[This corrects the article DOI: 10.1371/journal.pone.0055839.].

The Tibetan medicine Wuwei Shaji powder (WWSJ) has been extensively applied to treating lung diseases such as chronic obstructive pulmonary disease (COPD). However, there are significant limitations in its quality control and evaluation. The purpose of this study was to analyze the overall chemical composition of WWSJ and to predict potential quality markers for WWSJ in the treatment of COPD. Using UHPLC-Q-Exactive Orbitrap-MS, 83 chemical constituents of WWSJ were identified or preliminarily characterized by 14 authentic reference standards, accurate mass counts, and characteristic fragment ions. In addition, serum pharmacology methods were employed to detect 13 blood-migrating components. Further network pharmacological research found that the potential mechanism of WWSJ in the treatment of COPD may be related to the regulation of the immune system and inflammatory response and identified 10 chemicals as key molecules in the treatment of COPD. Finally, the contents of six potential quality markers were determined simultaneously by high-performance liquid chromatography (HPLC). This study lays the foundation for further research on the mechanism of WWSJ in the treatment of COPD.

Background: Data on the use of rivaroxaban in children with giant coronary artery aneurysm (GCAA) after Kawasaki disease (KD) remain limited. Objectives: This study evaluated the feasibility of rivaroxaban in Chinese children with GCAA after KD. Methods: This study was conducted at the Children’s Hospital of Fudan University. Children aged 1 month to 18 years with persistent GCAA (diameter ≥ 8 mm or Z-score ≥ 10) during the postacute period of KD were included and followed up for at least 6 months. The study consisted of 2 stages. During the first stage (January-December 2023), patients received rivaroxaban following the 20-mg-equivalent regimen. In the second stage (January-November 2024), a pharmacometric model–informed rivaroxaban regimen was implemented. The primary outcome was a composite of GCAA thrombosis and major adverse cardiovascular event within 6 months. The secondary outcome included major bleeding and clinically relevant nonmajor (CRNM) bleeding. Results: In the first stage, 6 patients were enrolled (median age, 14.6 months; range, 4.7-130.8 months; median weight, 9.9; range, 6.6-33 kg; Z-score, 14.9; range, 10.6-28.0). No primary outcome or major bleeding occurred. Four CRNM bleedings were documented, leading to 6 dose adjustments. Two patients discontinued rivaroxaban due to improved coronary status. In the second stage, 14 patients received the 15-mg-equivalent rivaroxaban regimen (median age, 69.7 months; range, 16.4-143.1 months; median weight, 19.5 kg; range, 12.5-57.5 kg; Z-score, 14.7; range, 10.6-39.1). No primary or secondary outcome occurred. Two patient important bleeding no intervention events were documented. All patients remained on rivaroxaban beyond 6 months. External validation supported the predictive performance of model extrapolation. Conclusion: The 15-mg-equivalent rivaroxaban regimen appeared feasible in Chinese children with GCAA after KD, with no GCAA thrombosis, major bleeding or CRNM bleeding observed within 6 months. Larger studies are required to confirm these preliminary findings.

Indirubin, an active component of the traditional Chinese medicine Indigo Naturalis, has drawn significant attention owing to its remarkable anti-leukemia activity. Nevertheless, it presents issues such as limited natural resources, poor solubility, and potential toxicity, which impede its clinical application. In recent years, within the research realm of indirubins, the efficient synthetic strategies and the exploration in the treatment of leukemia have remained the central research focuses in this field. This article comprehensively reviews the research advancements of indirubin derivatives in synthesis strategies and anti-leukemia effects since 2010s. Firstly, in this review, the synthetic methods of indirubin derivatives are categorized into two main types: chemical synthesis and bio & biomimetic synthesis. Among these, chemical methods assume a dominant position. These chemical synthesis approaches encompass acid-catalyze, organophosphorus-catalyzed, metal-catalyzed reactions, and one-step reduction reactions using KBH4. Secondly, based on the modification sites within the structure of indirubin, this paper undertakes a classified review of its derivatives and further delves deeply into the anti-leukemia activities of these derivatives. Additionally, we also discuss the future development directions of synthesizing indirubin derivatives and explore their structure-activity relationships in the context of anti-leukemia research. We firmly believe that this review can offer information support for scientific researchers engaged in the study of indirubin's anti-leukemia effects, thereby facilitating in-depth development.

