The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019 “Chinese Guidelines on the Management of Liver Cirrhosis” to “Chinese Guidelines for Clinical Diagnosis, Treatment, and Management of Cirrhosis (2025)”. These updated guidelines are aimed at providing recommendations for the clinical diagnosis and management of liver cirrhosis across the compensated, decompensated, and recompensated stages, as well as guidance on cirrhosis reversal and associated complications.

The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.

We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.

Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).

This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.

Ischemic stroke is a complex cerebrovascular disorder characterized by highly unpredictable outcomes influenced by patient-specific variables, including age, stroke severity, and preventable stroke-related complications such as infections. Analyses of clinical data have indicated a cumulative post-stroke infection rate of approximately 30%, with reported rates ranging from 5% to 65%. Post-stroke infections pose a significant challenge, as they not only increase the financial burden of stroke care but are also associated with adverse clinical outcomes, prolonged hospital stays, and a higher risk of stroke recurrence. The inflammatory response plays a pivotal role in the pathophysiology of ischemic stroke, encompassing the activation of inflammatory cells, the release of inflammatory mediators, and the engagement of inflammatory signaling pathways. Recent advances in molecular biology have facilitated the identification and investigation of numerous inflammation-related biomarkers. This article reviews the roles and mechanisms of key inflammatory biomarkers, including cytokines, chemokines, adhesion molecules, inflammation-related enzymes and mediators, receptors, signaling pathway molecules, and acute-phase proteins in the context of ischemic stroke, highlighting their significance in stroke pathophysiology and prognostic assessment. Additionally, in conjunction with the latest research advances, the article discusses novel biomarkers such as microRNAs and galectin-3, which are emerging as important tools in multiple domains, including diagnosis and treatment. Drawing on clinical diagnostic and therapeutic practices, this review analyzes the diagnostic and therapeutic roles of both novel and traditional biomarkers in the progression of ischemic stroke, following the temporal sequence from disease onset to prognosis. Finally, the article addresses the limitations of current research and offers perspectives on future directions, providing insights that may contribute to the advancement of precision medicine in the management of ischemic stroke.

Drug discovery is an exceptionally long and costly process, often taking over 10 years and costing billions of dollars. Despite these efforts, more than 90% of drug candidates fail, with most failures occurring during clinical trials due to issues related to efficacy, safety, or poor pharmacokinetics. A major contributor to these failures is biopharmaceutic barriers, including poor solubility, limited permeability, active efflux by transporters such as P-glycoprotein and breast cancer resistance protein, and extensive first-pass metabolism by CYP450 enzymes. These factors severely limit drug absorption and bioavailability, reducing therapeutic efficacy. Although traditional approaches, such as high-throughput absorption, distribution, metabolism, and excretion screening and improved chemical design, have achieved some progress, a major shift is now occurring through the use of in silico modeling, artificial intelligence (AI), and machine learning. These AI-driven tools enhance the prediction accuracy of absorption, distribution, metabolism, and excretion profiles, identify transporter interactions, and even simulate metabolic pathways. Additionally, modern formulation technologies, such as three-dimensional printing, lipid-based nanocarriers, and biodegradable delivery systems, are increasingly being integrated with AI-powered design platforms to personalize and optimize drug delivery. However, these promising advancements also raise regulatory and ethical concerns that must be addressed before widespread adoption. This review examines the major biopharmaceutic barriers responsible for drug development failures and explores how emerging AI-driven strategies and formulation innovations are being used to overcome these limitations. It also discusses current regulatory challenges and ethical considerations associated with adopting these technologies.

Aging is characterized by a progressive decline in physiological function, an increased risk of chronic diseases, and multiple molecular and cellular alterations, including inflammation, oxidative stress, and mitochondrial dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for the treatment of type 2 diabetes and obesity, may modulate pathways associated with the hallmarks of aging. This review aims to summarize the mechanistic and therapeutic evidence for GLP-1 RAs in targeting key aging processes and their potential to restore cellular homeostasis and enhance healthspan. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to August 2025. Both preclinical and clinical studies were included if they evaluated the effects of GLP-1 RAs on the major biological processes encompassed by the 12 hallmarks of aging, such as mitochondrial dysfunction, insulin resistance, dysbiosis, inflammaging, autophagy, proteostasis, and genomic stability. Data were analyzed narratively to elucidate potential mechanisms and translational relevance. Evidence from animal and human studies demonstrates that GLP-1 RAs improve mitochondrial function, reduce oxidative stress, attenuate chronic inflammation, and enhance autophagic activity. Additionally, they modulate nutrient-sensing pathways and metabolic processes, thereby improving cellular resilience. Preclinical studies indicate neuroprotective, cardioprotective, and hepatoprotective effects, while emerging clinical data support improvements in metabolic and inflammatory profiles in older adults. Taken together, GLP-1 RAs exert pleiotropic effects across all 12 hallmarks of aging. Although long-term safety and efficacy require further evaluation, current evidence positions GLP-1 RAs as promising therapeutic agents in translational geroscience, with the potential to mitigate age-related physiological decline and promote a longer, healthier lifespan.

High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization classification. This study aimed to characterize the clinicopathologic, immunohistochemical, and molecular features of high-grade serous carcinoma identified in cervical or endocervical biopsies, to assess tumor origin and ensure accurate classification.

Fifty-nine cases originally diagnosed as “serous carcinoma” or “high-grade serous carcinoma” in cervical or endocervical biopsies from 2013 to 2023 were retrospectively reviewed. Clinical data, radiologic findings, and follow-up information were analyzed. Histologic features and immunohistochemical profiles were re-evaluated. Targeted next-generation sequencing was performed on a subset of cases.

