Objective To explore the relationship between perceived social support,pro-social behavior and self-esteem of children affected by AIDS,and provide a theoretical basis for the children affected by AIDS to establish good pro-social behavior.Methods 300 children affected by AIDS were taken from Henan province where seriously affected by HIV.Perceive social support scale,self-esteem scale and pro-social behavior scale were used to test the 300 children affected by AIDS.Multiple linear regression analysis,bootstrap testing and other statistical analysis were used for data correlation analysis.Results (1) Children affected by AIDS perceived social support effects are significantly positively related to their self-esteem(r=0.436,P＜0.01) and pro-social behavior(r=0.457,P＜0.01).Children affected by AIDS self-esteem was significantly positively related to pro-social behavior (r=0.477,P＜0.01).(2)The variance of the interpretation of the mutation rate of perceived social support to the pro-social behavior of children affected by AIDS was 20.8％ (F=67.944,P＜0.01).The variance of the interpretation of the mutation rate of self-esteem to the pro-social behavior of children affected by AIDS was 22.8％ (F=76.146,P＜0.01).(3)Self-esteem as an intermediary variable,perceived social support of children affected by AIDS were significantly for both direct effect and indirect effect.The estimation value of the self-esteem's mediating effect was 0.208(P＜0.01) and the estimation value of direct effect between perceived social support and pro-social behavior was 0.272(P=0.02).Conclusion Perceived social support and self-esteem are the chief influencing factors of pro-social behavior of the children affected by AIDS.Self-esteem is the mediator of perceived social support and pro-social behavior.

Objective To explore the mediation effect of the peer attachment between the self-esteem and the school adjustment of the children affected by AIDS/HIV.Methods 250 children affected by the AIDS/HIV were investigated in the research in a district affected by AIDS/HIV in the Henan province.Self-esteem scale,peer attachment questionnaire and school adjustment questionnaire was adopted in the study.Results ①Self-esteem had a positive significant effect on the school adjustment (β=0.227,P＜0.01).(②)self-esteem had a positive significant effect on the peer attachment (β=0.236,P＜ 0.01).(③When controlled the indirect effect of peer attachment,the effect of the self-esteem on the school adjustment had still been significant (β =0.145,P＜0.05),it proved that the peer attachment played a partly mediation between the relationship of the self-esteem and the school adjustment.Conclusion Self-esteem has a positive significant effect on the school adjustment; and self-esteem can not only affect the school adjustment directly,but also affect the school adjustment through the peer attachment.

Dysfunction in tyrosine kinase activity disrupts the nor-mal control of cellular phosphorylation signaling pathways,which plays a vital role in genesis and development of various tumors, and makes tyrosine kinases a class of targets of many anti-tumor drugs. Currently most approved tyrosine kinase inhibitors ( TKIs) are based on irreversible binding mechanisms, making them poorly selective, not potent or sustained enough regarding pharmacological effects and prone to triggering resistance. In the past decade, much progress has been made in the development of
a new class of TKIs which irreversibly inhibit their target proteins via the formation of covalent bonds, overcoming the drawbacks of irreversible TKIs. Several irreversible TKIs have entered markets or clinical research phases. This review is to summarize the structural, pharmacological and medicinal chemical properties of investigational and marketed irreversible TKIs as well as their re-cent developments.

