Acta Universitatis Medicinalis Anhui

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Anhui Provincial Education Department

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Anhui Medical University

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Weng Jianping

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Follow-up study on hypertriglyceridemia after acute pancreatitis

Zhao Xinyue1,2,Shi Xiaolei1,2,Hu Lianghao3,Lu Guotao1,2,Pan Jiajia4

DOI: 专辑：医药卫生科技

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abstract:
To analyze the temporal changes in lipid levels in patients following acute pancreatitis(AP) and explore the factors associated with post-AP serum triglyceride(TG) level changes. Methods Patients diagnosed with AP at a Hospital in Yangzhou between January 2017 and December 2020 were included in this study. Clinical data were collected retrospectively, and lipid profile data from follow-up visits after discharge were tracked. The follow-up period extended until January 1, 2024. Kaplan-Meier(K-M) curves were used to stratify follow-up duration, while Spearman correlation analysis assessed the relationship between lipid levels and follow- up time. A linear regression model was used to investigate factors influencing TG level changes post-AP. Results A total of 141 patients with 306 follow-up visits were included. Spearman correlation analysis showed a mild increase in lipid levels over time post-discharge: TG(r=0.159, P=0.005), total cholesterol(TC)(r=0.231, P＜0.000 1), High-Density Lipoprotein Cholesterol(HDL-C)(r=0.181, P=0.002), and ApolipoproteinA1(ApoA1)(r=0.371, P < 0.000 1). In the univariate linear mixed model,male gender(β=0.160,P=0.007), Body Mass Index(BMI) (β=0.017, P=0.007), diabetes history(β=0.138, P=0.030), smoking history(β=0.166,P=0.004),and recurrent AP(β=0.119, P=0.029) were significantly associated with Lg(TG) levels (P<0.05). In the multivariate model, BMI(β=0.019, P=0.042), smoking history(β=0.155, P=0.049), and recurrent AP(β=0.148,P=0.032) remained significantly positively correlated with changes in Lg(TG) levels after AP, albeit with a low correlation strength (r < 0.200). Conclusion Lipid levels, including TG, TC, HDL-Cand ApoA1, tend to increase over time in AP patients after discharge, with this trend being more pronounced in those with hypertriglyceridemic acute pancreatitis. Post-AP TG levels are significantly influenced by BMI at the time of onset, smoking history and recurrent AP.

Bioinformatics analysis of differentially expressed genes in DCX-overexpression glioma Cells

Zhou Lingxin1 ，Iqra Nadeem2 ，Qin Yuxia 1 ，Xiong Ye 1

DOI: 专辑：医药卫生科技

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abstract:
To investigate the role mechanism of doublecortin (DCX) in glioma and screen DCX overexpression-related differentially expressed genes, so as to provide new targets for glioma targeted therapy.Methods Using rat glioma C6 cells as the target cells, LV-DCX-EGFP, LV-Cas9-Puro, and LV-Ctrl-EGFP lentiviruses were constructed. DCX overexpressing and control C6 cell lines were established through Cas9 dual- vector system transfection and screening. Transcriptome sequencing was used to obtain the differentially expressed gene profiles. iDEP and DESeq2 were applied to screen differentially expressed genes with the threshold of |log2FC|>2 and P<0.05. STRING and Cytoscape were utilized to construct protein-protein interaction networks and screen key genes. DAVID was employed for Gene Ontology (GO) enrichment analysis. BUSCA and UniProt were used to predict the subcellular localization of key genes. Receiver operating characteristic (ROC) curves were plotted to verify the diagnostic value of key genes. Enrichr was adopted to predict the regulatory networks of transcription factors and miRNAs. Real-time quantitative PCR (RT-qPCR) was performed to validate the expression of key genes. Results A total of 45 upregulated and 47 downregulated differentially expressed genes were screened, and 6 upregulated key genes including POU2F3 and 5 downregulated key genes including UBB were identified. GO enrichment analysis showed that upregulated genes were enriched in biological processes such as the positive regulation of lipid biosynthesis, whereas downregulated genes were linked to molecular functions including the regulation of alkaline phosphatase activity. Key genes were mainly distributed in the nucleus and cytoplasm. Except for RPS17, all key genes had an AUC value >0.7, indicating good diagnostic value. RT-qPCR validation showed that the mRNA expression levels of some upregulated genes (POU2F3,LPAR6, SREBF1) significantly increased (P<0.001), while the mRNA expression levels of some downregulated genes (UBB, ACTB, UBE2I) also significantly increased (P<0.001), which might be related to transcriptional and post-transcriptional regulation. Conclusion Differentially expressed genes and their regulatory networks related to DCX overexpression in glioma are successfully screened, providing a theoretical basis for revealing the role mechanism of DCX in glioma development and laying a foundation for the development of potential therapeutic strategies.

