The development of traditional Chinese medicine (TCM) diagnosis and treatment has undergone multiple paradigms, evolving from sporadic experiential practices to systematic approaches in syndrome differentiation and treatment and further integration of disease and syndrome frameworks. TCM is a vital component of the medical system, valued alongside Western medicine. Treatment based on syndrome differentiation embodies both personalized treatment and holistic approaches; however, the inconsistency and lack of stability in syndrome differentiation limit clinical efficacy. The existing integration of diseases and syndromes primarily relies on patchwork and embedded systems, where the full advantages of synergy between Chinese and Western medicine are not fully realized. Recently, driven by the development of diagnosis and treatment concepts and advances in analytical technology, Western medicine has been rapidly transforming from a traditional biological model to a precision medicine model. TCM faces a similar need to progress beyond traditional syndrome differentiation and disease-syndrome integration toward a more precise diagnosis and treatment paradigm. Unlike the micro-level precision trend of Western medicine, precision diagnosis and treatment in TCM is primarily reflected in data-driven applications that incorporate information at various levels, including precise syndrome differentiation, medication, disease management, and efficacy evaluation. The current priority is to accelerate the development of TCM precision diagnosis and treatment technology platforms and advance discipline construction in this area.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Nanoparticles/chemistry* ; Animals ; Nanomedicine/methods* ; Drug Delivery Systems/methods* ; Drug Carriers/chemistry* ; Radiotherapy/methods*

The triterpenoid saponins of Centella asiatica, including asiaticoside, madecassoside, asiatic acid, and madecassic acid, are pivotal bioactive compounds of the plant. These constituents exhibit a spectrum of pharmacological activities, such as antioxidant, antitumor, and antidepressant effects, promotion of wound healing, and enhancement of microcirculation. Owing to these therapeutic properties, C. asiatica is widely employed in pharmaceutical and cosmetic industries. However, the escalating global demand for its extracts has led to potential supply shortages, prompting researchers to use multiple strategies such as multi-omics, molecular biology, and synthetic biology to conduct extensive studies. These studies encompass the elucidation of the biosynthetic pathways of triterpenoid saponins in C. asiatica, metabolic regulation, the hormonal induction of secondary metabolite synthesis, and the application of biotechnological strategies for natural product production to increase the yield of secondary metabolites in C. asiatica, or to produce active components via microbial chassis, thus satisfying market demands and promoting the sustainable exploitation of wild C. asiatica resources. This article first introduced the triterpenoid saponins of C. asiatica and their biological activities, then summarized the latest research advancements in their biosynthetic pathways, metabolic regulation, and heterologous biosynthesis, and provided an outlook on future development directions, with the aim of providing reference for comprehensive resource development and biotechnological synthesis of active components from C. asiatica.
Centella/genetics* ; Triterpenes/chemistry* ; Biosynthetic Pathways ; Humans ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts