1.Integrating data mining and network pharmacology to decode the therapeutic principles of contemporary Xin'an medicine for chronic glomerulonephritis
Xulei HU ; Xiaowei DUAN ; Le WANG ; Zhengyang ZHU ; Yong LYU ; Hua JIN ; Dong WANG ; Lei ZHANG ; Kejun REN
Chinese Journal of Pharmacoepidemiology 2025;34(6):676-689
Objective To systematically summarize medication patterns and explore the potential mechanisms of core herbal combinations in treating chronic glomerulonephritis(CGN)based on data mining and network pharmacology,and to provide a reference for clinical treatment strategies.Methods Electronic book databases were searched to screen the CGN prescription from the works of contemporary Xin'an medical practitioners.Frequency statistics,association rule analysis,and clustering algorithms via the traditional Chinese medicine(TCM)Inheritance Support Platform V3.5 were applied to identify high-frequency herbs(frequency of use>10%)and core combinations.Active ingredients and potential targets were predicted using TCMSP,PubChem,and SwissTargetPrediction databases.Disease-related targets were retrieved from OMIM and GeneCards,after obtaining the intersecting targets,followed by protein-protein interaction(PPI)network construction(STRING platform),Cytoscape topological analysis,and GO and KEGG pathway enrichment(DAVID).Results A total of 151 prescriptions related to the treatment of CGN were included,involving 213 flavours of TCM,including 42 varites of high frequency drugs,mainly in the categories of supplementing deficiency,eliminating dampness and diuresis and clearing heat.Theherb properties were mainly cold,warm,and neutral,with flavors of sweet,bitter,and pungent.Herbs primarily targeted the liver,lung,kidney,and spleen meridians.Thecore combination"Astragali Radix,Dioscorea Rhizome,Atractylodis Macrocephalae Rhizoma,Imperata Rhizome,Pyrrosiae Folium,Poria"was identified,with key active ingredients including quercetin,stigmasterol,and β-sitosterol.Core targets involved IL6,EGFR,TNF,AKT1,and PIK3CA,while enriched pathways included PI3K-Akt and AGE-RAGE signaling.Conclusion Contemporary Xin'an practitioners primarily treat CGN by tonifying the spleen,nourishing the kidney,and clearing damp-heat.Thecore herbal combination exerts synergistic effects through multi-target intervention in immune-inflammatory pathways,oxidative stress,and fibrotic pathways,highlighting the holistic therapeutic advantages of TCM formulas via multi-component synergistic regulation and multi-target interactions.This study provides a theoretical foundation for further experimental validation and clinical applications.
2.The computer-aided diagnosis model of middle ear cholesteatoma based on integrated convolutional neural networks
Yutong ZHAO ; Ruixia MA ; Hailing REN ; Ningyu FENG ; Ning ZHANG ; Le WANG ; Yongchun LI ; Xueliang SHEN ; Jiao HE
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(5):511-519
Objective:Middle ear cholesteatoma is a common otolaryngological disease, and traditional diagnostic methods have certain limitations. This study aims to construct a computer-aided diagnosis model for middle ear cholesteatoma based on integrated convolutional neural networks (CNNs) to improve diagnostic accuracy and efficiency.Methods:Firstly, Data were collected from patients who visited the Department of Otorhinolaryngology Head and Neck Surgery at the First People′s Hospital of Yinchuan between January 2020 and December 2021. 8 000 temporal bone CT images were collected, including 5 000 images diagnosed pathologically as middle ear cholesteatoma and 3 000 normal images. A five-fold cross-validation method was used to divide the dataset into training and testing sets. Next, a transfer learning approach was used to initialize model parameters, and the AlexNet, GoogleNet, and ResNet networks were pre-trained to extract deep features from the images. Then, the Softmax classification algorithm was applied to classify the features, resulting in three independent classifiers. These classifiers were combined using an ensemble learning method with a weighted voting approach to obtain the final diagnostic results. Finally, the model was evaluated by comparing the ensemble classifier with individual classifiers to assess its accuracy, precision, sensitivity, specificity, and diagnostic time, and a comparison with low-mid-and high-experience physician groups was conducted to comprehensively evaluate the model′s diagnostic performance.Results:The experimental results showed that the model achieved an accuracy of 88.8%(178/200), precision of 92.9%,(112/120) sensitivity of 89.8%(108/120), and specificity of 88.1%(70/80). The average diagnostic time for individual patient temporal bone CT images was reduced to 2-3 seconds. Compared to the diagnostic results from low-mid-and high-experience physician groups, the model demonstrated significant advantages and effectively assisted clinicians in making rapid and accurate middle ear cholesteatoma diagnoses.Conclusion:The proposed middle ear cholesteatoma diagnostic model based on integrated convolutional neural networks exhibits high recognition accuracy and rapid diagnostic speed, significantly improving clinical diagnostic efficiency, especially in early screening and auxiliary diagnosis, making it of considerable value in clinical practice.
