Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Objective:To study the epidemiological characteristics and clinical diagnosis of human brucellosis in Qujing City, Yunnan Province.Methods:Through the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System, the basic information and clinical diagnostic data of brucellosis cases reported in Qujing City from January 2008 to December 2023 were retrospectively collected. Descriptive epidemiological methods were used to analyze the epidemic profile, three distribution characteristics (time, population, region), and diagnosis of brucellosis.Results:A total of 1 417 brucellosis cases were reported in Qujing City from 2008 to 2023, with no death. The annual average incidence of brucellosis was 1.49/100 000, with no cases reported in 2009 and 2010, and the highest incidence in 2023 (7.82/100 000). The incidence of brucellosis showed an increasing trend year by year (χ 2trend = 1 874.58, P < 0.001). The number of cases from June to November accounted for 61.54% (872/1 417). The majority of brucellosis cases were in the age group of 36 - 65 years old, accounting for 67.82% (961/1 417). Among them, there were 954 males and 463 females, with a gender ratio of 2.06 ∶ 1.00. Farmers were the main occupation, accounting for 84.33% (1 195/1 417). The cases were mainly distributed in Luliang County (621 cases), Xuanwei City (282 cases) and Shizong County (137 cases), accounting for 73.39% (1 040/1 417). The median interval between onset and diagnosis was 13 days, and the cases with intervals ≤7 d, 8 - 30 d, and ≥31 d accounted for 32.11% (455/1 417), 40.16% (569/1 417), and 27.73% (393/1 417), respectively. Totally 63.94% (906/1 417) of the cases were confirmed in medical institutions in Qujing City. Conclusions:The incidence of brucellosis in Qujing City is increasing year by year, with men, middle-aged and elderly people and farmers as the main population, summer and autumn as the peak period, and Luliang County, Xuanwei City and Shizong County as the high incidence areas. Most cases have an interval of less than 30 days between onset and diagnosis, and can be diagnosed within the jurisdiction.

Objective To explore the objective characteristics of tongue in primary immune thrombocytopenia(ITP);To provide references for accurate syndrome differentiation.Methods Totally 112 patients with ITP were divided into groups according to their platelet count,TCM symptoms and drug treatment lines.Infrared thermal imager,hygrometer,colorimetry and image analysis software were used to detect the temperature,humidity,colorimetry and morphology of tongue body(TB),tongue coating(TC)and sublingual vessel(SV),and analyze their characteristics.The tongue was divided into five areas:tip of tongue(T),middle of tongue(M),behind of tongue(B),middle left of tongue(ML)and middle right of tongue(MR),and its temperature was measured.Humility(H)of tongue and tongue coating were measured by hygrometer.The images of tongue body,tongue coating and sublingual collaterals were taken,and the chromaticity indexes of R,G,B,L,a,b were analyzed by Adobe Photoshop 2023.The width,length and tortuosity of sublingual collaterals were under morphological analysis.Results ① Comparison of platelet count groups:compared with 30-50 platelet count group and more than 100 platelet count group,the TB-R of 51-100 platelet count group decreased(P<0.05,P<0.01),and compared with 30-50 platelet count group,the TB-a of 51-100 platelet count group decreased(P<0.01);compared with platelet<30 group and platelet 30-50 group,the TC-H of platelet>100 group increased(P<0.05,P<0.01);compared with platelet>100 group,the length of sublingual collaterals in platelet<30 group was longer(P<0.05).② Comparison of different TCM symptom groups:compared with the bleeding group and asymptomatic group,the M and SV-B in the fatigue group decreased(P<0.05,P<0.01);compared with the asymptomatic group,the TC-b in the anxious group was significantly higher(P<0.05).③ Comparison of administration groups:compared with the Danazol group and Chinese materia medica group,the TC-H in the glucocorticoid group was significantly higher(P<0.05,P<0.01).Conclusion There are differences in tongue characteristic indexes among ITP patients with different platelet counts,TCM symptoms and drug treatment lines,which can measure of tongue indexes to provide references for accurate syndrome differentiation of ITP.

