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

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Objective:To evaluate the diagnostic performance of resting echocardiography in detecting severe coronary artery stenosis.Methods:A total of 136 patients with suspected coronary artery disease（CAD）who presented to Sichuan Provincial People's Hospital between January 2021 and December 2024 were prospectively enrolled. All patients underwent both coronary computed tomography angiography（CCTA）and transthoracic echocardiography within one week. Based on CCTA results，the patients were divided into non-severe stenosis group（ n=78）and severe stenosis group（ n=58）. Echocardiographic parameters including left atrial maximum volume（LAVmax），left ventricular global longitudinal strain（GLS），left ventricular longitudinal strain of endo-myocardium，mid-myocardium，epi-myocardium（LSendo，LSmid，LSepi），early diastolic mitral inflow velocity（E），early diastolic mitral annular velocity of the lateral and septal walls（e'），and E/e' were measured. Predictive factors for severe coronary stenosis were identified using LASSO regression，and a nomogram model was developed via multivariate Logistic regression. Model performance was evaluated using ROC curves，calibration curves，and decision curve analysis. Results:Multivariate Logistic regression analysis revealed LSendo，LAVmax，and E/e' as independent predictors of severe coronary artery stenosis. The nomogram constructed based on these predictors achieved an area under the curve of 0.798（95% CI=0.723-0.873），with sensitivity and specificity of 0.756 and 0.759，respectively. Conclusions:The resting echocardiography-based nomogram model demonstrates good diagnostic efficacy for severe coronary artery stenosis. It may serve as a noninvasive tool to assist in risk stratification and clinical decision-making in patients with suspected CAD.

Objective:To investigate biomarkers that are significantly associated with the immune checkpoint(ICs)genes of colorectal cancer(CRC)and have a key impact on the prognosis of patients,and to search for related sensitive drugs by using bioinformatics methods.Methods:Genes with up-regulated expression in TCGA database and associated with poor prognosis of patients were screened,and molecules with high correlation with immune checkpoint were extracted to verify their impact on the prognosis of patients with colorectal cancer.Finally,their im-pact on immune cell infiltration and correlation were detected,and sensitive drugs that act on target genes were ana-lyzed and searched.Results:Colorectal cancer patients with up-regulated expression of tissue inhibitor of metallo-proteinase 1(TIMP1)had poor prognosis.Different TIMP1 expression levels showed significant differences in the infil-tration levels of various immune cells.Further drug sensitivity analysis predicted that bleomycin and middotolin could be highly sensitive to samples with high TIMP1 expression.Conclusion:TIMP1 is expected to be a new predictive biomarker to identify the benefits of cancer immunotherapy,and bleomycin and middotolin may be potential individualized treatment options for patients with high expression of TIMP1.

Objective: To investigate the methylation status of the RUNX family transcription factor 3 ( RUNX3)promoter and its mRNA expression in sepsis patients , and to analyze their relationship with the prognosis of sepsis. Methods: Differentially expressed genes related to sepsis , including RUNX3 , were identified from multiple datasets obtained from the gene expression omnibus (GEO) database. The gene expression and methylation sites were validated. A total of 120 patients with sepsis were included. Clinical data were recorded , and blood samples were collected at enrollment. Relative expression levels of RUNX3 in blood samples and promoter methylation status were detected using qPCR and methylation⁃specific PCR ( MSP) , respectively. Pearson correlation coefficients were used to analyze the correlation between RUNX3 levels in patient blood and clinical indicators. Kaplan⁃Meier analysis was performed to plot survival curves , and Cox proportional hazards regression analysis was conducted to identify factors affecting the prognosis of sepsis patients. Results: Data set analysis revealed that RUNX3 was a differentially methylated gene associated with the prognosis of sepsis. The mRNA expression level of RUNX3 was lower in the non-survivor group compared to the survivor group (P < 0. 05) , and the methylation ratio of RUNX3 was higher in the non-survivor group than in the survivor group (P < 0. 05) . In sepsis patients , RUNX3 mRNA expression levels were negatively correlated with interleukin-6 ( IL-6) , procalcitonin ( PCT) , C-reactive protein ( CRP) , acute physiology and chronic health evaluation ( APACHE Ⅱ ) score , and sequential organ failure assessment ( SOFA) score. Kaplan-Meier analysis showed that the 28-day survival rate in the methylated group was lower than that in the unmethylated group ( P < 0. 05) . Cox regression analysis results indicated that RUNX3 promoter methylation was an independent risk factor for predicting the 28-day prognosis of sepsis patients. Conclusion In sepsis patients , the mRNA levels of RUNX3 were reduced , and the degree of promoter methylation was higher. RUNX3 promoter methylation was an independent risk factor for the 28-day prognosis of sepsis patients and could serve as a prognostic biomarker for sepsis.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:Based on the background of high-quality development,we analyze the operational efficiency of traditional Chinese medicine(TCM)hospitals in China's Yangtze River Economic Belt in 2021 and explore the impact of external environmental factors on operational efficiency,so as to provide a reference for promoting the high-quality development of TCM hospitals in the Yangtze River Economic Belt.Methods:The three-stage DEA model was used to analyze the operational efficiency of TCM hospitals in 11 provinces and cities in the Yangtze River Economic Zone in China in 2021.Results:After three-stage DEA analysis,the values of comprehensive efficiency,pure technical efficiency and scale efficiency of TCM hospitals in China's Yangtze River Economic Belt are 0.976,0.986 and 0.990,respectively.5 provinces and cities,Shanghai,Jiangsu,Hunan,Chongqing and Guizhou,are efficient before and after the adjustment,and the comprehensive efficiency of Zhejiang,Anhui,Hubei,Jiangxi,Sichuan and Yunnan have increased compared with that before the adjustment.Ranking of the average value of the comprehensive efficiency of TCM hospitals operation in the three major city clusters of the Yangtze River Economic Belt after adjustment:Chengdu-Chongqing city cluster(0.998)>city cluster in the Yangtze River Delta(0.964)>city cluster in the middle reaches of the Yangtze River(0.962).Conclusion:The operational efficiency of TCM hospitals in the Yangtze River Economic Zone has been underestimated,and the comprehensive efficiency is mainly affected by scale efficiency;there are differences in the operational efficiency of TCM hospitals in the three major urban agglomerations,and balanced development is needed between regions;the operational efficiency of TCM hospitals is affected by the external environment,and it is necessary to improve the external environment;it is necessary to strengthen the construction of digital and informatization of TCM,and to pay attention to the role of talents in TCM,so as to promote the high-quality development of TCM hospitals.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To investigate biomarkers that are significantly associated with the immune checkpoint(ICs)genes of colorectal cancer(CRC)and have a key impact on the prognosis of patients,and to search for related sensitive drugs by using bioinformatics methods.Methods:Genes with up-regulated expression in TCGA database and associated with poor prognosis of patients were screened,and molecules with high correlation with immune checkpoint were extracted to verify their impact on the prognosis of patients with colorectal cancer.Finally,their im-pact on immune cell infiltration and correlation were detected,and sensitive drugs that act on target genes were ana-lyzed and searched.Results:Colorectal cancer patients with up-regulated expression of tissue inhibitor of metallo-proteinase 1(TIMP1)had poor prognosis.Different TIMP1 expression levels showed significant differences in the infil-tration levels of various immune cells.Further drug sensitivity analysis predicted that bleomycin and middotolin could be highly sensitive to samples with high TIMP1 expression.Conclusion:TIMP1 is expected to be a new predictive biomarker to identify the benefits of cancer immunotherapy,and bleomycin and middotolin may be potential individualized treatment options for patients with high expression of TIMP1.