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ObjectiveTo investigate the effect of NOD-like receptor family pyrin domain containing 3 (NLRP3) knockdown on a mouse model of nonalcoholic steatohepatitis (NASH) induced by high-fat high-carbohydrate (HFHC) diet. MethodsA total of 44 mice were randomly divided into normal diet group (CON group) with 20 mice and HFHC group with 24 mice. At the end of week 14 of modeling, 4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus (AAV) by tail vein injection, and NLRP3 knockdown was verified after 4 weeks. After NLRP3 knockdown was verified at the end of week 18, the remaining 40 mice were given a single tail vein injection of AAV, and then they were divided into CON+NLRP3 knockdown negative control group (CON+NLRP3-NC group), CON+NLRP3 knockdown group (CON+NLRP3-KD group), HFHC+NLRP3-NC group, and HFHC+NLRP3-KD group, with 10 mice in each group. At the end of week 24, the activation of NLRP3 inflammasome was observed; related indicators were measured, including body weight, liver weight, liver index, and glucose metabolism (fasting blood glucose, fasting insulin, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] index); the indicators of liver lipid content (liver triglyceride [TG] and oil red O staining), liver inflammation (serum alanine aminotransferase [ALT] activity, HE staining, and inflammation-related genes), and liver fibrosis (Sirius Red staining and fibrosis-related genes) were measured. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the CON+NLRP3-NC group based on the results of Western Blot, the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3, pro-Caspase1, Caspase1, ASC, and IL-1β, while the HFHC+NLRP3-KD group had significant reductions in these levels (all P<0.05). The HFHC+NLRP3-NC group showed varying degrees of increase in body weight, liver weight, liver index, and glucose metabolism indicators, while the HFHC+NLRP3-KD group showed significant improvements in these indicators (all P<0.05). As for hepatic fat deposition, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had a significant increase in liver TG, with a large number of red lipid droplets shown by oil red O staining, and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver (all P<0.01). In terms of liver inflammation, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had significant increases in serum ALT, NAFLD activity score, and inflammation-related genes, while the HFHC+NLRP3-KD group had significant reductions in these indicators (all P<0.01). As for liver fibrosis, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes, and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes (all P<0.05) and a tendency of reduction in collagen fiber area (P>0.05). ConclusionNLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.
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Objective:To evaluate the use of serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery for gastrointestinal mesenchymal tumors at difficult sites of the stomach.Methods:From Jul 2019 to Apr 2021, 18 gastric mesenchymal tumor patients undergoing serosa muscular layers circumferential incision combined with mucosal layer cutting and closure by laparoscopic or robotic surgery at the Department of Surgery, the Fourth Hospital of Hebei Medical University were retrospectively analyzed.Results:All 18 patients had successful surgery, including 7 cases of robotic surgery, 11 cases of laparoscopic surgery, and there was no conversion to open surgery. Tumors were at the gastric in cardia, 8 cases at the gastric body and lesser curvature in 4 cases, and at the gastric antrum in 6 cases, respectively. Eleven cases were of endogenous and 7 cases were of dumbbell type. The average operation time was (99±29) min, the intraoperative blood loss was (10±5) ml, the first time taking food per mouth was (2.0±1.0) d, and the postoperative hospital stay was (4.9 ± 1.2) d. Pathology showed gastrointestinal stromal tumor in 11 cases, leiomyoma in 5 cases and schwannoma in 2 cases. All were with negative margins. The average tumor diameter was (4.7±1.4) cm. The median follow-up time was 16.5 months, and there was no sign of tumor recurrence or metastasis.Conclusion:The serosa muscular layers circumferential incision combined with mucosal layer cutting and closure technique in laparoscopic or robotic surgery is a safe and feasible procedure for treating gastrointestinal mesenchymal tumor at difficult sites of the stomach.
