Drug target inference by mining transcriptional data using a novel graph convolutional network framework

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.

Population-based study on infection and genotype distribution of high-risk human among women in rural areas of China, 2014 / 中华预防医学杂志

Objective@#To explore the epidemiologic characterization of high-risk human papillomavirus (HR-HPV) infection and genotype distribution of HR-HPV among women in rural areas of China.@*Methods@#This study used multiple layers of stratified cluster random sampling method. During January to December in 2014, 117 counties of 27 provinces were selected as the HPV test screening pilot project counties. The women aged 35-64 years with rural areas Hukou in these project counties were selected as the study subjects. A total 457 799 women received HPV DNA test. Among them, 118 237 women from 32 counties in 11 provinces received qualified HPV DNA test by fluorescent PCR to detect HPV genotypes.@*Results@#Among 118 237 rural women, the overall HR-HPV positive infection rate was 7.8% (9 249/118 237). The infection rate increased with age and reached an infection peak at the 60-64 age groups (9.9%, 831/8 394). The HR-HPV positive infection rate in western regions (6.9%, 2 144/31 130) was statistical significantly lower than in central regions (8.2%, 1 894/23 023) and eastern regions (8.1%, 5 211/64 084) (χ2=51.46, P<0.001). Among 9 249 women with specific genotypes of HR-HPV, 6 496 (97.6%) cases were infected with single HR-HPV type, and 163 cases (2.4% ) were infected with multiple types. HR-HPV type 52, 16 and 58 were the most common infection types in rural areas of China. The single infection rates were 20.9% (1 355/6 496), 18.7% (1 215/6 496), and 11.2% (725/6 496), respectively. The multiple infection rates were 47.2% (77/163), 17.8% (29/163), and 18.4% (30/163), respectively.@*Conclusion@#The HR-HPV positive infection rate in rural areas of Chinese woman was 7.8%, western region has lower infection rate compared with central and eastern regions. HPV 52 was first of the most common genotypes in rural areas of China.

Genital Chlamydia trachomatis infection and associated risk factors in male clients attending sexually transmitted disease clinics in 9 cities in Guangdong province / 中华流行病学杂志

Objective To investigate the prevalence of genital Chlamydia trachomatis (GCT) infection and associated risk factors in male clients attending sexually transmitted disease (STD) clinics in Guangdong and provide integrated intervention strategy for this group.Methods Convenient sampling was used to recruit participants from April to June in 2015 in Guangdong province.The information about their socio-demographic characteristics and sexual behaviors were collected by using a questionnaire,and blood samples were taken from them to test the antibodies against HIV,syphilis and HCV.First pass urine was taken to test GCT and gonorrhea.Results A total of 1 749 participants with the average age of 39.53 years were recruited.The majority of them were married (73.87％,1 292/1 749),residents of Guangdong (92.28％,1 614/1 749) and in Han ethnic group (99.49％,1 740/1 749).The positive rates for GCT,HIV,syphilis,HCV,Neisseria gonorrhea,and WBC in urinalysis were 6.06％ (106/1 749),0.46％ (8/1 749),3.43％ (60/1 749),0.45％ (7/1 550),2.74％ (48/1 749),7.89％ (138/1 749) respectively.Multivariate analysis showed that risk factors for GCT infection include IDUs (OR=13.98,95％CI:3.35-58.38),anal sex with men (OR=3.11,95％ CI:1.45-6.71),Neisseria gonorrhea positive (OR =9.64,95％ CI:5.09-18.24),and WBC positive (OR =1.96,95％ CI:1.08-3.55).Conclusions This study demonstrated the high prevalence of GCT infection in male clients attending STD clinics in Guangdong.Therefore precision intervention should target this population at high-risk.

Genital Chlamydia trachomatis infection and associated risk factors in male clients attending sexually transmitted disease clinics in 9 cities in Guangdong province / 中华流行病学杂志