Aim To investigate the effect of polysac-charide of Cistanche deserticola ( CDPS) on the impro-ving ability of synaptic plasticity in memory acquisition impairment model mice induced by scopolamine. Methods The KM mice were randomly divided into six groups:scopolamine group, control group, CDPS-treated (25, 50, 100 mg·kg-1 ) group and donepezil group. Memory acquisition impairment model in mice was established with i. p. scopolamine (4 mg·kg-1 ) only once, and orally administered CDPS (25, 50, or 100 mg · kg-1 ) daily for 6 weeks before scopolamine injection. Experimental groups were subjected to step-down test and Morris water maze test. Western blot and RT-PCR analysis were used to examine the expression of GAP-43 , SYP and PSD-95 . Transmission electron
microscope was used to observe the change of synaptic number and structures. Results CDPS (25,50,100 mg·kg-1 ) could shorten the incubation period of mice in the water maze test. Control group and CDPS-treated group swam longer in Q3 than scopolamine group. Mo-reover, CDPS (50,100 mg·kg-1 ) could significantly reduce the error times and extend the incubation period in the step-down test. The results of Western blot and RT-PCR showed that CDPS significantly improved the expression of GAP-43 at the dose of 25 ,50 mg · kg-1 and SYP at the dose of 25,50, 100 mg·kg-1 in hip-pocampus of mice. However, the biochemical assays did not reveal a significant difference in the basal hipp-ocampal levels of the PSD-95 . The ultra-thin speci-mens of hippocampus showed that the number of syn-
apse was increased in CDPS-treated group. Conclu-sions Scopolamine can induce the learning and mem-ory deficits in mice to make related protein expression abnormalities in hippocampus mice, thus this causes the change of synaptic plasticity, which leads to a change in the ability of learning and memory. And CDPS can improve the expression of SYP and GAP-43 ,
increase number of synapses, recover synaptic plastici-ty, and improve the ability of learning and memory in mice.

The relatively high abundance of geochemical elements such as Nb, Zr, Y and other elements shows serious interferences in the determination of trace silver in geochemical samples by inductively coupled plasma-mass spectrometry ( ICP-MS) . Thus it will lead to large deviation in the determination of geochemical samples without separation and enrichment. The traditional emission spectrum or graphite furnace atomic absorption method is only single-element analysis to the silver and with bad sample representativeness. In this study, load diphenylthiourea ( DPTU) foam selective enrichment was used for the separation of Au and Ag from other interfering elements in geological samples, and thiourea liberation-ICP-MS method was developed for the simultaneous determination of Au and Ag. The samples were first decomposed by 1:1 aqua regia. After addition of 50 mL of water, the samples were adsorbed under oscillation for 30 min at 20℃. The detection limits of the Au and Ag were 0. 02 ng/g and 0. 007μg/g, respectively. The proposed method was successfully applied to the determination of Au and Ag in eight national standard materials.

Objective To investigate the estimated values of sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) for diagnosis and prognosis in patients with sepsis according to the new diagnostic criteria in Sepsis 3.0.Methods A retrospective study was conducted.All the clinical data were collected from patients with definite diagnosis of infection and they were admitted into the Intensive Care Unit (ICU) of Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical University from July 2014 to June 2016.The patients' gender,age,infectious location,respiratory rate (RR),oxygenation index (PaO2/FiO2),Glasgow coma scale (GCS),total bilirubin (TBil),platelet count (PLT),serum creatinine (SCr),serum lactate level,etc.general data on admission were collected to carry out SOFA and qSOFA scorings.And then the septic patients in accord with the diagnostic criteria of Sepsis 3.0 were screened out.According to outcome after admission,the septic patients were divided into survival group and death group,and the differences in diagnosis and in estimation value of prognosis between SOFA scoring and qSOFA scoring were assessed as SOFA group and qSOFA group.Results From 545 septic patients enrolled,189 septic patients consistent with the diagnostic criteria of Sepsis 3.0 were selected.In SOFA scoring group,the morbidity of septic patients was 34.68％,while in qSOFA scoring group,it was 15.96％,the difference between the two groups being statistically significant (P ＜0.01).The mortality was significantly lower in SOFA scoring group than that in qSOFA scoring group [28.04％ (53/189)vs.42.53％ (38/87),P ＜ 0.05].The mortality of qSOFA scoring group was about 1.52 times that of SOFA scoring group.On the aspect of scoring,in patients with SOFA scoring the score of death group was significantly higher than that in survival group (8.74 ± 0.417 vs.7.10 ± 0.235,P ＜ 0.01);in the patients with qSOFA scoring,the score in death group compared with that in survival group showed uo statistical significant difference (2.32 ± 0.48 vs.2.16 ± 0.37,P ＞ 0.05).On the aspect of laboratory indexes,the levels of GCS score in death group was significantly lower than that in the survival group (8.15 ± 0.67 vs.12.48 ± 0.36),blood lactate level in death group was significantly higher than that in the survival group (mmol/L:8.55 ± 4.66 vs.2.31 ± 0.16,P ＜ 0.01);the PaO2/FiO2,TBil,PLT and SCr showed no significant differences between the two groups (all P ＞ 0.05).Conclusions The new diagnostic criteria (Sepsis 3.0) can be used for diagnosis of sepsis in ICU.Compared with qSOFA scoring,the SOFA scoring is more suitable to be used for diagnosis and predicting prognosis of septic patients in ICU;SOFA scoring,GCS scoring and serum lactate level can be applied to estimate outcome of septic patients.

