OBJECTIVE To investigate the improvement effects of Compound qinbai granules on ulcerative colitis （UC） in rats and its mechanism based on short-chain fatty acid （SCFA） and their targets G protein-coupled receptor （GPR）. METHODS Male SD rats were randomly divided into normal group （12 rats） and model group （30 rats）； the model group was given 5% dextran sulfate sodium solution to induce the UC model. Model rats were divided into the model group， positive control group [Mesalazine enteric-coated tablets 270 mg/（kg·d）] and Compound qinbai granules group [2.52 g/（kg·d）]， with 9 rats in each group. Rats in each group were orally administered with normal saline or corresponding medication twice a day， for three consecutive weeks. During intragastric administration， the general conditions of rats in each group were observed， and the disease activity index （DAI） scores were assessed after the last administration. Serum levels of pro-inflammatory cytokines （tumor necrosis factor-α， interleukin-6） and anti-inflammatory cytokines （transforming growth factor-β1， interleukin-10） were measured. Pathological changes in their colonic tissues were observed and scored. Additionally， the content of SCFA （acetic acid， propionic acid and butyric acid） in their feces as well as the protein and mRNA expressions of GPR41， GPR43 and GPR109A in colonic tissues were detected. RESULTS Compared with the normal group， rats in the model group exhibited lethargy and obvious blood in their feces； the colonic tissue structure was severely damaged， with pathological changes such as notable glandular loss， edema， and inflammatory cell infiltration visible； the serum levels of pro- inflammatory cytokines， DAI score and colonic pathology score were significantly increased， while the levels of anti-inflammatory cytokines， SCFA content， and protein and mRNA expressions of GPR41， GPR43 and GPR109A were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the general condition and pathological changes of colonic tissue in each administration group showed improvement， with significant reversal observed in the aforementioned quantitative indicators （P＜0.05 or P＜0.01）. CONCLUSIONS Compound qinbai granules can alleviate intestinal inflammation and intestinal mucosal damage in UC rats. These effects may be related to its ability to restore intestinal SCFA levels and the expression of their target GPR.

Objective:To study effect and mechanism of Wu-Mei-Wan on improving colonic mucosal inflammatory response and pyroptosis in rats with ulcerative colitis(UC)via regulating NOD-like receptor family pyrin domain containing 3(NLRP3)inflam-masome.Methods:Male SD rats were selected for animal experiments.UC model was established by enema with 2,4,6-trinitroben-zene sulfonic acid.After model was established,different doses of Wu-Mei-Wan were given by gavage,negative control(NC)-lentivi-rus(LV)or NLRP3-LV were injected by tail vein.Disease activity index(DAI)of rats in each group was evaluated,length of colon was measured,pathological changes and histopathological scores,contents of IL-1β,IL-18,GSDMD-N,NLRP3 and Cleaved cas-pase-1 expressions in colon tissues were detected.Results:Typical UC pathological changes were found in colon mucosa of UC group,DAI,histopathological score,IL-1β,IL-18 contents,GSDMD-N,NLRP3 and Cleaved caspase-1 expressions in colon tissues of UC group were higher than control group,and colon length was shorter than control group(P<0.05).UC pathological changes of colon mucosa of rats in different concentrations of Wu-Mei-Wan groups were improved,DAI,histopathological score,IL-1β,IL-18 con-tents,GSDMD-N,NLRP3 and Cleaved caspase-1 expressions in colon tissues were lower than UC group,and colon length was longer than UC group(P<0.05).LV was injected simultaneously with intragastric administration of high-dose Wu-Mei-Wan,pathological changes of UC in colon mucosa of rats in NLRP3-LV+NC+high-dose Wu-Mei-Wan group was aggravated,DAI,histopathological score,IL-1β,IL-18 contents,GSDMD-N,NLRP3 and Cleaved caspase-1 expressions in colon tissues were higher than NC-LV+NC+ high-dose Wu-Mei-Wan group,and colon length was shorter than NC-LV+NC+high-dose Wu-Mei-Wan group(P<0.05).Conclusion:Wu-Mei-Wan improves colonic mucosal inflammation and pyroptosis in UC rats by inhibiting NLRP3 inflammasome.

