Beijing Red Cross Blood Center

Cirrhotic ascites develops when portal hypertension and arterial under-filling chronically activate neuro-hormonal pathways that drive renal sodium-water retention. Augmented proximal tubular sodium reabsorption, predominantly mediated by the apical sodium/hydrogen exchanger 3 (NHE3), plays a fundamental role in this process. Given the spatial coupling of NHE3 and the sodium-glucose cotransporter 2 (SGLT2), selective SGLT2 inhibition reduces NHE3 activity via functional suppression within the apical microdomain. The increased sodium chloride delivery to the macula densa augments tubuloglomerular feedback and modulates the renin–angiotensin–aldosterone system. Early clinical investigations, ranging from case reports and retrospective analyses to pilot randomized trials, indicated potential benefits in controlling ascites and reducing decompensation events. However, their limited sample size, heterogeneous endpoints, and predominantly observational design constrain the generalizability of the findings. This review concentrates on the molecular mechanisms and emerging clinical evidence supporting the therapeutic potential of SGLT2 inhibitors in the management of cirrhotic ascites.

Pyroptosis is a pathogenenic mechanism of polycystic ovary syndrome (PCOS). N5-methylcytosine (m5C) methylation is a RNA modification that affects the progression of diseases. However, its role in PCOS remains not understood. This study aimed to investigate the role of NSUN7 in PCOS, particularly its impact on pyroptosis. KGN cells were treated with LPS to establish a cell model, and pyroptosis was evaluated using enzyme-linked immunosorbent assay, flow cytometry, and western blotting. The effect of NSUN7 on the m5C modification of NLRP3 was assessed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and actinomycin D treatment experiment. A PCOS rat model was generated, hormones were detected using ELISA, and pyroptosis was evaluated in the ovaries and primary granulosa cells. The results showed that NSUN7 expression was reduced in patients with PCOS and LPS-treated KGN cells. Silencing of NSUN7 inhibited LPS-induced cell pyroptosis. Moreover, NSUN7 knockdown inhibited m5C methylation of NLRP3 and reduced NLRP3 mRNA stability. Overexpression of NLRP3 reversed the pyroptosis inhibition induced by NSUN7 knockdown. Furthermore, interfering with NSUN7 alleviated hormone abnormalities and suppressed granulosa cell pyroptosis in PCOS rats. In conclusion, silencing of NSUN7 attenuates PCOS progression by inhibiting pyroptosis of granulosa cells by suppressing m5C methylation of NLRP3.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-19209-x.

This article addresses the genetic and genomic determinants that influence susceptibility or resistance to human infections, whether caused by bacteria, viruses, fungi, parasites or even prions. A large number of genes are involved in susceptibility or resistance, and this is because Homo sapiens sapiens evolutionarily acquired key DNA modifications adaptable to defence as a result of the interaction of infectious agents with their genetic properties, natural selection and mutations. This article provides a description of the methods used in the investigation of this evolution and mutual host-infectious agent adaptation. The genes involved in susceptibility and resistance are presented, as well as the polymorphic variants that provide greater or lesser reaction capacity. The high number of genes, which produce specific defence proteins, have intricate relationships among them. Relationships among these genes have been analysed. A list of variants, and even mutations of the 70 to 153 proteins/genes that are involved in the immune response to infectious diseases has been compiled. Additionally, we designed a network of physical interactions as predictable, with BioGrid data and enrichment data obtained by the g:Profiler platform, finding 57 of the 70 genes with protein-to-protein interactions. The network detected is composed of 1,049 interacting genes (in total 1,106 genes and 1,910 interactions). This analysis shows the importance of immunity genes in the defence against infectious agents, as well as the effects of the genes involved such as HLA, immunoglobulins, interleukins, immune cells, among others. Based on the functional analysis of genes involved in susceptibility and resistance to infections, we compiled a list of genetic disorders that increase an individual’s risk of developing infectious diseases. It is known that infectious diseases manifest general clinical characteristics, which are a good guide to suspect a disease. Furthermore, we describe general clinical signs that may suggest underlying genetic immunodeficiency and highlight specific infectious diseases—such as HIV/AIDS, amebiasis, malaria, Chagas disease, tuberculosis, and COVID-19—where genetic susceptibility factors have been well-characterised.

The novel allele HLA-B*58:01:46 differs from HLA-B*58:01:01:03 by a single nucleotide substitution in codon 49 GCG → GCC in exon 2.

