Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Objective To observe the protective effect of Zhilong Huoxue Tongyu Capsule(Zhilong Capsule)on myocardial ischemia reperfusion injury(MIRI)in mice,and explore its regulatory mechanism using metabolomics.Methods Using a random number table method,30 C57BL/6J mice were randomly divided into the following three groups:sham operation group,model group,and Zhilong Capsule group(6.24 g/kg),with 10 mice in each group.In mice in the model group and the Zhilong Capsule group,a mouse MIRI model was established by ligating the left anterior descending branch,while mice in the sham operation group underwent threading without ligation.The Zhilong Capsule group began modeling one week after pre-administration and continued to receive intragastric administration for two weeks after modeling once daily.The cardiac function,including the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS),was assessed by color echocardiography.The myocardial fibrosis and apoptosis were observed by Masson staining and TUNEL staining,respectively.Enzyme-linked immunosorbent assay was used to measure the serum contents of lactate dehydrogenase(LDH)and brain natriuretic peptide(BNP).Liquid chromatography-mass spectrometry combined with multivariate statistical method was performed for serum metabolite detection and identification analysis.Results Compared with the model group,the mice in the Zhilong Capsule group exhibited an increase in LVEF and LVFS,a reduction in cardiac tissue structure disorder,a decrease in myocardial fibrosis,a decrease in cell apoptosis rate,and a decrease in serum LDH and BNP contents(P<0.05).Metabolomics result showed that intervention with Zhilong Capsule significantly regulated 30 differential metabolites related to MIRI.Important metabolic pathways involved 20 pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.Conclusion Zhilong Capsule has a protective effect on MIRI,and it may achieve this effect by regulating pathways related to tyrosine metabolism,arginine and proline metabolism,and vitamin digestion and absorption.

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

OBJECTIVE To investigate the protective effect of paeoniflorin(PF) on cardiac dysfunction and myocardial cell injury induced by cisplatin(CDDP) in rats. METHODS SD male rats were randomly divided into control group, CPPD group, and CDDP PF+low-dose, high-dose group. PowerLab multifunctional recorder was used to detect the related indexes of cardiac function: the changes of left ventricular peak pressure(LVSP), left ventricular end-diastolic pressure(LVEDP) and left ventricular pressure change rate(±dp/dt). Serum levels of inflammatory factors TNF-α, IL-1β and IL-6 were measured in each group. Myocardial tissue was stained to observe the changes of tissue structure. H9c2 cardiomyocytes were divided into control group, CDDP group, PF group and CDDP+PF group. The activity of H9c2 cardiomyocytes was measured by CCK-8. The apoptosis of cardiomyocytes in each group was detected by flow cytometry. The expressions of MAPK signaling pathway related proteins p38, ERK, JNK and their phosphorylated proteins and apoptosis-related proteins Bax, Bcl-2, Casp3, Cl-casp3 were detected in cardiomyocytes by Western blotting. RESULTS Compared with the control group, LVSP and ±dp/dt decreased, LVEDP increased in rats of CDDP group(P<0.01). Compared with CDDP group, both CDDP+low-dose and high-dose PF pretreatment increased LVSP and ±dp/dt value(P<0.05 or P<0.01), decreased LVEDP(P<0.01), and could decrease the serum inflammatory factor TNF-α, IL-1β and IL-6(P<0.01). Cell level results showed that compared with control group, in CDDP group, the cell activity decreased, the apoptosis-related protein Bax, Cl-casp3 increased(P<0.01), expression of anti-apoptotic protein Bcl-2 decreased(P<0.01), and the expression of p38 and ERK phosphorylation also increased(P<0.01). Compared with CDDP group, PF could restore cell activit, down-regulate apoptosis-related protein Bax, Cl-casp3(P<0.05 or P<0.01), and increase anti-apoptotic protein Bcl-2 expression(P<0.01), inhibit MAPK pathway p38 and ERK phosphorylation expression(P<0.01). CONCLUSION PF can restore cardiac dysfunction and myocardial cell injury induced by cisplatin in rats, which may be related to inhibiting inflammation and apoptosis by regulating ERK/p38 MAPK signal expression.