Angiogenesis is a critical process in the treatment of cardiac ischemic injury,and numerous research findings indicate that macrophages play a vital role in angiogenesis.This review summarizes how macrophages regulate an-giogenesis through the secretion of key factors and the interactions with other cells.M1 macrophages promote new blood vessel formation in the early stages by secreting pro-angiogenic factors,while M2 macrophages are involved in vascular re-modeling and maintaining vessel homeostasis.This review also discusses several new therapeutic strategies for promoting angiogenesis,including direct injection of macrophages,modulation of macrophage phenotype and function,and the use of macrophage-derived exosomes.Numerous studies have shown that macrophages have multiple functions in angiogenesis,and targeting macrophages provides new therapeutic targets and directions for promoting angiogenesis and treating ischemic diseases.

Objective:To determine the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition). Methods:A preliminary list of clinical issues for the guidelines was developed through literature review, clinical surveys, and expert interviews. This was followed by two rounds of Delphi questionnaire surveys, with quality control and statistical analysis conducted using expert positive coefficient, mean item scores, full score ratio, coefficient of variation, Cronbach′s α coefficient, and expert authority level to finalize the list of clinical issues.Results:The experts participating in the Delphi questionnaire surveys had multidisciplinary collaborative backgrounds and regional representativeness, with a high level of authority. The overall positive coefficient of expert participation in the surveys was 78.9%. Through two rounds of the Delphi method and based on the screening criteria of a mean score ≥3.5, coefficient of variation ≤30%, and full score ratio ≥30%, 17 clinical issues were ultimately included following an expert consensus meeting.Conclusions:Through the Delphi method and rigorous quality control, the clinical issues in the Clinical practice guidelines for postoperative pain management in adults (2024 edition) are determined, laying a foundation for the subsequent development of the guidelines.

Objective:To study the epidemiological characteristics and clinical diagnosis of human brucellosis in Qujing City, Yunnan Province.Methods:Through the Infectious Disease Reporting Information Management System of the China Disease Prevention and Control Information System, the basic information and clinical diagnostic data of brucellosis cases reported in Qujing City from January 2008 to December 2023 were retrospectively collected. Descriptive epidemiological methods were used to analyze the epidemic profile, three distribution characteristics (time, population, region), and diagnosis of brucellosis.Results:A total of 1 417 brucellosis cases were reported in Qujing City from 2008 to 2023, with no death. The annual average incidence of brucellosis was 1.49/100 000, with no cases reported in 2009 and 2010, and the highest incidence in 2023 (7.82/100 000). The incidence of brucellosis showed an increasing trend year by year (χ 2trend = 1 874.58, P < 0.001). The number of cases from June to November accounted for 61.54% (872/1 417). The majority of brucellosis cases were in the age group of 36 - 65 years old, accounting for 67.82% (961/1 417). Among them, there were 954 males and 463 females, with a gender ratio of 2.06 ∶ 1.00. Farmers were the main occupation, accounting for 84.33% (1 195/1 417). The cases were mainly distributed in Luliang County (621 cases), Xuanwei City (282 cases) and Shizong County (137 cases), accounting for 73.39% (1 040/1 417). The median interval between onset and diagnosis was 13 days, and the cases with intervals ≤7 d, 8 - 30 d, and ≥31 d accounted for 32.11% (455/1 417), 40.16% (569/1 417), and 27.73% (393/1 417), respectively. Totally 63.94% (906/1 417) of the cases were confirmed in medical institutions in Qujing City. Conclusions:The incidence of brucellosis in Qujing City is increasing year by year, with men, middle-aged and elderly people and farmers as the main population, summer and autumn as the peak period, and Luliang County, Xuanwei City and Shizong County as the high incidence areas. Most cases have an interval of less than 30 days between onset and diagnosis, and can be diagnosed within the jurisdiction.

Angiogenesis is a critical process in the treatment of cardiac ischemic injury,and numerous research findings indicate that macrophages play a vital role in angiogenesis.This review summarizes how macrophages regulate an-giogenesis through the secretion of key factors and the interactions with other cells.M1 macrophages promote new blood vessel formation in the early stages by secreting pro-angiogenic factors,while M2 macrophages are involved in vascular re-modeling and maintaining vessel homeostasis.This review also discusses several new therapeutic strategies for promoting angiogenesis,including direct injection of macrophages,modulation of macrophage phenotype and function,and the use of macrophage-derived exosomes.Numerous studies have shown that macrophages have multiple functions in angiogenesis,and targeting macrophages provides new therapeutic targets and directions for promoting angiogenesis and treating ischemic diseases.

