1.Mechanism of 1,25(OH)2D3 improving liver inflammation in a rat model of nonalcoholic steatohepatitis induced by choline-deficient L-amino acid-defined diet
Haiyang ZHU ; Jingshu CUI ; Liu YANG ; Mengting ZHOU ; Jian TONG ; Hongmei HAN
Journal of Clinical Hepatology 2025;41(2):254-262
ObjectiveTo investigate the effect of 1,25(OH)2D3 on the level of peroxisome proliferator-activated receptor-γ (PPAR-γ) in the liver, the phenotype of hepatic macrophages, and liver inflammation in a rat model of nonalcoholic steatohepatitis (NASH), as well as the mechanism of 1,25(OH)2D3 improving liver inflammation. MethodsAfter 1 week of adaptive feeding, 24 specific pathogen-free Wistar rats were randomly divided into normal group [choline-supplemented L-amino acid-defined (CSAA) diet], normal+1,25(OH)2D3 group [CSAA diet+1,25(OH)2D3], model group [choline-deficient L-amino acid-defined diet (CDAA) diet], and model+1,25(OH)2D3 group [CDAA diet+1,25(OH)2D3], with 6 rats in each group. The dose of 1,25(OH)2D3 was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured, liver histopathology was observed, and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages, and ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in liver tissue, and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups, and the least significant difference t-test was used for further comparison; the Pearson method was used for correlation analysis. ResultsCompared with the normal group, the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT (P=0.019 and P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P<0.001), as well as a significant increase in the level of TNF-α (P<0.001) and a significant reduction in the level of IL-4 in liver tissue (P=0.025). The 1,25(OH)2D3 group had significant reductions in the serum levels of ALT (P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P=0.001), the level of IL-1β (P<0.001) and a significant increase in the level of M2 hepatic macrophages (P=0.017), the level of IL-10 (P=0.039), the level of IL-4 (P<0.001), the level of PPAR-γ (P=0.016). There were significant interactions between CDAA diet-induced NASH model and 1,25(OH)2D3 in serum the levels of AST and ALT (P=0.007 and P=0.008), the SAF scores of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), the level of M2 hepatic macrophages (P=0.008), the ratio of M1 and M2 of hepatic macrophages (P=0.005), the level of TNF-α (P<0.001), the level of IL-10 (P=0.038), the level of IL-4 (P<0.001) and the level of PPAR-γ (P=0.009). The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages (r=-0.415, P=0.044) and was positively correlated with M2 hepatic macrophages (r=0.435, P=0.033), IL-10 (r=0.433, P=0.035), and IL-4 (r=0.532, P=0.007). ConclusionThis study shows that 1,25(OH)2D3 improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.
2.A framework of the influencing factors of the therapeutic effect of Tuina treatment on pain based on the Delphi method
Yanji ZHOU ; Shuangshuang WANG ; Xiyou WANG ; Yi AN ; Ye GUO ; Hejing TANG ; Changxin LIU ; Duoduo LI ; Changhe YU
International Journal of Traditional Chinese Medicine 2023;45(4):391-396
Based on the resutls of literature review and interviews of experts, two rounds of Delphi surveys were conducted. The mean, importance ratio, coefficient of variation and coordination coefficient were used for assessment of survey from multiple perspectives, and finally form a framework model of factors affecting the efficacy of Tuina therapy. A total of 37 experts were selected for questionnaire surveys, the positive coefficients of experts' participatation in the first round and second round were 92.5% and 80.0%, respectively. The overall coordination coefficient in the second round is 0.68. The items were included into the consensus meeting if the importance ratio of items were equal to and more than 80%. After the expert consensus meeting, 22 items were included to form a framework model of factors affecting the efficacy of Tuina therapy, and summarized as 5 major influencing factors, including diagnostic factors, treatment factors, prognostic factors, patient factors, and doctor-patient communication. This framework can guide and help young Tuina practitioners to improve clinical efficacy. It is also clearly pointed out that the effect of Tuina for pain is not only related to disease diagnosis or manipulation, but also related to home exercise, health care, and doctor-patient communication.
3.Discussion on the factors influencing the curative effect of Tuina (Chinese massage)
Hejing TANG ; Duoduo LI ; Fuke ZANG ; Yanji ZHOU ; Junming GUO ; Jingyi MA ; Yang ZHANG ; Xiaoming YANG ; Changhe YU
International Journal of Traditional Chinese Medicine 2023;45(9):1065-1069
Tuina (Chinese massage) is an important part of Traditional Chinese Medicine. It is a simple and inexpensive technique, and has shown effectiveness for muscle and bone diseases, visceral diseases, gynecological diseases, and common diseases in children. This paper aims to analyze the factors influencing the effects of Tuina. The factors included the aspects of diagnosis, treatment, prognosis, patient factors and doctor-patient communication. During the treatment of Tuina, doctors should carry out good doctor-patient communication, properly evaluate and exam patients, and clarify diagnosis, take appropriate Tuina techniques according to the patients' constitution, health condition, and comorbidity. Only in such way, could Tuina achieve effectiveness and safety.
5.Analysis on the clinical outcomes and measurement tools of chronic back pain with integrated traditional Chinese and western medicine
Ying WAN ; Changxin LIU ; Ying ZHANG ; Qianji CHEN ; Han SHI ; Yanji ZHOU ; Yi AN ; Yanan SUN ; Changhe YU
International Journal of Traditional Chinese Medicine 2023;45(10):1313-1318
Objective:To summarize the characteristics of the participants (P), interventions (I), control measures (C), outcomes (O) and study design (S) of the clinical study of chronic back pain (CBP) in recent years; To further systematically organize the outcomes of the clinical study of CBP and their corresponding measurement tools.Methods:Clinical studies of CBP were retrieved from various databases including CNKI, Wanfang Database, VIP, SinoMed, Cochrane Library, Pubmed, Embase, Web of Science, etc. The search period was from January 1, 2015 to December 31, 2019. The retrieved literature was extracted and analyzed.The retrieved literatures will be extracted and analyzed. The retrieved literature was subjected to data extraction and analysis, and the quality of outcome indicators was evaluated according to 6 items. The Newcastle-Ottawa Scale ( NOS ) was used to evaluate the quality of cohort studies and case-control studies. Analyze the relationship between outcome indicators and interventions.Results:A total of 3 028 articles were finally included after examination and screening. The top 7 diagnoses of CBP were low back pain, lumbar disc protrusion, lumbar vertebral stenosis, lumbar vertebral slip, lumbar disc degression, non-specific chronic low back pain and post-operative pain syndrome. The top 7 intervention measures in clinical studies of CBP were surgery, acupuncture, physiotherapy, Tuina, exercise therapy, Western medicine painkillers and oral Chinese patent medicines. A total of 47 outcomes and 348 outcome measurement tools were reported in the literature included.Conclusion:In the clinical study of CBP in the recent years, there are problems such as incomplete and low quality of reporting, a wide variety of outcome measurement tools and lack of uniform reporting standards. The characteristics of patients determine the common characteristics of outcomes selection and it is also necessary to consider the specific outcomes related to interventions.
6.A Clinical Study on the Intervention of a Comprehensive Program of Traditional Chinese Medicine on Degenerative Lumbar Spinal Stenosis
Yanji ZHOU ; Yi AN ; Yuan LEI ; Yang ZHANG ; Xiaoming YANG ; Hui SHAO ; Naiwen ZHANG ; Zhiwen WENG ; Changxin LIU ; Xiyou WANG ; Changhe YU
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(6):2188-2195
Objective To preliminarily verify the effectiveness and safety of bloodletting combined with drug bamboo cups in intervention of degenerative lumbar spinal stenosis,and to explore the prognostic factors that affect the efficacy of TCM regimens in the treatment of DLSS.Methods 64 consecutive patients with degenerative lumbar spinal stenosis were enrolled.Bloodletting combined with drug bamboo cup intervention was used.Acupoints were selected and treated with the same length of the governor channel of the lumbar spine,the first and second side lines of the bladder meridian and Ashi point,weekly 2 times,8 times per course,2 consecutive courses of treatment.Before treatment,after treatment,and 1 month follow-up,the changes of the patient's lumbar spinal stenosis specific scale(SSM),modified Oswestry dysfunction index(ODI),and 12 health survey summary scores(SF-12)were observed.Using SSM symptom or function score≥0.5,the criteria for grouping were first single-factor analysis,and then logistic regression was used to analyze the prognostic factors of the treatment.Results After 2 courses of treatment,the patient's SSM symptom score(2.25±0.56),SSM function score(2.06±0.67),ODI index(15.49±8.72),and SF-12 physiological score(36.31±7.35)were more significant than before treatment Improved,the difference was statistically significant(P<0.05),the SF-12 psychological score(49.70±9.47),the difference was not statistically significant compared with before treatment(P>0.05);the patient's SSM symptom score(2.22±0.54)was followed up for one month,SSM function score(2.09±0.66),ODI index(15.53±8.23),SF-12 physiological score(36.55±7.25),SF-12 psychological score(50.62±9.17),which are significantly better than before treatment,and the difference is statistically significant(P<0.05),the difference was not statistically significant(P>0.05)after 2 courses of treatment.The univariate logistic regression analysis of each influencing factor showed that:BMI,baseline symptom dimension,baseline functional dimension,foraminal stenosis,lateral recess stenosis,and two-stage stenosis had statistically significant differences between the effective and ineffective groups(P<0.05).Conclusion Bloodletting combined with drug bamboo cups has a certain clinical effect on degenerative lumbar spinal stenosis.
