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Relationship between Clopidogrel Response ,Early Neurological Deterioration and CYP2C19 Gene Polymorphism in Symptomatic Intracranial Atherosclerotic Stenosis (sICAS)Patients

qing Han GAO ; Qun XUE ; yu Xiao DUAN ; hua Jue ZHU ; Qi FANG

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):854-859,885.

[Objective]To investigate the relationship between clopidogrel response , early neurological deterioration and CYP2C19 gene polymorphism in sICAS patients.[Methods]116 sICAS patients were divided into deterioration group and non-deterio?ration group by whether appear early nervous function deterioration. Record included the baseline data,the genotypes of CYP2C19, platelet maximum aggregation rate after 7 days of given clopidogrel,CYP2C19 genotype and clopidogrel reaction were compared be?tween two groups.[Results]The deterioration group combination with diabetes ,stroke/TIA were significantly higher than the non-de?terioration group(P<0.05);The frequency of CYP2C19*2 AA genotype and A allele were significantly higher than those in non-dete?rioration group. The frequency of GG genotype were significantly lower than non-deterioration group (27.27% vs 2.13%,50.00% vs 14.84%,27.27% vs 72.34%)(P<0.01);The poor metabolic genotype platelet maximum aggregation rate were significantly higher than that of the fast-metabolic genotype and middle metabolic genotype(P<0.01,P<0.05),Middle metabolic genotype platelet maxi?mum aggregation rate were significantly higher than fast-metabolic genotype(P<0.01);The deterioration group fast-metabolic geno?type were significantly lower than non-deterioration group ,poor metabolic genotype were significantly higher than non-deterioration group(22.73% vs 65.96%,36.36% vs 5.32%)(P<0.01);Clopidogrel resistance rate 59.09% were significantly higher non-deteriora?tion group 28.72%(P<0.05).[Conclusion]Clopidogrel response and early neurological deterioration in sICAS patients is associatedwith CYP2C19 gene polymorphism.

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Preparation and Preclinical Study of 99mTc-labeled Prostate Cancer Aptamer

Ting YANG ; Ju JIAO ; ting Yin LÜ ; Qiong ZOU ; e Su CAO ; qin Shu JIANG ; Yong ZHANG

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):848-853.

[Objective]To radiolabel the PSMA aptamer A10-3.2 with 99mTc , and explore its biological characteristics in vivo and in vitro.[Methods]Using Succinimidyl 6-hydrazinonicotinate hydrochloride (SHNH) as the bifunctional chelating agent to label aptamer A10-3.2 with 99mTc, then tested for the stability in vitro, the specific uptake by prostate cancer LNCaP cells (PSMA+) , the characteristics of SPECT/CT imaging and biodistribution in LNCaP tumor-bearing NOD/SCID mice.[Results]The labeling rate and radiochemical purity of the products (99mTc-SHNH-A10-3.2) are(71.31 ± 6.78)% and 97.03%,respectively. 99mTc-SHNH-A10-3.2 had obvious target specificity for PSMA positive prostate cancer LNCaP cells, its uptake rate was significantly higher than PSMA nega?tive PC-3 cells (P<0.01). And in tumor-bearing mice, the tumor has a certain uptake and a high ratio of the tumor tissue to the mus?cle.[Conclusion]This study successfully constructed 99mTc-labeled PSMA-targeted aptamer A10-3.2, which has a good stability and targeting in vivo and in vitro, has a high tumor tissue/muscle ratio in tumor-bearing mice, which show that it may be a potential target?ed molecular imaging agent for prostate cancer.

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Effects of Human Umbilical Cord Mesenchymal Stem Cells on Infected State of Human Alveolar type Ⅱ Epithelial Cells

mei Shu YANG ; er Xuan ZHENG ; ming Hao YANG ; min Chun LU ; ming Wei LAI ; bei Yun RAO ; xiao Zhu REN ; Jie YANG

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):842-847.

[Objective]To investigate the effect of human umbilical cord mesenchymal stem cells on infected state of human alve?olar type Ⅱ epithelial cells.[Methods]Human alveolar type Ⅱ epithelial cells A549(1×105/mL)2 mL and PA(3×104 CFU/mL)2 mL has grown after 6 hours,add hUCMSC(1 × 106/mL)2 mL as the experimental group,add equal amounts of phosphate buffer (PBS)for infection,A549 and PBS and the medium has grown as the control group. A549 cells morphological changes between the compared groups(Transmission electron microscope,TEM),A549 cell viability(new CCK-8 cell proliferation assay Kit),A549 cells apoptosis(Annexin V-FITC/PI double staining flow cytometry)and the expression of A549 pulmonary surfactant A(SP-A) (Western blot).[Results]Transmission electron microscope cell morphology observation displayed ,infection group A549 cell dam?aged obviously,cell quality appeared empty bubble degeneration,chromatin height agglutination,visible apoptosis bodies;experi?ment group cell package film structure full,nuclear film full,nucleolus obviously,nuclear chromatin electronic density low,chroma? tin uniform,no apoptotic bodies;control group A549 cell structure full,membrane surface micro-fluff rich,nuclear film full,nucle?ar week clearance structure normal,chromatin uniform;infection group and control group compared,Infection group A549 cell sur?vival significantly reduced[(70.35±2.89)% and(97.37±2.07)%,n=3,P<0.01],apoptosis rate significantly increased[(8.63%± 0.16)%and(2.55±0.11)%,n=3,P<0.01],In the infected group,PA could damage A549 cells and decrease the amount of SP-A ex?pression(n=5,P<0.05). In the experiment group,the protective effect of hUCMSC on the A549 cells after infection may increase the expression of SP-A(n=5,P<0.05);[Conclusions]HUCMSC inhibits the infection of A549 cells apoptosis and protection of A549 cells secrete SP-A.

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Curcumin Attenuates Allergic Airway Inflammation of Young Mice through Inhibiting the Activation of p38 MAPK and AKT

qiu Yan CHEN ; lin Bin CHEN ; hui Bai MA ; xiang Qing ZENG ; long Wen LIU ; lin Feng SONG ; Yan YANG

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):833-841.

[Objective]To investigate the effects of dietary curcumin on the prevention and treatment of allergic airway inflamma?tion in young mice for simulating the allergic airway inflammation of 3-12 years old children.[Methods]The 4 weeks young female BALB/c mice were randomly divided into three groups (n=8): Control group, Model group and curcumin group (800 mg curcumin/ kg diet). 24 h after the last OVA challenge, the symptoms of mice in each group were observed, the inflammatory cells in the bronchoalve?olar lavage fluid (BALF) were measured, various kinds of blood cells were detected, the inflammatory cells around the peribronchial ar?eas stained by H&E and the goblet cell hyperplasia in the lungs stained by PAS were analyzed. Additionally, the IL-4, IL-5, IL-13 in the BALF and the total IgE level in the plasma were detected by ELISA, and the activation of p38 MAPK and AKT was measured by western blot.[Results]The mice of model group showed the symptoms of allergic airway inflammation, such as repeatedly scratched the noses, showed nodding breath, notably, the weight of model mice was decreased significantly during the OVA challenge phase, while the symptoms mentioned above were alleviated in curcurmin group. The blood cells test found that the curcumin could in?hibit the elevation of the eosinophils significantly (P<0.05). Dietary curcumin treatment significantly decreased the inflammatory cells in the BALF and peribronchial areas, and the IL-4, IL-5, IL-13 levels in the BALF were significantly inhibited (P<0.05). The goblet cell hyperplasia was attenuated by curcumin treatment, and the dietary curcumin inhibited the activation of p38 MAPK and AKT sig?naling.[Conclusions]Dietary curcumin can alleviate the allergic airway inflammation of young mice, which may through inhibiting the transduction of p-38 MAPK and AKT signaling.

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Preimplantation Genetic Diagnosis of X-linked Severe Combined Immunodeficiency

tao Hai WU ; ting Xiao SHEN ; jian Qing YE ; liang Yu LIU ; ping Yi ZHONG ; hong Yan ZENG ; wen Yan XU ; quan Can ZHOU

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):955-960.