Primary immune thrombocytopenia(ITP)is an acquired autoimmune hemorrhagic disease characterized by reduced isolated peripheral blood platelet counts for which pathogenesis and etiology are not well defined.Present diagnosis of ITP is to be excluding other diseases,whose pathogenesis generally involves multiple aspects of immunology,biology,epigenetics and environ-mental factors.Recognition of epigenetic alterations in dysregulation of immune tolerance and autoimmune diseases has been deepened in recent years with progress by molecular biology.DNA methylation,an important epigenetic modification,has been shown to play a role in pathogenesis of ITP.Abnormal DNA methylation leads to cellular abnormalities in proliferation,differentiation,apoptosis and immune response in body,induces immune intolerance to autologous platelet antigens in patients,resulting in abnormal activation of immune cells which makes excessive platelet destruction or insufficient platelet production.Therefore,this article reviews latest research progress of DNA methylation genes in ITP to provide a reference for further recovery of immune tolerance of patients.

Objective:To identify the serotype and genotype characteristics of the first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province. Methods:The information of seven suspected cluster brucellosis cases reported in Lanping County, Nujiang Lisu Autonomous Prefecture in April 2023 were collected, blood samples were collected, and the strains were isolated and cultured. Serological methods were employed for brucellosis diagnosis, bacterial species identification was performed using BCSP31-PCR and AMOS-PCR. Multilocus locus variable-number tandem repeat analysis (MLVA) was conducted for strain genotyping, followed by phylogenetic analysis comparing the strains with those from other regions of China.Results:All seven cases were diagnosed with brucellosis, they were all villagers from the same village and had daily contact with sheeps. Four suspected Brucella strains were isolated, identified as Brucella melitensis biotype by BCSP31-PCR and AMOS-PCR. The four isolated strains exhibited identical MLVA-16 genotype, with MLVA-8 genotype 42 and MLVA-11 genotype 180, belonging to the Eastern Mediterranean lineage. Compared with the MLVA-16 of the isolated strains from other regions of China, the four isolated strains formed an independent cluster. Conclusion:The first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province is caused by Brucella melitensis biotype, and the four isolated strains have showed unique MLVA genotype.

Objective:To learn about the geographical distribution and bio-tying diversity characteristics of Brucella strains isolated in Yunnan Province. Methods:From March 2017 to December 2023, 516 suspected Brucella strains were collected from brucellosis surveillance sites and hospitals in Yunnan Province, and Yunnan Institute of Endemic Disease Control and Prevention. The Brucella isolates were confirmed to genus level by BCSP31-PCR, and subsequently identified to species and biovar level using conventional biotyping methods and AMOS-PCR. The geographical distribution of the strains was visualized using ArcGIS 10.8 software, simultaneously analyze the general characteristics of brucellosis patients. Results:Among the 516 suspected Brucella strains, 514 strains were isolated from patient blood samples and 2 strains were isolated from sheep blood samples. BCSP31-PCR identification showed that all strains were Brucella spp. The results of conventional biotyping and AMOS-PCR identification revealed that the isolates comprised 514 Brucella melitensis strains (16 strains of Brucella melitensis biovar 1 and 498 strains of Brucella melitensis biovar 3), one Brucella abortus (biovar 1) strain, and one Brucella canis strain. The strain was distributed in 69 counties/cities of 13 prefectures/cities in Yunnan Province, involving 390 administrative villages in 186 townships. Brucella melitensis was the dominant epidemic strain, and the largest number of Brucella melitensis was distributed in Kunming City( n = 205), followed by Honghe Hani and Yi Autonomous Prefecture ( n = 98) and Qujing City ( n = 72). Brucella abortus was only distributed in Lincang City ( n = 1), and Brucella canis was distributed Wenshan Zhuang and Miao Autonomous Prefecture ( n = 1). The age range of 514 brucellosis patients ranged from 10 months to 88 years, with the majority being between 40 and 60 years old (52.72%, 271/514). The predominant occupational group was farmers (89.11%, 458/514), followed by students (5.06%, 26/514). Conclusion:Brucella exhibits a wide distribution and species/biovar diversity in Yunnan Province, with infection among the farming population emerging as a serious public health problem in the area.