Remodeling characteristics and construction of a survival prediction model based on enhancers and regulome in intestinal type gastric cancer / 陆军军医大学学报

Objective To explore the genome-wide distribution of histone H3K27ac in intestinal type gastric cancer,analyze remodeling features of enhancers and regulome and construct a prediction model for prognosis.Methods H3K27ac CUT&Tag sequencing and RNA sequencing were performed in intestinal type gastric cancer tissues from 15 patients and normal gastric mucosa tissues from 18 healthy volunteers.Bioinformatics analysis was performed to identify the differences in genome distribution of H3K27ac modifications.Based on the distribution characteristics of H3K27ac,the enhancer elements were identified and the remodeling characteristics of enhancer and related regulome were explored.The prediction model for prognosis based on enhancer related target genes was constructed by univariate Cox and multivariate Cox regression analyses.Results The histone H3K27ac modification was mainly distributed in the enhancer region and displayed no significant differences in the genomic distribution patterns between normal and cancer tissues.Compared with normal gastric mucosa,the level of enhancer H3K27ac modification was higher in intestinal type gastric cancer.A total of 8847 enhancers with increased activity in intestinal type gastric cancer were identified,accounting for 8.3%of all enhancers,which might promote malignant behaviors such as proliferation and adhesion of gastric cancer cells.A prognosis-predicting model established based on a panel of 6 genes that upregulated by the acquired enhancer in cancers,which was able to predict the overall survival of patients.Conclusion Enhancer remodeling is one of the significant epigenetic features of intestinal type gastric cancer.These enhancers may drive malignant growth and adhesion of cancer cells by upregulating the expression of MYC,E2F3 and other genes.A prognosis model based on enhancer target genes is constructed.

Application of T-SPOT.TB in the Early Diagnosis of Tuberculosis / 现代检验医学杂志

Objective This study aims to explore the application value of tuberculosis T lymphocytes enzyme-linked immune SPOT test (T-SPOT.TB) on early diagnosis of tuberculosis.Methods The TB infection in 189 inpatients suspected tuberculosis in pneumology department of Shaanxi Provincial People's Hospital was detected with T-SPOT.TB,fluorescence RQPCR,tuberculosis (TB-Ab)protein chip and PPD methods.Results The sensitivity of four methods was 91.54％ (119/130),73.85％(96/130),63.08％(82/130) and 57.69％ (75/130) respectively and the specificity of those was 89.83％ (53/59),86.44％(51/59),67.79％(40/59) and 66.10％(39/59),respectively.The sensitivity of T-SPOT.TB method was statistically higher than those of other three tests,respectively (P＜0.05).The specificity of T-SPOT.TB was significantly higher than those of TB-AB and PPD (P＜0.05),but there was no statistical difference between RQ-PCR and T-SPOT.TB (P＞0.05).The positive predictive values of T-SPOT.TB,fluorescent quantitative PCR,TB-Ab and PPD assays were 95.2％ (119/1250),92.3％ (96/104),81.2％ (82/101) and 78.9％ (75/95) respectively while the negative predictive values of those were 82.8％ (53/64),60％ (51/85),45.5％ (40/88) and 41.5％ (39/94),respectively.The false-positive rates (misdiagnosis rate) of four assays were 10.2％ (6/59),13.6％ (8/59),32.2％ (19/59) and 33.9％ (20/59) respectively and the false-negative rates (rates of missed diagnosis) of those were 8.5％ (11/130),26.2％ (34/130),36.9％ (48/130)and 42.3 ％ (55/130),respectively.The negative likelihood ratios of T SPOT.TB,fluorescent quantitative PCR,TB-Ab and PPD assays were 0.11,0.16,0.48 and 0.51 respectively,meanwhile the positive likelihood ratios of T-SPOT.TB,fluorescent quantitative PCR,TB-Ab andPPD assays were 9.0,5.4,2.0 and 1.7,respectively.What' s more,the diagnostic accordance rates of the four assays were 91.0％ (172 189),77.8％ (147 189).64.6％ (122/189) and 60.3％ (114/189),respectively.Conclusion T-SPOT.TB test is a more sensitive and specific method and of great significance to the early diagnosis of TB,which has more clinical value in different stages of tuberculosis diagnosis.

