1.Mechanism of action of the nuclear factor-kappa B signaling pathway in liver diseases and its potential as a therapeutic target
Wenqian FENG ; Yang DU ; Dewen MAO ; Weiyu CHEN ; Lei FU ; Luyi YAN ; Chun YAO ; Yanmei LAN
Journal of Clinical Hepatology 2025;41(9):1949-1955
Nuclear factor-kappa B (NF-κB) is an important intracellular transcription factor widely involved in the processes such as immune response, inflammatory response, cell proliferation, and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds, such as matrine and salvianolic acid B, have shown the potential in suppressing NF-κB activity, thereby exerting anti-inflammatory, anti-fibrotic, and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target, in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.
2.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.
3.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.
4.Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy: A study based on the PI3K/AKT/mTOR signaling pathway
Guangfa ZHANG ; Yingying CAI ; Long LIN ; Lei FU ; Fan YAO ; Meng WANG ; Rongzhen ZHANG ; Yueqiao CHEN ; Liangjiang HUANG ; Han WANG ; Yun SU ; Yanmei LAN ; Yingyu LE ; Dewen MAO ; Chun YAO
Journal of Clinical Hepatology 2024;40(2):312-318
ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction (RD) retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy (MHE). MethodsA total of 60 male Sprague-Dawley rats were divided into blank group (CON group with 6 rats) and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks, 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group (MOD group), lactulose group (LT group), low-dose RD group (RD1 group), middle-dose RD group (RD2 group), and high-dose RD group (RD3 group), with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day; the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day; the rats in the RD1, RD2, and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5, 5.0, and 7.5 g/kg, respectively, once a day. After 10 days of treatment, the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects: behavioral status; the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the level of blood ammonia; pathological changes of liver tissue and brain tissue; the mRNA and protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in brain tissue. 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 MOD group, the RD1, RD2, and RD3 groups had a significantly shorter escape latency (all P<0.01), significant reductions in the levels of ALT, AST, IL-1β, IL-6, TNF-α, and blood ammonia (all P<0.05), significant alleviation of the degeneration, necrosis, and inflammation of hepatocytes and brain cells, and significant reductions in the mRNA and protein expression levels of PI3K, AKT, and mTOR in brain tissue (all P<0.05), and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats, possibly by regulating the PI3K/AKT/mTOR signaling pathway.
5.The relationship between the Wnt signaling pathway and liver regeneration and its role in liver diseases
Yupei LIN ; Xiaoping LIU ; Yinbing LUO ; Feiyan LI ; Yingying LIAO ; Shicong MO ; Dewen MAO ; Yanmei LAN
Journal of Clinical Hepatology 2024;40(5):1050-1056
The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration.In healthy livers,the Wnt signaling pathway is mostly inactive,but it is continuously overactivated during cell renewal or regeneration processes,as well as in certain pathological conditions,diseases,precancerous states,and cancers.Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis,liver cirrhosis,and liver cancer.This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases,so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.
6.Study on the effects of Qingjie huagong decoction on the regulation of intestinal flora and intestinal mucosal barrier in severe acute pancreatitis model rats
Baijun QIN ; Xiping TANG ; Xin YANG ; Lei YANG ; Minchao FENG ; Chi ZHANG ; Xiaohua HONG ; Yanmei LAN ; Guozhong CHEN
China Pharmacy 2022;33(15):1825-1832
OBJECTIVE To explore the the reg ulation of intestinal flora and effects of Qingjie huagong decoction on intestinal mucosal barrier in severe acute pancreatitis (SAP)mode rats . METHODS SAP rat model was induced by intraperitoneal injection of caerulein and lipopolysaccharide.The survival state of rats in each group were observed.The levels of serum amylase ,interleukin 10(IL-10),IL-18 and IL- 1β in serum were all detected. The pathological changes of pancreatic and small intestinal tissue were observed. The expressions of Occludin,ZO-1 and HMGB1 were detected in small intestinal tissue of rats. The structure and relative abundance of intestinal microflora in rats were detected by 16S rRNA high throughput sequencing. RESULTS After the intervention of Qingjie huagong decoction ,abdominal distension symptoms of SAP model rats were significantly relieved ,and their mental state recovered better ;the levels of serum amylase and IL- 18 in serum were decreased significantly (P<0.05),while the level of IL- 10 was increased significantly (P<0.05). The necrotic area of pancreatic tissue and the infiltration of inflammatory cells were reduced , the degree of intestinal epithelial cell structural disorder was alleviated ,and the shedding of intestinal mucosal epithelium was reduced.The protein expression of HMGB 1 in small intestinal tissue was decreased significantly (P<0.05),and the protein expression of Occludin and ZO- 1 were increased significantly . Results of 16S rRNA high throughput sequencing showed that Qingjie huagong decoction could increased the relative abundance of probiotics such as Bacteroidea and Lactobacillus in rat intestine ,reduced the colonization of harmful bacteria such as Firmicutes. CONCLUSIONS Qingjie huagong decoction can improve the intestinal barrier by up-regulating the expression of Occludin and ZO- 1 in small intestinal tissue and down-regulating the protein expression of HMGB 1. It can also adjust the relative abundances of different flora to protect the intestinal tract.
