BACKGROUND:The national and subnational burden of asthma in China remains insufficiently characterized. We aimed to assess the long-term trends in asthma burden and associated risk factors across China from 1990 to 2023. METHODS:Using data from the Global Burden of Disease 2023 study, we assessed asthma deaths, prevalence, and disability-adjusted life years (DALYs) in China and its provincial-level administrative regions from 1990 to 2023, stratified by age and sex. Decomposition analyses were conducted to quantify the contributions of demographic changes and level 2 risk factors to changes in the asthma burden estimates. RESULTS:Between 1990 and 2023, the age-standardized asthma death rate (95% uncertainty interval [UI]) in China declined from 2.4 (1.1-4.0) to 1.1 (0.7-2.0) per 100,000, while the age-standardized prevalence rate (95% UI) increased from 2902.7 (2392.7-3550.4) to 3066.8 (2529.4-3675.7) per 100,000. Age-standardized DALY rates decreased overall, with years lived with disability (YLDs) accounting for an increasing proportion of total DALYs. Substantial provincial heterogeneity was also observed. Tobacco use remained the leading contributor to the asthma burden, particularly among males, whereas the contribution of high body mass index (BMI) increased steadily. Population aging was the main driver of changes in asthma mortality, while increasing exposure to high BMI drove increases in DALYs. CONCLUSIONS:Asthma mortality in China has declined substantially, but the nonfatal burden continues to rise, driven by increasing prevalence and metabolic risk factors. Integrated strategies targeting both respiratory risk factors and metabolic risks are required to reduce asthma-related disabilities, especially in high-burden regions.
Vibrio cholerae, typically associated with cholera, rarely causes invasive disease. This case report describes a 59-year-old man with pancreatectomy, splenectomy and diabetes, admitted with nontoxigenic V. cholerae O1 bacteraemia after returning from Sri Lanka, with suspected exposure, including contaminated well water. He presented with fever, upper abdominal pain, and elevated inflammatory, liver, and biliary markers. CT findings and clinical history raised suspicion of cholangitis. Targeted ciprofloxacin led to full recovery. This case highlights the invasive potential of nontoxigenic V. cholerae O1.
The treatment of bilateral recurrent laryngeal paralysis is usually tracheotomy or various forms of irreversible surgery with removal of parts of the larynx. Since recurrent laryngeal paralysis is reversible in 33% of cases, tracheotomy is usually the treatment of choice. Here, in this case, we present an alternative reversible solution in a patient where a tracheostomy tube was a suboptimal solution.
Transcranial magnetic stimulation is a non-invasive brain stimulation technique which generates an electrical current in the cerebral cortex and alters excitability. This review focuses on repetitive transcranial magnetic stimulation and its use in therapy. It describes which stimulation parameters and localisation are used in rehabilitation after brain injury, neuropathic pain, complex pain disorders and depression. While current results are promising, there is still a need to uncover stimulation parameters and localisation for optimal treatment.
Coronary artery calcium (CAC) scoring is a widely available method for detecting subclinical atherosclerosis. This review finds CAC scoring strongly predicts future cardiovascular events and may refine risk assessment beyond traditional factors. Guidelines recommend CAC scoring mainly for low-intermediate-risk patients, while evidence for treatment decisions based solely on CAC is limited. Broader use of CAC, including standardized reporting of routine chest CT, holds promise and may enable earlier prevention, but requires randomized trials.
Advanced therapy medicinal products are a rapidly expanding drug class based on genes, cells, and tissues, transforming the treatment of diseases, including haematologic cancers and genetic disorders, such as sickle cell disease and haemophilia. This review highlights that successful clinical implementation requires coordinated national strategies, regulatory support, sustainable funding, robust clinical and production infrastructure, and trained specialised personnel to ensure timely, safe, and equitable patient access.
