Objective Hypothyroidism is a common clinical disease of systemic metabolic reduction,the incidence and detection rate increased year by year.Based on the clinical characteristics of hypothyroidism,the study constructed and improved animal models to provide reference for the study of hypothyroidism prevention and treatment.Methods By reviewing relevant domestic and foreign literatures,the modeling methods of hypothyroidism were summarized and analyzed.According to the etiology,pathogenesis and clinical diagnostic criteria of hypothyroidism in Chinese medicine and Western medicine,the modeling methods and principles of hypothyroidism animal models were summarized,and the advantages and disadvantages of animal models and the evaluation of clinical conformity were analyzed.Results It was found that the model of drug induction,iodine restriction and 131 I-induced hypothyroidism had high clinical anastomosis in Western medicine,and had the advantages of simple operation,high model formation rate and good repeatability,the combination of the disease model and the syndrome model of kidney yang deficiency and spleen and kidney yang deficiency have a high degree of clinical conformity in TCM.Congenital induced hypothyroidism,autoimmune induced hypothyroidism and genetic induced hypothyroidism can be studied for their unique etiology and pathogenesis,but their clinical manifestations are relatively simple and their clinical anastomosis is relatively low.At present,the construction of hypothyroidism animal model is mainly based on the pathogenesis of Western medicine,and the evaluation of the model mostly relies on laboratory detection indicators.The clinical anastomosis score of traditional Chinese medicine is generally low,and the record of animal apparent indicators is generally insufficient.Conclusion In the process of building hypothyroidism animal model,based on the pathogenesis of traditional Chinese medicine,combining the etiology of traditional Chinese medicine and the pathogenesis of Western medicine,multi-factor comprehensive modeling method can be adopted to increase the record of apparent indicators,improve the accuracy of the four diagnoses and symptoms of traditional Chinese medicine,and systematically and dynamically observe the interaction process of disease and syndrome,so as to build an animal model of hypothyroidism which is more closely aligns with with the clinical characteristics of traditional Chinese medicine and Western medicine.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

The theory of"qi cycle in round"originates from HUANG Yuanyu's Sisheng Xinyuan,which takes qi monism as the philosophical foundation,and constructs a qi circulation system with the spleen and stomach as the hub,linking the liver,heart,lung,and kidney on the basis of the gasification theory of Huangdi Neijing.Based on theory of"qi cycle in round,"the pathogenesis of Hashimoto thyroiditis begins with liver depression,leading to liver and spleen imbalance,which in turn develops into spleen and kidney deficiency.In the treatment,guided by the principle of"treating same disease with different methods,"combined with objective indicators such as the thyroid function,autoantibody,and ultrasound imaging characteristics,Hashimoto thyroiditis was treated in three stages:early,middle,and late stages.In the early stage,characterized by liver depression and qi stagnation,therapy focuses on regulating wood qi to facilitate the pivot;in the middle stage,marked by liver depression and spleen deficiency,and the method of pungent opening and bitter descending should be adopted to restore the ascending and descending of the spleen and stomach;in the late stage,characterized by spleen and kidney yang deficiency,treatment aims to warm the kidney and tonify the spleen,which helps"qi cycle in round"and restores the normal state of qi transformation of zang-fu viscera.Stage-specific differentiation and treatment aims to restore the qi transformation of zang-fu viscera,promote"qi cycle in round,"improve thyroid function,and delay the progression of Hashimoto thyroiditis,thereby providing insights and methods for clinical differentiation and treatment of this disease.

