Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

Objective To investigate the comparative efficacy of different frequencies of pelvic floor electrical stimulation(PFES)on stress urinary incontinence(SUI)in rats.Methods Twenty female Sprague-Dawley rats were randomly divided into 6,15,30 and 50 Hz group by random number table method.All rats underwent vaginal dilatation(VD)to simulate postpartum SUI.One week after VD,the sneeze test was conducted to determine whether the modeling was successful.If the sneeze test was positive,the modeling was successful.The miniature and wireless electric pelvic floor stimulator were implanted into the pelvic floor muscle of the modeled rats,and PFES were treated for 2 weeks in each group at the rates of 6,15,30 and 50 Hz,respectively.The Leak point pressure(LPP)of all rats before VD,1 week after VD and 2 weeks after stimulation were measured by cystometrograms(CMGs)for comparison.Results LPP was significantly reduced in all groups of rats after VD 1 week(P<0.001).Compared with after VD 1 week,after two consecutive weeks of PFES at four different frequencies of 6,15,30 and 50 Hz,LPP was again significantly increased(P<0.001)and reached the baseline level(P>0.05)in all groups of rats.In the between-group comparison of the rats in each group,there was no significant difference in their LPP at baseline value,after VD 1 week and after stimulation 2 weeks(P>0.05).Conclusion The present study suggests that of the several stimulation frequencies explored so far,6 Hz may be a more appropriate choice for PFES.Further studies are still needed to evaluate more frequencies and the long-term efficacy of PFES.

Background and Aims:Single-incision laparoscopic cholecystectomy(LC)has become increasingly popular due to its minimal invasiveness and cosmetic advantages,but challenges remain in biliary identification and limited operative space.Indocyanine green(ICG)fluorescence navigation enables real-time visualization of the biliary tract and may enhance surgical safety and efficiency.This study aimed to evaluate the clinical application value of ICG fluorescence navigation in single-incision LC.Methods:A retrospective analysis was conducted on 59 patients with benign gallbladder diseases who underwent elective single-incision LC at Yixing Hospital affiliated to Jiangsu University from January 2023 to December 2024.Patients were divided into a fluorescence group(n=27)and a white-light group(n=32)according to whether ICG fluorescence navigation was applied.The two groups were compared in terms of Calot's triangle dissection time,operative time,intraoperative blood loss,surgeon satisfaction,hospital stay,and postoperative complications.Results:No significant differences were observed in baseline clinical characteristics between the two groups(all P＞0.05).In the fluorescence group,the cystic duct,common hepatic duct,and common bile duct were all successfully visualized.Compared with the white-light group,the fluorescence group had significantly shorter Calot's triangle dissection time[(25.56±3.49)min vs.(38.81±5.59)min],shorter operative time[(44.67±3.06)min vs.(61.31±4.96)min],and less intraoperative blood loss[(13.44±1.70)mL vs.(14.50±2.11)mL](all P＜0.05),with significantly higher surgeon satisfaction(P＜0.05).No intraoperative bile duct injury,conversion to three-port surgery,or postoperative complications occurred in either group.Conclusion:ICG fluorescence navigation can significantly improve biliary identification efficiency in single-incision LC,shorten operative time,reduce blood loss,and enhance surgeon satisfaction,demonstrating promising clinical application prospects.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

Objective To investigate the effect of two treatment regimens combining Tacrolimus(TAC)with different Rituximab(RTX)dosages,and to provide clinical reference for treatment strategies.Methods A retrospective analysis was conducted on patients diagnosed with idiopathic membranous nephropathy(IMN)and treated with RTX combined with TAC regimen(RTX+TAC group and low-dose RTX+TAC group)in The First Affiliated Hospital of Xinxiang Medical University.Propensity score matching(PSM)was performed at a 1:1 ratio,and a total of 60 patients were enrolled,with 30 in each group.In low-dose RTX(375 mg/m2 at the first and fifteenth day respectively)+TAC group,if circulating B cells(CD19?)exceeded 5 cells/μL after 3 months,a 200 mg RTX infusion was administered.In RTX(1g at the first and fifteenth day respectively)+TAC group,if complete remission(CR)was not achieved by 6 months,an additional 1000 mg RTX infusion was administered.The incidence of CR,partial remission,and adverse events were followed up for 12 months after medication in both groups.Results(1)Both groups showed significant reductions in 24-hour proteinuria,with the RTX+TAC group demonstrating a notably higher decrease compared to the low-dose RTX+TAC group.Statistical differences were observed between the two groups at the 1st and 3rd months of treatment(P<0.05).Albumin levels gradually increased,and there were differ-ences between the two groups at both the 1st and 3rd months(P<0.05).The anti-phospholipase A2 antibody levels decreased significantly after one month of treatment[3.45(1.90,22.10)vs.3.28(8.30,23.08)RU/mL],P>0.05.At 3 months of treatment,the overall clinical remission rate was 63.3％for the RTX+TAC group compared to 36.7％for the low-dose RTX+TAC group(P<0.05).At 12 months,the RTX+TAC group achieved an overall remission rate of 86.7％,while the low-dose RTX+TAC group reached 83.3％,showing no statistical significance(P>0.05).After one month of treatment,the RTX+TAC group achieved a complete serological immunological remission rate of 33.3％,significantly higher than the 3.3％in the low-dose RTX+TAC group(P<0.05).(2)The cumulative remission rate of the RTX+TAC group was higher than that of the low-dose RTX+TAC group during the first 6 months of follow-up.The remission rate in the low-dose RTX+TAC group increased significantly after 6 months.Log-rank test showed no statistical difference between the survival curves of the two groups(P=0.37).(3)Based on a multifactorial COX regression analysis of factors related to remission in patients with IMN,for every unit increase in serum immunological remission time,the risk of patients achieving remission decreased by 13.5％(HR=0.87,P=0.016).The risk of remission for patients with high titers of anti-PLA2R antibodies decreased by 60.2％(HR=0.39,P=0.018).Conclusions Different RTX dosages yielded comparable overall clinical remission rates without significantly increasing adverse events.RTX+TAC regimen achieves higher early CR rate.Serological remission time and high titer anti-PLA2R antibodies are associated with clinical outcomes.

