Objective To explore the incidence rate and independent risk factors of synchronous multiple early gastric cancer (SMEGC) in patients with early gastric cancer, and to provide evidence for early screening and intervention of high-risk population. Methods A retrospective analysis was performed on 308 patients with early gastric cancer who received treatment in the hospital from March 2019 to March 2024. The incidence rate of SMEGC was counted, and the risk factors were analyzed by univariate and multivariate Logistic regression analyses. Results Among the 308 patients with early gastric cancer in this study, 23 cases were SMEGC and 285 were single early gastric cancer, which were included in the SMEGC group and the single group respectively. The incidence rate of SMEGC was 7.47% (23/308). Compared with the single group, the proportions of male, smoking history, tumor diameter≤2 mm, chronic atrophic gastritis and intestinal metaplasia degree were higher in the SMEGC group (2=4.331、8.608、4.618、6.490、4.897，P=0.037、0.003、0.032、0.001、0.027). Logistic regression analysis suggested that chronic atrophic gastritis (OR=3.133, 95%CI: 1.240-7.918) and moderate-to-severe intestinal metaplasia (OR=3.171, 95%CI: 1.252-8.029) were independent risk factors for SMEGC (P<0.05). Conclusion Some patients with early gastric cancer are SMEGC. Chronic atrophic gastritis and moderate-to-severe intestinal metaplasia are independent risk factors affecting the occurrence of SMEGC. It is recommended to regularly screen high-risk patients and optimize management strategies to reduce the risk of SMEGC.

OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology* ; Humans ; Airway Remodeling/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Signal Transduction/drug effects* ; Medicine, Chinese Traditional ; Transforming Growth Factor beta1/metabolism*

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Background In vitro-in vivo extrapolation (IVIVE) is an approach utilizing in vitro experimental data to predict in vivo phenomena. It is a promising tool for chemical risk assessment. Objective To learn the hotspots, evolution path, and trend of IVIVE in risk assessment by literature search and bibliometric analysis, and provide reference and data support for subsequent research. Methods PubMed and Web of Science Core Collection were selected as foreign databases to search for literature about IVIVE applied in risk assessment published by December 31, 2023. The number of relevant documents in CNKI and Wanfang database was too small, so the Chinese databases were not included in this study. This study employed bibilometric analysis using VOSviewer and CiteSpace for visualizing networks categorized by author, institution, country, journal, keyword, and co-citation. Results A total of 189 articles were included in this study. The first article was published in 2006, and since then the number of publications overall showed an upward trend and increased significantly after 2016. The institution with the most publications was the United States Environmental Protection Agency (28 articles). The United States was the most productive country (87 articles), and had a close cooperation with the United Kingdom. The journal with the most publications and the highest number of citations per article was Archives of Toxicology (19 articles). The keyword co-occurrence analysis suggested that research on IVIVE in risk assessment mainly studied the methods and models of IVIVE and prediction of chemical toxicity, and toxicity, in vitro, and models were the research hotspots in this field. Keyword timeline cluster analysis suggested that the assessment objects gradually expanded from drugs to environmental chemicals, organic chemicals and food additives. The co-citation analysis suggested that articles about IVIVE in risk assessment mostly cited journals in the environment, food, and drug fields, and these articles were mainly methodological studies followed by literature reviews. Conclusion The research of IVIVE in risk assessment has developed rapidly. With the improvement of prediction models and the expansion of application scope, animal experiments in risk assessment may be greatly reduced and the efficiency of risk assessment can be increased. At present, the United States has a leading position in this field, while China has few relevant studies and needs to actively carry out international cooperation to improve the level of applied research of IVIVE. In the future, it is hoped that the IVIVE method can be further refined to improve its application and expand its research fields.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective:To analyze and summarize the trends and hot spots in the field of neurological damage caused by electric welding operations, and to provide ideas for new researches by searching the domestic and international literature.Methods:In December 2022, using Web of Science Citation Index (Web of Science), China Journal Full-Text Database (CNKI) and Wanfang Database as search databases, literature search was conducted on the Chinese and English search terms related to eletrical welding operations and neurological damage. The bibliometric analysis software VOSviewer 1.6.18 and CiteSpace 6.1.6 were used to visualize the publication year, publication quantity, country, research institution and key words of the literature.Results:A total of 309 articles (112 in Chinese and 197 in English) were included in this study. The first domestic and international papers were published in 1976 and 1994 respectively, and the number of papers reached the peak in 2006 and 2018, and then showed a downward trend to varying degrees. In China, Shandong First Medical University (including Shandong Institute of Occupational Health and Occupational Disease Prevention and Shandong Academy of Medical Sciences) and Wuhan University of Science and Technology had the largest number of publications. The 309 articles were from 52 Chinese journals and 86 English journals. The co-occurrence analysis of key words showed that the domestic research mainly focused on eletrical welding operation, welding workers, neurobehavioral function and manganese, and the nervous system damage caused by manganese in welding smoke was the field of international attention. Long term exposure, risk, and performance were key buzzwords in the field.Conclusion:The research focus in the field of nervous system damage caused by electric welding operation has an obvious trend of time evolution, gradually transiting from clinical manifestations to its toxic mechanism and early biomarkers.

Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.