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Objective To explore the breeding and genotyping of CCR2 knockout mice, and to verify the applicability of the polymerase chain reaction(PCR) method for genotype detection of CCR2 knockout mice. Methods The introduced CCR2 pure male mice and wild-type female mice were mated and bred to produce the offspring generation, the obtained F1 generation heterozygous mice were continued to be mated. DNA was extracted by clipping the tail tissues of the mice at the age of 2 weeks, the target gene fragment was amplified by PCR, and the genotypic results were determined by agarose gel electrophoresis. The proportion of purebred progeny carrying the CCR2 knockout gene was increased by genetic crosses, the effect of CCR2 knockout in the progeny mice was verified by using Western blot against major immune cells and key organs, and flow cytometry was used to detect whether the knockout of the CCR2 gene had any effect on the function of the immune system by targeting the major immune cells. Results CCR2 knockout mice were successfully bred and characterized, and three genotypes of F2 generation mice were obtained: CCR2+/+, CCR2+/-, and CCR2-/-. The offspring genotypes were identified by PCR, and Western blot showed extremely low CCR2 protein expression in CCR2 knockout mice. Flow analysis showed that CCR2 knockdown reduced the expression of CD4+T and Th1 cells in mouse spleen-derived T cells, but did not affect macrophage function. Conclusion Correct breeding and identification are important ways to get the pure CCR2 knockout mice, and PCR method for identifying mouse genotypes is simple, fast and reliable.

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Objective To investigate the effects of astragalus mongholicus extract(AME) on lung injury and the myeloid differentiation factor 88(MyD88)/Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB) p65 pathway in rheumatoid arthritis induced interstitial lung disease(RA-ILD) rats. Methods SD rats were randomly divided into a control group, RA-ILD group, low-dose AME group(5 g/L), high-dose AME group(10 g/L), and high-dose AME+lipopolysaccharide(LPS) group(10 g/L AME+1 mg/L TLR4 activator LPS). Except for the control group, rats in all other groups were injected with bovine type Ⅱ collagen, Freund's complete adjuvant, and bleomycin to establish the RA-ILD model. The arthritis index and lung tissue wet-dry weight ratio of rats were tested. ELISA was applied to detect the levels of inflammatory factors interleukin(IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α) in bronchoalveolar lavage fluid. Hematoxylin eosin staining was used to observe pathological changes of rat knee joint tissue and lung tissue. Western blot was applied to detect the expression of autophagy factors Beclin 1, microtubule-associated protein 1A/1B-light chain 3(LC3) Ⅱ/Ⅰ, and MyD88/TLR4/NF-κB p65 pathway related proteins in lung tissue. Results Compared with control group, knee joint tissue and lung tissue of rats in RA-ILD group were damaged, the arthritis index, lung tissue wet-dry weight ratio, levels of IL-1β, IL-6, and TNF-α, the expression levels of MyD88 and TLR4 proteins, and p-NF-κB p65/NF-κB p65 ratio increased(P

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Objective To explore the effects of the antihypertensive drug Amlodipine on calcium influx and autophagy in human podocytes(HPC). Methods HPC cells were routinely cultured in vitro. HPC cells were treated with angiotensin Ⅱ(Ang Ⅱ), the L-type Ca2+ blocker Amlodipine alone or in combination. The Ca2+ imaging system was used to detect the transient changes in the intracellular Ca2+ flux of HPC cells in real time after drug treatment. Western blot was employed to detect the changes in the ratio of autophagy marker proteins LC3B-Ⅱ/LC3B-Ⅰ, and the expression levels of Beclin-1, P62, as well as apoptosis-related proteins Bcl-2 and Bax. Flow cytometry was used to detect the number of Fluo-4AM positive cells at 488 nm to analyze the level of intracellular Ca2+ influx in HPC cells. Lyso-Tracker Green live cell staining was applied to analyze the fluorescence intensity of lysosomes. Flow cytometry was also used to detect the apoptosis rate of HPC cells. Results Compared with the control group, in the Ang Ⅱ group, the transient Ca2+ flux and the number of Fluo-4AM positive cells increased significantly(P

