ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To explore the effects of proteasome 20S subunit beta 8(PSMB8)on the prolif-eration,migration,and invasion of clear cell renal cell carcinoma(ccRCC)cells and whether PSMB8 promotes tumor progression by activating the mitogen-activated protein kinase kinase(MEK)/extracellular signal-regula-ted kinase(ERK)signaling pathway.Methods The Cancer Genome Atlas was employed to analyze the mRNA levels of PSMB8 in ccRCC and normal tissue,and the expression levels of PSMB8 in ccRCC tissue and cells were determined by real-time quantitative PCR,Western blotting,and immunohistochemistry.Furthermore,the cell lines with stable overexpression and knockdown of PSMB8 were constructed.The CCK-8 assay and colony forma-tion assay were employed to examine the cell proliferation,and the wound healing assay and Transwell assay were employed to examine the invasion and migration of cells.Kyoto Encyclopedia of Genes and Genomes pathway enrich-ment was performed to analyze the co-expressed genes of PSMB8.Western blotting was used to measure the phospho-rylation levels of the proteins in the MEK/ERK signaling pathway.Finally,the rescue experiment was carried out with the ERK agonist C16-PAF.Results Compared with the normal tissue,the ccRCC tissue showed up-regulated mRNA and protein levels of PSMB8(both P＜0.001),which were associated with the TNM stage of patients with ccRCC(P＜0.001).Compared with the negative control group,overexpression of PSMB8 promoted the prolifera-tion(P=0.021,P=0.039),migration and invasion(all P＜0.001)of 786-O and ACHN cells,and the knock-down of PSMB8 inhibited the proliferation(P=0.022,P=0.005),migration and invasion(all P＜0.001)of 786-O and ACHN cells.The pathway enrichment analysis of co-expressed genes of PSMB8 predicted the mitogen-ac-tivated protein kinase signaling pathway(P＜0.001).After the knockdown of PSMB8,786-O and ACHN cells showed lowered phosphorylation levels of MEK1/2(P=0.017,P=0.016)and ERK1/2(P=0.010,P=0.040)and down-regulated transcription levels of ERK downstream factors c-Myc(P=0.043,P=0.038),c-Fos(P=0.025,P=0.008),and CyclinD1(P=0.006,P=0.047).Compared with the ERK agonist C16-PAF group,the PSMB8 knockdown+C16-PAF group showed inhibited proliferation(P=0.003,P=0.002),migration and invasion(all P＜0.001)of 786-O and ACHN cells.Conclusion PSMB8 may promote the proliferation,migration,and invasion of ccRCC cells by activating the MEK/ERK signaling pathway.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective To investigate the potential categories of exercise perception in patients with end-stage renal disease(ESRD),and analyze the relationship between different latent categories and change in physical activity,so as to provide references for targeted intervention.The latent profile analysis was used to extract potential categories of exercise perception,and multiple linear regression analysis was conducted with potential categories as independent variables and change in physical activity as dependent variables.Methods A total of 265 ESRD patients from a tertiary hospital were selected from June 2022 to May 2023 by convenience sampling method.The general data questionnaire,the Dialysis Patient-perceived Exercise Benefits and Barriers Scale(DPEBBS)and the Measuring Change in Physical Activity Questionnaire(MCPAQ)were used for investigation.Results A total of 241 ESRD patients completed the survey.The results of multiple linear regression analysis showed that education level,family per capita monthly income and potential categories of exercise perception were the influencing factors of change in physical activity in ESRD patients(P＜0.05).Conclusion There was group heterogeneity in the exercise perception in patients with ESRD.Clinical workers should give targeted intervention according to the potential categories of patients'exercise perception,so as to promote the initiation and long-term maintenance of the change in physical activity.

Objective This study aims to explore the associations between threat and deprivation childhood traumas and dysfunctional attitudes among patients with major depressive episode,based on the dimensional model of adversity and psychopathology(DMAP).Methods Data from 970 patients with major depressive episode were collected and categorized based on the childhood trauma questionnaire-short form(CTQ-SF)scores into no trauma(426),threat-only(86),deprivation-only(210),and mixed groups(248).Cognitive distortions were assessed using the dysfunctional attitudes scale(DAS),with scores above the upper quartile indicating significant distortions.Multifactorial logistic regression analysis was employed to examine the association between threat and deprivation and dysfunctional attitudes.Results There were significant differences in the proportion of cognitive distortions among the no trauma,threat-only,deprivation-only,and mixed groups(19.25% vs.30.23% vs.20.00% vs.35.89%,P<0.001),with differences across all dimensions(P≤0.001).Multifactorial logistic regression revealed a positive correlation between threat and overall cognitive distortions(OR=2.031,P<0.001),and specific positive correlations with dimensions such as vulnerability(OR=1.709,P<0.001),appeal and repulsion(OR=2.088,P<0.001),perfectionism(OR=2.321,P<0.001),compulsivity(OR=1.765,P=0.001),approval seeking(OR=1.837,P<0.001),dependency(OR=1.554,P=0.006),and autonomous attitudes(OR=1.864,P<0.001).In contrast,deprivation was only positively correlated with the cognitive philosophy dimension(OR=1.495,P=0.015).Conclusion Childhood trauma is closely associated with dysfunctional attitudes in patients with major depressive episode.Threat correlates positively with cognitive distortions in all dimensions except cognitive philosophy,whereas deprivation correlates only with the cognitive philosophy dimension.

Objective·To analyze the clinical and genetic characteristics of Chinese pediatric patients with Barth syndrome(BTHS)and provide data to support the prevention and treatment of BTHS.Methods·Eighteen pediatric patients diagnosed with BTHS at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,from January 2010 to November 2023,were included.Clinical data(age,birth weight,family history,electrocardiogram,echocardiogram,urine tandem mass spectrometry,complete blood count,blood biochemistry,and genetic test results)were collected to analyze the clinical characteristics,genetic findings,and prognoses of the patients.Results·The study included 18 male patients with BTHS(including 2 monozygotic twins),consisting of one Yi ethnic and 17 Han Chinese patients.The median age at diagnosis was 3.0(1.0,5.6)months.Fifteen patients experienced decreased cardiac function at disease onset,with a left ventricular ejection fraction(LVEF)below 50%.Dilated cardiomyopathy(DCM)was observed in 15 patients,left ventricular non-compaction(LVNC)in 12 patients,and myocardial hypertrophy in 9 patients.During the diagnosis and follow-up,QTc interval prolongation occurred in 9 patients,ventricular arrhythmias in 2 patients,neutropenia in 9 patients,and monocytosis in 10 patients.Urine tandem mass spectrometry revealed 3-methylglutaconic aciduria(3-MGCA)in 8 of 13 tested patients.Fifteen types of TAZ gene mutation were identified in the 18 patients,including 5 novel mutations.Genetic testing of the parents of 16 patients indicated maternal inheritance in 15 cases.The median follow-up period was 8.5(2.6,29.3)months,during which 12 patients died.The median age at death was 7.5(6.0,12.8)months.Causes of death included heart failure(7 cases,with 4 concurrent infections),sudden death(3 cases),ventricular fibrillation(1 case),and accidental death(1 case).Conclusion·BTHS is a rare genetic disorder with multisystem involvement.Its primary clinical manifestations include cardiomyopathy and neutropenia.The condition typically presents early in life,with severe progression and poor prognosis.Prompt recognition,accurate diagnosis,and early intervention are essential for managing this disease.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.