Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

BackgroundClinical supervision is a critical component in the training and professional development of psychological counselors. Scientifically evaluating the effectiveness of clinical supervision is essential， yet reliable and effective tools for such assessments are lacing in China. ObjectiveTo translate Supervision Evaluation and Supervision Competence （SE-SC） Scale into Chinese version and evaluate its reliability and validity in clinical supervision in China， so as to provide a tool for the evaluation of supervisory effectiveness. MethodsThe SE-SC scale was translated， back-translated and culturally adapted， followed by a pilot survey to develop the Chinese version of SE-SC scale. A total of 42 counselors engaged in clinical counseling and receiving supervision at a counseling center in Shanghai from July 2021 to February 2022 were selected as the study participants. Item analysis was conducted to assess item discrimination， with critical ratio method applied to determine which items retention. Hierarchical cluster analysis was performed to compare the structure of Chinese version with the original scale. Criterion-related validity and convergent validity were used to evaluate the validity of the scale， while Cronbach's α coefficient was used to assess its reliability. ResultsChinese version of SE-SC scale consisted of a total of 28 item， including six clusters. Registered supervisors scored significantly higher than internship supervisors on the total score and on clusters three， four， five and six （t=2.536， 2.747， 5.881， 3.718， 6.090， P<0.05）. The total and cluster scores of the Chinese version of the SE-SC scale were positively correlated with self-rated supervision helpfulness and overall satisfaction （r=0.492~0.758， 0.412~0.815， P<0.01）. The Cronbach's α coefficient for the overall scale was 0.975，with values for the six clusters were 0.938， 0.821， 0.962， 0.871， 0.884 and 0.823， respectively. ConclusionChinese version of SE-SC scale demonstrates good reliability and validity， and it can be considered as a promising assessment tool for evaluating the effectiveness of clinical supervision.

Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.

Aim To investigate the effect of vanillin on the regulation of cyclic guanylate adenylate synthetase(cGAS)/stimulator of interferon gene(STING)signa-ling pathway on hepatic tissue injury in rats with intra-hepatic cholestasis(IC).Methods SD rats were randomly divided into normal group,IC group,vanillin group,cGAS overexpression group,and vanillin+cGAS overexpression group,with continuous adminis-tration for seven days.The body weight,liver weight and liver to body weight ratio of rats were measured.Liver function(ALT,AST,ALP,LDH),IC(TBIL,TBA)and liver fibrosis(HA,LN,PC Ⅲ)index were determined by ELISA.Liver pathology and fibrosis were observed using HE and Masson staining,and col-lagen volume fraction was calculated.The expression of cGAS/STING pathway related proteins in liver tissue was detected by Western blot.Results Vanillin could improve liver pathology and fibrosis,increase body weight,and decrease liver weight,ALT,AST,ALP,LDH,TBIL,TBA,HA,LN,PC Ⅲ,collagen volume fraction,cGAS,STING protein in IC rats(P＜0.05).Overexpression of cGAS could reverse the effects of vanillin on the above indicators in IC rats(P＜0.05).Conclusions Vanillin may improve liver function,IC,liver fibrosis,and liver tissue damage in IC rats by downregulating the cGAS/STING signaling pathway.

Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

Objective To explore influencing factors of functional recovery after ankle fracture of type Ⅱ degree and above supination-external rotation.Methods Clinical data of 120 patients with ankle fractures of type Ⅱ degree and above supination-external rotation admitted from February 2019 to April 2021 were retrospectively analyzed.According to American Orthopaedic Foot and Ankle Society(AOFAS),patients were divided into excellent group with 73 patients(90 to 100 points),good group with 35 patients(75 to 89 points),and fair group with 12 patients(＜50 points).The differences of ankle active range of motion(ROM)and AOFAS score were compared among three groups at the latest follow-up.Multivariate Logistic regression analy-sis was performed to analyze the factors related to functional recovery after ankle fracture of supination-external rotation.Results There were significant differences in postoperative ROM(dorsoextension,plantar flexion,varus and valgus)and com-plications between excellent group and good and acceptable group(P＜0.05).Univariate analysis showed there were differences in age above 50 years old,Ⅳ degree of supination-external rotation fracture,lower tibiofibular ligament injury,posterior ankle fracture,no drainage tube placed,infection,antibiotic use time above 7 days(P＜0.05).Multivariate Logistic regression analy-sis showed age above 50 years old[OR=2.829,95％CI(1.049,7.628),P=0.040],Ⅳ degree fracture of supination-external ro-tation[OR=6.13,95％CI(1.153,32.593),P=0.033],lower tibiofibular ligament injury[OR=10.785,95％CI(3.338,34.894),P=0.000],and posterior ankle fracture[OR=6.349,95％CI(1.869,21.560),P=0.003]were independent risk factors for func-tional recovery after ankle fracture of supination-external rotation(P＜0.05).Conclusion The postoperative excellent outcome of ankle fracture was good,and the recovery of joint motion was better.The older age of patient,Ⅳ degree of supination-exter-nal rotation fracture,the lower tibiofibular ligament injury,and posterior ankle fracture are all adverse factors affecting func-tional recovery after supination-external rotation ankle fracture.In clinical,effective measures should be taken to deal with these influencing factors,and strive to improve the functional recovery after the operation of this type of fracture and reduce the occurrence of related complications.