Objective Hypothyroidism is a common clinical disease of systemic metabolic reduction,the incidence and detection rate increased year by year.Based on the clinical characteristics of hypothyroidism,the study constructed and improved animal models to provide reference for the study of hypothyroidism prevention and treatment.Methods By reviewing relevant domestic and foreign literatures,the modeling methods of hypothyroidism were summarized and analyzed.According to the etiology,pathogenesis and clinical diagnostic criteria of hypothyroidism in Chinese medicine and Western medicine,the modeling methods and principles of hypothyroidism animal models were summarized,and the advantages and disadvantages of animal models and the evaluation of clinical conformity were analyzed.Results It was found that the model of drug induction,iodine restriction and 131 I-induced hypothyroidism had high clinical anastomosis in Western medicine,and had the advantages of simple operation,high model formation rate and good repeatability,the combination of the disease model and the syndrome model of kidney yang deficiency and spleen and kidney yang deficiency have a high degree of clinical conformity in TCM.Congenital induced hypothyroidism,autoimmune induced hypothyroidism and genetic induced hypothyroidism can be studied for their unique etiology and pathogenesis,but their clinical manifestations are relatively simple and their clinical anastomosis is relatively low.At present,the construction of hypothyroidism animal model is mainly based on the pathogenesis of Western medicine,and the evaluation of the model mostly relies on laboratory detection indicators.The clinical anastomosis score of traditional Chinese medicine is generally low,and the record of animal apparent indicators is generally insufficient.Conclusion In the process of building hypothyroidism animal model,based on the pathogenesis of traditional Chinese medicine,combining the etiology of traditional Chinese medicine and the pathogenesis of Western medicine,multi-factor comprehensive modeling method can be adopted to increase the record of apparent indicators,improve the accuracy of the four diagnoses and symptoms of traditional Chinese medicine,and systematically and dynamically observe the interaction process of disease and syndrome,so as to build an animal model of hypothyroidism which is more closely aligns with with the clinical characteristics of traditional Chinese medicine and Western medicine.

The theory of"qi cycle in round"originates from HUANG Yuanyu's Sisheng Xinyuan,which takes qi monism as the philosophical foundation,and constructs a qi circulation system with the spleen and stomach as the hub,linking the liver,heart,lung,and kidney on the basis of the gasification theory of Huangdi Neijing.Based on theory of"qi cycle in round,"the pathogenesis of Hashimoto thyroiditis begins with liver depression,leading to liver and spleen imbalance,which in turn develops into spleen and kidney deficiency.In the treatment,guided by the principle of"treating same disease with different methods,"combined with objective indicators such as the thyroid function,autoantibody,and ultrasound imaging characteristics,Hashimoto thyroiditis was treated in three stages:early,middle,and late stages.In the early stage,characterized by liver depression and qi stagnation,therapy focuses on regulating wood qi to facilitate the pivot;in the middle stage,marked by liver depression and spleen deficiency,and the method of pungent opening and bitter descending should be adopted to restore the ascending and descending of the spleen and stomach;in the late stage,characterized by spleen and kidney yang deficiency,treatment aims to warm the kidney and tonify the spleen,which helps"qi cycle in round"and restores the normal state of qi transformation of zang-fu viscera.Stage-specific differentiation and treatment aims to restore the qi transformation of zang-fu viscera,promote"qi cycle in round,"improve thyroid function,and delay the progression of Hashimoto thyroiditis,thereby providing insights and methods for clinical differentiation and treatment of this disease.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

Nonalcoholic fatty liver disease （NAFLD） is currently the main cause of chronic liver disease worldwide， and it can progress to hepatitis， liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. Although obesity plays a key role in the development of NAFLD， more and more studies have confirmed that NAFLD still exists in lean individuals， and lean NAFLD is associated with an increased risk of death and accelerated disease progression. Therefore， lean NAFLD also deserves careful evaluation and follow-up； however， we still know little about the pathophysiological mechanism of lean NAFLD. This article reviews the etiology， diagnosis， treatment， and prognosis of lean NAFLD.

Objective:To explore whether NSBB is suitable for the primary prevention of liver cirrhosis accompanied by CSPH with no or small esophageal varices.Methods:Relevant literatures were retrieved from Cochrane library, PubMed, EMBASE, SinoMed, CNKI and Wanfang databases until December 12, 2020. All randomized controlled trials (RCTs) on NSBB use for primary prevention of cirrhosis accompanied by CSPH with no or small esophageal varices were collected. The literature was strictly screened according to the established inclusion and exclusion criteria, odds ratio (OR), and 95% confidence interval (CI) combined effect size. The development of esophageal varices and the initial upper gastrointestinal bleeding were the primary outcome measures. Death (with a maximum average follow-up of about five years) and adverse events (adverse drug reactions, etc.) were the secondary outcome measures.Results:A total of 9 RCTs with 1396 cases were included. Meta-analysis results showed that, compared with placebo, NSBB significantly reduced the incidence of liver cirrhosis accompanied by CSPH with no or small esophageal varices to large esophageal varices progression ( OR=0.51, 95% CI: 0.29-0.89, P=0.02), and mortality (with maximum average follow-up of about five years) ( OR=0.64, 95% CI: 0.44-0.92, P=0.02); however, there was no statistically significant difference in the initial upper gastrointestinal bleeding rate between the two groups ( OR=0.82, 95% CI: 0.44-1.52, P=0.53). Adverse event incidence was greater in the NSBB than the placebo group ( OR=1.74, 95% CI: 1.27-2.37, P=0.0005). Conclusions:NSBB use cannot reduce the initial upper gastrointestinal bleeding rate or adverse event incidence in patients with liver cirrhosis accompanied by CSPH with no or small esophageal varices, but it can delay the progression of gastroesophageal varices and reduce patient mortality.