Myopia is a significant global public health issue. Key interventions for managing myopia include atropine treatment, optical correction, and surgical methods. This study focused on evaluating alterations in retinal protein expression after atropine therapy for myopia. Guinea pigs were randomly divided into four groups: control (CON), monocular form-deprivation myopia (FDM), FDM with 2-week atropine treatment (FDM+ATR), and atropine-only treatment (ATR). After two weeks of FDM induction, the FDM group showed significant differences in refractive error and increased axial lengths. In comparing the retinas of myopic and normal eyes, 30 proteins were found to have increased expression, while 8 proteins showed decreased expression. Atropine-treated retinas exhibited 73 proteins with increased expression and 29 proteins with decreased expression compared to the normal eyes. A total of 11 regulated proteins overlapped between the FDM+ATR vs FDM and FDM vs CON groups. IPA analysis indicates significant alterations in amino acid metabolism, energy production, post-translational modification, small molecule biochemistry, and free radical scavenging. Our study identifies retinal protein changes in myopic guinea pigs and in guinea pigs treated with atropine after myopia. These proteins could serve as potential targets for atropine treatment of myopia.

Liver fibrosis is a progressive pathological disorder characterized by excessive extracellular matrix (ECM) deposition, resulting in hepatic architectural distortion and functional impairment. Despite its clinical importance, effective therapeutic options remain limited. This study evaluated the antifibrotic potential of senkyunolide I (SI), a bioactive phthalide compound derived from Ligusticum chuanxiong Hort., in both in vivo and in vitro models. In a CCl4-induced mouse model of liver fibrosis, SI treatment significantly attenuated fibrosis progression, as indicated by a reduced liver index, decreased serum ALT and AST levels, diminished histopathological damage, suppressed collagen deposition, and ameliorated hepatocyte ultrastructural injury. Additionally, SI inhibited hepatic inflammation by modulating the CXCR4/NLRP3/GSDMD pathway. In vitro experiments demonstrated that SI effectively mitigated LPS + nigericin (Nig)-induced pyroptosis in AML-12 cells and reduced collagen deposition in primary hepatic stellate cells (HSCs) exposed to conditioned medium from injured hepatocytes. Mechanistic studies revealed that SI directly binds to CXCR4, suppressing its expression and subsequently inactivating the NLRP3/GSDMD signalling cascade. These findings suggest that SI exerts its antifibrotic effects via CXCR4 pathway inhibition, positioning it as a promising therapeutic candidate for liver fibrosis treatment.

Myopic maculopathy(MM)is a severe complication of high myopia,character-ized by degenerative lesions in the mac-ular retina,choroid and sclera[1].The pooled prevalence of MM is estimated to be 2.1％in the world population and 47.4％among highly myopic adults[2].