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Objective:To explore the clinico-pathological characteristics and risk factors affecting prognosis in elderly patients with gastric cancer.Methods:A retrospective study was used to retrospectively analyze 2386 patients with gastric cancer undergoing radical surgery in Surgery Department of the Fourth Hospital of Hebei Medical University from 1 January 2012 to 1 January 2015.Patients aged 70 years and older were screened so as to analyze clinical characteristics and influencing factors for the prognosis.Results:A total of 2386 patients with gastric cancer were divided into the elderly group aged 70 years and older(342 of 2386 cases, 14.3%). There were statistically significant differences between the two groups in gender, number of concomitant diseases, NRS2002 score, PG-SGA score, tumor location, tumor diameter, histological type, Borrmann classification, tumor invasion depth staging(pT), lymph node metastasis staging(pN), the anatomic extent of tumor staging(TNM, pTNM), and Lauren classifications( P<0.05). The 981 of 2386 cases(41.4%)had postoperative complications, accompanied by 413 cases(17.3%)of surgery-related complications and 568 cases(24.0%)of non-surgery-related complications.A multivariate logistic analysis showed that the number of preoperative co-existing diseases ≥ 2 was an independent influencing factor for postoperative complications in elderly gastric cancer patients( HR=4.478, 95% CI: 1.121-7.918, P=0.006). The 5-year OS and DSS was 21.10% and 62.73% in the ≥70 years gastric cancer group, and was 54.1% and 70.0% in the <70 years gastric cancer group, respectively.The difference in the 5-year OS between the two groups was statistically significant( P<0.05), while the difference in the 5-year DSS between the two groups was not statistically significant( P>0.05). Multivariate analysis by the Cox proportional hazard model showed that the independent risk factors for the prognosis of elderly patients with gastric cancer included the low-undifferentiated histological type of the tumor( P=0.004), the depth of tumor invasion pT stage of pT4a-pT4b( P=0.007), lymph node metastasis( P=0.034), tumor pTNM stage ⅢA-ⅢC( P=0.002)and vascular tumor thrombus( P=0.034). Conclusions:Elderly patients with gastric cancer have many preoperative co-existing diseases, which increases the risk of postoperative non-surgical complications.Therefore, we should focus on the peri-operative management of their comorbid diseases so as to improve the safety and efficacy of surgery.The advanced age is not the independent risk factors for the prognosis.
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Nonalcoholic fatty liver disease (NAFLD) is a typical chronic liver disease closely associated with gut dysbiosis, and dietary factor may be the most important driving factor affecting the composition and function of intestinal bacteria. Based on the concept of enterotype, this article summarizes the effect of diet on enterotype-related gut microbiota in NAFLD, including Firmicutes/Bacteroidetes ratio, Bacteroides, Prevotella, Ruminococcus, Proteobacteria, Actinobacteria, and other bacteria. It is pointed out that improving diet to regulate gut microbiota is one of the important strategies for the prevention and treatment of NAFLD and has a good prospect, which needs further mechanism and clinical research.
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Background & AimsThe abnormal liver function and even liver failure related death were reported in the COVID-19 patients, but less of studies focus on the dynamic liver function changes. We analysed the liver function indexes of COVID-19 patients to explore the characteristics of liver function changes in patients with different severity. MethodsThis study included 54 moderate, 50 severe, and 31 death nucleic acid-confirmed COVID-19 patients hospitalized at the central hospital of Wuhan, China. Epidemiological histories, clinical features, imaging materials, medications and especially major liver function laboratory tests were collected for analysis. ResultsThe clinical symptoms did not present any significant difference in the patients at admission, but the older male patients had pronounced mortality risk. The normal ratio of ALT, TB, and DBIL of moderate patients was 96.3%, 94.44%, and 98.15% separately at the first test, but 59.26% of patients showed declined ALB levels. The normal ratio of all liver function indexes declined after admission, but most abnormalities were mild (1-2 times of upper limit unit) and went back normal before discharge. In severe patients, the normal ratio of ALB dropped down to 30.61% at admission along with the dramatic impaired normal ratio of bilirubin at the second test. The severe patients liver function dysfunction was worse than the moderate patients but without a significant difference. The dead patients showed a significantly higher level of DBIL, AST, GGT and CRP than other groups patients in the final test, along with the hypoalbuminemia. What is worse, 16.13% of non-survivors were diagnosed with liver failure. No medication was found to be related to ALT, AST, and GGT abnormality in our study. ConclusionIn moderate and severe patients, liver dysfunction was mild. Patients widely presented lower level of ALB. The higher level of bilirubin, AST, and GGT was likely to indicate the worse outcome. Dynamic monitoring of liver function indexes could be considered and liver failure related death should be noticed and prevented in the early stage.
