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.

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.

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 investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR).Methods Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled.The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively.The subjects were divided into 4 groups according to the SUA level quartiles.Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups.Results Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin (30 minINS), 2 hours postprandial insulin(2hlNS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P ＜ 0.01).The SUA level was positively correlated with age (r =0.157, P ＜ 0.01), BMI (r =0.262, P ＜ 0.01), waist circumference(r =0.372, P ＜ 0.01), systolic blood pressure (r =0.200, P ＜ 0.01), diastolic blood pressure(r =0.254,P ＜ 0.01) , 30 minutes postprandial plasma glucose(r =0.118 ,P =0.023), FINS(r =0.249, P ＜ 0.01), 30minlNS (r =0.189, P ＜ 0.01) ,2hlNS (r =0.206, P ＜ 0.01), glycosylated hemoglobin (HbAlc, r=0.106,P =0.042), HOMA-IR(r =0.244,P ＜0.01), TG(r =0.350,P ＜0.01), ΔI30/ΔG30 (r =0.144, P ＜ 0.01), and negatively correlated with HDL-C level (r =-0.321, P ＜ 0.01).Multiple stepwise regression analysis showed that SUA (β =0.292, P ＜ 0.01) and HOMA-IR (β3 =29.821, P ＜ 0.01)were positively associated with ΔI30/ΔG30.Conclusion SUA level is closely related with the early-phase insulin secretion in NGR subjects.

Objective To investigate the prevalence of renal insufficiency and its associated factors in type 2 diabetes mellitus with normoalbuminuria using estimated glomerular filtration rate ( eGFR) .Methods We retrospectively analyzed 10-year data of chronic complications in type 2 diabetics in-patient from the Chinese Diabetes Society.eGFR was estimated using the equation from Modification of Diet in Renal Disease(MDRD) study.The clinical characteristics as well as associated factors for low eGFR were analyzed among the normoalbuminuric type 2 diabetic patients.Results A total of 1351 type 2 diabetic patients were included, 755 patients with normoalbuminuria, 466 patients with microalbuminuria and 130 patients with macroalbuminuria respectively.Among the patients, 310 (22.9% ) had low eGFR (GFR <60 ml · min~(-1) · 1.73 m~(-2) ) , 19.7% (149/755) in the patients with normoalbuminuria, 21.9% (102/466) in microalbuminuria and 45.4% ( 59/130 ) in macroalbuminuria Patients with normoalbuminuria and low eGFR suffered more chronic complications than those with normoalbuminuria and normal eGFR, mainly retinopathy, cerebrovascular diseases and sensory neuropathy.Stepwise logistic regression analysis revealed that age ( OR = 1.042, P < 0.001), diabetic duration ( OR = 1.038, P = 0.045), systolic blood pressure (OR = 1.017, P < 0.001) were independently associated with renal impairment among the patients with normoalbuminuria.Body mass index ( OR = 0.868, P < 0.001) and HbAlc (OR =0.898, P =0.021) were also related with renal insufficiency.Conclusion A considerable proportion in type 2 diabetic patients without albuminuria may exist renal impairment, and eGFR estimation could benefit the evaluation of renal function in such patients.