Drug Resistance of Pathogens in Blood Culture Specimens in Shaanxi Antimicrobial Resistant Investigation Net from 2013 to 2015 / 现代检验医学杂志

Objective To explore the Gram-positive bacterial drug resistance in blood culture in 2013 to 2015 from the members of Antimicrobial Resistant Investigation Net of Shaanxi province,and guide the clinicians touse antimicrobial drugs rationally.Methods All the objective bacterial isolates were collected and identified susceptibility date by software WHONET 5.6.Results 8 824 Gran positive bacterial isolates and their antibacterial susceptibilitydata were collected.The top five populations of Gram-positive bacterial isolates were Staphylococcus epidermidis,Staphylococcus hominis,Staphylococcus haemolyticus,Staphylococcus aureus and Enterococcus feacium.The isolating rates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase negative Staphylococcus(MRCNS) were 33.9 ～ 54.9％ and 72.1 ～88.6 ％ respectively.No vancomycin,Linezolid and teicoplanin resistant Staphylococcus isolates were found.There were 0.9 ～2％ E.faecium vancomycin-resistant isolates.Conclusion The composition of blood culture from 2013 to 2015 was not changed,The rate of MRSA and MRSE showed downward trend.But it was severe that the situation of bacterial drug resistance in blood culture in Shaanxi province.Should fully use bacterial drug resistance surveillance results for supervision and administration,and take effective measures for controlling the spread of resistant isolates.

TORCH Serological Screening and Infection Characteristic in Neonate in Tianjin Area / 现代检验医学杂志

Objective The purpose of this study was to explore the infection characteristic of Toxoplasma gondii (TOX),Rubella virus (RV),Cytomegalovirus (CMV) and Herpes simplex virus Ⅱ type (HSV-Ⅱ) (TORCH) infection in neonate in Tianjin area.Methods TOX-IgM/IgG,RV-IgM/IgG,CMV-IgM/IgG and HSV-Ⅱ-IgM/IgG were detected in serum of 2 273 neonate during 2015～2016 with enzymelinked immunosorbent assay (ELISA).Results The positive rates of TOX IgM,RV-IgM,CMV-IgM and HSV-Ⅱ-IgM were 0.00％(0/2 273),0.00％(0/2 273),0.88％(20/2 273) and 0.00％(0/2 273),respectively and those of TOX-IgG,RV-IgG,CMV-IgG and HSV-Ⅱ-IgG were 3.65％ (83/2 273),86.45％ (1 965/2 273),95.82％(2 178/2 273) and 8.27％(188/2 273),respectively.There was 0.66％ percent (15/2 273) of examinees who were infected by none of TORCH pathogens.There existed significant statistical difference for positive rate between TOX-IgG,RV-IgG,CMV-IgG and HSV-Ⅱ-IgG (x2 =6.747,P =0.000) with consequence of the highest positive rate being CMV-IgG.The positive rates of TOX-IgG and CMV-IgM in neonate of 2016 were significantly less than those in 2015 (x2 =5.789～7.505,P=0.006～0.016) but that of HSV-Ⅱ-IgG of 2016 was statistically higher than that in 2015 (x2 =6.073,P =0.014).The positive rate of CMV-IgM in male neonate in 2015 was significantly higher than that in 2016 (x2 =5.054,P =0.025).As a whole the positive rates of TOX-IgG,RV-IgG,CMV-IgG and HSV-Ⅱ IgG had no differences between different years,so did those between gender groups (x2 =2.23～6.963,P=0.073～0.526).The positive rates of TOX-IgG,RV IgG,CMV-IgG and HSV-Ⅱ-IgG in female neonate in 2015 were statistically different from those in 2016 (x2 =8.247,P =0.041).The female neonate in 2015 had higher infection proportion of TOX-IgG compared with that in 2016 (x2 =6.992,P=0.008).TORCH infection detected in 2 273 cases of neonate had one pathogen infection and multi-pathogen infection with overall six patterns of TORCH infection and all infection patterns had no relationship with year and gender,respectively (P＞0.05).Conclusion RV and CMV were primary pathogens in TORCH infection for neonate in Tianjin area and there were recent infections by CMV.TORCH infection varied in different years and gender groups,which provided experimental data and basis for epidemiology and prevention of TORCH in neonate.