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Gut microecology plays an important role in the pathogenesis of nonalcoholic fatty liver disease. With reference to the research on traditional Chinese medicine in regulating gut microecology and treating nonalcoholic fatty liver disease, this article systematically elaborates on the association of nonalcoholic fatty liver disease with intestinal flora, gut bacterial metabolites, and gut barrier function and points out that the regulation of gut microecology and the maintenance of intestinal homeostasis are important measures for traditional Chinese medicine in the treatment of nonalcoholic fatty liver disease.
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Nonalcoholic fatty liver disease (NAFLD) and hypertension are both important components of metabolic syndrome, and there is a strong association between these two diseases. This article analyzes the association between NAFLD and hypertension based on clinical data and describes the common pathogeneses of the two diseases, among which insulin resistance, gut microbiota, renin-angiotensin-aldosterone system play an important role in the pathogenesis of these two diseases. In addition, this article briefly summarizes the application of renin-angiotensin-aldosterone system inhibitors and diuretics in the treatment of NAFLD, which provides a reference for further clarifying the association between these two diseases, understanding the mechanism of interaction between the two diseases, and exploring the treatment methods for NAFLD with hypertension.
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At present, nonalcoholic fatty liver fibrosis is one of the highlights of the research on nonalcoholic fatty liver disease (NAFLD), and there is an urgent need for exploring its pathogenesis and treatment drugs in clinical practice. Animal model is an important tool for basic research, and the mouse model becomes the most widely used animal model of nonalcoholic fatty liver fibrosis because of susceptibility, low costs, and genomes highly homologous to those of the human being. This article reviews the methods for establishing a mouse model of nonalcoholic fatty liver fibrosis, including nutritional factor, gene knockout or mutation, and induction with various factors, as well as the features of these models, in order to provide a reference for the selection of model tools in the basic research on this disease.
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Stearoyl-CoA desaturase-1 (SCD-1) is the key rate-limiting enzyme to catalyze the conversion of saturated fatty acids to monounsaturated fatty acids. The monounsaturated fatty acids in the catalytic products are important substrates for the formation of triglycerides, cholesteryl esters and phospholipids. Therefore, SCD-1 plays an important regulatory role in the metabolic process of fat. Currently, obesity and non-alcoholic fatty liver disease are widely prevalent worldwide. SCD-1 has gradually become a potential drug target for the treatment of such diseases due to its important regulatory role in fat metabolism. We summarize the recent research progress of SCD-1 in obesity and non-alcoholic fatty liver disease and the developmental status of SCD-1 inhibitors in order to provide new ideas and references related to disease and target drugs.
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Based on recent studies which have shown that gut microbiota plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the article elaborates on the relationship of NAFLD with intestinal endotoxemia, short-chain fatty acids, bile acid metabolism, and endogenous ethanol. By illustrating the author′s research progress in the relationship between traditional Chinese medicine (TCM) regulation of gut microbiota and NAFLD treatment, the article proposes that this approach is not only a clinical practice of TCM in the modern era, it may also become a new strategy in the treatment of NAFLD.
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The compound of active ingredients of traditional Chinese medicine (TCM),whose material base is relatively clear,adheres to the concept and advantages of formula compatibility of TCM.Thus,it is an important approach to modern TCMresearch.The significance of research on compound of TCMcomponents/ingredients,as well as the research ideas,is sketched out,and the current research on compound of TCMcomponents for the prevention and treatment of liver diseases is reviewed.The research strategies for TCMcomposition/compound for the prevention and treatment of liver diseases are elucidated from the following two aspects:exploring the compound of TCM components based on clinical TCM compound and studying the composition aiming at the effective components or ingredients of TCM that have been known;it is pointed out that the compatibility of effective TCM components,which provides the method and technology system for innovative drug research,is an innovative research model for inheriting and developing the TCMtheory and is one of the important approaches to modern TCM research.