3.Exploring Academic Characteristics of Contemporary Experts and Schools in Traditional Chinese Medicine Gynecology in Treating Endometriosis Diseases Based on SrTO
Zhiran LI ; Xiaojun BU ; Xiaodan WANG ; Le ZHANG ; Ruixue LIU ; Jingyu REN ; Xing LIAO ; Weiwei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):249-259
ObjectiveStarting from the etiology, pathogenesis, and treatment strategies of endometriosis and adenomyosis, to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology. MethodsAccording to the systematic review of text and opinion (SrTO) process developed by the Joanna Briggs Institute (JBI) in Australia, this paper determined literature screening criteria by searching China National Knowledge Infrastructure (CNKI), VIP, Wanfang, and China Biomedical Literature Database. Information was extracted after literature screening, and quality evaluation was conducted using the JBI Narrative, Text, and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative, Opinion, Text Evaluation, and Review Tool Summary Table was used for information synthesis, and data analysis and display were conducted in the form of text and charts. ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics, meridian circulation location, pathological product evolution, disease duration, emotional psychology, lifestyle habits, preference for food and drink, innate endowment, and acquired injury. In terms of treatment, it was advocated to divide the stage, treat according to different types, adapt to the times, integrate nature and humans, and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects, make good use of classic formulas and small prescriptions, pay attention to protecting the spleen and stomach and regulating emotions, and make good use of self-formulated empirical formulas for internal or external use. Besides, individualized long-term management of patients was also advocated. ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes, mechanisms, diagnosis, and treatments of endometriosis, providing a scientific and standardized reference for future theoretical exploration.
4.Association of Co-Exposure to Polycyclic Aromatic Hydrocarbons and Metal(loid)s with the Risk of Neural Tube Defects: A Case-Control Study in Northern China.
Xiao Qian JIA ; Yuan LI ; Lei JIN ; Lai Lai YAN ; Ya Li ZHANG ; Ju Fen LIU ; Le ZHANG ; Linlin WANG ; Ai Guo REN ; Zhi Wen LI
Biomedical and Environmental Sciences 2025;38(2):154-166
OBJECTIVE:
Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD.
METHODS:
Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with 32P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects.
RESULTS:
In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs.
