1.Immunomodulatory effect of short-chain fatty acids in hepatic encephalopathy and its potential diagnostic value
Weiyu CHEN ; Dewen MAO ; Han WANG ; Yang DU ; Wenqian FENG ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(5):954-962
Hepatic encephalopathy (HE) is a common complication of severe liver disease in the end stage, and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation, and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora, short-chain fatty acids (SCFAs) play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways, thereby playing an important role in the diagnosis, treatment, and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs, this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE, in order to provide new ideas for optimizing clinical prevention and treatment strategies.
2.The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in liver diseases
Yangling ZENG ; Yunyong WANG ; Haimei GUAN ; Tianwen WANG ; Baohua XIE ; Guobao LI ; Riyun ZHANG ; Tingshuai WANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(5):983-990
Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation, and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis, uptake, secretion, and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important, and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism, the degradation and regulatory mechanisms of HMGCR, and the application of inhibitors, as well as the role of HMGCR in liver diseases, in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.
3.Comparison of three different doses of DEN induced primary liver cancer models in rats
Riyun ZHANG ; Fenglan WU ; Dewen MAO ; Minggang WANG ; Hao PEI ; Feiyan LI
Acta Laboratorium Animalis Scientia Sinica 2025;33(2):169-179
Objective Three different doses of diethylnitrosamine(DEN)were used to establish a rat primary liver cancer(PLC)model to establish an efficient,stable,and economical animal model of PLC.Methods Forty-five male SD rats were randomly divided into four groups:normal group,DEN 50 mg/kg dose group(low dose group),70 mg/kg dose group(medium dose group),and 200 mg/kg dose group(high dose group).There were 6 animals in the normal group and 13 animals in each of the other groups.The normal control group received no treatment.The model group and low dose groups were injected intraperitoneally twice a week during weeks 1~4 and once a week during weeks 5~12;the medium dose group was injected intraperitoneally once a week for 16 consecutive weeks;and the high dose group was administered only once in the first week.The rats in each group were then followed for 16 weeks.The establishment of the model and optimal evaluation were verified by survival rate,pathological tests,biochemical tests,liver and spleen index calculation,immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and other assays.Results The survival rate was 100%in the normal group,46.15%in the low dose group,69.23%in the medium dose group,and 84.61%in the high dose group.The liver tissues of the rats in the normal group showed no abnormality to the naked eye;the liver of the rats in the low dose group became darker in color,rougher in surface,with a small number of cancerous nodules and slightly hard texture;the liver of the rats in the medium dose group was rough in surface,with several small cancerous nodules and scattered massive occupying nodules and hard texture;The liver of rats in the high dose group became lighter in color,slightly rougher in surface,with no obvious cancerous nodules;HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cells.HE staining showed that the liver tissues of rats in the low and medium dose groups were structurally disorganized,with large cellular heterogeneity and tumor cell formation,while the structure of the liver lobules of the high dose group was unclear,with different degrees of edema,degeneration and necrosis of liver cells,and no obvious tumor cell formation was seen.Compared with the normal group,serum liver function alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)were elevated in the low,medium,and high dose groups;ALT and AST were significantly elevated in the low dose group(P<0.05),the difference was statistically significant,ALT,AST and TBIL were significantly elevated in the medium dose group(P<0.05),the difference was statistically significant,and the difference was statistically significant,although liver function in the high dose group was elevated,he increase was not significant,the difference was not statistically significant(P>0.05);compared with the normal group,the international normalized ratio(INR)of coagulation function was significantly higher in the low dose group,with a statistically significant difference(P<0.05),and the activated partial thromboplastin time(APTT),prothrombin time(PT),and alpha-fetoprotein(AFP)levels were increased(P<0.05),and the difference was not statistically significant;serum APTT,PT,INR,and AFP levels were significantly increased in the medium dose group(P<0.05),and the difference was statistically significant;serum PT and AFP levels were increased in the high dose group(P<0.05),the difference was statistically significant,and plasma APTT levels were slightly increased(P>0.05),the difference was not statistically significant;liver and spleen indexes were increased in the medium dose group(P<0.05),the spleen index increased in the low dose group(P<0.05),and the liver index increased in the high dose group(P<0.05),the difference was statistically significant;the optical density value of liver tissue AFP increased significantly in the low,medium and high dose groups(P<0.05),the difference was statistically significant.Conclusions Both the low and medium dose groups could successfully induce the PLC rat model,but the pathological changes and biochemical findings of the medium dose group were more consistent with the pathogenesis of human liver tissue from liver injury to hepatic fibrosis to cirrhosis to hepatocellular carcinoma,and the number of administrations of the drug is less,and the survival rate of the rats is higher so that a more cost-effective and superior PLC model can be established.
