ABSTRACT
Radiation-induced lung injury is a common complication of radiotherapy for thoracic tumor, usually involves the radiation-induced pneumonitis at early stage and radiation-induced pulmonary fibrosis at late stage, which seriously affects the treatment and prognosis of patients. At present the common treatments for radiation-induced pulmonary fibrosis include anti-inflammatory therapy, glucocorticoid therapy, antioxidant therapy and so on. Recentlywith the further research of radiation-induced pulmonary fibrosis, more and more attention has attracted in molecular targeted therapy. Molecular targeted inhibitors is a new class of drugs for the treatment of radiation-induced lung injury, mainly targeting a variety of cytokines, signaling pathways, tyrosine kinase receptors and other targets. This article systematically reviews the pathogenesis and molecular targeted therapy of radiation-induced lung injury.
ABSTRACT
Objective To investigate the molecular epidemiology and antimicrobial resistance status of uropathogenic Escherichia coli (UPEC) in senior population in Putuo District ,Shanghai .Methods A total of 72 UPEC strains were isolated from elderly inpatients with urinary tract infections in Putuo Hospital ,Shanghai University of Traditional Chinese Medicine from January 2013 to March 2015 .The strains were characterized by multi‐locus sequence typing (MLST ) .The β‐lactamase gene and the plasmid mediated quinolone resistance (PMQR) gene were detected ,and the mutations of quinolone resistance‐determining regions (QRDR) in gyrA and parC genes were demonstrated .In vitro drug susceptibility test was performed .Continuous variables were compared using t test and categorical variables were compared using chi‐squared test or Fisher exact test .Results The UPEC strains showed different resistance rates to ciprofloxacin ,cefotaxime and trimethoprim‐sulfamethoxazole ,which were 76 .4% ,73 .6% and 65 .3% , respectively .UPEC still remained highly sensitive to imipenem ,meropenem ,amikacin and piperacillin‐tazobactam .Among 72 isolates ,55 (76 .4% ) of 49 (68 .1% ) extended‐spectrum β‐lactamase (ESBL )‐positive strains harbored blaCTX‐M genes .Among the 55 ciprofloxacin resistant strains ,51 (92 .7% ) had three or four mutations in QRDR of gyrA and parC genes .The “hot‐spot” mutations of QRDR were located at amino acid position 83 and 87 in gyrA gene and at positions 80 and 84 in parC gene .Forward analysis by MLST showed that the most frequent sequence types (ST ) were ST131 (18/72 ,25 .0% ) , ST1193(7/72 ,9 .7% ) ,ST405 (7/72 ,9 .7% ) ,ST38 (5/72 ,6 .9% ) and ST648 (3/72 ,4 .2% ) .ST131 isolates were predominant in ST which caused community‐onset urinary tract infections .Multiple drug‐resistance were detected in ST 131 ,ST405 ,ST38 and ST648 which were mainly producing blaCTX‐M ESBL .Conclusions Community‐acquired multiple drug‐resistant UPEC strains such as ST131 clone are prevalent in elderly patients .Thus ,monitoring of molecular epidemiology would be beneficial to prevent the prevalence of multiple drug‐resistant UPEC .
ABSTRACT
Objective To investigate the association of the polymorphism of the N-acetyltransferase 2 (NAT2 )gene with isoniazid-induced hepatotoxicity and anti-tuberculous treatment efficacy in Chinese Han patients with tuberculosis(TB).Methods A total of 108 TB patients who received initial anti-TB treatment were followed up prospectively.A polymerase chain reaction direct sequencing approach was used to detect genetic polymorphisms of the NAT2 gene.Associations between NAT2 genotype and isoniazid-induced hepatitis/early treatment were analyzed.Chi-square test was used for statistical analysis. Results Among the 108 TB patients, intermediate-acetylators (IA ) was the most frequent NAT2 genotype with the proportion of 54.63%(59/108).The proportion of rapid-acetylators(RA)was 33.33%(36/108),slow-acetylators (SA)was 10.19%(11/108)and super-rapid acetylators was 1 .85 % (2/108). Among the 20 patients who developed drug-induced hepatitis,2 were RA,5 were SA and 13 were IA. Regarding NAT2 genotype,RA patients had a lower incidence of hepatotoxicity (OR =0.176,95 %CI :0.038-0.809,P =0.014)and SA patients were more likely to developed drug-induced hepatic injury (OR=4.556,95 %CI :1 .231 -16.854,P =0.044 ).Statistical analysis revealed that the frequency of variant diplotypes,NAT2*4/*6A (OR=7.741 ,95 %CI :2.653-22.586,P <0.01 )and NAT2 *6A/*6A (OR=15 .353,95 %CI :1 .506 -156.552,P =0.020)were significantly increased in TB patients with hepatotoxicity.NAT2 *4/*4 was less likely to developed hepatic injury (OR =0.176,95 %CI :0.038-0.809,P =0.014).Among the 58 culture-positive patients,12(31 .03%)were persistent culture positive after 2 months standard therapy.Early treatment failure was observed with significantly higher incidence rate in RA than other genotypes (OR = 7.200, 95 % CI :1 .794-28.900, P = 0.008). Conclusions In Chinese Han TB patients,IA is the most frequent NAT2 genotype.The SA status of NAT2 is a risk factor of isoniazid-induced hepatotoxicity.The diplotype of NAT2 *6A has clearly high risk of isoniazid-induced hepatotoxicity.In contrast,NAT2 * 4/* 4 is protective diplotype.RA is associated with early treatment failure in culture-positive patients.