OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules （CQYG） improving hepatocellular carcinoma （HCC）. METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group （normal saline）， sorafenib group （positive control， 50 mg/kg）， and CQYG low-， medium- and high-dose groups （24.83， 49.66， 99.32 g/kg）， with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， for 14 consecutive days. After last administration， pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition （EMT） [N-cadherin， E-cadherin， Vimentin， matrix metalloproteinase 7 （MMP7）] and the mitogen-activated protein kinase （MAPK） signaling pathway [p38 MAPK， phosphorylated p38 MAPK， c-Jun N-terminal kinase （JNK）， phosphorylated JNK， extracellular regulated protein kinase 1/2 （ERK1/2）， phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways， pathways in cancer， and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments， the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group， CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover， the expression levels of Ki-67， N-cadherin， MMP7 and Vimentin proteins， along with the phosphorylation levels of ERK1/2 and JNK proteins， were all significantly reduced （ P ＜0.05）. The expression level of E-cadherin protein was significantly increased （ P ＜0.05）， the phosphorylation level of p38 MAPK protein was increased， the difference was not statistically significant （ P ＞0.05）. CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway， thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.

OBJECTIVE To investigate the effects and mechanism of Yigan huayu formula in alleviating liver fibrosis in mice. METHODS Mice were randomly divided into blank group （normal saline）， model group （normal saline）， Yigan huayu formula low- and high-dose groups （28.98， 57.96 g/kg， calculated by crude drug）， with 8 mice in each group. Except for the blank group， the liver fibrosis model was induced by intraperitoneal injection of 15%CCl 4 -olive oil solution. From the third week， the mice received the medicine/normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， liver indexes were calculated， the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， as well as the hydroxyproline （HYP） content in liver tissue， were measured. Liver histopathology was evaluated. Differentially expressed proteins （DEPs） in liver tissue were analyzed based on proteomics， followed by bioinfo rmatics analysis. The expressions of core DEPs were validated using Western blot （WB） and immunohistochemistry （IHC） methods. RESULTS Compared with the blank group， the model group showed significantly elevated liver indexes， serum activities of ALT and AST， and hepatic HYP content （ P ＜0.05）， along with obvious pathological damage and collagen deposition. Compared with the model group， the above indexes of mice in the Yigan huayu formula high-dose group were decreased significantly （ P ＜0.05）， with marked improvement in liver pathological damage and collagen deposition. Proteomics identified 210 DEPs between the model group and Yigan huayu formula high-dose group. DEPs were significantly enriched in extracellular matrix （ECM）-receptor interaction and lipid metabolism pathways. WB and IHC confirmed that Yigan huayu formula could significantly inhibit the abnormally elevated expressions of collagen type Ⅳ alpha1 chain （COL4A1）， secreted protein acidic and rich in cysteine （SPARC）， vitronectin （VTN） and laminin subunit alpha5 （LAMA5） in liver tissue of mice （ P ＜0.05）. CONCLUSIONS Yigan huayu formula may exert anti-hepatic fibrosis effects by inhibiting the expressions of proteins such as COL4A1， LAMA5， SPARC， and VTN， thereby blocking the ECM-receptor interaction signaling pathway， and subsequently suppressing excessive ECM deposition and basement membrane remodeling.

OBJECTIVE To explore the mechanism of Chaiqi yigan granules （CQYG） against liver cancer through the ferroptosis pathway. METHODS Network pharmacology combined with ferroptosis-related database was used to screen key targets and main effective components of CQYG against liver cancer via regulating ferroptosis； molecular docking technology was employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank serum control （CON） group， CQYG drug-containing serum （CQYGKL） group， ferroptosis inducer （RSL3） group， mammalian target of rapamycin complex 1 （mTORC1） inhibitor （RMC-5552） group， mTORC1 agonist （CCT007093） group， and CCT007093+CQYGKL group. The levels of Fe 2+ ， malondialdehyde （MDA）， and glutathione （GSH） in the cells were detected in the former three groups； mRNA expressions of mammalian target of rapamycin （mTOR）， sterol regulatory element-binding protein 1 （SREBP1）， and stearoyl-CoA desaturase 1 （SCD1）， protein expressions of SREBP1 and SCD1 as well as phosphorylation levels of mTOR and ribosomal S6 kinase （S6K） proteins were detected in all groups. RESULTS Key targets of CQYG for anti-liver cancer through the ferroptosis pathway were mTOR， SREBP1， SCD1，etc. The main active components included quercetin， tanshinone Ⅱ A ， baicalein， etc. The binding energies of main active components to key targets were all less than －5 kJ/mol. Compared with CON group， the levels of Fe 2+ and MDA in the cells in CQYGKL group and RSL3 group were significantly increased， while the levels of GSH were significantly decreased （ P ＜0.05）. mRNA expressions of mTOR， SREBP1 and SCD1， protein expressions of SREBP1 and SCD1， as well as the phosphorylation levels of mTOR and S6K proteins were significantly decreased in the CQYGKL group， RSL3 group， and RMC-5552 group， whereas all the above indicators were significantly increased in the CCT007093 group （ P ＜0.05）. Compared with CCT007093 group， the changes in all the above indicators were significantly suppressed in the CCT007093+CQYGKL group （ P ＜0.05）. CONCLUSIONS CQYG may induce ferroptosis by inhibiting mTORC1/SREBP1/SCD1 axis， thereby exerting anti-liver cancer effects.

ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine （TCM） constitution and factors associated with hyperuricemia （HUA） in the HUA population， providing a reference for persona-lized prevention and management of HUA. MethodsA cross-sectional study was conducted among individuals who had completed both serum uric acid （SUA） testing and TCM constitution identification during health examinations. According to SUA levels， participants were divided into a hyperuricemia group and a normal SUA group； according to the constitution identification results， participants were classified into balanced constitution， single biased constitution， and mixed constitution. The distribution characteristics of TCM constitution were compared between the two groups； participants in the hyperuricemia group were stratified by sex and age （≥18 years and ＜40 years， ≥40 years）， and the distribution characteristics of TCM constitution were compared across different sex and age groups. Logistic regression was used to analyze factors associated with HUA， with further stratified analyses by sex and age. ResultsA total of 10 920 participants were included， comprising 4170 cases （38.19%） in the hyperuricemia group and 6750 cases （61.81%） in the normal serum uric acid group. According to TCM constitution， there were 420 cases （3.85%） with balanced constitution， 6108 cases （55.93%） with single biased constitution， and 4392 cases （40.22%） with mixed constitution. In the hyperuricemia group， there were 80 cases （19.05%） with balanced constitution； 2275 cases （37.25%） with single biased constitution， among which damp-heat constitution （1205 cases， 52.97%）， phlegm-dampness constitution （500 cases， 21.98%）， and qi-stagnation constitution （181 cases， 7.96%） accounted for relatively high proportions； and 1815 cases （41.33%） with mixed constitution， among which mixed constitution involving phlegm-dampness （51.35%， 932 cases）， mixed constitution involving blood stasis （47.00%， 853 cases）， and mixed constitution involving damp-heat （41.21%， 748 cases） accounted for relatively high proportions. Logistic regression showed that qi-stagnation constitution （OR=1.68）， mixed constitution involving qi-stagnation （OR=1.53）， mixed constitution involving phlegm-dampness （OR=1.55）， and mixed constitution involving blood stasis （OR=1.50） were independently associated with HUA （P＜0.05）. Sex-stratified analysis showed that mixed constitution involving phlegm-dampness was positively associated with HUA risk in females； age-stratified analysis showed that， among individuals aged ≥18 and ＜40 years， qi-stagnation constitution， mixed constitution involving qi stagnation， and mixed constitution involving phlegm-dampness were positively associated with HUA risk （all P＜0.05）. ConclusionThe prevalence of HUA differs markedly by sex and age. Mixed constitution accounts for a higher proportion of HUA patients. Qi-stagnation constitution， mixed constitution involving qi stagnation， mixed constitution involving phlegm-dampness， and mixed constitution involving blood stasis are associated with HUA. Notably， the specific association of mixed constitution involving phlegm-dampness in females and qi-stagnation constitution in young adults is particularly prominent.

Objective:To investigate the effects of Yisui Shengxue Decoction on the regulation of Notch signaling pathway on bone marrow hematopoiesis in mice with aplastic anemia(AA).Methods:A total of 60 CByB6F1 mice were randomly divided into blank group,model group,positive control cyclosporine(CsA)group,low-dose(YSSX-L)group and high-dose(YSSX-H)group of Chinese herbal compound Yisui Shengxue Decoction,with 12 mice in each group.Except for the blank group,the mice in each group were given 5 Gy X-ray irradiation combined with tail vein infusion of lymphocytes to establish the immune-mediated AA mouse model.The low and high dose groups were given 8.6 and 17.2 g/(kg?d)of Yisui Shengxue Decoction by gavage,the model group and the blank group were given equal volume of saline by gavage,and the positive control group was given 25 mg/(kg?d)of cyclosporine by ga-vage for 14 days.The mice were tested for white blood cell count(WBC),red blood cell count(RBC),hemoglobin(Hb),platelet count(PLT)and bone marrow nucleated cell count in peripheral blood,bone marrow pathological changes and the levels of IFN-γ,IL-4 and IL-5 in peripheral serum,and T-lymphocyte transcription factors T-bet,GATA3,RORγt,FOXP3 mRNA and protein in spleen tissues,as well as the expression levels of Notch signaling pathway-related genes and protein in spleen tissues.Results:Compared with the blank group,the peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,expressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly lower in the model group(P<0.01),and the expressions of serum IFN-γ,spleen tissue T-bet,RORγt mRNA and protein,and Notch1,Jagged1,DLL4 mRNA and protein were significantly in-creased(P<0.05).Compared with the model group,peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,ex-pressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly higher in each intervention group(P<0.05),and the expression of serum IFN-γ and spleen tissue T-bet,RORγt mRNA and protein as well as Notch1,Jagged1,DLL4 mRNA and protein were significantly reduced(P<0.05).Conclusion:Yisui Shengxue Decoction can improve bone marrow he-matopoietic function and regulate immune disorders in AA mice,and its mechanism of action may be related to the regulation of Notch signaling pathway.