7.Multicenter study on the effect of early screening skills training for autism spectrum disorders in primary care hospitals in Chengdu
Wenxu YANG ; Jiao LE ; Lan ZHANG ; Ying ZHANG ; Ping YANG ; Chunxia ZHAO ; Chunhua DU ; Junni HE ; Yanmei CAO ; Jia SHANG ; Li LI ; Yan LIU ; Shenglan WU ; Xia LI ; Xiujin CHEN ; Hai LAN ; Hua LI ; Xiang KONG ; Hengli LI ; Defang MI ; Jie ZHAO ; Yang NIE ; Jinxiu GAO ; Ling LI
Sichuan Mental Health 2022;35(4):337-342
ObjectiveTo investigate effect of conducting training of autism spectrum disorder (ASD) early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021, the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training, the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals, confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training, the number of children with suspected ASD referred by primary care hospitals was more than that before training [(16.65±11.60) vs. (3.40±2.23), t=5.431, P<0.01], the number of children diagnosed with ASD was more than that before training[(6.85±4.93) vs. (2.45±1.67), t=4.171, P<0.01], and the differences were statistically significant. As for the diagnosed age of ASD children, after training, the average age was lower than that before training [(34.95±11.67) vs. (42.2±14.64), t=-2.553, P=0.019]. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.
8.Mechanism of action of bile acid-farnesoid X receptor-intestinal microecological axis in the development of liver failure and liver regeneration
Yanyan CHEN ; Yanmei LAN ; Minggang WANG ; Dewen MAO
Journal of Clinical Hepatology 2021;37(2):480-484
Liver failure is a common critical medical disease, and extensive liver cell necrosis within a short period of time exceeds the regeneration capacity of liver cells and thus results in an extremely high fatality rate. Promotion of effective liver regeneration is the key to antagonizing liver failure. Recent studies have shown that bile acid, farnesoid X receptor (FXR), and intestinal microecology play an important role in liver failure and liver regeneration. This article reviews the association between bile acid, FXR, and intestinal microecology and their role in liver failure and liver regeneration, so as to provide new ideas for the treatment of liver failure in clinical practice.
9.Mechanism of action of Jieduhuayu granules for remission of oxidative stress in hepatocytes
Rongzhen ZHANG ; Dewen MAO ; Kewei SUN ; Xiufeng WANG ; Yin LIU ; Tingshuai WANG ; Yanmei LAN
Chinese Journal of Hepatology 2021;29(12):1188-1193
Objective:To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells.Methods:Human liver L02 oxidative injury model was established with 0.1 mmol/ L H 2O 2 intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H 2O 2, H 2O 2 + JDHY (0.5 mg/ml), H 2O 2 + JDHY (1 mg/ml), and H 2O 2 + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results:Compared with the normal group, the cell proliferation activity ( P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H 2O 2 group were all significantly reduced ( P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased ( P < 0.05). Compared with H 2O 2 group, the cell proliferation activity ( P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H 2O 2 + JDHY (1 mg/ml) and H 2O 2 + JDHY (1.5 mg/ml) group ( P < 0.05) were all significantly increased ( P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased ( P < 0.05). Conclusion:Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.
10.An epidemiological survey of mental disorders among people aged 18 and above in Shandong Province
Ruzhan WANG ; Jingxuan ZHANG ; Yanhu WANG ; Can WANG ; Xiuzhe CHEN ; Guolin MI ; Xu CHEN ; Xiaojing CHENG ; Lina WANG ; Lili HU ; Lingxi GU ; Shiquan ZHENG ; Lan DONG ; Ligang WANG ; Li CHEN ; Wu LI ; Yanhua LIU ; Jun ZHU ; Yanmei WANG ; Qinghua WEN ; Xiaopeng LI ; Yusheng ZHANG ; Zongyin HOU ; Xiuru ZHANG ; Tingxia ZHANG ; Sumei GUO ; Xiucheng YANG
Chinese Journal of Psychiatry 2021;54(2):138-146
Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.

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