4.Effect of joint management of type 2 diabetes mellitus between specialty department and community health under National Diabetes Prevention and Control Center (DPCC) model
Ying HUANG ; Yi QIAN ; Xuchi WU ; Zhongyu ZHOU ; Cong WANG ; Lin WANG ; Caiyan HUANG ; Zhuangsen CHEN ; Yanrong ZHANG ; Shanshan WANG ; Lu WANG ; Jie WAN ; Ruihong YANG ; Huiya WANG ; Yan CHEN ; Cheng HE ; Kun FENG ; Dewen YAN
Journal of Chinese Physician 2025;27(3):338-342
Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.
5.Practice and thinking of diabetes prevention and control in Shenzhen Bao′an
Jisu XUE ; Minqin WANG ; Ling ZHONG ; Jiao LU ; Li HUANG ; Xiangyang HE ; Dewen YAN
Journal of Chinese Physician 2025;27(3):353-356
China now has the largest number of people living with diabetes worldwide. To address such a burden, the Healthy China 2030 initiative and subsequent Healthy China Initiative-Diabetes Prevention and Treatment Action Plan(2024-2030)were launched. A shift from " disease-centred" approach to " health-centred" approach and from treatment to prevention is the core of diabetes management in China. Various regions have formed some characteristic prevention and control models with local features in their long-term diabetes prevention and control work, such as the " Community Three-in-One" management model, hospital-community integrated prevention and control model, " Three Doctors Shared Management" model, and family doctor model. Based on the description of the current situation of diabetes prevention and control in China, this article elaborates on the diabetes prevention and control model, key measures, and practical effects in Bao′an District, Shenzhen. It aims to introduce the practices and reflections on diabetes prevention and control in Bao′an, Shenzhen, and provide experiential reference for diabetes prevention and control in other areas.
6.Preparation of a rat model of chronic liver failure
Na WANG ; Zhengfeng LU ; Minggang WANG ; Fenglan WU ; Riyun ZHANG ; Rongzhen ZHANG ; Wenqian FENG ; Hao LIU ; Yang DU ; Faming SHU ; Yanmei LAN ; Dewen MAO
Acta Laboratorium Animalis Scientia Sinica 2025;33(6):811-822
Objective To prepare a stable rat model of chronic liver failure to provide a tool for basic research.Methods Sixty-six SPF SD rats were divided into a normal group(n=18)and a modeling group(n=48).Rats in the modeling group received an intraperitoneal injection of 50%CCl4 olive oil solution(1.5 mL/kg,twice a week).Multidimensional assessment was performed at 8,16,and 24 weeks,respectively,including ultrasonic examination of liver morphology,hardness,portal vein diameter,and ascites,and collection of serum,plasma,and liver tissue to detect liver function,coagulation function,and blood ammonia levels.Liver tissue injury and fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Cognitive function was assessed using the water maze test.Survival were recorded simultaneously.Results Rats in the model group showed decreased activity and appetite,yellow urine,and increased abdominal circumference compared with the normal group.Ultrasound showed enhanced liver parenchyma echo in the model group that thickened with time,secondary ascites formation,portal vein dilation,and portal hypertension.Water maze and blood ammonia tests confirmed cognitive decline(memory and orientation loss)and hepatic encephalopathy in the model group.Gross observation showed that the liver in the model group was atrophied and appeared rough and uneven.HE staining showed hepatocyte swelling,steatosis,and necrosis,and Masson staining confirmed fibrosis progression with pseudolobule formation.The liver function indexes AST,ALT,TBIL and blood ammonia continued to increase,and coagulation dysfunction(prolonged PT and increased INR)gradually increased with the modeling process.Conclusions Intraperitoneal injection of 50%CCl4 olive oil solution(1.5 mL/kg,every week)for 24 weeks can stably simulate persistent chronic liver injury in rats and lead to the typical pathological changes and complications of chronic liver failure,based on the decompensation stage of cirrhosis.This model replicates the pathological evolution of human hepatitis from liver fibrosis → liver cirrhosis compensation → decompensation → chronic liver failure,providing a reliable modeling reference for the study of the mechanism of chronic liver failure.
7.Association between bile acid/short-chain fatty acid metabolic disorders and hepatic encephalopathy based on the traditional Chinese medicine theory of Yin and Yang
Luyi YAN ; Weiyu CHEN ; Han WANG ; Wenqian FENG ; Yang DU ; Xueru TIAN ; Yang HONG ; Dewen MAO ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(7):1443-1449
Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.
