2016 Vol. 29, No. 4
ObjectiveTo investigate distinctive features in drug-resistant mutations(DRMs) and interpretations for reverse transcriptase inhibitors (RTIs) between proviral DNA and paired viral RNA in HIV-1-infected patients.
MethodsForty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared
between viral RNA and paired proviral DNA.
ResultsCompared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher’s exact test,P<0.05). Considering‘majority resistant variants’,15 samples (19.48%) showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs.Considering‘minority resistant variants’, 22 samples (28.57%) were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA.
ConclusionCompared with viral RNA, the distinctive information of DRMsand drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.
MethodsForty-three HIV-1-infected individuals receiving first-line antiretroviral therapy were recruited to participate in a multicenter AIDS Cohort Study in Anhui and Henan Provinces in China in 2004. Drug resistance genotyping was performed by bulk sequencing and deep sequencing on the plasma and whole blood of 77 samples, respectively. Drug-resistance interpretation was compared
between viral RNA and paired proviral DNA.
ResultsCompared with bulk sequencing, deep sequencing could detect more DRMs and samples with DRMs in both viral RNA and proviral DNA. The mutations M184I and M230I were more prevalent in proviral DNA than in viral RNA (Fisher’s exact test,P<0.05). Considering‘majority resistant variants’,15 samples (19.48%) showed differences in drug resistance interpretation between viral RNA and proviral DNA, and 5 of these samples with different DRMs between proviral DNA and paired viral RNA showed a higher level of drug resistance to the first-line drugs.Considering‘minority resistant variants’, 22 samples (28.57%) were associated with a higher level of drug resistance to the tested RTIs for proviral DNA when compared with paired viral RNA.
ConclusionCompared with viral RNA, the distinctive information of DRMsand drug resistance interpretations for proviral DNA could be obtained by deep sequencing, which could provide more detailed and precise information for drug resistance monitoring and the rational design of optimal antiretroviral therapy regimens.
2016, 29(4): 248-253.
doi: 10.3967/bes2016.032
Objective To compare the performance of MTBDRplus V2 and Xpert MTB/RIF for detecting smear negative pulmonary tuberculosis (PTB).
Methods Clinical PTB suspects were enrolled consecutively in Anhui Chest Hospital and Xi’an Chest Hospital from January to December in 2014. The sputum samples of smear negative PTB suspects were collected and decontaminated. The sediment was used to conduct MTBDRplus V2, Xpert MTB/RIF and drug susceptibility test (DST). All the samples with discrepant drug susceptibility result between molecular methods and phenotypic method were confirmed by DNA sequencing.
Results A total of 1973 cases were enrolled in this study. The detection rates ofMycobacterium tuberculosiscomplex (MTBC) by MTBDRplus V2 and Xpert MTB/RIF were 27.67% and 27.98%, respectively. When setting MGIT culture result as a gold standard, the sensitivity and specificity of MTBDRplus V2 were 86.74% and 93.84%, and the sensitivity and specificity of Xpert MTB/RIF were 86.55% and 93.43%, respectively. For the detection of the resistance to rifampin, the sensitivity and specificity of MTBDRplus V2 were 94.34% and 96.62%, and the sensitivity and specificity of Xpert MTB/RIF were 88.68% and 95.96%, respectively. For the detection of the resistance to isoniazid, the sensitivity and specificity of MTBDRplus V2 were 77.38% and 98.02%, respectively.
Conclusion MTBDRplus V2 and Xpert MTB/RIF can be used to detect MTBC in smear negative samples with satisfactory performance.
Methods Clinical PTB suspects were enrolled consecutively in Anhui Chest Hospital and Xi’an Chest Hospital from January to December in 2014. The sputum samples of smear negative PTB suspects were collected and decontaminated. The sediment was used to conduct MTBDRplus V2, Xpert MTB/RIF and drug susceptibility test (DST). All the samples with discrepant drug susceptibility result between molecular methods and phenotypic method were confirmed by DNA sequencing.
Results A total of 1973 cases were enrolled in this study. The detection rates ofMycobacterium tuberculosiscomplex (MTBC) by MTBDRplus V2 and Xpert MTB/RIF were 27.67% and 27.98%, respectively. When setting MGIT culture result as a gold standard, the sensitivity and specificity of MTBDRplus V2 were 86.74% and 93.84%, and the sensitivity and specificity of Xpert MTB/RIF were 86.55% and 93.43%, respectively. For the detection of the resistance to rifampin, the sensitivity and specificity of MTBDRplus V2 were 94.34% and 96.62%, and the sensitivity and specificity of Xpert MTB/RIF were 88.68% and 95.96%, respectively. For the detection of the resistance to isoniazid, the sensitivity and specificity of MTBDRplus V2 were 77.38% and 98.02%, respectively.
