and fertility quality of life in male infertility patients: the parallel mediating roles of mindfulness and total sperm motility

Zhi Lihuan； Mireyi Jumanali； Maierhaba Abulizi； Xu Hua； He Lijuan

DOI: 专辑：医药卫生科技

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Abstract:
ObjectiveTo investigate the relationship between social support and fertility quality of life in male infertility patients, and to analyze the parallel mediating roles of mindfulness and total sperm motility, thereby providing a theoretical basis for interventions aimed at improving fertility quality of life in this population. MethodsThis study conducted a survey using anonymized electronic questionnaires among 680 infertile men from 2021 to 2024. The social support rating scale, mindful attention awareness scale, and fertility quality of life scale were used to assess social support, mindfulness, and fertility Quality of Life, respectively. Total sperm motility was evaluated through routine semen analysis. Pearson correlation analysis was performed to examine the relationships among scale scores, and the PROCESS macro was used to analyze the mediating effects of mindfulness and total sperm motility between social support and fertility quality of life. ResultsPearson correlation analysis showed that The fertility quality of life score was significantly positively correlated with the social support score ( r=0.350), subjective hosting score ( r=0.279), objective support score ( r=0.274), support utilization score ( r=0.206), mindfulness score ( r=0.434), and total sperm motility level ( r=0.155) (all P< 0.05). Mediation analysis demonstrated that both mindfulness and total sperm motility partially mediated the relationship between social support scores and fertility quality of life, with mediation effect proportions of 28.42% and 2.73%, respectively. Additionally, mindfulness scores and total sperm motility partially mediated the relationship between objective support (a subdimension of social support) and fertility quality of life, accounting for 28.78% and 3.7% of the effect, respectively. However, total sperm motility did not show significant mediation effects between subjective support, support utilization (other social support subdimensions), and fertility quality of life. ConclusionMindfulness and total sperm motility are potential factors through which social support influences fertility quality of life in male infertility patients. Clinically, mindfulness-based interventions to cultivate positive psychological traits, along with strategies to improve sperm motility, may enhance fertility quality of life in this population.

Development and validation of a blood-based differential diagnosis model for pulmonary tuberculosis and community-acquired pneumonia

Su Xiaolan1 , Zhang Rui1, Yang Zeqing1, Wang Xinrui3, Bi Ziyu1 , Liu Nian1 , Han Yunyan2 , Ren Qi1

DOI: 专辑：医药卫生科技

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Immunogenic cell death-related key gene screening and validation in primary sjögren’s syndrome

Hao Wanting； Wu Wenfeng； Hou Lei； Ma Wukai； Yang Peng

DOI: 专辑：医药卫生科技

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Abstract:
Objective To systematically screen and validate key immunogenic cell death (ICD)-related genes that play important roles in primary sjögren’s syndrome (pSS) using multi-omics data. MethodsGene expression profiles of pSS patients and healthy controls (GSE66795, 131pSS patients/29 healthy controls) were obtained from the Gene Expression Omnibus (GEO) database. Candidate genes were selected by intersecting these profiles with known ICD core gene sets and pSS-related targets. The CIBERSORT algorithm was used to analyze immune cell infiltration characteristics. Validation of gene expression was performed using transcriptomic data from sorted CD8 + T cell subsets (GSE93683). Finally, labial gland tissues and peripheral blood samples from 10 pSS patients and 4 healthy controls were collected, and key genes were experimentally validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). ResultsSeven intersecting genes from the ICD-differentially expressed genes (DEGs)-pSS intersection were identified [caspase 1 ( CASP1), forkhead box P3 ( FOXP3), interferon-gamma ( IFNG), myeloid differentiation primary response 88 ( MYD88), toll-like receptor 7 ( TLR7), DExD/H-box helicase 58 ( DDX58), and interferon induced helicase C domain 1 ( IFIH1)]. Immune infiltration analysis showed that in pSS labial gland tissues, the proportions of naïve B cells and dendritic cells significantly increased, while the proportions of resting NK cells and M0 macrophages decreased ( P<0.05). Transcriptomic data of CD8 +T cell subsets indicated that IFIH1 expression was significantly elevated in central memory CD8 +T cells ( P<0.05). RT-qPCR experimental validation revealed that DDX58, IFIH1, and CASP1 were significantly upregulated in both peripheral blood leukocytes and labial gland tissues of pSS patients (all P<0.05), whereas IFNG expression increased in peripheral blood but decreased in labial gland tissues ( P<0.05). Conclusion This study identified and confirmed DDX58, IFIH1, CASP1, and IFNG as key ICD-related genes in pSS through a combination of bioinformatics and experimental validation, providing new candidate targets for further understanding the immunopathological mechanisms of pSS.

Exploring the association between periodontitis and brain function in cognitively normal middle-aged and elderly individuals

Ma Ju； Li Xiaoshu； Tao Yufei； Zhu Wanqiu； Chen Xiao； Yu Yongqiang

DOI: 专辑：医药卫生科技

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The effect of IL-8 secreted by tumor-associated macrophages on colorectal cancer metastasis

Su Ya1, Yuan Luyun2, Zhang Qiang1, Wang Haijing3

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the role of interleukin-8 (IL-8) secreted by tumor-associated macrophages (TAMs) in colorectal cancer (CRC) metastasis and its potential therapeutic value. Methods The TAMs model was constructed by phorbol ester (PMA) combined with IL-4/IL-13, and the model phenotype was verified by flow cytometry, RT-qPCR and ELISA. Human CRC HCT116 cells were treated with conditioned medium (CM) from M0 macrophages and TAMs, and the metastatic capacity of HCT116 cells was evaluated by wound-healing assay and Transwell assay. The expression levels of IL-8 in M0 macrophages and TAMs were detected by Western blot, RT- qPCR and ELISA. The expression level of epithelial-mesenchymal transition (EMT) markers (E- cadherin, N-cadherin) in HCT116 cells treated with CM-M0 and CM-TAMs were detected by Western blot and RT-qPCR. HCT116 cells were stimulated with CM-TAMs supplemented with IL- 8 receptor inhibitor Reparixin. The HCT116 cells metastasis ability was evaluated by wound-healing assay and Transwell assay, and the expression levels of E-cadherin and N-cadherin were detected by Western blot and RT-qPCR. Finally, a splenic injection liver metastasis model was established using murine CRC cells CT26-LUC, and the effect of Reparixin on this animal model was observed by in vivo imaging. Results Flow cytometry showed that the proportion of M2 macrophages (CD11b+CD206+ cells) was elevated in the TAMs model. RT-qPCR and ELISA assays revealed that the levels of M2 macrophage markers IL-10 and TGF-βsignificantly increased. Wound-healing assay and Transwell assay demonstrated that CM-TAMs significantly enhanced the migration and invasion ability of HCT116 cells. Western blot, RT-qPCR and ELISA assays showed that TAMs highly expressed IL-8 and simultaneously induced downregulation of E-cadherin and upregulation of N-cadherin in HCT116 cells. Reparixin not only reversed the pro-metastatic effects of CM-TAMs, but also upregulated the expression level of E-cadherin and downregulated that of N-cadherin in HCT116 cells. Furthermore, it reduced the bioluminescence signal intensity of liver metastatic lesions in the splenic injection liver metastasis model. Conclusion The TAMs promote CRC metastasis by secreting IL-8 to induce EMT. Inhibiting IL-8 secretion in TAMs or blocking the binding of IL-8 to its receptor may provide a new strategy for CRC treatment.

Construction,breeding,and genotypic identification of an inducible mouse model with skin CD4+T cell deficiency

Shao Na； Zhou Xuyang； Cao Ting； Zou Ying

DOI: 专辑：医药卫生科技

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Analysis of the impact of high progesterone ovulation induction protocols on embryo euploidy rates and clinical pregnancy outcomes in infertile patients

Wang Minjie； Zhang Yongjing； Qian Jin； Wang Chao； Xu Yuping； Wang Tianjuan； Chen Dawei； Hao Yan； Xing Qiong

