1.Programmed Cell Death in Endometriosis and Traditional Chinese Medicine Intervention: A Review
Zuoliang ZHANG ; Wanrun WANG ; Wen LI ; Xue HAN ; Xiaohong CHEN ; Nan SU ; Huiling LIU ; Quansheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):48-57
Endometriosis (EMT) is a common disease with frequent occurrence and difficult to be cured in modern clinical practice of obstetrics and gynaecology. It is characterized by progressively worsening dysmenorrhoea, pelvic mass, and infertility. The incidence of EMT is growing and increasingly younger patients are diagnosed with this disease, which poses a serious threat to the reproductive and psychological health of women of childbearing age and adolescent females. However, the pathogenesis of EMT is still not completely clear, and the disease has a long course. Therefore, developing new therapies is an urgent clinical problem to be solved. Great progress has been achieved in the treatment of EMT with traditional Chinese medicine (TCM), while the underlying mechanism remains in exploration. Programmed cell death (PCD) is a cell death mode mediated by a variety of bio-molecules with specific signaling cascades. The known PCD processes include apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis, which all play a pivotal role in the development of EMT. Researchers have made achievements in the treatment of EMT with TCM, which regulates PCD via multiple pathways, routes, targets, and mechanisms. However, the progress in the regulation of PCD in the treatment of EMT with TCM remains to be reviewed. This paper reviews the research progress in the treatment of EMT with TCM from five PCD processes (apoptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis), with the aim of providing a theoretical basis for the clinical prevention and treatment of EMT.
2.Drug resistance of multidrug-resistant organism in hospitalized children at a children's hospital in Hebei Province
SUN Ling ; LIU Yuanqing ; LIU Xinguang ; ZHANG Nan ; WEN Chan ; HAO Jianzong ; LI Mei
Journal of Preventive Medicine 2025;37(6):616-621
Objective:
To analyze the drug resistance of multidrug-resistant organism (MDRO) among hospitalized children in a children's hospital in Hebei Province from 2019 to 2023, so as to provide the basis for the rational clinical application of antibacterial drugs.
Methods:
Specimens including sputum, blood, urine, pus, bronchoalveolar lavage fluid, secretions, pleural fluid, and peritoneal fluid of hospitalized children from January 2019 to December 2023 were collected. Pathogen identification and drug susceptibility tests were performed on methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum β-lactamase-producing Escherichia coli (ESBLs-EC), extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBLs-KP), carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Escherichia coli (CREC). The department distribution, specimen distribution, and drug resistance of MDROs were analyzed.
Results:
A total of 279 086 samples were submitted for testing, with 3 512 MDROs detected. Among these, MRSA and ESBLs-EC had relatively high detection rates of 35.76% and 41.50%, respectively. In the internal medicine pediatric patients, 1 869 MDROs were detected, accounting for 53.22%. The main departments were respiratory medicine, neonatology, and intensive care. In the surgical department, 1 643 MDROs were detected, accounting for 46.78%, with the main sources being general surgery and cardiac surgery. The highest numbers of MDROs were detected in sputum, pus, and urine samples, with 1 372, 527, and 494 isolates, representing 39.07%, 15.01%, and 14.07%, respectively. The resistance rates of MRSA to penicillin, oxacillin, and erythromycin were between 81.76% and 100.00%. ESBLs-EC and ESBLs-KP had a resistance rate of 100.00% to ceftriaxone. CRKP had a resistance rate of 100.00% to ampicillin/sulbactam and imipenem. CRAB had a resistance rate of 100.00% to cefoxitin, imipenem, and meropenem. CRPA had a resistance rate of 100.00% to ampicillin/sulbactam, ceftriaxone, cefoxitin, and imipenem. CREC had a resistance rate of 100.00% to imipenem.
Conclusions
In a children's hospital in Hebei Province, infections with MDROs among hospitalized pediatric patients are primarily caused by MRSA and ESBLs-EC. These infections are mainly distributed in the departments of respiratory medicine, neonatology, intensive care, general surgery, and cardiac surgery, with the highest detection rates in sputum, pus, and urine samples. Additionally, MRSA, ESBLs-EC, ESBLs-KP, CRKP, CRAB, CRPA, and CREC show high resistance rate to most antimicrobial agents.
3.Chemical constituents of Sophorae Flavescentis Radix and its residue based on UPLC-Q-TOF-MS.
Qian-Wen LIU ; Rong-Qing ZHU ; Qian-Nan HU ; Xiang LI ; Guang YANG ; Zi-Dong QIU ; Zhi-Lai ZHAN ; Tie-Gui NAN ; Mei-Lan CHEN ; Li-Ping KANG
China Journal of Chinese Materia Medica 2025;50(3):708-718
Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Mass Spectrometry/methods*
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Sophora/chemistry*
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Flavonoids/chemistry*
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Alkaloids/chemistry*
4.Optimization of extraction process for Shenxiong Huanglian Jiedu Granules based on AHP-CRITIC hybrid weighting method, grey correlation analysis, and BP-ANN.