8.Association between bile acid/short-chain fatty acid metabolic disorders and hepatic encephalopathy based on the traditional Chinese medicine theory of Yin and Yang
Luyi YAN ; Weiyu CHEN ; Han WANG ; Wenqian FENG ; Yang DU ; Xueru TIAN ; Yang HONG ; Dewen MAO ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(7):1443-1449
Hepatic encephalopathy is a neuropsychiatric syndrome secondary to severe liver disease.Recent studies have shown that the development of hepatic encephalopathy is closely associated with bile acid/short-chain fatty acid metabolic disorder.As the core theory of traditional Chinese medicine,the theory of Yin and Yang provides a unique perspective for analyzing the association between bile acids/short-chain fatty acids and hepatic encephalopathy.Bile acids function like Yang,governing the free flow of Qi and assisting in metabolic processes,while short-chain fatty acids belong to Yin,maintaining internal stability and conservation,preserving the intestinal barrier,and combating inflammation and toxins.Bile acids and short-chain fatty acids constrain each other and are interdependent to regulate the dynamic equilibrium of the gut-liver-brain axis.On this basis,by regulating the metabolic imbalance of bile acids and short-chain fatty acids,it is expected to restore the dynamic balance of Yin and Yang in patients with hepatic encephalopathy under the synergistic intervention of traditional Chinese medicine and Western medicine.
9.Construction and practice of the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine
Zhipeng WU ; Yuqin ZHANG ; Chun YAO ; Minggang WANG ; Na WANG ; Mengru PENG ; Ningfang MO ; Yaqing ZHENG ; Rongzhen ZHANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(2):370-374
Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease, and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine, proposes a new theory of “turbid toxin pathogenesis”, analyzes the scientific connotations of “turbid”, “toxin”, and the theory of “turbid toxin pathogenesis”, and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy, thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy, in order to provide a reference for the prevention and treatment of hepatic encephalopathy.
10.Comprehensive Application of AHP-CRITIC Hybrid Weighting Method, Grey Correlation Analysis and BP-ANN in Optimization of Extraction Process of Qizhi Prescription
Qun LAN ; Yi CHENG ; Zian LI ; Bingyu WU ; Jinyu WANG ; Dewen LIU ; Yan TONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):176-186
ObjectiveBased on analytic hierarchy process(AHP)-criteria importance through intercriteria correlation(CRITIC) hybrid weighting method, grey relational analysis and backpropagation artificial neural network(BP-ANN), to optimize the water extraction process of Qizhi prescription, so as to provide an experimental basis for optimization of the preparation process of this prescription and the establishment of quality standards. MethodsL9(34) orthogonal test was employed, and the AHP-CRITIC hybrid weighting method was utilized to determine the weight coefficients of the quality fractions of various components, including astragaloside Ⅳ, polygalaxanthone Ⅲ, calycosin-7-O-β-D-glucoside, tenuifolin, and 3,6′-disinapoylsucrose, as well as the dry extract yield. The comprehensive score of each factor level combination in the orthogonal test were calculated as evaluation indicator to select the optimal extraction process parameters. The effects of extraction times, extraction time, and solvent dosage on the aqueous extraction process of the formula were investigated through intuitive analysis, variance analysis, and grey relational analysis. Meanwhile, a BP-ANN model was established to reverse-predict the optimal extraction process parameters of Qizhi prescription, and the optimized process parameters were validated. ResultsThe weight coefficients of the five index components(astragaloside Ⅳ, tenuifolin, calycosin-7-O-β-D-glucoside, polygalaxanthone Ⅲ, and 3,6′-disinapoylsucrose) and dry extract yield were 25.7%, 20.82%, 16.41%, 12.45%, 15.96% and 8.67%, respectively. The optimized extraction process parameters were extracted 3 times with 8, 6, 6 times the amount of water, each time for 1 h. The network prediction results of BP-ANN test samples were consistent with the orthogonal test results, and the mean square error(MSE) of the predicted and measured values of the network was <1%. The water extraction process of Qizhi prescription analyzed and predicted by relevant mathematical models was stable and feasible, which could effectively improve the extraction efficiency of the active ingredients of Astragali Radix and Polygalae Radix, and the average comprehensive score of the validation test was 90.85 with the relative standard deviation(RSD) of 1.55%. ConclusionThis study establishes a water extraction process for compound Qizhi granules, and the optimized extraction process can effectively improve the extraction efficiency of active ingredients, which provides useful references for the optimization of preparation process and the establishment of quality standards for other clinical experience formulas.

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