1.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.
2.Preventive and intervention effect of bioactive compounds on gestational diabetes mellitus based on endoplasmic reticulum stress pathway
Nannan HU ; Chengao ZHAO ; Qin GAO ; Qingfeng ZHAI
Chinese Journal of Pathophysiology 2024;40(7):1316-1323
The global prevalence of gestational diabetes mellitus(GDM)is approximately 13.4%and is ex-pected to increase annually.However,the precise mechanism behind GDM remains to be established.Increasing evi-dence suggests that insulin resistance(IR)and β-cell impairment are key factors in the pathogenesis of GDM.Endoplas-mic reticulum stress(ERS)is characterized by the activation of the unfolded protein response through three key endoplas-mic reticulum transmembrane proteins:protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring enzyme 1α(IRE1α),and activating transcription factor 6(ATF6).ERS is implicated in IR in adipose tissue,liver,skeletal muscle,and placenta,and also plays a crucial role in β-cell impairment through processes such as apopto-sis,pyroptosis,and autophagy.Therefore,targeting ERS could be a potential therapeutic approach for the prevention and treatment of GDM.This review explores the potential role of ERS in IR and β-cell dysfunction in GDM,and provides evi-dence for the preventive and intervention effects of bioactive compounds on GDM based on the ERS pathway.This aims to enhance our understanding of the molecular pathological basis of GDM and offer new strategies for its prevention and treat-ment.
3.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.
4.Methodology for the Development of Clinical Practice Guideline for Chinese Patent Medicine(Part 1): Development Status and Characteristics
Ning LIANG ; Lijiao YAN ; Yujing ZHANG ; Fuqiang ZHANG ; Ziteng HU ; Yaxin CHEN ; Huizhen LI ; Haili ZHANG ; Zhao CHEN ; Yin JIANG ; Bin LIU ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(1):44-49
The irrational use of Chinese patent medicines (CPM) is becoming more and more prominent, which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines, and promote its development, this paper introduced the concept of CPM guidelines, summarized the characteristics of the two development modes, namely “taking CPM as the key” and “taking disease/syndrome as the key”, and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems, three suggestions have been put forward to optimize the quality of CPM guidelines, which were clarifying the target users and scope of CPM guidelines, establishing an open and transparent mechanism of the personnel involvement and process steps, and formulating implementable and operable recommendations for the use of CPM.
5.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine: 2.Establishment of Guideline Working Group and Management of Conflict of Interests
Yaxin CHEN ; Ning LIANG ; Lijiao YAN ; Ziteng HU ; Yujing ZHANG ; Fuqiang ZHANG ; Haili ZHANG ; Huizhen LI ; Yijiu YANG ; Jing GUO ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(1):50-54
This paper summarized the key points and methods in terms of the establishment of the guideline working group and the management of conflict of interests, trying to provide reference for the development of clinical practice guidelines for Chinese patent medicine (CPM). The establishment of the working group is the first important step for developing CPM guidelines. Considering the characteristics of the clinical practice guidelines for CPM, this study suggests that the three key elements of ‘multidisciplinarity’, ‘clinical relevance’ and ‘geographical representativeness’ should be put focus on when forming the working group. The guideline advisory committee, clinical expert group, evidence systematic evaluation group, secretary group and the external review group should be established. All group members should clarify the conflict of interest, and the process and management method of the conflict of interest should be clearly reported.