Objective To investigate the predictive value of tissue plasminogen activator(t-PA),chro-mogranin A(CgA),and lipoprotein related phospholipase A2(LP-PLA2)in serum for major adverse cardio-vascular event(MACE)after percutaneous coronary intervention(PCI).Methods A total of 120 patients with coronary heart disease who underwent PCI in the hospital from August 2020 to August 2022 were en-rolled in the study.According to whether MACE occurred within 1 year after PCI,the patients were divided into MACE group(33 cases)and non-MACE group(87 cases).The levels of serum t-PA,CgA,LP-PLA2 and clinical data were compared between the MACE group and the non-MACE group.Multivariate Logistic regres-sion was used to analyze the risk factors of MACE after PCI.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of t-PA,CgA and LP-PLA2 alone or in combination for MACE after PCI.Results The proportion of patients with smoking history,NT-proBNP,CgA,LP-PLA2,and the propor-tion of patients with hypertension in the MACE group were higher than those in the non-MACE group(P＜0.05),while left ventricular ejection fraction(LVEF)and t-PA were lower than those in the non-MACE group(P＜0.05).There were no significant differences in age,gender composition,serum creatinine,triglyc-erides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),drinking history,NYHA cardiac function classification,combined diabetes,application of aspirin,and application of clopidogrel between the two groups(P＞0.05).Multivariate Logistic regression analysis showed that smoking history,increased NT-proBNP,hypertension,decreased LVEF,decreased t-PA,increased CgA and increased LP-PLA2 were risk factors for MACE after PCI(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum t-PA,CgA and LP-PLA2 alone or in combination for predicting MACE after PCI were 0.785(95％CI:0.693-0.877),0.678(95％CI:0.564-0.791),0.730(95％CI:0.636-0.824),0.888(95％CI:0.830-0.946),respectively.The efficacy of combined prediction was bet-ter than those of single detections(P＜0.05).Conclusion The lower the serum t-PA level is and the higher the CgA and LP-PLA2 levels are,the greater the risk of MACE after PCI is.The combination of the three in-dicators has higher value in predicting MACE after PCI.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective:To investigate the effect of tofacitinib on early atherosclerosis of patients with systemic lupus erythematosus and explore the possible relationship between lupus nephritis and early atherosclerosis of systemic lupus erythematosus.Methods:Sixteen 8-week-old female MRL/lpr mice with a body weight of 20~25 g were selected and randomly divided into the treatment group and placebo group, with 8 mice in each group. The treatment group diluted tofacitinib by normal saline, and given at a dose of 10 mg·kg -1·d -1, and the placebo group (starch tablets) administered the medication in the same way as the treatment group for a total of 8 weeks. The ELISA method was applied to detect serum anti-dsDNA antibody levels in the two groups of mice. Bradford method protein concentration was used to determine the level of urine protein in mice. Automatic biochemical analyzer was used to detect blood lipids, urea nitrogen, serum creatinine, complement C3, complement C4 levels. Western blotting was used to determine the protein expression levels of monocyte chemoattractant protein-1 (MCP-1), non-receptor protein tyrosine kinase family 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 2 (STAT2) in aortic and kidney tissues. After the aortic arch section were prepared, oil red O was used to stain the sections, and the vascular plaque area and intimal thickness were evaluated by ImageJ software. The kidneys were dissected and stained with HE, and the active