1.Zuogui Wan Improve Ovarian Inflammatory Microenvironment and Stemness of Ovarian Germline Stem Cells in Ovarian Aging via cGAS/STING Signaling Pathway
Yunling ZHENG ; Xinyi PAN ; Zuang LI ; Yixuan WANG ; Junyi AN ; Yuxin ZOU ; Mengting XIAO ; Zheng CHEN ; Ling ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):1-10
ObjectiveTo investigate the mechanism of Zuogui Wan (ZGW) in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells (OSCs) for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group, a model group, a low-dose ZGW group (2.7 g·kg-1), a high-dose ZGW group (5.4 g·kg-1), and an estradiol valerate group (0.15 mg·kg-1), with 8 mice in each group. Except the blank group, all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg-1 to establish an ovarian aging mouse model. After successful modeling, each group was continuously administered for 4 weeks, once daily. The physiological status of the mice was observed, and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin (HE) staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and mouse interleukin-6 (IL-6) levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS, STING, p-STING, TANK-binding kinase 1 (TBK1), p-TBK1, interferon-induced transmembrane protein 3 (Fragilis), and Vasa homolog protein (MVH). Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues, and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 (Oct4) were calculated. ResultsCompared with the blank group, the model group showed reduced body weight, ovarian wet weight, and ovarian index (P<0.01) and a disordered estrus cycle (P<0.01). In addition, the levels of serum follicle-stimulating hormone (FSH), TNF-α, IL-6, and IL-1β were increased (P<0.01), while anti-Müllerian hormone (AMH) and estradiol (E2) levels were decreased (P<0.01). The protein expression of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue was increased (P<0.05, P<0.01), while that of OSCs stemness factors MVH and Fragilis was reduced (P<0.01). Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs (P<0.01). The mRNA expression of inflammatory factors TNF-α, IL-6, and IL-1β in ovarian tissue was increased (P<0.05, P<0.01). Compared with the model group, the treatment groups exhibited improved body weight, ovarian wet weight, and ovarian index (P<0.05) and a reduced rate of estrus cycle disorder (P<0.05, P<0.01). The levels of serum FSH, TNF-α, IL-6, and IL-1β were decreased (P<0.05, P<0.01), while AMH and E2 levels were increased (P<0.01). The protein expression levels of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue were decreased (P<0.05), while the protein expression of MVH and Fragilis was increased (P<0.05), and the fluorescence intensities of MVH and Oct4 were increased (P<0.05, P<0.01). The mRNA expression of inflammatory factors in ovarian tissue was decreased (P<0.05). ConclusionZGW alleviate ovarian inflammatory response, regulate ovarian microenvironment homeostasis, and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway, thereby improving ovarian function and delaying ovarian aging.
2.Reconsideraton of Stroke with Syndrome of Combined Blood Stasis and Toxin from the Perspective of Xiang Thinking
Yunfan ZHANG ; Di ZHAO ; Lina MIAO ; Hongxi LIU ; Jingjing WEI ; Xiao LIANG ; Liuding WANG ; Xueru ZHANG ; Yunmeng CHEN ; Yunling ZHANG
Journal of Traditional Chinese Medicine 2025;66(13):1305-1310
Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy, reasoning, deduction, and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind, fire, phlegm, and blood stasis" in stroke, thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile, the article traced the construction process of xiang thinking, and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives, state, attribute, origin, and law. Furthermore, the relationship between the process of constructing xiang thinking and the origin of etiology, identification methods, pathogenesis evolution, and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored, so as to provide insights into research on the etiology and pathogenesis of stroke, as well as clinical diagnosis and treatment approaches.
