Objective To analyze molecular evolution of carbapenemase KPC-12 and its binding free energies with β-lactams.Methods Class A beta-lactamases were divided into 2 clusters:those with carbapenemase activities and those without.Minimum Evolution method in MEGA4.1 software was used to analyze molecular evolution of class A beta-lactamases with carbapenemase activity,including KPC-2 to KPC-13,SFC-1,SME-1,IMI-1,NMC-A,and class A beta-lactamases without carbapenemase activity,including TEM-1,SHV-1.Then,tertiary structure of KPC-12 was predicted by homology modeling as reported in SWISS-MODEL database depending on tertiary structure of KPC-2.Moreover,DOCK module in ArgusLab 4.1 software was used to perform molecular docking of KPC-12 to 10 kinds of beta-lactams substrates,and the binding free energies (△ G) were calculated.Results Molecular evolution between KPC-12 and KPC-2 was the closest.The top three decline in binding free energies of β-lactams were penicillin G sodium salt (△G =-8.45149 kcal/mol),ertapenem (△G =-8.36383 kcal/mol) and ampicillin (△G =-8.19326 kcal/mol),while the last two decline in binding free energies of β-lactams were aztreonam (△G =-6.50614 kca]/mol) and clavulanic acid (△G =-6.88533 kcal/mol).Conclusion Carbapenemase KPC-12 has high catalytic activities to penicillin G sodium salt,ertapenem and ampicillin,while has low catalytic activities to aztreonam and clavulanic acid.

Objective To study the homocysteine induced gene(HCY-2) expression in human fetus arterial smooth muscle cells(hASMCs) in culture and explore the effects of homocysteine(HCY) and folic acid on HCY-2 expression and cell proliferation of hASMCs. Methods Immunohistochemistry ABC staining method was used to observe and analyze HCY-2 expression in hASMCs in culture.The image analysis system was used to research of hASMCs quantificationally.The effect of different HCY concentration on the proliferation of hASMCs was investigated by the cell counting. Results Immunoreactive substance of HCY-2 was chiefly found in cytoplasm of hASMCs.The expression of HCY-2 could be affected by HCY concentrations.There was a positive dose-dependent correlation with HCY concentrations in the culture medium.Folic acid increased the expression of HCY-2.The different concentration of HCY enhanced the proliferation of hASMCs,and this enhancement was maximal at the concentration of 1.25 mmol/L of HCY,while the proliferation was decreased when the concentration of HCY was over 1.25 mmol/L.Conclusion HCY increases the expression of HCY-2,and affects the proliferation of hASMCs.HCY is inhibited by folic acid.

Objective:To explore the change characteristics of event-related potential P300 in different violence risk levels of schizophrenic patients and analyze the risk factors of violence in schizophrenic patients.Methods:Totally 158 schizophrenic patients in Lyuzhou hospital of Shihezi City from January 2019 to August 2020 were collected and assessed with the violence risk scale for 3 days.According to the assessment results, the patients who met the inclusion criteria were divided into low-risk group( n=78), medium-risk group( n=51) and high-risk group( n=29). The auditory P300 of patients in each group was completed within 3 days and act of violence was observed and recorded within one week.Data analysis was carried out by SPSS 20.0 software.The changes of P300 in different violence risk groups were analyzed by ANOVA, and the influencing factors of violence in patients with schizophrenia were analyzed by logistic regression. Results:There was no significant difference in latency of P300 among the three groups (χ 2=4.71, P=0.10), but there was significant difference in amplitude of P300( F=6.67, P<0.01). Compared with the low-risk group ((12.14±9.19) μV), the amplitude of P300 in medium-risk group ((8.25±7.13) μV) and high risk group ((6.71±4.97) μV) decreased significantly ( t=-3.14, -5.45, both P<0.05). There was no significant difference in amplitude of P300 between the high-risk group and the middle-risk group( t=-2.31, P>0.05). The latency and amplitude of schizophrenia patients with violent behavior were significantly different from those without violent behavior ( Z=-6.30, 9.78, both P<0.01). High BVC grade (compared with high-risk group, low-risk group: OR=0.03, 95% CI : 0.00-0.35; the middle risk group: OR=0.09, 95% CI : 0.01-0.62), prolonged P300 latency ( OR=1.30, 95% CI : 1.13-1.48) and decreased P300 amplitude ( OR=0.50, 95% CI: 0.36-0.70), delusion of victimization ( OR=0.12, 95% CI: 0.02-0.76)were the risk factors for violent behavior. Conclusion:The latency and amplitude of P300 can be used as the reliable neuroelectrophysiological indicators for evaluating violence risk in patients with schizophrenia.It has important clinical application value for evaluating violence in patients with schizophrenia.

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.