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 clone the HnGUA gene from Hirudo nipponia and conduct bioinformatics analysis,protein prokaryotic expression analysis and gene differential expression analysis.Methods Based on the transcriptome data of H.nipponia in the previous study,the full-length cDNA of HnGUA was cloned by rapid amplification of cDNA ends(RACE),and bioinformatics analysis was performed.The prokaryotic expression vector was constructed,transformed into Escherichia coli BL21(DE3)competent cells and the expression of recombinant protein was induced by IPTG.The qPCR was used to further analyze the tissue-specific expression of HnGUA.Results The size of HnGUA gene was 504 bp,containing an open reading frame(ORF)of 231 bp and encoding 76 amino acids.Its protein molecular weight and isoelectric point are 8.17 kDa and 4.44,respectively.Multiple sequence alignment analysis showed that HnGUA was highly homologous to genes in other leech species that encode inhibitory proteins.The results of the prokaryotic expression analysis showed that the constructed pET32a-HnGUA vector could be successfully expressed in E.coli BL21(DE3),and the SDS-PAGE results showed that the induced recombinantly expressed HnGUA protein was around 6 kDa,which was basically consistent with the predicted protein size.The results of the Real-time PCR revealed spatial and temporal differences in the expression profiles of HnGUA,with high levels of expression detected in the skin and crop tissues.Conclusion This study represents the first successful cloning of the HnGUA gene from H.nipponia and the expression of the corresponding recombinant protein in E.coli.It provides a foundation for future exploration of the biosynthetic pathways and molecular regulatory mechanisms of active small anticoagulant molecules in leeches.

Objective To evaluate the efficacy and safety of the new left ventricular circulation assist device iVAC 2L in high-risk percutaneous coronaryintervention(HR-PCI)in Chinese patients.Methods We reported 6 PCIs in 5 patients supported by iVAC 2L,a new left ventricular circulation assist device,performed in Macao from September 2022 to March 2023.All patients were assessed by heart team and categorize to be high-risk for procedure.Clinical and intra-procedural data were analyzed.iVAC 2L-related complications and 30-day results were also documented.Results Insertion and removement of iVAC 2L successfully performed in all the 5 patients.Three of them underwent complete revascularization in the index procedure;one failed for the first time due to intolerance of the prolonged procedure,but succeeded for the reattempt of complete revascularization a month later,with the support of iVAC 2L.PCI was abandoned due to poor vessel condition.iVAC 2L,the new left ventricular circulation assist device,supported effectively during the 6 procedures.The patients were stable during the procedure.The success rate of hemodynamic support was 100％.No iVAC 2L-related complications and 30-day major adverse cardiac and cerebral events occurred,the 30-day survival was 100％.Conclusions Initial experience suggested that the new left ventricular circulation assist device iVAC 2L could provide effective and safe support in high-risk PCI.

Background: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. Methods: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. Results: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) Conclusions: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China. Clinical trial registration NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

OBJECTIVE To explore the mechanisms of the volatiles of Wendan granule for the treatment of senile dementia,network pharmacology method integrating absorption,distribution,metab-olism, and excretion (ADME) screening, target fishing, network constructing, pathway analyzing, and correlated diseases prediction was applied. METHODS Twelve small molecular compounds of WDG were selected as the objects from 74 volatiles with the relative abundances above 2%,and their ADME parameters were collected from Traditional Chinese Medicine Systems Pharmacology platform (TCMSP), and then the corresponding targets, genes, pathways and diseases were predicted according to the data provided by TCMSP,DrugBank,Uniport and the Database for Annotation,Visualization and Integrated Discovery(DAVID).The related pathways and correlation analysis were explored by the Kyoto Encyclo-pedia and Genomes (KEGG) database. Finally, the networks of compound-target, target-pathway and pathway-disease of WDG were constructed by Cytoscape software. RESULTS Twelve compounds interacted with 49 targets, of which top three targets were Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), Prostaglandin G/H synthase 2 (PGHS-2) and Sodium-dependent noradrenaline transporter.Interestingly,these targets were highly associated with depression,insomnia and Alzheimer′s disease that mainly corresponded to mental and emotional illnesses. CONCLUSION The integrated network pharmacology method provides precise probe to illuminate the molecular mechanisms of volatiles of WDG for relieving senile dementia related syndromes,which will also facilitate the application of traditional Chinese medicine in modern medicine,as well as follow-up studies such as upgrading the quality stan-dard of clinical medicine and novel drug development.

