Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

ObjectiveTo investigate the association between triglyceride-glucose (TyG) index and the risk of stroke in middle-aged and elderly individuals with hypertension, so as to provide more evidence for the prevention and treatment of stroke. MethodsMiddle-aged and elderly hypertensive individuals who took part in all four surveys in 2011, 2013, 2015, and 2018 were selected as the research subjects based on data from the China Health and Retirement Longitudinal Study (CHARLS). Participants were divided into four groups (≤Q1， >Q1~Q2， >Q2~Q3， and >Q3) based on TyG index quartiles, and the cumulative risk of stroke in different groups was analyzed using the Kaplan-Meier method. Different Cox proportional hazards regression models were constructed to analyze the relationship between the TyG index and stroke risk. Sensitivity analysis were performed to evaluate the robustness of the results. ResultsA total of 4 596 participants were included in the study. Among them, 338 individuals (7.35%) had a stroke during the 7-year follow-up period. The cumulative risk of stroke increased with higher TyG index levels. Results from the Cox regression models indicated that higher TyG levels were associated with an increased risk of stroke among middle-aged and elderly individuals with hypertension. Compared with the lowest TyG index quartile (≤Q1: TyG index ≤8.33) group, the highest quartile (>Q3: TyG index >9.17) group showed a 45.10% increased risk of stroke (HR=1.451, 95% CI:1.017‒2.072). ConclusionA higher TyG index is associated with an increased risk of stroke in middle-aged and elderly individuals with hypertension.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

The chemical constituents of the petroleum ether extract derived from the 90% ethanol extract of Elephantopus scaber were investigated. By silica gel column chromatography, C_(18), MCI column chromatography and semi-preparative high performance liquid chromatography, ten compounds were isolated. Their structures were identified as 3β-hydroxy-6β,7β-epoxytaraxeran-14-ene(1), 3β-hydroxyolean-12-en-28-oic acid(2), D-friedoolean-14-ene-3β,7α-diol(3), 3β-hydroxy-11α-methoxyolean-12-ene(4), 3β-hydroxyolean-11,13(18)-diene(5), 11α-hydroxy-β-amyrin(6), betulinic acid(7), 3β-hydroxy-30-norlupan-20-one(8), 6-acetonylchelerythrine(9), and 4',5'-dehydrodiodictyonema A(10) by analysis of the 1D NMR, 2D NMR, MS, and IR spectral data. Among them, compound 1 was a new triterpene and other compounds except compounds 2 and 7 were isolated from this plant for the first time.
Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Asteraceae/chemistry* ; Chromatography, High Pressure Liquid ; Magnetic Resonance Spectroscopy

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

With the development of education and technology, the construction of research public platforms has emerged as a critical initiative for many universities and top-tier public hospitals. The core and most fundamental function of a basic public platform is to aggregate large instruments and specific resources, providing open services for instrumental analysis and sample testing. Optimized management and high-quality, efficient services are essential for such platforms. This article elucidates the construction of a research public platform in West China Hospital, focusing on the adoption of hierarchical management and precise services. The core of the hierarchical management lies in building a multi-level service platform composed of routine support platforms, advanced technology platforms, and specially qualification platforms, while establishing a talent hierarchy that differentiates between core and routine positions. This structure is designed to accurately meet the diverse needs of users and enhance resource efficiency. By implementing user access control with differentiated permissions for internal and external users and a dynamic credit-based review system, the laboratory can ensure safe and efficient operations. The four service modes-instrument usage, in-lab experiments, sample testing, and collaborative projects-are precisely aligned with various research scenarios. Proactive engagement with grant-funded projects, customized services for research groups, and a multidimensional training system further strengthen the platform's support for major scientific research tasks. Through systematic management and service innovation, this model achieves efficient integration and sustainable development of platform resources, providing a valuable reference for the construction of public platforms in similar medical institutions.
China ; Research ; Laboratories/organization & administration*

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVES: In recent years, the role of remnant cholesterol (RC) in the development and progression of cardiovascular diseases has gained increasing attention. However, evidence on the association between RC and subclinical atherosclerosis is limited. This study aims to examine the relationship between RC and atherosclerotic plaques in single and multiple vascular territories. METHODS: This retrospective cross-sectional study used baseline data from participants enrolled between October 2022 and May 2024 in the National Key Research Program "Study on the Prevention and Control System of Risk Factors for Panvascular Diseases". Color Doppler ultrasonography was performed to detect plaques in 4 vascular territories: Bilateral carotid arteries, bilateral subclavian arteries, abdominal aorta, and iliac-femoral arteries. RC was calculated as total cholesterol minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Participants were categorized into quartiles (Q1-Q4) according to RC levels. The proportions of participants with ≥2 plaques in a single vascular territory and with plaques in ≥2 vascular territories were compared across RC quartiles. Multivariate ordinal Logistic regression was used to assess the association between RC and the number of plaques in a single vascular territory, as well as the risk of multiple vascular territory involvement. Additionally, the effects of LDL-C/RC concordance on plaque distribution were analyzed. RESULTS: A total of 3 539 participants were included, of whom 2 169 (61.29%) were male, with a age of (51.94±9.22) years. From Q1 to Q4, the proportion of participants with ≥2 plaques in a single vascular territory (bilateral carotid, subclavian, abdominal aorta, and iliac-femoral arteries), as well as those with plaques in ≥2 vascular territories, increased progressively. Compared with Q1, both Q3 and Q4 were significantly associated with higher plaque numbers in a single vascular territory (both P<0.05). When treated as a continuous variable, higher RC levels were associated with an increased risk of greater plaque numbers within a single vascular territory (all P<0.05). RC levels were also significantly associated with multiple vascular territory involvement: Compared with Q1, Q4 had a 1.015-fold higher risk [odds ratio (OR)=2.015, 95% confidence interval (CI) 1.669 to 2.433], and each 1 mmol/L increase in RC corresponded to a 0.160-fold increased risk (OR=1.160, 95% CI 1.073 to 1.271). In LDL-C/RC coordination analysis, compared with the low LDL-C/low RC group, the low LDL-C/high RC group was significantly associated with multiple vascular territory involvement (OR=1.576, 95% CI 1.220 to 2.036). CONCLUSIONS Elevated RC levels are closely associated with atherosclerotic plaques in both single and multiple vascular territories, even among individuals with normal LDL-C, suggesting that RC should be considered in clinical risk assessment and management of atherosclerosis.
Humans ; Plaque, Atherosclerotic/diagnostic imaging* ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Retrospective Studies ; Cholesterol/blood* ; Cholesterol, LDL/blood* ; Aged ; Cholesterol, HDL/blood* ; Risk Factors ; Atherosclerosis ; Ultrasonography, Doppler, Color ; Femoral Artery/diagnostic imaging*