Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drug...Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drugs. Ethanol is reward drug and a CNS depressant especially at high doses. The study determined the effect of sustained heavy ethanol drinking by HIV-infected patients on d4T/3TC/NVP regimen on CD4+ cell counts in Uganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A case control study using repeated measures design with serial measurements model was used. The patients on stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg and nevirapine (NVP) 200 mg and chronic alcohol use were recruited. A total of 41 patients (20 in alcohol group and 21 in control group) were screened for chronic alcohol use by WHO AUDIT tool and chronic alcohol use biomarkers. They were followed up for 9 months with blood sampling done at 3 months intervals. CD4+ cell count was determined using Facscalibur Flow Cytometer system. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ ALT ratio). Data were analysed using SAS 2003 version 9.1 statistical package with repeated measures fixed model and the means were compared using student t-test. The mean CD4+ cell counts in all the groups were lower than the reference ranges at baseline and gradually increased at 3, 6 and 9 months of follow-up. The mean CD4+ cell counts were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p > 0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV-infected patients on d4T/3TC/NVP treatment regimen.展开更多
Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adu...Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir,emtricitabine,and tenofovir alafenamide(BIC/FTC/TAF)or lamivudine,efavirenz,and tenofovir disoproxil fumarate(3TC+EFV+TDF),monitoring at weeks 4,12,24,and 48.Methods:A case-control retrospective study was conducted.The newly diagnosed HIV-infected individuals attending the sexual transmission disease(STD)/AIDS clinic of Beijing Youan Hospital,Capital Medical University,from January to December 2021.The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group.High-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),and total cholesterol(TC)at different time points over 48 weeks between two groups were compared.A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results:A total of 870 participants,with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group.There were no statistically significant differences in median age,baseline CD4/CD8 ratio,median body mass index(BMI)between the two groups.In both two groups,levels of TG,TC,and LDL-C were higher at 4 weeks,12 weeks,and 24 weeks of treatment(all P<0.05),and there were no statistically significant differences at 48 weeks compared to those at baseline(all P>0.05).In addition,the differences in average changes of the level of TG,TC,HDL-C,and LDL-C from weeks 4,12,24,and 48 to baseline between two groups were not statistically significant(all P>0.05).Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA≥10^(5)copies/mL(compared with<10^(5)copies/mL)was associated with an increased risk of elevated LDL-C(hazard ratio=1.26,95%confidence interval:1.07-1.48,P=0.005).Conclusions:Transient elevations in blood lipid levels(TC,TG,HDL-C,and LDL-C)were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks,12 weeks,and 24 weeks of treatment.However,these levels did not differ significantly from baseline after 48 weeks of treatment,regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.展开更多
目的评价符合入排条件的接受EFV+3TC+TDF方案的HIV-1感染者转换为艾诺米替(艾诺韦林/拉米夫定/替诺福韦,ANV/3TC/TDF)治疗144周,以及EFV+3TC+TDF转换艾考恩丙替(艾维雷韦/考比司他/恩曲他滨/丙酚替诺福韦,EVG/c/FTC/TAF)治疗48周后,继...目的评价符合入排条件的接受EFV+3TC+TDF方案的HIV-1感染者转换为艾诺米替(艾诺韦林/拉米夫定/替诺福韦,ANV/3TC/TDF)治疗144周,以及EFV+3TC+TDF转换艾考恩丙替(艾维雷韦/考比司他/恩曲他滨/丙酚替诺福韦,EVG/c/FTC/TAF)治疗48周后,继续转换为ANV/3TC/TDF治疗至144周的有效性和代谢安全性。方法本研究为SPRINT(Switching people with HIV to receive innovative NNRTI-based therapy)研究的拓展性用药研究,将研究对象分为即刻转换组(指ANV/3TC/TDF自基线治疗至第144周)和延迟转换组(指EVG/c/FTC/TAF自基线治疗48周后,转换为ANV/3TC/TDF治疗至第144周)。研究的有效性终点为治疗144周时HIV-1病毒得到抑制的研究对象百分比,代谢安全性结局包括低密度脂蛋白胆固醇(LDL-C)、动脉粥样硬化性心血管疾病(ASCVD)风险相关LDL-C分层,估计肾小球滤过率(eGFR)用于评估肾功能安全性。结果研究共纳入731例研究对象,其中即刻转换组370例,延迟转换组361例。治疗144周时,即刻转换组与延迟转换组的研究对象病毒学抑制百分比分别为95.3%与95%,两组的CD4细胞计数自48周到144周分别上升(70.9±8.7)与(64.4±9.7)个/μL。延迟转换组的LDL-C值由于经历了0到48周上升过程,在48到144周时的降幅显著大于即刻转换组(-0.44±0.03 vs.-0.06±0.03 mmol/L,P<0.001),两组LDL-C高风险分层百分比自基线到144周分别下降60.0%和78.1%。治疗144周时两组eGFR值分别为(109.1±20.4)mL/min/1.73 m^(2)与(106.3±13.9)mL/min/1.73 m^(2),组间差异无统计学意义(P>0.05)。结论EFV为核心的cART方案以及含TAF的整合酶抑制剂(INSTIs)方案转换为ANV/3TC/TDF均可实现持续病毒学抑制,同时持续改善LDL-C水平及ASCVD风险分层。由含TAF的INSTIs方案转换为ANV/3TC/TDF方案后,可显著降低LDL-C异常的研究对象比例。展开更多
