Background/Aims: MicroRNA (miRNA) isoforms (isomiRs) broaden the regulatory landscape of canonical miRNAs, but their role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. We aimed to characterize the hepatic isomiR landscape in MASLD and define their association with disease activity and fibrosis. Methods: Small RNA (sRNA) sequencing was performed on liver biopsies from 79 patients across the histological spectrum of MASLD. IsomiRs were annotated and quantified. Their association to disease activity and fibrosis score was assessed by differential expression, ordinal regression, and machine learning. Parallel mRNA sequencing and pathway enrichment were used to map isomiR–mRNA interactions and regulatory networks, which were validated against an independent dataset. Results: MiRNAs accounted for 75% of sRNAs in liver tissue, of which 67% were isomiRs. Across MASLD severity, 173 isomiRs correlated with disease activity and 58 with fibrosis stage. Key findings included a miR-122 isomiR uniquely targeting INSIG1 (cholesterol metabolism) and a miR-21 isomiR targeting PPARA and HMGCS2 (lipid and fibrosis pathways). Integration with mRNA data revealed 33 dysregulated pathways, including PPAR signaling, insulin resistance, and TGF-β response. Several novel isomiRs from miR-26b, let-7c, and miR-32 families were also linked to lipid metabolism and fibrosis progression. Conclusions IsomiRs represent the majority of hepatic miRNAs and uncover novel regulatory networks masked by canonical miRNA analysis. These findings provide new insights into the molecular heterogeneity of MASLD, highlight candidate pathways driving disease progression, and identify potential biomarkers and therapeutic targets for precision hepatology.

Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.
Child ; Humans ; Spinal Cord Injuries/complications* ; Spinal Cord

Cerebral Cortex ; Immune System

Implementation of information technology in clinical research has resulted in revolutionary changes in drug development. Based on the good clinical practice (GCP) requirements on data, processes and documentations, and the era of fast growth in clinical studies using up-to-date information technology, we explore an integrated e-clinical solution in clinical studies in China.
China ; Clinical Trials as Topic ; Data Collection ; methods ; Medical Informatics ; methods

Catdiomyopathies are diseases that primarily affect the myocardium,leading to serious cardiac dysfimction and heart failure.Out of the three major categories of candiomyopathies(hypertrophic,dilated and restrictive),restrictive cardiomyopathy(RCM)is less common and also the least studied However,the prognosis for RCM is poor as some patients dying in their childhood The molecular mechanisms behind the disease development and progression are not very clear and the treatment of RCM is very difficult and often ineffective.In this article,we reviewed the recent progress in RCM research from the clinical studies and the translational studies done on diseased transgenic animal models.This will help for a better understanding of tare mechanisms underlying the etiology and development of RCM and for the design of better treatments for the disease.

Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have been associated with amyotrophic lateral sclerosis (ALS). FUS-positive neuropathology is reported in a range of neurodegenerative diseases, including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology (FTLDU). To examine protein aggregation and cytotoxicity, we expressed human FUS protein in yeast. Expression of either wild type or ALS-associated R524S or P525L mutant FUS in yeast cells led to formation of aggregates and cytotoxicity, with the two ALS mutants showing increased cytotoxicity. Therefore, yeast cells expressing human FUS protein recapitulate key features of FUS-positive neurodegenerative diseases. Interestingly, a significant fraction of FUS expressing yeast cells stained by propidium iodide were without detectable protein aggregates, suggesting that membrane impairment and cellular damage caused by FUS expression may occur before protein aggregates become microscopically detectable and that aggregate formation might protect cells from FUS-mediated cytotoxicity. The N-terminus of FUS, containing the QGSY and G rich regions, is sufficient for the formation of aggregates but not cytotoxicity. The C-terminal domain, which contains a cluster of mutations, did not show aggregation or cytotoxicity. Similar to TDP-43 when expressed in yeast, FUS protein has the intrinsic property of forming aggregates in the absence of other human proteins. On the other hand, the aggregates formed by FUS are thioflavin T-positive and resistant to 0.5% sarkosyl, unlike TDP-43 when expressed in yeast cells. Furthermore, TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity.
Amino Acid Sequence ; Amino Acid Substitution ; DNA-Binding Proteins ; genetics ; metabolism ; Humans ; Mutation ; Neurodegenerative Diseases ; pathology ; Protein Structure, Tertiary ; RNA-Binding Protein FUS ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; toxicity ; Saccharomyces cerevisiae ; growth & development ; metabolism ; Sarcosine ; analogs & derivatives ; pharmacology ; Thiazoles ; metabolism