Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective: This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry. Results: Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility. Conclusion This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.

Objective:To develop the Fecal Microbiota Transplantation Knowledge, Attitude, and Practice Scale for Patients with Inflammatory Bowel Disease (IBD), and test its reliability and validity.Methods:Guided by the theory of knowledge, attitude, and practice, a preliminary draft of the scale was formed through literature review, Delphi expert consultation, and pre-survey. From May to August 2022, convenience sampling was used to select 200 IBD patients who visited the Gastroenterology Clinic of three ClassⅢ Grade A comprehensive hospitals in Jiangsu Province as the research subject for a questionnaire survey. The critical ratio method, correlation analysis method, internal consistency method, commonality and factor loadings were used for item analysis of the scale. Exploratory factor analysis, content validity index, and internal consistency reliability were applied to test the reliability and validity of the scale.Results:A total of 200 questionnaires were distributed, and 181 valid questionnaires were collected, with an effective response rate of 90.50% (181/200). The Fecal Microbiota Transplantation Knowledge, Attitude, and Practice Scale for Patients with IBD included three dimensions of knowledge, attitude and practice, with a total of 21 items. The content validity index at the scale level was 0.917, and the content validity index at the item level ranged from 0.833 to 1.000. Exploratory factor analysis extracted three common factors, with a cumulative variance contribution rate of 74.197%. The Cronbach's α coefficient of the total scale was 0.951, and the coefficients of each dimension were 0.914 to 0.942. The test-retest reliability coefficient of the total scale was 0.918, and the test-retest reliability coefficients of each dimension ranged from 0.737 to 0.833.Conclusions:The Fecal Microbiota Transplantation Knowledge, Attitude, and Practice Scale for Patients with IBD has good reliability and validity, which can help medical and nursing staff evaluate patients' understanding and acceptance of microbial transplantation, so as to provide a basis for personalized communication in shared decision making between doctors and patients.

Objective To investigate the expression characteristics of S100 calcium binding protein P(Sl00P)and thymic stromal lymphopoietin(TSLP)in patients with breast cancer and their relationship with prognosis.Methods GEPIA database and bc-GenExMiner v4.3 were used to analyze the expression levels of S100P and TSLP in breast cancer tissues,and Kaplan-Meier Plotter was used to analyze effects of S100P and TSLP on patient prognosis.The protein interaction network analysis of S100P and TSLP were carried out by using STRING database.The co-expressed genes of S100P and TSLP were analyzed using Linked Omics database,and the role of S100P and TSLP co-expressed genes in related biological processes and signaling pathways were evaluated by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.The correlation between S100P and TSLP and breast cancer immunoinfiltration was analyzed by TIMER.Results The expression of S100P in breast cancer patients was significantly higher than that in normal population,and the expression of TSLP was significantly lower than that in normal population(P＜0.05).The overall survival,disease-free survival and distant metastasis-free survival of patients with high S100P expression were significantly shorter than those of patients with low S100P expression(P＜0.05).The distant metastasis-free survival of patients with high expression of TSLP was significantly longer than that of patients with low expression of TSLP(P＜0.05).The results of protein interaction showed that S100P had a strong interaction with interleukin-11,and TSLP had a strong interaction with interleukin family proteins.The co-expressed genes of S100P and TSLP were mainly responsible for biological functions such as DNA replication and immune function.TSLP was correlated with breast cancer immune cell infiltration.Conclusion S100P and TSLP can be used as biomarkers to predict the prognosis of breast cancer,and they can also help to evaluate the tumor immunoinfiltration in breast cancer patients,and TSLP could provide theoretical basis for predicting the prognosis and tumor immunotherapy in breast cancer patients.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.