This study aims to investigate the effects of Pulsatilla decoction(PD)on the 5-HT sig-naling system in the hippocampus of damp-heat diarrhoea(DHD)rats.Twenty-four male SD rats were randomly divided into four groups including the blank group,the model group,the PD group and the self-healing group.Except for the blank group,the rats in each group were induced by"high sugar and high fat,high temperature and high humidity,and E.coli poisoning"to establish a of rat model DHD,and were treated by gavage with PD.Changes in body weight,temperature,food intake and water intake,routine blood tests and histopathological changes in the colon were recor-ded to comprehensively determine the modelling condition of rats with DHD;histopathological changes in the hippocampus of rats were observed,and real-time fluorescence PCR was used to de-termine the expression of IL-1β3,IL-6,TNF-α,IFN-γ and TPH1 mRNA in the hippocampus;West-ern blot and immunohistochemistry were used to detect the protein expression of tryptophan hydroxylase 1(TPH1),receptors(5-HT3R,5-HT4R,5-HT7R)in 5-HT signaling pathway in the hippocampus.The results showed that:PD significantly regulated the abnormal changes of body weight,food and water intake and blood routine indexes in rats with DHD,and significantly im-proved the pathological damage of colonic tissues;PD significantly lowered the expression of in-flammatory cytokines IL-1β,IL-6,IFN-γ,and TNF-α in hippocampus of rats with DHD(P＜0.05),and significantly reduced the expression of TPH1 mRNA in hippocampus of rats with DHD(P＜0.05).PD could increased the expression of 5-HT4R and 5-HT7R in the hippocampus of rats with DHD;reduced the expression of 5-HT3R and TPH in the hippocampus,among which 5-HT3R expression was significantly reduced.This study suggests that PD can affect the function of hippocampus in rats with DHD by regulating the 5-HT signaling pathway.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.

Objective:To select low-dose radiation-activated genes with intrinsic radiation protection by developing a model for adaptive responses to low-dose ionizing radiation, in order to explore the mechanisms behind the radiation resistance of the candidate genes.Methods:The cells were divided into adaptive response induction group and whole transcriptome sequencing group. The level of DNA damage was assessed using the γ-H2AX immunofluorescence assay. The low-dose radiation-activated candidate genes with radiation protection were selected through whole transcriptome sequencing and quantitative reverse transcription PCR (RT-qPCR)-based validation. The anti-radiation effect of candidate gene CCND1 was assessed based on CCK-8 cell proliferation and γ-H2AX immunofluorescence assay. After up- and down-regulation of CCND1 expression, the anti-radiation mechanism of CCND1 was preliminarily explored through transcriptome sequencing analysis.Results:A model for low-dose ionizing radiation-induced adaptive responses of lymphocytes was constructed. Using this model, six candidate genes with radiation protection, including CCND1, ZMAT3, MGAT3, DFFB, CYP4F2, ITGA6, were selected. Compared to the control group, overexpressed CCND1 led to significantly enhanced proliferation ability of AHH-1 cells ( t = 7.92-14.76, P < 0.05) and distinctly lowered level of DNA damage ( t = 2.79-9.68, P < 0.05) after 2 Gy of X-ray irradiation. Furthermore, compared to the control group, the CCND1 knockdown caused significantly decreased cell proliferation ability ( t = 13.58-26.25, P < 0.05) and notably elevated level of DNA damage of cells ( t = 2.87-7.61, P < 0.05). Transcriptome sequencing revealed that up- and down-regulation of CCND1 expression resulted in the activation of pathways related to cell growth, death, and damage repair. Conclusions:By selecting six low-dose-activated candidate genes with radiation protection and revealing the function of CCND1 in radiation protection, this study provides a new perspective for the development of radiation protection agents from the perspective of adaptive responses to low-dose radiation.