Background Ambulatory care sensitive conditions (ACSCs) serve as a critical indicator for assessing healthcare system performance globally. However, China lacks a standardized ACSCs list adapted to its unique healthcare context and evolving medical needs. Methods This study employed a modified Delphi method combined with evidence-based medicine. First, we systematically reviewed international ACSCs lists and their development methodologies to identify potential diseases. Next, we evaluated the evidence of these potential conditions within China's healthcare system. Finally, a two-round Delphi survey was performed to finalize a consensus-based ACSCs list for China. Findings The finalized ACSCs list comprises 14 conditions, categorized into: five core conditions (chronic obstructive pulmonary disease [COPD], bronchial asthma, hypertension, chronic kidney disease [CKD], and diabetes mellitus) and nine general conditions (bronchiectasis, chronic heart failure, atrial fibrillation, chronic hepatitis B, tuberculosis, iron-deficiency anemia, primary osteoporosis, gastroenteritis, and influenza). Based on the prevailing classification framework in academia, the list includes 12 chronic ACSCs, one acute ACSC, and one infectious ACSC. Compared to most international lists (typically covering about 20 ACSCs), China's ACSCs list prioritizes diagnostic specificity over breadth, ensuring practical applicability in China's current healthcare setting. Interpretation This study developed the first evidence-based ACSCs list tailored to China, providing a tool for healthcare performance evaluation and policy development. Future studies should validate its real-world applicability and implement mechanisms for dynamic updates. Funding This work is supported by National Science and Technology Major Project of China (Grant No. 2024ZD0523902), National Natural Science Foundation of China (Grant No. 72374149), and Institutional Research Fund from Sichuan University (Grant No. 2023SCUH0025).

Senkyunolide I (SI), a natural phthalide compound extracted from the traditional Chinese medicine Ligusticum chuanxiong, exhibits significant potential in the treatment of fibrosis-related diseases. This study focuses on the forms of cell death as an entry point to investigate the impact of SI on renal fibrosis (RF) and related mechanisms in a unilateral ureteral obstruction (UUO) mouse model. We established a UUO mouse model for SI treatment and evaluated the alleviating effect of SI on fibrosis. We investigated how SI exerts renal protective effects by suppressing ferroptosis and pyroptosis through modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/cystine-glutamate antiporter (xCT)/glutathione peroxidase 4 (GPX4) and Nod-like receptor family pyrin domain-containing 3 (NLRP3)/cysteine-requiring aspartate protease-1 (Caspase-1)/Gasdermin D (GSDMD) axis. We found that SI effectively alleviated renal fibrosis in UUO mice by suppressing key fibrotic markers (fibronectin 1, collagen I, α-SMA) and inhibiting the TGF-β1-Smad2/3 pathway. Furthermore, through the Gene Expression Omnibus (GEO) database, we found that ferroptosis/pyroptosis has a clinical correlation with RF. Mechanistically, SI markedly reversed the abnormal changes in key markers associated with ferroptosis and pyroptosis in both in vivo and in vitro fibrosis models, and regulated the Nrf2/xCT/GPX4 and NLRP3/Caspase-1/GSDMD signaling pathways to inhibit ferroptosis and pyroptosis and exert renal protective effects. In conclusion, SI alleviated RF in UUO mice by inhibiting ferroptosis and pyroptosis, providing a directly transformable candidate molecule, new ideas, and a theoretical basis for innovative drugs targeting the intersection of ferroptosis and pyroptosis in renal fibrosis.

Purpose:Ambulatory Care Sensitive Conditions (ACSCs) refer to hospital encounters that could potentially be prevented with improved primary care. Chronic Obstructive Pulmonary Disease (COPD) as one of the typical ACSCs, and its hospitalization is considered potentially preventable through the quality primary care. However, the literature on factors influencing Potentially Preventable Hospitalization (PPH) has rarely been conducted from the patient perspective, especially in China. Our study aims to explore the factors influencing PPH for COPD patients. Patients and Methods:This was a qualitative study. Twenty participants hospitalized by COPD were recruited from the healthcare institutions in China. The semi-structured interviews were conducted from July to August 2022. The data were gathered and analyzed systematically using thematic analysis. Results:Patients' experiences for PPH generated two main themes: environmental characteristics and personal characteristics. Sub-themes included accessibility of healthcare resources, medical services capability, healthcare insurance policy, working environment, disease cognition, health awareness, disease burden, income constrain, disease perception, negative emotions, and comorbidity. Conclusion:Environmental characteristics and personal characteristics are factors associated with PPH for COPD patients. It is important to enhance the medical service ability, improve the accessibility of healthcare resources and the health literacy of patients.

Pediatric patients with coronary artery lesions (CALs) after Kawasaki disease (KD) may be complicated with myocardial ischemia. Although previous studies in adults have proven the diagnostic value of 99mTc-MIBI myocardial perfusion imaging (MPI) for ischemic heart disease, its feasibility and accuracy in this pediatric population remain uncertain. In this retrospective study, we collected data of 177 pediatric patients (Age range: 6 months to 14 years) who had undergone MPI and coronary artery angiography (CAG) between July 2019 and February 2023. Using the positive result of CAG as the reference standard of myocardial ischemia, we compared the results of 99mTc-MIBI MPI with other non-invasive examinations, including cardiac magnetic resonance imaging (CMRI), echocardiogram, and comprehensive electrocardiogram-related examinations. All patients finished adenosine triphosphate stress MPI without major side effects. The sensitivity of MPI was 79.17

In this study, we aimed to study the mechanism of costunolide (COS) and dehydrocostus lactone (DEH) in the treatment of ulcerative colitis (UC) based on network pharmacology, molecular docking and animal experiments. Firstly, network pharmacology was used to predict the target proteins of compounds and diseases. Subsequently, the network analysis was performed, and the key target proteins were screened out. Finally, molecular docking and animal experiments were conducted to validate the network pharmacology analysis results. A total of 39 common target proteins of compounds and diseases were collected. The target proteins TLR4, PIK3R1, PTGS2, RELA, NOS3, MPO and CHUK were obtained from PPI network analysis, GO analysis, KEGG enrichment analysis, and the compound-target-pathway network. Molecular docking results showed that COS and DEH could bind to these target proteins. The results of animal experiments showed that dextran sulfate sodium (DSS) induced UC in mice, resulting in weight loss, colon shortening, and significantly upregulated expression of TLR4, PIK3R1 and RELA in colon tissue. COS and DEH could reduce these pathological changes in UC mice. And they could alleviate UC by downregulating TLR4, PIK3R1 and RELA. Our findings suggested that COS and DEH could exert protective effects on UC by downregulating TLR4, PIK3R1, and RELA.

Kawasaki disease (KD) is an acute, systemic vasculitis that primarily affects children aged under the age of 5. While environmental factors have been linked to the development of KD, the specific role of ozone (O3) pollution in triggering the disease onset remains uncertain. This study aimed to examine the associations between short-term O3 exposure and KD onset in children. Utilizing a satellite-based model with a spatial resolution of 1 × 1 km, we matched 1808 KD patients (out of a total of 6115 eligible individuals) to pre-onset ozone exposures based on their home addresses in East China between 2013 and 2020. Our findings revealed a significant association of O3 exposure with KD onset on the day of onset (lag 0 day). However, this association attenuated and became statistically insignificant on lag 1 and lag 2 days. Each interquartile range (52.32 μg/m3) increase in O3 concentration at lag 0 day was associated with a 16.2% (95% CI: 3.6%, 30.3%) increased risk of KD onset. The E-R curve for O3 exhibited a plateau at low concentrations and then increased rapidly at concentrations ≥75 μg/m3. Notably, these associations were stronger in male children, younger children (<2 years of age) and patients experiencing KD onset during the warm season. This study provides novel epidemiological evidence indicating that short-term O3 exposure is associated with an increased risk of childhood KD onset. These findings emphasized the importance of considering this environmental risk factor in KD prevention strategies.

