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.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Plant-derived exosome-like nanovesicles refer to spherical lipid bilayer vesicles isolated from plants that contain lipids,proteins,RNAs,and various small molecules.These nanovesicles exhibit di-verse biological activities,including anti-inflammatory,anti-tumor,antioxidant,and drug delivery prop-erties.However,the functional characteristics of nanovesicles derived from rhizoma polygonati remain un-explored.In this study,exosome-like nanovesicles derived from rhizoma polygonati(referred to as RP-EVs)were successfully isolated using ultracentrifugation and density gradient centrifugation.Their physi-cochemical properties and anti-inflammatory functions were systematically characterized.Our results show that RP-EVs are predominantly negatively charged,with an average particle size of 166.5±3.3 nm,and are spherical lipid vesicles.Cellular uptake assays demonstrated that RP-EVs can be phagocytized by macrophages.qPCR and ELISA experiments revealed that RP-EVs can inhibit the elevation of interleukin 6(IL-6),interleukin 1 β(IL-1 β),and tumor necrosis factor-alpha(TNF-α)induced by lipopolysac-charide(LPS)stimulation(****P＜0.0001).Additionally,reactive oxygen species(ROS)and 2,2-diphenyl-1-picrylhydrazyl(DPPH)scavenging assays confirmed that RP-EVs exhibit antioxidant proper-ties(*P＜0.05).Further investigation of the underlying mechanisms through immunofluorescence and Western blotting revealed that RP-EVs inhibit the nuclear translocation(**P＜0.01)and phosphoryla-tion(***P＜0.001)of nuclear factor kappa-B p65(NF-κB p65)via the IκBα/NF-κB signaling path-way,thereby regulating the expression of inflammatory mediators.In animal experiments,intraperitoneal injection of RP-EVs into mice for 48 hours showed predominant localization in the liver and spleen.Fi-nally,an acute inflammatory mouse model was established via intraperitoneal injection of LPS.qPCR and ELISA analyses demonstrated that RP-EVs alleviated the expression of inflammatory factors in both the serum and spleen of LPS-treated mice(*P＜0.05).In conclusion,this study isolated RP-EVs and elu-cidated their anti-inflammatory properties and potential mechanisms.These findings provide valuable in-sights into the functional exploration of nanoparticle vesicles derived from traditional Chinese medicine and suggest a novel therapeutic strategy for the treatment of inflammation-related diseases.

Objective:To explore the mediating role of activity of daily living between social support and cognitive function of rural elderly.Methods:A face-to-face questionnaire survey was conducted from July to August 2019 among 1 626 rural elderly people selected by multi-stage cluster random method in Guiyang City and Qiannan Prefecture, Guizhou Province.The contents include general situation, social support rate scale (SSRS), activity of daily living scale (ADL) and mini-mental state examination (MMSE). Partial correlation analysis and multiple linear regression analysis were used to analyze the relationship among social support, activity of daily living and cognitive function in the elderly by SPSS 23.0 software. AMOS 28.0 software was used to construct structural equation models, and Bootstrap method was used to test the mediating role of activity of daily living.Results:The scores of cognitive function, social support and activity of daily living of the rural elderly were (20.83±5.47), (34.96±6.42) and (16.51±3.29), respectively.There were statistically significant differences in the cognitive function scores among rural elderly with different levels of social support and activity of daily living( F=33.418, t=25.533, P<0.01). The partial correlation analysis showed that the social support score was positively correlated with the cognitive function score ( r=0.161, P<0.01), and the activity of daily living score was negatively correlated with scores of social support and cognitive function ( r=-0.083, -0.453, both P<0.01). Multiple linear stepwise regression analysis showed that social support, objective support dimensions, activity of daily living and instrumental activity of daily living were influencing factors of cognitive function of rural elderly( P<0.001).The results of structural equation model showed that the activity of daily living played a partial mediating role between social support and cognitive function in rural elderly, with the mediating effect of 0.046 (95% CI=0.025-0.075), accounting for 13.18% of total effect (effect value=0.349, 95% CI=0.277-0.415). Conclusion:The activity of daily living of rural elderly plays a partial mediating effect between social support and cognitive functioning.

Objective To analyze the clinical diagnostic value of whole-body bone imaging combined with serum N-terminal osteo-calcin(N-Osrteoc)and vascular endothelial growth factor receptor 2(VEGFR2)for evaluating bone metastasis in elderly patients with lung cancer.Methods General data of 100 elderly patients with lung cancer diagnozed for the first time at Tianjin Hospital between December 2021 and December 2023 were retrospectively collected.Based on the pathological results,the patients were separated into a lung cancer bone metastasis group of 42 cases and a lung cancer non-bone metastasis group of 58 cases.Serum N-Osrteoc and VEGFR2 levels were detected by using an enzyme-linked immunosorbent assay(ELISA).All patients underwent whole-body bone imaging using SPECT diagnostic equipment.Receiver operator characteristic(ROC)curve analysis was performed to determine the diagnostic value of serum N-Osrteoc,VEGFR2,and whole-body bone imaging for lung cancer bone metastasis.Furthermore,Kappa test was performed to analyze the consistency between different examination methods for diagnozing lung cancer bone metastasis and pathological diagnosis results.Results The serum N-Osrteoc and VEGFR2 levels in the bone metastasis group were significantly higher than those in the non-bone metastasis group(P＜0.05).The area under the curve(AUC)for serum N-Osrteoc and VEGFR2 levels,whole-body bone imaging,and their combination for diagnozing lung cancer bone metastasis were 0.847,0.846,0.907,and 0.956,respectively.Furthermore,com-pared with the pathological results,the numbers of false-positive cases were 14,19,8,and 1,those of false-negative cases were 7,7,2,and 3,and the Kappa values were 0.579,0.487,0.799,and 0.917,respectively(P＜0.05).The specificity of whole-body bone imaging combined with serum N-Osrteoc and VEGFR2 in diagnozing lung cancer bone metastasis was significantly higher than alone(P＜0.05).Conclusion The combination of whole-body bone imaging and serum N-Osrteoc and VEGFR2 levels is of great significance for early diagnosis of bone metastasis in elderly patients with lung cancer.This combined diagnosis has high sensitivity and specificity and can be widely used in clinical practice.

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.