ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 （CCK-8） assay was employed to measure the viability of human ovarian granulosa cells （KGN cells） treated with Tusizi prescription extracts 1-11， and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and encyclopedia of traditional Chinese medicine （ETCM）. The common targets shared by Tusizi prescription and diminished ovarian reserve （DOR） were selected and imported into search tool for the retrieval of interacting genes/proteins （STRING） to construct a protein-protein interaction （PPI） network and into gene function annotation database （DAVID） for gene ontology （GO） analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay， 5-ethynyl-2'-deoxyuridine （EdU） staining， terminal-deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL）， and enzyme-linked immunosorbent assay （ELISA） were employed to examine the proliferation， apoptosis， and estradiol （E₂） secretion of KGN cells treated with the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design. On this basis， the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes， primarily involving cellular responses to exogenous compound stimuli， negative regulation of apoptotic process， and positive regulation of cell proliferation. It identified 84 cellular components， including cell membrane， mitochondria， and neuronal cell body， as well as 144 molecular functions such as enzyme binding， estrogen response element binding， and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen， Lycii Fructus， Dioscoreae Rhizoma， Poria， and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14， the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group， the hyperoside group demonstrated increased viability of ovarian germline stem cells （P<0.01）. The CCK-8， EdU， and ELISA results showed that compared with the normal group， the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells （P<0.05， P<0.01）. ELISA results showed that compared with the normal group， the water extract 11 of Tusizi prescription promoted the E₂ secretion of KGN cells （P<0.05）， while the optimal prescription screened by uniform design had no significant effect on the E₂ secretion. ConclusionBoth the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14） can improve the ovarian reserve function， and the former has better effect. Tusizi prescription can modulate biological processes （such as cell proliferation and apoptosis） and molecular functions （such as enzyme binding and estrogen response element binding） through active components like hyperoside to promote the proliferation and E₂ secretion and inhibit the apoptosis of KGN cells， thereby protecting the ovarian reserve function.

ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 （CCK-8） assay was employed to measure the viability of human ovarian granulosa cells （KGN cells） treated with Tusizi prescription extracts 1-11， and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and encyclopedia of traditional Chinese medicine （ETCM）. The common targets shared by Tusizi prescription and diminished ovarian reserve （DOR） were selected and imported into search tool for the retrieval of interacting genes/proteins （STRING） to construct a protein-protein interaction （PPI） network and into gene function annotation database （DAVID） for gene ontology （GO） analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay， 5-ethynyl-2'-deoxyuridine （EdU） staining， terminal-deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL）， and enzyme-linked immunosorbent assay （ELISA） were employed to examine the proliferation， apoptosis， and estradiol （E₂） secretion of KGN cells treated with the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design. On this basis， the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes， primarily involving cellular responses to exogenous compound stimuli， negative regulation of apoptotic process， and positive regulation of cell proliferation. It identified 84 cellular components， including cell membrane， mitochondria， and neuronal cell body， as well as 144 molecular functions such as enzyme binding， estrogen response element binding， and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen， Lycii Fructus， Dioscoreae Rhizoma， Poria， and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14， the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group， the hyperoside group demonstrated increased viability of ovarian germline stem cells （P<0.01）. The CCK-8， EdU， and ELISA results showed that compared with the normal group， the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells （P<0.05， P<0.01）. ELISA results showed that compared with the normal group， the water extract 11 of Tusizi prescription promoted the E₂ secretion of KGN cells （P<0.05）， while the optimal prescription screened by uniform design had no significant effect on the E₂ secretion. ConclusionBoth the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14） can improve the ovarian reserve function， and the former has better effect. Tusizi prescription can modulate biological processes （such as cell proliferation and apoptosis） and molecular functions （such as enzyme binding and estrogen response element binding） through active components like hyperoside to promote the proliferation and E₂ secretion and inhibit the apoptosis of KGN cells， thereby protecting the ovarian reserve function.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

OBJECTIVE To evaluate the efficacy， safety and economics of the centrally procured generic versus original esomeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding （ANVUGIB）. METHODS A retrospective collection of real-world clinical data was conducted for ANVUGIB patients who received treatment at Shenzhen People’s Hospital and University of Hong Kong-Shenzhen Hospital from January 2018 to March 2024. Patients were divided into imported original drug group （original drug group， 221 cases） and centrally procured generic drug group （generic drug group， 75 cases） according to the types of drug used. Propensity score matching （PSM） was performed at a ratio of 3∶1 to compare the clinical efficacy， safety and economics between the two groups. RESULTS Totally 241 patients were included after PSM， with 170 in the original drug group and 71 in the generic drug group. There were no significant differences between the two groups in terms of rebleeding rate， rate of second endoscopic intervention， blood transfusion rate， length of hospital stay， mortality due to gastrointestinal bleeding， 30-day readmission due to rebleeding， and overall survival rate （P＞0.05）. The incidence of adverse events among all patients in both groups also showed no statistically significant difference （P＞0.05）； furthermore， the adverse events reported by the respective hospitals to the National Center for ADR Monitoring were comparable between the two groups. After PSM， the median total drug cost and high-dose esomeprazole cost in the generic drug group were significantly lower than those in the original drug group， while the median nursing fee and bed fee were significantly higher than those in the original drug group （P＜0.05）. There was no statistically significant difference between the two groups in terms of median total hospitalization expenses， total treatment costs， laboratory fees， examination fees， material costs， or consultation fees （P＞0.05）. CONCLUSIONS The clinical efficacy and safety of centrally procured generic esomeprazole in the treatment of ANVUGIB are comparable to those of the original drug， and it is more economical.

ObjectiveTo investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

Objective To study the effects of scutellarin on endometrial carcinoma Ishikawa cells,and analyze the correlation between the effects and phosphatidyl inositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway.Methods Ishikawa cells were divided into blank group and experimental-L,-M,-H groups,each group was treated with complete medium containing 0,5,10 and 20 μmol·L-1 scutellarin,respectively.Cell viability,clonal formation ability,metastatic ability,invasion,apoptosis and protein expression were detected by cell counting kit-8(CCK-8),plate cloning,scratch,Transwell,flow cytometry and Western blot assay,respectively.Results The cell viability of blank group and experimental-L,-M,-H groups at 48 h were(100.00±0.00)％,(78.51±7.54)％,(52.93±4.91)％and(41.62±5.33)％;the clone formation rate were(100.00±0.00)％,(56.59±6.34)％,(35.23±4.62)％and(10.66±1.91)％;the scratch healing rate were(53.70±6.19)％,(40.59±4.75)％,(34.25±4.40)％and(15.78±2.14)％;the number of invasive cells were 189.70±14.06,106.82±12.67,84.37±8.13 and 53.74±6.78;the relative expression levels of matrixmetallo proteinase-2 were 0.96±0.10,0.73±0.06,0.68±0.08 and 0.42±0.05;tissue inhibitor of MMP-1(TIMP-1)were 0.35±0.04,0.51±0.05,0.74±0.08 and 1.20±0.14;the apoptosis rates were(4.21±0.53)％,(15.83±2.42)％,(22.72±3.85)％and(34.41±4.67)％;the relative expression levels of B cell lymphoma-2(Bcl-2)were 1.38±0.15,0.90±0.10,0.56±0.06 and 0.24±0.03;Bcl-2 associated X protein(Bax)were 0.31±0.02,0.44±0.04,0.93±0.11 and 1.26±0.14;the relative expression levels of PI3Kp85 were 0.67±0.05,0.42±0.04,0.36±0.02 and 0.28±0.03;phosphorylated Akt(p-Akt)were 0.78±0.06,0.53±0.04,0.46±0.05 and 0.42±0.03.Compared with the blank group,the above indexes in the experimental-L,-M,-H groups were statistically significant(P＜0.05 or P＜0.01).Conclusion Scutellarin can inhibit the proliferation,metastatic ability and invasion of endometrial carcinoma Ishikawa cells and promote apoptosis by regulating PI3K/Akt signaling pathway.