CONCLUSION
Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans
;
Neural Tube Defects/chemically induced*
;
Polycyclic Aromatic Hydrocarbons/adverse effects*
;
Female
;
Case-Control Studies
;
China/epidemiology*
;
Adult
;
Pregnancy
;
Environmental Pollutants
;
Maternal Exposure/adverse effects*
;
Metals/toxicity*
;
Young Adult
;
Risk Factors
5.Analysis of cases of progressive multifocal leukoencephalopathy treated with immune checkpoint inhibitors
Siyuan FAN ; Le ZHANG ; Manqing XIE ; Nan LIN ; Ying TAN ; Haitao REN ; Hongzhi GUAN
Chinese Journal of Neurology 2025;58(5):501-505
Objective:To investigate the treatment regimens, therapeutic effects, and adverse events of immune checkpoint inhibitors (ICI) in the treatment of progressive multifocal leukoencephalopathy (PML).Methods:A retrospective analysis was performed on patients with PML who received ICI treatment at the Department of Neurology of Peking Union Medical College Hospital from October 2020 to September 2024. The patients′ demographic characteristics, baseline immune status, clinical manifestations, laboratory tests, treatment regimens, and clinical outcomes were analyzed.Results:A total of 2 male patients with PML, aged 40 and 59 years, received ICI treatment. One patient had underlying combined immunodeficiency, while the other had acute myeloid leukemia subtype M2 and had previously undergone umbilical cord blood stem cell transplantation. Both patients were treated with pembrolizumab (dosage range: 2-3 mg/kg, administered every 3-4 weeks), receiving a total of 2-4 courses of treatment. In terms of therapeutic effects, both patients showed significant improvement. Regarding adverse events, 1 patient experienced immune-related adverse event (irAE) of immune-related pneumonia combined with immune-related hypophysitis.Conclusions:ICI may be an effective treatment option for PML. However, the use of ICI may be accompanied by the occurrence of irAE, necessitating close monitoring during treatment.
6.Dynamic changes of lymphocyte subsets in a patient with anti-N-methyl-D-aspartate receptor encephalitis overlaping with myelin oligodendrocyte glycoprotein antibody-associated diseases
Li LI ; Hongzhi GUAN ; Siyuan FAN ; Le ZHANG ; Mange LIU ; Lin BAI ; Haitao REN
Chinese Journal of Neurology 2025;58(7):750-756
Objective:To explore the relationship between the dynamic alterations of immune cell subsets in a patient with autoimmune encephalitis and the clinical relapses.Methods:For a patient with multiple relapses of anti-N-methyl-D-aspartate receptor encephalitis superimposed with myelin oligodendrocyte glycoprotein antibody-associated disease who visited Peking Union Medical College Hospital on July 18, 2018, the lymphocyte subsets were monitored dynamically over a long period and the relationship between lymphocyte subsets and the relapses was summarized.Results:The 38-year old male patient experienced a total of 5 episodes (including 4 relapses) during the six-year immunotherapy and follow-up process, and responded well to first-line and maintenance immunotherapy. His relapses occurred during drug reduction. Finally, the neurological symptoms resolved after rituximab treatment. A total of 39 tests of peripheral blood lymphocyte subsets were conducted during the follow-up, and 5 peaks of elevated CD19 positive B cells, 9 peaks of elevated CD3 positive T cells and 11 peaks of elevated natural killer cells were observed. The peak period of peripheral blood CD19 positive B cells exactly coincided with clinical relapses. While the consistency rates of clinical relapse and the peaks of peripheral blood CD3 positive T cells and natural killer cells were 5/9 and 2/11, respectively.Conclusions:The dynamic alterations of CD19 positive B cells in peripheral blood are correlated with the clinical relapse of autoimmune encephalitis and can predict clinical relapse.
7.Research progress on regulatory mechanism of AQP4 polarization distribution in glymphatic system
Xue-ling LIN ; Ying LI ; Jia-le REN ; Yan-jun ZHANG ; Peng-wei ZHUANG ; Qing-sheng YIN
Chinese Pharmacological Bulletin 2025;41(5):811-815
The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.
8.Research progress on regulatory mechanism of AQP4 polarization distribution in glymphatic system
Xue-ling LIN ; Ying LI ; Jia-le REN ; Yan-jun ZHANG ; Peng-wei ZHUANG ; Qing-sheng YIN
Chinese Pharmacological Bulletin 2025;41(5):811-815
The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.
