1.Clinical Application and Pharmacological Mechanism of Sishenwan in Treatment of Ulcerative Colitis: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Sifeng JIA ; Yuyu DUAN ; Zixing QIAN ; Yifan CAI ; Junyi SHEN ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):261-270
Ulcerative colitis (UC), a chronic, non-specific inflammatory bowel disease with typical symptoms such as abdominal pain, diarrhea, and bloody stools, demonstrates a high relapse rate and difficulty in curing. Sishenwan, first recorded in Internal Medicine Abstract (Nei Ke Zhai Yao), are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney, and astringing the intestine and stopping diarrhea. In recent years, Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors, including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term, its side effects, high relapse rate, and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan, used alone or in combination with Western medicine or other Chinese medicine compound prescriptions, significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus, pus, and blood in stools, and persistent abdominal pain, reduce Mayo scores and the relapse rate, and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen, isopsoralen, and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level, Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future, a full-chain system covering syndrome differentiation, targeting, and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics, providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.
2.Clinical Application and Pharmacological Mechanism of Sishenwan in Treatment of Ulcerative Colitis: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Sifeng JIA ; Yuyu DUAN ; Zixing QIAN ; Yifan CAI ; Junyi SHEN ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):261-270
Ulcerative colitis (UC), a chronic, non-specific inflammatory bowel disease with typical symptoms such as abdominal pain, diarrhea, and bloody stools, demonstrates a high relapse rate and difficulty in curing. Sishenwan, first recorded in Internal Medicine Abstract (Nei Ke Zhai Yao), are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney, and astringing the intestine and stopping diarrhea. In recent years, Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors, including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term, its side effects, high relapse rate, and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan, used alone or in combination with Western medicine or other Chinese medicine compound prescriptions, significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus, pus, and blood in stools, and persistent abdominal pain, reduce Mayo scores and the relapse rate, and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen, isopsoralen, and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level, Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future, a full-chain system covering syndrome differentiation, targeting, and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics, providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.
3.Analysis of surveillance data of chronic obstructive pulmonary disease among residents aged 40 years and older in Inner Mongolia Autonomous Region
LIU Huimin ; QIAN Yonggang ; CHEN Wenjie ; HU Wei
Journal of Preventive Medicine 2025;37(8):846-851,857
Objective:
To understand the distribution characteristics of high-risk populations for chronic obstructive pulmonary disease (COPD) among residents aged ≥40 years in Inner Mongolia Autonomous Region, so as to provide a basis for comprehensive prevention and control of COPD.
Methods:
A multi-stage stratified cluster random sampling method combined with probability proportional to size sampling was used to select residents aged ≥40 years from May to December 2019 in 4 monitoring sites in Inner Mongolia Autonomous Region for a questionnaire survey. Information on demographics, current or past smoking, severe respiratory infections in childhood, exposure to occupational harmful factors, exposure to indoor polluting fuels, chronic respiratory symptoms, personal history of chronic respiratory diseases, and family history of chronic respiratory diseases was collected. The distribution characteristics of high risk populations of COPD and high-risk factors were analyzed.
