1.Hygiene status and influencing factors of swimming venues: Based on surveillance data from 2010 to 2024 in Shanghai
Fengchan HAN ; Tian CHEN ; Ting PENG ; Shaofeng SUI ; Weiwei ZHENG ; Ling TONG ; Mingjing XU ; Ming ZHAN ; Yewen SHI
Journal of Environmental and Occupational Medicine 2025;42(10):1225-1233
Background Swimming is becoming increasingly popular for its combined leisure and fitness benefits. However, polluted swimming pool water may pose various health risks. Previous studies have indicated that health indicators of swimming venues have lower qualification rates compared to other public places, highlighting the urgent need to optimize hygiene management measures. Objective To assess the overall hygiene status and identify the key factors influencing water quality in Shanghai’s swimming venues from 2010 to 2024, and to provide a scientific basis for optimizing water quality management. Methods Water quality was assessed in three stages (2010—2019, 2020—2022, and 2023—2024) based on the monitoring data of Shanghai’s swimming venues (2010—2024). The influences of monitoring stage, region, season, scale, day of week, and per capita attendance on water quality were analyzed using chi-square tests and logistic regression. Results From 2010 to 2024, water quality was monitored in
2.Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.
Aijie HUANG ; Guangyu SUN ; Baolin TANG ; Yongsheng HAN ; Xiang WAN ; Wen YAO ; Kaidi SONG ; Yaxin CHENG ; Weiwei WU ; Meijuan TU ; Yue WU ; Tianzhong PAN ; Xiaoyu ZHU
Chinese Medical Journal 2025;138(9):1072-1083
BACKGROUND:
Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation.
RESULTS:
Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P = 0.003).
CONCLUSION
Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans
;
Female
;
Male
;
Thrombocytopenia/etiology*
;
Adult
;
Retrospective Studies
;
Cord Blood Stem Cell Transplantation/adverse effects*
;
Middle Aged
;
Adolescent
;
Young Adult
;
Thiazoles/adverse effects*
;
Platelet Count
;
Receptors, Thrombopoietin/agonists*
;
Child
;
Thiophenes
3.High PRELID1 expression promotes epithelial-mesenchymal transition in gastric cancer cells and is associated with poor prognosis.
Xuan WU ; Jiamin FANG ; Weiwei HAN ; Lin CHEN ; Jing SUN ; Qili JIN
Journal of Southern Medical University 2025;45(7):1535-1542
OBJECTIVES:
To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms.
METHODS:
We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT.
RESULTS:
Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G3-4 stages (P=0.001), T3-4 stages (P=0.001), and N2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown.
CONCLUSIONS
PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans
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Stomach Neoplasms/metabolism*
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Epithelial-Mesenchymal Transition
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Prognosis
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Cell Movement
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Cell Line, Tumor
;
Male
;
Female
;
Middle Aged
;
Signal Transduction
;
Neoplasm Invasiveness
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Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
4.Tongue squamous cell carcinoma-targeting Au-HN-1 nanosystem for CT imaging and photothermal therapy.
Ming HAO ; Xingchen LI ; Xinxin ZHANG ; Boqiang TAO ; He SHI ; Jianing WU ; Yuyang LI ; Xiang LI ; Shuangji LI ; Han WU ; Jingcheng XIANG ; Dongxu WANG ; Weiwei LIU ; Guoqing WANG
International Journal of Oral Science 2025;17(1):9-9
Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging*
;
Carcinoma, Squamous Cell/diagnostic imaging*
;
Animals
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Gold/chemistry*
;
Mice
;
Photothermal Therapy/methods*
;
Tomography, X-Ray Computed
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Photosensitizing Agents
;
Metal Nanoparticles
;
Humans
;
Cell Line, Tumor
5.Predicting cardiotoxicity in drug development: A deep learning approach.
