Background: Type 2 diabetes mellitus (T2DM) is a complex, multifactorial disease with a significant global burden. Although genome-wide association studies (GWAS) have identified many T2DM-associated variants, most lie in non-coding regions, making it difficult to interpret their functional roles. Methods: We aimed to identify genetically regulated Cytosine–phosphate–Guanine (CpG) sites associated with T2DM by conducting a methylome-wide association study (MWAS), followed by Mendelian randomization (MR) and functional validation using human pancreatic cells and mouse models. MWAS was performed using summary statistics from large-scale GWAS and a DNA methylation (DNAm) prediction model to test associations between genetically predicted DNAm and T2DM. Results: We identified 111 CpG sites significantly associated with T2DM in Europeans, including 8 novel sites near genes not previously linked to T2DM. These findings were replicated in independent datasets. Many CpGs also showed associations with cardiometabolic traits, highlighting shared epigenetic mechanisms. Trans-ethnic MR analysis confirmed consistent effects for six CpGs in East Asians. Functional analysis revealed that several CpGs regulate gene expression in human pancreatic α- and β-cells. Among them, 2´-5´-oligoadenylate synthetase like (OASL) expression, regulated by a significant CpG, was differentially expressed in α-cells of T2DM cases compared to controls. Supporting evidence from mouse models suggests a role for OASL in glucose regulation. Conclusion Our study identifies novel genetically regulated CpG sites associated with T2DM risk and highlights OASL as a potential epigenetic regulator of glucose metabolism in α-cells. These findings provide mechanistic insights into the epigenetic architecture of T2DM and suggest potential targets for cross-ethnic biomarker development and therapeutic intervention.

Diarrhea-predominant irritable bowel syndrome （IBS-D） exhibits typical characteristics of psychosomatic comorbidity. Its core pathogenesis is considered to involve simultaneous disorders of both the body and the spirit， for which the former is attributed to liver constraint and spleen deficiency， and dysfunction of large intestine conduction， whereas the latter is induced by spirit restlessness of zang （脏） organs， and gate insecurity of the corporeal soul. Based on this understanding， the therapeutic principle of "simultaneous regulation of body and spirit" is established. For regulating the body， the methods include soothing the liver， fortifying the spleen， consolidating the intestines， and stopping diarrhea， with emphasis on the front-mu （募） points of the related zang-fu （脏腑） organs and acupoints of the foot yangming （阳明） stomach channel and foot taiyin （太阴） spleen channel. For regulating the spirit， the methods include calming the brain spirit， tranquilizing the zang organs spirit， and securing the corporeal soul gate， mainly selecting acupoints of Governer Vessel （督脉） and the back-shu （背俞） points of the corresponding zang-fu organs. Needle manipulation techniques for supplementation and drainage are flexibly applied according to the deficiency or excess nature of the syndrome. In addition， comprehensive application of moxibustion， electroacupuncture， and auricular therapy is emphasized， with the aim of providing clinical insights for diagnosis and treatment.