DOI: 专辑：医药卫生科技

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Abstract:
ObjectiveTo analyze the effects of the Progestin-Primed Ovarian Stimulation (PPOS) protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation Genetic Testing for Aneuploidy (PGT-A) cycles were selected as study participants (a total of 656 cycles and 3081 blastocysts). Participants were divided into two age groups (≤35 years and >35 years) and further stratified by ovarian stimulation protocol: the Progestin-Primed Ovarian Stimulation (PPOS) group (n=48 and 60, respectively), the Luteal Phase Long Protocol (LP) group (n=160 and 57, respectively), and the Gonadotropin-Releasing Hormone Antagonist Protocol (AP) group (n=220 and 111, respectively). Baseline characteristics, ovarian stimulation outcomes, and embryo development parameters were compared among the three protocols within each age group. Additionally, clinical pregnancy outcomes of the first frozen embryo transfer (FET) cycle were compared. The primary outcome measure was the embryo euploidy rate. Results1. In the ≤35 years age group, baseline follicle-stimulating hormone (bFSH) levels were significantly higher in the PPOS group compared to the LP and AP groups, and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group ( P < 0.05). In the >35 years age group, bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group ( P < 0.05).2. In the ≤35 years group, there were no significant differences in the rates of metaphase II (MII) oocytes, 2-pronuclei (2 PN) fertilization, cleavage, 2 PN cleavage, blastocyst formation, high-quality embryos, or embryo euploidy between the PPOS group and either the LP or AP groups. However, the PPOS group showed significantly lower values for the following parameters compared to the other two groups: total oocytes retrieved, number of MII oocytes, number of 2 PN zygotes, number of cleaved embryos, number of 2 PN cleaved embryos, number of blastocysts formed, number of high-quality embryos, number of high-grade blastocysts, number of transferable embryos, number of cryopreserved embryos, number of biopsied blastocysts, number of euploid embryos, and the rate of obtaining at least one euploid embryo. In the >35 years group, no significant differences were observed among the PPOS, LP, and AP groups in the rates of MII oocytes, 2 PN cleavage, blastocyst formation, or in the number of euploid embryos, euploidy rate, and the rate of obtaining at least one euploid embryo. However, the PPOS group had significantly lower numbers of total oocytes retrieved, MII oocytes, 2 PN zygotes, cleaved embryos, 2 PN cleaved embryos, blastocysts formed, transferable embryos, and cryopreserved embryos compared to the LP group ( P < 0.05). The high-quality embryo rate was significantly lower in the PPOS group than in the AP group ( P < 0.05). The numbers of high-quality embryos, high-grade blastocysts, and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups ( P < 0.05). Notably, the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group, and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups ( P < 0.05).3. No significant differences were found among the three groups in the biochemical pregnancy rate, clinical pregnancy rate, live birth rate, early miscarriage rate, and late miscarriage rate following the first FET cycle ( P ≥ 0.05). ConclusionCompared to the other two protocols, the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However, in freeze-all cycles with PGT-A, the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women, but it can be considered as a viable option for women of advanced maternal age.

Effect of luteinising hormone levels on the outcome of in vitro fertilization and embryo transfer in an infertile population with normal ovarian reserve

Zheng Qi1, Su Xun1, Yang Jing1,Ji Dongmei1,2

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the effects of luteinizing hormone (LH) levels on in vitro fertilization and embryo transfer (IVF-ET) outcomes in an infertile population with normal ovarian reserve (NOR) undergoing controlled ovarian hyperstimulation (COH) with an gonadotropin-releasing hormone antagonist protocol, and to explore the reasonable level intervals of LH during the follicular phase. Methods A retrospective analysis was conducted on 911 NOR infertility patients undergoing IVF-ET treated with an antagonist protocol. Patients were grouped based on baseline LH (bLH) levels, LH levels on the day of antagonist addition, and LH levels on the day of human chorionic gonadotropin (hCG) injection. According to bLH levels, patients were divided into Group A (n=391) and Group B2 (n=391). Based on LH levels on the day of antagonist addition, patients were divided into Group A3 (n=600) and Group B3 (n=311). According to LH levels on the day of hCG injection, patients were classified into Group A4 (n=225), Group B4 (n=227), Group C4 (n=231), and Group D4 (n=228). The clinical characteristics, COH outcomes, and pregnancy outcomes of patients in each group were compared. Results ① The bLH level could be used as a predictor of assisted reproduction outcomes in an infertile population with NOR, and going for assisted reproduction at bLH≥4.51 IU/L was more favorable for the development of pregnancy outcomes; ② Addition of antagonist at LH≥5 IU/L on the day of antagonist addition improved pregnancy outcome ;③ On the day of hCG injection, there was no statistically significant difference in pregnancy outcomes among the four groups; ④ Analyses using generalized linear models revealed that basal follicle-stimulating hormone (bFSH), basal estradiol (bE2), Gn days, Gn volume and 2PN affected the number of good quality embryos. Conclusion In an infertile population with NOR using an gonadotropin-releasing hormone antagonist, bLH and an gonadotropin-releasing hormone antagonist addition day LH levels may influence IVF outcomes. LH levels should be controlled at 5 IU/L and above on antagonist addition days, and bLH levels should be controlled at 4.51 IU/L and above.

Pregnancy outcomes in dichorionic twins: comparing assisted reproductive technology and spontaneous conception

Yin Jiancai1, 2, 3 ，Zhao Ziyan1, 2, 3 ，Zhao Baojing1, 2, 3 ，Yu Zhen1, 2, 3 ，Yang Yuanyuan1, 2, 3

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the differences in pregnancy outcomes between dichorionic diamniotic (DCDA) twin pregnancies conceived via assisted reproductive technology (ART) and those from spontaneous conception, in order to provide evidence for the perinatal management of ART-conceived DCDA twins. Methods A retrospective analysis was conducted on the clinical data of 549 DCDA twin parturients who delivered at the Department of Obstetrics, The First Affiliated Hospital of Anhui Medical University. Based on the mode of conception, they were divided into ART group (423 cases) and spontaneous conception group (126 cases). The baseline characteristics, pregnancy complications and neonatal outcomes were compared between the two groups. Results Regarding baseline characteristics, the ART group had higher maternal age, number of previous abortions, proportions of primiparas, proportions of advanced maternal age and greater 24-hour postpartum blood loss, but lower parity and proportion of scarred uterus compared to the spontaneous conception group (P＜0.05). For pregnancy complications, the ART group exhibited higher incidences of hypertensive disorders of pregnancy, placental adhesion, postpartum hemorrhage and a higher application rate of uterine artery ascending branch ligation (P＜0.05). There were no statistically significant differences in neonatal-related indicators between the two groups (P＞0.05). After adjusting for confounding factors such as age, number of abortions and parities, ART remained an independent risk factor for hypertensive disorders of pregnancy, placental adhesion and postpartum hemorrhage (P＜0.05), while it did not increase the risk of adverse neonatal outcomes(P＞0.05). Further subgroup analysis by gestational age showed that in the late preterm subgroup, the risk of ART-related pregnancy complications remained elevated (P＜0.05). Additionally, neonatal outcomes showed no significant difference between the two groups in both the late preterm and term subgroups (P＞0.05). Conclusion ART increases the risk of hypertensive disorders of pregnancy, placental adhesion and postpartum hemorrhage in DCDA twin parturients. Clinically, enhanced monitoring of blood pressure during pregnancy and blood loss during delivery and postpartum, along with targeted prevention and management of these complications, are crucial for improving pregnancy outcomes.

Evaluate the effect of morphology driven preparation technique in indirect restoration of posterior teeth

Gao Qikun, Liu Shiming, Wu Mingyue, Wu Xiaoting, Wang Zehua, Du Mingliang, Chen Huiming

DOI: 专辑：医药卫生科技

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Abstract:
Objective To evaluate the application effect of morphology driven preparation technique in indirect restoration of posterior teeth. Methods 84 patients with dental defects were selected and divided into the control group and the experimental group randomly, with 42 patients in each group (a total of 84 teeth). Traditional preparation and morphology driven preparation techniques were used to complete dental preparation and adhesive glass ceramic restorations, respectively. The satisfaction, masticatory function, World Dental Federation (FDI) Scores for edge fracture and fixation ，edge adaptability index ，periodontal bleeding index (BI) and plaque index (PLI) of the two groups of patients were evaluated and various indicator data were recorded and statistically analyzed at 3 and 6 months after restoration completion. Results There was no statistically significant difference in satisfaction between the two groups after 3 and 6 months of repair; Both groups of data showed a significant improvement in masticatory function. There was no statistical difference after 3 and 6 months of repair. However, a statistically significant difference in masticatory function was noted after 6 months of repair compared with before and after 3 months of repair. As the repair time increased, the masticatory effect improved significantly. There was no statistically significant difference in the edge fracture and fixation index between the two groups at 3 months after repair, but there was a statistically significant difference between the two groups at 6 months with the experimental group outperforming the control group(P<0.05). The edge adaptability, BI, and PLI index were statistically significant between the two groups after 3 and 6 months of repair and the experimental group had a significant advantage (P<0.05). Conclusion Both types of tooth preparation techniques can improve patient masticatory function and reach high satisfaction after repair. However, morphology driven preparation technique has significant advantages in edge adaptability, edge fracture and fixation index scores and improve periodontal conditions. This technique is an effective method for improving dental preparation in adhesive indirect restoration of posterior teeth.

Mechanisms and current applications of mechanical forces in cranial bone defect repair

Du Bingcheng； Chen Qi； Wang Yu； Zhao Zhijun

DOI: 专辑：医药卫生科技

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Honokiol inhibits the malignant progression of gastric cancer cells by regulating the ATF4/CHOP/TRIB3 pathway

Dai Kaihong； Wen Xianhui； Huang Yun； Wei Sixi； Huang Hai

DOI: 专辑：医药卫生科技

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Evaluate the anti-inflammatory activity of the magnolol ester derivative YW and investigate its mechanism of action on chondrocyte senescence

Xu Haochen¹,Peng Jie¹,Yang Pingting¹,Zhang Meihua¹,Hu Weiwen¹,Wang Xulei2 ，Wei Wei1, Wang Chun¹,Yan Shangxue1, 2

DOI: 专辑：医药卫生科技

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Abstract:
Objective To evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. Methods Magnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW (Molecular Formula: C26H24O3, Molecular Weight: 384.17, HPLC Purity >96%) via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide (LPS)-induced RAW264.7 macrophage activation model and an interleukin-1β (IL-1β)-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide (NO), IL-1β, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), Griess reagent method, and quantitative real-time PCR (RT-qPCR). The expression of senescence markers such as inducible nitric oxide synthase (iNOS), pro-interleukin-1β (pro-IL-1β), lysine acetyltransferase 7 (KAT7), cyclin-dependent kinase inhibitor 1A (p21), and cyclin-dependent kinase inhibitor 2A (p16), as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism, were analyzed by Western blot (WB). Molecular docking was performed using Discovery Studio 2019 to validate target binding. Results YW exhibited no significant cytotoxicity at concentrations ≤ 20μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release, significantly downregulated iNOS, Pro-IL-1β protein, and inflammatory cytokine mRNA expression (P<0.01). YW stably bound to KAT7 protein (binding energy: _94.2 kcal/mol); YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models (P<0.01); YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes (P<0.01). Conclusion YW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes, thereby blocking chondrocyte senescence.