Background： SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive （AR） Charcot-Marie-Tooth （CMT） disease type 1, autosomal dominant （AD）-CMTI, and AD-CMT2, respectively. Pathogenic variants in these ...Background： SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive （AR） Charcot-Marie-Tooth （CMT） disease type 1, autosomal dominant （AD）-CMTI, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. Methods： A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMTI probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB 1, GDAP1, HSPB1, HSPB8, EGR2, NEFL. and RABT. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics （ACMG）. Clinical features were reevaluated. Results： We identified three novel heterozygous variants such as p.L95V （c.283C〉G）, p.L 1048P （c.3143T〉C）, and p.V 1105 M （c.3313G〉A） of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.LI048P, and p.V1105M were considered to be of uncertain significance. Conclusions： SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.展开更多
Memory catalysis and conventional Fenton reactions are intended to counteract prevailing energy and environmental crises;however,poor performance and the need for UV irradiation question their sustain-ability.Herein,w...Memory catalysis and conventional Fenton reactions are intended to counteract prevailing energy and environmental crises;however,poor performance and the need for UV irradiation question their sustain-ability.Herein,we demonstrate defect-engineered,dual Z-scheme MoS_(2)/WO_(3-x)/Ag_(2)S exhibiting enhanced photo-Fenton(PFR),night-Fenton(NFR),and photocatalytic activities(PR)against tetracycline(TC)and Rhodamine B(RhB).Defects enable the catalyst to store ample electrons just like metals,which play a vi-tal role by exciting H2 O2 during Fenton reactions.It removed 91.54%,76.43%,and 83.39%TC(40 mg L^(-1))in 100 min and registered degradation rate constants of 0.05379,0.02858,and 0.04133 min^(-1)against RhB(20 mg L^(-1))during PFR,NFR,and PR respectively.The total organic carbon(TOC)removal rates reached 58.56%and 60.88%during TC and RhB degradations in PFR,respectively.Solid and Liquid EPR analy-sis shows it can excite H_(2)O_(2)to carry Fenton reactions with and without light.It demonstrates wide pH adaptability and tremendous potential to simultaneously counter energy and environmental crises.展开更多
文摘Sustained heavy ethanol drinking is a common problem globally and ethanol is one of the most abused drugs among individuals of different socio-economic status including the HIV-infected patients on antiretroviral drugs. Ethanol is reward drug and a CNS depressant especially at high doses. The study determined the effect of sustained heavy ethanol drinking by HIV-infected patients on d4T/3TC/NVP regimen on CD4+ cell counts in Uganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A case control study using repeated measures design with serial measurements model was used. The patients on stavudine (d4T) 30 mg, lamivudine (3TC) 150 mg and nevirapine (NVP) 200 mg and chronic alcohol use were recruited. A total of 41 patients (20 in alcohol group and 21 in control group) were screened for chronic alcohol use by WHO AUDIT tool and chronic alcohol use biomarkers. They were followed up for 9 months with blood sampling done at 3 months intervals. CD4+ cell count was determined using Facscalibur Flow Cytometer system. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ ALT ratio). Data were analysed using SAS 2003 version 9.1 statistical package with repeated measures fixed model and the means were compared using student t-test. The mean CD4+ cell counts in all the groups were lower than the reference ranges at baseline and gradually increased at 3, 6 and 9 months of follow-up. The mean CD4+ cell counts were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p > 0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV-infected patients on d4T/3TC/NVP treatment regimen.