Conclusion MTBDRplus V2 and Xpert MTB/RIF can be used to detect MTBC in smear negative samples with satisfactory performance.
ObjectiveThis study exploredthe correlation of longitudinal changes in serumalanine aminotransferase (ALT) and aspartate aminotransferase (AST)levels with the incidence of metabolic syndrome (Mets)based on a dynamic health examination cohort.
MethodsA Mets-free dynamic cohortinvolving 4541 participants who underwent at leastthree health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definitionthat included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation (GEE) model was used to analyze multivariate relative risk (RR) of repeated observations ofALT and AST in quartiles for Mets or its components according to gender.
ResultsIn all, 826Mets cases were reported. Adjustmentof relevant parameters indicated that time-varyingchanges in ALT and ASTlevels were positively associated with the incidenceof Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in maleparticipants. These associations were consistently observed in the following subgroups: participants with ALT and ASTlevels of <40U/L, participants withof <25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component.
ConclusionThese results suggested that elevated serum ALT and AST levels wereearly biomarkers of Mets or its components.
MethodsA Mets-free dynamic cohortinvolving 4541 participants who underwent at leastthree health examinations from 2006 to 2011 was included in the study. Mets was defined according to the Chinese Medical Association Diabetes Branch definitionthat included hypertension, obesity, hyperlipidemia, and hyperglycemia. Generalized estimating equation (GEE) model was used to analyze multivariate relative risk (RR) of repeated observations ofALT and AST in quartiles for Mets or its components according to gender.
ResultsIn all, 826Mets cases were reported. Adjustmentof relevant parameters indicated that time-varyingchanges in ALT and ASTlevels were positively associated with the incidenceof Mets in a dose-response manner. Positive association between high ALT levels and fatty liver was much stronger than that between high AST levels and fatty liver, particularly in maleparticipants. These associations were consistently observed in the following subgroups: participants with ALT and ASTlevels of <40U/L, participants withof <25 kg/m2, and participants with non-fatty liver. Furthermore, participants with 2 Mets components at baseline showed lower multivariate adjusted RRs of ALT and AST for Mets than participants with 0-1 Mets component.
ConclusionThese results suggested that elevated serum ALT and AST levels wereearly biomarkers of Mets or its components.
ObjectiveTo evaluatethehealth effects of parental dietary exposure to GM rice TT51 on the male reproductive system of rat offspring.
MethodsRice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats (15 males/30 females each group) for 70 days prior mating and throughout pregnancy and lactation. After weaning, eightmale offspringratswere randomly selected at each group and fed with dietscorrespondent to their parents’ for 70 days. The effects of exposure to TT51 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serumhormones (FSH, LH, and testosterone levels), testis histopathological examination, and the relativeexpression levels of selected genes along the hypothalamic-pituitary-testicular (HPT) axis.
ResultsNo significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis.
ConclusionThe resultsof this studydemonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.
MethodsRice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats (15 males/30 females each group) for 70 days prior mating and throughout pregnancy and lactation. After weaning, eightmale offspringratswere randomly selected at each group and fed with dietscorrespondent to their parents’ for 70 days. The effects of exposure to TT51 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serumhormones (FSH, LH, and testosterone levels), testis histopathological examination, and the relativeexpression levels of selected genes along the hypothalamic-pituitary-testicular (HPT) axis.
ResultsNo significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis.
ConclusionThe resultsof this studydemonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.
2016, 29(4): 275-285.
doi: 10.3967/bes2016.035
ObjectiveWe evaluate the effects ofThymus algeriensis (TEO) against hydrogen peroxide (H2O2) toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats.
MethodsRats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg).
ResultsThe results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P<0.05), sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H2O2 compared to controls.The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity andsignificant increase (P<0.05) in MDAconcentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2generated oxidative stress.These results were confirmed byhistological architecture examinations.
ConclusionH2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.
MethodsRats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg).
ResultsThe results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P<0.05), sperm motility and percentage of sperm viability, leading to complete arrest, in sperm flagellar beat frequency by the gavage of 1 mmol/L H2O2 compared to controls.The administration of H2O2 resulted in a significant reduction in testis GSH, GPx, CAT, SOD, and GST activity andsignificant increase (P<0.05) in MDAconcentration compared with the untreated control animals. TEO pre-treatment protected testis from the H2O2generated oxidative stress.These results were confirmed byhistological architecture examinations.
ConclusionH2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.
2016, 29(4): 305-313.
doi: 10.3967/bes2016.040