Zi-An LI ; De-Wen LIU ; Xin-Jian LI ; Bing-Yu WU ; Qun LAN ; Meng-Jia GUO ; Jia-Hui SUN ; Nan-Yang LIU ; Hui PEI ; Hao LI ; Hong YI ; Jin-Yu WANG ; Liang-Mian CHEN
China Journal of Chinese Materia Medica 2025;50(10):2674-2683
By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis*
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Neural Networks, Computer
5.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C
6.Clinical Efficacy of CAG Regimen Combined with Venetoclax, Chidamide, and Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia.
Qing-Yang LIU ; Yu JING ; Meng LI ; Sai HUANG ; Yu-Chen LIU ; Ya-Nan WEN ; Jing-Jing YANG ; Wen-Jing GAO ; Ning LE ; Yi-Fan JIAO ; Xia-Wei ZHANG ; Li-Ping DOU
Journal of Experimental Hematology 2025;33(4):945-950
OBJECTIVE:
To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML).
METHODS:
15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed.
RESULTS:
After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process.
CONCLUSION
The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans
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Leukemia, Myeloid, Acute/drug therapy*
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Bridged Bicyclo Compounds, Heterocyclic/therapeutic use*
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Sulfonamides/therapeutic use*
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Aminopyridines/therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Azacitidine/therapeutic use*
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Aged
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Benzamides/therapeutic use*
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Male
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Female
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Treatment Outcome
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Middle Aged
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Cytarabine
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Aclarubicin
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Granulocyte Colony-Stimulating Factor
7."Relative symmetry with electronegativity of different key-groups" strategy for MRGPRX2 antagonist design and its effect on antigen-induced pulmonary inflammation.
Jiayu LU ; Zhaomin XIA ; Yongjing ZHANG ; He WANG ; Wen YANG ; Siqi WANG ; Nan WANG ; Yun LIU ; Huaizhen HE ; Cheng WANG ; Langchong HE
Acta Pharmaceutica Sinica B 2025;15(1):494-507
MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC50 values in vitro. However, the structure-activity relationship remains unclear. Herein, we adopted a "relative symmetry with electronegativity of different key-groups" strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC50 in vitro and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the "relative symmetry with electronegativity of different key-groups" strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.
8.Intercellular communication interference through energy metabolism-related exosome secretion inhibition for liver fibrosis treatment.
Mengyao ZHANG ; Huaqing JING ; Xinyi LIU ; Valentin A MILICHKO ; Yunsheng DOU ; Yingzi REN ; Zitong QIU ; Wen LI ; Weili LIU ; Xinxing WANG ; Nan LI
Acta Pharmaceutica Sinica B 2025;15(9):4900-4916
As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.
9.Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
Wen-Yan ZHOU ; Jian-Kui DU ; Hong-Hong LIU ; Lei DENG ; Kai MA ; Jian XIAO ; Sheng ZHANG ; Chang-Nan WANG
Journal of Integrative Medicine 2025;23(5):560-575
OBJECTIVE:
Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).
METHODS:
A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.
RESULTS:
Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.
CONCLUSION
Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology*
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Animals
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MicroRNAs/genetics*
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Lipopolysaccharides
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Ferroptosis/drug effects*
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Mice
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Myocytes, Cardiac/metabolism*
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Signal Transduction/drug effects*
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Rats
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Male
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Mice, Inbred C57BL
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Cardiomyopathies/etiology*
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Cell Line
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Sepsis/complications*
10.Hepatitis C virus infection:surveillance report from China Healthcare-as-sociated Infection Surveillance System in 2020
Xi-Mao WEN ; Nan REN ; Fu-Qin LI ; Rong ZHAN ; Xu FANG ; Qing-Lan MENG ; Huai YANG ; Wei-Guang LI ; Ding LIU ; Feng-Ling GUO ; Shu-Ming XIANYU ; Xiao-Quan LAI ; Chong-Jie PANG ; Xun HUANG ; An-Hua WU
Chinese Journal of Infection Control 2024;23(1):1-8
Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93%and a HCV positive rate of 0.54%.The positive rate of HCV in male and female patients were 0.60%and 0.48%,respectively,with a statistically sig-nificant difference(x2=47.18,P<0.001).The HCV positive rate in the 50-<60 age group was the highest(0.76%),followed by the 40-<50 age group(0.71%).Difference among all age groups was statistically signifi-cant(x2=696.74,P<0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57%;775 patients were infected with HCV,with a positive rate of 2.21%.In 2020,HCV positive rates in hospitals of different scales were 0.46%-0.63%,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P<0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19%-0.81%,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06%-0.82%,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95%and 3.48%,respectively.Followed by departments of orthopedics(7.72%),gastroenterology(3.77%),nephrology(3.57%)and general intensive care unit(ICU,3.10%)in 2003,as well as departments of gastroenterology(1.35%),nephrology(1.18%),endocrinology(0.91%),and general intensive care unit(ICU,0.79%)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.


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