1.Effect of Modified Gegen Qinlian Decoction (加味葛根芩连汤) on the Intestinal Mucus Barrier and Intestinal Stem Cell Proliferation and Differentiation in Ulcerative Colitis Model Mice
Jinke HUANG ; Jiaqi ZHANG ; Fengyun WANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2025;66(9):941-947
ObjectiveTo explore the possible mechanism of Modified Gegen Qinlian Decoction (加味葛根芩连汤, MGQD) in the treatment of ulcerative colitis (UC) based on intestinal mucus barrier. MethodsThirty C57BL/6 mice were randomly divided into a control group, a model group and a MGQD group with 10 mice in each. Dextran Sulfate Sodium Salt (DSS) was used to construct the UC model in all groups except for the control group. Meanwhile, mice in the MGQD group were given 20 g/kg of MGQD decoction by gavage according to their body weight, while those in the control group and model group were given 0.2 ml/20 g of pure water by gavage, once a day for 7 consecutive days. On the day following the last gavage, the body weight, disease activity index (DAI) score, spleen weight, and colon length were compared. The pathological changes of the intestinal mucosal tissues were observed by HE staining; the protein expression levels of mucin 2 (MUC2) and leucine-rich repeat G protein-coupled receptor 5 (Lgr5) in the intestinal mucosal tissues were detected by immunofluorescence; the cuprocytes in the intestinal mucosal tissues were detected by AB/PAS staining; and the expression level of Ki67 in the intestinal mucosal tissues was detected by immunohistochemistry. ResultsHE staining showed that the colon mucosal tissue of the mice in the control group was intact. In the model group, the colon mucosal epithelial structure was severely damaged, with a large amount of inflammatory cell infiltration in the mucosal propria. In the MGQD group, the mucosal tissue structure was partially lost, with a small amount of inflammatory cell infiltration.The body weight and colon length of mice in the model group decreased significantly compared to those in the control group, while DAI scores and spleen weight increased, and the levels of MUC2, Ki67, Lgr5 proteins, and the number of goblet cells were significantly reduced (P<0.01). Compared to the model group, the MGQD group had increased body weight of mice, colon length, and decreased DAI scores and spleen weight; the levels of MUC2, Ki67, Lgr5 proteins, and the number of goblet cells were increased (P<0.05 or P<0.01). ConclusionMGQD has a favorable ameliorative effect on UC-related symptoms and pathological tissue damage, and its mechanism of action may be related to the restoration of the prolife-ration and differentiation of intestinal stem cells into goblet cells, thereby promoting the repair of the intestinal mucus barrier.
2.Analysis of Animal Model Construction Methods of Different Subtypes of Gastroesophageal Reflux Disease Based on Literature
Mi LYU ; Kaiyue HUANG ; Xiaokang WANG ; Yuqian WANG ; Xiyun QIAO ; Lin LYU ; Hui CHE ; Shan LIU ; Fengyun WANG
Journal of Traditional Chinese Medicine 2025;66(13):1386-1394
ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease (GERD) based on literature, providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis (RE), nonerosive reflux disease (NERD) and Barrett's esophagus (BE) model construction from January 1, 2014 to January 27, 2024, were retrieved from databases such as CNKI, Wanfang, VIP, Web of Science, and Pubmed. Information on animal strains, genders, modeling methods including disease-syndrome combination models, modeling cycles were extracted; for studies with model evaluation, the methods of model evaluation were also extracted; then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE (88/148, 59.46%) and NERD (9/14, 64.29%). For BE, C57BL/6 mice were most commonly used (11/20, 55.00%). Male animals (RE: 111/135, 82.22%; NERD: 11/14, 78.57%; BE: 10/12, 83.33%) were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer, gastric content reflux, or mixed reflux, among which forestomach ligation + incomplete pylorus ligation (42/158, 26.58%) was the most common modeling method; the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa, visceral hypersensitivity, and emotional problems, and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus (8/14, 57.14%) was the most common modeling method; the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux, and constructing interleukin 2-interleukin 1β transgenic mice (7/25, 28.00%) was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE, NERD, and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics (e.g., RE focusing on structural damage, NERD emphasizing visceral hypersensitivity). Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches (e.g., composite etiology simulation) and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.