The effect and mechanism of Saponin Ⅰ ofSchizocapsa plantagineaHance on nasopharyngeal carcinoma cell line HONE-1in vitro

Guo Xinyi； Liang Ziying； Wang Jinni； Ding Xiaolian； Wang Yanxue； Liang Gang

DOI: 专辑：医药卫生科技

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Integrated bioinformatics analysis and experimental validation of angiogenesis-related genes in diabetic retinopathy

Li Peng1, Liang Kun2, Wu Feng1, Li Jia3, Liu Lun4, Tao Yulin2

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the molecular mechanisms related to angiogenesis during the development and progression of diabetic retinopathy (DR). Methods Angiogenesis-related genes were obtained from the Gencard website and intersected with differentially expressed genes from DR datasets (GSE60436 and GSE94019). Functional enrichment and protein-protein interaction (PPI) networks were then used to screen candidate genes and evaluate their diagnostic value. Gene set enrichment analysis (GSEA) was used to explore potential pathways underlying candidate genes, and immune infiltration analysis revealed associations between candidate genes and immune cells. Cellular experiments were conducted to validate the role of fibronectin 1 (FN1) in human retinal microvascular endothelial cells (HRMECs) under high glucose (HG) conditions. Results A total of 237 differentially expressed genes related to angiogenesis were identified, enriched in pathways such as phosphoinositide 3-kinase/protein kinase B signaling pathway (PI3K-Akt), tumor suppressor protein 53 (P53), tumor necrosis factor (TNF), and Janus kinase (JAK)/signal transducer and activator of transcription signaling pathway (STAT). Among them, collagen type I alpha 1 chain (COL1A1), COL1A2, FN1, tumor necrosis factor (TNF), and tumor protein p53 (TP53) were key genes with high diagnostic value. GSEA indicated that these genes were involved in multiple signaling pathways, including P53. CIBERSORTx analysis revealed significant associations with the infiltration of multiple immune cells. HG treatment led to the upregulation of FN1. In HG-induced HRMECs, compared with the si-NC control group, si-FN1 significantly reduced cell proliferation, migration, and tube formation, while P53 protein expression was increased. Conclusion This study reveals the important role of FN1 in angiogenesis in DR and suggests that it may be a potential diagnostic and therapeutic target.

Incidence and influencing factors of major low anterior resection syndrome within six months after sphincter-preserving surgery for rectal cancer patients

Shen Minjing1,2,Ren Chunxia1,Sun Lin2,Liu Lei1,Zhu Yaodong1,Zhou Qiang2

DOI: 专辑：医药卫生科技

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Abstract:
Objective To explore the incidence of major low anterior resection syndrome (LARS) within six months after sphincter-preserving surgery for rectal cancer and to analyze its associated factors. Methods Clinical records, postoperative rehabilitation data and LARS scores were col- lected from 889 patients at 3 months postoperatively and from 844 patients at 6 months postopera- tively. Patients were divided into a major LARS group (3 months postoperatively, n=247; 6 months postoperatively, n=181) and a non-major LARS group (3 months postoperatively, n=642; 6 months postoperatively, n=663). Multivariable logistic regression was used to analyze factors associated with major LARS at 3 and 6 months postoperatively, and the predictive value of the models was assessed using the Hosmer–Lemeshow goodness-of-fit test and the receiver operating characteristic (ROC).Results Among patients undergoing sphincter-preserving surgery for rectal cancer, 247 patients (27.8%) had major LARS at 3 months postoperatively and 181 patients (21.4%) at 6 months postoperatively. Multivariable logistic regression showed that Kegel exercis- es, preoperative radiotherapy, anastomotic leakage, a tumor distance from the anal verge of ≤5 cm, and an anastomotic distance from the anal verge of ≤5 cm were independent factors for major LARS at 3 months postoperatively (P<0.05). At 6 months postoperatively, occasional Kegel exer- cises during 0⁓3 months, Kegel exercises during 4⁓6 months, hydrotherapy during 4⁓6 months, preoperative chemotherapy, a tumor distance from the anal verge of ≤5 cm, and an anastomotic distance from the anal verge of ≤5 cm were independent factors (P<0.05). The models at 3 and 6 months postoperatively showed goodness-of-fit test P values of 0.986 and 0.517 and area under the curve (AUCs) of 0.843 and 0.870, indicating good predictive value. Conclusion The incidence of major LARS within six months after sphincter-preserving surgery for rectal cancer is relatively high, and greater attention should be paid to patients who receive preoperative chemoradiotherapy, develop anastomotic leakage, or have tumor and anastomotic distances from the anal verge of ≤5 cm. Patients should also be advised that early postoperative Kegel exercises and hydrotherapy may reduce the incidence of major LARS.

Change and significance of IL-18 and Th1 in cytomegalovirus infection after pediatric liver transplantation

Gao Yiwen; Liu Chun; Li Dan; Mu Jiawei; Wang Yuliang

DOI: 专辑：医药卫生科技

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Cornelia de Lange Syndrome:Advances in Genetic and Molecular Mechanisms

An Yuqin; Cao Ning; Kong Fanchao; Zhang Huirong

DOI: 专辑：医药卫生科技

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The effect of TNF-α-regulated circWBSCR22 on the migration and invasion of cervical cancer cells through the miR-512-5p/FAM60A axis

Bai Lili 1,2,3,4, Zhang Jin5, Fan Yatong 1,2,3,4, Zhang Pengyu 1,2,3,4

DOI: 专辑：医药卫生科技

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Abstract:
Objective To explore the effect and mechanism of tumor necrosis factor alpha (TNF-α)-regulated circular RNA Williams Beuren syndrome chromosomal region 22 (circWBSCR22) on the malignant behaviors of cervical cancer cells. Methods Human cervical cancer HeLa cells were treated with TNF-α . Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of circWBSCR22. Nuclear-cytoplasmic RNA separation experiments were conducted to determine the localization of circWBSCR22 in cells. Cell migration, invasion, viability, and proliferation were assessed through Transwell assay, tetrazolium salt (MTT) assay, and colony formation assay, respectively. Dual-luciferase reporter gene assays were performed to verify the targeting relationship between microRNA-512-5p (miR-512-5p) and circWBSCR22 or family with sequence similarity 60A (FAM60A). RT-qPCR was used to detect the RNA levels of miR-512-5p and FAM60A. Western blot was used to detect the protein level ofFAM60A. Results Compared with the Control group,the expression level of circWBSCR22 in HeLa cells treated with TNF-α increased (P<0.05). About 66% of circWBSCR22 was found in the cytoplasm. Compared with the control group, the migration (P<0.01) and invasion (P<0.01) of HeLa cells transfected with circWBSCR22 were enhanced, but the cell activity and cell proliferation were not significantly affected (P>0.05). The double luciferase reporter gene assay showed that the relative luciferase activity of the co transfected circWBSCR22-WT and miR-512-5p groups was lower than that of the co transfected circWBSCR22-WT and miR-NC groups (P<0.01). Compared with the control group, the expression level of miR-512-5p in HeLa cells transfected with circWBSCR22 decreased (P<0.01). Compared with the control group, the migration (P<0.01) and invasion (P<0.05) ability of HeLa cells transfected with miR-512-5p decreased. Double luciferase reporter gene assay showed that compared with the co transfected FAM60A 3´-UTR-WT and miR-NC groups, the fluorescence activity of the co transfected FAM60A 3´-UTR-WT and miR-512-5p groups decreased (P<0.01).Compared with the control group, the expression levels of FAM60A mRNA (P<0.05) and protein (P<0.01) in HeLa cells transfected with miR-512-5p decreased. Compared with the control group, the migration (P<0.01) and invasion (P<0.01) of cervical cancer HeLa cells transfected with FAM60A were enhanced. Compared with the control group, the expression levels of FAM60A mRNA (P<0.01) and protein (P<0.05) in the cells transfected with circWBSCR22 increased. The results of rescue experiment showed that compared with the pcDNA+miR-NC group, the expression levels of FAM60A RNA (P<0.01) and protein (P<0.001) in the pcDNA+miR-512-5p group decreased, and the ability of migration (P<0.01) and invasion (P<0.05) decreased; Compared with pcDNA+miR-512-5p group, the expression levels of FAM60A RNA (P<0.01) and protein (P<0.001) in circWBSCR22+miR-512-5p group increased, and the ability of migration (P<0.01) and invasion (P<0.05) was enhanced. Conclusion TNF-α promotes the migration and invasion of cervical cancer cells through the circWBSCR22/miR-512-5p/FAM60A regulatory axis.