Investigation on the Serum NGAL Reference Range of Healthy Populations in Xi'an / 现代检验医学杂志

Objective To establish serum NGAL reference range of healthy populations in Xi'an Area.Methods 2 665 cases (aged 6 to 95 years old,male 1 370,female 1 295) of health-check people were collected from March 2014 to October 2016 in Medical Examination Center of Shaanxi Provincial People's Hospital,and 682 cases (aged 0 to 6 years old,male 356,female 326) were collected from preschool children of prevention.Serum NGAL concentration of them were analysed by immunoturbidimetry method with the Automatic Biochemical Analysis Assembly Line of Beckman-AU5800,and the detection data for statistical analysis.Then established the reference range of serum NGAL population of different age and different sex in Xi'an.Results The serum NGAL levels in healthy subjects showed a skewed distribution,which were preschool children under 6 years of age 37.66±23.12 ng/ml,6～15 years 39.25±25.34 ng/ml,16～49 years 46.68±27.06 ng/ml,and 50～ 69 years 57.82±29.13 ng/ml.Compared the first two with the latter,there was a significant difference (t=0.589,P＜ 0.05).The serum NGAL levels of over 70 years were 61.87 ± 32.64 ng/ml,and there was a significant difference between the ages of 15 and 49 and over 70 years (t=8.529,P＜0.01).At the same time,the serum NGAL was closely correlated with age (r=0.298,P＜0.01).But there was no significant difference in serum NGAL level between male and female (t=0.263～0.542,all P＞0.05).87ng/ml was the upper limit of the reference value for the age of 50 years.Conclusion The level of serum NGAL was related to age and increased with age,but not with gender.

Detection of Human Papillomavirus Subtypes in Male Urethra in Xi'an Area / 现代检验医学杂志

Objective To investigate the infection of HPV subtypes in male urethra in Xi'an area.Methods The eighteen subtypes of HPV DNA were detected in 478 cases of male patients by PCR-reverse dot hybridization assay (RDB) including low risk subtypes (HPV6,11,43) and high risk subtypes (HPV16,18,31,33) during 2015～2016.Results The total infection rate of HPV subtypes in 478 subjects was 44.97％ (215/478).The percents of subjects infected by one subtype,two ones,three ones,four ones and five ones were 32.85％ (157/478),8.79％ (42/478),2.09％ (10/478),0.42％ (2/478) and 0.84％ (4/478),respectively.The detection rates of low risk subtypes and high risk ones were 40.17％ and 22.38％ in which the most common subtypes were HPV6 (24.69％),HPV11 (12.13％),HPV16 (5.65％),HPV43 (3.35％) and HPV52 (2.30％) and those of others were from 0％ to 2.09％.The infection pattern of HPV subtypes gave priority to one subtype infection in all age groups.There was statistically different between H PVs (6,11,16,43,52,66) in twenty years or older subjects (x2 =12.879～109.7,P=0.000～0.025).Conclusion The majority of HPV subtypes detected in male urethra were HPV6,HPV11,HPV16,HPV43 and HPV52 in Xi'an area which provided epidemiological data for HPV infection in males.

Clinical Implication of HBV Serum Markers Detected with Chemiluminescent Immunoassay in Inpatients of Xi'an Area / 现代检验医学杂志

Objective To obtain serological prevalence data for HBV markers in inpatients of Xi'an area with consequence of providing basis for nosocomial infection control and clinical stuff.Methods The serological markers of HBV (HBsAg,HBsAb,HBeAg,HBeAb,HBcAb) in serum of inpatients including 5 248 males and 5 345 females in 2015 were quantitatively detected by chemiluminescent analyzer ARCHITECT i4000SR.Results The infection rate of HBV was 7.01％ (743/10593) and there were 14 patterns of HBV serum markers in inpatients.Of all patterns of HBV infection in this study,there were 5.17 ％ (548/10 593) with HBsAg+ HBeAb+ HBcAb+,1.34 ％ (142/10 593) with HBsAg+ HBeAg+ HBcAb+,0.25％ (27/10 593) with HBsAg+HBcAb+ and 0.25％ (26/10 593) with other uncommon ones.Of all patterns of HBV convalescent stage,there were 21.02％ (2 227/10 593) with HBsAb+,13.71％ (1 452/10 593) with HBsAb+HBeAb+ HBcAb+,and 15.07％ (1 596/10 593) with HBsAb+HBcAb+.The percentage of five serum markers with negative was 31.38％ (3 324/10 593).There existed statistical difference for patterns of HBV serum markers concerning gender and different age groups,respectively (P＜0.05).The clinical departments with highest percentages of HBsAg-+-HBeAg+ HBcAb +-,HBsAg+ HBeAb+ HBcAb+ and HBsAb+ were department of gastroenterology with 7.39 ％ (36/487),department of gastroenterology with 16.43％ (80/487) and thoracic surgery one with 89.23％ (58/65),respectively.Conclusion This study provided clinical data of management and controlling the transmitting of HBV and promotion of HBV vaccination.Meanwhile it is necessary for government to take effective measures to reduce the infection rate of HBV in Xi'an area.