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Objective To investigate the effect of solasonine regulation of the STAT3 signaling pathway on the biological behavior of lung adenocarcinoma cells. Methods H1299 cells were treated with 0.125, 0.25, 0.5 and 0.75 mmol/L solasonine, respectively. The proliferative activity of H1299 cells was detected by CCK-8. The migration and invasion ability of H1299 cells were detected by scratch, Transwell migration and invasion assay. The apoptosis level of H1299 cells was detected by flow cytometry and Hoechest 33258/PI double staining. The protein expression levels of STAT3, p-STAT3, Bcl-2, Bax, Caspase-3, Cl-Caspase-3, Snail, Slug, N-cadherin and E-cadherin in H1299 cells were detected by Western blot assay. Results Solasonine at different concentrations significantly reduced the proliferation of H1299 cells(P

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Objective To investigate the role and mechanism of PGC-1α-mediated mitochondrial biosynthesis in AMP-activated protein kinase(AMPK) agonist anti-hepatic ischemia-reperfusion injury(HIRI).Methods SD rats were randomly divided into Control group, HIRI group, HIRI+AICAR group, HIRI+SR-18292 group and HIRI+AICAR+SR-18292 group, with 8 rats in each group.The rats were intraperitoneally injected with AICAR(500 mg/kg) or SR-18292(32 mg/kg) before operation, and then the HIRI model was established by non-invasive vascular clamp clamping method.The samples were taken 24 hours after reperfusion.The contents of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in serum and the levels of malondialdehyde(MDA),superoxide dismutase(SOD) and adenosine triphosphate(ATP) in liver tissue were detected.HE staining was used to observe the pathological changes of liver tissue.The level of reactive oxygen species(ROS) and the changes of mitochondrial membrane potential in liver tissue were detected by fluorescence probe.The copy number of mitochondrial DNA(mtDNA) and the mitochondrial biosynthesis-related genes PGC-1α,NRF1,TFAM,UQCRC2 and other mRNA expression levels were detected by qRT-PCR.Western blot was used to detect the protein expression levels of AMPKα,p-AMPKα,mTOR,p-mTOR,PGC-1α and TFAM in liver tissue.Results Compared with the control group, the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI group increased, while the levels of SOD and ATP decreased(all P

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Objective To explore the role and mechanism of 25-hydroxycholesterol(25-HC) in inflammatory bowel disease(IBD) in mice. Methods All mice were divided into three groups: the control group was fed normally; the DSS model group was fed with 2.5% dextran sulfate sodium(DSS) solution; the DSS + 25-HC experimental group was fed with 2.5% DSS solution and he mice in the experimental group were intraperitoneally injected with 25-HC. The symptom changes of the mice were evaluated by assessing the disease activity index( DAI),and the tissue changes were judged by histological scoring. The expression of interleukin-17 and its signaling pathways in the mice were detected by Western blot,qRT-PCR,immunohistochemistry/fluorescence,and flow cytometry. Combined with the detection of tight junction proteins in the intestinal epithelium of the mice,the mechanism by which 25-HC affects IBD in mice was explored. Results In comparison to the DSS control group,The DSS + 25-HC experimental group mice exhibited a reduction in body weight(F = 30. 1,P

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Objective To investigate the effect of environmental enrichment on cognitive impairment and hippocampus GAP-43 changes induced by exposure to obstructive sleep apnea-hypopnea syndrome(OSAHS) during the period of late pregnancy in mice, and to explore relative inflammatory pathway mechanism. Methods The experimental group of C57BL/6J pregnant mice were exposed to an intermittent hypoxic environment for 7 consecutive days starting from gestational day 15. The corresponding offspring were then placed in an enriched environment from postnatal day 21 to 2 months of age(designated as OSAHS+EE group) or in a normal environment(designated as OSAHS group). Pregnant mice in the control group were maintained in a normal oxygen environment, and their corresponding offspring were placed in an enriched environment(designated as Control+EE group) or a normal environment(designated as Control group) at the same ages. The spatial learning and memory ability of the mice was assessed by Morris water maze at the age of 2 months. The mRNA levels of NF-kB, NLRP3 and GAP-43 in the hippocampus were detected by real-time fluorescence quantitative PCR, and the protein levels of NLRP3 and GAP-43 in the hippocampus were detected by Western blot. Results Compared with Control group, the swimming distance increased(P