Objective To observe the effects of Shengxue Tongbian Granules on colonic myoelectricity and Ca2+/CaM/MLCK signaling pathway in rats with slow transit constipation(STC)of blood deficiency and intestinal dryness syndrome;To explore its mechanism for the treatment of STC.Methods The STC model of blood deficiency and intestinal dryness syndrome was established by intragastric administration of loperamide combined with tail bloodletting.The rats were divided into control group,model group,mosapride citrate group and Shengxue Tongbian Granules group,with 8 rats in each group.The administration group was given corresponding drugs by gavage for 14 days.The general condition of rats before and after treatment was observed,the fecal water content was detected,the slow wave frequency,amplitude,and coefficient of variation of colonic electromyography were detected using a biological function experimental system,and intestinal propulsion rate was detected.HE staining was used to observe the pathological changes of colon tissue,the concentration of Ca2+ in colonic smooth muscle cells was detected by colorimetry,the expression of Cx43,calmodulin(CaM),myosin light chain kinase(MLCK)and p-MLC20 in smooth muscle tissue were detected by Western blot.Results Compared with the control group,the body mass,fecal water content and intestinal propulsion rate of rats in the model group decreased(P<0.01),the slow wave frequency of colonic electromyography slowed down,the coefficient of variation of frequency increased(P<0.01),and the amplitude and coefficient of variation of slow wave increased(P<0.01);colonic mucosal structure was damaged,with visible inflammatory changes and significant erosion,and the concentration of Ca2+ and the expressions of Cx43,CaM,MLCK,p-MLC20 proteins in colonic smooth muscle cells were significantly decreased(P<0.01).Compared with the model group,the body mass,fecal water content and intestinal propulsion rate of the rats in the mosapride citrate group and the Shengxue Tongbian Granules group significantly increased(P<0.05,P<0.01),the slow wave frequency of colonic electromyography increased and the coefficient of variation of frequency decreased(P<0.01),and the slow wave amplitude and amplitude variation coefficient decreased(P<0.05,P<0.01);the colonic mucosal structure was relatively intact,the erosion situation was improved,and the Ca2+ concentration,Cx43,CaM,MLCK and p-MLC20 protein expressions in colonic smooth muscle cells significantly increased(P<0.01).Conclusion Shengxue Tongbian Granules can improve defecation symptoms and promote colonic motility in STC rats with blood deficiency and intestinal dryness syndrome,which may be related to regulating colonic myoelectric rhythm and activating Ca2+/CaM/MLCK signaling pathway.

Objective To explore the action mechanism of tauroursodeoxycholic acid(TUDCA)promoting intracellular clearance of Burkholderia pseudomallei(B.pseudomallei)in RAW264.7 macrophages.Methods After TUDCA of different concentrations were used to treat RAW264.7 cells pre-infected with B.pseudomallei for 8 h or not,flow cytometry was applied to detect the apoptosis of the infected and control cells.In addition,another endoplasmic reticulum stress(ERS)inhibitor 4-PBA was used to detect the apoptosis and proliferation of host cells after B.pseudomallei infection with Annexin-V/PI double staining and MTT cell proliferation assay.Furthermore,after transfected with CHOP siRNA,Western blotting and flow cytometry were employed to detect the effect of TUDCA on the expression levels of Caspase-3 and Caspase-12 and the changes in apoptotic rate after B.pseudomallei infection,respectively.Finally,the effect of TUDCA on intracellular multiplication of infected RAW264.7 cells were observed to estimate the CFU value in the presence and absence of CHOP siRNA.Results Under different concentrations of TUDCA,100 or 200 μmol/L TUDCA significantly reduced B.pseudomallei-induced apoptosis in RAW264.7 cells(P＜0.05).Meanwhile,both TUDCA and 4-PBA treatment could decrease the apoptosis induced by B.pseudomallei infection by ERS(P＜0.05).Further,the expression levels of Caspase-3 and Caspase-12 were obviously increased after B.pseudomallei infection compared with uninfected groups,but their expression levels in the siCHOP group was significantly lower than that in the siC group.Besides,flow cytometry also showed that TUDCA could reduce apoptosis induced by B.pseudomallei infection(P＜0.05),but no significant effect of TUDCA on apoptosis was observed under CHOP knockdown.Finally,intracellular CFU assay indicated that TUDCA treatment promoted the host cell clearance of B.pseudomallei(P＜0.05),but no such effect was observed in siCHOP group.Conclusion In B.pseudomallei infected RAW264.7 cells,TUDCA promotes the intracellular clearance of the bacteria by inhibiting ERS-induced apoptosis.

