Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Febuxostat, as a xanthine oxidase inhibitor, is a classic anti-gout drug with significant therapeutic effects and good tolerability. The structures of febuxostat and its derivatives can be divided into two parts: a substituted phenyl ring and a five-membered or six-membered heterocyclic ring with a carboxyl substitution. This paper reviewed the research progress of febuxostat derivatives in recent ten years and classified the structure-activity relationships of various febuxostat derivatives. Exploring the action mechanisms and structure-activity relationships of xanthine oxidase inhibitors might be significant for the rational design and development of new anti-gout chemical entities.

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
Bortezomib/therapeutic use* ; Chromosome Aberrations ; Humans ; Multiple Myeloma/drug therapy* ; Prognosis ; Retrospective Studies

Objective To establish a real time PCR assay with a novel fluorescence quencher for identification of mutation of clarithromycin -resistance gene of Helicobacter pylori.Methods Two mutations of 23S rDNA gene in Helicobacter pylori,No.2142 and 2143,were chosen as targets for detection,and then the primers and the probe with a novel fluorescence quencher were designed.The genome DNA of Helicobacter pylori was extracted,and then detected by real time PCR reported here.Meanwhile,the specificity,reproducibility and sensitivity of the assay were evaluated.Finally,the real time PCR described here,the real time PCR based on TaqMan,and a sequencing assay were applied to detect 55 Helicobacter pylori strains isolated from clinical specimens,respectively.The results from three assays were compared with each other in order to further evaluate the applicability of this assay in clinic.Results It indicated that the mutation points related to clarithromycin -resistance,A2142G and A2143G,were identified by real time PCR with a novel fluorescence quencher rapidly and accurately.Moreover the coefficient of variation was less than 5%.The limit of detection was 100 copies/reaction.While this assay was applied directly to detect 55 Helicobacter pylori strains,the results were in accordance with those obtained from a TaqMan real time PCR and a sequencing assay,respectively.Conclusion The real time PCR described here was a simple,reliable and accurate approach and substituted for the TaqMan real time PCR for identification of two mutation points of clarithromycin -resistance,A2142G and A2143G in Helicobacter pylori.Thus,a novel tool for diagnosis of gene mutation was provided and the results might be regarded as a substantial evidence for clinical individual therapy.

China ; Genes, Bacterial ; Sequence Analysis ; Streptococcus suis ; classification ; genetics ; isolation & purification ; Virulence Factors ; genetics

Objective To develop a rapid, sensitive and specific assay method, based on multiplex real time PCR for identifying Vibrio cholerae and distinguishing Vibrio cholerae O139 serotype from Vibrio cholerae. Methods Cholera toxin A subunit gene (ctxA) and glycosyltransferase gene (LPSgt) were chosen as targets according to Vibrio cholerae and Vibrio cholerae O139 serotype,and then the primers and TaqMan-MGB probe were designed. The 5'end of probes was labeled with FAM and VIC fluoresceins respectively while the 3' end of probes was labeled with MGB. The PCR reaction was optimized systematically. Then the specificity, sensitivity and reproducibility of multiplex real time PCR were estimated. Finally, multiplex real time PCR was applied to detect the clinical specimens. Results Vibrio cholerae was identified by multiplex real time PCR accurately and quickly,which could distinguish Vibrio cholerae O139 serotype from Vibrio cholerae. Vibrio cholerae was identified positive for primer pairs and probes from ctxA gene, and Vibrio cholerae O139 serotype tested was positive for LPSgt gene. Meanwhile, none of other bacteria was identified. Sensitivity of the test was 2 × 102 cfu/ml. When this assay was applied directly to identify 45 clinical specimens, results showed that 10 were positive to Vibrio cholerae, in which 4 clinical specimens were positive to Vibrio cholerae O139 serotype. All the results were the same to the one that had been obtained from the conventional assays. Conclusion Our rsults showed that the multiplex real time PCR was a reliable,accurate and feasible method for identifying Vibrio cholerae that carrying toxin gene and distinguishing Vibrio cholerae O139 serotype from Vibrio cholerae. This method could be applied to the cholera surveillance, prevention and control system for identifying and distinguishing Vibrio cholerae in the labs.