3.Development of the Chinese Premature Ovarian Insufficiency Quality of Life Scale
Yunling ZHENG ; Yuxin ZOU ; Yucheng LI ; Zhuoting CHEN ; Liuqian HUANG ; Xinyi PAN ; Ling ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(5):1287-1296
Objective To develop a quality of life(QoL)scale for Premature Ovarian Insufficiency(POI)with high reliability and validity in accordance with China's national conditions.Methods The theoretical framework of the scale was constructed under the guidance of traditional Chinese medicine theory with reference to the development method of the QoL scale.Literature analysis method,medical record review method,patient interview method,Delphi expert consultation method and clinical investigation were used to establish,improve and screen the scale items to form the final scale,and the characteristics and differentiation in terms of reliability and validity and feasibility of the final scale were evaluated.Results After screening the entries by the Delphi method and clinical surveys,the Chinese Premature Ovarian Insufficiency Quality of Life Scale was formed,which included three domains of physiology,psychology,and society,and eleven aspects such as menstruation,fertility,and physical symptoms,with 30 entries and two overall evaluations.The Cronbach's coefficient of this scale was 0.910,the fold-half coefficient was 0.956,and the re-test correlation coefficient was 0.868,which showed good internal consistency,fold-half and re-test reliabilities;the scale extracted 9 factors with characteristic root>1,and the cumulative variance contribution rate was 71.063%,the comparative fit index was 0.959,and the goodness-of-fit index was 0.919,and the degree of correlation was tested has showed that the content validity,structural validity and calibration correlation validity were good;the difference in the total scores of the scale between patients with POI and the healthy population was statistically significant,and the scale had a good degree of differentiation.Conclusion As confirmed by this study,the Chinese Premature Ovarian Insufficiency Quality of Life Scale has good reliability,validity,differentiation and feasibility,and can be used as a tool for evaluating the quality of life of POI patients in China as well as enriching the efficacy evaluation system of TCM in treating POI,and it is suitable for clinical popularization and application.
4.Investigation and safety analysis on off-label drug use in patients with nontuberculous mycobacterial pulmonary disease at a specialty hospital
Yunling GAO ; Lanxin LIN ; Qingming YANG ; Xiaohong CHEN
Adverse Drug Reactions Journal 2025;27(8):458-464
Objective:To investigate off-label drug use and the incidence of adverse events (AE) in patients with nontuberculous mycobacterial (NTM) pulmonary disease, and to provide reference in standardization of off-label drug use in this population.Methods:The medical records of NTM pulmonary disease patients in our hospital from January to December 2024 were retrieved based on the presence of "nontuberculous mycobacteria" in the diagnosis. The demographic characteristics of patients (gender, age), underlying diseases, identified NTM species, details of off-label prescribing (clinical medication indications and the name, duration and frequency of drugs), and the AE occurrence were collected. The utilization rate, AE incidence, and off-label use rate of the anti-NTM drugs were calculated.Results:A total of 259 patients with NTM pulmonary disease were included in the analysis, including 125 males and 134 females, aged (61±11) years with a range of 20-83 years; 243 patients (93.8%) were complicated with underlying diseases, 99 cases (38.2%) of which had 2 or more underlying diseases. Among the 259 patients, the top 3 pathogenic bacteria in the sputum and bronchoalveolar lavage fluid were Mycobacterium intracellulare (126 cases, 48.6%), Mycobacterium abscessus (50 cases, 19.3%), and Mycobacterium avium (30 cases, 11.6%); 16 patients (6.2%) were co-infected with 2 strains. All of the 259 patients were treated with a combination therapy of 4 drugs without discontinuation at least 1 year after the negative sputum culture. All 259 patients had off-label drug use, mainly including off-label indication [98.8%(256/259)] and prolonged treatment duration(100%). Among the 259 patients, 17 kinds of off-label drugs were involved, and the top 5 in terms of usage frequency were ethambutol (182 cases, 70.3%), amikacin (141 cases, 54.4%), azithromycin (140 cases, 54.1%), clarithromycin (135 cases, 52.1%), and rifabutin (106 cases, 40.9%). The overall AE incidence was 37.5% (97/259), mainly including gastrointestinal reactions [17.4% (45/259)], skin pruritus [12.0% (31/259)], and abnormal liver function [9.7% (25/259)]. The incidences of severe AE and AE involving 2 or more systems were 5.0% (13/259) and 17.4% (45/259), respectively. Conclusions:Off-label drug use is prevalent in patients with NTM pulmonary disease, mainly characterized by off-label indications and prolonged treatment duration. A variety of drugs are involved, among which ethambutol, amikacin, macrolides, and rifabutin are the most common. The types of AE reported are all common, mainly including gastrointestinal reactions, allergic reactions, and abnormal liver function, with a low proportion of severe AE. However, off-label use carries inherent risks, it is necessary to strengthen therapeutic drug monitoring and management during the treatment of NTM pulmonary disease.
5.Development of the Chinese Premature Ovarian Insufficiency Quality of Life Scale
Yunling ZHENG ; Yuxin ZOU ; Yucheng LI ; Zhuoting CHEN ; Liuqian HUANG ; Xinyi PAN ; Ling ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(5):1287-1296
Objective To develop a quality of life(QoL)scale for Premature Ovarian Insufficiency(POI)with high reliability and validity in accordance with China's national conditions.Methods The theoretical framework of the scale was constructed under the guidance of traditional Chinese medicine theory with reference to the development method of the QoL scale.Literature analysis method,medical record review method,patient interview method,Delphi expert consultation method and clinical investigation were used to establish,improve and screen the scale items to form the final scale,and the characteristics and differentiation in terms of reliability and validity and feasibility of the final scale were evaluated.Results After screening the entries by the Delphi method and clinical surveys,the Chinese Premature Ovarian Insufficiency Quality of Life Scale was formed,which included three domains of physiology,psychology,and society,and eleven aspects such as menstruation,fertility,and physical symptoms,with 30 entries and two overall evaluations.The Cronbach's coefficient of this scale was 0.910,the fold-half coefficient was 0.956,and the re-test correlation coefficient was 0.868,which showed good internal consistency,fold-half and re-test reliabilities;the scale extracted 9 factors with characteristic root>1,and the cumulative variance contribution rate was 71.063%,the comparative fit index was 0.959,and the goodness-of-fit index was 0.919,and the degree of correlation was tested has showed that the content validity,structural validity and calibration correlation validity were good;the difference in the total scores of the scale between patients with POI and the healthy population was statistically significant,and the scale had a good degree of differentiation.Conclusion As confirmed by this study,the Chinese Premature Ovarian Insufficiency Quality of Life Scale has good reliability,validity,differentiation and feasibility,and can be used as a tool for evaluating the quality of life of POI patients in China as well as enriching the efficacy evaluation system of TCM in treating POI,and it is suitable for clinical popularization and application.
6.Investigation and safety analysis on off-label drug use in patients with nontuberculous mycobacterial pulmonary disease at a specialty hospital
Yunling GAO ; Lanxin LIN ; Qingming YANG ; Xiaohong CHEN
Adverse Drug Reactions Journal 2025;27(8):458-464
Objective:To investigate off-label drug use and the incidence of adverse events (AE) in patients with nontuberculous mycobacterial (NTM) pulmonary disease, and to provide reference in standardization of off-label drug use in this population.Methods:The medical records of NTM pulmonary disease patients in our hospital from January to December 2024 were retrieved based on the presence of "nontuberculous mycobacteria" in the diagnosis. The demographic characteristics of patients (gender, age), underlying diseases, identified NTM species, details of off-label prescribing (clinical medication indications and the name, duration and frequency of drugs), and the AE occurrence were collected. The utilization rate, AE incidence, and off-label use rate of the anti-NTM drugs were calculated.Results:A total of 259 patients with NTM pulmonary disease were included in the analysis, including 125 males and 134 females, aged (61±11) years with a range of 20-83 years; 243 patients (93.8%) were complicated with underlying