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.

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.

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.

After the information construction in grass-root medical and health institutions was considered according to the thinking of Internet+, the action plan for Internet+ in grass-root medical and health institutions was elaborated, and the target of Internet+ and information construction in grass-root medical and health institutions was defined, the information communication-oriented, use-oriented, and users-oriented strategies were put forward for the Internet+ and information construction in grass-root medical and health institutions.

In the macrocosmic perspective,the development trend of the rights and obligations of doctors and patients is regarded as changes in the healthcare mode.In the microcosmic perspective,it is regarded as a clarification and emphasis of the informed consent of the patients as required by laws and regulations.However,medical workers tend to neglect their obligation of informing the patients of the medical expenses to be paid out of their own pocket.In this consideration,informing the patients in writing of their self-payment in medical expenses is obligatory and important,i.e,the self-payment agreement is highly important in clinical work.This paper analyzed the legal at-tributes of self-payment agreement in the aspects of both the informed consent and the signing of the medical service contract,with discussions of the tining of signature,in the hope of inspiring and helping medical workers in their clinical practice.

OBJECTIVETo map and identify the disease gene for the epidermolytic palmoplantar keratoderma (EPPK) in a Uighur family of China.

METHODSBlood samples were collected and genomic DNA was extracted from 48 members of the Xinjiang Uighur family. Six microsatellite repeat sequences on chromosome region 17q12-q21 and 12q13 were selected based on the two known candidate genes KRT9 and KRT1. Two-point linkage analysis and haplotype analysis were performed. Exons and their flanking intronic sequence of the KRT9 gene were amplified by polymerase chain reaction (PCR) and sequenced.

RESULTSData from the marker D17S1787 suggested linkage and yielded a Lod score of 8.65 at theta=0 by using MLINK software. Genotypes and haplotypes were acquired. The disease gene of the EPPK family is located between markers 17/TG/36620115 and D17S846. Chromosome 12q13 region was excluded with the negative Lod score obtained in marker D12S96 (Lod=-infinity at theta=0). No pathogenic mutation was detected in the KRT9 gene.

CONCLUSIONThe disease gene of the EPPK family is located on chromosome region 17q21.2. The keratin 9 gene might not be the disease gene.

China ; Chromosomes, Human, Pair 17 ; genetics ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; ethnology ; genetics ; Male ; Microsatellite Repeats ; Mutation ; Pedigree