Investigating the mechanism of Xanthatin in inhibiting proliferation of laryngeal squamous cell carcinoma cells based on network pharmacology, transcriptomics, and experimental validation

Ma Zichuang1, Su Dan2, Wang Chun3, Wu Na4, Wang Haikun1,4, Shen Aizong5

DOI: 专辑：医药卫生科技

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abstract:
To investigate the potential mechanisms of Xanthatin in inhibiting the proliferation of laryngeal squamous cell carcinoma (LSCC) cells by integrating network pharmacology and in vitro experiments. Methods The targets of Xanthatin were identified using databases such as PharmMapper, while disease-related targets for LSCC were obtained from databases such as DisGeNET. The overlapping targets between Xanthatin and LSCC were determined by intersecting these datasets. A protein-protein interaction (PPI) network was constructed based on the overlapping targets, and key targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping targets were performed using R software. A "Xanthatin-target-pathway" network was visualized using Cytoscape 3.8.0 software. The preliminary validation of the aforementioned results was performed using molecular docking and transcriptomics. The effects of Xanthatin on the proliferation of TU177 cells were assessed using CCK-8 and colony formation assays. Additionally, Western blot analysis was employed to measure the expression levels of PI3K, p-PI3K, Akt, and p-Akt proteins. Results A total of 159 overlapping targets between Xanthatin and LSCC were identified, and seven key targets, including AKT1, were screened. GO enrichment analysis yielded 2,455 entries, and KEGG enrichment analysis identified 172 pathways, such as the PI3K-Akt signaling pathway. Xanthatin exhibited favorable binding activity with the core target proteins of LSCC in molecular docking experiments. The transcriptomics results showed high consistency with the predictions from network pharmacology. CCK-8 and colony formation assays demonstrated that Xanthatin at concentrations of 1, 2, and 4 μmol/L significantly inhibited the proliferation of TU177 cells in a dose-dependent manner. The expression levels of p-PI3K and p-Akt proteins decreased with increasing concentrations of Xanthatin. Conclusion Xanthatin may exert an inhibitory effect on the proliferation of laryngeal squamous cell carcinoma (LSCC) cells by modulating the PI3K-Akt signaling pathway.

Recent advances in the study of CGRP receptor antagonists in migraine

Song Xiaowen1 ，Li Bin1 ，Wu Xintong2 ，Sun Linshan1 ，Zhuang Wei1

DOI: 专辑：医药卫生科技

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Clinical characteristics and risk factors of 2054 cases of mycoplasma pneumoniae pneumonia in children based on imaging and clinical severity classification