Quantum dots (QDs), nanoscale semiconductor crystals, have emerged as a revolutionary class of nanomaterials with unique optical and electrochemical properties, making them highly promising for applications in disease diagnosis and treatment. Their tunable emission spectra, long-term photostability, high quantum yield, and excellent charge carrier mobility enable precise control over light emission and efficient charge utilization, which are critical for biomedical applications. This article provides a comprehensive review of recent advancements in the use of quantum dots for disease diagnosis and therapy, highlighting their potential and the challenges involved in clinical translation. Quantum dots can be classified based on their elemental composition and structural configuration. For instance, IB-IIIA-VIA group quantum dots and core-shell structured quantum dots are among the most widely studied types. These classifications are essential for understanding their diverse functionalities and applications. In disease diagnosis, quantum dots have demonstrated remarkable potential due to their high brightness, photostability, and ability to provide precise biomarker detection. They are extensively used in bioimaging technologies, enabling high-resolution imaging of cells, tissues, and even individual biomolecules. As fluorescent markers, quantum dots facilitate cell tracking, biosensing, and the detection of diseases such as cancer, bacterial and viral infections, and immune-related disorders. Their ability to provide real-time, in vivo tracking of cellular processes has opened new avenues for early and accurate disease detection. In the realm of disease treatment, quantum dots serve as versatile nanocarriers for targeted drug delivery. Their nanoscale size and surface modifiability allow them to transport therapeutic agents to specific sites, improving drug bioavailability and reducing off-target effects. Additionally, quantum dots have shown promise as photosensitizers in photodynamic therapy (PDT). When exposed to specific wavelengths of light, quantum dots interact with oxygen molecules to generate reactive oxygen species (ROS), which can selectively destroy malignant cells, vascular lesions, and microbial infections. This targeted approach minimizes damage to healthy tissues, making PDT a promising strategy for treating complex diseases. Despite these advancements, the translation of quantum dots from research to clinical application faces significant challenges. Issues such as toxicity, stability, and scalability in industrial production remain major obstacles. The potential toxicity of quantum dots, particularly to vital organs, has raised concerns about their long-term safety. Researchers are actively exploring strategies to mitigate these risks, including surface modification, coating, and encapsulation techniques, which can enhance biocompatibility and reduce toxicity. Furthermore, improving the stability of quantum dots under physiological conditions is crucial for their effective use in biomedical applications. Advances in surface engineering and the development of novel encapsulation methods have shown promise in addressing these stability concerns. Industrial production of quantum dots also presents challenges, particularly in achieving consistent quality and scalability. Recent innovations in synthesis techniques and manufacturing processes are paving the way for large-scale production, which is essential for their widespread adoption in clinical settings. This article provides an in-depth analysis of the latest research progress in quantum dot applications, including drug delivery, bioimaging, biosensing, photodynamic therapy, and pathogen detection. It also discusses the multiple barriers hindering their clinical use and explores potential solutions to overcome these challenges. The review concludes with a forward-looking perspective on the future directions of quantum dot research, emphasizing the need for further studies on toxicity mitigation, stability enhancement, and scalable production. By addressing these critical issues, quantum dots can realize their full potential as transformative tools in disease diagnosis and treatment, ultimately improving patient outcomes and advancing biomedical science.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

In order to support the implementation of the Opinions on Improving the Quality of Traditional Chinese Medicine and Promoting the High-Quality Development of the Traditional Chinese Medicine Industry and fundamentally promote the high-quality development of Chinese materia medica(CMM) industry, this article analyzed the quality and safety issues arising during the transition of CMM from wild harvesting to cultivation. Root causes of these issues were identified, including changes in the habitats of medicinal plants caused by inappropriate field cultivation patterns, excessive use of chemical inputs such as fertilizers and pesticides, and shortened cultivation periods due to rising economic costs. To address the above issues, the following countermeasures and suggestions were proposed to advance the high-quality development of CMM:(1) comprehensively adjust the cultivation patterns, vigorously promote ecological cultivation of CMM, and ensure production quality and safety of CMM from the source;(2) strengthen the breeding of high-quality, stress-resistant CMM varieties, improve cultivation techniques to reduce the use of fertilizers and pesticides, and improve the quality and efficiency of ecological cultivation of CMM;(3) systematically design the production, operation, and supervision models for ecological cultivation of CMM, carry out demonstrations of "high quality with fair price", and ensure the sustainable development of ecological cultivation of CMM.
Drugs, Chinese Herbal/standards* ; Quality Control ; Plants, Medicinal/chemistry* ; Plant Roots/chemistry* ; China ; Fertilizers/analysis* ; Materia Medica/standards* ; Medicine, Chinese Traditional/standards*

OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

Malignant tumors(commonly referred to as cancer)represent a major global public health challenge and contribute significantly to the worldwide disease burden.Early screening plays a critical role in improving detection rates,enabling timely intervention,and enhancing pa-tient survival rates.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifical-ly rational,multi-cancer screening approach offers several advantages:it optimizes the use of bio-logical samples,reduces time costs for participants,enhances the efficiency and comprehensive-ness of screening,and minimizes overall expenses.Such an approach also facilitates the rational allocation of healthcare resources,ultimately helping to reduce the societal burden of cancer.To address this need,the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China.This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and interna-tional researches on cancer screening,early detection,and treatment for prevalent malignancies.Drawing upon China's unique demographic and healthcare context,as well as practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the principles and methodologies established by the World Health Organization(WHO),aiming to:enhance the effectiveness of combined cancer screening in China,improve early detec-tion rates,and provide a scientific foundation for national cancer prevention and control strategies.