[Objective]To establish a reliable and accurate preimplantation genetic diagnosis (PGD)method using multiple dis?placement amplification (MDA), which can be applied to the diagnosis of X-linked severe combined immunodeficiency disease (X-SCID).[Methods]Haplotype analysis for the X-SCID family was performedusing five short tandem repeats (STR) markers flanking the both sides of the interleukin-2 (IL-2) receptor gamma chain (IL2RG) gene. MDA technique was used for single-cell whole genomic amplification. The products were used as template in polymerase chain reaction (PCR) of informative STR markers found by linkage analysis for haplotype analysis as well as sequencing of the IL2RG gene exon 5.The amelogenin (AMEL) locus was used to do sex diag?nosis.[Results]Linked analysis revealed 3 STR markers were informative. The method was evaluated with 10 single lymphocytes and 10 single blastomeres. MDA was successful in all single cell. The detection efficiency of gene sequencing of pathogenic IL 2RG exon5 was 100%. The PCR efficiency of 3 STR informative markers and AMEL was 96.3%(77/80)and the average allele drop-out (ADO) rate was 11.5%(7/61). A cycle of PGD was performed on the family, and seven embryos were diagnosed, two of which were normal embry?os. Twin pregnancy occurred after transplantation which were given a healthy baby boy and a healthy baby girl.[Conclusion]In this study, multiple displacement amplification combined with specific amplification/sequencing of pathogenic gene and haplotype analysis in the single cell level of X-linked severe combined immunodeficiency disease were performed. The protocol can avoid misdiagnosis caused by contamination and ADO, and improve the diagnostic efficiency of PGD.

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Detection of KIT gene of a case with serious phenotypes of piebaldism

ping Wei DENG ; Chen PENG ; hua Min CHEN ; xia Shao DAI

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):949-954.

[Objective]To investigate the mutations of KIT gene and SLUG(SNAI2)gene in one patients with piebaldism in Chi?na.[Methods]All coding exons and exon-intron boundaries of KIT gene and SLUG gene were amplified by PCR. The PCR products were sequenced. The DNA samples from 50 normal subjects were also sequenced for control.[Results]The novel mutation,c.860T>A (p.V287E),was detected in patient. This mutation was absent in his parents and the controls ,indicating a de novo mutation. The de?tection result of all coding exons and exon-intron boundaries of SLUG gene was normal.This p.V287E mutation was located in the ex?tracellular ligand-bindingdomain(ectodomain)of KIT,which may generate clash with E249 and disrupt the conformation ofβD andβD/βE of D3 that required for SCF(stem cell factor)binding.[Conclusion]We have identified a novel mutation of KIT gene,c.860T>A(p.V287E),which is probably associated with serious phenotypes of piebaldism.

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Effects of Family Cohesion and Child-Teacher Dependency on Children's Attention-Deficit/Hyperactivity Behaviors at one Year after Kindergarten Entry

jun Jian LIANG ; Li LIU ; li Deng SUN ; na Xiao YIN ; di Zhao CHEN ; an Chuan WU ; qing Wei CHEN

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):943-948.

[Objective]To explore the effects of family cohesion and child-teacher dependency on children's attention-deficit/hy?peractivity behaviors at one year after their kindergarten entry.[Methods]Based on a cohort of 7465 first-year preschoolers in Long?hua district of Shenzhen in 2014,the information about social-demographic characteristics,family cohesion(assessed with Family Environment Scale-Chinese Version)were collected from their primary-caregivers at kindergarten entry. The teacher rating scores of child-teacher dependency(assessed with Student-Teacher Relationship Scale)and parental rating scores of attention-deficit/hyperac?tivity behaviors(assessed with Conners'Parent Symptom Questionnaire)were examined at one year after their kindergarten entry. Lo?gistic regression were performed to analyze the relationship and interaction between family cohesion and child-teacher dependency in attention-deficit/hyperactivity behaviors,after adjusting for potential confounders.[Results]Children's attention-deficit/hyperactivity behaviors at one year after kindergarten entry were negatively associated with family cohesion (OR=0.85,95% CI=0.75~0.97,P=0.01),but were not significantly associated with child-teacher dependency(OR=1.00,95%CI=0.93~1.08,P=0.98). Furthermore, family cohesion moderated the impact of child-teacher dependency on children ' s attention-deficit/hyperactivity behaviors at one year after kindergarten entry(OR=0.96,95% CI=0.92~0.99,P=0.03). In addition,neither family cohesion(OR=1.08,95%CI=0.88~1.34,P=0.47)nor child-teacher dependency(OR=1.03,95%CI=0.93~1.15,P=0.53)could protect preschoolers from persistence of attention-deficit/hyperactivity behaviors in the first year of kindergarten.[Conclusion]The association of child-teacher dependency and onset of attention-deficit/hyperactivity behaviors is modified by the level of family cohesion in preschool children.

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Optimization of Strategy for Image Guided Radiotherapy in Tomotherapy

yan Wen YAO ; wen Jian HUANG ; guang Xuan CHEN ; kui Sen XU

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):921-925.