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Objective To investigate the expression and clinical significance of kynurenine-3-monooxygenase(KMO) in peripheral blood mononuclear cells(PBMC), synovial tissue, and fibroblastic-like synovial cells(FLS) of rheumatoid arthritis(RA) patients. Methods Peripheral blood samples from 25 healthy control(HC) individuals and 25 patients diagnosed with RA were collected, and real-time fluorescence quantitative PCR and Western blot were used to detect KMO gene and protein expression in PBMC of RA and HC groups, and to analyze the correlation between the expression level of the KMO gene in the PBMC of the RA patients and the indexes of the laboratory tests. Meanwhile, immunohistochemistry and immunofluorescence were used to detect KMO expression in synovial tissue and FLS in RA and HC groups. Results(1) KMO gene and protein expression in PBMC of RA group were higher than that of HC group, and the difference was statistically significant(Ps=0.417, P=0.038; r=0.545, P=0.005; rs=0.433, P=0.031), and had no correlation with C-reactive protein and anti-cyclic citrullinated polypeptide antibody.(3) KMO expression in synovial tissue of RA group was higher than that of HC group, and the difference was statistically significant(P

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Objective To analyze the distribution characteristics of free water(FW) and FW-corrected fractional anisotropy(FAt) in the white matter of the brain in patients with anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis and to explore their correlation with cognitive function. Methods A total of 38 patients with anti-NMDAR encephalitis and 30 controls were recruited from three hospitals in Hefei. Diffusion tensor imaging data and neuropsychological assessment results were collected. Tract-Based Spatial Statistics was applied to compare group differences in FW and FAt across the whole brain white matter. Correlation analyses were further performed to examine the relationships between FW/FAt metrics and cognitive function. Results Compared to the control group, patients with anti-NMDAR encephalitis showed significantly lower scores on the montreal cognitive assessment, immediate recall, delayed recall, and the verbal fluency test(all P

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Objective To explore the molecular mechanism of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1(MALAT1)/microRNA-15b-5p(miR-15b-5p) regulating the Wnt/β-catenin pathway in lipopolysaccharide(LPS)-induced chondrocyte injury in osteoarthritis. Methods ATDC5 cells were treated with 5 mg/L LPS to establish the osteoarthritis cell injury model, and the expression levels of MALAT1 and miR-15b-5p in the cells were detected by RT-qPCR. The MTT, flow cytometry, Alizarin red staining, and ELISA were used to assess the effects of MALAT1 and miR-15b-5p on LPS-induced chondrocyte injury. The dual-luciferase reporter gene assay was used to examine the regulatory relationship between MALAT1 and miR-15b-5p. Western blot assay was used to evaluate the expression of relevant proteins. Results In LPS-induced ATDC5 cells, MALAT1 expression decreased(P

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Objective To construct a lentiviral overexpression cell line of HACE1 and to investigate its effects on the proliferation and migration of glioma cells. Methods Using the bacterial liquid containing the full-length cDNA sequence of human HACE1 as a template, the lentiviral expression plasmid pCDH-HACE1 was constructed, and the lentiviral cell line was screened. Western blot was employed to detect the expression of HACE1 in glioma cells. Meanwhile, the CCK-8 assay and the cell scratch assay were utilized to assess the impacts of HACE1 on the proliferation and migration of glioma cells. Results The lentiviral cell line with HACE1 overexpression was successfully established. Western blot analysis demonstrated that HACE1 could be effectively expressed in eukaryotic cells. The results of the CCK-8 assay showed that, compared with the control group, the cell proliferation in the HACE1 overexpression group was significantly enhanced at 24 hours and 48 hours after cultivation(both P

