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.

ObjectiveTo investigate the mechanism of Hei Xiaoyaosan （HXS） in ameliorating cognitive impairment in the rat model of Alzheimer's disease （AD） by regulating the adenosine 5'-monophosphate-activated protein kinase （AMPK）/sterol regulatory element-binding protein 2 （SREBP2）/proprotein convertase subtilisin/kexin type 9 （PCSK9）/low-density lipoprotein receptor-related protein 1 （LRP-1） signaling pathway to clear amyloid-β （Aβ） from the peripheral circulation. MethodsNinety 8-week-old specific pathogen-free （SPF）-grade male Sprague-Dawley （SD） rats were acclimatized for 1 week. After acclimatization， 10 rats were randomly selected as the blank control group， and the remaining 80 rats were prepared for surgical modeling. Among the 80 rats for modeling， 70 were anesthetized and injected with 1 μL of amyloid-β_1-42 （Aβ_1-42） solution into the bilateral hippocampal CA1 region for the modeling of AD， and the remaining 10 were assigned to the sham operation group， which received an injection of 1 μL normal saline at the same anatomical site. The successfully modeled rats were randomly assigned into 6 groups （n=10 per group）： a model group， a donepezil hydrochloride group， an acadesine （AICAR， an AMPK agonist） group， and high-， medium-， and low-dose HXS groups. After 42 consecutive days of administration intervention， the Morris water maze test and T-maze test were performed to evaluate the learning and memory abilities of rats. Fluoro-Jade B （FJB） staining was conducted to observe pathological changes of neurons in the rat hippocampus， and thioflavin S staining to quantify the area of Aβ deposition in the hippocampal region. Immunofluorescence double staining （IF-DS） was performed to detect the expression of LRP-1 and Aβ signals in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of Aβ_1-42 and soluble LRP-1 （sLRP-1） in the serum. Western blot was performed to determine the protein levels of AMPK， phosphorylated AMPK （p-AMPK）， SREBP2， PCSK9， and LRP-1 in the liver tissue. Real time polymerase chain reaction（Real-time PCR） was adopted to assess the mRNA levels of AMPK， SREBP2， PCSK9， and LRP-1 in the liver tissue. ResultsCompared with the blank control group， the model group showed increased total swimming distance on day 6 and path length in the target quadrant on day 7 （P<0.01）， a decreased correct alternation rate in the T-maze test （P<0.01）， disarrangement of hippocampal neurons， increased FJB-positive cells （P<0.01）， enlarged area of Aβ deposition （P<0.01）. reduced LRP-1 fluorescence signals and enhanced Aβ fluorescence signals in the liver tissue （P<0.01）， elevated serum level of Aβ_1-42， declined serum level of sLRP-1 （P<0.01）， downregulated protein levels of p-AMPK and LRP-1 as well as mRNA levels of AMPK and LRP-1， and upregulated protein and mRNA levels of SREBP2 and PCSK9 in the liver tissue （P<0.01）. Compared with the model group， the high-dose HXS group， donepezil hydrochloride group， and AICAR group exhibited reduced total swimming distance and target quadrant path length （P<0.05， P<0.01）， an increased correct alternation rate in the T-maze test （P<0.05）， decreased FJB-positive cells （P<0.01）， reduced Aβ deposition （P<0.01） in the hippocampal tissue， enhanced LRP-1 signals and weakened Aβ signals in the liver tissue （P<0.01）， a declined serum level of Aβ_1-42 and an elevated serum level of sLRP-1 （P<0.01）， upregulated protein levels of p-AMPK and LRP-1 as well as mRNA levels of AMPK and LRP-1， and downregulated protein and mRNA levels of SREBP2 and PCSK9 in the liver tissue （P<0.01）. ConclusionHei Xiaoyaosan can regulate the AMPK/SREBP2/PCSK9/LRP-1 signaling pathway to enhance the clearance of peripheral Aβ by the liver tissue and reduce Aβ deposition in the brain， thereby improving the learning and memory abilities of AD rats.