Objective To investigate the comparative efficacy of different frequencies of pelvic floor electrical stimulation(PFES)on stress urinary incontinence(SUI)in rats.Methods Twenty female Sprague-Dawley rats were randomly divided into 6,15,30 and 50 Hz group by random number table method.All rats underwent vaginal dilatation(VD)to simulate postpartum SUI.One week after VD,the sneeze test was conducted to determine whether the modeling was successful.If the sneeze test was positive,the modeling was successful.The miniature and wireless electric pelvic floor stimulator were implanted into the pelvic floor muscle of the modeled rats,and PFES were treated for 2 weeks in each group at the rates of 6,15,30 and 50 Hz,respectively.The Leak point pressure(LPP)of all rats before VD,1 week after VD and 2 weeks after stimulation were measured by cystometrograms(CMGs)for comparison.Results LPP was significantly reduced in all groups of rats after VD 1 week(P<0.001).Compared with after VD 1 week,after two consecutive weeks of PFES at four different frequencies of 6,15,30 and 50 Hz,LPP was again significantly increased(P<0.001)and reached the baseline level(P>0.05)in all groups of rats.In the between-group comparison of the rats in each group,there was no significant difference in their LPP at baseline value,after VD 1 week and after stimulation 2 weeks(P>0.05).Conclusion The present study suggests that of the several stimulation frequencies explored so far,6 Hz may be a more appropriate choice for PFES.Further studies are still needed to evaluate more frequencies and the long-term efficacy of PFES.

Neuropathic pain(NP)is a type of chronic pain caused by damage or disease of the nervous system.It is mainly characterized by spontaneous pain,hyperalgesia,and allodynia,which seriously af-fect the quality of life of patients.The pathogenesis of NP is complex,involving abnormal regulation such as peripheral sensitization,central sensitization,ion channel changes,and glial cell activation.In recent years,the role of m6A in NP has attracted extensive attention.However,the research on the role of m6A modification in different diseases and pain models is still limited.Therefore,it is particularly important to clarify the role of m6A modification in different diseases and pain models.This article reviews the re-search progress on the role and mechanism of m6A methylation modification in the pathogenesis of NP in recent years,especially the role mechanism of the five classical m6A modification factors,METTL3,METTL14,FTO,ALKBH5 and YTHDF1,in mediating the formation of NP in different diseases and pain models,with the expectation of providing new insights and ideas for the drug development and pre-vention of NP from the perspective of m6A modification.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

Background and Aims:Single-incision laparoscopic cholecystectomy(LC)has become increasingly popular due to its minimal invasiveness and cosmetic advantages,but challenges remain in biliary identification and limited operative space.Indocyanine green(ICG)fluorescence navigation enables real-time visualization of the biliary tract and may enhance surgical safety and efficiency.This study aimed to evaluate the clinical application value of ICG fluorescence navigation in single-incision LC.Methods:A retrospective analysis was conducted on 59 patients with benign gallbladder diseases who underwent elective single-incision LC at Yixing Hospital affiliated to Jiangsu University from January 2023 to December 2024.Patients were divided into a fluorescence group(n=27)and a white-light group(n=32)according to whether ICG fluorescence navigation was applied.The two groups were compared in terms of Calot's triangle dissection time,operative time,intraoperative blood loss,surgeon satisfaction,hospital stay,and postoperative complications.Results:No significant differences were observed in baseline clinical characteristics between the two groups(all P＞0.05).In the fluorescence group,the cystic duct,common hepatic duct,and common bile duct were all successfully visualized.Compared with the white-light group,the fluorescence group had significantly shorter Calot's triangle dissection time[(25.56±3.49)min vs.(38.81±5.59)min],shorter operative time[(44.67±3.06)min vs.(61.31±4.96)min],and less intraoperative blood loss[(13.44±1.70)mL vs.(14.50±2.11)mL](all P＜0.05),with significantly higher surgeon satisfaction(P＜0.05).No intraoperative bile duct injury,conversion to three-port surgery,or postoperative complications occurred in either group.Conclusion:ICG fluorescence navigation can significantly improve biliary identification efficiency in single-incision LC,shorten operative time,reduce blood loss,and enhance surgeon satisfaction,demonstrating promising clinical application prospects.

The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.