OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

ObjectiveTo investigate the association between serum creatinine/cystatin C ratio （CCR） and nonalcoholic fatty liver disease （NAFLD） based on the NHANES database， and to evaluate the potential significance of CCR as an indicator reflecting the metabolic status of the body. MethodsBased on the data from the NHANES database in 1999‍ ‍—‍ ‍2004， a total of 4 217 participants were enrolled and divided into NAFLD group with 1 726 participants and non-NAFLD group with 2 491 participants. CCR was compared between the two groups， and the association between CCR and NAFLD was analyzed. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression model was used to investigate the association between CCR and NAFLD； CCR was divided into 4 groups based on quartiles， and odds ratio （OR） and 95% confidence interval （CI） in the regression model was calculated with the first quartile as reference. In addition， the restricted cubic spline analysis was used to investigate whether there was a non-linear relationship between CCR and NAFLD， and interaction items were introduced into the Logistic regression model to perform an interaction analysis. Subgroup analyses were performed based on the stratification of variables to investigate the difference in the association between CCR and NAFLD in different populations. ResultsThe non-NAFLD group had a significantly higher CCR than the NAFLD group （Z=-4.76，P<0.01）. The Logistic regression analysis showed that in model 1 without adjustment of variables， CCR was negatively associated with NAFLD （OR=0.993，95%CI：0.989‍ ‍—‍ ‍0.996，P<0.01）， and in model 3 with adjustment of all variables， CCR was still negatively associated with NAFLD （OR=0.986，95%CI：0.981‍ ‍—‍ ‍0.991，P<0.01）. The analysis of CCR based on quartiles showed a significant association between the increase in CCR and the reduction in the risk of NAFLD. In model 3， compared with the individuals with the lowest quartile of CCR， the individuals with the highest quartile of CCR had a significantly lower risk of NAFLD （OR=0.426，95%CI：0.316‍ ‍—‍ ‍0.574，P<0.01）. Further interaction and subgroup analyses showed that the interaction between CCR and age/sex had a statistical significance （P_interaction<0.01 and P_interaction=0.04）. The subgroup analysis based on age showed a more significant association between CCR and NAFLD in the middle-aged population （≤60 years） （OR=0.982，95%CI：0.976‍ ‍—‍ ‍0.987）， and the subgroup analysis based on sex showed a stronger association between CCR and NAFLD in women （OR=0.979，95%CI：0.972‍ ‍—‍ ‍0.986）. ConclusionThis study shows a significant negative association between CCR and NAFLD， and such association is more significant in middle-aged individuals and women.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective To investigate the association between 8 insulin resistance(IR)surrogate markers and incident atherosclerotic cardiovascular disease(ASCVD)in population with cardiovascular-kidney-metabolic syndrome(CKM)of stages 0-3,and to identify the surrogate marker with the best predictive performance.Methods A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort.A Cox proportional hazards model was used to calculate hazard ratios(HRs)between each IR surrogate marker and incident ASCVD.Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD.The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs(RHRs).Time-dependent area under the receiver operating characteristic curve(TDAUC)and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD.Based on the PREVENT equation components and the 8 surrogate markers under analysis,random forest feature selection was used to determine the contribution of each marker to accurate prediction.Results During a follow-up period of82 741.93 person-years,1447 incident cases of ASCVD were recorded,with an incidence density of 17.49 per 1000 person-years.Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL)and the TyG/(TG/HDL)index were not associated with incident ASCVD(P＞0.05).The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence.The most promising indicator,TyG index with waist-to-height ratio(TyG_WHtR),exhibited an inverted J-shaped association with incident ASCVD(P for nonlinearity=0.045;TDAUC=0.640;C=0.634),while the TyG index with body mass index(TyG_BMI),waist circumference(TyG_WC),and waist-to-hip ratio(TyG_WHR)showed positive linear associations(all P for trend＜0.05),with relatively lower predictive performance(C=0.564,0.588,and 0.598,respectively).Although both the TyG index and the metabolic score for insulin resistance(METS-IR)were associated with increased ASCVD risk(TyG:Q2 vs.Q1,HR=1.23 and Q4 vs.Q1,HR=1.24;METS-IR:P for non-linearity=0.045),they exhibited poor predictive performance for incident ASCVD.Conclusion The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM.Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.

Since the 1970s, the laboratory animal industry in Suzhou has gone through five stages: its inception, emergence, growth, transformation, and scaling up. It began with the manufacturing of caging equipment for laboratory animals, initially by imitation and later through independent innovation. The industry evolved from sporadic factories to clustered enterprises, gradually growing and opening up the export market for caging equipment. In the 21st century, with industrial upgrading and transformation, purification systems and related products began to develop, and industry organizations emerged. As China has modernized, the rise of automation and intelligent production has led to technological innovation in enterprises and the emergence of various outsourcing services in the laboratory animal industry, driving the large-scale development of the industrial chain. After nearly half a century of growth, the laboratory animal industry in Suzhou has formed a complete industrial chain, including the production of laboratory animals, caging equipment, feed and bedding materials, design and construction of laboratory animal facilities, quality testing of laboratory animals and environments, and animal experimentation services. Laboratory animal breeding equipment, the core of the industry, has reached the level of developed countries, and the industry's scale and influence are unmatched in China. Since the 21st century, biopharmaceuticals have become the "No.1 industry" in the development of Suzhou. With government support, the guidance of the local economy, and the assistance from universities and research institutes, the animal experiment outsourcing industry has begun to cluster in Suzhou. The continuous influx of CROs has driven the construction of large-scale laboratory animal facilities, and key research projects have been initiated, significantly enhancing the industry's R&D capabilities. The Suzhou laboratory animal industry has quickly expanded alongside the "No. 1 industry," creating a unique "Suzhou Path" for laboratory animals. Over nearly fifty years, the laboratory animal industry in Suzhou has been essential to the rapid development of the biopharmaceutical industry in Suzhou and China.

Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.