6.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine(Part 3): Identification of Clinical Questions
Ziteng HU ; Ning LIANG ; Lijiao YAN ; Yujing ZHANG ; Yaxin CHEN ; Fuqiang ZHANG ; Zhao CHEN ; Yin JIANG ; Cuicui CHENG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(1):55-59
The identification of clinical questions for clinical practice guidelines of Chinese patent medicine (CPM) is important for subsequent evidence retrieval, evaluation of evidence quality, formation of recommendations. This paper described a methodological proposal for the identification of clinical questions for CPM guidelines to highlight the characteristics of Chinese patent medicine and reflect its effect in specific stage of the disease. Considering four aspects, namely, the drug of Chinese patent medicine (D), the specific disease stage (S), comparison (C), and specific outcome (O), DSCO framework has been proposed to formulate the clinical questions. Multi-source information through scientific research, policy or standard documents, and clinical data are suggested for collecting clinical questions, and clear selection criteria should be set to finalize the clinical questions to be addressed by the guideline. In addition, the above process needs to be transparently and publicly reported in order to ensure the clarity and completeness of the guidelines.
7.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine(Part 4): Evidence Retrieval and Evaluation
Fuqiang ZHANG ; Lijiao YAN ; Ziteng HU ; Yujing ZHANG ; Yaxin CHEN ; Xingyu ZONG ; Zhao CHEN ; Weili WANG ; He LI ; Ning LIANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(1):60-65
The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine, there is certain differences in terms of evidence composition, retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature, and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine, the corresponding evaluation tools have been recommended, and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally, a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed, which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.
8.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine(Part 5): Retrieval and Synthesis of Key Information on Rational Drug Use
Ziteng HU ; Ning LIANG ; Lijiao YAN ; Yujing ZHANG ; Fuqiang ZHANG ; Yaxin CHEN ; Bin LIU ; Qianzi CHE ; Yixiang LI ; Jing GUO ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(2):167-171
Recommendations for Chinese patent medicine (CPM) based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study, we discussed in detail of the key information on the rational use of CPM in five aspects, which are dosage, drug discontinuation, drug-drug and drug-food interactions, safety and economy. Following the process of multi-source search, synthesis and prioritization, it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions, policy documents, literature, and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally, methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.
9.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine (Part 6): Formation and Presentation of Recommendations
Yujing ZHANG ; Ning LIANG ; Lijiao YAN ; Ziteng HU ; Yaxin CHEN ; Fuqiang ZHANG ; Qianzi CHE ; Zhao CHEN ; Yuqi LIU ; Dingyi WANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(2):172-177
Recommendation formation is a key component of clinical practice guidelines for Chinese patent medicine (CPM), and should encompass the determination of the strength and direction of the recommendation, the rationale for the recommendation, and the methodology for implementing the recommendation. Recommendations can be formed through formal consensus and informal consensus. The strength and direction of recommendations for CPM guidelines should be determined by considering the quality of evidence for CPMs, the priority of the clinical questions, the pros and cons of efficacy and adverse effects, patient acceptance, the feasibility of the recommendation and the availability of resources, social fairness, economic benefits, and other influencing factors. In order to better guide guideline developers to consider these factors more rationally, this article provideed a detailed explanation of each factor in the context of the characteristics of TCM.
10.Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine (Part 7): Introduction and Interpretation of the Guideline Reporting Checklist
Yujing ZHANG ; Fuqiang ZHANG ; Lijiao YAN ; Ziteng HU ; Yaxin CHEN ; Haili ZHANG ; Huizhen LI ; Qianzi CHE ; Ning LIANG ; Nannan SHI ; Yanping WANG
Journal of Traditional Chinese Medicine 2024;65(2):178-184
The systematic and comprehensive introduction and interpretation of the Reporting Checklist of Clinical Practice Guidelines for Chinese Patent Medicines V1.0 is conducive to the presentation of high-quality clinical practice guidelines for Chinese patent medicines (CPMs), thus improving their dissemination and use. The Reporting Checklist of Clinical Practice Guidelines for Chinese Patent Medicines V1.0 specifies the requirements for clear, complete and transparent reporting of the whole process of developing CPMs guidelines, containing 4 domains, 17 topics and 43 items, and involving the basic information, recommendations and methods of guideline development. Especially, it details the items related to the rules and regulations of the use of CPMs in the recommendations, which is helpful for improving the completeness, scientificity and practicality of the reporting of CPMs guideline.

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