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This study was aimed to explore five Chinese medicine components or ingredients from Qu-Shi Hua-Y u Decoction (QSHYD) with uniform design method and screen ingredients assembling of Chinese medicine BZL pre-scription in order to verify its therapeutic effect on experimental fatty liver rats. High-fat diet was used in the estab-lishment of fatty liver rat models. Five effective ingredients (i.e., chlorogenic acid, geniposide, curcumin, polydatin and polysaccharide of Atractylodes macrocephala Koidz) of QSHYD were used as study subjects. Uniform design was applied in the grouping design. The intragastric administration was given for four weeks. The screening index was the content of liver triglyceride (TG). The ingredients assembling of Chinese medicine BZL prescription was screened through uniform design and regression analysis. The same fatty liver animal model was used in the comparison be-tween QSHYD and rosiglitazone. The TG content in liver tissues of rats and serum ALT activity were detected. The pathological changes of liver tissues were observed (HE stain and oil red O stain) with Ridit analysis to verify its therapeutic effect. The results showed that through screening, the regression equation was Y = 15.083X1 + 5.321X2- 5.186X3 - 16.157X4 + 9.35X5 + 17.667X3X4 - 8.422X1X2 - 6.617X3X5 + 16.571 (X1: chlorogenic acid, X2:polydatin, X3: polysaccharide of Atractylodes macrocephala Koidz, X4: geniposide, X5: curcumin). According to this equation, the best TG reducing effect occurred when the chlorogenic acid (X1), polysaccharide of Atractylodes macrocephala Koidz (X3), and geniposide (X4) were the maximum dosage. It showed that the best combination in inhibiting TG content in liver tissues was X3, X4 and X1 (i.e. BLZ prescription). Among fatty liver rat mod-els induced with same high-fat diet, the screened Chinese medicine ingredient BZL prescription can obviously reduce its TG content in liver tissues and serum ALT activity ( P < 0 . 01 ) . It obviously improved the fatty degen-eration of rat's liver. It was concluded that ingredients assembling of Chinese medicine BZL prescription screened through uniform design can obviously prevent and treat fat deposition and injury of the liver among rat models induced by high-fat diet .
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Systems biology, which includes genomics, proteomics, transcriptomics and metabolomics, is an integration of system theory and biology. It studies the life phenomena with thinking method of systems theory. And it provides an important methodological basis and technical conditions for recognizing syndrome of traditional Chinese medicine (TCM) and mechanism of therapeutic effect from multiple disciplines and perspectives. Systems biology is similar to the core idea of TCM system and holism concept. Therefore, systems biology can be used as a platform and pivot of non-alcoholic fatty liver disease (NAFLD) in modern TCM study. Systems biology will accelerate the modernization research of TCM in the prevention and treatment of NAFLD. It will also provide new ideas and methods for TCM study on NAFLD.
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This article was aimed to expound current complexity and diversity about Chinese medicine dose-ef-fect relationship . It demonstrated that the study on Chinese medicine dose-effect relationship should be based on clinical effect as its foundation , and be guided by the traditional Chinese medicine ( TCM ) theories . Differ-ent modern science and technology means and methods should be applied for the multi-perspective , multi-lev-el and multidisciplinary systematic study of the Chinese medicine dose-effect relationship .