7.Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation
Jia-Yi DOU ; Yu-Chen JIANG ; Zhong-He HU ; Kun-Chen YAO ; Ming-Hui YUAN ; Xiao-Xue BAO ; Mei-Jie ZHOU ; Yue LIU ; Zhao-Xu LI ; Li-Hua LIAN ; Ji-Xing NAN ; Yan-Ling WU
Biomolecules & Therapeutics 2022;30(3):246-256
The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.
8.A diagnosis of atypical autoimmune hepatitis: A case report
Journal of Clinical Hepatology 2022;38(11):2565-2567
9.Mechanism study of Shaoyao-Gancao Decoction treating tension-type headache based on network pharmacology
Ying ZHOU ; Fanxing MENG ; Xinyang ZHANG ; Qingyuan ZHOU ; Yanji ZHOU ; Xuelei CHU ; Fengli WANG
International Journal of Traditional Chinese Medicine 2021;43(7):680-689
Objective:Based on network pharmacology to study the mechanism of Shaoyao-Gancao Decoction in treating tension-type headache. Methods:Searched for the active ingredients and potential targets of Shaoyao-Gancao Decoction from TCMSP database, and adopted the targets of tension-type headache from GeneCards, DisGeNET, Drugbank and OMIM databases. Then obtained all the intersections of Shaoyao-Gancao Decoction and tension-type headache, and uploaded them to the STRING databases to construct a PPI network and conduct topological properties analysis. Finally, established a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease by Cytoscape 3.6.1 software. To perform the GO function enrichment analysis and KEGG analysis on the core targets. Results:There were 51 intersections of Shaoyao-Gancao Decoction and tension-type headache. The topological properties analysis suggested that CASP3, JUN, HSP90AA1, MAPK1, STAT3, CCND1, ESR1, RELA, PTGS2, MAPK14 may be the potential targets for the treatment of tension-type headache in Shaoyao-Gancao Decoction. Gene ontology enrichment analysis showed 876 biological processes, 101 molecular functions and 62 cellular components. KEGG pathway enrichment analysis showed 25 related signaling pathways, including TNF signaling pathway, serotonergic synapse, NOD-like receptor signaling pathway, Dopaminergic synapse and Sphingolipid signaling pathway. Conclusion:The treatment of tension-type headache by Shaoyao-Gancao Decoction verified the characteristics of multi-component, multi-target and multi-pathway, which provided reference for the clinical medication.
10.Overview of systematic reviews/meta analyses on traditional exercise for the improvement of cardiopulmonary function
Yanji ZHOU ; Changxin LIU ; Meiling CAI ; Ying ZHOU ; Duoduo LI ; Changhe YU
International Journal of Traditional Chinese Medicine 2021;43(12):1272-1281
Objective:To evaluate the methodological quality and evidence quality of outcome of the systematic reviews/meta analyses on traditional exercise for the improvement of cardiopulmonary function.Methods:By searching for PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM databases in Chinese or English, the Systematic Reviews/meta analysis of traditional exercises for improving cardiopulmonary function was conducted. The retrieval time was March 8th, 2020. The AMSTAR 2 scale was used to evaluate the methodological quality of the systematic review/meta-analysis that met the inclusion criteria. Since the included studies cannot reflect the overall effect of traditional exercises on improving cardiopulmonary function, and the methodological quality of systematic reviews was generally low, a secondary analysis of the RCT studies included in the systematic reviews was conducted. The methodological quality evaluation of the original RCT study adopted the Cochrane Reviewers’ Handbook Version 5.0.0 bias risk assessment method (Risk of Bias, ROB), and applied the Revman 5.3 software to merge the original RCT data. The GRADE system was used for evidence evaluation.Results:A total of 32 systematic reviews/meta analysis were included, and the AMSTAR2 scale indicated that only one of the 32 systematic reviews/meta included was of high-quality, 1 was of low-quality, and the others were of extremely low quality. A total of 57 RCTs were included in the 32 systematic reviews for bias risk assessment and data consolidation. GRADE evidence quality evaluation showed that 14 evidences were of medium quality, 26 evidences were of low quality, and 5 evidences were of extremely low quality.Conclusions:Traditional exercises can improve cardiopulmonary function, but with low evidence quality. Thus, clinicians should make clinical decisions based on conditions.

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