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Objective To investigate the effects of acarbose and pioglitazone on the levels of sex hormones in adult female rats, and to explore their regulatory effects on the hypothalamic-pituitary-ovarian axis(HPOA) and its mechanism. Methods Adult female SD rats aged 2 months were randomly divided into 0.9% sodium chloride solution control group(NS), acarbose low(AL), medium(AM) and high(AH) dose groups and pioglitazone low(PL), medium(PM) and high(PH) dose groups. AL, AM and AH groups were given 20, 40 and 60 mg/(kg·d) acarbose, and PL, PM and PH groups were given 5, 10 and 15 mg/(kg·d) pioglitazone, respectively. After 28 days of intervention, serum gonadotropin(FSH, LH) and ovarian secreted hormone(E2, P, T) were detected by ELISA, and the effects of acarbose and pioglitazone on HPOA were investigated by organ index analysis and histopathological observation of pituitary gland and ovary. Results Compared with the NS group, the serum FSH in the PL, PM and PH groups decreased(all P

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Objective To construct the K64 capsule depolymerase recombinant protein, Dep44, and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP) infections. Methods The depolymerase-encoding phage vB＿Kpn＿HF1013(GenBank: PP803128) was isolated and genomically analyzed to screen for candidate depolymerases. The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity. Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by biofilm disruption and serum sterilization assays. Results The tail spike protein of phage vB＿Kpn＿HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule. Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial biofilms relative to the control. Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum, dependent on the complement system, as Dep44 alone lacked bactericidal properties. Conclusion Dep44 effectively targets and degrades K64 CRKP capsule, disrupts biofilms, and enhances serum bactericidal activity, highlighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

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Objective To explore the effect and mechanism of total saponins of astragalus membranaceus combined with bone marrow mesenchymal stem cells(BMSCs) regulating the stromal cell-derived factor-1(SDF-1)/chemokine receptor 4(CXCR4) pathway in the treatment of autoimmune premature ovarian failure(POF) model rats. Methods Rats were randomly divided into POF group, total saponins of astragalus membranaceus group, BMSCs group, combination group, combination+SDF-1/CXCR4 pathway inhibitor(AMD3100) group, and control group, with 12 rats in each group. Except for the control group, all other groups of rats needed to construct a POF model. After successful modeling, treatment would begin. The drug injected into the tail vein once a week, and the drug injected into the abdominal cavity once a day for 4 weeks. ELISA was applied to detect the levels of anti ovarian antibodies(AOAB), β-endorphin(β-EP), vascular endothelial growth factor(VEGF), tumor necrosis factor-α(TNF-α), and interferon-γ(INF-γ) in serum. Changes in ovarian index were detected. HE staining was applied to detect the number of mature follicles, developing follicles, and blocked follicles in the ovary. Flow cytometry was applied to detect the proportion of BMSCs in the ovaries. QRT-PCR was applied to detect the mRNA expression of mesenchymal transition factor(cMET), hepatocyte growth factor(HGF), SDF-1, and CXCR4 in ovarian tissue. Western blot was applied to detect SDF-1 and CXCR4 proteins in ovarian tissue. Results Compared with the control group, the serum levels of AOAB, TNF-α, INF-γ, and the number of blocked follicles in the ovaries were higher, while the serum levels of β-EP, VEGF, ovarian index, the numbers of mature follicles and developing follicles in the ovary, the expression of SDF-1, CXCR4 mRNA and protein were lower in the POF group(P

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Objective To explore the mechanism of cistanche deserticola(meat cistanche) in treating Alzheimer′s disease(AD) through network pharmacology, molecular docking, and animal experiments. Methods Effective components of meat cistanche were mined from the TCMSP database, and AD-related targets were filtered using the SwissTargetPrediction, DisGeNET, and GeneCards databases. The intersection of these targets was analyzed using protein-protein interaction(PPI) networks. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were conducted via the Metascape database. Molecular docking of meat cistanche′s active components with core targets was performed using AutoDock Vina. Based on network pharmacology predictions, an AD model was established using 8-month-old SAMP8 mice, with Morris water maze tests assessing learning and cognitive functions, Nissl staining observing hippocampal neuron morphology, and enzyme-linked immunosorbent assays and Western blotting detecting the expression levels of cAMP signaling pathway-related proteins in hippocampal tissues. Results Network pharmacology analysis predicted that meat cistanche might act on 74 AD targets through 8 active components. Molecular docking showed high affinity of active components like acteoside with core targets such as ESR1, BDNF, MAPK1, and APP. KEGG analysis indicated involvement in pathways related to cancer, cAMP signaling, and AD. Animal experiments demonstrated that meat cistanche effectively improved learning and cognitive impairments in AD mice and alleviated hippocampal neuron damage. ELISA and Western blotting results indicated that meat cistanche significantly increased the expression levels of cAMP, PKA, P-CREB in the cAMP pathway and promoted the expression of downstream neurotrophic factor BDNF. Conclusion Meat cistanche can improve learning and cognitive disorders in AD model mice and may exert therapeutic effects on AD by up-regulating the cAMP signaling pathway and the expression of downstream BDNF protein targets, thereby improving hippocampal neuron injury.