3.Protective Effect of Bushen Zhuyun Prescription on Abortion Rats with Kidney Deficiency-Corpus Luteum Inhibition Syndrome via ERα/PI3K/Akt Signaling Pathwa
Changyue SONG ; Siyu LI ; Fengyu HUANG ; Mingzhu QI ; Daiyue DING ; Shuangfei DENG ; Heqiao LI ; Jinghong XIE ; Guohua WANG ; Chen ZANG ; Hong XU ; Xiaohui SU ; Xiangying KONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):107-116
ObjectiveTo investigate the protective effects and mechanisms of Bushen Zhuyun prescription (BSZY) on abortion rats with kidney deficiency-corpus luteum inhibition syndrome. MethodsAn abortion rat model with kidney deficiency-corpus luteum inhibition syndrome was constructed. Pregnant mice aged 8-10 weeks were randomly divided into a control group (Control), a model group (Model), low-dose BSZY (BSZY-L), medium-dose BSZY (BSZY-M), and high-dose BSZY (BSZY-H) groups (2.57, 5.14, 10.28 g·kg-¹), and a Zishen Yutai Pill (ZSYT) group (1.575 g·kg-¹). Hematoxylin-eosin (HE) staining was used to evaluate histopathological changes in ovarian and decidual tissue of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was employed to measure levels of estrogen (E₂), progesterone (P), luteinizing hormone (LH), prolactin (PRL), and follicle-stimulating hormone (FSH) in serum. The candidate targets of BSZY were obtained from the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 databases, while disease targets for recurrent spontaneous abortion (RSA) were retrieved from GeneCards, DrugBank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). The intersection targets were identified by the Venny 2.1.0 platform. Pathway enrichment analysis was conducted based on the Metascape database to predict the potential mechanisms of BSZY. Additionally. Western blot was used to verify the effects of BSZY on the expression of estrogen receptor (ERα), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) and explore its protective mechanism on RSA rats. ResultsCompared with the control group, the model group exhibited significantly decreased uterine, ovarian, and embryonic wet weights (P<0.05, P<0.01), with an abortion rate of 57.18%. The ovarian tissue showed varying degrees of reduction in primordial follicles, primary follicles, mature follicles, and corpora lutea, along with a large number of atretic follicles. The endometrium was thinner, and decidual tissue exhibited cellular edema and disorganized arrangement. In contrast, compared with the model group, the BSZY groups at all doses and the ZSYT group demonstrated increased uterine, ovarian, and embryonic wet weights, along with a reduced abortion rate. The number of primordial follicles, primary follicles, mature follicles, and corpora lutea increased, while atretic follicles decreased. The endometrium thickened, and decidual tissue displayed normal cellular structure with tight arrangement. Additionally, the model group showed significantly decreased levels of E₂, P, PRL, and FSH in serum (P<0.05, P<0.01), along with a decreasing trend in LH level. In contrast, the BSZY groups at all doses exhibited significantly elevated levels of E₂, P, LH, PRL, and FSH in serum (P<0.05, P<0.01). Network pharmacology predictions suggested that BSZY may exert protective effects against abortion in rats by activating the ERα/PI3K/Akt signaling pathway. Western blot results confirmed that BSZY significantly upregulated the expression of ERα, PI3K, and p-Akt proteins (P<0.05, P<0.01). ConclusionBSZY has a protective effect on the abortion rats with kidney deficiency-corpus luteum inhibition syndrome, possibly by activating the ERα/PI3K/Akt signaling pathway to reduce ovarian apoptosis and regulate endocrine function, thereby lowering the abortion rate.