Background: The occurrence of gastrointestinal symptoms in cirrhotic patients with gastroesophageal varices (GOV) after endoscopic treatment is obvious, and the role of gastric myoelectrical activity (GMA) and autonomic nerve function imbalance in the development of gastrointestinal symptoms has not been clarified. Aims: To investigate the changes of GMA and autonomic nerve function in cirrhotic patients with GOV after endoscopic treatment. Methods: Twenty-five cirrhotic patients with GOV from May 2019 to October 2019 at the First Affiliated Hospital of Nanjing Medical University were enrolled, and 10 patients with gastric polyp were served as controls. Electrogastrogram (EGG) and heart rate variability (HRV) were detected before the operation, 1 day after the operation and 5 days after the operation in GOV group. For the gastric polyp group, EGG and HRV were detected before the operation and 1 day after the operation. Changes of GMA and autonomic nerve function were compared between the two groups. Results: No significant differences in GMA and autonomic nerve function were found between GOV group and gastric polyp group before and 1 day after the operation (P>0.05). LF, LF/HF were significantly increased 1 day after the operation in GOV group (P<0.05), while HF was significantly decreased (P<0.01), and the percentage of bradygastria was significantly increased (P<0.01). There were no significant differences in GMA and autonomic nerve function between pre-operation and 5 days after the operation in GOV group (P>0.05). There were no significant differences in GMA and autonomic nerve function 1 day after the operation compared with pre-operation in gastric polyp group (P>0.05). Compared with Child-Pugh A group, Child-Pugh B group had more obvious GMA abnormalities, and the difference was statistically significant (P<0.05). Conclusions: In cirrhotic patients with GOV, the percentage of bradygastria and the sympathetic activity increased, and the vagal activity decreased 1 day after the operation. These results suggest that GMA and autonomic nerve dysfunction may be related to the gastrointestinal symptoms after endoscopic treatment.

Background:Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases worldwide and specific targeted therapy is still lacking up to now. Aims:To investigate the protective effect of berberine on high fat diet(HFD)-induced hepatic lipotoxicity in mice and its potential mechanisms. Methods:Thirty male C57BL/6J mice were randomly assigned to three groups,then fed either with standard diet or HFD or HFD plus berberine(200 mg/kg per day intragastrically)for 12 weeks. Serum biochemical indices including ALT,AST,TC,TG and glucose were measured at the end of the 12th week. HE staining was used to observe liver inflammation,and fatty infiltration was detected with oil red staining. Ileocecal feces was collected and the composition of gut microbiota was analyzed by 16S rRNA sequencing. Serum level of LPS and hepatic levels of TNF-α and IL-6 were detected by ELISA. In vitro,the primary hepatic macrophages of C57BL/6J mice were challenged with palmitic acid,LPS and/or berberine,respectively;the ultrastructure of macrophages was observed using electron microscope,and the proinflammatory cytokines were detected by real-time PCR. Results:In vivo,the treatment of berberine improved the liver dysfunction,hyperlipidemia and hyperglycemia in mice fed with HFD. Also,berberine significantly inhibited the HFD-induced hepatic lipid accumulation,and alleviated hepatocytes ballooning and lobular inflammatory cell infiltration;the levels of serum LPS and hepatic IL-6 were markedly decreased. 16S rRNA sequencing showed that berberine supplementation restored the abundance of Bacteroidaceae and Desulfovibrionaceae in ileocecus,which were disturbed by HFD. In vitro,berberine not only significantly reduced the palmitic acid-induced lipid accumulation in primary hepatic macrophages,but also decreased the expressions of TNF-α and IL-6 in macrophages stimulated with LPS. Conclusions:Berberine can ameliorate effectively the hepatic lipid accumulation and inflammation in mice with experimental NAFLD. The mechanism of its antiinflammatory effect might be related with regulating the gut microbiota,reducing the LPS production,and subsequently inhibiting the release of inflammatory cytokines by hepatic macrophages.