BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

Objective:To explore the related risk factors contributing to re-fracture after hip surgery in elderly patients.Methods:This retrospective analysis was conducted on the clinical data of 2 415 elderly individuals who underwent surgical treatment for hip fractures and were discharged from Shanghai Sixth People's Hospital between January 2016 and December 2021.Patients were grouped into re-fracture and non-re-fracture cohorts based on whether a second fracture occurred within three years after surgery.Demographics, clinical data, and postoperative functional rehabilitation outcomes of the two groups were collected, and univariate and multivariate logistic regression analyses were applied to identify the independent risk factors for re-fractures after surgery.Results:A total of 2, 000 patients who completed follow-up were included in the final analysis, aged 60~91 years, with a mean age of (75.4±8.2) years.Among them, 855 were male(42.75%), and the postoperative re-fracture incidence was 28.25% (565/2 000). Univariate analysis indicated that advanced age, fracture type at first onset, lower Harris scores, insufficient rehabilitation training, osteoporosis, diabetes, cerebrovascular disorders, visual impairment, and syncope were all significantly associated with re-fracture (all P<0.05), while gender differences were not statistically significant ( P>0.05). Multivariate regression confirmed the following as independent risk factors: age ≥75 years, postoperative Harris score <80, non-standard rehabilitation training, combined osteoporosis, diabetes, cerebrovascular disease, visual impairment, and syncope ( OR、 RR>1). Conclusions:Elderly patients are prone to re-fracture after hip surgery, and its occurrence is closely related to advanced age, inadequate functional rehabilitation, osteoporosis, and multiple internal medical comorbidities.In clinical practice, attention should be paid to standardized postoperative rehabilitation, systematic anti-osteoporotic therapy, and active intervention of comorbidities to reduce the incidence of re-fracture and improve the long-term prognosis of patients.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Objective To explore the effect of maternal exercise on blood pressure,cardiac pheno-type and susceptibility to myocardial is chemia/reperfusion(MI/R)injury in adult male offsprings of mice.Methods Pregnant mice were randomly divided into a sedentary group(p-Ctr)and an exercise group(p-EX),each of 12.The exercise group underwent daily 60-minutenon-weight bearing swim-ming from gestational day(GD)1 to 18,6 days a week.Then,their male offsprings at 3 months of age(3M)were selected as the research subjects,namely the Ctr-3M group and the EX-3M group,with 12 mice in each group.The MI/R model was established by ligation of the anterior descending branch of the left coronary artery(LAD)surgery(30 min of ischemia,24 h of reperfusion).Then,the systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)were monitored non-invasively via tail artery blood pressure measurement,while the cardiac function was detected by using the small animal ultrasound.Moreover,the cardiac morphology and col-lagen volume fraction(CVF)of myocardium was observed by HE staining and Masson staining,respec-tively.Meanwhile,the cross-sectional area(CSA)of myocardial cells and myocardial infarction area(INF/AAR)was measured using WGA staining and Evans Blue-TTC double staining,accordingly.What's more,the apoptosis index(AI)of myocardial cells and serum cardiac troponin I(cTnI)were de-tected by using TUNEL staining and ELISA,respectively,while the expression levels of Bax and Bcl-2 proteins were determined by using Western blotting.Results 1)From GD11 to GD19,the body weight of females in the p-EX group was always significantly lower than that in the p-Ctr group(GD11,GD13;P<0.05;GD12,GD14～GD19;P<0.01),but there was no significant difference in the litter size and abortion rate(P>0.05).2)There were no significant differences between the EX-3M and Ctr-3M groups in the heart weight(HW),body weight(BW)and heart weight to body weight ratio(HW/BW),SBP,DBP,MAP,myocardial CVF,and CSA of male offsprings(P>0.05).After MI/R surgery,in both p-Ctr and p-EX groups,myocardial transverse striations disappeared and cardiomyocytes were disarranged with degeneration and necrosis.Moreover,CVF of the EX-3M group was significantly lower than the Ctr-3M group after MI/R surgery(P<0.05).3)No significant differenc-es were found between the Ctr-3M and EX-3M groups in the average cardiac ejection fraction(EF),fractional shortening(FS),left ventricle internal diameter in diastole(LVIDd),and left ventricle inter-nal diameter in systole(LVIDs)(P>0.05).However,after the MI/R surgery,the postoperative EF and FS(P<0.01),and LVIDs(P<0.05)in the EX-3M group were significantly higher than the Ctr-3M group,without significant difference in LVIDd(P>0.05).4)After MI/R surgery,the average AI,INF/AAR and serum cTnI level of the EX-3M group were significantly lower than the Ctr-3M group(P<0.01 for all).5)The relative expression level of myocardial Bcl-2 protein after MI/R surgery in the EX-3M group was significantly higher than the Ctr-3M group(P<0.05),while that of myocardial Bax protein(P<0.05)and the Bax/Bcl-2 ratio(P<0.01)were significantly lower than the latter.Conclu-sions Prenatal exercise significantly reduces the susceptibility to myocardial ischemia injury in 3-month-old male mice offspring,improves the contractile function of their heart,and attenuates the degree of cardiomyocyte apoptosis and necrosis,exerting a cardioprotective effect in MI/R injury.