BACKGROUND:N6-methyladenosine (m6A) drives T-cell acute lymphoblastic leukemia (T-ALL); however, its roles in leukemic heterogeneity and tumor microenvironment remodeling unclear. This study characterized N6-methyladenosine regulator-defined subpopulations and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in leukemogenesis. METHODS:Integrated single-cell and bulk RNA sequencing from 17 pediatric T-cell acute lymphoblastic leukemia patients and 3 healthy donors were analyzed. Non-negative matrix factorization based on m6A regulator expression identified distinct T-cell subpopulations. CellChat, Monocle, and single-cell regulatory network inference and clustering analyses revealed intercellular communication patterns, developmental trajectories, and transcriptional regulatory programs. Functional validations included lentiviral-mediated YTHDF1 knockdown in Jurkat and Molt4 cells for proliferation, apoptosis, and migration assays, and a non-obese diabetic severe combined immunodeficiency mouse xenograft model. Methylated RNA immunoprecipitation quantitative polymerase chain reaction, RNA immunoprecipitation quantitative polymerase chain reaction, RNA stability assays, and Western blotting characterized YTHDF1 interactions with heat shock protein 90 alpha family class B member 1 (HSP90AB1). RESULTS:Single-cell transcriptomics identified m6A-defined T-cell subpopulations in T-ALL. YTHDF1-enriched cells exhibited hypoxia and cell-cycle programs, occupied early developmental states, and communicated with macrophages. Knockdown suppressed proliferation and migration, increased apoptosis, and reduced leukemic burden in vivo. The protein bound and stabilized m6A-modified HSP90AB1 to sustain MYC proto-oncogene signaling. CONCLUSION:This study identified a YTHDF1-high m6A-associated T-cell subpopulation in T-ALL. YTHDF1 promoted leukemic progression through regulation of the HSP90AB1-MYC axis and was associated with altered macrophage-related intercellular signaling.
ABSTRACT:Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. The etiology of liver cancer is complex and diverse; it is mainly caused by hepatitis virus infection, liver cirrhosis, and/or alcoholic hepatitis, among other contributing factors. However, the complex pathogenesis of HCC remains to be elucidated. Tumor suppressor proteins can inhibit the occurrence and development of tumors. Posttranslational modifications (PTMs) of proteins affect protein function, and lactylation is an important form of PTM. Recent studies have reported that after lactylation, tumor suppressor proteins regulate various biological processes, such as tumor immune tolerance. Therefore, lactylation of tumor suppressor proteins may promote the occurrence and development of HCC. Since the immune escape of HCC after lactylation of tumor suppressor proteins has rarely been reported, the exact molecular mechanism has not yet been clarified. In this article, we comprehensively analyzed the functional changes in tumor suppressor proteins after lactylation modification and reviewed the effects on immune escape in HCC and its regulatory mechanism, to identify targets for the development of lactylation inhibitors to enhance immunotherapy of HCC.
BACKGROUND:The cognitive-enhancing effects of dietary lecithin are gaining increasing attention, but evidence supporting these claims remains limited. This study aims to explore the relationship between dietary lecithin intake and cognitive function, as well as the prevalence of mild cognitive impairment (MCI), in adults aged over 60 years. METHODS:This cross-sectional study included participants aged over 60 years recruited from Beijing, Jincheng City (Shanxi Province), and Linyi City (Shandong Province) from 2020 to 2023. Cognitive function and dietary intake were assessed using neuropsychological tests and a food frequency questionnaire, respectively. Body composition was measured by bioelectrical impedance analysis, and blood lipids by an automated biochemistry analyzer. Spearman correlation analysis, multiple linear regression, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed. RESULTS:Among the 1917 participants enrolled, 1023 (1023/1917, 53.4%) had MCI, of whom 542 (542/1023, 53.0%) were women. Multiple linear regression showed that after dichotomizing lecithin and serum cholesterol indicators according to the median, high levels of dietary lecithin, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were associated with higher Montreal Cog-nitive Assessment (MoCA, regression coefficients were 0.49, 0.44, and 0.38, respectively); logistic regression showed that, compared with low intake level, the odds ratio (95% confidence interval [CI]) of MCI in high dietary lecithin intake group was 0.80 (95% CI: 0.64, 0.99). ROC analysis of a model incorporating dietary lecithin, energy intake, demographic, and clinical characteristics yielded an area under the curve (AUC) of 0.735 (95% CI: 0.713-0.757). Targeted lipidomic analysis revealed that the MCI group exhibited a lower total phosphatidylcholine (PC) level, a reduced proportion of PC containing polyunsaturated fatty acid (PUFA), and a higher proportion of PC containing saturated fatty acid (SFA). CONCLUSION:Higher dietary lecithin intake was associated with better cognitive performance and a lower prevalence of MCI among the elderly population aged 60 and above.
