OBJECTIVE To investigate the protective effect of Yishen tongluo formula on high glucose-induced injury in renal tubular epithelial cells and its impact on the silence information regulator 3 （SIRT3）-adenosine monophosphate-activated protein kinase （AMPK）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/carnitine palmitoyltransferase 1A （CPT1A） signaling pathway. METHODS Human renal tubular epithelial cells HK-2 were used as the subject. The cells were divided into a normal glucose group （NC group）， a high glucose group （HG group）， a high glucose+low-dose Yishen tongluo formula group [HG+L group， 0.5 mg/mL （calculated by crude drugs）]， and a high glucose+high-dose Yishen tongluo formula group [HG+H group， 1.0 mg/mL （calculated by crude drugs）]. Except for the NC group， cells in all other groups were cultured under high glucose conditions （30 mmol/L）， and cells in the HG+L and HG+H groups were simultaneously treated with the corresponding mass concentrations of medicinal liquid. Cell viability was assessed at 0， 24， and 48 h post-incubation， and reactive oxygen species （ROS） level， adenosine triphosphate （ATP） content， and the expression of molecules related to the SIRT3-AMPK/PGC-1α/CPT1A signaling pathway were measured after 48 h of incubation. RESULTS Compared with the NC group， the HG group showed significantly reduced cell viabilities （at 24 and 48 h） and ATP content， along with significantly elevated ROS levels （ P ＜0.05）. Additionally， the protein expressions of SIRT3， PGC-1α and CPT1A， as well as the mRNA expressions of PGC-1α and CPT1A， and the phosphorylation level of AMPK protein were all significantly downregulated or decreased（ P ＜0.05）. Compared with the HG group， the aforementioned indicators were significantly improved in both HG+L and HG+H groups， with the improvement being more pronounced in the HG+H group （ P ＜0.05）. CONCLUSIONS The Yishen tongluo formula can improve high-glucose-induced damage to renal tubular epithelial cells； its action may be related to activating the SIRT3-AMPK/PGC-1α/CPT1A signaling pathway， improving mitochondrial energy metabolism， and alleviating oxidative stress.

OBJECTIVE To investigate the protective effect of Yishen tongluo formula on high glucose-induced injury in renal tubular epithelial cells and its impact on the silence information regulator 3 （SIRT3）-adenosine monophosphate-activated protein kinase （AMPK）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/carnitine palmitoyltransferase 1A （CPT1A） signaling pathway. METHODS Human renal tubular epithelial cells HK-2 were used as the subject. The cells were divided into a normal glucose group （NC group）， a high glucose group （HG group）， a high glucose+low-dose Yishen tongluo formula group [HG+L group， 0.5 mg/mL （calculated by crude drugs）]， and a high glucose+high-dose Yishen tongluo formula group [HG+H group， 1.0 mg/mL （calculated by crude drugs）]. Except for the NC group， cells in all other groups were cultured under high glucose conditions （30 mmol/L）， and cells in the HG+L and HG+H groups were simultaneously treated with the corresponding mass concentrations of medicinal liquid. Cell viability was assessed at 0， 24， and 48 h post-incubation， and reactive oxygen species （ROS） level， adenosine triphosphate （ATP） content， and the expression of molecules related to the SIRT3-AMPK/PGC-1α/CPT1A signaling pathway were measured after 48 h of incubation. RESULTS Compared with the NC group， the HG group showed significantly reduced cell viabilities （at 24 and 48 h） and ATP content， along with significantly elevated ROS levels （ P ＜0.05）. Additionally， the protein expressions of SIRT3， PGC-1α and CPT1A， as well as the mRNA expressions of PGC-1α and CPT1A， and the phosphorylation level of AMPK protein were all significantly downregulated or decreased（ P ＜0.05）. Compared with the HG group， the aforementioned indicators were significantly improved in both HG+L and HG+H groups， with the improvement being more pronounced in the HG+H group （ P ＜0.05）. CONCLUSIONS The Yishen tongluo formula can improve high-glucose-induced damage to renal tubular epithelial cells； its action may be related to activating the SIRT3-AMPK/PGC-1α/CPT1A signaling pathway， improving mitochondrial energy metabolism， and alleviating oxidative stress.