This study aims to investigate the effects of Pulsatilla decoction(PD)on the 5-HT sig-naling system in the hippocampus of damp-heat diarrhoea(DHD)rats.Twenty-four male SD rats were randomly divided into four groups including the blank group,the model group,the PD group and the self-healing group.Except for the blank group,the rats in each group were induced by"high sugar and high fat,high temperature and high humidity,and E.coli poisoning"to establish a of rat model DHD,and were treated by gavage with PD.Changes in body weight,temperature,food intake and water intake,routine blood tests and histopathological changes in the colon were recor-ded to comprehensively determine the modelling condition of rats with DHD;histopathological changes in the hippocampus of rats were observed,and real-time fluorescence PCR was used to de-termine the expression of IL-1β3,IL-6,TNF-α,IFN-γ and TPH1 mRNA in the hippocampus;West-ern blot and immunohistochemistry were used to detect the protein expression of tryptophan hydroxylase 1(TPH1),receptors(5-HT3R,5-HT4R,5-HT7R)in 5-HT signaling pathway in the hippocampus.The results showed that:PD significantly regulated the abnormal changes of body weight,food and water intake and blood routine indexes in rats with DHD,and significantly im-proved the pathological damage of colonic tissues;PD significantly lowered the expression of in-flammatory cytokines IL-1β,IL-6,IFN-γ,and TNF-α in hippocampus of rats with DHD(P＜0.05),and significantly reduced the expression of TPH1 mRNA in hippocampus of rats with DHD(P＜0.05).PD could increased the expression of 5-HT4R and 5-HT7R in the hippocampus of rats with DHD;reduced the expression of 5-HT3R and TPH in the hippocampus,among which 5-HT3R expression was significantly reduced.This study suggests that PD can affect the function of hippocampus in rats with DHD by regulating the 5-HT signaling pathway.

Ischemic stroke,due to its high prevalence and mortality,has become one of the most important public health concerns globally.Nerve cell damage is the main biological event in its patho-logical process and there is still a lack of effective neuroprotective drugs for clinical use.Numerous studies have shown that inhibitions of histone deacetylases(HDACs)can exert neuroprotective effects in ischemic stroke.Due to the multiple types of HDACs and the relatively poor specificity of HDAC inhib-itors,it has been difficult to identify any HDAC that plays a key role in ischemic stroke.ClassⅠHDACs include four members:HDAC1,HDAC2,HDAC3,and HDAC8,and have been more in-depth in isch-emic stroke.The complex mechanisms of classⅠHDAC inhibitors that have been discovered so far involve neural cell function,neuroinflammation and blood-brain barriers.This article is intended to study the regulatory role of classⅠHDACs in ischemic stroke in the hopes of providing reference for the developments of effective drugs targeting HDACs.

Objective To compare the effect of posterior cruciate ligament retaining(CR)and posterior cruciate substituting(PS)prosthesis in knee arthroplasty.Methods 64 patients with knee osteoarthritis were admitted to our department from June 2021 to June 2022 and whom met the selection criteria were randomly selected and divided into observation group and control group(n = 32).CR prosthesis was used in the observation group,and PS prosthesis was used in the control group.Operation time,postoperative drainage volume,difference of hemoglobin(HGB)before and after operation,postoperative hospital stay,postoperative range of motion at 7 d,14 d,45 d,3 months and 1 year were recorded.ROM,visual analog pain Scale(VAS),Hospital for special surgery(HSS)score,and maximum forward and backward displacement of knee joint and the regular radiographs were also recorded,too.Results The two groups were similar in terms of operation time,postoperative hospital stay,postoperative VAS score and maximum anterior and posterior displacement of knee joint,with P values greater than 0.05,which had no statistical significance.The postoperative drainage volume in the observation group was significantly less than that in the control group,with statistical significance(P＜0.05).The HGB difference of observation group was significantly lower than that of control group,with statistical significance(P＜0.05).There was no statistically significant differ-ence in ROM and HSS scores between the two groups before surgery;the ROM and HSS scores of the control group at 7,14 and 45 days after surgery was better than that of the observation group,with statistical significance(P＜0.05);the ROM and HSS scores of the two groups at 3 months after surgery was not statistically significant.The ROM and HSS scores in the observation group was better than that in the control group at 6 months and 1 year after operation,and the difference was statistically significant(P＜0.05).Conclusions CR prosthesis is superior to PS prosthesis in terms of intraoperative blood loss and post-operative drainage volume,which can reduce surgical risk.Both kinds of prosthesis can achieve good knee stability after surgery,while PS prosthesis has better early clinical effect,while CR prosthesis has better long-term clinical effect.

