Objective To investigate the effect and potential mechanism of Desmodium renifolium(Linn.)Schindl on ovariectomized osteoporosis rat model.Methods Sixty 3-month-old female SD rats were randomly divided into Sham group,model group,Xianlin Gubao group(0.24 g·kg-1),Desmodium renifolium low-dose group(1.35 g·kg-1,medium-dose group(2.7 g·kg-1)and high-dose group(5.4 g·kg-1).Osteoporosis was induced by performing double ovariectomy in rats.After 14 weeks treatment,the contents of osteocalcin(BGP),osteoprotectin(OPG)and alkaline phosphatase(ALP)in serum were determined.Hematoxylin-eosin(HE)staining was used to observe the changes of bone trabeculae.The osteoclast progenitor-cell line RAW264.7 was divided into negative control group,Receptor activator of nuclear factor-κB ligand(RANKL)group,Xianlin Gubao group,Desmodium renifolium low-dose,medium-dose and high-dose drug groups.The RANKL group and drug groups were induced with 50 ng·mL-1 RANKL.Meanwhile,Xianlin Gubao group and different concentrations of drug-containing serum of Desmodium renifolium,were added for intervention.Tartrate-resistant acid phosphatase(TRAP)staining was performed 10 days after intervention to observe the differentiation of osteoclasts,and quantitative real-time PCR(qPCR)was used to determine the mRNA expression.Results Compared with Sham group,the contents of OPG in serum of model group were significantly decreased(P<0.01),while ALP and BGP were significantly increased(P<0.01),bone trabeculae were significantly reduced,broken,sparsely arranged,and the space between bone trabeculae was large,the OPG mRNA expression in model group were significantly decreased(P<0.01),and the mRNA expression of receptor activator of nuclear factor-κB ligand(RANKL),TNF receptor associated factor 6(TRAF6),nuclear factor of activated t-cells,cytoplasmic 1(NFATC1),cathepsin K(CTK)and calcitonin receptor(CALCR)in model group were significantly increased(P<0.01),all these aspects showed remarkable improvement after Desmodium renifolium intervention.After 10 days of RAW264.7 culture,no osteoclasts were found in the Control group.Compared with the negative control group,osteoclasts in RANKL group were significantly increased,treatment with Desmodium renifolium markedly decreased osteoclast number,the result of RANKL/RANK/OPG signaling mRNA expression were consistent with the animal experiments.Conclusion Desmodium renifolium exerts effects on osteoporosis in ovariectomized rats,its mechanism might be realized by inhibiting osteoclast proliferation and differentiation,and regulating OPG/RANKL/RANK signaling pathway.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.

Objective:To assess the differences in multidimensional clinical manifestations between patients with irritable bowel syndrome (IBS) matching the Rome Ⅲ criteria but not matching Rome Ⅳ and IBS patients matching the Rome Ⅳ criteria, among patients diagnosed with IBS according to Rome Ⅲ criteria.Methods:From November 2016 to October 2017, a total of 472 IBS patients admitted to six hospitals were selected, which included Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (139 cases), Sir Run Run Shaw Hospital, School of Medicine of Zhejiang University (95 cases), the First Affiliated Hospital of Dalian Medical University (96 cases), the Affiliated Hospital of Guizhou Medical University (90 cases), the People′s Hospital of Guangxi Zhuang Autonomous Region (20 cases), and the Second Affiliated Hospital of Xi′an Jiaotong University (32 cases). The 472 IBS patients were divided into the group that matching the Rome Ⅳ criteria (Rome Ⅳ group), and the group that matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria (Rome Ⅲ group). The basic characteristics (IBS course, post-infectious IBS, history of smoking or drinking, etc.), abdominal symptoms, and defecation-related symptoms of two groups were compared and analyzed by face-to-face questionnaires. Multi-dimensional clinical manifestations assessment was completed by questionnaires, which included gastrointestinal symptom rating scale (GSRS), irritable bowel syndrome-severity scoring system (IBS-SSS), irritable bowel syndrome-quality of life (IBS-QOL), and hospital anxiety and