The majority of tumors (96%) were determined to originate from the endometrium (n = 47) or the tubo-ovarian region (n = 4), with only one case confirmed as a primary cervical carcinoma. Morphologic patterns varied and could mimic human papillomavirus-associated adenocarcinoma. All tumors showed aberrant p53 expression and diffuse p16 positivity. WT-1 was expressed in all tubo-ovarian tumors but in only 12% of endometrial cases. Estrogen receptor and progesterone receptor were frequently positive in endometrial tumors; human epidermal growth factor receptor 2 was positive in 31% of cases. Molecular analysis confirmed tumor protein p53 mutations and other alterations typical of uterine serous carcinoma.

High-grade serous carcinoma identified in cervical biopsies is overwhelmingly secondary to upper genital tract tumors, most commonly of endometrial origin. A small subset of endocervical adenocarcinomas may mimic serous carcinoma. These findings support the exclusion of primary cervical serous carcinoma from the current World Health Organization classification and emphasize the importance of accurate diagnosis for appropriate management.

Hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer and continues to be a major cause of cancer-related mortality, particularly in regions of China with a high hepatitis B virus prevalence. Early-stage diagnosis remains challenging due to its asymptomatic onset and the limited sensitivity of conventional biomarkers, which together contribute to delayed detection, suboptimal therapeutic outcomes, and poor prognosis. These limitations underscore the urgent need for reliable, sensitive, and specific biomarkers to enable timely detection and targeted intervention. Protein induced by vitamin K absence or antagonist-II, an abnormal prothrombin variant generated under vitamin K deficiency or antagonism, has emerged as a promising candidate with diagnostic and therapeutic relevance in HCC. This review critically examines the molecular and biological characteristics of protein induced by vitamin K absence or antagonist-II, evaluates its clinical utility in HCC diagnosis and management, and delineates the current limitations hindering its broader application. Furthermore, future perspectives are proposed to guide translational research and clinical implementation. Collectively, this review aims to provide a comprehensive theoretical framework to advance precision diagnosis and individualized treatment strategies for HCC.

Laboratory-acquired infections (LAIs) have been documented since the first report of typhoid fever in 1885 and continue to endanger laboratory professionals despite decades of biosafety advances. This review provides a comprehensive overview of LAIs, emphasizing their history, modes of transmission, and strategies for prevention.

A historical narrative review of records, case series, and biosafety guidance (1885–2025) identified documented LAIs, their transmission routes, and preventive measures. Data were extracted on pathogen spectrum, geographic distribution, incident outcomes, and the effectiveness of biosafety interventions.

Historical analysis identified 50 laboratory-acquired typhoid infections with six deaths from 1885 to 1915, largely due to mouth pipetting and aerosol exposure. A sharp decline in fatal bacterial infections was observed following the introduction of Class II biosafety cabinets in the 1960s. From 2000 to 2021, 309 LAIs were reported across 94 studies, most commonly Salmonella enterica (56.6%), vaccinia virus (4.2%), and Brucella species (3.9%), with Brucella responsible for over half of hospital-laboratory cases (60 per 100,000 personnel-years). In Canada during 2023, 63 exposure events occurred, including three confirmed infections despite adherence to biosafety level protocols. Environmental persistence studies underscored surface-borne risks. The most effective preventative measures included abolishing mouth pipetting, mandatory use of gloves and eye/face protection, routine Class II biosafety cabinet use for aerosol-generating procedures, surface disinfection with 0.5% sodium hypochlorite, and annual competency-based biosafety training with incident reporting.

LAIs remain geographically widespread and pathogen-diverse. Quantitative historical trends and contemporary surveillance highlight critical transmission routes, including ingestion, inoculation, mucosal splash, and inhalation, while reinforcing evidence-based prevention strategies. Sustained investment in biosafety infrastructure, real-time exposure reporting, and pathogen-specific training is essential to further reduce LAI incidence and severity in the face of emerging antimicrobial resistance and novel agents.

Precision medicine represents a paradigm shift in healthcare, emphasizing individualized approaches to disease prevention, diagnosis, and treatment based on a patient’s genetic, proteomic, and immunologic profile. In the field of oncology, this paradigm has gained traction, particularly with the integration of immunotherapeutic modalities. Among the most promising advancements are therapeutic cancer vaccines, which harness the body’s immune system to fight tumors more effectively. This mini-review highlights recent developments in therapeutic vaccine engineering. It also discusses key barriers to clinical translation and summarizes findings from contemporary human clinical trials evaluating personalized cancer vaccines. In addition, it evaluates the growing potential of these therapies to redefine cancer treatment.

Metabolic dysfunction-associated fatty liver disease (MAFLD) poses a significant challenge in modern medicine due to its high prevalence. The pathogenesis of MAFLD involves a complex dysmetabolic process consistent with the “multiple-hit” hypothesis. This process includes excessive triglyceride (TC) accumulation within hepatocytes, lipotoxicity, insulin resistance (IR), chronic low-grade inflammation, and increased oxidative stress. The role of leptin in the liver has been extensively studied, demonstrating both direct effects on hepatic cells and indirect actions mediated through the central nervous system (CNS). In MAFLD, leptin modulates several physiological processes: it improves glucose metabolism by enhancing insulin sensitivity and lowering glucose levels; regulates lipid metabolism by promoting β-oxidation and TC export while inhibiting lipogenesis; and contributes to fibrogenesis by upregulating transforming growth factor-β (TGF-β) expression and activating hepatic stellate cells (HSCs) and the immune response. This review explores the structure of leptin, its primary physiological functions, its potential role in MAFLD pathogenesis, and its promise as a novel therapeutic target.