4.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
;
Drugs, Chinese Herbal/therapeutic use*
;
Hypertension/pathology*
;
Renin-Angiotensin System/drug effects*
;
Rats, Inbred SHR
;
Oxidative Stress/drug effects*
;
Male
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Rats, Inbred WKY
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Blood Pressure/drug effects*
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Myocardium/pathology*
;
Rats
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Inflammation/pathology*
6.Method for Developing Patient Decision Aid in China
Yao LU ; Qian ZHANG ; Qianji CHENG ; Jianing LIU ; Mingyao SUN ; Jinling NING ; Jiajie HUANG ; Simeng REN ; Wenzheng ZHANG ; Yajie LIU ; Xiyuan DENG ; Jinhui TIAN ; Jie LIU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1422-1431
To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids. Through a literature review of international methodological guidance for developing patient decision aids, sorting out the similarities and differences in the processes and methods for developing patient decision aids, and combining them with the topic discussion of the working group, the initial guideline was drafted. A total of 13 guidances was included, with the initial version containing 3 phases, 13 steps, and 48 points. We invited 19 multidisciplinary domain experts for forming consensus. The final version of the guideline contains 3 phases, 11 steps, and 24 points. The guideline has great potential to guide the development of patient decision aids in China and is expected to fill the methodological gap in the field. In the future, several rounds of pilot testing of the guideline based on specific decision issues will be conducted, and the guideline will be further revised and improved.
7.Treatment of Endometriosis from the Perspective of "Retention due to Deficiency Qi"
Yujuan ZHANG ; Youhua ZHU ; Jiajing ZHAO ; Yanan YANG ; Mengya BU ; Mengxin FANG ; Yuxiao HUANG
Journal of Traditional Chinese Medicine 2024;65(9):954-957
It is believed that retention due to deficient qi is an important pathogenesis of endometriosis (EMs). Deficient qi is the root of the disease, mainly manifested as spleen deficiency, while retention is the branch pathogenesis of the disease, mainly with blood stasis, complicated with constraint, phlegm, heat, toxin and other pathological factors. Therefore, it is proposed to follow the treatment principle of supplementing deficiency and unblocking stagnation, and take the methods of replenishing qi and fortifying the spleen, removing stasis and eliminating concretions. Self-made Fuzheng Huayu Formula (扶正化瘀方) is taken as the basic formula, and can be modified with the symptoms in menstrual and non-menstrual periods. Additionally, the methods of moving qi, dispelling phlegm, clearing heat, relieving toxin and others can be combined, and it is recommended to treat the root and the branch simultaneously.
8.Meta-Analysis of the Placebo Effect of Chinese Herbal Medicine in Clinical Trials of Traditional Chinese Medicine for Functional Dyspepsia
Kaiyue HUANG ; Jinke HUANG ; Fengyun WANG ; Xiangxue MA ; Xudong TANG ; Lin LYU
Journal of Traditional Chinese Medicine 2024;65(5):479-488
ObjectiveTo analyse the current implementation status of Chinese herbal medicine (CHM) placebo and systematically evaluate the placebo effect in randomised controlled trials (RCTs) of traditional Chinese medicine (TCM) for the treatment of functional dyspepsia (FD). MethodsA combination of medical subject terms and free words was used to search six databases, including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and Wanfang, for RCTs with CHM placebo group for FD published from January 31st, 1994 to September 30th, 2023. The dosage forms, composition, and methodological quality were collected and evaluated. The quality of the included articles was evaluated by Cochrane risk of bias assessment tool, and meta-analysis was performed on the CHM placebo response rate of patients with FD, and subgroup analysis and meta-regression was performed according to diagnostic criteria, efficacy criteria, duration of treatment, type of placebo, whether it contained active ingredient, and whether it evaluated placebo effects. ResultsA total of 34 publications were included involving 5046 participants, of which 2221 FD patients received CHM placebo treatment. Granules were the predominant placebo preparation, accounting for 71% (24/34); 32.35% (11/34) of the studies added real CHM to the placebo, and only 12 (35%) of the studies described appearance, odour, and taste. The placebo response rate in FD patients in the placebo group was 41% (95% CI: 0.35 to 0.47; P<0.01, I2 = 87%); there was significant difference between groups with different diagnostic criteria and different treatment durations (P<0.05 or P<0.01), but there was no significant difference between the different efficacy evaluation criteria, the different placebo preparation, the presence of a low-dose active ingredient, and the presence or absence of placebo assessment (P>0.05). ConclusionThere was a significant CHM placebo effect in patients with FD, with granules as the main preparation of placebop. Different diagnostic criteria and different treatment times may affect the response rate of patients, and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate. Clinical investigators have not paid enough attention to placebos, and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.