Kaifeng LIU ; Huizi CUI ; Xiangyu YU ; Wannan LI ; Weiwei HAN
Journal of Pharmaceutical Analysis 2025;15(8):101263-101263
Cardiotoxicity is a critical issue in drug development that poses serious health risks, including potentially fatal arrhythmias. The human ether-à-go-go related gene (hERG) potassium channel, as one of the primary targets of cardiotoxicity, has garnered widespread attention. Traditional cardiotoxicity testing methods are expensive and time-consuming, making computational virtual screening a suitable alternative. In this study, we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds, with the aim of improving prediction accuracy and efficiency. We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms, including Gaussian naive Bayes (NB), random forest (RF), support vector machine (SVM), K-nearest neighbors (KNN), eXtreme gradient boosting (XGBoost), and Transformer models, to build predictive models. Our models demonstrated advanced predictive performance. The best machine learning model, XGBoost Morgan, achieved an accuracy (ACC) value of 0.84, and the deep learning model, Transformer_Morgan, achieved the best ACC value of 0.85, showing a high ability to distinguish between toxic and non-toxic compounds. On an external independent validation set, it achieved the best area under the curve (AUC) value of 0.93, surpassing ADMETlab3.0, Cardpred, and CardioDPi. In addition, we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods, such as voting and stacking, provided slight improvements in model stability. Furthermore, the SHapley Additive exPlanations (SHAP) explanations revealed the relationship between benzene rings, fluorine-containing groups, NH groups, oxygen in ether groups, and cardiotoxicity, highlighting the importance of these features. This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment. Using computational methods, this study facilitates a more efficient drug development process, reduces costs, and improves the safety of new drug candidates, ultimately benefiting medical and public health.
6.Study on the Incidence of Intraoperative Hypothermia and Rewarming Efficacy in Elderly Patients with Different Traditional Chinese Medicine Constitutions Undergoing General Anesthesia
Shujun HAN ; Weiwei OU ; Dinghua ZHENG ; Huifen HE ; Li CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(8):1849-1855
Objective To investigate the incidence of intraoperative hypothermia(IH)and rewarming efficacy in elderly patients with different traditional Chinese medicine(TCM)constitutions undergoing general anesthesia.Methods A total of 500 elderly patients undergoing general anesthesia at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2022 to November 2022 were enrolled.The patients were divided into IH group and non-IH group depending on the occurrence of IH.Baseline data of the patients were collected,and univariate and multivariate logistic regression analyses were performed to identify risk factors for IH.A risk prediction model was constructed after value-assignment of influencing factors and its diagnostic efficiency was assessed by receiver operating characteristic(ROC)curve.External validation of the model was conducted in 50 elderly patients undergoing general anesthesia at the same period.From December 2022 to February 2023,80 elderly patients undergoing general anesthesia and complicated with IH were randomized into a control group(routine measures for keeping warm)and an observation group(keeping warm with forced-air-warming blanket)to compare the rewarming efficacy.Results(1)Among 500 elderly patients undergoing general anesthesia,180 cases developed IH,with an incidence of 36.0%.(2)Except for age,sex,type of surgery,American Society of Anesthesiologists(ASA)classification,type of anesthesia,and total fluid output volume,statistically significant differences were presented in body mass index(BMI),TCM constitution type,surgical complexity grading,preoperative core body temperature,operating room temperature,rewarming strategy,surgical duration,anesthesia duration,total fluid intake volume,intraoperative irrigation volume,and intraoperative blood transfusion between the two groups(P<0.05 or P<0.01).(3)Multivariate logistic regression analysis identified BMI,TCM constitution type,surgical complexity grading,preoperative core body temperature,operating room temperature,rewarming strategy,anesthesia duration,total fluid intake volume,and intraoperative irrigation volume as independent influencing factors for the occurrence of IH in elderly patients undergoing general anesthesia.ROC curve analysis demonstrated that the area under the curve(AUC)of the constructed risk prediction model was 0.816,with a sensitivity of 74.40%and a specificity of 77.50%.(4)In an external validation cohort of 50 elderly patients undergoing general anesthesia(19 IH cases versus 31 non-IH cases),the constructed risk prediction model exhibited a sensitivity of 73.68%and a specificity of 77.42%.(5)The observation group exhibited lower tympanic temperature upon post-anesthesia care unit(PACU)admission,shorter rewarming time and PACU stay duration,faster rewarming rate,and lower incidence of shivering than the control group,the differences being statistically significant(P<0.05 or P<0.01).Conclusion IH is common in elderly patients undergoing general anesthesia,particularly in those under the conditions of low BMI,qi/yang/blood deficiency constitutions,major surgery,low preoperative core body temperature,low operating room temperature,passive rewarming,prolonged anesthesia,high fluid intake volume,and high and intraoperative irrigation volume.The constructed risk prediction model demonstrates favorable diagnostic performance.Proactive use of forced-air-warming blankets effectively improves rewarming outcomes in elderly patients undergoing general anesthesia and complicated with IH.
7.Predicting cardiotoxicity in drug development:A deep learning approach
Kaifeng LIU ; Huizi CUI ; Xiangyu YU ; Wannan LI ; Weiwei HAN
Journal of Pharmaceutical Analysis 2025;15(8):1774-1786
Cardiotoxicity is a critical issue in drug development that poses serious health risks,including potentially fatal arrhythmias.The human ether-à-go-go related gene(hERG)potassium channel,as one of the pri-mary targets of cardiotoxicity,has garnered widespread attention.Traditional cardiotoxicity testing methods are expensive and time-consuming,making computational virtual screening a suitable alter-native.In this study,we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds,with the aim of improving prediction accuracy and efficiency.We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms,including Gaussian naive Bayes(NB),random forest(RF),support vector machine(SVM),K-nearest neighbors(KNN),eXtreme gradient boosting(XGBoost),and Trans-former models,to build predictive models.Our models demonstrated advanced predictive performance.The best machine learning model,XGBoost Morgan,achieved an accuracy(ACC)value of 0.84,and the deep learning model,Transformer_Morgan,achieved the best ACC value of 0.85,showing a high ability to distinguish between toxic and non-toxic compounds.On an external independent validation set,it achieved the best area under the curve(AUC)value of 0.93,surpassing ADMETlab3.0,Cardpred,and CardioDPi.In addition,we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods,such as voting and stacking,provided slight improvements in model stability.Furthermore,the SHapley Additive exPlanations(SHAP)explanations revealed the relationship between benzene rings,fluorine-containing groups,NH groups,oxygen in ether groups,and cardiotoxicity,highlighting the importance of these features.This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment.Using computational methods,this study facilitates a more efficient drug development process,reduces costs,and improves the safety of new drug candidates,ultimately benefiting medical and public health.
8.Application of quality monitoring indicators of blood testing in blood banks of Shandong province
Xuemei LI ; Weiwei ZHAI ; Zhongsi YANG ; Shuhong ZHAO ; Yuqing WU ; Qun LIU ; Zhe SONG ; Zhiquan RONG ; Shuli SUN ; Xiaojuan FAN ; Wei ZHANG ; Jinyu HAN ; Lin ZHU ; Xianwu AN ; Hui ZHANG ; Junxia REN ; Xuejing LI ; Chenxi YANG ; Bo ZHOU ; Haiyan HUANG ; Guangcai LIU ; Ping CHEN ; Hui YE ; Mingming QIAO ; Hua SHEN ; Dunzhu GONGJUE ; Yunlong ZHUANG
Chinese Journal of Blood Transfusion 2024;37(3):258-266
【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.