Objective: To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment. Methods: A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment. Results: A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P < .05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P = .006 and P = .021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics. Conclusions WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

Objective To investigate the distribution of B cells in both tumor and non-tumor tissues of gastric cancer patients,analyze their phenotypic characteristics and explore the impact on T cell proliferation.Methods Immunohistochemical staining was utilized to detect the expression of B cell surface marker CD 19 in tumor and non-tumor tissues from 33 gastric cancer patients.The expression levels of chemokine receptors and immunoglobulin molecules on B cells in both tumor and non-tumor tissues were measured using flow cytometry.Chemotaxis experiments were conducted to examine the role of the CXCL12-CXCR4 axis in B cell chemotaxis.B cells isolated and purified from both tissue types were co-cultured with autologous peripheral T cells to assess their effect on T cell proliferation.Results There were significantly more B cells infiltrated in tumor tissues than those infitrated in the non-tumor tissues of gastric cancer patients(P＜0.01),and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues(P＜0.05).The Cancer Genome Atlas(TCGA)analysis indicated that the expression level of CXCL12 in tumor tissues was positively correlated with the expression level of CD19 in gastric cancer patients(r=0.15,P＜0.01).And the expression level of CXCL12 in tumor tissues of the gastric cancer patients was also positively correlated with the number of B cells infiltrated in tumor tissues.Chemotaxis experiments confirmed that the CXCL12-CXCR4 axis was involved in promoting B cell chemotaxis(P＜0.05).Although B cells in tumor and non-tumor tissues had similar levels of IgM,IgG,and IgA expression,tumor-infiltrating B cells significantly inhibited the proliferation of T cells when compared with B cells derived from non-tumor tissues(P＜0.01).Conclusion There are more B cells infiltrated in gastric cancer tissues,which may be recruited to tumor tissues through the CXCL12-CXCR4 axis,and then inhibit T cell proliferation to promote the progression of gastric cancer.

Objective:Osteoarthritis is a degenerative disease with slow progress, which is caused by aging, obesity, trauma and other factors.It has a great impact on the daily life of middle-aged and elderly patients.Compared with traditional drug, protein and antibody therapies, stem cells are expected to radically change the medical treatment of osteoarthritis, because they have the ability to replace and repair tissues and organs such as osteoarthritis and joints, and have better homology and lower immune rejection.In different types of stem cells, mesenchymal stem cells originate from the mesoderm and can differentiate into different cells to form organs originating from the mesoderm lineage.In view of its ability to differentiate into other types of cells, MSCs have also been used to treat tissues and organs of ectodermal and endodermal lineages such as diabetes mellitus and Parkinson's disease.Whether MSCs can differentiate into lineages other than mesoderm lineages and the efficacy of treating organ diseases of ectoderm and endoderm lineages have been debated.This review will discuss the clinical features of osteoarthritis, the developmental origin and differentiation potential of MSCs, and the role of MSCs and scaffolds in the treatment of osteoarthritis.

OBJECTIVE： To study the mechanism of couplet medicine of Tripterygium hypoglaucum-Spatholobus suberectus in the treatment of rheumatoid arthritis （RA）. METHODS： The RA targets were retrieved and obtained by therapeutic target database （TTD）， DrugBank and DisGeNET databases， and the protein protein interaction （PPI） network was constructed to screen its key targets. Using oral bioavailability（OB）≥30％， drug like（DL）≥0.18 and drug half-life （HL） ≥4 h as index， active components were obtained from couplet medicine of T. hypoglaucum-S. suberectus by using TCM systematic pharmacological analysis platform （TCMSP） and TCM integrated database （TCMID）， and the targets were predicted. The active component-target network of couplet medicine of T. hypoglaucum-S. suberectus was constructed. Systems Dock Web Site online platform and Genomics platform were used to screen the active component and common targets of RA of couplet medicine of T. hypoglaucum-S. suberectus； KEGG signaling pathways of common targets were analyzed by using Cluego plug-in unit of Cytoscape 3.2.1 software. RESULTS： Totally 1 956 RA targets were retrieved， involving 11 key targets [such as IL-6， TNF， VEGFA]. The couplet medicine contained 30 active components （including luteolin， erythroxanthin， β-sitosterol and triptolide） and 229 targets. There were 37 common targets for couplet medicine of T. hypoglaucum-S. suberectus and RA （including MMP2， TNF， VEGFA）. KEGG signaling way involved cell apoptosis， IL-17 signaling pathway， Th17 cell differentiation pathway and TNF signaling pathway. CONCLUSIONS： The couplet medicine of T. hypoglaucum-S. suberectus may play a role in the treatment of RA by acting on cell apoptosis， IL-17 signaling pathway and other signaling pathways through MMP2， TNF， and VEGFA target. The results of this study can provide a reference for further study on the mechanism of the effects of couplet medicine of T. hypoglaucum-S. suberectus on RA.