Retrospective Analysis on Serological Detection of Hepatitis Viruses in Physical Examination Population in Xi’an During 2009~2014 / 现代检验医学杂志

Objective To investigate retrospective analysis on serological detection of hepatitis viruses in physical examination population.Methods Hepatitis A virus (HAV)IgM,HBsAg,HCV IgG,HDV IgM,HEV IgM and HEV IgG were detected by ELISA assay in physical examination population during 2009~2014.Results The positive rate of HAV IgM was 0.15%(2/1 315)in 1 315 physical examinees and that of HBsAg was 2.83% (3 360/109 965)in 109 965 ones during 2009~2014. The positive rates of HBsAg decreased trend in the last 6 years in general (χ2 =63.070,P =0.001).There was no signifi-cant difference for HBsAg positive rate among male physical examinees in last six years (χ2 =4.804,P =0.441),but the positive rate of HBsAg in female population decreased trend in the last 6 years in general (χ2 =18.046,P =0.003),moreo-ver the positive rate of HBsAg in male popolation was significantly higher than that in female ones (χ2 =126.9,P =0.000). The positive rate of HCV IgG was 0.79% (333/41 898)in 41 898 physical examinees during 2009~2014 and that decreased trend in last 6 years (χ2 = 18.380,P =0.003).There was no HDV IgM detected in 1 079 physical examinees serum.The positive rate of HEV IgM and IgG were 0.25% (3/1 195)and 3.93% (47/1 195)respectively in 1 195 physical examinees. Conculsion The physical examination population during 2009~2014 were mainly infected by HBV and HCV and the infec-tion rate decreased trendly in last 6 years,which provided important data for epidemiology of serological hepatitis viruses in Shaanxi provice.

Study on Biological Characters and Genetic Characteristics of Oidiomycetes Mutant Strains Like Bacterial Morphology / 现代检验医学杂志

Objective To investigate the changes of the morphology,structure and biological characters of mutated Candida and through its genetic characteristics,research and reveal the mechanism of the variation at the molecular level.Methods Used different nutritional conditions,different growth conditions and different azole antifungal agents to induce mutation of the standard strains of Candida albicans.In clinical study,Candida mutant strains was isolated from vaginal secretions,pleu-ral effusion and gastric juice samples in patients of poor effect with Antifungal therapy,and studied on the morphological characteristics,and the nuclear structure,the biochemical reaction,the drug resistance,the bacterial composition and the ge-netic characteristics of above variants,etc.Results Mycelial?morphology:Candida were prone to mutation like bacteria, mutant bacteria could show G+ Aureus shape,G+ Bacillus,G+ long filamentous,G- Aureus shape,G- Bacillus and G- long filamentous;Nuclear structure:Candida mutant strains changed like prokaryotes under the electron microscope because it lost the original structure of eukaryotic cells.Biochemical reaction:there were 5 different items in 20 biochemical test ob-served.Drug sensitivity test:Candida mutated to antifungal drugs being originally sensitive was completely resistant,sensi-tive and resistant originally was completely sensitive,and the same as ordinary bacteria resistant.The cell component chan-ges:there was significantly different in Candida variant strain and the atavism of variant strain identified by mass spectrome-try.The most conservative fungalgene expression:Candida mutated had conservative gene expression of eukaryotes.It could be demonstrated that oidiomycetes mutant strains like bacterial morphology with prokaryotic cell biological characteristics was derived from Candida with eukaryotic cells.Conclusion Candida was prone to variation like bacterial morphology.The biological characteristics of mutant resembled prokaryote.There was a qualitative change among the standard strains of Can-dida albicans,mutant strains of oidiomycetes like bacterial morphology and the atavism of variant strain with clear genetic re-lationship under the electron microscope in the form of nuclear matter.The study on biological evolution,especially contact in prokaryotic cells and eukaryotic evolution has very important significance.

Variation analysis of HPV16 cell-type-specific enhancer in cervical carcinoma / 西安交通大学学报·英文版

Objective: To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods: CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results: HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41% (14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion: CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.

VARIATION ANALYSIS OF HPV16 CELL-TYPE-SPECIFIC ENHANCER IN CERVICAL CARCINOMA / 药物分析学报

Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.