Association between epicardial adipose parameters and microvascular obstruction following acute myocardial infarction based on CMR

Cheng Wei; Li Yao; Shen Ailian; Mu Dan; Zhao Jinxuan

DOI: 专辑：医药卫生科技

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Abstract:
Objective To evaluate the predictive value of epicardial adipose tissue (EAT) parameters for microvascular obstruction (MVO) formation in patients with ST segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance quantification. MethodsA total of 139 STEMI patients were included in this study, and various parameters such as EAT thickness, volume, and mass index were measured utilizing cardiac magnetic resonance. All included patients were divided into MVO group and non-MVO group according to whether MVO occurred. Differences in EAT related parameters between two groups were compared and correlation analysis was applied to evaluate the correlation between quantitative indicators of EAT and indicators such as infarct size and ejection fraction. Logistic regression analysis was used to identify the relevant risk factors for MVO formation. Receiver Operating Characteristic (ROC) curve analysis was performed to assess the predictive value of the epicardial adipose tissue (EAT) quality index and other indicators for the occurrence of MVO. ResultsCompared with non MVO group, patients in MVO group presented with higher peak troponin T levels, increase of neutrophil lymphocyte ratio (NLR) and C-reactive protein (CRP), larger infarct size and compromised left ventricular ejection fraction (LVEF%) ( P<0.05). Total EAT volume, EAT mass index, left atrioventricular EAT volume, left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were significantly higher in patients with MVO. Multivariate logistic regression analysis demonstrated that NLR, peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. The ROC curve suggested that the left atrioventricular EAT mass index had the highest predictive power for MVO formation in STEMI patients. Conclusion The parameters of EAT quantified by cardiac magnetic resonance serve as imaging biomarkers for predicting MVO formation in STEMI patients. These metrics enable risk stratification post-myocardial infarction and facilitate early identification of high-risk individuals, thereby supporting personalized therapeutic decision-making.

Analysis of risk factors for cardiovascular events and construction of a nomogram prediction model in patients undergoing long-term peritoneal dialysis

Zhou Xinyuan; Jiang Yuxin; Wang Xiaoxia; Yang Xiangjie; Zhou Runzhe; Meng Yuqing; Zhang Dingxin; Zhang Jin; Wang Ying

DOI: 专辑：医药卫生科技

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Abstract:
ObjectiveTo analyze the risk factors for long-term cardiovascular events in patients undergoing long-term peritoneal dialysis (PD), and to construct and validate a visual nomogram prediction model based on multiple parameters. MethodsA prospective cohort study was conducted, consecutively enrolling 248 maintenance PD patients (dialysis duration ≥ 3 months). Demographic characteristics, clinical indicators, laboratory parameters, and echocardiographic indices (including left ventricular ejection fraction [LVEF], E/e' ratio, etc.) were collected. The composite endpoint was defined as the occurrence of cardiovascular events or cardiovascular death, with non-cardiovascular death as the competing risk and loss to follow-up or the end of follow-up as censoring events. Fine-Gray competing risks model was used to screen independent predictors, based on which a nomogram model was constructed. Internal validation was performed using the Bootstrap method (1 000 resamplings), and the concordance index (C-index) and time-dependent receiver operating characteristic (time-dependent ROC) curve were calculated to evaluate the model performance. Results With a median follow-up of 29 months (interquartile range: 24–35 months), 88 patients (35.48%) reached the composite endpoint, including 80 cases of cardiovascular events and 8 cases of cardiovascular death, and 4 patients died of non-cardiovascular causes. Multivariate Fine-Gray analysis revealed that age, diabetes mellitus, hemoglobin (HGB) level and E/e' ratio were independent influencing factors of the composite endpoint. Specifically, each 1-year increase in age was associated with a 3.0% increase in the risk of the composite endpoint ( HR=1.030 , P=0.006); patients with diabetes mellitus had a 167.9% higher risk compared with non-diabetic patients ( HR=2.679, P=0.007); each 1g/L increase in HGB level contributed to a 1.5% reduction in the risk ( HR=0.985, P=0.003); and each 0.1 increase in E/e' ratio led to a 7.2% increase in the risk ( HR=1.072, P=0.045). The nomogram model had a C-index of 0.76 (95% CI0.698–0.820), and the AUC of the time-dependent ROC curve reached 0.849 (95% CI0.761–0.938) at 23 months of follow-up. Conclusion Increased age, complicated with diabetes mellitus, decreased HGB, and elevated E/e' ratio are independent risk factors of long-term occurrence of cardiovascular events and cardiovascular death in patients undergoing long-term PD. The nomogram model constructed based on the above variables has good predictive value and clinical applicability, which can provide a reference for cardiovascular risk stratification and individualized intervention in long-term PD patients.

FAH promotes glioblastoma progression by activating the PI3K/AKT/mTOR signaling pathway

Li Shihao1, Zhao Bing2, Yang Tieniu1, Yang Jinliang1, Zhang Yongliang1, Li Zhongsen1, Li Shunli1, Chen Ning1, Wang Jianbiao1, Li Jia1, Ma Qingfang1

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase (FAH) in the progression of glioblastoma (GBM). Methods Differential expression analysis was performed on the TCGA-GBM, GSE4290, and GSE116520 datasets. Weighted gene co-expression network analysis (WGCNA) was used to identify key modules, and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments, and pathway analysis was performed to explore the underlying mechanisms. Results A total of 152 overlapping genes were identified across the three GBM datasets. WGCNA revealed that the turquoise module was most strongly associated with tumor purity, stromal score, immune score, and ESTIMATE score (P < 0.001). Compared with normal tissues, three prognostic genes (CTSD, FAH, and THBD) were upregulated in GBM and correlated with immune infiltration (P < 0.05). FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues, and its expression was significantly associated with age stratification and TP53 mutation (P < 0.05). CCK-8 assay results showed that, compared with the shNC group, the proliferative activity of GBM cells in the shFAH group was reduced (P < 0.001). Transwell migration and invasion assays demonstrated that, relative to the shNC group, the numbers of migrated and invaded cells in the shFAH group decreased (P < 0.05). Western blot analysis revealed that the protein expression levels of PI3K, p-AKT, and p-mTOR in the shFAH group decreased compared with those in the shNC group (P < 0.05). In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group (P < 0.001). Conclusion FAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

PET/CT imaging of PD-1 receptor probe targeting S180 sarcoma in mice

Huang Haifeng1, Sun Jiangnan2, Zou Huan3, Bao Tao2, Zhu Hua4, Yang Xianteng1, Li Shanshan5

DOI: 专辑：医药卫生科技

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Etiological characteristics and risk factors of urinary tract infection in elderly patients with polycystic kidney disease

Pang Zhe,Wang Jingjing, Li Dashan, Qi Xiangming

DOI: 专辑：医药卫生科技

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Abstract:
Objective To analyze the etiological characteristics and risk factors of autosomal dominant polycystic kidney disease (ADPKD) complicated with urinary tract infection (UTI). Methods A retrospective analysis was performed on 244 patients with ADPKD admitted to the Department of Nephrology between March 2018 and March 2024. The patients were stratified into a study group (n=138) and a control group (n=106) according to the presence or absence of concurrent UTI. All patients in the study group underwent etiological testing and drug susceptibility testing. Clinical data of both groups were collected to identify the risk factors for ADPKD complicated with UTI. Results A total of 105 pathogens were detected in 138 cases in the study group, including 79 Gram-negative bacteria, 20 Gram-positive bacteria and 6 fungi. Escherichia coli showed a relatively high resistance rate to ampicillin, piperacillin and ciprofloxacin. Enterococcus faecalis had a relatively high resistance rate to tetracycline. There were statistically significant differences between the study group and the control group in terms of gender, history of urinary tract infection, C-reactive protein (CRP), increased urine red blood cells, increased urine white blood cells, increased percentage of neutrophils, blood sodium, blood calcium, total cholesterol, serum iron and transferrin saturation (P<0.05). Multivariate binary Logistic regression analysis revealed that female gender (OR = 2.236, P = 0.004), history of urinary tract infection (OR = 2.383, P = 0.002), increased urine white blood cells (OR = 2.726, P = 0.001), increased percentage of neutrophils (OR = 1.040, P = 0.010), elevated C-reactive protein (OR = 1.011, P = 0.007) and elevated blood calcium (OR = 4.389, P = 0.024) were risk factors of urinary tract infection in ADPKD patients (P<0.05). Conclusion The main pathogens of UTI in patients with ADPKD are Gram-negative bacteria. Female, previous history of urinary tract infection, urinary leukocytosis, increased percentage of neutrophils, increased CRP and increased serum calcium are risk factors of UTI.

