Objective To summarize the pathogenic spectrum and antimicrobial susceptibility of hospital-acquired bloodstream infections (HABSI) in children,and to provide evidence for clinical antiinfection treatment.Methods During January 2004 to December 2011,the clinical data and drug susceptibility results of 168 children who were diagnosed with HABSI based on positive results of pathogen tests were reviewed retrospectively in Yuying Children's Hospital affiliated to Wenzhou Medical College.Results A total of 171 strains were isolated from blood specimens of the 168 children.The majority of HABSI occurred in the intensive care unit (73.7 ％),followed by department of hematology (22.6％).Gram-positive bacteria,gram-negative bacteria and fungi accounted for 53.8％,34.5％ and 11.7％,respectively.The predominant pathogens were Stagphylococcus epidermidis (14.1％),followed by Klebsiella pneumonia (13.5 ％),Staphylococcus haemolyticus (7.6％),Staphylococcus aureus (6.4％),Enterococcus faecium (6.4％) and Escherichia coli (6.4 ％).Staphylococcus aureus and Staphylococcus epidermidis resistant to methicillin were detected in 9.1 ％ and 91.7 ％ of specimens,respectively.Staphylococcus and enterococcus which were resistant to vancomycin or linezolid were not detected.The isolation rates of Klebsiella pneumoniae and Escherichia coli with extended-spectrum beta-lactamases (ESBL) were 95.7％ and 72.7％,respectively.One hundred and sixty cases (95.2 ％) had underlying diseases including premature birth and low birth weight (60.7％).One hundred and twenty-six cases (75.0％) underwent invasive procedures.The peak incidence of HABSI occurred in children less than 3 months old (75.6％).Conclusions HABSI is most common in infants younger than 3 months old,with underlying diseases or undergone invasive procedures.The pathogens are mainly gram-positive bacteria.Very low birth weight infants can acquire unusual infection of Kodamaea ohmeri.Thus,it is essential to strengthen the prevention of hospital-acquired infection.

Objective To investigate the apoptotic and proliferation effects of signal transduction inhibitors on human endometrial carcinoma cells with different PTEN gene expression. Methods FTEN antisense oligonucleotide and pcDNA3.1/PTEN vector contained PTEN gene were transfected into endometrial carcinoma cells (HEC-1A and Ishikawa). The expression of PTEN protein was detected by confocal spectral microscopy. The endometrial carcinoma cells (HEC-1A, HEC-1A-PTEN-null, Ishikawa, Ishikawa-PTEN) were treated with signal transduction inhibitors, RG-14620, SB203580 (SB) and rapamycin, respectively. Cell apoptosis morphology, cell apoptosis and cell cycle were detected by Hoechst 33258 staining and flow cytometry. Cell viability was determined by methyl thiazolyl tetrazolium assay. Results The PTEN protein expression in two endometrial carcinoma cells (Ishikawa, HEC-1A) was exchanged by PTEN antisense oligonucleotide blocked and pcDNA3. 1/PTEN stable transfected. After treated with RG-14620, SB and rapamycin, marked morphological changes of apoptosis were observed in HEC-1A-PTEN-null and Ishikawa cells. The cell apoptosis of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were significantly increase [(31.6±0.8)% and (37.8±0.8)%, respectively], the G1 phase cells were increased to (84.1±3.2)% and (87.5±1.9)%. While cell viability was significantly decreased in HEC-1A-PTEN-null and Ishikawa cells, the cell viability of HEC-1A-PTEN-null and Ishikawa cells exposed to SB were (54.0±2.1) % and (49.0±1.7) %. Conclusion Loss of PTEN in endometrial carcinoma cells may improve the G_1 phase cells and apoptotic effects, inhibit the cell proliferation, which due to the sensitivity of cells to related signal transduction inhibitors.

Objective To observe the expressions of RANTES , FKN and IP-10 at mRNA and pro-tein levels in human lung epithelial cells (A549) infected by respiratory syncytial virus (RSV), and to eval-uate the changes of them interfered with 15-deoxy-delta12,14prostaglandin J2(15d-PGJ2), rosiglitazone or 2-chloro-5-nitrobenzanilide ( GW9662 ) .Methods A549 cells were seeded in 6-well culture plates and cul-tured overnight in F12K culture solution.Then they were randomly divided into five groups , including group A (15d-PGJ2+RSV group), group B (rosiglitazone+RSV group), group C (DMSO+RSV group), group D (GW9662+rosiglitazone+RSV group) and group E (cell control group).Cells and supernatants were harves-ted from each group at different time points (12 h, 24 h and 48 h) of culture.The expressions of RANTES , FKN and IP-10 at mRNA and protein levels were measured by ELISA and real-time quantitative RT-PCR analysis.Results The expressions of RANTES , FKN and IP-10 at mRNA and protein levels in group C were significantly higher than those in group E at time points of 12 h, 24 h and 48 h (all P<0.05).In group C, the expressions of the three chemokines at mRNA level reached a peak at 24 h, but began to de-crease at 48 h, which showed no statistical significance compared with those at 12 h (all P>0.05).Moreo-ver, the expressions at protein level were peaked at 48h, and had significant difference with those expressed at 12 h and 24 h (all P<0.05).Compared with group C, the expressions of the three chemokines both at mRNA level and protein level were decreased in group A and B as the dose was increased (all P<0.05), and the lowest levels were observed with the intervention of 20 μmol/L of 15d-PGJ2 in group A and 30μmol/L of rosiglitazone in group B .Conclusion The expressions of RANTES , FKN and IP-10 at mRNA and protein levels were increased with RSV infection , and the peaks of mRNA level and protein level were respectively achieved at 24 h and 48 h after infection.PPARγagonists played an anti-inflammatory role through inhibiting the expressions of the three chemokines both at mRNA level and protein level in a dose -de-pendent manner .

Objective To investigate the characteristics of epidemic and genotype/subtype distribution of hepatitis C virus (HCV) among entry travelers at Tengchong port,to provide references for HCV prophylaxis and treatment.Methods A total of 54 serum samples were collected from anti-HCV positive travelers at Tengchong port from June 2009 to June 2016.HCV NS5B gene was amplified using reverse transcription polyonerase chain reation (RT-PCR) and subsequently sequenced.Based on the obtained sequences and retrieved reference sequences,phylogenetic analysis was conducted to determine HCV genotype/subtype.Results HCV infection rate among entry travelers at Tengchong ports was 0.45 ％ (54/12 059).Forty five samples were successfully genotyped.Phylogenetically,HCV genotype 3b was revealed to be the predominant subtype (28.89 ％,13/45) in this population,followed by genotype 6n (20.0％,9/45),genotype 1b (17.78％,8/45),genotype 3a (13.33％,6/45),genotype 2a (11.11％,5/45),genotype 1a (2.22％,1/45) and genotype 6a (2.22％,1/45).The major genotype in Myanmar travelers was genotype 6,while in Chinese population,genotype 1 predominated.Genotype 6 in the population showed close phylogenetic relationship with strains prevalent in China and Southeast Asia.Genotype 3 was closely clustered with strains prevalent in China.Conclusions The distribution of HCV genotypes among entry travelers at Tengchong port is impacted by HCV epidemic strains both in Yunnan province and neighboring regions.This population serves as a transmitting media which may influence the epidemiological characteristics of HCV in Tengchong and neighboring areas.

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
Antigens, CD19/therapeutic use* ; Antineoplastic Agents/pharmacology* ; Humans ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; T-Lymphocytes