ObjectiveTo explore the mechanism by which Yinchenhao Tang intervenes in α-naphthylisothiocyanate （ANIT）-induced cholestatic liver injury by regulating the Takeda G-protein-coupled receptor 5（TGR5）/NOD-like receptor protein 3（NLRP3）/cysteine aspartate-specific protease-1 （Caspase-1） pyroptosis signaling pathway. MethodsForty male Wistar rats were randomly assigned into blank， model， ursodeoxycholic acid， and Yinchenhao Tang groups. Except the blank group， other groups were treated with ANIT dissolved in olive oil for the modeling of cholestatic liver injury. Ursodeoxycholic acid （0.1 g·kg^-1） and Yinchenhao Tang （9.23 g·kg^-1） were administered by gavage. The blank group and the model group were administrated with the same amount of pure water， once a day for 3 days. The blood and liver tissue samples were collected， and the serum levels of liver function indicators were measured by an automatic biochemical analyzer. Hematoxylin-eosin staining was employed to observe the pathological changes of the liver. The levels of interleukin （IL）-1β and IL-18 in the liver tissue were determined by ELISA. The mRNA levels of IL-1β， IL-18， TGR5， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， and GSDMD in the liver tissue were assessed by Real-time PCR. The protein levels of TGR5， NLRP3， ASC， Caspase-1， and GSDMD in the liver tissue were determined by Western blot. ResultsCompared with the blank group， the model group showed elevated levels of alanine amino-transferase （ALT）， aspartate transferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， and total bilirubin （TBil） in the serum （P<0.01）， inflammatory cell infiltration， hepatocyte swelling， and bile duct epithelial cell proliferation in the liver， raised levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA and protein levels of TGR5 （P<0.01）， up-regulated mRNA levels of IL-18 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， and NLRP3 （P<0.05）， and up-regulated protein levels of NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， and GSDMD （P<0.05）. Compared with the model group， the ursodeoxycholic acid group showed declined levels of AST （P<0.01）， TBA （P<0.01）， TBil （P<0.01）， and ALT （P<0.05） in the serum， lowered levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of NLRP3 （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， IL-1β （P<0.05）， IL-18 （P<0.05）， and ASC （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.05）， and down-regulated protein levels of NLRP3， ASC， Caspase-1， and GSDMD （P<0.05）. Compared with the model group， the Yinchenhao Tang group showed lowered levels of ALT， AST， ALP， TBA， and TBil in the serum （P<0.01）， declined levels of IL-1β and IL-18 in the liver tissue （P<0.01）， down-regulated mRNA levels of IL-1β （P<0.01）， NLRP3 （P<0.01）， ASC （P<0.01）， Caspase-1 （P<0.01）， GSDMD （P<0.01）， and IL-18 （P<0.05）， up-regulated mRNA and protein levels of TGR5 （P<0.01）， and down-regulated protein levels of Caspase-1 and GSDMD （P<0.05）. The liver tissue of the administration groups showed reduced infiltration of inflammatory cells， reduced swelling of hepatocytes， and alleviated proliferation of bile duct epithelial cells. ConclusionYinchenhao Tang can ameliorate ANIT-induced cholestatic liver injury by regulating the hepatocyte pyroptosis mediated by the TGR5/NLRP3/Caspase-1 signaling pathway.