Serum short-chain fatty acid levels and their association with atopic dermatitis in pediatric patients

Wang Zhenxiang 1,2,3，Chen Lele 1,2,3，Dong Liping 1,2,3，Wang Sheng4，Xu Jinlei 1,2,3， Cai Xinying1,2,3，Xiao Fengli 1,2,3,4,5

DOI: 专辑：医药卫生科技

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Biological functions of SMYD5 and its role in disease

Zhang Fangfang; Liu Haodan; Yang Ruirui; Li Xuan; Wang Changli; Ye Guangbin; Bin Xiaoyun

DOI: 专辑：医药卫生科技

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The role of ion channels in the therapeutic management of temporomandibular joint disorders

Han Quancheng, Liu Xiaoyu, Wu Tingting

DOI: 专辑：医药卫生科技

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Reactive oxygen species mediate promoting effect of fullerene C60 on DHPN-induced lung tumors

Zhang Wen 1，2，Xu Jiegou 1

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate whether fullerene C60 administered by intratracheal spraying promotes N-bis (2-hydroxypropyl) nitrosamine (DHPN) induced-lung tumor development and the underlying mechanisms. Methods A rat lung tumor model was induced by the DHPN drinking water method. Eight-week-old male Fisher 344 rats were randomly divided into 5 groups (n = 15): DHPN+Veh group (0.2% DHPN + vehicle solution), DHPN+C60-L group (0.2% DHPN + 250 μ g/mL C60), DHPN+C60-H group (0.2% DHPN + 500 μg/mL C60), DHPN group (0.2% DHPN), and C60-H group (normal drinking water + 500 μg/mL C60). 0.2% DHPN in drinking water was given to initiate carcinogenesis, and 2 weeks later, different concentrations of fullerene C60 were administered by intratracheal spraying every two weeks for a total of 20 times. Two weeks after the last spraying, the incidence, number and size of lung tumors were statistically analyzed. In another mechanism animal experiment, 8-week-old male Fisher rats were divided into two groups with 5 rats in each group: C60 group and the control vehicle group. 500 μg/mL C60 or the control vehicle intratracheally sprayed every two days for a total of 5 times. Six hours after the last spraying, the lungs were removed and used for observation ofC60 distribution and for detection of SOD, 8-OHdG and cytokines in lung tissues. Results No lung tumorigenesis was observed in the C60-H group; the incidence, number and size of lung tumors in the DHPN+C60-H group were significantly higher than those in the DHPN+Veh group (P < 0.05, P < 0.001, P < 0.05) and the DHPN group (P < 0.01, P < 0.001, P < 0.01), respectively. In additional animal experiments designed for mechanistic investigation, the levels of SOD and 8-OHdG in the experimental group were markedly elevated compared with the control group (both P < 0.001), with statistically significant differences. Conclusion Intratracheal nebulization of high-concentration fullerene C60 promoted DHPN- induced lung tumorigenesis; C60 led to an increase in reactive oxygen species (ROS) production, thereby elevating the potential for gene mutation. This may represent one of the mechanisms underlying C60-induced promotion of lung tumorigenesis.

Role of IL-17A in acute inhalational pneumonia caused by highly virulent and multidrug-resistantStaphylococcus aureus

Kuang Qi; Zhu Xiaoyu; Li Lu; Wang Xueyan; Yan Peijie; Zhang Lili; Lü Meng; Hu Lingfei; Zhou Dongsheng; Yang Wenhui

DOI: 专辑：医药卫生科技

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The effect of Chuju total flavonoids on the current and protein expression of BKCa channels in rat middle cerebral artery VSMC

Li Yuwen1，Wang Xiao1，Wu Miao1，Chen Shuo2，Chen Zhiwu1

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.001

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Nomogram based on multimodal MRI radiomics for discriminating molecular subtypes of HER-2-negative breast cancer

Wang Qun 1, Pan Hongli 1, Li Xiaohu 1,Yu Yongqiang 1,Yan Yunwen2, Hou Weishu 1

DOI: 专辑：医药卫生科技

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Analysis of risk factors in patients with nonvalvular persistent atrial fibrillation complicated with ventricular hypertrophy and construction and validation of prediction model

Liu Fang，Zheng Peiyang，Wang Huimin，Li Danni，Liang Ao，Zhao Ren

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.023

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Abstract:
Objective To construct a nomogram prediction model for non-valvular persistent atrial fibrillation （PeAF）patients with left ventricular hypertrophy（LVH），followed by prognostic analysis through follow-up. . Methods This study retrospectively enrolled 949 patients with newly diagnosed and hospitalized non-valvular PeAF. Among them，403 patients presented with LVH. The cohort was randomly stratified into a training set（n= 665）and a validation set（n=284）. Univariate and multivariate Logistic regression analyses were employed to identify independent risk factors for PeAF complicated by LVH. A nomogram prediction model was subsequently constructed and evaluated for discriminative ability，calibration，and clinical utility using receiver operating character⁃ istic（ROC）curve analysis，calibration plots，and decision curve analysis（DCA）. Results Seven independent risk factors were ultimately identified and included in the prediction model：female sex，hypertension，diabetes， red blood cell distribution width-SD（RDW-SD）， body mass index（BMI）， left atrial diameter（LAD）， and left ventricular ejection fraction（LVEF）. The area under the ROC curve（AUC）in the training set was 0. 862（95% CI：0. 834-0. 890），and in the validation set，it was 0. 870（95% CI：0. 829-0. 911），demonstrating excellent pre⁃ dictive performance. Conclusion Independent risk factors for LVH in PeAF patients include female，hyperten⁃ sion，diabetes，RDW-SD，BMI，LAD，and LVEF. The prediction model built based on this can help early identi ⁃ fication of PeAF patients with high risk of LVH. At the same time，the incidence of major adverse cardiovascular events（MACE）is higher in PeAF patients with LVH. Patients with atrial fibrillation combined with LVH may ben ⁃ efit from catheter ablation.

RUNX3 regulates FAP to influence the proliferation of mouse lung primary fibroblasts

You Junbo; Wang Xianchen; Ling Hui; Fan Jiahao; Chen Qi; Tao Hui; Sha Jiming

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the role of runt-related transcription factor 3 (RUNX3) in transforming growth factor-β 1 (TGF-β 1)–induced activation of mouse primary pulmonary fibroblasts (PFs), and its effects on fibroblast activation protein (FAP) expression, cell proliferation, and collagen synthesis. Methods PFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA (siRNA). Cells were assigned to the control group (Control), TGF-β 1-treated group (TGF-β 1), negative control group (TGF-β 1+siRNA-NC), and RUNX3-silenced group (TGF-β 1+si-RUNX3). In addition, a RUNX3 overexpression rescue experiment was performed based on TGF-β 1stimulation. Protein and mRNA levels of RUNX3, FAP, and typeⅠcollagen (COL1A1) were measured by Western blot and reverse transcription quantitative real-time PCR (RT-qPCR). Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. Results Compared with the Control group, RUNX3, FAP, and COL1A1 expression levels were upregulated in PFs in the TGF-β 1 group ( P < 0.01). The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group ( P < 0.01). Consistently, the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group ( P < 0.01). Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions, these fluorescence signals exhibited a partial rebound ( P < 0.01). ConclusionRUNX3 in TGF-β1–induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.

The application value of deep jearning image reconstruction algorithm in ultra-low dose abdominal CT scanning

Tang Xing; Li Yuncheng; Shu Hongmin; Hou Weishu; Wang Jun; Li Xiaohu

DOI: 专辑：医药卫生科技;信息科技

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Abstract:
Obj ective To evaluate the feasibility of various strength levels of deep learning image reconstruction (DLIR) algorithms for improving non-contrast abdominal CT image quality at ultra-low radiation doses, by comparing ultra-low-dose DLIR images with low-dose filtered back projection FBP images. Methods A prospective collection of 85 patients undergoing non-contrast abdominal CT scans was performed, and a self-controlled study method was employed to conduct low-dose (LD) group and ultra-low-dose (ULD) group scans. The LD group used a noise index of 10 and employed FBP for image reconstruction (LD-FBP group). The ULD group used a noise index of 30 and employed DLIR at different levels (low, medium, high), resulting in three subgroups of reconstructed images: ULD-DLIR-L, ULD-DLIR-M, and ULD-DLIR-H. For each group, CT values, standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured and calculated for the liver, spleen, kidneys, aorta, psoas major, and subcutaneous fat. Effective dose (ED) was also recorded. Two radiologists independently performed subjective evaluations of image quality using a 5-point scale. ResultsCompared with the LD-FBP group, the ULD-DLIR-L group showed significantly lower SNR and CNR values in the liver, spleen, kidneys, aorta, and psoas major ( P<0.001), while the ULD-DLIR-H group exhibited significantly higher values ( P<0.001). The difference of SNR and CNR values for the ULD-DLIR-M group showed no statistically significant difference. For subjective evaluation, the scores of the ULD-DLIR-L and ULD-DLIR-M groups were lower than those of the LD-FBP group, while there was no statistically significant difference in scores between the ULD-DLIR-H group and the LD-FBP group. The ED value of the ULD group was approximately 88% lower than that of the LD group. ConclusionCompared with the LD-FBP group, the ULD-DLIR-H group significantly reduces SD values while increasing SNR and CNR values, effectively improving the image quality of non-contrast abdominal CT scans.

