ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

[Objective] To explore the accuracy and feasibility of non-invasive prenatal diagnosis of fetal RhE genotype using cell-free fetal DNA (cff-DNA) from maternal peripheral blood. [Methods] A total of 134 pregnant women with single fetuses and RhE-negative blood group were selected from our hospital from November 2023 to August 2024. Free DNA extraction kit was used to extract free DNA from peripheral blood of pregnant women, and the RhE blood group genotype of free DNA was detected by real-time fluorescent quantitative PCR (RT-qPCR). If the qPCR amplification signal of the sample was negative, the methylated RASSF1A gene was amplified, and the positive amplification result was used as a sign of successful extraction of cff-DNA. Serological microcolumn gel method was used to detect the phenotype of RhE blood group in neonatal peripheral blood. [Results] Among the 134 maternal peripheral blood samples, the cff-DNA detection of RhE blood group phenotypes was consistent with the RhE blood group genotyping of neonatal peripheral blood in 133 cases, including 90 cases of Rhee genotype and 43 cases of RhE genotype, with diagnostic concordance rate of 99.3%, sensitivity of 97.7%, specificity of 100%, youden index of 0.977, area under ROC curve of 0.995, the Kappa value of 0.983, positive predictive value of 100%, and negative predictive value of 98.9%. The sample of 1 case failed to be detected. After the amplification of methylated RASSFIA gene, it was confirmed that the reason for the failure was that no cff-DNA was extracted from the sample. The diagnostic concordance rates of the first, second and third trimesters were 93.8% (15/16), 100% (51/51) and 100% (67/67), respectively. Fisher's exact test method was used to calculate the P value, which was P>0.05, indicating that there was no statistical significance in the difference of diagnostic concordance rate among the three pregnancy periods, and there was no difference in the detection concordance rate of this method in different pregnancy periods. [Conclusion] The use of cff-DNA in maternal peripheral blood for the detection of fetal RhE blood group genotype is an accurate and highly feasible non-invasive prenatal diagnostic method, which is helpful for the clinical diagnosis of fetal and neonatal hemolytic disease caused by anti-E antibody.

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Humans ; Animals

Objective To analyze the changing trends of the burden of non-alcoholic fatty liver disease(NAFLD)in China from 1990 to 2021 and provide a basis for formulating prevention and treatment strategies.Methods The standardized incidence rate,prevalence,mortality,and disability-adjusted life year(DALY)rate of NAFLD in China from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021.The average annual percentage change of rate data was calculated by Joinpoint 4.2 and the age,period,and birth cohort effects of the prevalence and DALY rate were analyzed by the age-period-cohort model.Results Compared to 1990,the incidence rate and prevalence of NAFLD have been on the rise,while the mortality and DALY rate have been declining.The age effect curves of prevalence and DALY rate showed an upward trend followed by a downward trend for both males and females.With the period from 1992 to 1996 as the reference group,the period effect curve of prevalence showed a downward trend followed by an upward trend,being the lowest in the period from 2002 to 2006(RR=0.93).The period effect curve of DALY rate showed a downward trend from 1992 to 2011 and then tended to flatten out.With the period from 1972 to 1981 as the reference group,the birth cohort effect curve of prevalence showed a steady upward trend in the general population and both male and female populations.The birth cohort effect curve of DALY rate showed an overall upward trend followed by a downward trend,with the peak occurring in the birth cohort group between 1922 and 1931.The DALY rate of NAFLD caused by smoking and high fasting blood glucose has shown a downward trend since 2014,and fasting blood glucose gradually became the dominant factor as age increased.Conclusions From 1990 to 2021,NAFLD in China has shown a rising prevalence but a significantly declining DALY rate.This suggests that current prevention and control strategies are effective,and further efforts should be made to raise residents' health awareness in controlling the occurrence and development of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/epidemiology* ; China/epidemiology* ; Prevalence ; Female ; Male ; Incidence ; Disability-Adjusted Life Years ; Middle Aged ; Adult

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.