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 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 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.

Objective:To systematically evaluate the intervention effect of oral immunotherapy (OIT) on ventilator-associated pneumonia (VAP) of premature infants.Methods:This study searched the Cochrane Library, PubMed, Embase, Web of Science, CINAHL, Chinese Biomedical Literature Service System, China National Knowledge Infrastructure (CNKI) , WanFang Database and VIP Database, and conducted a comprehensive search for randomized controlled trials of OIT applied to premature infants published from database establishment to October 2020. Two researchers independently screened literature, extracted data, and evaluated methodological quality. RevMan 5.3 software was used for Meta-analysis.Results:A total of 8 studies were included, with a total of 351 premature infants in the intervention group and 352 premature infants in the control group. Meta-analysis results showed that OIT could reduce the incidence of VAP in premature infants [ RR=0.36, 95% CI (0.23-0.56) , P<0.05] and the detection rate of pathogenic microorganisms in the tracheal tube [ RR=0.33, 95% CI (0.18-0.59) , P=0.000 2], and could shorten the length of hospital stay [ MD=-6.70, 95% CI (-13.34--0.06) , P=0.05]. However, there was no statistically significant difference in the mechanical ventilation time, detection rate of oropharyngeal pathogenic microorganisms and mortality rate between the two groups after the intervention (all P>0.05) . Conclusions:OIT can reduce the incidence of VAP in premature infants and the detection rate of pathogenic microorganisms in the tracheal tube, and shorten the length of hospital stay to a certain extent. However, high-quality, large-sample, multi-center randomized controlled studies are still needed for further verification in the future.

Objective:To understand the clinical features and outcomes of chronic liver diseases overlapping with CMV infection.Methods:Clinical characteristics, treatment and outcome of patients of chronic liver diseases overlapping with CMV infection were analyzed retrospectively. T-test was used for measurement data and χ2 test was used for count data. All measurement data were expressed by ( ± s). P > 0.05 was not determined as significant. P < 0.05 was regarded as statistically significant. Results:Chronic liver diseases overlapping with CMV infections had similar clinical features. Etiopathogenic treatment + symptomatic supportive treatment + CMV overlapping infection treatment (including antiviral therapy, corticosteroids consideration, clearing heat and traditional Chinese choleretic medicine, etc) were the primary principles of therapy. The incidence of cytomegalovirus infection accounted for 4.125% during the corresponding hospitalization period. Cytomegalovirus infection had relatively caused liver function damage in patients with milder clinical symptoms and signs. Biochemical indicators before and after treatment showed that there was no significant difference in total bilirubin (TBil) before (262.93 ± 178.944) μmol/L and after one week of treatment (245.08 ± 179.332) μmol/L ( P > 0.05). However, when TBIL was compared with three (156.58 ± 147.461) μmol/L and four weeks (103.39 ± 102.218) μmol/L) of treatment, the decrease was significant ( P < 0.05, P < 0.01). Alanine aminotransferase (ALT) after one week (293.57 ± 467.438) U/L ( P < 0.01) of treatment was significantly lower than before treatment (782.34 ± 828.801) U/L. Gamma-glutamyl transferase (GGT) after treatment (202.52 ± 155.174)U/L was significantly lower than before treatment(280.69 ± 205.619)U/L). Total bile acid (TBA) was increased after treatment (198.04 ± 155.174)μmol/L, when compared with that of before treatment (62.93 ± 178.944)μmol/L. Biochemical indicators of liver diseases had shown typical features of cholestasis, and the slow and reduced flow of bile acid was tracked and observed. Compared with the advanced group (182.45 ± 214.169) umol/L, the total bilirubin in inflammation group (50.36 ± 26.282) umol/L was decreased ( P < 0.05). Moreover, advanced group (122.18 ± 106.780) umol/L ( P < 0.05) had elevated total bile acid normalization rate than that of bile acid group (54.82 ± 56.123) umol/L, and the inflammatory phase had significantly better outcome than those with advanced-stage. Conclusion:Chronic liver diseases overlapping with cytomegalovirus infection has a good therapeutic outcome in the inflammatory phase, but in the advanced-stage; the therapeutic efficacy and outcome is poor and perilous.