Objective To investigate the prevalence of genital Chlamydia trachomatis (GCT) infection and associated risk factors in male clients attending sexually transmitted disease (STD) clinics in Guangdong and provide integrated intervention strategy for this group.Methods Convenient sampling was used to recruit participants from April to June in 2015 in Guangdong province.The information about their socio-demographic characteristics and sexual behaviors were collected by using a questionnaire,and blood samples were taken from them to test the antibodies against HIV,syphilis and HCV.First pass urine was taken to test GCT and gonorrhea.Results A total of 1 749 participants with the average age of 39.53 years were recruited.The majority of them were married (73.87％,1 292/1 749),residents of Guangdong (92.28％,1 614/1 749) and in Han ethnic group (99.49％,1 740/1 749).The positive rates for GCT,HIV,syphilis,HCV,Neisseria gonorrhea,and WBC in urinalysis were 6.06％ (106/1 749),0.46％ (8/1 749),3.43％ (60/1 749),0.45％ (7/1 550),2.74％ (48/1 749),7.89％ (138/1 749) respectively.Multivariate analysis showed that risk factors for GCT infection include IDUs (OR=13.98,95％CI:3.35-58.38),anal sex with men (OR=3.11,95％ CI:1.45-6.71),Neisseria gonorrhea positive (OR =9.64,95％ CI:5.09-18.24),and WBC positive (OR =1.96,95％ CI:1.08-3.55).Conclusions This study demonstrated the high prevalence of GCT infection in male clients attending STD clinics in Guangdong.Therefore precision intervention should target this population at high-risk.

Research of postoperative epidural analgesia for sufentanil combined with ropivacaine under lower limb surgery in elderly / 中国医师进修杂志

Objective To investigate the safty and proper concentration of using the sufentanil combined with ropivacaine in patient-controlled epidural analgesia (PCEA) under lower limb surgery in elderly. Methods Eighty patients scheduled for lower limb surgery were divided into 4 groups by random digits table with 20 cases in each. The concentration of the sufentanil were 0.1,0.2,0.3 and 0.4 μ g/ml in group A, B, C, D respectively. The concentration of the ropivacaine were 0.125% in each group for the PCEA.R-VAS, C-VAS , Bromage score, Ramsay score, press times ,dosage and side effects were monitored and recorded at 4,10,24 and 48 h after operation. Results Compared with those in group C, D, C-VAS,dosage of the analgesia,press times of PCEA were higher in group A,B (P＜0.01 or ＜ 0.05),the efficacy of press was lower in group A, B(P＜0.05), but there was no significant difference between group C and group D(P＞0.05 ).The Ramsay score 10,24 h after operation in group D[(4.5 ± 0.5 ), (4.6 ± 0.6) scores] was higher than that in group A,B,C [(2.7 ±0.8), (2.7 ±0.8) scores vs.(2.9 ± 0.9), (2.7 ± 0.9) scores vs. (3.0 ±0.7), (2.9 ±0.5) scores] (P ＜0.05). There were no case with hypotension and respiratory depression.Conclusion PCEA of four methods are safe and effective in elderly which 0.3 μ g/ml sufentanil combined with 0.125% ropivacaine have good analgesic effect and less side effect.

Clinical analysis of influencing factors of fluid extravasation in patients with calyceal calculi treated by ureteroscopic holmium laser lithotripsy / 中华泌尿外科杂志

Objective To explore the underlying clinical factors and precautionary measures of fluid extravasation in patients with calyceal calculi treated by ureteroscopic holmium laser lithotripsy.Methods A retrospective review was made on clinical records of 138 patients with calyceal calculi receiving retrograde ureteroscopic holmium laser lithotripsy from May 2005 to March 2009. The relevance was studied between the occurance of fluid extravasation complications and various clinical factors using x2 test and binary Logistic regression. The clinical factors included patients' sexes, age groups (＜30 years, 30-50 years, ＞50 years), history of treatment (ESWL or open surgery) for upper urinary tract calculi, preoperative upper urinary tract infection, intraoperative placement of ureteral catheter and the length of procedure duration (＜ 50 min, 50-80 min, ＞ 80 min). Results Fluid extravasation complications occurred in 24 patients. The sexes and age groups were irrelevant to the occurance of fluid extravasation complications; while history of ESWL or open surgery and preoperative infection in upper urinary tract, without intraoperative ureteral catheter placement and long duration of procedure were responsible for the higher rates of the fluid extravasation complications.Conclusion Reasonable selection of patients and timing of operation, regular intraoperative ureteral catheter placement and control the length of procedure duration help to reduce fluid extravasation during retrograde ureteroscopic lithotripsy.

