Objective To characterize composition and antibiotic resistance of the pathogens isolated from patients' deep sputum with ventilator-associated pneumonia(VAP) in PICU of our hospital,and give support to the administration of antibiotics early and reasonably in clinic.Methods The study was conducted during the period of January 2009 to December 2013 at PICU of the Children's Hospital of Zhejiang University School of Medicine.One hundred and twenty-one cases of children who conformed to the diagnostic criteria of VAP after treated with ventilator were the object,the endotracheal aspirates were collected and transported to microbiology laboratory within 15 minutes.The pathogens were routinely analyzed and identified with WITEK60 and used Kirby-Bauer method for drug sensitive test,and identified with the special drug-resistant bacteria.Results Among 121 VAP diagnosed patients,127 pathogenic strains isolated from sputum specimen.Gram negative,Gram positive bacteria and fungi accounted for 64.57％ (82/127),29.92％ (38/127)and 5.51％ (7/127) respectively.Acinetobacter baumannii (25.61％,21/127),Escherichia coli (20.27％,17/127),Stenotrophomonas maltophilia (20.27 ％,17/127),Klebsiella pneumoniae (16.22％,12/127) and Pseudomonas aeruginosa (9.46％,11/127) were frequently identified isolates among Gram negative bacteria.The resistant rate of Gram negative bacteria in β lactam antibiotics was 77.62％.Ten strains of Staphylococcus epidermis and 6 strains of Staphylococcus aureus were identified isolates among Gram positive bacteria.Except the sensitive to vancomycin and linezolid,Gram positive bacteria were resistance to cephalosporin and aminoglycosides.All fungi were sensitive to the anti-microbial agents.Conclusion The Gram negative bacteria were more prevalent than Gram positive bacteria and fungi in VAP and show high drug resistance.It is pivotal to administer anti-microbial agents early and reasonably for VAP children.To emphasize surveillance to the antibiotic resistance and grasp the characteristics of the drug resistance are much important to VAP therapy.

Objective: To explore the effect of breastfeeding duration on age at adiposity rebound, and provide a scientific theoretical basis for identifying early life factors of obesity in children and adolescents, while promoting early intervention. Methods: In September 2019, first graders from a primary school in Minhang District, Shanghai, were selected to participate in this study, and their growth information was retrospectively collected. The natural cubic spline function was used to fit the body mass index trajectory of the subjects from 1 to 80 months, and age at adiposity rebound was calculated. A total of 6 148 subjects were selected, and complete data of adiposity rebound timing and breastfeeding duration were obtained. A multiple linear regression model was used to analyze the relationship between these two variables. Results: The average breastfeeding duration of all children included in the study was (3.71±3.28) months, and most of the subjects (69.63% for male and 70.45% for female) were breastfed for less than 4 months. A positive linear relationship was found between them [male, B =0.16(0.02-0.30), female, B =0.34(0.18- 0.51 ), total, B =0.23(0.12-0.34), P <0.05]. The linear relationship was determined using the multivariate model. Conclusion Breastfeeding duration independently affected age at adiposity rebound. Prolonging the duration of breastfeeding within 24 months of age may help to delay the timing of adiposity rebound,and thus reduce later risks of overweight and obesity.

Objective: To explore the influence of birth weight and growth patterns during infancy on overweight and obesity among first grade primary school pupils, so as to provide a theoretical basis for the formulation of early life prevention and intervention policies. Methods: In 2019, data related to routine physical examinations were collected for primary school pupils in the Minhang District of Shanghai, and information regarding birth and follow ups was collected retrospectively. Physical examination data of 4 434 pupils at 12 months of age were obtained. A multiple linear regression model was used to analyze the relationship between growth patterns during infancy and body mass index (BMI) in the first grade of primary school. A generalized linear model was employed to analyze the relationship between birth weight and growth patterns during infancy and overweight and obesity in the first grade of primary school. A hierarchical analysis was conducted. Results: A linear relationship was observed between growth patterns during infancy and BMI and the BMI Z score of first grade primary school pupils [ β(β 95%CI)=0.30(0.24-0.35),0.12(0.10- 0.15 ), P <0.01]. In addition to subjects classified as small for gestational age (SGA), catch up growth during infancy was identified among subjects who were classified as appropriate for gestational age (AGA) and large for gestational age (LGA). LGA at birth and catch up growth during infancy were independent risk factors for overweight and obesity among first grade primary school children ( RR =1.31-1.55, P <0.05). The hierarchical analysis showed that catch up growth increased the risk of overweight and obesity among first grade primary school pupils classified as AGA [ RR(RR 95%CI )=1.74(1.42-2.14),1.87(1.56-2.26)], and increased the risk of obesity among first grade primary school pupils classified as SGA and LGA [ RR(RR 95%CI )=3.74(1.04-13.49),3.24(1.62-6.46)]( P <0.05). Among those who exhibited catch up growth during infancy, LGA increased the risk of obesity among first grade primary school pupils ( RR= 2.60 , 95%CI=1.35-5.02, P <0.01), but not the risk of being overweight ( P =0.13). Conclusion Birth weight and growth patterns during infancy have an impact on overweight and obesity among children in the first grade of primary school. It is suggested that attention should be paid to growth and physical development in early life for those classified as LGA and AGA, and catch up growth in children should be closely monitored.

Objective: To explore the characteristics of the adiposity peak and rebound in early life among first year primary school students with different body weight measures, so as to provide scientific evidence for the development of prevention interventions to manage childhood overweight and obesity. Methods: A total of 2 330 first year primary school students who received routine physical examinations from September to December in 2019 were selected. According to body mass index (BMI) status, participants were divided into three categories:healthy weight, overweight, and obese. The BMI growth trajectories of the three groups were fitted by gender using the generalized additive mixed model from 1 to 80 months, retrospectively. Each subject s age at the adiposity peak and rebound, and associated BMI values, were calculated. Results: The prevalence of overweight and obesity was 16.31 % (380/ 2 330 ) and 16.09% (375/2 330), respectively. For first year students with obesity, the BMI value continued to be higher than their overweight or healthy weight counterparts during the first 80 months of life. The age at the adiposity peak for these students, whose BMI status varied, was about nine months. However, the BMI of children with overweight or obesity was much higher than that of healthy weight subjects. Age at adiposity rebound was 72 months for healthy weight children, 52 to 55 months in children defined as overweight, and 22 to 23 months in children with obesity. For healthy weight children, the fitted value of BMI at the adiposity rebound was less than that of overweight and obese children. Conclusion Age at the adiposity peak was largely similar among first year students with different BMI patterns; however, age at adiposity rebound was different. Age at adiposity rebound among children with obesity was much earlier than that of other subjects, and their BMI values were much higher.

Objective:To investigate the overlapping prevalence and risk factors of gastroesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) among rural adults in Shaanxi Province.Methods:From February 1 to October 31 in 2019, 12 villages in Shaanxi Province were randomly selected for household questionnaire survey through multistage stratified cluster sampling. A total of 2 423 subjects were enrolled, including 1 037 males and 1 386 females, with age of (45.3±16.9) years old. GERD was diagnosed according to the Montreal criteria, FD and IBS were diagnosed according to the Rome Ⅳ criteria. The overlapping prevalence of the three diseases were calculated. The risk factors for the overlapping of GERD, FD and IBS were analyzed. Multivariate logistic regression was used for statistical analysis.Results:Among the 2 423 subjects, 624 cases had GERD (302 cases), FD (377 cases) or IBS (167 cases), of which 30.77% (192/624) patients had overlap of ≥two diseases. The overlap rates of GERD and FD, GERD and IBS, FD and IBS, GERD, FD and IBS were 2.56% (62/2 423), 1.61% (39/2 423), 2.52% (61/2 423) and 1.24% (30/2 423), respectively. The results of Multivariate analysis showed that female and migraine without aura were positively correlated with the overlap of GERD and FD, FD and IBS, and GERD and IBS (odds ratio ( OR)=3.08, 2.68, 3.66, 7.37, 5.91 and 4.46, 95% confidence interval ( CI) 1.35 to 7.01, 1.35 to 5.30, 1.52 to 8.83, 3.97 to 13.69, 1.78 to 19.60 and 2.01 to 9.92; all P<0.05). Heavy drinking (alcohol intake≥50 g/d (male) or≥30 g/d (female)) was positively correlated with the overlap of FD and IBS, GERD and IBS, and GERD, FD and IBS ( OR=3.69, 4.20 and 4.91, 95% CI 1.19 to 11.48, 1.01 to 17.50 and 1.23 to 19.52; all P<0.05). Heavy smoking (smoking≥20 cigarettes per day) was positively correlated with the overlap of GERD and FD, FD and IBS, GERD and IBS, and GERD, FD and IBS ( OR=3.44, 6.25, 8.27 and 7.04, 95% CI 1.07 to 11.01, 1.60 to 24.44, 1.80 to 38.07 and 1.76 to 28.12; all P<0.05). The educational level of junior or senior high school and age≥60 years old were negatively correlated with the overlap of GERD and FD, FD and IBS, GERD and IBS, and GERD, FD and IBS ( OR=0.47, 0.29, 0.20, 0.05, 0.23, 0.10, 0.37 and 0.16, 95% CI 0.23 to 0.93, 0.09 to 0.95, 0.09 to 0.42, 0.01 to 0.19, 0.09 to 0.60, 0.02 to 0.65, 0.15 to 0.87 and 0.03 to 0.81; all P<0.05). Conclusions:The overlap of GERD, FD and IBS is common and affected by many factors. Female, age≥60 years old, heavy smoking, heavy drinking, low education level and history of migraine without aura are associated with multiple overlaps of GERD, FD and IBS.

Background: Previous studies have found that patients with gastrointestinal diseases have a higher incidence of headache, while migraine patients are often accompanied by gastrointestinal symptoms. Understanding the relationship between diseases can provide new ideas for the study of its mechanism. Aims: To explore the co-occurrence and related risk factors of gastroesophageal reflux disease (GERD), functional dyspepsia (FD), irritable bowel syndrome (IBS) and migraine without aura (MWoA). Methods: A total of 2 696 adult rural residents in Shaanxi Province were investigated by random stratified sampling. MWoA, GERD, FD and IBS were diagnosed based on ICHD-IIIβ, Montreal classification and Rome , respectively. The prevalence of the single disease and overlapping prevalence of MWoA were calculated. The prevalence rates of GERD, FD and IBS between MWoA group and non-MWoA group were compared, and the disease-related risk factors were analyzed. Results: In this study, a total of 2 423 valid questionnaires were collected. The prevalence rates of GERD, FD and IBS were 12.5%, 15.6% and 6.9%, respectively, and the prevalence rate of MWoA was 8.8%. The prevalence rates of GERD (30.5% vs. 10.7%), FD (37.1% vs. 13.5%) and IBS (27.2% vs. 4.9%) in MWoA group were all higher than those in non-MWoA group (P all < 0.001). Multivariate analysis showed that female, hypertension, chronic motor system diseases were positively correlated with GERD, FD, IBS and MWoA. Conclusions: There is a certain association between GERD, FD, IBS and MWoA.

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.