9.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
10.Effects of Modified Gegen Qinlian Decoction (葛根芩连汤) on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice
Lihui FANG ; Jiaqi ZHANG ; Lanshuo HU ; Xintong WANG ; Shan LIU ; Yuedan WANG ; Jinke HUANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2024;65(24):2580-2588
ObjectiveTo investigate the possible mechanism of modified Gegen Qinlian Decoction (葛根芩连汤) in treatment of ulcerative colitis (UC) from the view of intestinal mucosal epithelial barrier damage and epithelial mesenchymal transition. MethodsSixty male C57BL/6J mice were divided into blank group, model group, western medicine control group, and low-, medium-, and high-dose modified Gegen Qinlian Decoction groups, with 10 mice in each group. Except for the blank group, 3% dextran sodium sulfate (DSS) was used to induce colitis model by free drinking for 7 days, and on the first day of modelling, 6, 12, and 24 g/(kg·d) of modified Gegen Qinlian Decoction were given to the low-, medium-, and high-dose groups respectively, 5-aminosalicylic acid (5-ASA) 100 mg/(kg·d) given by gavage to western medicine control group, and 10 ml/kg distilled water were given to blank and model group by gavage, once a day for 7 days. Body mass of mice was recorded and disease activity index (DAI) scores were performed daily. The mice were anesthetized after 24h of the last administration and the colon was taken to observe the length of colon, HE staining was applied to observe the damage of colonic mucosa and score pathological states, Masson staining to detect the deposition of colonic collagen fibers, immunofluorescence to observe the distribution of F-actin in colonic mucosal epithelium, and immunohistochemistry to detect the expression of tight junction protein ZO-1, Occludin, E-cadherin and Vimentin. ResultsCompared with the blank group at the same time, the percentage of body mass of mice in the model group on day 7 of modelling significantly reduced and the DAI score was significantly increased (P<0.01); compared with the model group at the same time, the body mass of mice in the western medicine control group and all of modified Gegen Qinlian Decoction groups decreased, and the DAI scores of mice in the western medicine control group and the high-dose modified Gegen Qinlian Decoction group decreased (P<0.05 or P<0.01); compared with the same time of mice in the low-dos Gegen Qinlian Decoction group, the body mass of mice in the high-dose Gegen Qinlian Decoction group and the western medicine control group significantly elevated (P<0.05). Compared with the blank group, the length of the colon of mice in the model group was significantly shortened, the pathological score and the percentage of collagen area were significantly increased, the average fluorescence intensity of F-actin was reduced, the protein levels of ZO-1, Occludin and E-cadherin in the colon tissue decreased, and the protein level of Vimentin elevated (P<0.01). Compared with the model group, the length of colon significantly increased, patholo-gical score, collagen area percentage decreased, ZO-1, Occludin, E-cadherin protein levels increased and Vimentin levels decreased in all medicated groups; the average fluorescence intensity of F-actin increased in the western medicine control group and the middle- and high-dose Gegen Qinlian Decoction groups (P<0.05 or P<0.01). Compared with the low-dose Gegen Qinlian Decoction group, the proportion of collagen fibre area in the middle-dose Gegen Qinlian Decoction group and the western medicine control group reduced; the mean fluorescence intensity of F-actin increased in the middle-dose Gegen Qinlian Decoction group; the protein levels of ZO-1 and E-cadherin increased in the western medicine control group, and the protein levels of ZO-1 increased in the high-dose Gegen Qinlian Decoction group (P<0.05). Compared with the medium-dose Gegen Qinlian Decoction group, the protein levels of ZO-1 elevated in the high-dose Gegen Qinlian Decoction group (P<0.05). Comapred with the high-dose Gegen Qinlian Decoction group, level of E-cadherin and Vimentin protein of the western medicine control group increased (P<0.05). ConclusionModified Gegen Qinlian Decoction was able to reduce colonic inflammation and mucosal barrier damage and inhibit the process of epithelial mesenchymal transition in mice models of ulcerative colitis, which may be one of its action mechanisms .

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