A case-control study of the risk factors for neurosis / 中国心理卫生杂志

Objective: To screen out suspected risk factors associated with neurosis, such as personality dis-order, life events, parental rearing behavior, and to explore degree of their associations. Methods: A case-control study was carried out among 100 cases with neurosis and 200 controls without mental disorder, matched by gender and age (+3 years) . The Life Events Scale (LES), Parental Rearing Style Questionnaire (EMBU), Personali-ty Diagnostic Questionnaire (PDQ-4) were self-reported by the subjects. Results: Single factor analysis showed that there were statistical differences (P <0.05) between case and control groups in negative life event (22.5 vs. 2.5), paternal rejection [(40.4±14.1) vs.(35.4±7.9)], paternal overprotection [(29.1±7.5)vs.(28.2±5.6)], maternal rejection rearing behavior [(40.4±13.7)vs.(36.8±8.5)], and overall personality disorder [(29.8±14.1)vs.(17.1±13.0)] . Using non-conditional logistic regression analysis, the potential protective factor was positive events (OR=0.92, 95% CI:0.87-0.98), and the potential risk factors included negative live events (OR=1.06, 95% CI:1.04～1.08) and overall personality disorder (OR=4.84, 95% CI: 2.24～10.49) . Conclusion: Positive life event may be a protective factor for neurosis, while negative life e-vent and personality disorder may be risk factors.

Different effects of imipramine and fluoxetine on depression and anxiety-related behavior induced by stress in adolescent rats / 中国神经精神疾病杂志

Objective To establish chronic stress model of depression in adolescent rats and to examine the effects of different antidepressant treatment on depression and anxiety-related behaviors.Methods Male Wistar rats were given 21-day chronic mild stress (CMS) during their adolescence (postnatal day 30～50, PND30～50).During stress period, rats were treated with fluoxetine (10 mg/kg i.p.) or imipramine (10 mg/kg i.p.), respectively.After stress, rats were tested for behavioral observation using body weight gain, saccharine test, open field and elevated plus-maze (EPM).Results Compared with control/vehicle (n=10) group, stress/vehicle (n=11) group displayed lower weight gain, saccharine preference index and the number of rearing in open field (P<0.05).Antidepressant fluoxetine, but not imipramine reversed anhedonia and the decrease of the number of rearing induced by stress.In addition, compared with early adolescent(PND29) rats, late adolescent (PND52) rats in control/vehicle group exhibited less open arm entries and open arm time, more closed arm time in EPM (P<0.05).Rats in stress/vehicle group showed more open arm entries and less closed arm time than controls(P<0.05).Both fluoxetine and imipramine had no effects on such changes.Conclusions Stress can induce the depression-like behavior in adolescent rats.Fluoxetine, but not imipramine,can effectively reverse anhedonia induced by stress.However, Both antidepressants have no significant effects on stress-induced decrease in developmental increment of anxious behavior during adolescence.These data suggest that chronic mild stress have complicated effects on depressive and anxious behavior in adolescent rats.

Histidine kinase (YycG) protein of Streptococcus pneumoniae: homology modeling and analysis / 生物工程学报

To construct a three-dimensional (3D) model of histidine kinase (HK) YycG protein in Streptococcus pneumoniae and to investigate the interaction between YycG and its substrate ADP for the purpose of providing a theoretical basis for YycG selective inhibitor discovery, we constructed a 3D model of YycG protein by homology modeling, and assessed the reliability of the model using ProCheck and Profile_3D software. Besides, the active-site cavity of YycG and the residues key for substrate interaction were analyzed by Autodock4.0. Sequence alignment indicated that the YycG of S. pneumoniae was homologous to that of Thermotoga maritima. The constructed 3D model of YycG adopted a similar folding pattern to the template and the two matched well. The conservative amino acids in the substrate-binding pocket, such as Asn145, Asn149 and Lys152, as well as the hydrophobic residues at the bottom of the pocket played important role in binding and hydrolyzing substrate ADP. We have successfully constructed a reliable model of YycG protein. The model can be used as a starting point for designing antibacterial drugs.

Mouse testicular gene expression pattern differences between spermatogonial stem cell proliferative and differential stages / 中华泌尿外科杂志