ObjectiveThis study aims to investigate the mechanism of Yinchenhao Tang （YCHT） in regulating macrophage polarization to alleviate cholestatic liver injury，focusing on the TLR4/NF-κB signaling pathway as the entry point. MethodsCholestasis was induced in Wistar rats through a single gavage of 100 mg·kg^-1 α-naphthyl isothiocyanate （ANIT） dissolved in olive oil. The animals were randomly divided into four groups：Model group，YCHT group，ursodeoxycholic acid （UDCA） group （n=10），and a blank group （n=10） that received only 5 mL·kg^-1 olive oil. The YCHT group received 9.23 g·kg^-1·day^-1 of YCHT by gavage，and the UDCA group was treated with 0.1 g·kg^-1·day^-1 of UDCA suspension. Both the normal and model groups were given an equal volume of normal saline，all for three consecutive days. Serum liver function was assessed using an automatic biochemical analyzer. Hematoxylin-eosin （HE） staining was used to observe liver tissue morphology. Levels of tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），transforming growth factor-β （TGF-β），and interleukin-10 （IL-10） were quantified in liver homogenate supernatants via enzyme-linked immunosorbent assay （ELISA）. Western blot analysis measured the relative protein expression of Toll-like receptor 4 （TLR4），nuclear factor-κB （NF-κB），CD206，inducible nitric oxide synthase （iNOS）， CD86，and arginase-1 （Arg-1）. The relative mRNA expression of TLR4/NF-κB，CD206，iNOS，CD86，and Arg-1 in liver tissue was evaluated using real-time quantitative PCR. ResultsCompared with the normal group，the model group exhibited significantly elevated levels of alkaline phosphatase （ALP），total bile acid （TBA），total bilirubin （TBil），aspartate aminotransferase （AST），and alanine aminotransferase （ALT） （P<0.01）. There was a portal area expansion and pronounced inflammatory cell infiltration. The expression of pro-inflammatory markers TNF-α and IL-1β was significantly upregulated （P<0.01），and macrophage markers CD86 and CD206 showed positive expression. Protein and mRNA expressions of iNOS and CD86 were significantly elevated （P<0.01）. The mRNA and protein expressions of the related pathway molecules TLR4 and NF-κB were significantly increased （P<0.01）. Compared with those in the model group， the liver function indicators in the YCHT group showed significant decreases （P<0.05， P<0.01）. The bile duct hyperplasia was significantly alleviated， and the tissue structure became more orderly. The levels of IL-1β and TNF-α were significantly reduced （P<0.01）， while the expression levels of IL-10 and TGF-β significantly increased （P<0.05， P<0.01）. The expression of CD86 significantly decreased （P<0.01）， and the expression of CD206 significantly increased （P<0.01）. The protein and mRNA expressions of iNOS and CD86 significantly decreased （P<0.01）， and those of Arg-1 significantly increased （P<0.01）. The protein and mRNA expressions of CD206 significantly increased （P<0.05， P<0.01）， and the mRNA and protein expressions of related pathway molecules TLR4 and NF-κB significantly decreased （P<0.01）. ConclusionYCHT ameliorates cholestatic liver injury in rats by improving bile metabolism，reducing bile duct dilatation，and mitigating inflammation. These effects are achieved through the inhibition of M1 macrophage activation and the promotion of M2 macrophage polarization，likely via modulation of the TLR4/NF-κB signaling pathway.

Cholestatic liver injury refers to the bile production， secretion， and excretion disorder caused by various reasons. It induces liver injury， metabolic disorders， and dysfunction of the hepatobiliary system， which can further develop into liver fibrosis， cirrhosis， liver failure， and even death. At present， the preferred drug for clinical treatment is ursodeoxycholic acid， which， however， induces adverse reactions and is intolerant in some patients. Yinchenhao Tang is a representative prescription of traditional Chinese medicine for the treatment of jaundice due to Yang jaundice. It has the effects of clearing heat， eliminating dampness， and removing jaundice and has shown good therapeutic effect in long-term clinical application. Modern pharmacological studies have found that this prescription has anti-inflammatory， anti-oxidation， bile acid balance-regulating， hepatocyte apoptosis-inhibiting and other liver-protecting effects. This paper reviews the relevant clinical and animal experimental studies on Yinchenhao Tang in the treatment of cholestatic liver injury in recent years. Yinchenhao Tang can intervene in the progression of cholestatic liver injury by regulating bile acid metabolism and excretion， reducing inflammatory response， inhibiting oxidative stress， alleviating endoplasmic reticulum stress， inhibiting hepatocyte apoptosis， and protecting intestinal mucosal barrier. This paper systematically expounds the molecular mechanisms by which Yinchenhao Tang regulates cholestatic liver injury that are confirmed by current research， aiming to provide reference for the clinical application and in-depth study of Yinchenhao Tang.

OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

As a type of endogenous small non-coding RNA， microRNA （miRNA） can regulate gene expression and thereby intervene against the development and progression of cardiovascular diseases， neurodegenerative diseases， metabolic diseases， and autoimmune diseases. The pathogenesis of cholestasis is complex and is mainly associated with the metabolism and transport of bile acids， oxidative stress， inflammatory response， and intestinal flora. Currently， ursodeoxycholic acid is the preferred drug for the clinical treatment of cholestasis， but it may cause adverse reactions and exhibit poor efficacy in some patients. Studies have shown that miRNA can intervene in the disease process of cholestasis through multiple mechanisms such as regulating bile acid metabolism and transport， alleviating oxidative stress， inhibiting inflammatory response， improving cholangiocyte proliferation， and regulating intestinal flora. It can be used as a new biomarker and action target for cholestasis， with high research potential and value. Therefore， this article summarizes the role and mechanisms of miRNA in regulating cholestasis in recent years， in order to provide a reference for further research on the prevention and treatment of cholestasis by targeting miRNA.

