OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

Peritoneal metastasis is a common form of metastasis and recurrence in advanced gastric cancer. In recent years, immunotherapy has shown promising applications in the treatment of various malignancies, including gastric cancer. Given the limited efficacy of conventional treatment modalities, such as surgery and chemotherapy, in managing gastric cancer peritoneal metastasis, immunotherapy has garnered increasing attention and recognition among researchers worldwide. However, the application of immunotherapy in gastric cancer peritoneal metastasis still faces significant challenges, including the immunosuppressive tumor microenvironment, drug delivery barriers, and tumor resistance. This review aims to summarize the immunological mechanisms underlying gastric cancer peritoneal metastasis and discuss the latest advances in immunotherapy from both domestic and international studies, with the goal of providing insights for the development of novel immunotherapeutic agents and the optimization of treatment strategies for patients.

Peritoneal metastasis is a common form of metastasis and recurrence in advanced gastric cancer. In recent years, immunotherapy has shown promising applications in the treatment of various malignancies, including gastric cancer. Given the limited efficacy of conventional treatment modalities, such as surgery and chemotherapy, in managing gastric cancer peritoneal metastasis, immunotherapy has garnered increasing attention and recognition among researchers worldwide. However, the application of immunotherapy in gastric cancer peritoneal metastasis still faces significant challenges, including the immunosuppressive tumor microenvironment, drug delivery barriers, and tumor resistance. This review aims to summarize the immunological mechanisms underlying gastric cancer peritoneal metastasis and discuss the latest advances in immunotherapy from both domestic and international studies, with the goal of providing insights for the development of novel immunotherapeutic agents and the optimization of treatment strategies for patients.

Objective To establish the fingerprint map and method of multi-component content determination of ginger and its processed products,and to evaluate their quality. Methods High performance liquid chromatography (HPLC) was used to establish the fingerprint of ginger and its processed products (dried ginger,baked ginger,ginger charcoal) and the method for the simultaneous determination of content of five components. The data were analyzed by similarity evaluation and chemical pattern recognition. Results The fingerprint of ginger and its processed products was established. The similarity was ranged from 0.931 to 0.996. A total of 15 common peaks were confirmed. Five components (6-ginger phenol,8-ginger phenol,10-ginger phenol,6-ginger enol,zingiberone) were identified when compared with the standard. The content of 6-ginger phenol,8-ginger phenol and 10-ginger phenol in ginger and its processed products(dried ginger,baked ginger,ginger charcoal),which were determined by HPLC,met the standard of Chinese Pharmacopoeia(2020 edition). The content of 6-ginger enol and zingiberone in fresh ginger was very low,but their content increased significantly after processing into dried ginger and baked ginger. Ginger and its processed products can be divided into different category in cluster analysis. Five components with VIP greater than one were selected by orthogonal partial least squares discriminant analysis. Conclusion The HPLC fingerprint and assay method established in this study are specific,simple and feasible,stable and reliable. With the help of chemical pattern recognition method,it can provide reference for the quality evaluation of ginger and its processed products.

In order to meet the fertility needs of infertile patients as much as possible during the pandemic of COVID-19 Omicron strain, this expert group reviewed global and domestic literature, combined with the current epidemic situation and prevention and control policies, fully considered the service procedures and characteristics of assisted reproductive institutions and sperm banks in China, and then put forward specific recommendations on institutional prevention and control management, and treatment and surgical management of COVID-19 infected patients, so as to guide and standardize the related practices in assisted reproductive institutions and sperm banks. In the practical application process, assisted reproductive institutions and sperm banks in various provinces and cities should develop personalized institutional prevention and control measures and patient management procedures based on local prevention and control requirements and the actual situation of their own institutions.

In order to meet the fertility needs of infertile patients as much as possible during the pandemic of COVID-19 Omicron strain, this expert group reviewed global and domestic literature, combined with the current epidemic situation and prevention and control policies, fully considered the service procedures and characteristics of assisted reproductive institutions and sperm banks in China, and then put forward specific recommendations on institutional prevention and control management, and treatment and surgical management of COVID-19 infected patients, so as to guide and standardize the related practices in assisted reproductive institutions and sperm banks. In the practical application process, assisted reproductive institutions and sperm banks in various provinces and cities should develop personalized institutional prevention and control measures and patient management procedures based on local prevention and control requirements and the actual situation of their own institutions.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To develop an R script that can efficiently and accurately filter genome-wide association studies (GWASs) from the GWAS Catalog Website.Methods:The selection principles of GWASs were established based on previous studies. The process of manual filtering in the GWAS Catalog was abstracted as standard algorithms. The R script (gwasfilter.R) was written by two programmers and tested many times.Results:It takes six steps for gwasfilter.R to filter GWASs. There are five main self-defined functions among this R script. GWASs can be filtered based on "whether the GWAS has been replicated" "sample size" "ethnicity of the study population" and other conditions. It takes no more than 1 second for this script to filter GWASs of a single trait.Conclusions:This R script (gwasfilter.R) is user-friendly and provides an efficient and standard process to filter GWASs flexibly. The source code is available at github ( https://github.com/lab319/gwas_filter).