In clinical practice,the diagnosis of hepatocellular carcinoma primarily relies on imaging findings.For cases with atypical imaging features or insufficient diagnostic specificity,pathological analysis remains essential.With the advancement of precision medicine,research focus has expanded from pure diagnostic evaluation to therapeutic efficacy prediction.Imaging-based prognostic biomarkers have emerged as a key research frontier in hepatocellular carcinoma management.Although accurate diagnosis remains paramount,current investigations increasingly prioritize the identification of biomarkers for treatment response prediction and outcome stratification.Recent studies demonstrate that radiological characteristics not only reflect tumor heterogeneity but also carry prognostic implications for hepatocellular carcinoma.These imaging biomarkers enable non-invasive outcome prediction and provide objective evidence to optimize therapeutic decision-making.This comprehensive review summarizes MRI-derived imaging features associated with hepatocellular carcinoma prognosis,aiming to guide personalized treatment strategies and ultimately improve survival outcomes for hepatocellular carcinoma patients.

Objective To explore the anti-inflammatory properties of the ethyl acetate extract(ETCB)derived from Trollius chinensis Bge.using in vitro RAW264.7 cells stimulated with lipopolysaccharide and an in vivo mouse auricle model induced by xylene.Utilizing UHPLC-Q-TOF-MS(LC-MS)and network pharmacology,the components of ETCB were analyzed,and its anti-inflammatory mechanisms were preliminarily explored.Methods The anti-inflammatory activity of various solvent extracts of Trollius chinensis Bge.was assessed through the Griess assay.The impact of ETCB on the production of TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharide was evaluated using ELISA.Real-time qPCR was conducted to determine the effect of ETCB on the expression levels of inflammatory factors such as TNF-α,IL-6,and iNOS in cells.The anti-inflammatory efficacy was further validated in a xylene-induced ear inflammation mouse model by measuring ear swelling and tissue levels of IL-6 and TNF-α.The composition of ETCB was analyzed using LC-MS.Network pharmacology was employed to screen for effective components,targets,and pathways involved in the anti-inflammatory effects of Trollius chinensis Bge.,followed by molecular docking verification between core components and targets.Results ETCB demonstrated the most potent inhibitory effect on NO production in RAW264.7 cells stimulated by lipopolysaccharide,indicating its primary role in the anti-inflammatory activity of Trollius chinensis Bge..ETCB significantly reduced TNF-α and IL-6 levels in inflammatory cells(P<0.01)and inhibited the mRNA expression of TNF-α,IL-6,and iNOS.In the xylene-induced mouse ear inflammation model,ETCB effectively alleviated ear swelling and decreased tissue levels of TNF-α and IL-6.LC-MS analysis identified 30 chemical components in ETCB,including 21 flavonoids,7 organic acids,1 polysaccharide,and 1 anthocyanin.Network pharmacology prediction and screening revealed TNF,Akt1,PTGS2,EGFR,SRC,and MMP9 as core targets,with hydroxyquercetin,lignin from fragrant leaves,zeaxanthin from willows,plantain,thistle,and sophora flavins as key anti-inflammatory active ingredients.The molecular docking analysis revealed positive interactions,characterized by favorable binding energy,between the active components and key targets.Conclusion ETCB demonstrates strong anti-inflammatory properties both inside and outside the body,functioning through various targets and pathways.This establishes a basis for deeper understanding of the anti-inflammatory mechanism of Trollius chinensis Bge.