Results:
A total of 2 302 people were surveyed, including 1 234 males (53.61%) and 1 068 females (46.39%). The mean age was (57.87±8.67) years. A total of 2 114 people (91.83%) were exposed to at least one high-risk factor. The exposure rate of risk factors was 87.88%. There were significant differences in the exposure rates of risk factors among residents of different genders, ages, residence, and occupations (all P<0.05). The exposure rate was higher in males than in females, higher in the 50-60 years than in the 60-<70 years, higher in rural areas than in urban areas, and higher among those engaged in agriculture, forestry, animal husbandry, fishery, and water conservancy than among national enterprise clerks, professional and technical personnel, and retirees (all P<0.05). The prevalence of chronic respiratory symptoms was 14.73%. There were significant differences in the prevalence of chronic respiratory symptoms among residents of different residence and occupations (all P<0.05). The prevalence was higher in rural areas than in urban areas, and higher among those engaged in agriculture, forestry, animal husbandry, fishery, and water conservancy than among retirees (all P<0.05). The exposure rate of personal history of chronic respiratory diseases was 10.90%. There were significant differences in the exposure rate of personal history of chronic respiratory diseases among residents of different educational levels, residence, and occupations (all P<0.05). The exposure rate was higher among those with primary education or below and junior high school education than among those with high school education or above, higher in rural areas than in urban areas, and higher among those engaged in agriculture, forestry, animal husbandry, fishery, and water conservancy than among retirees (all P<0.05). The exposure rate of family history of chronic respiratory diseases was 22.85%. The exposure rate was higher in rural areas than in urban areas (P<0.05). Among residents exposed to risk factors, the exposure rate of current or past smoking was 38.84%, the exposure rate of severe respiratory infections in childhood was 2.13%, the exposure rate of occupational harmful factors was 44.27%, and the exposure rate of indoor polluting fuels was 60.12%. The exposure rates of current or past smoking and occupational harmful factors were higher in males and rural residents (all P<0.05).
Conclusions
The proportion of high-risk populations for COPD among residents aged ≥40 years in Inner Mongolia Autonomous Region is relatively high. It is recommended to strengthen health education for male residents, rural residents, and those engaged in agriculture, forestry, animal husbandry, fishery, and water conservancy, and to adopt comprehensive prevention and control strategies to reduce the exposure level of risk factors among residents.
4.Mechanism of mitochondrial oxidative phosphorylation disorder in male infertility.
Kai MENG ; Qian LIU ; Yiding QIN ; Wenjie QIN ; Ziming ZHU ; Longlong SUN ; Mingchao JIANG ; Joseph ADU-AMANKWAAH ; Fei GAO ; Rubin TAN ; Jinxiang YUAN
Chinese Medical Journal 2025;138(4):379-388
Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male
;
Humans
;
Infertility, Male/metabolism*
;
Oxidative Phosphorylation
;
Mitochondria/metabolism*
;
Spermatogenesis/physiology*
;
Sertoli Cells/metabolism*
;
Oxidative Stress/physiology*
;
Animals
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Reactive Oxygen Species/metabolism*
5.Effect of lidocaine medicated plaster combined with pregabalin on patients with postherpetic neuralgia and the impact on serum pain mediators
Xiaodan WANG ; Wenjie LIU ; Chang SONG ; Wenxing DONG ; Qian ZHAO ; Xiaolong MA
Journal of Pharmaceutical Practice and Service 2025;43(11):572-576
Objective To investigate the effect of lidocaine medicated plaster (LMP) combined with pregabalin (PGB) on patients with postherpetic neuralgia (PHN), and the impact on serum pain mediators. Methods 108 PHN patients admitted in our hospital from January 2024 to December 2024 were selected and grouped according to the time point of receiving treatment, 54 PHN patients treated with PGB from January 2024 to June 2024 were included in the PGB group, and 54 PHN patients treated with LMP on top of the PGB group from July 2024 to December 2024 were included in the PGB+LMP group. Comparisons were made between the two groups in terms of pain score, serum pain mediator levels, dosage of PGB, and incidence of adverse reactions. Results After 4 weeks of treatment, both groups showed a decrease in Pain Rating Index scores (sensory score and affective score), Present Pain Intensity score, Visual Analog Scale score, and total score. Meanwhile, above scores of the PGB+LMP group were lower than those of the PGB group (P<0.05). After 4 weeks of treatment, the levels of substance P(SP) and neuropeptide Y (NPY) in both groups were lower than those before treatment, while serum 5-hydroxytryptamine (5-HT) levels were higher than those before treatment. Moreover, the levels of SP and NPY were lower, and 5-HT level was higher in the PGB+LMP group than in the PGB group (P<0.05). The dosages of PGB in the PGB+LMP group at T1, T, T3 and T4 were significantly lower than those in the PGB group (P<0.05). The incidence of adverse reactions was 1.85%(1/54) in the PGB+LMP group. Compared to 5.56%(3/54) in the PGB group, and the difference was not statistically significant (P>0.05). Conclusion LMP combined with PGB was effective in the treatment of patients with PHN, which could effectively alleviate pain and lower the levels of serum pain mediators, with good safety.
6.Risk factors for sarcopenia in patients with Wilson’s disease-related liver cirrhosis and their impact on clinical outcomes
Weiqi WANG ; Taohua WEI ; Nannan QIAN ; Wenming YANG ; Yulong YANG ; Yuqi SONG ; Wenjie HAO ; Yue YANG ; Hu XI ; Wei HE
Journal of Clinical Hepatology 2025;41(10):2075-2081
ObjectiveTo investigate the incidence rate of sarcopenia in patients with Wilson’s disease (WD)-related liver cirrhosis, as well as the risk factors for sarcopenia and their impact on clinical outcomes. MethodsA total of 140 patients with WD-related liver cirrhosis who were treated in The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to June 2020, and according to the third lumbar skeletal muscle mass index (L3 SMI), the patients were divided into sarcopenia group and non-sarcopenia group. Nutritional risk screening, anthropometric measurements, and blood biochemical tests were performed for the patients to identify the influencing factors for sarcopenia. The patients were followed up for 36 — 48 months, and survival status and complications were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the chi-square test and the Mann-Whitney U rank sum test were used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for sarcopenia, and univariate and multivariate Cox regression analyses were used to investigate the risk factors for the prognosis of patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve was plotted, and the Log-rank test was used for comparison between groups. ResultsAmong the 140 patients with WD-related liver cirrhosis, 53 (37.9%) developed sarcopenia, with significantly lower body mass index (BMI) and L3 SMI than the patients without sarcopenia (t=10.550 and 3.982, both P<0.001). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=2.243, 95% confidence interval [CI]: 1.196 — 4.208, P=0.012), sex (OR=0.450, 95%CI: 0.232 — 0.872, P=0.018), BMI (OR=0.126, 95%CI: 0.089 — 0.294, P<0.001), and hepatic encephalopathy (OR=8.367, 95%CI: 2.423 — 28.897, P<0.001) were the main influencing factors for sarcopenia in patients with WD-related liver cirrhosis. Compared with the non-sarcopenia group, the sarcopenia group had significantly higher mortality rate (χ2=6.158, P=0.019) and significantly higher incidence rates of infection (χ2=8.008, P=0.040), recurrent abdominal/pleural efflux (χ2=17.742, P<0.001), and hepatic encephalopathy (χ2=4.338, P=0.039). The multivariate Cox regression analysis showed that sarcopenia (hazard ratio [HR]=4.685, P=0.002) and hepatic encephalopathy (HR=19.156, P<0.001) were independent risk factors for death in patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve analysis showed a significant reduction in survival rate in the patients with sarcopenia (P=0.003). ConclusionSarcopenia is one of the manifestations of malnutrition in patients with WD-related liver cirrhosis, which increases the risk of mortality and other complications and has an adverse effect on prognosis. There is an increased risk of sarcopenia in male patients or patients with hepatic encephalopathy, a lower level of BMI or an older age.
7.Mechanism of Sanhuang Ointment in Treatment of Haemorrhoids Based on Network Pharmacology and Experimental Verification
Wenjie LI ; Qian YU ; Yi ZHENG ; Yiliu YANG ; Xinyue ZHANG ; Guangzhe LI ; Mingming YAN
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1591-1603
OBJECTIVE
To predict the core ingredients, targets and signaling pathways of Sanhuang ointment in the treatment of haemorrhoids based on network pharmacology, and preliminarily discuss the mechanism of action preliminarily by means of molecular docking and experimental verification.
METHODS
Active ingredients, targets and haemorrhoid related targets of Sanhuang ointment were obtained through literature research and database screening. Association networks were constructed and core targets were screened by Cytoscape, and gene function analysis and pathway enrichment analysis were conducted. Autodock Vina was used for molecular docking verification, and the regulatory effects of Sanhuang ointment on core targets were verified by ELISA and immunohistochemistry.
