Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective To explore the expression level of visceral adipose tissue-derived serine protease inhibitor(Vaspin)and secreted frizzled-related protein5(SFRP5)in the serum of children with idiopathic short stature(ISS)and its diagnostic value.Methods 70 children with ISS diagnosed in the First Hospital of Zhangjiakou from December 2021 to February 2023 were selected as the disease group,while 72 healthy volunteer children who underwent physical examination were collected as the control group.Immunoluminescence was applied to detect the expression level of VASPIN,Enzyme-linked immunosorbent assay(ELISA)was applied to detect the expression level of SFRP5 the clinical data of children in two groups were analyzed.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum Vaspin and SFRP5 for ISS,multivariate Logistic regression was used to analyze the influencing factors of ISS.Results Compared with the control group,the serum Vaspin level in the disease group was obviously increased(2.89±0.92 ng/ml vs 1.81±0.42 ng/ml),while the SFRP5 level was obviously reduced(10.22±2.84 pg/ml vs 13.21±3.53 pg/ml),the differences were statistically significant(t=9.040,5.552,all P＜0.05).The weight,height,body mass index(BMI)and proportion of sexual development stage II～V of children in the disease group were obviously lower than those in the control group,and the differences were statistically significant(t=7.687,6.330,5.559,7.024,all P＜0.05).The area under ROC curve showed that the AUC of Vaspin and SFRP5 and their combined detection in the diagnosis of ISS were 0.768,0.849 and 0.925,respectively,the combined diagnosis efficacy of Vaspin and SFRP5 was better than that of serum Vaspin and SFRP5 alone(Z =3.829,P＜0.001;Z =2.141,P=0.032).Multivariate Logistic regression analysis showed that BMI(OR=0.508,95%CI:0.260～0.991),Vaspin(OR=3.458,95%CI:1.125～10.631)and SFRP5(OR=0.378,95%CI:0.153～0.935)were the influencing factors for ISS(all P＜0.05).Conclusion The expression level of Vaspin in the serum of children with ISS is obviously increased,while the expression level of SFRP5 is obviously reduced.The two are influencing factors of ISS,and the combined detection of their expression levels has certain value in the diagnosis of ISS.

ObjectiveTo systematically review the efficacy and safety of laparoscopic choledochoscopy combined with holmium laser lithotripsy through a meta－analysis. MethodsThis study was conducted based on PRISMA guidelines， with a PROSPERO registration number of CRD42023406221. Chinese databases including CNKI， Wanfang Data， and VIP and foreign language databases such as PubMed， Embase， the Cochrane Library， and Web of Science were searched for original articles on traditional laparotomy versus laparoscopic choledochoscopy combined with holmium laser lithotripsy in the treatment of bile duct stones. Dichotomous variables were assessed by odds ratio （OR） and 95% confidence interval （CI）， while continuous variables were assessed by weighted mean difference （WMD） and 95%CI， and a sensitivity analysis was performed for outcome measures with relatively high heterogeneity. The Begg test and Egger test were used to evaluate publication bias. Stata 15.0 and Review Manager 5.3 were used to perform the statistical analysis. ResultsA total of 26 retrospective studies from China were included in this study， with 2 238 patients in total. The meta－analysis showed that compared with traditional laparotomy for the treatment of bile duct stones， laparoscopic choledochoscopy combined with holmium laser lithotripsy had significantly shorter time of operation （WMD＝－1.26， 95%CI： －1.36 to －1.16， P<0.001）， length of hospital stay （WMD＝－1.93， 95%CI： －2.64 to －1.12， P <0.001）， and time to bowel function recovery （WMD＝－1.52， 95%CI： －1.68 to －1.35， P<0.001）， significantly less intraoperative blood loss （WMD＝－1.79， 95%CI： －1.93 to －1.66， P<0.001）， a significantly lower rate of intraoperative residual stone （OR＝0.15， 95%CI： 0.11－0.20， P<0.001）， and significantly fewer complications （OR＝0.17， 95%CI： 0.13－0.23， P<0.001）. ConclusionCompared with traditional laparotomy， laparoscopic choledochoscopy combined with holmium laser lithotripsy shows better efficacy in the treatment of bile duct stones.

The prognosis of gastric cancer patients is still poor although big progress has been made in the diagnosis and therapy.Peritoneal metastasis is always considered as the end stage of gastric cancer.The treatments such as cytoreductive surgery,intraoperative peritoneal hyperthermic chemotherapy,combined chemotherapy,molecular targeted therapy and gene therapy are applied to clinical management.However,no standard regimens are recommended.The multidisciplinary and individualized treatment will be put more emphasis in the future.This paper reviews the current status and progress of the diagnosis and treatment of peritoneal metastasis in gastric cancer.

Objective To evaluate the potential use of a probe melting analysis (PMA) assay in detecting the embB mutations which confer resistance against ethambutol in Mycobacterium tuberculosis. Methods The analysis sensitivity and specificity of PMA were investigated by detecting a serially diluted H37 Rv DNA and a reference panel from National Institute for the Control of Pharmaceutical and Biological Product. Six hundred and thirteen sputum samples were collected from the Xiamen Center for Disease Control and Prevention, Xiamen First Hospital and Center for Zhangzhou Disease Control and Prevention from September 2009 to April 2010. The PMA assay was then evaluated by detecting 613 clinical isolates and the results were compared with the sequencing results. Results The PMA assay could specifically detect Mycobacterium tuberculosis and had a limit of detection of 3 copies per reaction. The assay results with 613 clinical isolates showed that PMA gave a 100% concordance with sequencing in the 583 qualified samples, among which 34 were mutations at embB 306,23 at embB 378-380, 3 at embB 406 and 3 at embB 497. Conclusions PMA assay is a sensitive and specific method enabling efficient detection of common embB mutations causing ethambutol-resistance. The rapidness of this method together with its reliability would facilitate its use in routine testing.