Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

ObjectiveTo systematically synthesize the illness experiences and unmet needs of patients with stroke during the rehabilitation phase. MethodsQualitative studies focusing on the illness experiences and needs of stroke patients in the rehabilitation period were retrieved from the databases of Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, CBM, Wanfang data and VIP. The search timeframe was from database inception to December, 2024. Methodological quality was evaluated using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A meta-synthesis method was adopted to categorize and integrate the findings. ResultsA total of ten studies were included. Forty-nine themes were extracted and further grouped into ten categories, which were finally integrated into three overarching themes: negative illness perceptions, multifaceted rehabilitation motivations and unmet multidimensional needs. ConclusionPatients with stroke undergo complex physical and psychological experiences during rehabilitation and present diverse and multidimensional needs.

ObjectiveTo systematically synthesize the illness experiences and unmet needs of patients with stroke during the rehabilitation phase. MethodsQualitative studies focusing on the illness experiences and needs of stroke patients in the rehabilitation period were retrieved from the databases of Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, CBM, Wanfang data and VIP. The search timeframe was from database inception to December, 2024. Methodological quality was evaluated using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A meta-synthesis method was adopted to categorize and integrate the findings. ResultsA total of ten studies were included. Forty-nine themes were extracted and further grouped into ten categories, which were finally integrated into three overarching themes: negative illness perceptions, multifaceted rehabilitation motivations and unmet multidimensional needs. ConclusionPatients with stroke undergo complex physical and psychological experiences during rehabilitation and present diverse and multidimensional needs.

ObjectiveTo systematically synthesize the illness experiences and unmet needs of patients with stroke during the rehabilitation phase. MethodsQualitative studies focusing on the illness experiences and needs of stroke patients in the rehabilitation period were retrieved from the databases of Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, CBM, Wanfang data and VIP. The search timeframe was from database inception to December, 2024. Methodological quality was evaluated using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. A meta-synthesis method was adopted to categorize and integrate the findings. ResultsA total of ten studies were included. Forty-nine themes were extracted and further grouped into ten categories, which were finally integrated into three overarching themes: negative illness perceptions, multifaceted rehabilitation motivations and unmet multidimensional needs. ConclusionPatients with stroke undergo complex physical and psychological experiences during rehabilitation and present diverse and multidimensional needs.

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

[Purpose]To analyze the changing trends of the disease burden of liver cancer related to hepatitis B virus(HBV)globally and in China from 1992 to 2021.[Methods]Based on the Global Burden of Disease database in 2021,indicators such as the age-standardized incidence rate and mortality rate of HBV-related liver cancer globally and in China from 1992 to 2021 were collected.The Joinpoint regression model was used to analyze the changing trends of epidemiologi-cal characteristics,and the age-period-cohort model was adopted to analyze the impacts of age,period,and cohort factors on the incidence and mortality risks of HBV-related liver cancer globally and in China.[Results]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer globally generally showed a trend of decreasing.The average annual percentage changes were-0.31％and-0.61％,respectively,and all the down-ward trends were statistically significant(both P＜0.05).During the same period,the average annu-al percentage changes of the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer in China were-0.45％and-0.90％,respectively,and all the downward trends were statistically significant(both P＜0.05).The results of the age-period-cohort model anal-ysis showed that from 1992 to 2021,the annual net drift rates of the incidence of HBV-related liver cancer globally and in China were-0.71％(95％CI:-0.84％～-0.57％)and-0.73％(95％CI:-1.01％～-0.44％),respectively.The annual net drift rates of the mortality were-1.15％(95％CI:-1.28％～-1.02％)and-1.42％(95％CI:-1.69％～-1.14％),respectively,all showing an over-all decline.The age effect showed that the risk of HBV-related liver cancer incidence in both the global and Chinese populations began to increase after 30 years of age,peaking in the 70～74 age group,while the risk of mortality surged after 40 years of age and peaked in the population aged 80 and above.The period effect indicated that the incidence and mortality risks were the highest from 1997 to 2001 and the lowest from 2017 to 2021.The cohort effect revealed that the inci-dence and mortality risks gradually decreased in populations born after 1962,with the 2007-2011 birth cohort having the lowest risks.The results of the Wald x2 test showed that there were statistically significant differences in the changing trends of the age,period,and cohort effects on the incidence and mortality of HBV-related liver cancer globally and in China(all P＜0.05).[Con-clusion]From 1992 to 2021,the age-standardized incidence rate and age-standardized mortality rate of HBV-related liver cancer showed a downward trend both globally and in China.The disease burden of HBV-related liver cancer in China was higher than the global level.The age-period-cohort model has revealed the historical changes in the incidence and mortality of HBV-related liver cancer.The current and future situation of the disease burden of HBV-related liver cancer is not optimistic.It is recommended to implement precise stratified interventions for populations of different ages,periods,and birth cohorts,and actively transform the prevention,treatment,and management strategies for HBV-related liver cancer.

This document targets digital human metabolic chamber platforms and specifies construction standards and testing protocols covering the full lifecycle of " build-test-operate." It encompasses chamber engineering and environmental control, digital platform and cybersecurity architecture, metabolic measurement and multimodal data acquisition, as well as quantitative system performance and data quality indicators with verifiable acceptance tests. By standardizing architecture, interfaces, and quality control, the specification enables multicenter data interoperability and harmonized quality management, providing high-quality, verifiable, and traceable infrastructure to support precision metabolism research and clinical translation in China.