Effect of LncRNA SNHG16 targeting miR-141-3p/HMGB1 axis on angiogenesis of endometrial stromal cells in ectopic adenomyosis

Liu Ting，Wang Mingyang，Zou Xiaofeng

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.020

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Abstract:
Objective To investigate the effect of interfering with long noncoding RNA（LncRNA）small nucleolar RNA host gene 16（SNHG16）on improving angiogenesis of ectopic endometrial stromal cells（EScs）in adenomyosis（AM）by targeting upregulation of miRNA（miR）-141-3p and inhibition of high mobility group box-1 protein （HMGB1）. Methods The expression levels of SNHG 16，miR-141-3p and HMGB 1 mRNA in endometrial tissues of 52 patients with adenomyosis（AM group）and 52 patients who needed hysterectomy due to cervical cancer or ovarian cancer（control group）were detected by quantitative reverse transcription polymerase chain reaction（qRT- PCR）. Y 14 cells were divided into small hairpin RNA（shRNA）NC group，shRNA SNHG 16 group，shRNA SNHG 16+miR-141-3p inhibitor（inhibitor）group，shRNA SNHG 16+inhibitor NC group and blank group. The tar_ geting relationship between miR-141-3p and SNHG 16 as well as HMGB 1 was verified. The expression levels of SNHG 16，miR-141-3p and HMGB 1 mRNA in Y 14 cells were detected by qRT-PCR. Cell counting assay（CCK-8） and Transwell assay were used to detect cell proliferation，invasion and migration. Microvascular density（MVD） was determined by immunofluorescence. The expressions of hypoxia-inducing factor α（HIF-1α), cyclooxygenase- 2（Cox-2），vascular endothelial growth factor（VEGF）and HMGB 1 were detected by Western blot. Results The expression of SNHG 16 and HMGB 1 mRNA in AM group was higher than that in control group，but the expression of miR-141-3p was lower than that in control group（P<0. 05）. The expression of SNHG 16，HMGB 1 mRNA，proliferation rate，migration，invasion number，MVD，expression of VEGF，HIF-1 α , Cox-2，and HMGB 1 proteins in the shRNA SNHG 16 group were lower than those in the blank group and shRNA NC group，while the expression of miR-141-3p was higher than that in the blank group and shRNA NC group（P<0. 05）. Inhibition of miR-141-3p reversed the improvement of EScs angiogenesis by interfering with SNHG 16. Conclusion Interference with LncRNA SNHG 16 improves EScs angiogenesis and inhibits proliferation，migration，and invasion of EScs by targeting upregulation of miR-141-3p and inhibition of HMGB 1.

Effect of isoacteoside on the replication respiratory syncytial virus

Liu Wei, Sun Zhiyang, Cao Xinwang

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the effect of isoacteoside on the replication process of respiratory syncytial virus (RSV) and its underlying mechanism. Methods RSV-infected HEp-2 cells (control group) were treated with isoacteoside (isoacteoside-treated group). Real-time quantitative PCR (qPCR) was used to analyze the mRNA expression levels of the RSV fusion protein (F) gene and matrix protein (M) gene in both groups. Viral titers were determined by plaque assay to assess the inhibitory effect of isoacteoside on viral replication. The number of RSV inclusion bodies formed was determined using cell transfection and laser confocal imaging to evaluate the role of isoacteoside in the formation of inclusion bodies required for RSV replication. 18 seven-week-old female BALB/c mice were randomly divided into three groups: uninfected control group (n = 6), RSV-infected group (n = 6), and RSV-infected group treated with isoacteoside (n = 6). 5 days after infection, the mice were euthanized and lung tissues were collected for pathological analysis to assess the therapeutic effects of isoacteoside on RSV-induced lung tissue injury. Results Compared to the control group, the isoacteoside-treated group exhibited the reduced mRNA levels ofthe RSV F gene (t = 17.13, P < 0.001) and M gene (t = 18.22, P < 0.001), as well as a decrease in viral titer (t = 15.32, P < 0.001). The number of inclusion bodies was also significantly reduced (t = 16.12, P < 0.001). In the RSV-infected mouse experiment, compared to the RSV-infected group, the isoacteoside-treated group showed a decrease in the levels of inflammatory cytokines IL-4 (t = 14.76, P < 0.01) and IL-6 (t = 21.13, P < 0.001) in lung tissues, as well as decreased mRNA levels of the viral load–associated genes F (t = 19.52, P < 0.001) and M (t = 18.76, P < 0.001) in lung tissues. Pathological damage to lung tissue caused by RSV infection was alleviated. Conclusion Isoacteoside inhibits RSV replication by interfering with the formation of RSV inclusion bodies and alleviates lung tissue injury induced by RSV infection in mice.

Research progress on the role of macrophages in atherosclerosis

Ma Wenxiu; Bai Li; Ma Wen; Qi Tingting; Zhang Haonan; Wang Xuan; Zhang Xin

DOI: 专辑：医药卫生科技

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Effect of vitamin B 12 eye drops on the expression of MMP-9 and TNF-αin the cornea of mice with dry eye disease

Dong Hui，Zheng Huacheng，Wang Weiting，Zhao Haixia

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.006

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Abstract:
Objective To investigate how vitamin B12 eye drops regulate MMP-9 and TNF-α expression levels in the corneas of dry eye disease（DED）mouse model induced by a combination of an artificially simulated dry environment（air humidity <30%）and subcutaneous injection of hyoscine hydrobromide. Methods Fifty C57BL/6 female mice were used in the study. 10 mice formed A group（blank control），while the remaining 40 mice were subjected to dry eye disease induction through subcutaneous injection of scopolamine hydrobromide in a controlled environment with <30% air humidity. All mice underwent schirmer I test（SIT），tear break-up time（TBUT）， and corneal fluorescence staining score（CFS）evaluations. Mice meeting modeling criteria were randomly assigned to three groups：B group（model group），C group（PBS control），and D group（vitamin B12 group）. 0，7，14，and 21 days after treatment，each group received TBUT，SIT，CFS，and corneal inflammation assessments. Macroscopic analysis evaluated the efficacy of vitamin B 12 eye drops in treating dry eye. After 21 days of treatment，all mice were euthanized via cervical dislocation and their corneas analyzed using HE staining to examine morphologi ⁃ cal changes. ELISA and immunohistochemical methods were employed to detect MMP-9 and TNF-α expression lev⁃ els in corneal tissues across groups. Results In dry environments（air humidity <30%），subcutaneous injection of scopolamine hydrobromide induced changes in dry eye-related indicators in mice：SIT significantly decreased， TBUT significantly shortened ，corneal fluorescein staining increased ，and CFS all significantly elevated（P < 0. 05），indicating successful establishment of the dry eye model. A total of 30 dry eye mice were enrolled. When the dry eye model was successfully established without drug intervention，no statistically significant differences were observed between B group，C group and D group in terms of TBUT，SIT，corneal fluorescein staining，or CFS. Compared with A group，B group，C group and D group showed statistically significant differences in re ⁃ duced SIT，shortened TBUT，increased corneal fluorescein staining，and elevated CFS（P <0. 05）. After drug intervention，D group（vitamin B12 group）exhibited significantly increased SIT，prolonged TBUT，reduced corneal fluorescein staining，clearer corneas，decreased fluorescein staining，and lower CFS compared with B and C groups （P<0. 05）. ELISA and immunohistochemical staining results showed that compared with A group，B and C groups exhibited significantly increased expression of MMP-9 and TNF-α in corneal tissues（P <0. 05）. D group showed decreased expression of MMP-9 and TNF-α compared with B and C groups but remained higher than A group（P < 0. 05）. Conclusion The expression of MMP-9 and TNF-α in the corneal tissues of mice with dry eye is elevated， suggesting that both inflammatory factors，MMP-9 and TNF-α , are involved in the development of dry eye. Vitamin B12 eye drops may improve the symptoms of ocular surface discomfort by promoting the repair of the corneal epithelium. Vitamin B12 eye drops may increase tear secretion，prolong tear film break up time，reduce corneal fluorescein staining，and alleviate the inflammatory reaction of the cornea by decreasing the expression of MMP-9 and TNF-α in the corneal tissues of the mice，thus playing a therapeutic role in the treatment of dry eye disease.

Construction of Enterococcus faecium -based recombinant Ef-PA0057 vaccine of Pseudomonas aeruginosa and its protection in mice

Li Wengui，Ou Xingkun，He Ailin

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.018

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Abstract:
Objective To construct an Enterococcus faecium（Ef）-based recombinant Ef-PA0057 vaccine of Pseu⁃ domonas aeruginosa（Pa）and to study its protective immune mechanism in mice. Methods The PA0057 gene was cloned from the genomic DNA of PA01 strain ATCC9027 by PCR and inserted into pGEX-1λT to construct pGEX- PA0057. The recombinant plasmid was electroporated into TX0016 strain to construct rEf-PA0057 vaccine. The plasmid was extracted from rEf for PCR. The rEf vaccine was expressed through IPTG induction，and the expres⁃ sion of protein was analyzed by SDS-PAGE and Western blot. BALB/c mice were immunized intragastrically with 5× 108 CFU rEf-PA0057 vaccine 3 times per week for 3 weeks. 4 weeks after the first immunization，mice were chal⁃ lenged intranasally with 5× 107 CFU of PA01 strain. 2 weeks after challenge，mice were sacrificed，and their lungs were separated. Bacteria in lungs were incubated and colonies were counted. Sera were collected at 0，4，and 6 weeks after the first immunization. The IgG and its subclasses，and IgE were detected by ELISA. Results The 900 bp PA0057 gene was successfully cloned by PCR. PCR showed that PA0057 gene was amplified when the ex⁃ tracted plasmid from rEf as template；the relative molecular mass（Mr）of the expressed PA0057-GST fusion pro⁃ tein was approximately 58 ku，detected by SDS-PAGE. The amount of the expressed protein was 18% of the total bacterial proteins. Western blot showed that the target protein could be recognized by Pa sera. The colony numbers of lung tissue in rEf-PA0057 vaccine group，blank vector group and Ef control group were（0. 297±0. 011）× 108 CFU ，（7. 576±0. 206）× 108 CFU and（7. 551±0. 185）× 108 CFU ，respectively. The levels of IgG ，IgG1， IgG2b，IgG3 and IgE increased. At the same time point，there was a significant difference compared with the two control groups（P<0. 01）. Conclusion The rEf-PA0057 vaccine is successfully constructed. It may induce mice to produce a humoral response against challenge with Pseudomonas aeruginosa.