Objective To evaluate the risk of right heart failure after heart transplantation by establishing nomogram based on preoperative pulmonary artery pressure.Methods A total of 184 patients undergoing heart transplantation were retrospectively collected and divided into the training group(126 cases)and the verification group(58 cases).Patients in the training set were divided into the right heart failure group(60 cases)and the non-right heart failure group(66 cases)according to whether right heart failure occurred after operation.The differences of clinical data between the two groups were compared,and the influencing factors of right heart failure occurred after operation in the training set were screened by Lasso-Logistic regression.According to the screened influencing factors,nomograms were drawn,and the predictive efficiency of the model was evaluated by using the receiver's operating characteristic(ROC)curve,calibration curve,receiver's operating characteristic(ROC)curve and clinical decision curve.Further vertification of the clinical application effect of centralized evaluation model was conducted.Results The Lasso-Logistic regression analysis identified the following independent risk factors for right heart failure after heart transplantation:elevated total bilirubin(OR=2.649,95％CI:1.339-5.239),increased mean pulmonary artery pressure(OR=3.082,95％CI:1.608-5.910),elevated pulmonary artery resistance(OR=3.171,95％CI:1.710-5.879),and widened right ventricular outflow tract diameter(OR=2.681,95％CI:1.361-5.281),all of which demonstrated statistical significance(P＜0.05).The nomogram model was constructed accordingly.The AUC of the nomogram model was 0.846(95％CI:0.813-0.947).The calibration curve demonstrated good fit via the goodness-of-fit test(Hosmer-Lemeshow x2=0.862,P=0.361).Clinical decision curve analysis revealed that the net benefit rate remained＞0 when the high-risk threshold probability ranged from 1％to 95％,indicating favorable clinical utility of this nomogram model.Based on the model predictions,among 58 heart transplant patients in the validation cohort,34 were classified as high-risk for right heart failure and 24 as low-risk.Actual diagnosis results showed 29 cases with right heart failure and 29 without.The Kappa coefficient reached 0.483(95％CI:0.261-0.705),demonstrating high consistency between model predictions and actual clinical outcomes.Conclusion Preoperative pulmonary systolic pressure increase is an independent risk factor for right heart failure after heart transplantation.A nomogram prediction model for right heart failure after heart transplantation is established by combining other clinical risk factors,and it has good prediction efficiency.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Objective To explore the pathological features of bronchiolar adenoma(BA)and its specific high-resolution computed tomography(HRCT)signs,and to differentiate BA from minimally invasive adenocarcinoma(MIA)using a non-invasive preoperative method.Methods A total of 80 patients with BA and 130 patients with MIA were retrospectively selected,and the clinical information and HRCT features were compared.All cases were divided into development set and test set at a 7︰3 ratio.Logistic regression analysis was used to screen the independent predictors of MIA and construct a model.Results There were significant differences in age,lobe distribution,density,vacuole sign,tumor-related vessels number(TVN),and distance to pleura(DTP)between BA and MIA patients(P<0.05).Age,density,TVN,DTP and long diameter were identified as independent predictors of MIA.A model was constructed,with area under the curve(AUC)of 0.887 and 0.884 in the development and test sets,respectively.Conclusion The model based on HRCT morphological features of BA and MIA demonstrates superior diagnostic performance compared to individual CT morphological features.

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.

Objective To evaluate the risk of right heart failure after heart transplantation by establishing nomogram based on preoperative pulmonary artery pressure.Methods A total of 184 patients undergoing heart transplantation were retrospectively collected and divided into the training group(126 cases)and the verification group(58 cases).Patients in the training set were divided into the right heart failure group(60 cases)and the non-right heart failure group(66 cases)according to whether right heart failure occurred after operation.The differences of clinical data between the two groups were compared,and the influencing factors of right heart failure occurred after operation in the training set were screened by Lasso-Logistic regression.According to the screened influencing factors,nomograms were drawn,and the predictive efficiency of the model was evaluated by using the receiver's operating characteristic(ROC)curve,calibration curve,receiver's operating characteristic(ROC)curve and clinical decision curve.Further vertification of the clinical application effect of centralized evaluation model was conducted.Results The Lasso-Logistic regression analysis identified the following independent risk factors for right heart failure after heart transplantation:elevated total bilirubin(OR=2.649,95％CI:1.339-5.239),increased mean pulmonary artery pressure(OR=3.082,95％CI:1.608-5.910),elevated pulmonary artery resistance(OR=3.171,95％CI:1.710-5.879),and widened right ventricular outflow tract diameter(OR=2.681,95％CI:1.361-5.281),all of which demonstrated statistical significance(P＜0.05).The nomogram model was constructed accordingly.The AUC of the nomogram model was 0.846(95％CI:0.813-0.947).The calibration curve demonstrated good fit via the goodness-of-fit test(Hosmer-Lemeshow x2=0.862,P=0.361).Clinical decision curve analysis revealed that the net benefit rate remained＞0 when the high-risk threshold probability ranged from 1％to 95％,indicating favorable clinical utility of this nomogram model.Based on the model predictions,among 58 heart transplant patients in the validation cohort,34 were classified as high-risk for right heart failure and 24 as low-risk.Actual diagnosis results showed 29 cases with right heart failure and 29 without.The Kappa coefficient reached 0.483(95％CI:0.261-0.705),demonstrating high consistency between model predictions and actual clinical outcomes.Conclusion Preoperative pulmonary systolic pressure increase is an independent risk factor for right heart failure after heart transplantation.A nomogram prediction model for right heart failure after heart transplantation is established by combining other clinical risk factors,and it has good prediction efficiency.

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.

Objective To explore the pathological features of bronchiolar adenoma(BA)and its specific high-resolution computed tomography(HRCT)signs,and to differentiate BA from minimally invasive adenocarcinoma(MIA)using a non-invasive preoperative method.Methods A total of 80 patients with BA and 130 patients with MIA were retrospectively selected,and the clinical information and HRCT features were compared.All cases were divided into development set and test set at a 7︰3 ratio.Logistic regression analysis was used to screen the independent predictors of MIA and construct a model.Results There were significant differences in age,lobe distribution,density,vacuole sign,tumor-related vessels number(TVN),and distance to pleura(DTP)between BA and MIA patients(P<0.05).Age,density,TVN,DTP and long diameter were identified as independent predictors of MIA.A model was constructed,with area under the curve(AUC)of 0.887 and 0.884 in the development and test sets,respectively.Conclusion The model based on HRCT morphological features of BA and MIA demonstrates superior diagnostic performance compared to individual CT morphological features.

BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.