ABSTRACT:Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) are characterized by a disastrous prognosis. For most patients with R/R AML, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option. It is important to conduct mutational analysis again when the disease relapses to identify any new genetic abnormalities that can be targeted with novel treatments. As part of a conditioning regimen or post-transplant maintenance therapy, new targeted agents support HSCT in patients with R/R AML in various forms, including combination chemotherapy to improve complete remission (CR) prior to HSCT. For R/R AML patients with mutated FMS-related tyrosine kinase 3 (FLT3), sorafenib and quizartinib have shown encouraging therapeutic effects either in combination with chemotherapy for bridging to transplantation or as maintenance therapy after HSCT. Ivosidenib and enasidenib, which are inhibitors that target mutated isocitrate dehydrogenase (IDH) 1 and 2, respectively, have been approved by the US Food and Drug Administration (FDA) for the treatment of IDH1/IDH2-mutated R/R AML. Venetoclax, an inhibitor of B-cell lymphoma-2 (BCL2), is widely used in the salvage treatment of R/R AML and has better therapeutic effects and controllable drug toxicity than traditional chemotherapy. In addition, chimeric antigen receptor (CAR) T-cell immunotherapy (targeting CD33, CD123, and CLL1) has achieved encouraging clinical response rates in phase I and phase II clinical trials for R/R-AML, and subsequent bridging HSCT has significantly improved patient survival.
ABSTRACT:Chronic dermatological conditions impose a significant burden on global health and quality of life. The etiology of these disorders is multifaceted, driven by complex interactions between endogenous factors and the "skin exposome", which comprises a person's environmental exposure and lifestyle. While digital health systems (DHSs) have transformed the management of numerous chronic diseases, a unified framework that captures the dynamic interplay of environment, behavior, and skin physiology has not been fully established to date. Therefore, this review proposes and evaluates a holistic "environment-behavior-skin health" integrated management paradigm. It aims to examine how DHSs can be leveraged to track external determinants and individual behaviors to facilitate personalized skin health management. A comprehensive review of relevant literature from the past 5 years was conducted across medical, public health, and computer science databases. The study analyzed digital technologies, environmental and behavioral influencing factors, and the application of artificial intelligence (AI) in dermatology. The review identifies that key DHS technologies provide the infrastructure necessary to elucidate the skin exposome. It elucidates how behavioral factors and environmental determinants influence skin health through five core physiological pathways. While AI has achieved a high level of proficiency in image-based diagnosis, current applications often lack integration with longitudinal lifestyle and environmental data. Moving beyond traditional visual assessments, the integration of multimodal data via DHSs enables a shift from reactive, symptomatic treatment to proactive, precision dermatology. By utilizing AI to synthesize environmental sensing and behavioral tracking data, the proposed "environment-behavior-skin health" paradigm offers a promising pathway for elucidating complex disease mechanisms and delivering tailored interventions for chronic skin disease management.
ABSTRACT:Metabolic reprogramming is a central regulator of cell fate and tissue homeostasis. By systematically remodeling metabolic pathways, cells adapt to specific physiological or pathological conditions to support survival and proliferation, often through enhanced glycolysis and lactate accumulation. Emerging evidence suggests that lactate accumulation can drive histone and nonhistone lactylation, thereby reshaping gene regulation and promoting inflammatory activation, matrix catabolism, and cellular senescence, which contribute to the initiation and progression of skeletal disorders such as osteoarthritis, osteoporosis, intervertebral disc degeneration, and rheumatoid arthritis. Importantly, these mechanisms also reveal actionable therapeutic opportunities involving lactate clearance and redox balance, mitochondrial quality control, and epigenetic modulation. Biomaterial-based strategies have emerged as powerful tools for modulating metabolic reprogramming through spatiotemporal and stimuli-responsive regulation. Representative systems include metabolism-responsive nanoparticles, cell-derived systems, composite hydrogels, and scaffold-based platforms. By restoring metabolic homeostasis, such biomaterials offer promising opportunities to slow degeneration and promote tissue regeneration. Overall, biomaterials represent an emerging strategy for modulating metabolic reprogramming in skeletal disorders, although most current evidence remains preclinical, and further mechanistic and translational validation is still needed.