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Objective To investigate whether armillariella tabescens polysaccharides(ATPS) alleviates inflammatory responses and tissue damage in 5-fluorouracil(5-FU)-induced chemotherapy-induced intestinal mucositis(CIM) by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Methods Thirty 8-weeks-old male C57BL/6J mice were randomly divided into five groups(n=6 per group): control group, model group, and ATPS-treated groups(low, medium, high dose: 100,200,400 mg/kg). Body weight changes were recorded; Disease activity index(DAI) scores were evaluated; small intestinal length and histopathology were measured; HE staining and histopathological scoring were performed; immunohistochemistry was used to detect the expression of tight junction proteins(ZO-1, Occludin) in the small intestine; serum levels of inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α) were analyzed by enzyme-linked immunosorbent assay(ELISA) kit; Western blot was employed to quantify ZO-1, Occludin, and TLR4/MyD88/NF-κB pathway-related protein TLR4, MyD88,NF-κB p65, IκBα, p-NF-κB p65, p-IκBα protein expression. Results Compared with the control group, mice in the model group exhibited significant reductions in body weight, elevated DAI scores, shortened small intestinal length, increased histopathological scores, marked downregulation of ZO-1 and Occludin expression, and elevated levels of inflammatory cytokines TNF-α and IL-6. Additionally, protein expression levels of TLR4, MyD88, p-NF-κB p65, and p-IκBα were significantly upregulated(all P

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Objective To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

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Objective To generate heterozygous TRAF2 knockout mice, the CRISPR/Cas9 technology was successfully employed. These mice were served as a valuable model to explore the pathological mechanisms underlying inflammatory and immune disorders mediated by abnormal TNF-α-TRAF2 signaling and to develop new therapeutic targets. Methods A vector targeting the knockout of the TRAF2 gene was constructed. Lead RNA and Cas9 Mrna were introduced into the fertilized eggs of C57BL/6JGpt mice through microinjection to mediate the TRAF2 gene mutation in mice. The mouse tail protein was extracted and the genotype of the F0 generation was determined by PCR and Western blot. TRAF2+/- mice were successfully obtained. F0 generation mice were backcrossed with C57BL/6JGpt wild-type mice to obtain stable TRAF2+/- mice for propagation and subsequent experiments. The body weight of TRAF2+/- mice was detected; Western blot was used to detect the expression of TRAF2 in the spleen, liver and kidney tissues of TRAF2+/- mice. The development of spleen, liver and kidney tissues in TRAF2+/- mice was detected by HE staining. Results PCR identification using specific primers demonstrated that TRAF2+/- mice exhibited a target band at 679 bp. Western blot analysis results indicated that, compared with the WT group, the expression of TRAF2 in the tail protein of TRAF2+/- mice was significantly reduced(P+/- mice had a lower body weight compared to their littermate WT mice(P+/- mice was decreased(P+/- mice and WT mice. Conclusion The successful construction of TRAF2+/- mice has provided an important animal model for exploring the role of TRAF2 in developmental regulation, revealing the mechanism of inflammatory immune diseases mediated by abnormal TNF-α-TRAF2 signaling, and screening related drug targets.