Li Jiao1, Zhou Jiantao1, Ha Qingxu1, Huo Shaohu1, Ding Junli1,2

DOI: 专辑：医药卫生科技

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abstract:
To investigate the clinical characteristics and risk factors of Mycoplasma pneumoniae pneumonia (MPP) based on a dual classification integrating imaging features and clinical severity. Methods Medical records of 2054 pediatric patients with MPP were retrospectively analyzed. The cohort was stratified into severe consolidation (n=253), severe non-consolidation (n=118), non-severe consolidation (n=393), and non-severe non-consolidation groups (n=1 290) based on clinical and radiological findings. Inter group data and characteristics were compared and multiple regression analysis was conducted to construct a prediction model for severe consolidation group. Results Significant differences were observed among the groups in terms of age, duration of fever, length of hospital stay, presence of pulmonary rales, inflammatory markers (CRP, LDH), the use of hormones, and bronchoscopic treatment (all P < 0.05). Compared with the severe non-consolidation group, non-severe consolidation group, and non-severe non-consolidation group, children with severe consolidation pneumonia caused by MPP exhibited the longest duration of fever [8 (6, 11) days vs 6 (2, 9), 7 (6, 9) and 6 (3, 8) days, respectively] and the longest length of hospital stay [7 (5, 8) days vs 6 (5, 8), 6 (5, 8) and 6 (4, 7) days, respectively]. They also had the highest incidence of reduced breath sounds [34 cases (13.4%) vs 2 cases (1.7%), 29 cases (7.4%) and 13 cases (1.0%), respectively] and a substantially higher rate of coinfections, particularly viral infections [63 cases (24.9%) vs 23 cases (19.5%), 60 cases (15.3%) and 190 cases (14.7%), respectively]. Multivariate analysis indicated that the independent risk factors for severe MPP (SMPP) were age > 4.5 years, length of hospital stay > 6.5 days, reduced breath sounds, neutrophil-to-lymphocyte ratio (NLR) > 1.66, LDH > 370.5 u/L, CRP > 9.5 mg/L, and coinfection with viruses. Reduced breath sounds (OR = 5.58, 95% CI: 2.45 - 12.69) and coinfection with bacteria (OR = 3.11, 95% CI: 1.43 - 6.75) were identified as the most significant risk factors for pulmonary consolidation in non-severe MPP children. Additionally, reduced breath sounds, coinfection with viruses, LDH > 365.5 u/L, and CRP > 32.1 mg/L were risk factors for severe pneumonia in children with pulmonary consolidation. For non-consolidation MPP children, the presence of pulmonary dry rales (OR = 2.28, 95% CI: 1.46 - 3.56) was the primary independent risk factor for the development of severe pneumonia. Conclusion The chest imaging findings of MPP are associated with clinical severity, and the risk factor model constructed based on this imaging-clinical classification can assist in achieving precise hierarchical diagnosis and treatment in clinical practice.

A Preliminary Study on Toxoplasma gondii Interfering with Copper Metabolism Pathways in Mouse Kidney

Yang Jun1,2,3, Ren Chuanming2,4, Liu Min1,2,3, Wang Kunting2,4, Chen He5, Cai Yihong1,3

DOI: 专辑：医药卫生科技

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abstract:
To investigate the effect of Toxoplasma gondii infection on copper metabolism in the kidneys of mice. Methods A total of 80 7-8-week-old C57BL/6 female mice were randomly divided into four groups of 20 mice in each group after one week of adaptation, including Control group, Cu group, TgCtwh6 group and Cu+TgCtwh6 group. Mice that were not infected and fed with normal diet and water were used as the Control group; Mice fed with 1 g/kg of copper chloride processing diet and 0.1% copper chloride water for 60 consecutive days were used as Cu group; Mice infected with 25-30 TgCtwh6 cysts (one of the predominant genotype Chinese 1 in China) fed with normal diet and water were used as the TgCtwh6 group; mice infected with 25-30 TgCtwh6 cysts and fed with a processed diet containing 1 g/kg of copper chloride and water with 0.1% copper chloride for 60 consecutive days were used as the Cu+TgCtwh6 group. ICP-MS was used to determine the changes in copper content in kidney tissues. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of mouse kidney tissue. The number of apoptotic cells was observed by PI staining. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD1, SOD2).RT-qPCR was used to detect the mRNA expression of cuproptosis-related genes. Results Pathological manifestations such as inflammatory cell infiltration in the Cu group and TgCtwh6 group were seen under the microscope, and the inflammatory infiltrating cells of the renal interstitial were reduced in the Cu+TgCtwh6 group, and the pathological manifestations of glomerular tubular structure were improved. The number of apoptotic cells in the Cu+TgCtwh6 group (88.36±19) was lower than that in the Cu group (119.0±20). Compared with the Cu+TgCtwh6 group, the expression of SOD1 protein was down-regulated, and the difference was statistically significant (P<0.05). TgCtwh6 infection could restore the down-regulation of renal GLS expression and the up-regulation of ATP7B expression caused by copper overload. Conclusion Toxoplasma gondii infection can interfere with the copper metabolism pathway in the kidney of mice, improve the kidney damage caused by copper overload, and provide new clues for the treatment of copper overload disease.