The authors declare no conflicts of interest.

Since the outbreak of novel coronavirus pneumonia (COVID-19), numerous T-cell epitopes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteome have been reported. However, most of the identified CD8+ T-cell epitopes have been restricted primarily by HLA-A allotypes. The epitopes restricted by HLA-B and HLA-C allotypes are limited. This study focuses on the screening of T-cell epitopes restricted by 13 prevalent HLA-B and 13 prevalent HLA-C allotypes, which cover over 70% and 90% of the Chinese and Northeast Asian populations, respectively. Totally, 67 HLA-B restricted and 53 HLA-C restricted epitopes were validated as immunogenic epitopes with a herd predominance rate by peptide-PBMCs ex vivo coculture experiments using the PBMCs from convalescent Chinese cohort. In addition, 26 transfected cell lines expressing indicated HLA-B or HLA-C allotype were established, and used in the competitive peptide binding assays to define the affinities and cross-restriction of each validated epitope binding to HLA-B or HLA-C allotypes. These data will facilitate the design of T-cell-directed vaccines and SARS-CoV-2-specific T-cell detection tools tailored to the Northeast Asian population. The herd test of functionally validated T-cell epitopes, and the competitive peptide binding assay onto cell line array expressing prevalent HLA allotypes may serve as an additional criterion for selecting T-cell epitopes used in vaccine.

Quality monitoring is a key component of the quality management system, closely related to the concept of quality improvement. The implementation of quality indicators (QIs), as a valuable quality monitoring tool, contributes to the achievement of quality objectives. During 2010, discussions about the importance and use of QIs in transfusion medicine intensified, and 3 years later, the Quality Management Working Party (QM-WP) of the International Society of Blood Transfusion (ISBT) published a set of QIs for blood establishments and hospital blood banks. QIs defined by ISBT QM-WP were further developed and revised considering data obtained from an international survey on QIs, targeted consultations with members of the ISBT QM-WP and individual expert opinions. Several revisions of quality indicators proposed by ISBT QM-WP have been published. The latest version from 2023 is presented in this paper and contains data on 50 QIs. Each indicator is defined, its importance is explained and the numerator and denominator required for its calculation are defined. The indicators are divided into seven groups according to areas of activity in the transfusion chain. This paper underlines the importance of QIs and provides resources for their selection, implementation and monitoring.

To analyze the Bel subtype gene mutation and its genetic mechanism in a family line. ABO blood groups were identified by serologic tests. ABO genotyping was performed by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sanger sequencing was performed on exons 1-7 of the ABO gene, the flanking intronic region, and exon 7 of the single strand of the gene confirmed the mutation site location. Missense3D software was used to predict the protein structure alteration caused by this mutation. Conventional serologic tests failed to detect erythrocyte B antigen in the proband and her three family members, and only trace amounts of B antigen expression could be detected by the absorption-dispersal test. DNA analysis showed that, on the basis of the normal ABO gene, there was a G>T substitution in the position of exon 7, position 803, which resulted in the change of amino acid 268 from Gly to Val. Further single-stranded sequencing analysis showed that the mutation site was located in the B gene. In this family line, the proband, her father, her son, and her daughter all have reduced B type glycosyltransferase activity due to the new point mutation (c.803G>T) in exon 7 of the B gene, and the B antigen can only be detected by the absorption-dispersal method, and the point mutation can be stably inherited by offspring.

The treatment of COVID-19 in the post-transplant individuals is challenging, primarily due to the drug-drug interaction between nirmatrelvir/ritonavir and tacrolimus. Deuremidevir hydrobromide tablets (VV116) is an orally small molecule agents target SARS-CoV-2 RdRp and inhibits viral replication. It may have a low likelihood of drug-drug interactions and has a potential to provide new treatment option. We described three cases of renal transplant patients with concomitant impaired renal function who developed COVID-19 pneumonia and were treated with VV116. Despite varying degrees of drug accumulation, these patients achieved rapid viral clearance and showed prompt improvement in pneumonia symptoms. Notably, tacrolimus blood concentrations remained within the therapeutic range throughout treatment, and no clinically significant adverse events were observed despite the drug accumulation.

The novel HLA-C*15:279 allele differs from HLA-C*15:02:01:01 by five nucleotide substitutions in exons 4 and 5.