Objective To detect the mouse testicular gene expression pattern differences be-tween spermatogonial stem cell (SSC) proliferative and differential stages and study the molecular reg-ulation mechanism in SSC proliferation and differentiation. Methods With the interval of 24 days, male Kunming mice were injected intraperitoneally with two doses of busulfan (10 mg/kg) to establish spermatogenesis regeneration models. 36 k Mouse Genome Array was used to detect the differential gene expression profiles between the stages of SSC proliferation and differentiation. Bioinforrnsties analysis was conducted in GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Ge-nomes) pathway to describe the potential roles that may play in spermatogonial stern cells behavior regulation. Results Nine hundred and eleven differential expression genes were identified by gene arrays in mice testes, consisting of 608 up-regulated and 303 down-regulated in SSC proliferation stage and SSC differentiation stage. The differential expression genes were classified by their biological process, molecular function and cellular component, respectively. Alterations with statistical signifi-cance (P<0.05)appeared in 84 KEG(;signal pathways, including Notch and Wnt signaling pathways which had been proved to be important for stem cell maintenance. Fifty-six differential expression genes were selected as genes related to stem cells, among which 40 genes were up-regulated, including some stem cell biomarkers(such as Cd9, StraS, hgbl-, Oct4 and Thyl)and some growth factors(such as Fgf2, Pdgfa and Csfl). Conclustion The regulation of SSC proliferation and differentiation involves inmany differentially expressed genes in various signal pathways. This study provides a molecular basis for the elucidation of the molecular mechanism behind self-renewal and differentiation of spermatogonial stem cells.

Analysis of prognostic factors of 324 patients with multiple traumas / 中华急诊医学杂志

Objective To explore the effective prognostic factors of patients with multiple traumas. Method During January 2003 to March 2007, totally 324 patients with multiple traumas were treated in the emergency department of Renmin Hospital, Wuhan University. The relationship between prognosis and age, visiting time after injury, injury severity score (ISS) ,main wounded part and shock degree was analyzed. The data were tested using ehi-square test and logistic regression method. Results Seventy-eight patients died and 246 patients survived, the total mortality was 24.1%. Statistical differences existed in mortalities of patients with different visiting time (visiting hospital within 1 h,16.7%; visiting hospital beyond 1h, 37.4%),ISS (16≤ISS≤24, 5.7%; 25≤ISS≤40, 19.2%; IS8>40, 41.3%) and shock degree (non-shock, 11.8%; mild shock, 13.6%; moderate shock,27.7%; severe shock,46.9% ) ( P<0.01). There were no significant difference in mortalities among patients with different age (<18, 23.8% ; 18～38, 21.7% ; 38～58, 24.2% ;>58, 32.5% ) and with various main wounded part (head, 26.0%; neck, 25.3%; chest, 27.3%; abdomen, 24.1%; limbs, spine and pelvis,16.3%), P>0.05. Logistic regression study showed that mortality increased with postponed visiting time after injury, augment of ISS and aggravation of shock degree, with the exception that there was no differenoe in mortality of patients with between non-shock and mild shock. Conclusions Visiting time after injury, ISS and shock degree were valuable progrostic predictors for multiple traumas. It's vital to follow principle of damage controlled surgery and emphasis on the timeliness and integrity of medical rescue and control shock actively to reduce mortality of patients with multiple injuries.

A Cross-sectional Study of Internet Addiction Disorder in High School Students in Beijing / 中国心理卫生杂志

Objective:To study the epidemiological features of internet addiction disorder(IAD)in high school students in Beijing and explore the related factors.Methods:A stratified cluster sampling method was used.Totally 5100 high schools students were measured with the Internet Addiction Scale,Personality Diagnostic Questionnaire and Egna Minnen av Bardndoms Uppfostran(EMBU).Results:(1)The prevalence of IAD was 8.8% in high school students in Beijing.(2)Logistic regression analysis indicated that the risk factors of IAD were male,school area in urban area,parents' divorce,parents' refusal,parents' over-protection,paranoid personality disorder,avoidant personality disorder,antisocial personality disorder and histrionic personality disorder.The protective factor was parents' emotional warmth.Conclusion:It should be paid more attention to internet addiction disorder IAD in high school students in Beijing.Prevention and intervention should be conducted to the risk factors of internet addiction disorder IAD.

Relationship between the diatolic/systolic oddi and the gold section ratio / 中华医学美学美容杂志

Objective To investige the diatolic/systolic oddi (DSO) of blood pressure and its relation to the gold section ratio (GSR)(0.618). Methods Blood pressures were measured and statistically analyzed in 604 patients with various types of hypertension. Dymamic changes of the blood presures were observed in patients treated with nitrobentin. Results The research on the aesthetic relationship between various types of blood pressure's DSO and GSR revealed that DSO of normal blood pressure approached the GSR, while that of the abnormal one deviated from GSR. Conclusion DSO may offer a new aesthetic parameter in assessing the human bodys aesthetics. This further verifies that the medical aesthetics of human body is natural collection of GSR.