AVBM study on gray matter structure alterations in patients with Alzheimer’s disease comorbid with apathy

Ji Yi1, Pang Xuerui1, Yang Chaoyi1, Dai Yulong1, Zhou Shanshan1, Wu Xingqi1, Wang Kai1,2

DOI: 专辑：医药卫生科技

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abstract:
To investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease (AD) comorbid with apathy (AD with apathy, AD-A). Methods The study included 30 patients with AD-A, 30 Alzheimer's disease patients without apathy (AD without apathy, AD-NA), and 30 healthy controls (HCs) matched in gender, age, and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) was used to analyze changes in gray matter volume among the three groups. Additionally, the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. Results There were no statistically significant differences among the three groups in terms of age, gender, years of education, or total intracranial volume. Compared with the HCs group, both the AD-A and AD-NA groups showed significantly lower scores in cognitive function (P<0.001). The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group (P<0.001). Compared with the AD-NA group, the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus, left orbitofrontal cortex, lingual gyrus, inferior frontal gyrus, superior frontal gyrus, entorhinal cortex, right middle frontal gyrus and posterior cingulate cortex (FWE-corrected, P<0.05 for all). Compared with the HCs group, the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus, left fusiform gyrus, calcarine sulcus, postcentral gyrus, right inferior frontal gyrus and supramarginal gyrus (FWE-corrected, P<0.05 for all). Compared with the HCs group, the AD-NA group showed reduced gray matter volume in the left precuneus, inferior temporal gyrus, and right inferior temporal gyrus (FWE-corrected, P<0.05 for all). In the AD-A group, changes in the gray matter volume of the left caudate nucleus (r= -0.557, P=0.002) and right middle frontal gyrus (r=-0.620, P=0.001) were negatively correlated with the apathy evaluation scale (AES) scores. Conclusion Patients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit, and the degree of gray matter atrophy was correlated with the severity of apathy.

Knockdown TMEM16B reduces brain edema and protects the blood-brain barrier after cerebral ischemia-reperfusion injury in rats

Zhang Jingbin1,2 ，Liu Qian1 ，Pan Ziyan1 ，Yao Tianxi1 ，Yin Jiangwen1,2

DOI: 专辑：医药卫生科技

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abstract:
To explore the effects of transmembrane protein 16B(TMEM16B) on brain edema and blood-brain barrier after cerebral ischemia-reperfusion injury in rats. Methods TMEM16B overexpression and knockdown was performed by adeno-associated virus (AAV), and then adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO). Rats were randomly divided into Sham group, MCAO group, AAV no-load group, TMEM16B overexpression group and TMEM16B knockdown group. Modified neurological severity scores, adhesive removal test and cylinder test were used to evaluate neurologic function.The ultrastructure of ischemic brain tissue was observed by transmission electron microscope. Brain water content was reflected by dry wet weight ratio of brain tissue. The expressions ofTMEM16B, aquaporin4(AQP4), Claudin5 and zonula occludens-1 (ZO-1) were investigated by immunofluorescence and Western blot. Results Compared with the AAV no-load group, the sensory and motor functions of rats in TMEM16B overexpression group were significantly impaired. Mitochondria were swollen; mitochondrial cristae and tight junctions disappeared. The brain water content was higher in overexpression group. The expression ofTMEM16B and AQP4 increased while the expression of Claudin5 and ZO-1 decreased. Compared with the AAV no-load group, the rats in TMEM16B knockdown group showed some recovery in motor function. The mitochondrial cristae and structure were clear, and the basement membrane was partially blurred. The brain water content was lower in knockdown group. The protein levels ofTMEM16B and AQP4 were lower while the levels ofClaudin5 and ZO-1 were higher than that in AAV no-load group. Conclusion An increase in TMEM16B aggravates brain edema and blood-brain barrier damage in rats after cerebral ischemia-reperfusion injury, while a decrease in TMEM16B expression alleviates brain edema and protects the blood-brain barrier.

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