Human and animal data show that youth nicotine exposure causes permanent brain changes and raises mental illness risk, including addiction to nicotine and other drugs. E-cigarettes (EC) and nicotine pouches (NP) are associated with subsequent tobacco smoking, and vice versa, but whether these links are mainly causal or due to common liability remains debated. Use of EC and NP is negatively correlated with tobacco use. Some studies suggest EC and NP add harm; others suggest they reduce harm. This review finds that misinterpreting data can lead to regulations that fail to improve public health.
Severe obesity is a growing health challenge, and some experience disabling functional problems despite major weight loss. In this case report, we present two male patients with giant pannus, resulting in limited mobility, recurrent infections, and social restrictions. Both underwent giant panniculectomy, removing 34.6 kg and 18.9 kg of tissue, respectively. Postoperative results included regaining the ability to walk without mobility aids, resuming physical activity, and increasing social interaction. Giant panniculectomy can provide substantial quality-of-life improvement in selected patients.
BACKGROUND:Programmed death-ligand 1 (PD-L1) expression and CD8-positive (CD8+) T-cell infiltration in tumor tissue are associated with prognosis in non-small cell lung cancer (NSCLC). However, the prognostic value of combined PD-L1/CD8 immune phenotyping in surgically treated NSCLC and the feasibility of predicting high-risk immune phenotypes using routine clinical indicators remain unclear. This study aimed to evaluate the prognostic significance of PD-L1/CD8 status and to develop machine learning models for predicting PD-L1-positive/CD8-negative (PD-L1+ CD8-) status. METHODS:This study included 844 patients with NSCLC who underwent surgical resection at Wuhan Union Hospital and Renmin Hospital of Wuhan University between March 2012 and November 2022. PD-L1 expression and CD8+ T-cell infiltration were assessed by immunohistochemistry, and preoperative clinical data were collected. Kaplan-Meier analysis, stratified survival analysis, univariable and multivariable Cox proportional hazards regression models were used to evaluate the association between PD-L1/CD8 status and overall survival (OS). Patients from Wuhan Union Hospital were divided into training, test, and internal validation sets, whereas patients from Renmin Hospital of Wuhan University were used as an external validation set. Multiple machine learning models were developed to predict PD-L1+ CD8- status. Feature importance and and SHapley Additive exPlanations (SHAP) analysis were used to interpret model predictions. RESULTS:Based on PD‑L1/CD8 status, tumors from the 844 patients were classified into four immune phenotypes. Kaplan-Meier analyses revealed significant differences in OS among the four PD-L1/CD8 subgroups, with the PD-L1+ CD8- subgroup displaying the poorest survival. This pattern was also observed in several stratified analyses. Multivariable Cox regression analysis further demonstrated that PD-L1+ CD8- status was independently associated with worse OS compared with PD-L1+ CD8+ status (hazard ratio = 3.261, 95% confidence interval: 1.310-8.116, P = 0.011). On this basis, machine learning models were developed to predict PD-L1+ CD8- status. Among the evaluated models, the stacking model showed the best overall performance, with area under the curve values of 0.998, 0.700, 0.853, and 0.783 in the training, test, internal validation, and external validation sets, respectively. Feature importance and SHAP analyses suggested that PD-L1+ CD8- status was associated with a composite pattern involving hematologic, biochemical, inflammatory, and coagulation-related indicators. CONCLUSIONS:PD-L1/CD8-based phenotyping identified prognostically distinct subgroups in surgically treated NSCLC, with PD-L1+ CD8- status defining a high-risk phenotype associated with poor survival. A machine learning model based on clinical indicators may enable efficient, noninvasive identification of PD-L1+ CD8- status and help guide treatment decisions.