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Objective To screen the risk factors of cesarean scar diverticula(CSD) after cesarean section and to construct a risk prediction model. Methods 491 cases of mothers who underwent cesarean section were recruited as the study subjects, and the data from the database of negative ultrasound of mothers who returned to the hospital 12 months after operation were collected, and the dataset was randomly divided into the training set and the test group according to 7 ∶3; the variables were screened to obtain the risk factors of CSD and the risk prediction model was constructed by the use of least absolute shrinkage and selection operator(LASSO); the variables were screened using the LASSO to obtain the characteristic variables, and the characteristic variables were analyzed by multifactorial logistic regression analysis, and the nomogram prediction model was constructed by using the R software. Results A total of 491 cases of sample data were included, including 344 cases in the training set and 147 cases in the test set; feature variables were screened by LASSO, and ten-fold cross-validation was used. Five variables were finally screened: number of cesarean deliveries, number of years between two cesarean deliveries, 24-hour hemorrhage, operation time and uterine position(P

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Objective To assess the association between Life eight(LE8) scores and diabetes mellitus(DM), and to examine the mediating effect of Methylmalonic acid(MMA). Methods Based on cross-sectional data from the 2011—2014 National Health and Nutrition Examination Survey(NHANES), weighted multivariable logistic regression analyses were conducted to assess the association between the LE8 score and DM. A mediation model was further constructed to evaluate the mediating effect of MMA. Results The weighted multivariable logistic regression analysis showed a significant negative correlation between LE8 score and the risk of DM. After adjusting for potential confounders, a 1-point increase in LE8 was associated with a 7% reduction in DM risk(OR=0.93, 95%CI: 0.92-0.93, P=0.000 1). In contrast, the level of circulating MMA did not show a statistically significant relationship with DM risk(OR=0.99, 95%CI: 0.89-1.10, P=0.886 8). Further subgroup analysis by age revealed that in participants under 60 years of age, circulating MMA levels were positively associated with DM risk(OR=1.39, 95%CI: 1.19-1.62, P

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Objective To investigate the hemolytic phenotypes of Staphylococcus aureus clinical isolates. Methods The hemolytic phenotypes of 105 Staphylococcus aureus isolates were analyzed and summarized using the three-point inoculation method. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of four hemolysin genes(hla, hlb, hlc, and hld); The VITEK 2 GP639 antimicrobial susceptibility card was used to detect resistance to commonly used antibiotics; DNA gel electrophoresis was performed to determine the prevalence of the mecA,sea,tst,and pvl genes; The microtiter plate crystal violet staining method was used to assess biofilm formation ability; The CCK-8 assay was used to evaluate cytotoxicity against macrophages. Results Seven hemolytic phenotypes were identified among the Staphylococcus aureus clinical isolates. Differences were found among Staphylococcus aureus clinical isolates with different hemolytic phenotypes in terms of mRNA expression levels of hemolysin genes,antibiotic resistance,virulence gene prevalence,biofilm formation ability,and cytotoxicity to mouse macrophages(P

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Objective To examine the relationship between the levels of endothelin-1(ET-1) and the severity of clinical symptoms in idiopathic inflammatory demyelinating diseases(IIDDs) of the central nervous system. Methods A total of 45 patients with central nervous system demyelinating diseases were enrolled in the study. Among them, 25 patients were diagnosed with idiopathic IIDDs, 20 had vascular demyelinating diseases of the central nervous system, and 10 healthy controls were also included. Serum ET-1 levels were assessed using ELISA, and a further analysis was conducted to investigate the correlation between these ET-1 levels, laboratory test results, and the degree of disease disability in the IIDDs patient group. Results(1) Of the three groups, ET-1 levels were highest in the IIDDs(Ps=0.503, P=0.010), CSF total protein(rs=0.475, P=0.016), CSF albumin(rs=0.480, P=0.020), CSF IgG(rs=0.544, P=0.007), IgA(rs=0.660, P=0.002) and IgM(rs=0.555, P=0.011) levels.(3) There was a positive correlation between serum ET-1 levels and CSF IgM levels(rs=0.455, P=0.044) in IIDDs group. Serum ET-1 level showed no significant correlation with peripheral immune reaction(P>0.05). Conclusion Serum ET-1 levels reflect the severity of clinical symptoms in IIDDs and show no significant correlation with peripheral immune markers, however, exhibit a positive correlation with disease severity and cerebrospinal fluid IgM levels. These findings suggest that serum ET-1 levels may indicate the degree of central nervous system inflammation and play an important role in the development and progression of IIDDs.

