0.05),the odds ratio(OR)being 0.873,[95% confidential interval(CI):0.428～1.782].(3)The relationship between ischemic stroke and the risk factors was illuminated by the Logistic Regression analysis.The results showed that there was no significant difference of the positive rate of IgA antibody between the case group and control group.Conclusion There may be not relationship between CP IgA antibody and ischemic stroke.There is no relationship between IgA CP antibody and the other risk factors of ischemic stroke.

Objective To study the effect of glutamate on the expression of vascular endothelial growth factor (VEGF) mRNA and protein in cultured rat astrocytes. Methods Cultured rat astrocytes were randomly divided into 6 groups: control group (C), glutamate group (G), QA group (Q), DCG-IV group (D), L-AP4 group (L) and glutanmte-FMCPG gronp (G+M). Cells were cultured under nomoxic condition (95% air, 5% CO2). RT-PCR and ELISA methods were used to detect the expression of VEGF mRNA and protein in cultured astrocytes, respectively. G+ M group was preincubated with lmM MCPG for 30 min prior to the stimulation with glutamate. There were 7 time points at 0,4,8,12,16,24 and 48 h in each group except G+M group. Results The expression of VEGF mRNA and protein did not differ significantly among D group, L group and C group. Different from that in C group, the expression of VEGF mRNA and protein could be enhanced both in a dose-dependent and time-dependent manner in G group and Q group. Meanwhile, the enhanced expression of VEGF mRNA and protein in G group was completely suppressed by MCPG after 24 h. Conclusion Glutamate can increase the expression of VEGF mRNA and protein in cultured astrocytes, which may be due to the activation of group I metabotropic glutamate receptors in astrocytes.

Objective To study the teaching effect of prevention in clinical epidemiology teaching.Methods 187 clinical medical students of Grade 2010 from China Medical University were selected as the research objectives.2 teaching hours of prevention content was increased in the clinical epidemiology teaching,and the anonymous questionnaire survey was used to assess the teaching effectiveness.A total of 187 questionnaires were issued and 187 valid questionnaires were collected.All the data were analyzed by SPSS 16.0.Results 82.9％ (155 people) of the students believed that the addition of preventive content was necessary,40.1％ (75 people) of the students believed that there was a significant increase in the content of the prevention.For the understanding of the content,only 11.2％ (21 people) of the students said they had a complete understanding of the class,but after teaching 51.3％ (96 people) of the students expressed a clear understanding of the content.82.4％ (154 people) of the students thought that the teaching contents of prevention was tightly combined with the clinical,and 74.9％ (140 people) of the students thought that 2 hours setting was appropriate.Students' demands for prevent content also included:1) how to strengthen prevention in daily life;2) tumor disease prevention,including current international popular tumor vaccine;3) of emergent public health event instance;4) occupational disease prevention measures,etc.Conclusion Increasing the contents of prevention in the clinical epidemiology teaching has made students of clinical medicine change their clinical concept and realize the key role of prevention in clinical treatment.At the same time,this study understands students' needs for the content of prevention,and provides a basis for the setting and op-timization of clinical epidemiology course in the future.

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

Objective To clone and identify the heat shock factors(HSFs)of Schistosoma japonicum and analyze its molec?ular structure and alternative splicing pattern. Methods The New Zealand rabbits were infected with the cercariae of Schistoso?ma japonicum and were killed and dissected 42 days post?infection,and the adult worms of S. japonicum and the livers of the rabbits were harvested. Then,the total RNA was extracted by using Trizol reagent. The Sj?hsf open reading frame(ORF)and the alternative splicing fragments were amplified by RT?PCR from the female,male and egg samples,then cloned and verified by enzyme digestion and sequencing. DNAMAN 8.0,InterPro,Mega 6 combined with the Internet databases were utilized to clarify the gene structure,functional domains,alternative splicing pattern,and the homology and phylogenetic tree of HSFs. Re?sults Sj?hsf ORF and the alternative splicing fragments were amplified from the female,male and egg samples of S. japonicum by RT?PCR. After cloning,the positive recombinant plasmids pBSjHSFf?F,pBSjHSFf?M,pBSjHSFf?E containing Sj?hsf ORF, pBSjHSFs?F,pBSjHSFs?M,pBSjHSFs?E with Sj?hsf alternative splicing fragments were identified by enzyme digestion and se?quencing. Three alternative splicing Sj?hsf isoforms were observed through sequence analysis:Sj?hsf?isoform1(2 050 bp),Sj?hsf ?isoform2(2 086 bp)and Sj?hsf?isoform3(2 111 bp);the GenBank accession numbers were KU954546,KX119143 and KX119144,respectively. All the three isoforms located in the same Contig SJC_S000780 of S. japonicum genome and all ex?pressed at female,male and egg stages,but Sj?hsf?isoform1 with a high?level expression. Sj?HSF?isoform1(671 aa)and Sj?HSF?isoform2(683 aa)had DBD(DNA binding domain),HR?A/B and HR?C domains,while Sj?HSF?isoform3(282 aa)stopped in advance without HR?C domain. Phylogenetic tree analysis of HSFs illustrated that Sj?HSFs belonged to HSF1 family,with a close phylogenetic relationship to Sm?HSFs. Conclusions There are three alternative splicing isoforms of Sj?HSF existing in the female,male and egg stages of S. japonicum,but Sj?HSF?isoform1 expresses in a high?level. This study lays the foundation for further study on molecular mechanisms of Sj?HSFs in regulating the heat shock response system.