ObjectiveTo investigate the effect and mechanism of Hei Xiaoyaosan in preventing and treating Alzheimer's disease （AD） by activating autophagy through regulating the adenosine monophosphate-activated protein kinase （AMPK）/UNC-51 like autophagy activating kinase 1 （ULK1） signaling pathway. MethodsNinety 8-week-old male SPF-grade SD rats were selected and randomized into two groups： a blank control group （n=10） and a modeling group （n=80）. From the modeling group， 10 rats were randomly assigned as a sham group （bilateral hippocampal injection of 1 μL normal saline）， while the remaining 70 rats were injected with 1 μL Aβ_1-42 solution bilaterally into the hippocampus to replicate the AD model. The Morris water maze test was conducted to screen the successfully modeled rats， which were then randomly allocated to the model， donepezil hydrochloride， 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside （AICAR， an AMPK agonist）， and high-， medium-， and low-dose Hei Xiaoyaosan groups， with 10 rats per group. After 42 days of drug intervention， the Morris water maze and open field tests were conducted to assess learning and memory abilities and motor function. Pathological changes in the hippocampal tissue were observed by Nissl staining， and autophagy-related pathological damage was examined via transmission electron microscopy （TEM）. The expression of LC3 in the hippocampus was observed by immunofluorescence staining. The protein levels of AMPK， phosphorylate （p）-AMPK， ULK1， p-ULK1， p62， and autophagy related 7 （Atg7） were determined by Western blot， while the mRNA levels of AMPK and ULK1 were measured by Real-time polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank control group， the model group showed increased escape latency （P<0.01） and decreased platform crossings （P<0.01） on day 6 in the water maze test， reduced total distance traveled and average speed in the open field test （P<0.01）， disarranged neurons with Nissl body loss and evident autophagic damage， weakened LC3 fluorescence signal （P<0.01）， downregulated protein levels of p-AMPK， p-ULK1， and Atg7 and mRNA levels of AMPK and ULK1 in the hippocampus （P<0.01）， and upregulated protein level of p62 （P<0.01）. Compared with the model group， the positive drug group， high-dose Hei Xiaoyaosan group， and AICAR group showed decreased escape latency （P<0.05， P<0.01） and increased platform crossings （P<0.01） on day 6， and increased total distance traveled and average speed in the open field test （P<0.05）. The positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group showed alleviated cellular structural damage， regular neuronal arrangement， increased Nissl bodies， and orderly distribution of autophagosomes. Furthermore， the LC3 fluorescence intensity was enhanced in the positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group （P<0.01）. The positive drug group， high-dose Hei Xiaoyaosan group， and the AICAR group exhibited upregulated protein and mRNA levels of p-AMPK and p-ULK1 （P<0.05， P<0.01）， upregulated protein level of Atg7 （P<0.05， P<0.01）， and downregulated protein level of p62 （P<0.01）. ConclusionHei Xiaoyaosan can improve learning and memory abilities and alleviate pathological status in the rat model of AD by regulating the AMPK/ULK1 signaling pathway， enhancing cellular autophagy， and repairing damaged nerve cells.

ObjectiveStarting from the etiology， pathogenesis， and treatment strategies of endometriosis and adenomyosis， to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology. MethodsAccording to the systematic review of text and opinion （SrTO） process developed by the Joanna Briggs Institute （JBI） in Australia， this paper determined literature screening criteria by searching China National Knowledge Infrastructure （CNKI）， VIP， Wanfang， and China Biomedical Literature Database. Information was extracted after literature screening， and quality evaluation was conducted using the JBI Narrative， Text， and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative， Opinion， Text Evaluation， and Review Tool Summary Table was used for information synthesis， and data analysis and display were conducted in the form of text and charts. ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics， meridian circulation location， pathological product evolution， disease duration， emotional psychology， lifestyle habits， preference for food and drink， innate endowment， and acquired injury. In terms of treatment， it was advocated to divide the stage， treat according to different types， adapt to the times， integrate nature and humans， and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects， make good use of classic formulas and small prescriptions， pay attention to protecting the spleen and stomach and regulating emotions， and make good use of self-formulated empirical formulas for internal or external use. Besides， individualized long-term management of patients was also advocated. ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes， mechanisms， diagnosis， and treatments of endometriosis， providing a scientific and standardized reference for future theoretical exploration.

Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.

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 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.