Objective:To investigate the effects of Yisui Shengxue Decoction on the regulation of Notch signaling pathway on bone marrow hematopoiesis in mice with aplastic anemia(AA).Methods:A total of 60 CByB6F1 mice were randomly divided into blank group,model group,positive control cyclosporine(CsA)group,low-dose(YSSX-L)group and high-dose(YSSX-H)group of Chinese herbal compound Yisui Shengxue Decoction,with 12 mice in each group.Except for the blank group,the mice in each group were given 5 Gy X-ray irradiation combined with tail vein infusion of lymphocytes to establish the immune-mediated AA mouse model.The low and high dose groups were given 8.6 and 17.2 g/(kg?d)of Yisui Shengxue Decoction by gavage,the model group and the blank group were given equal volume of saline by gavage,and the positive control group was given 25 mg/(kg?d)of cyclosporine by ga-vage for 14 days.The mice were tested for white blood cell count(WBC),red blood cell count(RBC),hemoglobin(Hb),platelet count(PLT)and bone marrow nucleated cell count in peripheral blood,bone marrow pathological changes and the levels of IFN-γ,IL-4 and IL-5 in peripheral serum,and T-lymphocyte transcription factors T-bet,GATA3,RORγt,FOXP3 mRNA and protein in spleen tissues,as well as the expression levels of Notch signaling pathway-related genes and protein in spleen tissues.Results:Compared with the blank group,the peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,expressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly lower in the model group(P<0.01),and the expressions of serum IFN-γ,spleen tissue T-bet,RORγt mRNA and protein,and Notch1,Jagged1,DLL4 mRNA and protein were significantly in-creased(P<0.05).Compared with the model group,peripheral blood WBC,RBC,Hb,PLT,bone marrow nucleated cell count,ex-pressions of serum IL-4,IL-5 and spleen tissue GATA3,FOXP3 mRNA and protein were significantly higher in each intervention group(P<0.05),and the expression of serum IFN-γ and spleen tissue T-bet,RORγt mRNA and protein as well as Notch1,Jagged1,DLL4 mRNA and protein were significantly reduced(P<0.05).Conclusion:Yisui Shengxue Decoction can improve bone marrow he-matopoietic function and regulate immune disorders in AA mice,and its mechanism of action may be related to the regulation of Notch signaling pathway.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