Objective To investigate the therapeutic effect and mechanism of paeoniflorin(PAE)on thrombosis angiitis obliterans(TAO)in rats.Methods TAO rat model was established by sodium laurate injection.Rats were randomly divided into sham operation group(intraperitoneal injection of 0.9％NaCl),model group(intraperitoneal injection of 0.9％NaCl),experimental-L,-H groups(intraperitoneal injection of PAE 5,20 mg·kg-1·d-1),experimental-H+agonist group(intraperitoneal injection of 20 mg·kg-1·d-1 PAE+caudal vein injection of 10 ng·mL-1·kg 1·d-1 740 Y-P).Thrombin time(TT)was measured by magnetic bead coagulation;the levels of interleukin(IL)-1 β and endothelin 1(ET-1)were detected by enzyme-linked immunosorbent assay kit;the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated-PI3K(p-PI3 K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,p-NF-κB p65 were detected by Western blotting.Results The TT of sham operation group,model group,experimental-L,-H groups and experimental-H+agonist group were(14.88±1.32),(10.02±0.95),(12.65±1.22),(14.70±1.36)and(10.64±1.21)s;IL-1β were(154.23±13.45),(356.69±31.17),(268.62±23.58),(199.64±20.87)and(337.48±31.46)pg·mL-1;ET-1 were(6.78±0.68),(14.43±1.14),(11.23±1.07),(8.20±0.81)and(13.33±1.27)pg·mL-1;p-PI3K/PI3K were 0.36±0.04,0.76±0.07,0.59±0.05,0.44±0.04 and 0.69±0.07;p-AKT/AKT were 0.52±0.05,0.90±0.09,0.74±0.08,0.61±0.06 and 0.86±0.08;p-NF-κB p65/NF-κB p65 were 0.28±0.03,0.95±0.04,0.69±0.07,0.35±0.05 and 0.87±0.08,respectively.There were statistically significant differences between model group and sham operation group(all P＜0.05);the above indexes in experimental-L group and experimental-H group were significantly different from those in medel group(all P＜0.05);the above indexes in experimental-H+agonist group were significantly different from those in experimental-H group(all P＜0.05).Conclusion PAE may improve disease progression in TAO rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.

Objective To investigate the effects of vitamin D mediated mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK)pathway on myocardial injury in rats with gestational diabetes mellitus.Methods Fifty SD rats were divided into control group,model group,experimental-L group,experimental-M group and experimental-H group,and the gestational diabetes rat model was established.After successful modeling,experimental-L,experimental-M,experimental-H groups were given intragastric administration of 0.05,0.10 and 0.15 μg·kg-1 concentration of vitamin D,while control group and model group were given intragastric administration of 0.9％NaCl at the same dose once a day for 2 weeks.Fasting blood glucose concentration and insulin level were detected before intervention,1 week and 2 weeks after intervention.Echocardiography was used to detect cardiac function[left ventricular ejection fraction(LVEF),maximum rate of rise(+dp/dtmax)and maximum rate of decline(-dp/dtmax)of left ventricular pressure].Myocardial enzyme indexes[troponin Ⅰ(cTn Ⅰ)kit,creatine kinase isoenzyme(CK-MB)]and inflammatory factors[tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)]in serum and myocardial tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA),and MEK/ERK pathway protein expression was detected by western blot.Results The levels of cTn Ⅰ in cardiac tissue of control group,model group,experimental-L group,experimental-M group,experimental-H group were(10.50±1.08),(42.26±4.30),(31.85±2.44),(23.31±2.15)and(14.85±1.19)ng·mL-1;serum cTn Ⅰ levels were(23.79±3.46),(63.59±5.52),(51.02±4.27),(42.75±3.19)and(29.20±2.11)ng·mL-1;myocardial tissue levels of CK-MB were(8.52±0.90),(17.65±1.75),(15.62±1.27),(13.11±1.24)and(9.85±0.87)ng·mL-1;serum levels of CK-MB were(11.32±0.98),(21.24±1.45),(18.75±1.32),(15.11±1.02)and(12.27±1.11)ng·mL-1;phosphorylated-MEK protein expression were 0.24±0.03,0.85±0.09,0.72±0.06,0.57±0.07 and 0.35±0.04;phosphorylated-ERK1/2 protein expression were 0.18±0.02,0.66±0.07,0.52±0.06,0.40±0.07 and 0.24±0.05,respectively.There were statistically significant differences of above indexes between control group and model group(all P＜0.05);the difference between model group and experimental-L,experimental-M,experimental-H groups were all statistically significant(all P＜0.05).Conclusion Vitamin D may reduce myocardial injury in rats with gestational diabetes by inhibiting the activation of MEK/ERK pathway.