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<p><b>OBJECTIVE</b>To study the effect of gypenosides on DMN-induced liver fibrosis in rats.</p><p><b>METHOD</b>A rat liver fibrosis model was established by injecting DMN intraperitoneally. Four weeks later, model rats were randomly devided into three groups: the model group, the gypenosides treated group (200 mg x kg(-1)) and the colchicine treated group (0.1 mg x kg(-1)), with 10 specimens for each group. After a 2-week treatment, following parameters were observed: (1) last body weight, weight ratio between liver and spleen; (2) content of liver hydroxyproline (Hyp); (3) activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), content of albumin (Alb) and total bilirubin( TBiL) in serum; (4) liver pathology (Sirius red staining and HE staining); (5) activity of liver superoxide dismutase (SOD), glutathione reduced (GSH), glutathione peroxidase (GSH-Px) and content of liver maleic dialdehyde (MDA).</p><p><b>RESULT</b>There were classic liver cirrhosis pathological changes in model groups. Compared with the normal group, liver Hyp content, activity of serum ATL, AST, gamma-GT and content of serum TBiL, MDA of model groups significantly increased; content of serum Alb and liver GSH, activity of liver SOD and GSH-Px decreased significantly in model groups. In comparison with the model group, liver cirrhosis remarkable improved in the gypenosides group, content of liver Hyp reduced significantly (P < 0.01), which was equal to the colchicine group. Compared with the model group, liver function parameters improved markedly in the gypenosides group; liver SOD and GSH-Px activities significantly increased; MDA content reduced significantly (P < 0.05).</p><p><b>CONCLUSION</b>Gypenosides shows an effect in treating DMN-induced liver fibrosis in rats.</p>
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Animais , Masculino , Ratos , Peso Corporal , Dimetilnitrosamina , Glutationa , Metabolismo , Glutationa Peroxidase , Metabolismo , Gynostemma , Hidroxiprolina , Metabolismo , Fígado , Metabolismo , Patologia , Cirrose Hepática , Tratamento Farmacológico , Metabolismo , Patologia , Malondialdeído , Metabolismo , Tamanho do Órgão , Extratos Vegetais , Farmacologia , Usos Terapêuticos , Ratos WistarRESUMO
To explore the diagnostic value of 75 commonly used clinical laboratory markers for differentiation of traditional Chinese medicine syndromes such as liver and gallbladder damp-heat and liver depression and spleen deficiency in patients with chronic hepatitis B.
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Objective: To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on collagen metabolism of hepatic tissues in rats with carbon tetrachloride (CCl(4))-induced liver fibrosis. Methods: Liver fibrosis was induced in rats by intraperitoneal injection of 50% CCl(4)-olive oil solution at a dose of 1 mL/kg body weight, twice per week for 9 consecutive weeks. Six rats were sacrificed for dynamic observation at the end of the 3rd and 6th week respectively, and the other rats were divided into 9-week untreated group and Yiguanjian Decoction group which was given Yiguanjian Decoction intragastrically in the subsequent 3-week modeling period. Another 6 rats were used as normal group. Rats in the normal group and 9-week untreated group were treated with distilled water. At the end of the 9th week, all rats were sacrificed, and their blood serum and liver tissue were collected for measuring hepatic histology and expressions of α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-13, MMP-14, collagen type I (Col I), and activities of MMP-2 and -9. Results: Compared with the normal group, collagen fiber deposition, expressions of α-SMA, Col I, TIMP-1, TIMP-2, MMP-13 and MMP-14 and activities of MMP-2 and -9 in the liver tissues gradually increased in the untreated group (P<0.05, P<0.01). These changes were significantly suppressed by Yiguanjian Decoction. Conclusion: Yiguanjian Decoction exerts inhibition on formation of CCl(4)-induced cirrhosis in rats. The therapeutic mechanism may be related to inhibiting hepatic stellate cell activation, collagen secretion, and promoting collagen fiber degradation.
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To evaluate the effects of Xiayuxue Decoction, a compound traditional Chinese medicine, on liver angiogenesis in rats with carbon tetrachloride (CCl(4))-induced liver fibrosis.
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To investigate the effects and characteristics of Fuzheng Huayu recipe, a compound Chinese herbal medicine, and its decomposed therapies against hepatocyte apoptosis in mice with hepatic injury.
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To investigate the herbal medicines which play a main role in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability and protect alcohol-induced liver injury and intestine damage, and to explore the analysis method for the material base of pharmacological effects of the Chinese herbal compound.