diseases, 99 cases (38.2%) of which had 2 or more underlying diseases. Among the 259 patients, the top 3 pathogenic bacteria in the sputum and bronchoalveolar lavage fluid were Mycobacterium intracellulare (126 cases, 48.6%), Mycobacterium abscessus (50 cases, 19.3%), and Mycobacterium avium (30 cases, 11.6%); 16 patients (6.2%) were co-infected with 2 strains. All of the 259 patients were treated with a combination therapy of 4 drugs without discontinuation at least 1 year after the negative sputum culture. All 259 patients had off-label drug use, mainly including off-label indication [98.8%(256/259)] and prolonged treatment duration(100%). Among the 259 patients, 17 kinds of off-label drugs were involved, and the top 5 in terms of usage frequency were ethambutol (182 cases, 70.3%), amikacin (141 cases, 54.4%), azithromycin (140 cases, 54.1%), clarithromycin (135 cases, 52.1%), and rifabutin (106 cases, 40.9%). The overall AE incidence was 37.5% (97/259), mainly including gastrointestinal reactions [17.4% (45/259)], skin pruritus [12.0% (31/259)], and abnormal liver function [9.7% (25/259)]. The incidences of severe AE and AE involving 2 or more systems were 5.0% (13/259) and 17.4% (45/259), respectively. Conclusions:Off-label drug use is prevalent in patients with NTM pulmonary disease, mainly characterized by off-label indications and prolonged treatment duration. A variety of drugs are involved, among which ethambutol, amikacin, macrolides, and rifabutin are the most common. The types of AE reported are all common, mainly including gastrointestinal reactions, allergic reactions, and abnormal liver function, with a low proportion of severe AE. However, off-label use carries inherent risks, it is necessary to strengthen therapeutic drug monitoring and management during the treatment of NTM pulmonary disease.
7.Exploring the Disease Mechanism and Treatment of Ischemic Stroke Based on Ascending and Descending of Qi Movement from the Perspective of Xiang Thinking
Liuding WANG ; Xiao LIANG ; Yifan CHEN ; Yue LIU ; Hongxi LIU ; Di ZHAO ; Yunfan ZHANG ; Yunmeng CHEN ; Xueru ZHANG ; Yunling ZHANG
Journal of Traditional Chinese Medicine 2024;65(14):1443-1448
Xiang thinking is the key way of thinking to construct the life model of human body in traditional Chinese medicine (TCM), and the theory of ascending and descending of qi movement is an important manifestation of xiang thinking in the theory of TCM. Based on the theory of qi movement, this paper interpreted the mechanism of ischemic stroke through the perspective of xiang thinking "earth weakness - wood constraint - fire hyperactivity", as "earth weakness in the central and dampness accumulated to phlegm" "wood constraint and stirring wind led to blood stasis" and "fire hyperactivity and fire toxin showed flaming upward" due to disorder of qi movement. Combined with the "xiang of medicinal properties and therapy methods" to discuss the treatment and prescriptions of ischaemic stroke, applying wind medicinals to elevate ji-earth (己土) and yi-wood (乙木), so that phlegm and stasis can be eliminated, and cold medicinals to descend jia-wood (甲木) and wu-earth (戊土) so that fire toxin can be cleared, with a view to restore ascending and descending of qi movement for ischaemic stroke.
8.Reliability and Validity Analysis on Symptom Identification Scale for Vascular Cognitive Impairment with Kidney Yang Deficiency
Chunyan GUO ; Chen FU ; Zhenmin XU ; Min WANG ; Ying ZHANG ; Xiaobing HOU ; Tao LI ; Huanmin NIU ; Linjuan SUN ; Yunling ZHANG ; Baoxin CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):153-157
Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.
9.Thought of Treatment of Orifices Based on Correspondence Between Drugs and Symptoms in Chinese Herbal Classics in Past Dynasties
Hongxi LIU ; Jingzi SHI ; Jingjing WEI ; Yue LIU ; Wei SHEN ; Yunmeng CHEN ; Liuding WANG ; Xiansu CHI ; Xiao LIANG ; Yunling ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):185-193
ObjectiveTo discuss the thought of treatment of orifices in the Chinese herbal classics in the past dynasties based on the correspondence between drugs and symptoms to guide the clinical treatment based on syndrome differentiation. MethodAll the literature data of Chinese herbal classics were retrieved from the database of the Chinese Medical Dictionary, involving 76 works of Chinese herbal classics and covering representative works from the Han dynasty to the Ming and Qing dynasties. The information on Chines herbal drugs for the treatment of orifices was collected and sorted out. According to Chinese Materia Medica (11th Edition) and Pharmacopoeia of the People's Republic of China (2020 Edition), the nature, flavor, and meridian tropism of the selected Chinese herbal drugs were statistically analyzed. The pathogenesis elements in the treatment of orifices were classified and counted, and the contents of syndrome differentiation and treatment in various Chinese herbal classics were extracted. ResultIn 76 Chinese herbal classics in the past dynasties, 93 Chinese herbal drugs for the treatment of orifices were selected. The nature of drugs was mainly warm, followed by cold and mild. The flavor was mainly pungent, followed by bitter and sweet. In terms of meridian tropism, drugs mainly acted on the lung meridian, followed by stomach, heart, liver, spleen, and kidney meridians. The pathogenesis elements of orifices could be divided into six categories, i.e., wind invasion, turbid obstruction and Qi stagnation, water and dampness stagnation, blood stasis and collaterals blockage, heat and toxin damage, deficiency of vital Qi and cold coagulation. ConclusionOrifices are mainly treated with drugs effective in dispelling wind and pathogenic factors, resolving turbidity and removing stagnation, inducing diuresis and eliminating dampness, promoting blood circulation and dredging collaterals, clearing heat and purging fire, tonifying deficiency and dispelling cold, which are used in combination. Eliminating pathogenic factors and dredging, tonifying deficiency and purging excess are the main characteristics of treatment of orifices based on syndrome differentiation, which is in line with the physiological dysfunction state of orifices in losing the function, evil Qi blockage and healthy Qi deficiency.
10.Study on medication law of TCM compounds with national patents for treatment of vascular dementia
Weiwei JIAO ; Wei SHEN ; Xiao LIANG ; Jingjing WEI ; Min JIA ; Lin LEI ; Qian CHEN ; Xinyun ZENG ; Yunling ZHANG ; Yan LU
International Journal of Traditional Chinese Medicine 2023;45(6):772-776
Objective:To explore the prescription and medication law of Traditional Chinese Medicine (TCM) compounds in the treatment of vascular dementia (VD) based on patent database.Methods:TCM compounds with patents about VD were retrieved from Chinese patent announcement website of the State Intellectual Property Office and CNKI. The retrieval time was from the establishment to the databases to 31 st, March 2022. The frequency, clusteringand association analysis were carried out with the help of TCM inheritance auxiliary platform (V2.5). The medication law was analyzed. Results:154 TCM compound patents for the treatment of vascular dementia were screened, involving 227 kinds of Chinese materia medica. Among them, Acori Tatarinowii Rhizoma (44 times, 28.57%) was used more frequently, and the common medicinal pair was Salviea Miltiorrhizae Radix et Rhizoma- Acori Tatarinowii Rhizoma (17 times, 11.03%). The medicinal property was mainly warm, the taste was mainly sweet, and the meridian was mainly liver meridian. Those with high confidence based on association rules were " Corni Fructus -Acori Tatarinowii Rhizoma" (0.90), " Corni Fructus -Rehmannize Radix et Praeparata" (0.90). Based on the complex network, it was concluded that the core drugs were 14 groups such as " Rehmannize Radix et Praeparata- Cistanches Herba- Corni Fructus". The new prescriptions extracted by entropy cluster analysis included 7 groups such as " Rehmannize Radix et Praeparata, Cistanches Herba, Corni Fructus and Asparagi Radix". Conclusion:The treatment of VD by TCM compounds with national patents is mainly based on tonifying deficiency, promoting blood circulation and removing blood stasis, eliminating phlegm and dampness, expelling wind and dredging collaterals, opening orifices and resuscitation, which can provide reference for clinical practice and new drug research and development.

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