Objective To determine the association of mutations in aldosterone synthase (CYPllB2)and 11 beta-hydroxylase(CYP11B1)genes with primary aldosteronism(PA).Methods Five mutations of CYP11B2 and CYP11B1 genes were analyzed in patients with PA and normal population.Among them,intron 2 was detected by 2 independent PCR reactions,and the others were analyzed using Taqman probes.The Haploview 4.0,SNPassoc 1.5-3 and Haplo.stats 1.3.8 were used to analyse the association between polymorphisms and PA.Results All the selected mutations were successfully genetyped.Only rs64lO allelic frequencies in patients with aldosterone-producing adenoma (APA)and idiopathic hyperaldosteronism(IHA)were significantly different with those in controls (P＜0.05).There was a relative excess of AA homozygotes and AG heterozygotes of rs6410 allele in APA group compared with control group(P＜0.01).There were significantly different genotypes AA and AG of rs6410 allele between patients with IHA and controls only after adjusted for age,gender,eeptible haplotype AAAWT was identified to be significantly associated with APA(OR=1.44,95%CI 1.19-1.76).Three susceptible haplotypes AAAWT,AGGWT and AGAWC were identified to be significantly associated with IHA(OR=1.55,95%CI 1.23-1.96;OR=1.49,95%CI 1.17-1.89;OR=1.40,95%CI 1.04-1.88).In contrast,1 protective haplotype GGAWT showed significant difference between patients with APA and controls(OR=0.73,95%CI 0.55-0.97).Conclusion There is a significant association between genetic variations in CYP11B2 and CYP11B1 genes and genetie predisposition to PA.

OBJECTIVETo study the effects of celecoxib on the cell proliferation and expression of vascular endothelial growth factor (VEGF) in human nasopharyngeal carcinoma line.

METHODS3-[ 4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) test was used to investigate the cell proliferation. Flow cytometry (FCM) was used to analyze the cell cycle arrest. Immunocytochemistry technique was to observe the expression of VEGF.

RESULTSCelecoxib inhibited the growth of nasopharyngeal carcinoma line, the cell number of G0/G1 phase increased from 62.13% to 91.35%, and the cell number of G2/M and S phase decreased from 21.59% to 3.56% and from 16.28% to 5.01%, respectively, cell cycle progression was arrested at G1/S phase. Celecoxib decreased the positive expression of VEGF in HNE-1 cells.

CONCLUSIONSCelecoxib inhibited the proliferation of nasopharyngeal carcinoma significantly and the expression of VEGF.

Celecoxib ; Cell Line, Tumor ; drug effects ; metabolism ; Cell Proliferation ; drug effects ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases