1.Yinchenhao Tang Regulates Pyroptosis to Intervene in Cholestatic Liver Injury
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Ruixue MA ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):55-62
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.
2.Investigation into Mechanism of Yinchenhao Tang in Modulating Macrophage Activation to Combat Cholestatic Liver Injury
Jinghan ZHAO ; Zhengwang ZHU ; Linlin WANG ; Ruixue MA ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):63-70
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.
3.Intervention Effect and Regulation Mechanism of Yinchenhao Tang on Cholestatic Liver Injury
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Ruixue MA ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):71-80
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.
4.Analysis of risk factors for venous thrombosis caused by peripherally inserted medium-length catheters in patients with critical illness
Ruixue WANG ; Wenxiang CHEN ; Mei XIANG
Chinese Journal of Postgraduates of Medicine 2025;48(4):361-364
Objective:To study the risk factors for venous thrombosis after peripheral vein placement of medium-length catheters in critically ill patients.Methods:A total of 212 critically ill patients who underwent medium-length catheter placement in Central Hospital of Jiaozhou from January 2021 to October 2022 were selected as the research subjects.Among them, 169 cases did not develop venous thrombosis (control group) and 43 cases did (observation group). Univariate and multivariate Logistic regression were used to analyze the risk factors for venous thrombosis after peripheral vein placement of medium-length catheters in critically ill patients.Results:Venous thrombosis occurred in 43 cases, the occurrence rate was 20.28% (43/212). The results of single factor analysis showed that age, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score, fibrinogen, Glasgow Coma Scale (GCS) score and catheter infection were the risk factors for venous thrombosis ( P<0.05). Multivariate Logistic regression analysis showed that age ≥65 years, APACHE-Ⅱ score ≥8 points, fibrinogen score ≥4 g/L, GCS score ≤8 points, and catheter infection were independent risk factors for venous thrombosis: OR values were 1.988 (95% CI 0.995 - 3.975), 4.269 (95% CI 2.063 - 8.834), 3.089 (95% CI 1.505 - 6.349), 3.931 (95% CI 1.920 - 8.045), 7.171 (95% CI 3.225 - 15.948), P<0.05 or <0.01. Conclusions:Age ≥ 65 years, APACHE -Ⅱ score ≥ 8 points, fibrinogen ≥ 4 g/L, GCS score ≤ 8 points, and catheter infection are independent risk factors for venous thrombosis in critically ill patients. Active monitoring should be carried out clinically to reduce the risk of venous thrombosis.
5.Researches on central post-stroke pain:a bibliometric analysis
Xinyue ZHOU ; Ruixue YE ; Yaqi MA ; Ying XU ; Longyao CAO ; Yulong WANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):1038-1049
Objective To analyze the research status,hotspots and development trends in the field of central post-stroke pain(CPSP).Methods Relevant literatures up to April 8,2025 were retrieved from the Web of Science Core Collection database.CiteSpace 6.4.R1 advanced version was used for bibliometric and visualization analysis of publication trends,country/institution/author collaboration networks,keywords and burst terms.Results A total of 119 publications were included.Researches on CPSP have shown an overall upward trend since 2002,which could be divided into a slow development period(from 2002 to 2015)and a rapid growth period(from 2016 onwards).The number of published papers reached its peak in 2024.China and the United States led in pub-lication volume.Harvard University was the most productive institution,and Asian institutions contributed a sig-nificant number of publications.The most prolific author was Gao Ju.The top five keywords by co-occurrence frequency were central post-stroke pain,neuropathic pain,pathophysiology,transcranial magnetic stimulation and motor cortex stimulation.Keyword clustering analysis generated ten clusters,which were integrated into four core research areas:pain types,clinical characteristics and diagnostic techniques,pathophysiological mecha-nisms,and treatment strategies.The bursting words included spinal cord and molecular expression in recent years;pathophysiology was the most bursting word.Conclusion In recent years,researches on CPSP are significantly increasing,focusing on pathophysiological mecha-nisms and intervention strategies.Future studies should strengthen the integration of basic and clinical research,promote multidisciplinary collaboration,and enhance research quality.
6.Meta-analysis of Reduning in the treatment of respiratory syncytial virus pneumonia in children
Hui WANG ; Xuefeng WANG ; Ruixue LI ; Jingwen MU ; Xiuying ZHANG
China Modern Doctor 2025;63(17):47-51
Objective To evaluate the clinical efficacy,safety and economy of Reduning injection in the treatment of respiratory syncytial virus pneumonia in children.Methods Randomized controlled trials that met the inclusion and exclusion criteria in database were searched.The data extraction and quality evaluation of the literature were performed independently by two people.Meta-analysis was performed.A total of 6 studies involving 514 children were included.Results The total effective rate of Reduning injection combined with western medicine in the treatment of children with respiratory syncytial virus pneumonia was higher than that in western medicine group.The cough,dyspnea,wheezing disappearance time,hospitalization time were shorter than those in western medicine group,and the levels of inflammatory factors and immune cells were better than those in western medicine group.The incidence of adverse events in Reduning injection combined with western medicine group was lower than that in western medicine group,and the hospitalization cost was lower than that in western medicine group.The above results were statistically significant(P<0.05).Conclusion Reduning injection combined with western medicine in the treatment of children with respiratory syncytial virus pneumonia can improve the clinical efficacy,with good safety and less hospitalization costs.
7.Tuihuang Mixture improves α-naphthylisothiocyanate-induced cholestasis in rats by inhibiting NLRP3 inflammasomes via regulating farnesoid X receptor
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Ruixue MA ; Yuchun YU ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Journal of Southern Medical University 2025;45(4):718-724
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.
8.Meta-analysis of Reduning in the treatment of respiratory syncytial virus pneumonia in children
Hui WANG ; Xuefeng WANG ; Ruixue LI ; Jingwen MU ; Xiuying ZHANG
China Modern Doctor 2025;63(17):47-51
Objective To evaluate the clinical efficacy,safety and economy of Reduning injection in the treatment of respiratory syncytial virus pneumonia in children.Methods Randomized controlled trials that met the inclusion and exclusion criteria in database were searched.The data extraction and quality evaluation of the literature were performed independently by two people.Meta-analysis was performed.A total of 6 studies involving 514 children were included.Results The total effective rate of Reduning injection combined with western medicine in the treatment of children with respiratory syncytial virus pneumonia was higher than that in western medicine group.The cough,dyspnea,wheezing disappearance time,hospitalization time were shorter than those in western medicine group,and the levels of inflammatory factors and immune cells were better than those in western medicine group.The incidence of adverse events in Reduning injection combined with western medicine group was lower than that in western medicine group,and the hospitalization cost was lower than that in western medicine group.The above results were statistically significant(P<0.05).Conclusion Reduning injection combined with western medicine in the treatment of children with respiratory syncytial virus pneumonia can improve the clinical efficacy,with good safety and less hospitalization costs.
9.SIRT1 inhibits D-galactose-induced cardiomyocyte aging and apoptosis through Wnt/β-catenin pathway
Ruixue CHEN ; Shujin PANG ; Xin CHEN ; Yining GUO ; Hongcheng FANG ; Hongxue LÜ ; Lingjun WANG
Chinese Journal of Pathophysiology 2025;41(3):463-471
AIM:To investigate the effect of silent information regulator 1(SIRT1)on the degree of aging and apoptosis in a mouse cardiomyocyte aging model through the regulation of Wnt/β-catenin pathway.METHODS:An in vi-tro aging model was established by inducing HL-1 cells with 40 μmol/L D-galactose(D-Gal).The HL-1 cells were trans-fected with a lentivirus overexpressing SIRT1,and the transfection efficiency was verified by Western blot.Western blot was used to detect the protein expression levels of SIRT1,P53,P21,cleaved caspase-3,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),β-catenin,Wnt3a and c-Myc.Senescence-associated β-galactosidase(SA-β-Gal)staining was used to detect cellular senescence level.MTT colorimetric assay was used to detect the cell viability,and flow cytometry was used to detect the apoptosis.RESULTS:Treatment of HL-1 mouse cardiomyocytes with D-Gal led to in-creases in the expression levels of aging-related proteins P53 and P21,as well as an increase in SIRT1 protein level.Addi-tionally,the SA-β-Gal staining showed a significant increase in the positive area(P<0.05).The expression levels of apop-tosis-related proteins cleaved caspase-3 and Bax were elevated,while the level of the anti-apoptotic protein Bcl-2 was re-duced(P<0.05).There was a marked decrease in cell viability(P<0.05),and flow cytometry analysis demonstrated a significant increase in cell apoptosis rate(P<0.05),which was positively correlated with the duration of D-Gal treatment.Overexpression of SIRT1 notably reduced both aging and apoptosis levels after 48 h of D-Gal treatment(P<0.05).After D-Gal treatment,the expression levels of β-catenin,c-Myc and Wnt3a proteins were up-regulated.However,these levels were reduced when SIRT1 was overexpressed.Moreover,the addition of LiCl,a Wnt/β-catenin pathway agonist,resulted in increased expression levels of β-catenin,c-Myc and Wnt3a proteins compared with the group with SIRT1 overexpres-sion and D-Gal treatment(P<0.05).CONCLUSION:SIRT1 inhibits cardiomyocyte apoptosis and alleviates cardiomyo-cyte aging through the Wnt/β-catenin pathway.
10.Researches on central post-stroke pain:a bibliometric analysis
Xinyue ZHOU ; Ruixue YE ; Yaqi MA ; Ying XU ; Longyao CAO ; Yulong WANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):1038-1049
Objective To analyze the research status,hotspots and development trends in the field of central post-stroke pain(CPSP).Methods Relevant literatures up to April 8,2025 were retrieved from the Web of Science Core Collection database.CiteSpace 6.4.R1 advanced version was used for bibliometric and visualization analysis of publication trends,country/institution/author collaboration networks,keywords and burst terms.Results A total of 119 publications were included.Researches on CPSP have shown an overall upward trend since 2002,which could be divided into a slow development period(from 2002 to 2015)and a rapid growth period(from 2016 onwards).The number of published papers reached its peak in 2024.China and the United States led in pub-lication volume.Harvard University was the most productive institution,and Asian institutions contributed a sig-nificant number of publications.The most prolific author was Gao Ju.The top five keywords by co-occurrence frequency were central post-stroke pain,neuropathic pain,pathophysiology,transcranial magnetic stimulation and motor cortex stimulation.Keyword clustering analysis generated ten clusters,which were integrated into four core research areas:pain types,clinical characteristics and diagnostic techniques,pathophysiological mecha-nisms,and treatment strategies.The bursting words included spinal cord and molecular expression in recent years;pathophysiology was the most bursting word.Conclusion In recent years,researches on CPSP are significantly increasing,focusing on pathophysiological mecha-nisms and intervention strategies.Future studies should strengthen the integration of basic and clinical research,promote multidisciplinary collaboration,and enhance research quality.

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