Objective To explore the effects of artesunate on the proliferation,cell cycle,apoptosis and apoptosis-related protein of bortezomib-resistant multiple myeloma (MM) cells.Methods Human MM cell line NCI-H929 was treated with bortezomib in a dose-dependent manner to establish a bortezomib-resistant cell line NCI-H929BR.The logarithmic growth phase NCI-H929BR cells were divided into control group(blank culture medium)and two concentration experimental groups (artesunate,25,50 μg · mL-1)and treated for 48 h.The inhibitory role of artesunate on NCI-H929BR proliferation was measured by MTT assay.Cell apoptosis and cell cycle were determined by flow cytometry.The Bcl-2 family proteins (Bcl-2,Bcl-Xl,Bax) were detected by Western blot.Results Bortezomib resistance index of NCI-H929BR is 20.12 times than NCI -H929.After administration artesunate for 48 h,the proliferation rate of NCI-H929BR in the low and high concentration experimental groups were 62.46％,33.48％;there was significant difference compared with control group (all P＜0.05).The artesunate dramatically decreases NCI-H929BR proliferation in a dose-dependent manner (P ＜ 0.05).After treatment for 48 h with artesunate,the proportion of G1 phase cell cycle in high concentration experimental group was increased compared with control group [(51.63 ± 4.02) ％ vs (34.72 ± 2.43) ％,P ＜ 0.05].The proportion of apoptosis cell was increased,early apoptosis in high concentration experimental group and control group were (13.10 ± 1.53)％,(2.32 ± 1.02)％;and late apoptosis in the two groups were (10.26 ±2.42)％,(1.93 ± 0.69) ％;comparison between two groups,the difference had significantly (all P ＜ 0.05).In addition,artesunate significant decreased of Bcl-2 and Bcl-Xl protein expression and increased of Bax protein expression in a dose -dependent manner.Conclusion Artesunate could inhibit NCI-H929BR proliferation,increase apoptosis,cause G0/G1-arrest and down-regulate Bcl-2 and Bcl-Xl expression,while up-regulate Bax expression.

Objective:To investigate the effect of standardized nutritional therapy for gastric cancer during perioperation.Methods:Seventy-six patients with gastric cancer who underwent nutritional therapy were randomly divided into observation group (38 patients) and control group (38 patients),between May 2015 and May 2016.In the observation group,the nutritional therapy was made by medical workers who had received the training of Total Nutritional Therapy (TNT) and Goal Nutrition Therapy (GNT) for Cancer Patient.In the control group,the nutritional therapy was given by doctors according to their conventional experience.Nutritional conditions,gastrointestinal function recovery conditions,complications and hospital stays were compared between the two groups.Results:First,the weight,triceps skinfold thickness and arm muscle circumference of preoperative 1 day and postoperative 7 day in the observation patients were significantly higher than those in the control patients (P ＜ 0.05).Second,the level of serum prealbumin of preoperative 1 day,postoperative 1 and 7 day in the observation patients was significantly higher than that in the control patients (P ＜ 0.05).Third,the time of anus exhaust and defecate in observation group was significantly shorter than that in the control group (P ＜ 0.01).Fourth,each group had one patient who suffered bleeding after operation,and 2 patients in control group had anastomotic leakage.Fifth,the time of hospital stays in the observation group was significantly shorter than that in the control group (P ＜ 0.01).Conclusion:The standardized nutritional therapy for gastric cancer can improve the patient's nutrition status,promote the recovery of gastrointestinal function,and then decrease the time of hospital stays during perioperation.

Objective To explore the role of microRNA-155 ( miR-155 )/suppressor of cytokine signaling 1 ( SOCS1 ) pathway combined with IL-17 in modulating the early progression of Schistosoma japonicum.Methods BALB/c mice were infected subcutaneously with cercariae of S.japonicum before being sacrificed at 8 and 14 weeks after infection to collect liver samples for pathological observation by H&E staining .The spleens of mice were collected to calculate the spleen index.The level of IL-17 in serum was determined using ELISA.Furthermore, qRT-PCR was used to detect the expression of miR-155 and SOCS1 mRNA in the spleens of mice .Results Compared with normal group , the spleen index in the model group was increased significantly along with the loss of relative body mass .H&E staining revealed that the deposition of parasite eggs began to appear in the liver tissue at week 8 post-infection.Meanwhile, there were a large number of inflammatory cells infiltrating to form the eosinophilic granuloma.Over time, the formation of egg granulomas and the infiltration of inflammatory cells were alleviated on week 14 post-infection.The level of IL-17 in serum and the expression of miR-155 in the spleen were peaked on week 8 post-infection, and decreased sharply on week 14, but were still evidently higher than those in normal group .The expression of SOCS1 mRNA was progressively increased both on week 8 and 14. Conclusion The data indicates that miR-155 might cooperate with IL-17 to modulate SOCS1 in the development of S.japonicum infection.

Adverse reactions like weight gain and lipid metabolism disorders are often observed in the treatment of atypical antipsychotic drugs,which have shown great individual differences,but the mechanism is still uncertain.Research on pharmacogenomics indicate that gene polymorphism may play an important role.The drugs could increase food intake by acting on some related central receptors,or effect lipid metabolism in the adipose cell and hepatocyte.In this review,genes and polymorphisms related to lipid metabolic adverse drug reactions of atypical antipsychotic drugs were analyzed in these two aspects,so as to provide references for individualized medication and research.