OBJECTIVE To systematically evaluate the efficacy and safety of probiotics in the treatment of nonalcoholic fatty liver disease （NAFLD）. METHODS Retrieved from CNKI， Wanfang data， VIP， SinoMed， PubMed， Embase， Web of Science， Cochrane library databases， the published randomized controlled trials （RCTs） about probiotics（treatment group） versus placebo or healthy lifestyle（control group） in the treatment of NAFLD were collected from the inception to Oct. 10th， 2023. The quality of the included literature was evaluated and rated by Cochrane system evaluator manual 5.1.0 and GRADE tools. Meta-analysis and Egger’s test were carried out by using RevMan 5.4 and Stata 17.0 software. RESULTS Overall 24 RCTs were included in this study， involving 1 391 patients with NAFLD. Meta-analysis showed that compared with control group， the levels of alanine aminotransferase [MD＝－6.29， 95%CI （－9.35， －3.22）， P＜0.000 1]， aspartate aminotransferase [MD＝－4.89， 95%CI （－7.55， －2.23）， P＝0.000 3] and γ-glutamyl transferase [MD＝－4.87， 95%CI （－6.54， －3.20）， P＜0.000 01]， the liver stiffness measurement [MD＝－0.36， 95%CI （－0.48， －0.24）， P＜0.000 01]， the levels of triglycerides [MD＝－0.22， 95%CI （－0.27， －0.16）， P＜0.000 01]， total cholesterol [MD＝－0.34， 95%CI （－0.44， －0.25）， P＜0.000 01] and insulin resistance assessed by homeostasis model [MD＝－0.38， 95%CI （－0.63， －0.13）， P＝0.003] were all significantly decreased in the treatment group. However， there was no statistically significant difference of probiotics therapy in the levels of tumor necrosis factor-α [MD＝－0.41， 95%CI （－1.29， 0.48）， P＝0.37]， interleukin-6 [MD＝0.39， 95%CI （ －0.10， 0.88）， P＝0.12]， high- sensitivity C-reactive protein [MD＝－0.30， 95%CI （－0.85，0.25）， P＝0.28]， high-density lipoprotein cholesterol [MD＝0.03， 95%CI （ －0.01， 0.06）， P＝0.10] and low-density lipoprotein cholesterol [MD＝－0.10， 95%CI （－0.27， 0.07）， P＝0.23] and body mass index [MD＝0.07， 95%CI （－0.26， 0.40）， P＝0.68]. Subgroup analysis based on different intervention measures showed that the levels of γ-glutamyl transferase， liver stiffness measurement， and homeostatic model assessment of insulin resistance in the synbiotic group were not significantly improved compared to the control group， with consistent results for the remaining outcomes. Egger’s test results showed no publication bias. CONCLUSIONS The probiotic therapy can regulate liver function indexes， liver stiffness measurement and insulin resistance levels in patients with NAFLD well.

Chronic hepatitis B （CHB） is still a malignant infectious disease that seriously threatens human health， and currently nucleos（t）ide analogues and interferon are the main treatment methods for CHB， but they cannot achieve functional cure. The development and progression of CHB are closely associated with immune function dysregulation in the host， and therefore， regulating host immunity has become a key link in the treatment of CHB. Recent studies have shown that traditional Chinese medicine exerts a therapeutic effect on CHB by regulating host immune function. This article introduces the relationship between traditional Chinese medicine theory and immunity and summarizes the theoretical basis and related studies for traditional Chinese medicine in the immune regulation of CHB， in order to provide new ideas for integrated traditional Chinese and Western medicine therapy for CHB.

ObjectiveTo study the clinical efficacy of dapagliflozin combined with Shexiang Baoxinwan （SXBXW） in the treatment of acute heart failure with reduced ejection fraction （HFrEF） and syndrome of Qi deficiency and blood stasis. MethodA total of 176 patients hospitalized due to acute HFrEF （syndrome of Qi deficiency and blood stasis） were selected and randomized into control group， SXBXW group， dapagliflozin group， and SXBXW + dapagliflozin group （the latter three groups were called the intervention groups）. The New York Heart Association （NYHA） class， 6-minute walk test （6MWT） score， Kansas City Cardiomyopathy Questionnaire （KCCQ） score， traditional Chinese medicine （TCM） syndrome score， N-terminal pro-brain natriuretic peptide （NT-proBNP）， soluble suppression of tumorigenicity 2 （sST2）， interleukin-6 （IL-6）， and hypersensitive C-reactive protein （hs-CRP） of the patients were evaluated and measured at the time of admission， 1 week after treatment， and 2 weeks of treatment. Furthermore， the hospital stay， in-hospital mortality， and 30-day re-admission rate were recorded. Statistical analysis was performed to evaluate the efficacy of each group. ResultAfter 1 week of treatment， the SXBXW group exhibited superior NYHA class， KCCQ score， TCM syndrome score and curative effect， IL-6， and hs-CRP to the control group （P<0.05， P<0.01）. After 2 weeks of treatment， the SXBXW group showed superior TCM syndrome score， TCM curative effect， and hs-CRP （P<0.05， P<0.01） to the control group. The dapagliflozin group was superior to the control group in terms of TCM syndrome score， NT-proBNP， and sST2 （P<0.05， P<0.01） after 1 week of treatment and in terms of NYHA class， KCCQ score， NT-proBNP， sST2， and hospital stay （P<0.05， P<0.01） after 2 weeks of treatment. The SXBXW + dapagliflozin group exhibited better efficacy than the control group in terms of NYHA class， 6MWT score， KCCQ score， TCM syndrome score and curative effect， NT-proBNP， sST2， IL-6， and hs-CRP （P=0.014） after 1 week of treatment and in terms of NYHA class， KCCQ score， TCM syndrome score and curative effect， NT-proBNP， sST2， IL-6， hs-CRP， and hospital stay （P<0.01） after 2 weeks of treatment. ConclusionSXBXW and dapagliflozin have good therapeutic effect on acute HFrEF and syndrome of Qi deficiency and blood stasis， and their combination demonstrated better therapeutic effect， with good safety and tolerability.