Objective The present study was conducted to investigate the infection of Lyme disease, Spotted fever, Ehrlichiosis (anaplasmosisin) in wild animals and ticks in the mountain areas of Zhejiang province. Methods Nested polymerase chain reaction was used to amplify specific DNA sequences of Lyme spirochetes, Spotted fever group rickettsiae, Ehrlichia (anaplasma) from samples of mice and ticks. Results 14 positive samples were identified from 121 mice and 105 groups of ticks. Among mice samples, one positive 5S-23S rDNA intergenic spacer of Borreia burgdorferi and two 5' fragments of Ehrlichia (anaplasma) 16S rDNA were obtained. 11 positive results were detected from tick samples including three 5S-23S rDNA intergenic spacer regions of Borreia burgdorferi and eight 5' fragments of Spotted fever group rickettsiae outer member protein A gene. One group of adult ticks, Haemaphysalis longicornis, which had been collected from eastern mountain area were detected to have co-infected with Lyme spirochetes and Spotted fever group rickettsiae. The positive sequences of 5S-23S rDNA intergenic spacer and ompA gene were tested and analyzed as Lyme spirochetes while rickettsia which was closely related to Borrelia valaisiana and R. massilliae. Conclusion This was the first report about co-infection of Lyme spirochetes and Spotted fever group rickettsiae found in the same group of adult Haemaphysalis longicornis. It is very important to strengthen the surveillance program on tick-borne infectious disease and their pathogenic in vectors, wild animals and targeted high risk groups and to differentiate the clinical manifestation and diagnosis to extend the knowledge of tick-borne infectious diseases in Zhejiang.

OBJECTIVETo examine vibrio cholera (V.C) in aquatic products of littoral area, Zhejiang Province and to provide scientific evidence for administration of aquatic products and cholera epidemic control.

METHODSAll 990 samples of aquatic products collected from local markets, eateries and aquafarms in three chosen areas. Samples were proliferated in alkaline liquid medium, and purified in NO: 4 medium, the isolations were identified biochemically, and phenotype of strains were defined by phagocyte and coagulation with V.C. diagnostic serum. Three virulence genes (ctx, ace, zct) of the isolated strains were detected by polymerase chain reaction (PCR).

RESULTSThere were 1.41% samples caught by V.C., having a carrying rate highest in turtles of 8.9%. 14 strains were defined as three serogroups, and the numbers of Inaba, Ogawa, and Hikojima types were 2, 2, 10 respectively. Virulence genes had detected in 9 of 12 stains. All genes were detected in 5 strains, only ZOT genes in 3 strains, and both CTX and ACE genes in 1 strain.

CONCLUSIONSAquatic products from inshore in Zhejiang Province caught with V.C. strains might be divided into three serogroups. Most of them should be virulence genes. Cholera epidemic outbreak might be caused by those contaminated products.

China ; Food Microbiology ; Genes, Bacterial ; Seafood ; microbiology ; Vibrio cholerae ; genetics ; isolation & purification ; Virulence Factors ; genetics

AIMTo study the effect of curcumin on the expression of prostate specific antigen (PSA).

METHODSAXSYM system-chemical luciferase method was used to examine the content of PSA in prostate cancer cell lines, LNCap after treated with different doses of curcumin. pGL3-PSA luciferase expression vector, containing 640 bp DNA of PSA gene 5' promoter region was constructed and transfected into LNCap cell with lipofectin. Through detecting the activity of luciferase, the effect of curcumin on the promoter of PSA was studied. Western blotting was used to detect expression of androgen receptor (AR) in LNCap cell with different concentrations of curcumin.

RESULTSThe expression of PSA was inhibited and activity of luciferase was reduced by curcumin. There was also significant difference in AR expression as shown by Western blotting experiment after treatment of different doses of curcumin.

CONCLUSIONThrough inhibiting AR expression, curcumin reduced the function of PSA promoter and inhibited PSA protein expression.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Curcumin ; pharmacology ; Humans ; Luciferases ; metabolism ; Male ; Promoter Regions, Genetic ; drug effects ; Prostate-Specific Antigen ; genetics ; metabolism ; Prostatic Neoplasms ; immunology ; metabolism ; pathology ; Receptors, Androgen ; metabolism

Air Conditioning ; Humans ; Legionella pneumophila ; isolation & purification ; RNA, Bacterial ; analysis ; Water Microbiology