9.Analysis of the distribution characteristics of traditional TCM syndromes in patients with pulmonary tuberculosis combined with coronary heart disease in Kunming area
Hanzhang SHEN ; Zhongxu MA ; Hongbang YIN ; Bin BAI ; Weiwei HAN ; Zhuhui LI
International Journal of Traditional Chinese Medicine 2024;46(6):707-712
Objective:To explore the distribution pattern of TCM syndromes in patients with pulmonary tuberculosis combined with coronary heart disease in Kunming area.Methods:A survey was conducted by research of questionnaires to the general information and TCM four diagnostic information of pulmonary tuberculosis patients (116 cases) with coronary heart disease admitted to our hospital from April 2019 to December 2020, and principal component analysis and clustering analysis were conducted. Frequency analysis and severity analysis methods were used for data processing.Results:The TCM symptoms of pulmonary tuberculosis patients with coronary heart disease were mainly cough [89.66%(104/116)], expectoration [73.28% (85/116)], dry mouth [70.69% (82/116)], chest tightness [64.66% (75/116)], fatigue [56.03%(65/116)], hot flashes [52.59% (61/116)], shortness of breath [50.00% (58/116)]; tongue color was more common with light red [43.10% (50/116)] and red [47.41% (55/116)]; the tongue shape was more common with cracked tongue [37.07% (43/116)], punctured tongue [27.59% (32/116)] and old tongue [23.28%(27/116)]; tongue coating with little or no coating [48.28%(56/116)], yellow and greasy coating [21.55% (25/116)] was more common; the pulse was usually thin (number) [54.31% (63/116)] and slippery (number) [25.86% (30/116)]. The principal component analysis method used a load coefficient >0.40 as the threshold to screen out the four diagnostic information of 10 principal components; the clustering analysis results were divided into three categories of TCM types: deficiency syndrome, excess syndrome, and mixed deficiency and excess syndrome. There were significant differences in TCM syndrome types among patients of different genders, ages, disease courses, and educational levels ( P<0.05). Deficiency syndrome was more common in male patients [41.18% (21/51)], and mixed syndrome of deficiency and excess was more common in female patients [63.08% (41/65)]; 43-59 years old patients were more likely to have excess syndrome [36.36%(24/66)], and ≥60 years old patients were more likely to have mixed syndrome [70.00% (35/50)]; patients with a course of disease <3 months had more excess syndrome [41.30% (19/46)], patients with a course of 3-12 months had more deficiency syndrome [57.14% (20/35)], and patients with a course of more than 1 year had more mixed syndrome of deficiency and excess [74.29% (26/35)]. male patients [54.17%(26/48)] were more serious in excess syndrome, and female patients [53.33% (24/45)]; were more serious in deficiency syndrome; deficiency syndrome [43-59 years old was 54.17% (42/84), ≥60 years old was 54.17% (12/24)] more serious in patients of different age groups; patients with a course of disease <3 months [56.86% (29/51)] were more serious in excess syndrome, and patients with a course of disease ≥3 months were more serious in mixed syndromes [3~12 months 52.38%(22/42), >1 year 53.33% (24/45)]. Conclusion:The pathogenesis of TCM in patients with pulmonary tuberculosis complicated with coronary heart disease in Kunming is deficiency in root and excess in superficiality; the syndrome is based on yin deficiency and qi deficiency, with blood stasis, phlegm heat, phlegm stasis and phlegm turbidity as the symptoms.
10.Clinical and experimental research progress of Wumei Pills in the treatment of digestive system diseases
Na REN ; Xiuzhen HAN ; Weiwei LIU ; Yan LI ; Shuihong LI ; Hongtao SHANG
International Journal of Traditional Chinese Medicine 2024;46(8):1102-1105
Wumei Pills is mostly used to treat ulcerative colitis, irritable bowel syndrome, intestinal polyps, chronic atrophic gastritis, gastroesophageal reflux disease, gastric cancer and other digestive system diseases with its modified formula or combination with Western medicine. Wumei Pills can play a role in treating digestive system diseases through antioxidant stress, Inhibiting inflammatory response, regulating intestinal flora, anti-tumor, promoting intestinal mucosal repair, etc. Most of the related research on the mechanism of Wumei Pills in the treatment of digestive system diseases were studied in a single pathway. The relationship between other mechanisms and pathways is worthy of further exploration. In addition, the current research mostly focuses on the lower digestive system diseases with diarrhea as the main manifestation, and there is still room for research and reporting in the treatment of upper digestive system diseases.

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