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.

OBJECTIVETo detect potential mutation of EXT1 gene in a pedigree affected with multiple osteochondroma and explore its pathogenic mechanism.

METHODSThe coding regions and their flanking sequences of the EXT1/EXT2 genes were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified by excluding possible single nucleotide polymorphisms and bioinformatics analysis. Transcripts of the EXT1 gene in the proband were analyzed by TA clone-sequencing, with its abundance compared with that of healthy controls.

RESULTSDNA sequencing has identified in the proband a novel heterozygous point mutation (c.1164+1G to A) at the 5'splice sites of intron 3 of the EXT1 gene. The same mutation was not found in the healthy controls. Bioinformatics analysis indicated that the mutation is highly conserved and can lead to skipping of exon 3 or aberrant splicing. TA clone-sequencing indicated that the numbers of transcripts with skipping of exon 3 has significantly increased in the proband (< 0.05) compared with the controls.

CONCLUSIONThe c.1164+1G to A mutation has resulted in skipping of exon 3 in a proportion of EXT1 gene transcripts. As the result, the number of transcripts with tumor suppressing function is relatively reduced and has ultimately led to the tumors.

Adult ; Base Sequence ; Child ; Exostoses, Multiple Hereditary ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; N-Acetylglucosaminyltransferases ; genetics ; Point Mutation ; RNA Splice Sites ; RNA Splicing

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

Objective:To investigate effects of extract of pinellia(EP)on proliferation and apoptosis of airway smooth muscle cells(ASMCs)in asthmatic rats and its mechanism.Methods:Asthma rat model was constructed by sensitization and challenge with ovalbumin and rat ASMCs were isolated and cultured.Immunofluorescence staining was used to identify α-actin in ASMCs.After iden-tifying as meeting characteristics of ASMCs,ASMCs were divided into control group,model group,EP group,Compound C group and EP+Compound C group.MTT was used to detect cell proliferation activity;flow cytometry was used to detect cell apoptosis;ELISA was used to detect levels of inflammatory factors IL-6 and TNF-α in cell supernatant;Western blot was used to detect expressions of CyclinD1,proliferating cell nuclear antigen(PCNA),Bcl-2 associated X protein(Bax),Caspase-3,Cleaved-Caspase-3,adenylate activated protein kinase(AMPK),p-AMPK,forkhead box protein O3a(FOXO3a),p-FOXO3a proteins.Results:Immunofluores-cence staining showed that 98%of cells showed green fluorescent filaments in cytoplasm,and α-actin was positively expressed,which proved that cultured cells were ASMCs.Compared with control group,cell OD490,CyclinD1,PCNA protein expressions and IL-6 and TNF-α levels in supernatant of model group were significantly increased,apoptosis rate,Bax,Caspase-3,Cleaved-Caspase-3 protein expressions and p-AMPK/AMPK,p-FOXO3a/FOXO3a levels were significantly reduced(P<0.05);compared with model group,cell OD490,CyclinD1,PCNA protein expressions and IL-6,TNF-α levels in supernatant of EP group were significantly reduced,apoptosis rate,Bax,Caspase-3,Cleaved-Caspase-3 protein expressions,and p-AMPK/AMPK,p-FOXO3a/FOXO3a levels were significantly increased(P<0.05),the above corresponding indicators of Compound C group showed opposite trend(P<0.05);compared with EP group,cell OD490,CyclinD1,PCNA protein expressions and IL-6,TNF-α levels in supernatant of EP+Compound C group were signifi-cantly increased,apoptosis rate,Bax,Caspase-3,Cleaved-Caspase-3 protein expressions,and p-AMPK/AMPK,p-FOXO3a/FOXO3a levels were significantly reduced(P<0.05).Conclusion:EP may inhibit proliferation of ASMCs and promote cell apoptosis in asthmatic rats by activating AMPK/FOXO3a pathway.