RESULTS
The 77 active ingredients and 61 potential targets of Sanhuang ointment for treating haemorrhoids were collected. KEGG showed that Sanhuang ointment could regulate calcium signaling pathways, neuroactive ligand receptor interactions, cGMP-PKG pathway, etc. Affect 6 core targets of CGRP, NK-1R, TRPV1, VEGF, IL-6 and TNF-α. Molecular docking showed that Sanhuang ointment had a good affinity with target protein, and animal experiments verified that Sanhuang ointment could inhibit the expression of IL-6, CGRP, substance P, and promote the expression of VEGF.
CONCLUSION
Sanhuang ointment may act on CGRP, NK-1R and other targets, regulate Calcium signaling pathway and PI3K-Akt pathways, and exert analgesic and anti-inflammatory effects, promoting blood circulation and removing blood stasis to treat haemorrhoids.
8.Pharmaceutical care in a patient with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation
Ling GAO ; Jing YUAN ; Wenjie QIN ; Bin ZHU ; Xianzhou LI ; Jiao QIAN
China Pharmacy 2024;35(24):3071-3075
OBJECTIVE To provide a reference for pharmaceutical care in patients with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. METHODS Clinical pharmacists participated in the treatment practice of a patient with hemorrhagic transformation after cerebral infarction complicated with atrial fibrillation. Because the patient had a hemorrhagic transformation after cerebral infarction after stent implantation and arterial thrombolysis, the clinical pharmacists recommended stopping antiplatelet drugs and giving plasma and cold precipitation; because D-dimer was significantly elevated, the clinical pharmacists recommended anticoagulant therapy with low-molecular heparin. Due to the patient’s recurrence of hemorrhagic transformation after cerebral infarction, the clinical pharmacists recommended discontinuing rivaroxaban and administering human prothrombin complex concentrate. RESULTS The physician adopted the clinical pharmacists’ recommendation. After treatment, the patient’s condition tended to improve steadily and was allowed to be discharged with medication. CONCLUSIONS The clinical pharmacists assessed the individualized risk and optimized the patient’s medication regimen by suggesting discontinuation of antiplatelet and anticoagulant drugs, carrying out pharmaceutical care such as coagulation index monitoring, determining the time and indications for restarting anticoagulation, and pharmaceutical monitoring, to ensure the safety and efficacy of the patient’s medication.
9.A pilot study on clinical application of three-dimensional morphological completion of lesioned mandibles assisted by generative adversarial networks
Ye LIANG ; Qian WANG ; Yiyi ZHANG ; Jingjing HUAN ; Jie CHEN ; Huixin WANG ; Zhuo QIU ; Peixuan LIU ; Wenjie REN ; Yujie MA ; Canhua JIANG ; Jiada LI
Chinese Journal of Stomatology 2024;59(12):1213-1220
Objective:To explore the clinical application pathway of the CT generative adversarial networks (CTGANs) algorithm in mandibular reconstruction surgery, aiming to provide a valuable reference for this procedure.Methods:A clinical exploratory study was conducted, 27 patients who visited the Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University between January 2022 and January 2024 and required mandibular reconstruction were selected. The cohort included 16 males and 11 females, with the age of (46.6±11.5) years; among them, 7 cases involved mandibular defects crossing the midline. The CTGANs generator produced 100 images, and the mean squared error (MSE) was calculated for differences between any two generated images. Preoperative cone-beam CT data from 5 patients were used to construct a labeled test database, divided into groups: normal maxilla, normal mandible, diseased mandible, and noise (each group containing 70 cross-sectional images). The CTGANs discriminator was used to evaluate the loss values for each group, and one-way ANOVA and intergroup comparisons were performed. Using the self-developed KuYe multioutcome-option-network generation system (KMG) software, the three-dimensional (3D) completion area of the mandible under cone-beam CT was defined for the 27 patients. The CTGANs algorithm was applied to obtain a reference model for the mandible. Virtual surgery was then performed, utilizing the fibular segment to reconstruct the mandible and design the surgical expectation model. The second-generation combined bone-cutting and prebent reconstruction