Effects of different concentrations and treatment durations of hyaluronidase on mouse zygote development and blastocyst formation

Zhang Jie1，3，Wang Hua2，3，Yang Di1，3，Lu Jinfang1，3，Zhang Jicong1，3

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.021

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Mechanism of transcription factor ZEB1 in the proliferation， migration，and invasion of lung adenocarcinoma cells

Zhao Yun 1，Ma Beibei 1，Xing Huaxue 1，Huang Shaofeng 1，Zhang Zhongwei 2，Ling Bo 1

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.012

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Abstract:
Objective To investigate the effects of zinc finger E-box binding homeobox 1（ZEB1）on the prolifera⁃ tion，migration，and invasion of lung adenocarcinoma H322 cells，as well as its underlying molecular mechanisms. Methods The gene expression characteristics of the transcription factor ZEB1 in lung adenocarcinoma were ana⁃ lyzed using data from the GEO and TCGA public databases. RT-qPCR and Western blotting were employed to mea ⁃ sure mRNA and protein expression levels of ZEB1 in lung adenocarcinoma cell lines（H322，A549，95-D）and normal human bronchial epithelial cells（BEAS-2B）. Lentiviral transduction was utilized to establish stable ZEB1- overexpressing（Oe-ZEB 1）and vector control（Oe-NC）H322 cell lines. Cell proliferation was assessed using CCK-8，colony formation，and EdU assays，while apoptosis was evaluated by Hoechst33258/PI double staining. Wound healing and Transwell assays were performed to examine cell migration and invasion capabilities. Cell cycle distribution was determined by flow cytometry ，and Western blotting was used to analyze protein expression changes in relevant signaling pathways. Results The findings from GEO and TCGA indicated that ZEB1 expres⁃ sion in lung adenocarcinoma varied with tumor malignancy grade. RT-qPCR and Western blot analyses revealed significantly higher ZEB1 expression in lung adenocarcinoma cell lines compared to BEAS-2B cells（P < 0. 05）. Results from the CCK-8，colony formation，EdU，wound healing，and Transwell assays demonstrated that，com⁃ pared with the un-transfected control（Control）group，Oe-ZEB 1 H322 cells exhibited enhanced proliferation，mi⁃ gration ，and invasion capabilities（P < 0. 05）. Hoechst33258/PI double staining and flow cytometry analyses showed that，relative to the Control group，apoptosis was reduced in Oe-ZEB 1 H322 cells（P < 0. 05）. Addition⁃ ally，a decreased proportion of cells in the G1 phase and an increased proportion in the S phase were observed in Oe-ZEB 1 cells，indicating accelerated cell cycle progression. Western blot analysis further revealed that，com⁃ pared with the Control group，Oe-ZEB 1 H322 cells exhibited upregulated expression of N-cadherin，mutant p53 （mutp53），and Cyclin D 1（P < 0. 05），while expression levels of E-cadherin，murine double minute 2（MDM2）， and p21 were downregulated（P < 0. 05）. Conclusion Overexpression of ZEB1 promotes the proliferation，migra⁃ tion，and invasion of lung adenocarcinoma H322 cells and may facilitate cell cycle progression by modulating the MDM2/mutp53/p21 signaling pathway，thereby promoting the transition of cells from the G0/G1 phase to the S phase.

Analysis of changes in serum UGRP1 level and influencing factors in pregnant patients with hashimoto’s thyroiditis

Ma Xingran; Wu Yue; Lu Chenyang; Zuo Chunlin

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the fluctuations in serum uteroglobin-related protein 1 (UGRP1) levels in hashimoto’s thyroiditis (HT) patients before and after pregnancy, and to analyze the influencing factors. MethodsTen healthy individuals and ten HT patients were enrolled. Thyroid fine needle aspiration cytology combined with immunohistochemistry was used to detect the expression of UGRP1 protein in thyroid cells between the two groups. A total of 30 healthy women were enrolled as the control group, and 149 HT patients were recruited, including 36 non-pregnant HT patients, 77 pregnant HT patients and 36 post-partum HT patients. According to levothyroxine sodium (L-T4) administration status, the pregnant HT group was further subdivided into the non-L-T4 subgroup ( n=36) and the L-T4 subgroup ( n=41). Kruskal-Wallis H test was used to compare the general clinical data, thyroid-related indicators and serum UGRP1 levels among groups. Spearman correlation analysis and univariate linear regression analysis were performed to explore the influencing factors of serum UGRP1 levels in HT patients. ResultsUGRP1 expression was negative in thyroid cells of all healthy individuals, while 80% of HT patients exhibited positive expression. The serum UGRP1 levels in the control group, non-pregnant HT group, pregnant HT group, and post-partum HT group were 359.52 (297.84, 440.60), 695.77 (518.55, 865.04), 207.96 (173.82, 264.91), and 582.08 (280.83, 735.87) pg/mL, respectively, with statistically significant differences among groups ( P<0.001). Correlation analysis showed no significant correlation between serum UGRP1 levels and thyroid-related indicators or gestational age in pregnant HT patients. Univariate linear regression analysis revealed that pregnancy status was negatively correlated with serum UGRP1 levels in HT patients ( β=-424.457, P<0.001), while L-T4 administration had no statistically significant effect on serum UGRP1 levels in pregnant HT patients ( P=0.890). ConclusionSerum UGRP1 levels are significantly higher in HT patients than in healthy individuals. Pregnancy is an important factor affecting serum UGRP1 levels in HT patients, which can lead to a decrease in UGRP1 levels, while L-T4 administration has no significant effect on serum UGRP1 levels.

Integrated network pharmacology analysis and cellular evidence reveal the mechanisms of Myristica fragrans against atherosclerosis

Lu Shuxian1, Zhou Zhiling 1, Zhang Yifeng 1,Yu Jun2

DOI: 专辑：医药卫生科技

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Abstract:
Objective To explore the potential mechanisms by which Myristica fragrans prevents and treats atherosclerosis (AS). Methods The major active components of Myristica fragrans and their shared targets with AS were obtained from databases. The shared targets were subjected to pathway enrichment analysis and PPI network construction using the ClusterProfile package and the STRING database. Molecular docking between key targets and major active components was performed using AutoDock. Gene expression data from early and late, as well as stable and unstable AS plaques, were used to validate changes of key targets and major pathways during AS progression. Western blot, flow cytometry, YO-PRO-1/PI staining, and TUNEL staining were applied to verify the main mechanisms.Results Nine active components of Myristica fragrans interacted with 293 AS-related targets, among which eight components acted on an average of 57.0% of the shared targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that the anti-AS effects mainly involved oxidative stress, inflammation, lipid metabolism, fluid shear stress, and apoptosis pathways. PPI network revealed JUN, CASP3,MAPK3, and AKT1 as key targets mainly involved in regulating apoptosis. Molecular docking showed stable binding conformations and high affinities between major components and these targets. Integrated analysis of gene expression in early and late, as well as stable and unstable AS plaques, showed significant enrichment of leukocyte apoptosis pathways in late and unstable plaques. Cell experiments further confirmed that Myristica fragrans significantly reduced Cleaved-CASP3（P=0 .04）and p-MAPK3（P=0 .0003）levels,increased p-AKT1（P=0 .004）levels,and inhibited macrophage apoptosis. Conclusion Myristica fragrans potentially interferes with AS development by modulating pathways related to oxidative stress, inflammation, lipid metabolism, fluid shear stress, and apoptosis, with CASP3 , MAPK3 , and AKT1 serving as key targets mediating its anti-apoptotic and anti-AS effects.