Background Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) poses a considerable challenge to patients and their families due to its severe complications. Previous researches have highlighted the critical role of immune disorders in its pathogenesis. However, fragmented studies based on isolated cases hinder a comprehensive understanding of this deadly illness. This study aimed to explore the overall landscape of peripheral blood mononuclear cells (PBMCs) in IVIG-resistant KD patients using single-cell RNA sequencing (scRNA-seq). Methods The scRNA-seq was used to characterize the transcriptomic profiles of IVIG-resistant KD patients, IVIG-responsive KD patients, and healthy controls. Data quality control (QC) and subsequent analysis were conducted using various R packages. These included DoubletFinder and Harmony for QC, Seurat and SingleR for identifying and annotating major cell types, ggpubr for calculating and visualizing the percentages of each cell type, Seurat for characterizing differentially expressed genes (DEGs) between groups, pheatmap for visualizing the DEGs, clusterProfiler for performing Gene Ontology (GO) enrichment analysis of DEGs, scRepertoire for TCR and BCR data analysis, Monocle for assessing cell differentiation trajectories, and CellChat for intercellular interaction evaluation. Results High-quality single-cell transcriptome data from 12 participants were analyzed, including five with IVIG-resistant KD, four with IVIG-responsive KD, and three healthy controls. We identified 10 major cell types and observed that the differentiation of CD8+ effector T cells was impeded in IVIG-resistant KD patients with coronary artery lesion (CAL) according to cell differentiation trajectory analysis. Subsequent cell communication analysis demonstrated that myeloid cluster with high expression of LCN2, S100P, and LTF played a key role, potentially signaling through MIF-CD74/CXCR4 and MIF-CD74/CD44 ligand-receptor pairs. Conclusion Complex immunopathological changes occur during the development of CAL in IVIG-resistant KD. Stunted differentiation of CD8+ effector T cells is noted in KD-CAL. Interactions between myeloid cells and T cells activates multiple inflammatory signaling pathways, with ligand-receptor pairs, including MIF-CD74/CXCR4 and MIF-CD74/CD44, potentially playing crucial roles.

Background The hospitalization rate of ambulatory care sensitive conditions (ACSCs) has been recognized as an essential indicator reflective of the overall performance of healthcare system. At present, ACSCs has been widely used in practice and research to evaluate health service quality and efficiency worldwide. The definition of ACSCs varies across countries due to different challenges posed on healthcare systems. However, China does not have its own list of ACSCs. The study aims to develop a list to meet health system monitoring, reporting and evaluation needs in China. Methods To develop the list, we will combine the best methodological evidence available with real-world evidence, adopt a systematic and rigorous process and absorb multidisciplinary expertise. Specific steps include: (1) establishment of working groups; (2) generations of the initial list (review of already published lists, semi-structured interviews, calculations of hospitalization rate); (3) optimization of the list (evidence evaluation, Delphi consensus survey); and (4) approval of a final version of China’s ACSCs list. Within each step of the process, we will calculate frequencies and proportions, use descriptive analysis to summarize and draw conclusions, discuss the results, draft a report, and refine the list. Discussion Once completed, China’s list of ACSCs can be used to comprehensively evaluate the current situation and performance of health services, identify flaws and deficiencies embedded in the healthcare system to provide evidence-based implications to inform decision-makings towards the optimization of China’s healthcare system. The experiences might be broadly applicable and serve the purpose of being a prime example for nations with similar conditions.

目的 文章梳理分析了 2018-2021年我国出台的与乡村振兴战略有关的政策文件,着重分析健康乡村建设有关内容,明确我国健康乡村内涵,为推动健康乡村建设提供参考.方法 采用文献研究法、政策文本分析法对政策文本中涉及健康乡村建设的内容进行研究,共纳入63份政策文件.结果 健康乡村政策靶点主要聚焦于生存需要和成长需要,对医疗和公共卫生、医保方面的内容涉及最多,而对优化疾病分类救治措施、医养结合融合发展、发展休闲农业涉及相对较少.能力建设型工具使用最多,象征劝诫型政策工具适中,命令型政策工具最少,政策工具应用失衡,内部结构存在较大差异.结论 健康乡村建设内容上不仅要关注医疗、公共卫生、医保等健康层面,也要从环境整治、健康文化、健康产业发展等多维角度考虑.政策力度上,需提高整体政策力度、针对政策靶点的不足精准发力、协调运用政策工具.