plate positioning method was used to design and 3D print surgical guides, which were subsequently applied in mandibular reconstruction surgery for the 27 patients. Postoperative cone-beam CT was used to compare the morphology of the reconstructed mandible with the surgical expectation model and the mandibular reference model to assess the three-dimensional deviation.Results:The MSE for the CTGANs generator was 2 411.9±833.6 (95% CI: 2 388.7-2 435.1). No significant difference in loss values was found between the normal mandible and diseased mandible groups ( P>0.05), while both groups demonstrated significantly lower loss values than the maxilla and noise groups ( P<0.001). All 27 patients successfully obtained mandibular reference models and surgical expectation models. In total, 14 162 negative deviation points and 15 346 positive deviation points were observed when comparing the reconstructed mandible morphology with the surgical expectation model, with mean deviations of -1.32 mm (95% CI:-1.33- -1.31 mm) and 1.90 mm (95% CI: 1.04-1.06 mm), respectively. Conclusions:The CTGANs algorithm is capable of generating diverse mandibular reference models that reflect the natural anatomical characteristics of the mandible and closely match individual patient morphology, thereby facilitating the design of surgical expectation models. This method shows promise for application in patients with mandibular defects crossing the midline.
10.Effect of Gandou Fumu Decoction on Autophagy in Mice with Liver Fibrosis in Wilson's Disease by Regulating Expression of miR-29b-3p/ULK1
Nannan QIAN ; Wenming YANG ; Taohua WEI ; Lulu TANG ; Hailin JIANG ; Wenjie HAO ; Yulong YANG ; Shuaishuai ZHANG ; Sheng HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):17-25
ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction (GDFMD) in the development of liver fibrosis in Wilson's disease (WD). MethodFirst, 30 TX-j mice were randomly divided into the model group, high-dose, medium-dose, and low-dose GDFMD groups, and penicillamine group, with six mice in each group, and another six wild-type mice were used as the normal group. The high-dose, medium-dose, and low-dose GDFMD groups were intragastrically administered drugs of 13.92, 6.96, 3.48 g·kg-1. In the penicillamine group, 0.1 g·kg-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline, once a day, for four consecutive weeks. Samples were collected four weeks after gavage, and enzyme-linked immunosorbent assay (ELISA) was used to detect type Ⅲ procollagen peptide (PCⅢ), collagen type Ⅳ (Col Ⅳ), hyaluronic acid (HA), and laminin (LN). Hematoxylin-eosin (HE), Masson, and picric acid-Sirus red collagen (Sirus Red) staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), immunohistochemistry, and Western blot were used to observe the expressions of α-smooth muscle actin (α-SMA) and collagen type Ⅰ (Col Ⅰ), which were related to the activation of hepatic stellate cells (HSCs). The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 (ULK1) and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group, the four items of liver fibrosis (PCⅢ, Col Ⅳ, HA, and LN) in the model group were significantly abnormal (P<0.01), and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ, as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated (P<0.05, P<0.01), and miR-29b-3p expression was down-regulated (P<0.01). ULK1, p-ULK1, autophagy-related gene 13 (Atg13), p-Atg13, Beclin-1, FAK family kinase-interacting protein of 200 kDa (FIP200), activating molecule in BECN1-regulated autophagy protein 1 (AMBKA1), and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ(LC3Ⅱ/Ⅰ) were up-regulated (P<0.05, P<0.01). p62 protein expression was down-regulated (P<0.01). Compared with the model group, the four items of liver fibrosis in the high-dose, medium-dose, and low-dose GDFMD groups and the penicillamine group were significantly improve (P<0.01), and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ, as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated (P<0.05, P<0.01), and the expression of miR-29b-3p was up-regulated (P<0.01). ULK1, p-ULK1, Atg13, p-Atg13, Beclin-1, FIP200, AMBKA1, and LC3Ⅱ/Ⅰ were down-regulated (P<0.05, P<0.01), and p62 protein expression was up-regulated (P<0.01). The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured (P<0.01). ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.


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