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Objective To explore the factors influencing the efficacy of first-generation EGFR tyrosine kinase inhibitors(EGFR-TKIs) in patients with EGFR-mutated advanced lung adenocarcinoma and to construct and validate a corresponding nomogram prediction model. Methods A total of 220 patients with EGFR-mutated advanced lung adenocarcinoma treated with icotinib were enrolled and randomly divided into a training group(154 cases) and a validation group(66 cases) in a 7 ∶3 ratio. Cox regression analysis was performed to identify factors affecting the efficacy of first-generation EGFR-TKIs in the training group. A prediction model was constructed, and calibration curves and receiver operating characteristic(ROC) curves were plotted to validate the model′s performance. Results In the training group, the objective response rate was 35.71%, the disease control rate was 77.27%, the median progression-free survival(PFS) was 12.5 months, the median overall survival was 18 months, the 2-year OS rate was 66.23%, and the PFS rate was 42.21%. Univariate analysis showed that brain metastasis, bone metastasis, TNM stage, differentiation degree, neutrophil-to-lymphocyte ratio(NLR), post-treatment p53 levels, p53 difference(Δp53), post-treatment cancer antigen gene(CAGE) levels, and CAGE difference(ΔCAGE) were associated with PFS(P2=4.429, P=0.351). ROC curve analysis in the training group showed that the nomogram model had a sensitivity of 80.00%, specificity of 77.53%, and AUC of 0.864 for predicting therapeutic efficacy, while the validation group showed a sensitivity of 74.08%, specificity of 71.43%, and AUC of 0.835. Conclusion Changes in lung cancer autoantibodies(Δp53 and ΔCAGE), TNM stage, and NLR are key factors influencing the efficacy of first-generation EGFR-TKIs in EGFR-mutated advanced lung adenocarcinoma. The nomogram prediction model based on p53 and CAGE demonstrates good predictive performance.

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Objective To investigate the correlation between the pan-immune inflammation value(PIV) and clinical and pathological features of primary IgA nephropathy(IgAN), and to evaluate the clinical significance of PIV in primary IgAN. Methods 200 patients with primary IgAN diagnosed by renal biopsy were selected as the research subjects. General information, laboratory indicators, pathologic features of renal biopsy, and calculations of platelet to lymphocyte count ratio(PLR), neutrophil to lymphocyte count ratio(NLR), PIV, and other relevant indices about patients were collected. According to the median PIV, subjects were divided into low PIV group(PIV≤194.81) and high PIV group(PIV >194.81), and the clinical and pathological data of the two groups were compared and analyzed. Using Spearman rank correlation analysis and logistic regression analysis, the relationship between PIV and primary IgAN in terms of clinical and pathological aspects was explored. Results There were statistical significance in age, gender, height, hyperuricemia, hemoglobin, absolute neutrophil count(ANC), absolute monocytes count, platelet, PLR, NLR, serum uric acid, immunoglobulin G(IgG), immunoglobulin A(IgA)/complement 3(C3), and fusion degree of the podocyte foot between the two sets(P

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Objective To investigate the differential expression of Yes-associated protein(YAP) in the healthy control group and in patients with rheumatoid arthritis(RA), and to explore its correlation with the progression of the disease. Methods Three cases each of synovial membranes from the healthy control group and RA group were selected for RNA-sequence detection to identify differentially expressed genes. Data and laboratory indicators from 50 healthy control cases and 150 RA patients who met the criteria were collected. ELISA was used to detect the expression of YAP in the serum of each group, and then its correlation with other laboratory indicators in RA patients was analyzed. The receiver operating characteristic curve was applied to explore the diagnostic efficacy of the related risk factors for RA. Results Expression of 14-3-3-gama, which regulated the disease process, was significantly down-regulated in the synovial membranes of RA patients compared to normal synovial membranes; YAP expression was significantly up-regulated in rheumatoid arthritis fibroblast-like synoviocytes compared to healthy controls and was correlated with haematological sedimentation, C-reactive protein, interleukin(IL)-1, IL-4, IL-6, IL-10, rheumatoid factor, anti-cyclic citrullinated polypeptide antibody, interferon alpha, tumour necrosis factor alpha, protein electrophoresis α1 globulin, protein electrophoresis alpha2 globulin, disease activity scores, disease activity index, and patient-reported outcome had correlations(P0.05); multifactor Logistic regression analysis showed that YAP expression was an independent influencing factor for the prognosis of RA patient. Conclusion YAP is differentially expressed between the healthy control group and RA group, which shows a significant positive correlation with the disease activity of RA, potentially becoming a new target for clinical treatment of RA.

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Objective To explore the diagnostic value of a column chart constructed based on composite inflammatory indicators for cardiac valve calcification(CVC) in peritoneal dialysis(PD) patients. Methods A retrospe-ctive analysis was conducted on the data of 117 PD patients admitted in the past 5 years, and the patients were divided into a CVC group and a non CVC group based on whether they had formed CVC. The general clinical data of the two groups were compared, and univariate and multivariate binary logistic regression analyses were used to determine the predictive variables and construct a predictive model. The two predictive models, which only included traditional factors and included composite inflammation indicators at the same time, were evaluated from the aspects of discrimination, calibration, and clinical practicality. Reclassification analysis was used to evaluate the improvement of the column chart model in identifying CVC formation in PD patients. Results A prediction model was established by incorporating six predictive variables: age, pan immune inflammatory value, blood calcium, C-reactive protein/albumin, low-density lipoprotein cholesterol, and parathyroid hormone. The area under the curve of the traditional prediction model without composite inflammatory indicators and the column chart prediction model with composite inflammatory indicators were 0.909 4(95%CI: 0.858 0-0.960 7) and 0.972 7(95%CI: 0.947 7-0.997 7), respectively, indicating good discriminability of the column chart prediction model. The calibration curve showed that the calibration curves before and after calibration were close to the fitting line, indicating that the calibration degree of the column chart prediction model was high. The decision curve showed that the column chart prediction model had a high net benefit. By calculating the net reclassification index and comprehensive discriminant improvement index. It was found that the column chart model had a significant improvement in identifying the risk of CVC formation in PD patients, indicating its good clinical effectiveness. Conclusion The column chart prediction model constructed with age, pan immune inflammatory value, blood calcium, C-reactive protein/albumin, low-density lipoprotein cholesterol, and parathyroid hormone can help identify the risk of CVC in PD patients and provide guidance for clinical diagnosis and treatment.

abstract:
Serine is a non-essential amino acid that plays a key role in the synthesis of biomolecules such as proteins, nucleotides and lipids, and changes in the uptake, absorption, synthesis and catabolic levels of serine in vivo all affect multiple physiological processes in tissue cells. Serine plays a key role in intracellular energy metabolism and signaling linkages, and has a profound impact on the developmental processes of a variety of metabolic diseases, cancer, neurodegenerative diseases and aging. In-depth study of serine metabolic pathways can provide new targets and strategies for early diagnosis, treatment and prevention of related diseases. Based on the physiological function of serine, this article expounds the synthetic and metabolic transformation of serine in cells, and reviews the research progress of intracellular serine metabolism on cell physiology and related diseases at home and abroad, which provides a theoretical reference for serine metabolism as an emerging target for disease treatment.

abstract:
Cardiovascular disease is one of the leading causes of death worldwide, and myocardial remodeling is at the core of the development and progression of most cardiovascular diseases. Purinergic ligand-gated ion channel 7 receptor(P2X7R) is a member of the purinergic receptor family, which is expressed in immune cells, cardiac smooth muscle cells, and endothelial cells, and plays an important role in pathological processes related to immune system regulation, neuroprotection, and inflammatory responses. Activation of P2X7R plays an important role in myocardial remodeling, including myocardial fibrosis, myocardial hypertrophy, and heart failure. Therefore, this article reviews the structural and functional properties of P2X7R and its mechanism of action in myocardial remodeling.