Objective:To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma(MS).Methods:Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences,The First People's Hospital of Lianyungang from September 2010 to December 2021.AML1-ETO fusion,PML-RARα fusion and CBFβ breakage were detected by fluorescence in situ hybridization(FISH),and the mutations of NPM1,CEBPA,FLT3,RUNX1,ASXL1,KIT and TP53 genes were detected by new generation sequencing(NGS).Results:Among 14 patients,the MS occurred in bone,breast,epididymis,lung,chest wall,cervix,small intestine,ovary,lymph nodes and central nervous system.The tumor cells expressed MPO(13 cases),CD34(7 cases),CD43(8 cases),CD68(7 cases),CD99(8 cases)and CD117(6 cases).Cytogenetic abnormalities were observed in 4 cases,including 3 cases of AML1-ETO fusion and 1 case of CBF β breakage,while no PML-RAR α fusion was detected.There were no significant differences in overall survival(OS)and leukemia-free survival(LFS)between patients with and without AML1-ETO fusion/CBFβ breakage(both P＞0.05).Among the 14 patients,the number of NPM1,CEBPA,FLT3-ITD,RUNX1,ASXL1,KIT and TP53 gene mutations was 5,3,5,3,2,2,1.respectively,of which 7 cases had at least one mutation in FLT3-ITD,RUNX1,ASXL1 and TP53 gene.The OS and LFS of patients with FLT3-ITD,RUNX1,ASXL1 or TP53 mutation were shorter than those without mutations(both P＜0.01).Conclusion:The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques.FLT3-ITD,RUNX1,ASXL1 or TP53 mutation indicates a worse prognosis,but further clinical studies are needed to confirm it.

Objective:This study aims to evaluate the impact of Diagnosis-Related-Groups(DRGs)payment on the average total cost,length of stay,service volume,effectiveness,and characteristics of traditional Chinese medicine(TCM)hospitals.Methods:A national medical center specializing in TCM was selected as the research subject.The Difference-in-Difference Model(DID)was utilized to analyze the differences in various indicators between insured patients(intervention group)and uninsured patients(control group)before and after the implementation of the payment reform policy.The reliability and stability of the model were verified through parallel trend tests and placebo tests.Results:The coefficients of DID interaction terms for eleven indicators including average total hospitalization cost,number of cases,length of stay,proportion of medical service revenue,and proportion of herbal medicine revenue were significant(P<0.05).The DID interaction term coefficients for four indicators including herbal medicine usage rate and proportion of non-pharmacological TCM therapy revenue were not significant(P>0.05).Conclusion:DRG payment significantly reduced the per-admission cost,with significant decreases in consumables and medical technology expenses,optimizing cost structure,and a slight decrease in the proportion of herbal medicine costs.It is necessary to further expand the sample size,track policy impacts,and comprehensively evaluate the effects of DRG payment on TCM hospitals in China.

Objective:To explore the expressions of zinc homeostasis-related proteins,G protein-coupled receptor 39(GPR39)and ANO1 mRNA in the sperm of patients with asthenozoospermia(AS),and analyze their correlation with sperm motility.Methods:We collected semen samples from 82 male subjects with PR+NP＜40％,PR＜32％and sperm concentration＞15 × 106/ml(the AS group,n=40)or PR+NP≥40％,PR≥32％and sperm concentration＞15 × 106/ml(the normal control group,n=42).We analyzed the routine semen parameters and measured the zinc content in the seminal plasma using the computer-assisted sperm analysis system,detected the expressions of zinc transporters(ZIP13,ZIP8 and ZNT10),metallothioneins(MT1G,MT1 and MTF),GPR39,and calcium-dependent chloride channel protein(ANO1)in the sperm by real-time quantitative PCR(RT qPCR),examined free zinc distribution in the sperm by laser confocal microscopy,and determined the expressions of GPR39 and MT1 proteins in the sperm by immunofluorescence staining,followed by Spearman rank correlation analysis of their correlation with semen parameters.Results:There was no statistically significant difference in the zinc concentration in the seminal plasma between the AS and normal control groups(P＞0.05).Compared with the controls,the AS patients showed a significantly reduced free zinc level(P＜0.05),relative expressions of MT1G,MTF,ZIP13,GPR39 and ANO1 mRNA(P＜0.05),and that of the GPR39 protein in the AS group(P＜0.05).No statistically significant differences were observed in the relative expression levels of ZIP8,ZNT10 and MT1 mRNA between the two groups(P＞0.05).The relative expression levels of GPR39,ANO1,MT1G and MTF mRNA were positively correlated with sperm motility and the percentage of progressively motile sperm(P＜0.05).Conclusion:The expressions of zinc homeostasis proteins(MT1G,MTF and ZIP13),GPR39 and ANO1 mRNA are downregulated in the sperm of asthenozoospermia pa-tients,and positively correlated with sperm motility.