lesions of lupus nephritis were evaluated using the glomerular activity scoring system. SPSS 23.0 software was used for statistical analysis, in which the between-group comparison was performed using two independent samples t-test, and the correlation analysis was performed using the Spearman method. Results:①The serum anti-dsDNA antibody expression level in the treatment group [(5.2±1.0) U/ml] was lower than that in the placebo group [(6.9±1.2) U/ml], ( Z=-3.07, P=0.008), and the levels of complement C3 and complement C4 were higher than those in the placebo group [(293±10) mg/L vs. (260±19) mg/L, Z=2.72, P=0.017]; (16±6) mg/L vs. (8±9) mg/L, Z=3.78, P=0.006]. There was no significant difference in serum BUN and Scr between the treatment group and the placebo group [(10.6±0.7) mmol/L vs. (11.5±1.1) mmol/L, Z=-1.96, P=0.071; (17±5) μmol/L vs. (22±6) μmol/L, Z=-1.79, P=0.095]. ② Compared with the placebo group, the levels of LDL, TC and TG in the treatment group decreased [(0.83±0.15) mmol/L vs. (1.08±1.05) mmol/L, Z=-3.95, P=0.001; (2.90±0.08) mmol/L vs. (1.81±0.97) mmol/L, Z=-5.17, P=0.001; (1.10±0.08) mmol/L vs. (1.60±0.42) mmol/L, Z=-3.23, P=0.013], and HDL level increased [(2.02±0.99) mmol/L vs. (1.81±0.97) mmol/L, Z=4.42, P=0.001]. ③ Compared with the placebo group, the levels of aortic MCP-1, JAK1, STAT1 and STAT2 in the treatment group were reduced [(0.17±0.30) vs. (0.23±0.05), Z=-3.06, P=0.009; (0.83±0.09) vs. (1.05±0.19), Z=-3.07, P=0.008; (0.77±0.07) vs. (0.94±0.13), Z=-2.83, P=0.014; (0.70±0.07) vs. (0.82±0.09), Z=-2.83, P=0.013], the aortic plaque area and aortic intimal thickness were lower than those in the placebo group [(12±31) μm 2vs. (1 242±1 101) μm 2, Z=-3.12, P=0.016; (63±7) μm vs. (82.10±8.06) μm, Z=-5.13, P<0.001]. ④ Compared with the placebo group, the urine protein level and glomerulonephritis activity score in the treatment group were decreased [(0.08±0.03) mg/mL vs. (0.20±0.11) mg/mL, Z=-3.08, P=0.015; (1.79±0.38) vs. (2.79±0.14) points, Z=-7.08, P<0.001)], and renal tissue MCP-1, JAK1, STAT1.Compared with the placebo group, STAT2 levels were reduced [(0.364±0.040) vs. (0.425±0.021), Z=-3.85, P=0.003; (0.689±0.074) vs. (0.838±0.068), Z=-4.19, P=0.001; (0.508±0.070) vs. (0.646±0.019), Z=-2.85, P=0.015; (0.618±0.062) vs. (0.740±0.101), Z=-2.94, P=0.013. ⑤ The glomerular mobility scores of the two groups were positively correlated with LDL, TCHO, TG, aortic plaque area and aortic intimal thickness ( r=0.51, P=0.043; r=0.79, P<0.001; r=0.64, P=0.008; r=0.82, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.53, P=0.036). The urine protein levels in the two groups were positively correlated with LDL, TC, TG, aortic plaque area and aortic intimal thickness ( r=0.67, P=0.004; r=0.68, P=0.004; r=0.53, P=0.033; r=0.80, P<0.001; r=0.74, P=0.001), and negatively correlated with HDL ( r=-0.57, P=0.021). Conclusion:The severity of lupus nephritis is correlated with atherosclerosis and dyslipidemia in the early stage of systemic lupus erythematosus. Tofacitinib may reduce the degree of early arteriosclerosis and lupus nephritis in MRL/LPR mice, and reduce blood lipid levels, which may be effective in improving the prognosis of SLE and improving the survival rate of patients.

The microbiome plays a role in the development of lower urinary tract diseases, but the impact of viruses on these conditions remains unclear. In recent years, research has emerged demonstrating a potential link between viruses and lower urinary tract diseases, including bladder cancer, prostate cancer, and overactive bladder. In this paper, the research of the correlation between viruses and lower urinary tract diseases and the related mechanisms were reviewed.

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L