A novel MRI radiomics-based nomogram for preoperative prediction of perineural invasion in intrahepatic cholangiocarcinoma

Sui Huize; Zhou Zheyu; Cao Shuya; Xu Xiaoliang; Li Guoqiang

DOI: 专辑：医药卫生科技

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Trpc6 knockout suppresses inflammasome activity and alleviates myocardial inflammatory damage in mice

Liang Haoyu ，Fan Lei ，Zhu Xing ，Huang Lei ，Li Weiping ，Li Weizu

DOI: 专辑：医药卫生科技

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Abstract:
Objective To investigate the effects ofTrpc6 knockout on chronic lipopolysaccharide (LPS)-induced myocardial inflammation and fibrosis in mice and its potential mechanisms. Methods Male C57BL/6 wild-type (WT) mice and Trpc6 knockout (Trpc6-/-) mice of the same background were randomly divided into four groups: WT control, WT+LPS (200 μg/kg), Trpc6-/- control, and Trpc6-/-+LPS (200 μg/kg). Group with LPS received intraperitoneal LPS injections for 21 consecutive days to induce chronic myocardial inflammatory injury. Cardiac ultrasound assessed changes in left ventricular ejection fraction (EF), left ventricular shortening fraction (FS), and cardiac output (CO). Hematoxylin and eosin (HE) staining and periodic acid-Schiff (PAS) staining were used to examine morphological alterations in myocardial tissue. Masson’s trichrome staining was used to assess myocardial fiber alterations; Western blot analysis was used to measure myocardial tissue expression of transient receptor potential calcium channel 6 (TRPC6), nucleotide-binding domain-containing receptor 3 inflammasome (NLRP3), interferon-induced molecule 2 inflammasome (AIM2), caspase-1, Interleukin-6 (IL-6), and Interleukin-1β (IL-1β) in mouse myocardial tissue. Results Compared with the WT control group, the WT+LPS group exhibited decreased cardiac EF (P < 0.01), FS (P < 0.01), and CO (P < 0.05), along with significantly increased myocardial tissue damage, glycoprotein deposition, and fibrosis (P < 0.01). Further analysis revealed that compared with the WT control group, the WT+LPS group exhibited markedly increased myocardial tissue expression of TRPC6, NLRP3, AIM2, Caspase-1, IL-6, and IL-1β (P < 0.01). Compared with the WT+LPS group, mice in the Trpc6-/- +LPS group exhibited elevated EF (P < 0.01) and FS (P < 0.05), along with reduced myocardial tissue injury, glycoprotein deposition, and fibrosis (P < 0.05). Conclusion Chronic LPS treatment can activate NLRP3/AIM2 inflammasomes through the up-regulation of TRPC6 expression, and then lead to chronic myocardial inflammatory injury and fibrosis, while Trpc6 knockdown can reduce myocardial inflammatory injury and fibrosis, and the mechanism is related to inhibiting the activation of NLRP3/AIM2 inflammasomes.

Role of TLR4-mediated NETs formation in isoproterenol-induced heart failure in aged mice

Liu Huan; Chen Xiangdong; Wu Zhilin

DOI:

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Abstract:
Objective To examine the impact of Toll-like receptor 4 (TLR4)-mediated neutrophil extracellular traps (NETs) formation on isoproterenol (ISO)-induced heart failure (HF) in aged mice. Methods The mice were randomly divided into Control group, Model group, TAK-242 (TLR4 inhibitor) group, LPS (TLR4 agonist) group and LPS+DNaseⅠ (NETs inhibitor) group, with 8 mice in each group. The HF model was established by continuous infusion of ISO through an osmotic pump, and TAK-242, LPS, and LPS+DNaseⅠ interventions were administered during the last week of infusion for 7 consecutive days. ELISA was used to detect the N-terminal pro-B-type natriuretic peptide (NT-pro BNP), cardiac troponin I (cTnI), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and serum and myocardial tissue myeloperoxidase-DNA (MPO-DNA) and neutrophil elastase-DNA (NE-DNA) levels. HE staining was used to observe the pathological changes of myocardial tissue. Masson staining was used to observe the deposition of collagen fibers in myocardial tissue. Immunofluorescence was used to observe the colocalization of Ly6G and MPO in myocardial tissue. The protein expressions of TLR4, MPO, NE and cit-H3 in myocardial tissue were detected by Western blot. Results Compared with the Control group, the end-diastolic interventricular septal thickness (IVSD), left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) in the Mode group significantly increased ( P<0.01), fractional shortening (FS) and ejection fraction (EF) significantly decreased ( P<0.01), and the myocardial structure was significantly damaged. The myocardial collagen fiber precipitation, serum NT-pro BNP, cTnI, IL-1β, IL-6 and TNF-α contents, MPO-DNA and NE-DNA contents in serum and myocardial tissue significantly increased ( P<0.01). The co-localization of Ly6G and MPO and the expression of TLR4, MPO, NE and cit-H3 proteins in myocardial tissue significantly increased ( P<0.01). After TAK-242 intervention, the above indicators were significantly reversed, while the injury was further aggravated in LPS group. DNaseⅠ treatment could partially alleviate the deterioration of myocardial structure and function induced by LPS. Conclusion TLR4 and NETs are abnormally elevated in the myocardial tissue of aged HF mice. Treatment with the TLR4 inhibitor TAK-242 effectively suppresses NET formation, attenuates inflammatory responses, and enhances cardiac function in aged HF mice.

New pathways in neurodegenerative disease pathogenesis: oxidative stress and ferroptosis

Wang Yurong; Yuan Jianlong; Liu Bingchun

DOI: 专辑：医药卫生科技

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Protective effect and mechanism of genistein on etoposide-induced chondrocyte senescence

Wang Jinhong; Chen Tianyu; Mao Lifang; Zhao Yingjie; Zhou Renpeng; Hu Wei; Lu Chao

DOI: 专辑：医药卫生科技

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Abstract:
ObjectiveTo investigate the protective effect of genistein (Gen) on etoposide-induced chondrocyte senescence and its underlying mechanism. Methods The C28/I2 cell line was treated with different concentrations of Gen and etoposide, and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide, with Gen intervention. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 (Prdx6), cyclin-dependent kinase inhibitor 1A (p21), and cyclin-dependent kinase inhibitor 2A (p16) were detected by Western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence staining. The activity of glutathione peroxidase (GPx) was determined using a glutathione peroxidase assay kit. The direct binding between Gen and Prdx6 was verified by molecular docking. Finally, Prdx6-siRNA silencing experiment was performed to clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group, the C28/I2 chondrocyte viability significantly increased ( P<0.01), the expression of senescence-associated proteins p21 and p16 decreased ( P<0.01, P<0.05), the expression of senescence-associated genes p21 and p16 reduced (both P<0.01), the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished ( P<0.05, P<0.01), and the proportion of SA-β-gal-positive cells decreased ( P<0.01) in the Gen+etoposide group. Compared with the Control group, the expression of Prdx6 was downregulated in the etoposide group ( P<0.05). Compared with the etoposide group, the expression of Prdx6 was upregulated in the Gen+etoposide group ( P<0.01). Compared with the Control group, the GPx activity significantly decreased in the si-Prdx6 group ( P<0.01). Furthermore, compared with the si-Prdx6 group, the GPx activity increased in the si-Prdx6+Gen group ( P<0.05). Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown, the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group (both P<0.01). Conclusion Gen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

Effects of androgens on cognitive function in castration male mice

Zhang Yaqi1，Hui Cancan² , Ren Fang³ , Xu Min1，Jiang Zilong⁴ , Deng Datong1，⁵

DOI: 10.19405/j.cnki.issn1000-1492.2026.03.010

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Abstract:
Objective To establish a castrated male mouse model and to preliminarily investigate the effects of tes_ tosterone replacement therapy（TRT）on behavior ，serum indices ，and histopathological changes in castrated mice，as well as to explore the role of androgens in cognitive function. Methods Forty 6-month-old male C57/ BL6J mice were randomly divided into sham operation group，castration group，testosterone propionate（0. 5 mg/ kg）treated group，and testosterone propionate（1. 0 mg/kg）treated group，with 10 mice in each group. Following castration and subcutaneous administration of testosterone propionate at different doses（0. 5 and 1. 0 mg/kg）for TRT，learning and memory abilities were assessed using the Morris water maze（MWM）test and the passive avoid_ ance test. Serum testosterone and serum brain-derived neurotrophic factor（BDNF）levels were measured by ELISA，and histopathological changes in the hippocampus were examined using hematoxylin-eosin（HE）staining. Results Routine observations：there were no statistically significant differences in body weight among groups at any time point. MWM test：compared with castration group，sham operation group and testosterone propionate- treated groups（0. 5，1. 0 mg/kg）showed significantly reduced escape latency on days 4 and 5（P<0. 05），while the number of platform crossings and the time spent in the target quadrant significantly increased（P<0. 05）. Pas_ sive avoidance test：the number of passive avoidance errors significantly decreased in sham operation group and tes_ tosterone propionate（1. 0 mg/kg）-treated group（P<0. 05）， and the passive avoidance latency was significantly prolonged in sham-operated group and testosterone propionate-treated groups（0. 5，1. 0 mg/kg）（P<0. 05）. Serum testosterone and serum BDNF assays：serum testosterone levels and serum BDNF concentrations significantly in_ creased in sham operation group and testosterone propionate-treated groups（0. 5 ，1. 0 mg/kg）（P<0. 01）. HE staining：compared with sham operation group，neuronal density in all hippocampal subregions was slightly re_ duced in castration group；in the testosterone propionate（0. 5 mg/kg）-treated group，neuronal arrangement in the CA 1 and CA3 regions was improved and apoptotic cells were reduced compared with castration group；in testoster_ one propionate（1. 0 mg/kg）-treated group，the pyramidal cell layer in the CA3 region was more compactly ar_ ranged，with fewer apoptotic cells than in castration group. Conclusion TRT improves learning and memory per_ formance in castration male mice，potentially through modulation of hippocampal BDNF signaling pathways.

Salidroside exerts cytoprotective effects on bone marrow-derived endothelial progenitor cellsviathe AMPK pathway in atherosclerotic mice

Jia Fang; Wang Mengfei; Fei Sifan; Xu Jiayi; Yu Tianhong; Zhu Lin; Zhou Min

DOI: 专辑：医药卫生科技

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