Objective To explore the risk prediction value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging(Gd-EOB-MRI)liver imaging reporting and data system version 2018(LI-RADS v2018)with contrast-enhanced ultrasound(CEUS)LI-RADS version 2017(LI-RADS v2017)in high-risk patients with hepatocellular carcinoma(HCC).Methods The clinical and imaging data of 122 high-risk patients for HCC(with a total of 134 liver lesions)who underwent both Gd-EOB-MRI and CEUS examination at the same time and obtained pathological results within one month were retrospectively col-lected.The nodules were classified according to the CT/MRI LI-RADS v2018 and CEUS LI-RADS v2017 criteria,and the LI-RADS classification results of the two imaging methods were subjected to Cohen's Kappa test.Using pathological results as the gold stand-ard,the diagnostic efficacy of LI-RADS v2018 and LI-RADS v2017 with LR-5 as the standard for HCC was calculated separately.Results The overall consistency between the Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classification standards was good(Kappa=0.691,P＜0.001).Using LR-5 as the standard for diagnosing HCC,the sensitivity of Gd-EOB-MRI and CEUS was 84.7％and 81.2％,the specificity was 79.6％and 73.5％,the positive predictive value was 87.8％and 84.1％,the negative predictive value was 75.0％and 69.2％,and the accuracy was 82.8％and 78.4％,respectively.There was no statistically significant difference in the diagnostic efficacy of the diagnosis of HCC by LR-5 between the two imaging methods(P＞0.05).Conclusion The Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classifica-tion standards show good overall agreement.The diagnostic efficacy of Gd-EOB-MRI for HCC using LR-5 classification is better than that of CEUS.

Background and Aims:Complex biliary stones are often accompanied by hilar adhesions,distorted anatomy,biliary variations,or biliary-enteric fistulas.Conventional laparoscopic surgery is limited in such settings,with high conversion and complication rates.Robotic surgical systems provide high-definition 3D vision and enhanced dexterity,potentially improving surgical outcomes.This study compared the clinical efficacy of robotic vs.laparoscopic surgery for complex biliary stones.Methods:A retrospective analysis was performed on 145 patients with complex biliary stones who underwent minimally invasive surgery at Fujian Provincial Hospital,Fuzhou University,from January 2023 to January 2025.Patients were divided into a robotic group(n=62)and a laparoscopic group(n=83).Intraoperative outcomes,postoperative complications,and recovery parameters were compared.Stone recurrence was assessed during follow-up.Results:Baseline characteristics were comparable between groups(all P＞0.05).The conversion rate was 0 in the robotic group vs.7.2％in the laparoscopic group(P=0.038).The postoperative complication rate was significantly lower in the robotic group(1.6％vs.10.7％,P=0.044).Time to first oral intake,first flatus,and postoperative hospital stay were all shorter in the robotic group(all P＜0.05).No stone recurrence was observed in either group during follow-up until June 2025.Conclusion:Robotic surgery is a safe and feasible approach for complex biliary stones,offering reduced conversion and complication rates and faster recovery compared with laparoscopy.It holds promise for wider clinical application in complex biliary disease.

Objective To explore the factors affecting the prognosis of patients with carbapenem-resistant Ente-robacterales(CRE)healthcare-associated infection(HAI)after neurosurgical procedure,construct and validate a nomogram prediction model.Methods Data of patients with CRE infection after neurosurgical procedure in a tertia-ry hospital in Shanghai from 2018 to 2023 were collected,patients were divided into death group and survival group based on prognosis.LASSO regression and multivariate COX regression analysis were adopted to screen indepen-dent risk factors and construct nomogram prediction model.Receiver operating characteristic(ROC)curve,calibra-tion curve,and decision curve analysis(DCA)were drawn based on Bootstrap internal validation method to evaluate the effectiveness of the model.Results A total of 241 patients were included in analysis,with 221 in the survival group and 20 in the death group.The LASSO and COX regression analysis results showed that gender,length of hospital stay＞30 days,decreased monocyte percentage(MONO％),and elevated creatinine(Cr)were independent risk factors for death in patients with CRE HAI after neurosurgical procedure.The nomogram prediction model for risk of death in CRE patients after neurosurgical procedure was established based on these findings.The model vali-dation results showed that at the 30th day,the calibration curve approached the ideal curve,the area under the ROC curve was 0.981(95％CI:0.947-1.000),the DC A curve showed that when the threshold of risk of death excee-ded 8.36％,there was a higher net benefit value.Conclusion The nomogram prediction model for prognosis during hospitalization in CRE HAI patients after neurosurgical procedure constructed based on LASSO-COX regression analysis has good goodness of fit and predictive performance,which can provide reference for early screening of high-risk patients and implementation of intervention measures in clinical practice.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.