Objective To study the therapeutic mechanism of Tuihuang Mixture against cholestasis.Methods Forty-eight Wistar rats were randomized equally into blank group,model group,ursodeoxycholic acid group and Tuihuang Mixture group.Except for those in the blank group,all the rats were given α-naphthylisothiocyanate(ANIT)to establish rat models of cholestasis,followed by treatments with indicated drugs or distilled water.Serum levels of ALT,AST,ALP,γ-GT,TBA and TBIL of the rats were determined,and hepatic expressions IL-1β,IL-18,FXR,NLRP3,ASC,Caspase-1 and GSDMD were detected using q-PCR,ELISA or Western blotting.Histopathological changes of the liver tissues were observed using HE staining.Results The rat models of cholestasis had significantly increased serum levels of ALT,AST,ALP,γ-GT,TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18,decreased protein and mRNA expressions of FXR,and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3,ASC,Caspase-1 and GSDMD in the liver tissue,showing also irregular arrangement of liver cells,proliferation of bile duct epithelial cells and inflammatory cells infiltration.Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT,AST,ALP,γ-GT,TBA and TBIL,lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions,and reduced NLRP3,ASC,Caspase-1 and GSDMD proteins and NLRP3,ASC and Caspase-1 mRNA expressions in the liver tissue.Tuihuang Mixture also significantly alleviated hepatocyte injury,bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models.Conclusion Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.

Objective:To investigate the levels of osteoporosis-related biomarkers in individuals with subclinical hypothyroidism complicated by type 2 diabetes mellitus.Methods:A cross-sectional study. From January 2021 to June 2022, 40 patients with subclinical hypothyroidism, 40 patients with type 2 diabetes, 40 patients with type 2 diabetes complicated with subclinical hypothyroidism, and 40 individuals receiving physical examination in Shanxi Bethune Hospital were selected as subjects in this study. The glucose and lipid metabolism indexes and bone metabolism indexes of the subjects were detected, and the differences and correlations of the metabolic indexes among the groups were analyzed by t-tests, nonparametric tests or correlation analysis. Results:Compared with healthy group, beta C-terminal cross-linked telopeptides of type Ⅰ collagen (β-CTX) level in type 2 diabetes group was higher [(344.60±125.61) vs (227.56±68.33) pg/ml] ( t=-5.176, P<0.001), osteocalcin (OC) and total procollagen type 1 aminoterminal peptide (t-PINP) were both lower [(15.76±4.70) vs (28.02±5.83)ng/ml, (43.49±13.63) vs (59.58±15.80) ng/ml] ( t=10.352, t=4.874, P<0.001). The β-CTX level in type 2 diabetes patients complicated with hypothyroidism was higher than that in patients with simple subclinical hypothyroidism [(380.51±122.22) vs (212.41±44.17) pg/ml] ( t=-8.180 ,P<0.001), but the levels of OC and t-PINP were both lower [(13.67±4.06) vs (26.12±4.55) ng/ml, (38.76±9.53) vs (61.50±12.31) ng/ml] ( t=12.897, P<0.001); but there was no significant difference in the three biomarkers between patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism and those with type 2 diabetes mellitus alone. [β-CTX: (380.51±122.22) vs (344.60±125.61) pg/ml, OC: (13.67±4.06) vs (15.76±4.70) ng/ml, t-PINP: (38.76±9.53) vs (43.49±13.63) ng/ml] ( t=1.296,1.890,-1.799 ,all P>0.05). In the patients with type 2 diabetes mellitus complicated by subclinical hypothyroidism, the β-CTX was positively correlated with fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c)( r=0.293,0.487,all P<0.05), while OC and t-PINP were negatively correlated with FBG and HbA1c ( r=-0.560,-0.502,-0.289,-0.326, P<0.05). Conclusion:Changes of serum osteoporosis-related biomarkers in subclinical hypothyroidism patients with type 2 diabetes indicate the increased risk of osteoporosis in those patients.

Objective:This study aimed to explore the effect of Vaspin on adipose tissue macrophage polarization and its underlying mechanism.Methods:Fifty male SD rats, aged 8 weeks, were chosen and randomly allocated into three groups: the normal control(NC), the type 2 diabetes(T2DM), and various concentrations of Vaspin intervention(V1: 480 ng/kg, V2: 960 ng/kg, V3: 1 440 ng/kg). Vaspin was administered via intraperitoneal injection for 8 weeks. Glucose tolerance and insulin sensitivity were evaluated via intraperitoneal glucose tolerance test(IPGTT), intraperitoneal insulin tolerance test(IPITT) and hyperinsulinemic-euglycemic clamp. Adipose tissue inflammation and macrophage polarization were assessed using immunofluorescence, RT-PCR and western blotting.Results:After 8 weeks of intervention, there were no statistically significant differences in body weight and blood lipid levels among groups. IPGTT, IPITT, and hyperinsulinemic-euglycemic clamp experiments demonstrated that Vaspin intervention improved blood glucose and insulin sensitivity, exhibiting a dose-dependent manner( P<0.05). IF and RT-PCR showed that Vaspin downregulated the expression of CD11c, IL-1β, and TNF-α in eWAT, while upregulating the expression of CD206, IL-10, and PPARγ, which correlated with Vaspin concentration( P<0.05). ELISA revealed that Vaspin intervention reduced the concentrations of IL-1β and TNF-α in serum, while increasing the concentration of IL-10( P<0.05). Western blotting demonstrated that Vaspin downregulated iNOS protein expression, while upregulating Arg1, p-Akt, and PPARγ expression in a dose-dependent manner( P<0.05). Conclusion:Vaspin promotes M2 polarization of adipose tissue macrophages via PPARγ pathway, leading to reduced inflammation and improved insulin sensitivity in T2DM rats.

The development mode of public hospitals has shifted from scale expansion to improving quality and efficien-cy,and specialized operation and management is an important means to improve the performance of surgical departments.Howev-er,at present,there is a gap in the performance appraisal of specialized operators,requiring the hospital to formulate a specific and accurate performance appraisal plan for the management department.Taking hospital Z as an example,based on post value(IPE),this paper analyzes the idea of its performance appraisal plan in detail,and analyzes the specific application of its per-formance allocation with specialized operation assistant as an example.Based on IPE,the responsibility,rank and performance distribution coefficient of hospital management positions can effectively solve the difficulties that the total work and quality of hos-pital management departments are difficult to quantify,and also provide some reference for the formulation of performance apprais-al plan of specialized operation staff in public hospitals.

Objective To investigate the diagnostic value of serum levels of leukocyte cell derived chemo-taxin 2(LECT2)and tumor necrosis factor ligand-related molecule-1A(TL1A)in children with atopic der-matitis(AD).Methods A total of 83 children with AD who were adimitted to the hospital from August 2021 to August 2023 were selected as the AD group,and 83 healthy children who underwent physical examination in the hospital during the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was applied to measure the expression levels of LECT2 and TL1A in serum.Spearman method was applied to analyze the correlation between serum LECT2,TL1A,and AD integral index(SCORAD).Multiva-riate Logistic regression was applied to analyze the factors that affected the severity of AD in children.Receiv-er operating characteristic(ROC)curve was applied to analyze the diagnostic efficacy of serum LECT2 and TL1A levels on the severity of AD in children.Results Compared with the control group,the expression lev-els of LECT2 and TL1A in the serum of the AD group were significantly increased(P＜0.05).Compared with the low-grade group,the serum LECT2,TL1 A,SCORAD score,EOS and total IgE in the moderate and severe groups were significantly increased in turn(P＜0.05).According to Spearman correlation analysis,the serum levels of LECT2 and TL1A in the AD group were positively correlated with the SCORAD score(r=0.776,0.693,both P＜0.05).According to the results of multivariate Logistic regression analysis,serum LECT2、TL1 A、EOS and total IgE were risk factors affecting the severity of AD in children(P＜0.05).In ad-dition,the combination of serum LECT2 and TL1A had the highest AUC for diagnosing the severity of AD in children,which was better than the individual diagnosis of serum LECT2 and TL1A(Z=2.249,1.989,P=0.025,0.047).Conclusion The elevated levels of serum LECT2 and TL1A in children with AD are closely re-lated to the severity of the disease,and the combination of the two can better evaluate the severity of the dis-ease in children with AD.