depression scale (HADS). Independent sample t-test, rank sum test, and chi-square test were used for statistical analysis. Results:There were 344 patients (72.9%) in Rome Ⅳ group and 128 patients (27.1%) in Rome Ⅲ group. The IBS course of patients in Rome Ⅳ group was longer than that in Rome Ⅲ group (3.0 years (7.0 years) vs. 2.0 years (5.7 years)), and the difference was statistically significant ( Z=-2.73, P=0.006). The GSRS scores of loose stools and abdominal pain of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group, and the GSRS scores of increased exhaust and abdominal distension of IBS patients in Rome Ⅳ group were lower than those in Rome Ⅲ group (3.0(2.0) vs. 2.0(4.0), 3.0(2.0) vs.1.0(2.0), 1.5(3.0) vs. 2.0(3.0), 1.0 (3.0) vs. 2.0(3.0)), and the differences were statistically significant ( Z=-2.48, -9.90, -2.11 and -2.06, P=0.013, <0.001, =0.035 and =0.040). The proportions of fatigue and dizziness of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (58.4% (201/344) vs. 43.0% (55/128), 30.8% (106/344) vs. 29.7% (38/128)), and the differences were statistically significant ( χ2=8.37 and 12.36, P=0.004 and <0.001). The scores of anxiety and depression subscales of the HADS of IBS patients in Rome Ⅳ group were higher than those in Rome Ⅲ group (6.5 (6.8) vs. 6.0 (6.0), 5.0 (6.0) vs. 3.0 (5.0)), and the differences were statistically significant ( Z=-2.58 and -2.40, P=0.010 and 0.017). The scores of IBS-SSS scale, abdominal pain severity, abdominal pain frequency, and impact on quality of life of IBS patients in Rome Ⅳ group were all higher than those in Rome Ⅲ group (249.5 (108.0) vs. 177.0 (111.8), 50.0 (25.0) vs. 20.0 (30.0), 50.0 (70.0) vs. 10.0 (30.0), 66.0 (42.0) vs. 42.5 (34.0)), and the differences were statistically significant ( Z=-7.79, -9.64, -10.65 and -2.48, P<0.001, <0.001, <0.001 and =0.013). The score of IBS-QOL for behavioral disorder of IBS patients in Rome Ⅳ group was lower than that in Rome Ⅲ group (74.5±21.6 vs. 79.2±17.7), and the difference was statistically significant ( t=-2.22, P=0.027). Conclusion:The clinical symptoms of patients mathching the Rome Ⅳ criteria are more typical and severe, as compared with those of IBS patients matching the Rome Ⅲ criteria but not matching the Rome Ⅳ criteria.

Objective To explore the intestinal barrier regulation effect of Butuyajie recipe on antibiotic-associated diarrhea rats.Methods 60 SD male rats were randomly divided into blank group,model group,positive drug group(1 g·kg-1),and high-dose,medium-dose and low-dose groups of Butuyajie recipe(40.5,20.25,10.125 g·kg-1).The model was replicated by intragastric administration of lincomycin hydrochloride(5 g·kg-1)for 7 consecutive days.After successful modeling,the materials were obtained after drug intervention for 7 days.Intestinal pathological morphology was observed by HE staining.ELISA kit to detect DAO,MPO,LPS.Take each organ tissue to detect bacterial translocation.Feces were collected for 16S rRNA gene high-throughput sequencing analysis.Results Compared with the normal group,the serum levels of DAO,MPO and LPS in the model group were significantly increased(P<0.001,P<0.01),and the sIgA content in the intestinal mucosa was significantly decreased(P<0.001).Promote intestinal bacterial translocation(P<0.001,P<0.01).The diversity of intestinal flora was significantly reduced,and the levels of intestinal microflora and genera were significantly changed.Butuyajie recipe can reduce the content of DAO,MPO and LPS(P<0.001,P<0.01,P<0.05),significantly increase the content of sIgA(P<0.01,P<0.05),and effectively inhibit the translocation of intestinal bacteria(P<0.001,P<0.01,P<0.05).At the same time,it corrects the intestinal microecological structure by increasing Firmicutes,inhibiting the proportion of Bacteroidetes and Proteobacteria,and regulating Lactobacillus,Sphingomonas,Pseudomonas,and Enterobacter.Conclusion Butuyajie recipe can reduce the permeability of intestinal mucosa,reduce the translocation of intestinal flora,protect the intestinal immune barrier,regulate the diversity of intestinal flora structure,improve the intestinal microecological disorder,and can effectively treat antibiotic-associated diarrhea.