Objective To investigate the status of self‐management of blood pressure (BP) among elderly hypertensive patients living in new rural communities of Shanghai. Methods We enrolled a total of 2 241 hypertensive patients over 60 years old who participated in the National Key Research and Development Project "Cohort study on hypertension" of the 13th Five‐Year Plan in Langxia, Shanghai from May to July 2018. Questionnaires, physical examinations, and laboratory tests were conducted. We collected participants' demographic information, cardiovascular history, and self‐management behaviors related to hypertension. The status of self‐management of BP among participants with hypertension was analyzed. Pearson's chi‐squared test was used to explore the differences between males and females. Results Participants'mean age was (70.0±6.8) years, and males accounted for 38.8% of all participants. The systolic and diastolic BP levels of participants were (147.8±15.4) mmHg (1 mmHg=0.133 kPa) and (82.8±9.8) mmHg, respectively. The systolic blood pressure level of women was higher than that of men, and the diastolic blood pressure level of men was higher; the difference was statistically significant (all P<0.05). The awareness, treatment, and control rate of hypertension were 79.0%, 78.0%, and 25.6%, respectively. Males had a significantly higher control rate than females (P<0.05). The status of self‐management of blood pressure was as follows: (1) As to lifestyle, 84.4% of participants lacked exercise, and 69.2% were overweight or obese. The prevalence of smoking and drinking was higher in males (40.7% and 46.2%, respectively), and the proportion of females (12.4%) with anxiety and/or depression was higher than that of males (P all<0.001). (2) Concerning BP‐monitoring, only 10.1% of participants measured BP every week, 22.9% had BP measurement instruments at home, and 4.6% recorded their BP levels. There was no significant difference in self‐blood pressure monitoring behavior between men and women. (3) Regarding adherence to medication treatment, 97.6% took antihypertensive drugs regularly, and 21.6% were on combination therapy. The proportion of men taking combined drugs was higher than that of women, but there was no significant difference. Conclusions The rates of awareness, treatment, and control of hypertension in elderly hypertensive patients in new rural communities of Shanghai were above the national average. However, the status of self‐management of BP was still not satisfactory. More attention should be paid to healthy lifestyle, home BP monitoring, and effective pharmaceutical treatment strategies for hypertension.

OBJECTIVE:To compare the clinical efficacy and safety of rivaroxaban and low molecular weight heparin calcium (LMWHA)in the prevention of deep venous thrombosis(DVT)after total hip arthroplasty(THA). METHODS:A total of 100 THA patients selected from orthopedics department of our hospital as research objects were divided into control group and observa-tion group according to random number table,with 50 cases in each group. Control group was treated with LMWHA injection 0.4 mL subcutaneously,qd;observation group was given Rivaroxaban tablet 10 mg orally,qd. Both groups received treatment on the first day after surgery,for consecutive 14 d. Coagulation indexes(PT,APTT,Fib,TT,D-D),VAS score,the incidence of DVT and PE were observed in 2 groups. The postoperative bleeding volume and ADR as hematoma and gastrointestinal bleeding were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in coagulation indexes or VAS scores between 2 groups(P>0.05). After treatment,PT,APTT,TT and D-D levels,VAS scores of 2 groups were decreased sig-nificantly,while Fib levels were increased significantly;VAS score of observation group was significantly lower than that of con-trol group,with statistical significance(P<0.05). There was no statistical significance in coagulation indexes between 2 groups (P>0.05). The incidence of DVT and PE in observation group were 8.00% and 7.50% ,which were significantly lower than 12.00% and 4.00% of control group,with no statistical significance(P>0.05). The postoperative bleeding volume of observation group was(298.31±52.18)mL,which was significantly lower than(327.40±54.20)mL of control group,with statistical signifi-cance(P<0.05). There was no statistical significance in the incidence of hematoma or gastrointestinal bleeding between 2 groups (P>0.05). CONCLUSIONS:Rivaroxaban and LMWHA can significantly improve coagulation state,prevent the generation of DVT after THA. While rivaroxaban is better in shortening pain time without increasing the risk of ADR.