Kawasaki disease(KD)is a disorder of immune responses.The prevalence of KD among 100,000 children aged 0-4 years was 71.9-110.0 in China,170.9-194.9 in Korea,and 18.1-21.3 in the USA[1].The most severe complication of KD is coronary artery lesions(CALs),including coronary dilatation and coronary aneurysms,which may even lead to myocardial ischemia,myocardial infarction,and sudden death.

In the context of China's development of modern environmental governance systems, it is crucial to recognise the vital role played by businesses. The internal impetus for environmental governance will be generated by accelerating the emergence of a universal industry trend of enterprises proactively fulfilling their environmental responsibilities. Therefore, this study utilises listed A-share companies in Shanghai and Shenzhen stock exchanges from 2010 to 2020 as samples to investigate the peer impacts of corporate environmental responsibility (CER). It was discovered that industry peers across and within regions might influence CER. When companies meet their environmental duties, the peer effects of CER may be seen as convergent responsiveness to external pressure. In a cross-regional context, the combination of industry competitive pressure and severe environmental uncertainty may greatly amplify the peer implications of CER, and small businesses are more susceptible to convergence. In an intra-regional scenario, environmental regulatory pressure has dramatically diminished the peer effects of CER, and the high-level marketisation process ensures that environmental regulatory pressure will favour the independent fulfilment of CER. Moreover, this phenomenon is magnified in state-owned enterprises.

To better elucidate the chemical constituents and evaluate the quality consistency of Chuanxiong dispensing granules (CDG), qualitative and quantitative analyses were performed in this study. Firstly, a high-performance liquid chromatography-diode array detector (HPLC-DAD) based fingerprint was constructed by 12 batches of CDGs from different manufacturers, in which 16 common peaks were assigned. Then, two of them were directionally isolated for structural elucidation. According to the nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, 5,6-dihydrophthalic acid was identified as novel compound, and 8-O-4/8-O-4-dehydrotriferulic acid was firstly discovered in plant belonging to the genus Ligusticum. Secondly, a total of 46 components were detected in CDG using high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS), and 14 of them were unambiguously identified by comparing with reference standards. Additionally, a HPLC-DAD method was firstly established to quantify 10 characteristic peaks specified in the China National Standard of CDG, and the results revealed that ferulic acid (1.71 mg/g), chlorogenic acid (1.14 mg/g), 5,6-dihydrophthalic acid (1.13 mg/g), and senkyunolide I (1.13 mg/g) are the major components in CDGs. Chemometrics analyses suggested that phenolic acids are more important than phthalides in discrimination of CDGs from different manufacturers.

BACKGROUND:To develop and validate a novel tool for predicting the development of malignant brain edema (MBE) in large vessel occlusion stroke patients after endovascular thrombectomy (EVT).METHODS:We used a prospectively registered population of EVT patients from three comprehensive stroke centers. The population was randomly divided into two subsets (7:3): a training cohort and an internal validation cohort. External validation was performed using the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China (ACTUAL) database. MBE was defined as (1) hypodense parenchyma in at least 50% of the middle cerebral artery and signs of local brain swelling, and (2) a midline shift of ≥5 mm at the septum pellucidum or pineal gland with obliteration of the basal cisterns. The model was constructed using logistic regression analysis. The performance of the model was examined in terms of discrimination and calibration.RESULTS:After adjusting for other confounders, baseline National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early CT (ASPECT) scores, a clinical history of hypertension, collateral status, intravenous thrombolysis before thrombectomy, fasting blood glucose, reperfusion status, and occlusion site were found to be independent predictors of MBE. These variables were combined to create the ACORNS grading scale. The areas under the curve in receiver operating curve analysis were 0.850 (95% CI 0.816 to 0.884), 0.874 (95% CI 0.821 to 0.926), and 0.785 (95% CI 0.740 to 0.829) for the training, internal validation, and external validation cohorts, respectively, indicating good discriminative performance in the validation cohorts.CONCLUSIONS:The ACORNS grading scale is an accurate and easily applicable model for the prediction of the development of MBE after EVT.