Objective In order to explore the preventive effect and potential mechanism of Dai medicine Shenyeshan leech on chronic renal failure(CRF).The rat model of chronic renal failure was induced and replicated by adenine,and the pharmacodynamics and mechanism of CRF prevention and treatment were discussed.Methods SD rats were randomly divided into normal group,model group,Yougui pill group,high-dose alcohol extract group,middle-dose group,low-dose group.Prophylactic administration was performed 5 days before modeling,and starting from the 6th day,rats in the model group and each administration group were given 1.0%adenine by gavage in the morning,and drug treatment was given in the afternoon for 15 days.24 hours after the last administration,urine specific gravity(SG)was determined by refraction method;urine creatinine(Ucr)and 24-hour proteinuria(PRO)were determined by biochemical analyzer;red blood cell count(RBC),platelet number(Plt)were determined by cell analyzer,hemoglobin(HGB),mean platelet volume(Mpv),mean corpuscular volume(Mcv).Enzyme-linked immunosorbent assay kits were used to determine blood urea nitrogen(BUN),serum creatinine(Scr)content and urinary α1-microglobulin(α1-MG),kidney injury molecule-1(KIM-1)expression.Hematoxylin-eosin staining was used to observe the pathological morphology of rat kidneys,and immunohistochemical staining was used to analyze the expression of aquaporin 2(AQP2),transforming growth factor-β1(TGF-β1),and hypoxia-inducible factor(HIF-1α)-related proteins.Results Compared with the model group,the rats were significantly improved in various symptoms such as lethargy,sluggish reaction,yellow and rough coat with falling off,and the pathological morphology of the kidneys after administration.Blood routine indexes RBC,HGB,Mpv,Mcv levels increased,Plt level decreased.The 24-hour total urine volume decreased significantly(P<0.05),and the SG in the low-dose group increased significantly(P<0.05).When URO=3.2 μmol·L-1,urinary PRO could be recovered to negative after drug treatment.The levels of renal function injury indexes BUN,α1-MG and KIM-1 were significantly decreased(P<0.05,P<0.01,P<0.001);the renal index and Ccr levels of the rats in the administration group were significantly improved(P<0.05,P<0.01).At the same time,the related AQP2,TGF-β1 and HIF-1α protein expressions were improved.To sum up,it can be seen that the leech of the kidney leaf mountain can improve the renal histopathology and various indicators of chronic renal failure rats,reduce the degree of renal injury and renal fibrosis,and has a positive effect on the prevention and treatment of CRF in rats.

Objective To explore the effect and possible mechanism of petroleum ether extract from Gastrodia elata on A amyloid β-protein deposition in Caenorhabditis elegans(C.elegans).Methods C.elegans was used as the model organism,and the experiment was divided into blank group(Control group),GEPEE 0.5 mg·mL-1 group and GEPEE 1 mg·mL-1 group.The effects of GEPEE on paralysis,life span,oxidative stress,heat stress,reactive oxygen species(ROS)level and Aβ aggregation of C.elegans were investigated,qRT-PCR was used to detect the changes of gene expression related to insulin/IGF-1 signaling pathway(IIS)in C.elegans.The main components were analyzed by high performance liquid chromatography(HPLC).Results Compared with Control group,GEPEE could significantly improve the paralysis phenotype of C.elegans(P<0.01),prolong the lifespan of C.elegans(P<0.01),enhance the motility of C.elegans(P<0.01),and increased the resistance to external oxidative stress(P<0.01),the stress ability of high temperature(P<0.01),improved the deposition of Aβ in vivo(P<0.01),decreased the ROS content in C.elegans(P<0.01),decreased the expression levels of Aβ and DAF-2(P<0.01),increased the expression levels of DAF-16 and its target genes SOD-3,GSH-Px,HSF-1 and its target gene HSP-16.2,SKN-1 and its target gene GST-4(P<0.01).Its main components were p-hydroxybenzyl alcohol and p-ethoxylbenzyl alcohol by HPLC.This study showed that GEPEE can reduce Aβ-induced toxicity in CL4176 C.elegans by reducing ROS level in vivo,increasing antioxidant level and regulating IIS pathway.Conclusion GEPEE can inhibit the toxicity of Aβ protein,and its mechanism is related to the regulation of IIS signaling pathway.