[Objective]To explore the different scanning frequency for the MVCT scanning in the tomotherapy , and seek the best strategy of the scanning.[Methods]Patients were treated by tomotherapy in SYSUCC from January 1, 2015 to May 15, 2016, includ?ing 88 head&neck patients, 63 chest&abdomen patients and 19 pelvis patients. All patients have had a daily MVCT scanning for po?sition verification before the treatment. The data retrieved from"the first five times of the very first week"and"the every first time of each week", were compared with"the whole course"data, respectively.[Results]There are no significant difference between"the whole course"and"the first five times of the very first week"or"the every first time of each week"for pelvis patients and chest and abdomen patients. There are significant differences between Z axis of"the whole course"and"the first five times of the very first week"only for head&neck patients.[Conclusion]It is a good scanning choice of"the first five times of the very first week"and"the every first time of each week"for the those patients with thoracic&abdominal or pelvic tumors to reduce the extra radiation dose from the MVCT. There are significant differences between Z axis of"the whole course"and"the first five times of the very first week"in the head&neck patients. Therefore,"the first five times of the very first week"cannot be used as a solid position information for daily verification. And"the every first time of each week"may be a good compromise solution.

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Autistic Traits,Empathy and Theory of Mind of College Students with Different Level of Prosocial Behaviors

Fan SUN ; zi Li LIN ; xia Mei DAI ; fang Mei LUO ; hua Cui GUO ; han Wen YANG ; Jin JING

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):938-942,960.

[Objective]To investigate autistic traits(AT)of college students with different levels of pro-social behavior,and their characteristics of empathy and theory of mind(ToM).[Methods]372 college students(91males)were recruited. The Chinese Version of Autism-Spectrum Quotient(AQ-C)and Prosocial Tendencies Measure(PTM)questionnaires were used to assess autistic traits and prosocial behaviors. 49 participants were drawn from the total sample for the next procedure. The Chinese Version of Inter?personal Reactivity Index(IRI-C)and Reading the Mind in the Eyes Test(RMET)were used to assess empathy and theory of mind.[Results]The AQ-C's total(14.8±5.3 vs 13.8±5.3,P=0.031)and Socialness subscale(29.8±6.1 vs 27.6±6.0,P=0.001)scores in the low PTM group were higher than those in high PTM group. The IRI-C's total(46.5±9.9 vs 52.8±8.6,P=0.025)and Perspective Taking subscale(10.3±3.6 vs 12.1±2.4,P=0.049)scores in the low level of prosocial behavior group were lower than those in high lev?el group. Scores of RMET showed no significant difference between the two groups.[Conclusions]Individuals with lower level of pro?social behaviors has higher AT,which may be related to deficits of cognitive empathy. No association between ToM and prosocial be?haviors has been found.

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Spatial Analysis on Primary Liver Cancer Incidence in Sihui County,Guangdong Province, 2004-2011

yi Wen LIU ; hong Qi HUANG ; hua Ai LIN

Journal of Sun Yat-sen University(Medical Sciences).2017;38(6):931-937.

[Objective]To explore the spatial distribution pattern of liver cancer in Sihui city ,Guangdong Province from 2004 to 2011,and to provide theoretical evidence for prevention and control of liver cancer.[Methods]Spatial scan statistic was applied,and analysis were conducted by using software SaTScan 9.4.4 to detect the clusters in Sihui from 2004 to 2011.Map making and results visualizing were carried out with software ArcGIS 10.2.[Results]A total of 1252 cases was reported in Sihui City,Guangdong Province from 2004 to 2011,with the incidence of liver cancer increasing from 32.67/100000 to 41.14/100000. Spatial scans results showed that highly clustered areas are mainly located in the south and southeast,which include Dasha,Longfu and Dongcheng countries in all people (LLR=6.34,P=0.019,RR=1.31) and the male (LLR=5.83,P=0.025,RR=1.33),respectively;highly clustered areas in female were include Dasha,Dongcheng,Chengzhong and other two countries(LLR=5.18,P=0.043,RR=1.41). Lowly clustered areas in all people are mainly located in the north,which include Luoyuan,Didou and Jiangfu countries(LLR=8.66, P=0.001,RR=0.67).[Conclusion]The incidence of primary liver cancer in Sihui was increasing over time,and spatial clustering of the cases were observed. Further study should be focused on the risk factors of liver cancer in related areas to strengthen the prevention and control of liver cancer.

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