Delirium is an acute cognitive impairment syndrome. The incidence of delirium in intensive care unit (ICU) is higher than that in general wards which is an independent risk factor of clinical outcomes of ICU patients. At present, there is no unified standards in assessment instrument for ICU delirium in China which has influences on early diagnosis and assessment by medical staff and makes the incidence of ICU delirium high. This paper reviewed the research progress of assessment instrument for ICU delirium at home and abroad so as to provide a basis for assessment of ICU patients with delirium in China.

Objective? To evaluate the impacts of early enteral nutrition (EEN) support and delayed enteral nutrition(DEN) support in the nutritional status and infection complications in patients with severe traumatic brain injury. Methods? The articles of randomized controlled trials about EEN support and DEN support on the nutritional status and infection complications in patients with severe traumatic brain injury were searched in CBMdisc, CNKI, Wanfang Data, VIP, Cochrane Library, Web of Science, PubMed, EMbase from 1990 to 2017. The quality evaluation method in Cochrane-Handbook5.0 handbook was adopted to evaluate the quality of articles and test the heterogeneity of the included articles. Fixed-effect model or random-effect model were used to merge the effects. Results? A total of 10 randomized controlled trials were included. Meta-analysis results proved that, compared with DEN support, EEN support can increase the level of serum total protein, albumin and peripheral lymphocyte count (Z=10.20, 4.23, 5.24;P＜0.01) and reduce the incidence of pulmonary infection and craniocerebral infection in patients with craniocerebral injury (Z=4.12, 2.15; P＜0.05), but it has no effect on the incidence of upper gastrointestinal hemorrhage in patients with craniocerebral injury (Z=0.82, P=0.41). Conclusions? Compared with DEN support (within 48 hours of admission), EEN support (48 hours after admission) can effectively improve serum total protein and albumin, improve nutritional status, increase peripheral lymphocyte count, increase patient resistance and reduce the occurrence of cranial infection and pulmonary infection. Therefore, patients with severe craniocerebral injury should receive EEN support if there is no contraindication.

OBJECTIVETo examine the expression profile and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum (Sjp40) during granuloma formation in the liver of infected New Zealand white rabbits.

METHODSNew Zealand white rabbits were infected with S. japonicum cercariae, and the livers were harvested at 29 and 45 days post-infection (dpi). The total RNA of the liver tissues was extracted for expression profiling of Sjp40 by quantitative reverse transcription-PCR (qRT-PCR) with GAPDH of S. japonicum as the endogenous reference gene. The expression of Sjp40 in the liver were detected by Western blotting using anti-Sjp40 monoclonal antibody (mAb) 9G7 or anti-Toxoplasma gondii tSAG1 mAb Y3A8 (control) as the primary antibody. Paraffin sections of the liver were prepared for observing egg granuloma formation using HE staining and for indirect immunofluorescence assay of Sjp40 location in the trapped eggs and egg granulomas.

RESULTSThe level of Sjp40 mRNA in the eggs trapped in rabbit livers was significantly higher at 45 dpi than that at 29 dpi (P<0.05), and Western blotting confirmed the presence of Sjp40 protein in the rabbit livers at both 29 and 45 dpi. Immunofluorescence assay demonstrated localized expression of Sjp40 in the immature eggs in the rabbit liver at 29 dpi, but at 45 dpi fluorescence was detected in clusters of mature eggs containing miracidium and in the surrounding egg granulomas.

CONCLUSIONSThe transcriptional levels of Sjp40 significantly increased with the maturation of eggs trapped in the rabbit livers. Sjp40 protein spread from the eggs to the surrounding egg granuloma at 45 dpi when acute liver granulomatous lesions occur, suggesting that Sjp40 plays a key role in egg granulomas formation in the livers of infected New Zealand white rabbits.

Animals ; Antibodies, Monoclonal ; Antigens, Helminth ; metabolism ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Granuloma ; parasitology ; Helminth Proteins ; metabolism ; Liver ; parasitology ; RNA, Messenger ; Rabbits ; Schistosoma japonicum ; Schistosomiasis japonica

Objective To examine the expression profile and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum (Sjp40) during granuloma formation in the liver of infected New Zealand white rabbits. Methods New Zealand white rabbits were infected with S. japonicum cercariae, and the livers were harvested at 29 and 45 days post-infection (dpi). The total RNA of the liver tissues was extracted for expression profiling of Sjp40 by quantitative reverse transcription-PCR (qRT-PCR) with GAPDH of S. japonicum as the endogenous reference gene. The expression of Sjp40 in the liver were detected by Western blotting using anti-Sjp40 monoclonal antibody (mAb) 9G7 or anti-Toxoplasma gondii tSAG1 mAb Y3A8 (control) as the primary antibody. Paraffin sections of the liver were prepared for observing egg granuloma formation using HE staining and for indirect immunofluorescence assay of Sjp40 location in the trapped eggs and egg granulomas. Results The level of Sjp40 mRNA in the eggs trapped in rabbit livers was significantly higher at 45 dpi than that at 29 dpi (P<0.05), and Western blotting confirmed the presence of Sjp40 protein in the rabbit livers at both 29 and 45 dpi. Immunofluorescence assay demonstrated localized expression of Sjp40 in the immature eggs in the rabbit liver at 29 dpi, but at 45 dpi fluorescence was detected in clusters of mature eggs containing miracidium and in the surrounding egg granulomas. Conclusion The transcriptional levels of Sjp40 significantly increased with the maturation of eggs trapped in the rabbit livers. Sjp40 protein spread from the eggs to the surrounding egg granuloma at 45 dpi when acute liver granulomatous lesions occur, suggesting that Sjp40 plays a key role in egg granulomas formation in the livers of infected New Zealand white rabbits.

ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC₅₀） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg^-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC₅₀ of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L^-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.