OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

In March 2025， the American Association for the Study of Liver Diseases published its latest practice statement on metabolic dysfunction-associated steatotic liver disease （MASLD） in children. Compared with previous guidelines， this statement adopts the latest nomenclature and diagnostic criteria for MASLD， emphasizes hepatic steatosis in the presence of at least one cardiovascular metabolic risk factor， and elaborates on the unique epidemiological characteristics， pathophysiological patterns， and natural history of pediatric MASLD. Based on evidence-based medicine， the statement provides comprehensive guidance on the screening， diagnosis， treatment and monitoring of MASLD in children and emphasizes that lifestyle interventions form the cornerstone of treatment， and at present， there are still no drugs approved for the treatment of MASLD in children. This article gives an excerpt of the key recommendations in the practice statement.

Objective To investigate the effect of Porphyromonas gingivalis(Pg)infection on immune escape of oesophageal cancer cells and the role of YTHDF2 and Fas in this regulatory mechanism.Methods We examined YTHDF2 and Fas protein expressions in esophageal squamous cell carcinoma(ESCC)tissues with and without Pg infection using immunohistochemistry and in Pg-infected KYSE150 cells using Western blotting.The interaction between YTHDF2 and Fas was investigated by co-immunoprecipitation(Co-IP).Pg-infected KYSE150 cells with lentivirus-mediated YTHDF2 knockdown were examined for changes in expression levels of YTHDF2,cathepsin B(CTSB),Fas and FasL proteins,and the effect of E64(a cathepsin inhibitor)on these proteins were observed.After Pg infection and E64 treatment,KYSE150 cells were co-cultured with human peripheral blood mononuclear cells(PBMCs),and the expressions of T cell-related effector molecules were detected by flow cytometry.Results ESCC tissues and cells with Pg infection showed significantly increased YTHDF2 expression and lowered Fas expression.The results of Co-IP demonstrated a direct interaction between YTHDF2 and Fas.In Pg-infected KYSE150 cells with YTHDF2 knockdown,the expression of CTSB was significantly reduced while Fas and FasL expressions were significantly increased.E64 treatment of KYSE150 cells significantly decreased the expression of CTSB without affecting YTHDF2 expression and obviously increased Fas and FasL expressions.Flow cytometry showed that in Pg-infected KYSE150 cells co-cultured with PBMCs,the expressions of Granzyme B and Ki67 were significantly decreased while PD-1 expression was significantly enhanced.Conclusion Pg infection YTHDF2-dependently regulates the expression of Fas to facilitate immune escape of esophageal cancer and thus promoting cancer progression,suggesting the key role of YTHDF2 in regulating immune escape of esophageal cancer.

Objective To investigate the effect of Porphyromonas gingivalis(Pg)infection on immune escape of oesophageal cancer cells and the role of YTHDF2 and Fas in this regulatory mechanism.Methods We examined YTHDF2 and Fas protein expressions in esophageal squamous cell carcinoma(ESCC)tissues with and without Pg infection using immunohistochemistry and in Pg-infected KYSE150 cells using Western blotting.The interaction between YTHDF2 and Fas was investigated by co-immunoprecipitation(Co-IP).Pg-infected KYSE150 cells with lentivirus-mediated YTHDF2 knockdown were examined for changes in expression levels of YTHDF2,cathepsin B(CTSB),Fas and FasL proteins,and the effect of E64(a cathepsin inhibitor)on these proteins were observed.After Pg infection and E64 treatment,KYSE150 cells were co-cultured with human peripheral blood mononuclear cells(PBMCs),and the expressions of T cell-related effector molecules were detected by flow cytometry.Results ESCC tissues and cells with Pg infection showed significantly increased YTHDF2 expression and lowered Fas expression.The results of Co-IP demonstrated a direct interaction between YTHDF2 and Fas.In Pg-infected KYSE150 cells with YTHDF2 knockdown,the expression of CTSB was significantly reduced while Fas and FasL expressions were significantly increased.E64 treatment of KYSE150 cells significantly decreased the expression of CTSB without affecting YTHDF2 expression and obviously increased Fas and FasL expressions.Flow cytometry showed that in Pg-infected KYSE150 cells co-cultured with PBMCs,the expressions of Granzyme B and Ki67 were significantly decreased while PD-1 expression was significantly enhanced.Conclusion Pg infection YTHDF2-dependently regulates the expression of Fas to facilitate immune escape of esophageal cancer and thus promoting cancer progression,suggesting the key role of YTHDF2 in regulating immune escape of esophageal cancer.

Objective To analyze the infectious indicators,HBV s gene mutations and changes in bioinformatics char-acteristics of HBV DNA+/HBsAg-blood donor.Methods A sample of HBV DNA+/HBsAg-was screened by PCR meth-od,and HBsAg/HBsAb/HBeAg/HBeAb/HBcAb of HBV in the sample were detected by ELISA and chemiluminescence methods.The mutation of the HBVs gene fragment in the sample was sequenced and analyzed,and the bioinformatics analy-sis was performed using analysis software.Results The sample showed HBV DNA+,HBsAg-,HBsAb+,HBeAg+,HBe-Ab-and HBcAb+,with an amino acid unit point mutation(P151L)occurred in the HBV s gene,and the spatial structure changed.Conclusion The spatial structural changes in the gene sequence of HBVs may be the reason for the appearance of serological HBsAg-/HBsAb+/HBV DNA+in the test results.

Objectives:To investigate the incidence and risk factors of perioperative complications after en bloc resection for thoracic and lumbar spinal tumors.Methods:The data of patients with thoracic and lumbar spinal tumors treated in our department with en bloc resection and anterior column reconstruction were retro-spectively analyzed.Between May 2016 and October 2022,90 consecutive patients underwent en bloc resec-tion on the basis of Weinstein-Boriani-Biagini surgical staging system,and anterior reconstruction was per-formed using 3D-printed artificial vertebral bodies.The demographic,oncological,and operative data of the patients were collected prospectively,and the intraoperative and postoperative complications occurring within three months were categorized into major and minor complications according to their impacts on the recovery process(Major complications were considered as any complication that appeared to substantially alter an other-wise full and expected course of recovery,and other complications were regarded as minor).All the patients were divided into the primary group(n=67)and revision group(n=23)based on their previous surgical history.Differences between the two groups in terms of age,gender,pathological type,tumor-involved segments,oper-ative time,intraoperative blood loss,and perioperative complications were compared.The predictive factors for major and minor complications were explored.Results:En bloc resection was achieved in all the patients,in-cluding total en bloc spondylectomy in 77 cases,sagittal resection in 12 cases,and vertebrectomy in one case.The mean operative time was 553.4min(210-1208min),and the mean intraoperative blood loss was 1534.1mL(260-5500mL).A total of 129 complications were observed in 65(72.2%)patients,including 29 ma-jor complications in 21(23.3%)patients.Two patients(2.2%)died as a result of complications.The revision group was more than primary group in tumor-involved segments(P=0.000)and incidence rate of major compli-cations(P=0.038).In univariate regression analysis,the combined approach[odds ratio(OR)=14.778,P=0.001],total blood loss(OR=1.004,P=0.004),staged surgery(OR=5.250,P=0.008),previous surgical history(OR=2.946,P=0.043),number of tumor-involved vertebrae(OR=1.607,P=0.023)and lumbar tumor(OR=3.509,P=0.015)were statistically significant risk factors for major complication occurrence,while the combined approach(OR= 6.375,P=0.036)was the independent risk factor.Conclusions:En bloc resection and anterior column recon-struction is associated with high risks of complications,especially when a combined approach is needed.

Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.

Objective·To evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.