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.

Objective Based on the gene expression omnibus(GEO)database,bioinformatics methods were employed to analyze the expression characteristics of hypoxia-related differentially expressed genes(HRDEGs)in ischemic stroke,and key genes were screened,to provide important support for a deeper understanding of ischemic stroke.Methods The GSE16561 and GSE58294 datasets were downloaded from the GEO database,and Python software was used for data integration.The Combat method was employed to eliminate batch effects while retaining disease grouping characteristics.Principal component analysis was conducted to reduce dimensionality of the data before and after batch effect removal,and intraclass correlation coefficient(ICC)testing was performed on the ischemic stroke and normal control groups.Gene set enrichment analysis(GSEA)and single-sample GSEA were conducted on the merged and batch effects eliminated dataset,with a nominal P-value(NOM P-val)＜0.05 and false discovery rate P-value(FDR P-val)＜0.25 used as criteria to select significantly different gene sets.Differential expression genes between the ischemic stroke samples and normal control samples after merging and eliminating batch effects of the GSE16561 and GSE58294 datasets were identified using R software,with an absolute value of log2 gene expression fold change(FC)≥0.58 and adjusted P-value(Padj)＜0.05 as selection criteria.Intersection with hypoxia-related genes obtained from the National Center for Biotechnology Information(NCBI)in the United States yielded the HRDEGs.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were performed on the HRDEGs,and the STRING database was used to construct a protein-protein interaction network of differentially expressed genes.The top 10 key genes were filtered using Cytoscape 3.8 software.Results The ICC analysis results showed excellent consistency in the ischemic stroke and normal control samples after batch effect removal,with ICC values of 0.94 and 0.98 for the GSE16561 and GSE58294datasets,respectively.GSEA results demonstrated significant enrichment of 34 gene sets in the stroke samples in the newly merged and batch effects removed dataset from GSE16561 and GSE58294,leading to the identification of 404 differentially expressed genes(all with Padj＜0.05),including 354 upregulated genes and 50 downregulated genes.Intersection with hypoxia-related genes yielded 64 HRDEGs.GO enrichment analysis indicated significant enrichment of HRDEGs in vesicle lumen,cytoplasmic vesicle lumen,secretory granule lumen,with molecular functions such as amide binding,peptide binding,phospholipid binding,and enzyme inhibitor activity.These genes are primarily involved in the positive regulation of cytokine production,regulation of immune response,response to bacterium-derived molecules,and response to lipopolysaccharide,among other biological processes.KEGG enrichment analysis revealed enrichment of HRDEGs in pathways related to lipid and atherosclerosis,Salmonella infection,neutrophil extracellular trap formation,nucleotide-binding oligomerization domain-like receptor signaling pathway,protein glycosylation in cancer,tuberculosis,and necroptosis.Based on the protein-protein interaction network,10 key genes were identified,including arginase1(ARG1),caspase1(CASP1),interleukin1 receptor type 1(IL-1R1),integrin subunit alpha M(ITGAM),matrix metalloproteinase9(MMP9),prostaglandin-endoperoxide synthase 2(PTGS2),signal transducer and activator of transcription 3(STAT3),Toll-like receptor2(TLR2),TLR4,and TLR8.Conclusion This study has identified 10 key genes associated with ischemic stroke and hypoxia through bioinformatics mining,which maybe provid potential targets for subsequent research and diagnostic and therapeutic interventions.