9.Integrating data mining and network pharmacology to decode the therapeutic principles of contemporary Xin'an medicine for chronic glomerulonephritis
Xulei HU ; Xiaowei DUAN ; Le WANG ; Zhengyang ZHU ; Yong LYU ; Hua JIN ; Dong WANG ; Lei ZHANG ; Kejun REN
Chinese Journal of Pharmacoepidemiology 2025;34(6):676-689
Objective To systematically summarize medication patterns and explore the potential mechanisms of core herbal combinations in treating chronic glomerulonephritis(CGN)based on data mining and network pharmacology,and to provide a reference for clinical treatment strategies.Methods Electronic book databases were searched to screen the CGN prescription from the works of contemporary Xin'an medical practitioners.Frequency statistics,association rule analysis,and clustering algorithms via the traditional Chinese medicine(TCM)Inheritance Support Platform V3.5 were applied to identify high-frequency herbs(frequency of use>10%)and core combinations.Active ingredients and potential targets were predicted using TCMSP,PubChem,and SwissTargetPrediction databases.Disease-related targets were retrieved from OMIM and GeneCards,after obtaining the intersecting targets,followed by protein-protein interaction(PPI)network construction(STRING platform),Cytoscape topological analysis,and GO and KEGG pathway enrichment(DAVID).Results A total of 151 prescriptions related to the treatment of CGN were included,involving 213 flavours of TCM,including 42 varites of high frequency drugs,mainly in the categories of supplementing deficiency,eliminating dampness and diuresis and clearing heat.Theherb properties were mainly cold,warm,and neutral,with flavors of sweet,bitter,and pungent.Herbs primarily targeted the liver,lung,kidney,and spleen meridians.Thecore combination"Astragali Radix,Dioscorea Rhizome,Atractylodis Macrocephalae Rhizoma,Imperata Rhizome,Pyrrosiae Folium,Poria"was identified,with key active ingredients including quercetin,stigmasterol,and β-sitosterol.Core targets involved IL6,EGFR,TNF,AKT1,and PIK3CA,while enriched pathways included PI3K-Akt and AGE-RAGE signaling.Conclusion Contemporary Xin'an practitioners primarily treat CGN by tonifying the spleen,nourishing the kidney,and clearing damp-heat.Thecore herbal combination exerts synergistic effects through multi-target intervention in immune-inflammatory pathways,oxidative stress,and fibrotic pathways,highlighting the holistic therapeutic advantages of TCM formulas via multi-component synergistic regulation and multi-target interactions.This study provides a theoretical foundation for further experimental validation and clinical applications.
10.Analysis of cases of progressive multifocal leukoencephalopathy treated with immune checkpoint inhibitors
Siyuan FAN ; Le ZHANG ; Manqing XIE ; Nan LIN ; Ying TAN ; Haitao REN ; Hongzhi GUAN
Chinese Journal of Neurology 2025;58(5):501-505
Objective:To investigate the treatment regimens, therapeutic effects, and adverse events of immune checkpoint inhibitors (ICI) in the treatment of progressive multifocal leukoencephalopathy (PML).Methods:A retrospective analysis was performed on patients with PML who received ICI treatment at the Department of Neurology of Peking Union Medical College Hospital from October 2020 to September 2024. The patients′ demographic characteristics, baseline immune status, clinical manifestations, laboratory tests, treatment regimens, and clinical outcomes were analyzed.Results:A total of 2 male patients with PML, aged 40 and 59 years, received ICI treatment. One patient had underlying combined immunodeficiency, while the other had acute myeloid leukemia subtype M2 and had previously undergone umbilical cord blood stem cell transplantation. Both patients were treated with pembrolizumab (dosage range: 2-3 mg/kg, administered every 3-4 weeks), receiving a total of 2-4 courses of treatment. In terms of therapeutic effects, both patients showed significant improvement. Regarding adverse events, 1 patient experienced immune-related adverse event (irAE) of immune-related pneumonia combined with immune-related hypophysitis.Conclusions:ICI may be an effective treatment option for PML. However, the use of ICI may be accompanied by the occurrence of irAE, necessitating close monitoring during treatment.

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