基金supported by the Gilead Sciences and the Capital Health Research and Development of Special Fund(No.2022-1G-3015)
文摘Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir,emtricitabine,and tenofovir alafenamide(BIC/FTC/TAF)or lamivudine,efavirenz,and tenofovir disoproxil fumarate(3TC+EFV+TDF),monitoring at weeks 4,12,24,and 48.Methods:A case-control retrospective study was conducted.The newly diagnosed HIV-infected individuals attending the sexual transmission disease(STD)/AIDS clinic of Beijing Youan Hospital,Capital Medical University,from January to December 2021.The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group.High-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),and total cholesterol(TC)at different time points over 48 weeks between two groups were compared.A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results:A total of 870 participants,with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group.There were no statistically significant differences in median age,baseline CD4/CD8 ratio,median body mass index(BMI)between the two groups.In both two groups,levels of TG,TC,and LDL-C were higher at 4 weeks,12 weeks,and 24 weeks of treatment(all P<0.05),and there were no statistically significant differences at 48 weeks compared to those at baseline(all P>0.05).In addition,the differences in average changes of the level of TG,TC,HDL-C,and LDL-C from weeks 4,12,24,and 48 to baseline between two groups were not statistically significant(all P>0.05).Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA≥10^(5)copies/mL(compared with<10^(5)copies/mL)was associated with an increased risk of elevated LDL-C(hazard ratio=1.26,95%confidence interval:1.07-1.48,P=0.005).Conclusions:Transient elevations in blood lipid levels(TC,TG,HDL-C,and LDL-C)were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks,12 weeks,and 24 weeks of treatment.However,these levels did not differ significantly from baseline after 48 weeks of treatment,regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.
文摘目的评价符合入排条件的接受EFV+3TC+TDF方案的HIV-1感染者转换为艾诺米替(艾诺韦林/拉米夫定/替诺福韦,ANV/3TC/TDF)治疗144周,以及EFV+3TC+TDF转换艾考恩丙替(艾维雷韦/考比司他/恩曲他滨/丙酚替诺福韦,EVG/c/FTC/TAF)治疗48周后,继续转换为ANV/3TC/TDF治疗至144周的有效性和代谢安全性。方法本研究为SPRINT(Switching people with HIV to receive innovative NNRTI-based therapy)研究的拓展性用药研究,将研究对象分为即刻转换组(指ANV/3TC/TDF自基线治疗至第144周)和延迟转换组(指EVG/c/FTC/TAF自基线治疗48周后,转换为ANV/3TC/TDF治疗至第144周)。研究的有效性终点为治疗144周时HIV-1病毒得到抑制的研究对象百分比,代谢安全性结局包括低密度脂蛋白胆固醇(LDL-C)、动脉粥样硬化性心血管疾病(ASCVD)风险相关LDL-C分层,估计肾小球滤过率(eGFR)用于评估肾功能安全性。结果研究共纳入731例研究对象,其中即刻转换组370例,延迟转换组361例。治疗144周时,即刻转换组与延迟转换组的研究对象病毒学抑制百分比分别为95.3%与95%,两组的CD4细胞计数自48周到144周分别上升(70.9±8.7)与(64.4±9.7)个/μL。延迟转换组的LDL-C值由于经历了0到48周上升过程,在48到144周时的降幅显著大于即刻转换组(-0.44±0.03 vs.-0.06±0.03 mmol/L,P<0.001),两组LDL-C高风险分层百分比自基线到144周分别下降60.0%和78.1%。治疗144周时两组eGFR值分别为(109.1±20.4)mL/min/1.73 m^(2)与(106.3±13.9)mL/min/1.73 m^(2),组间差异无统计学意义(P>0.05)。结论EFV为核心的cART方案以及含TAF的整合酶抑制剂(INSTIs)方案转换为ANV/3TC/TDF均可实现持续病毒学抑制,同时持续改善LDL-C水平及ASCVD风险分层。由含TAF的INSTIs方案转换为ANV/3TC/TDF方案后,可显著降低LDL-C异常的研究对象比例。
文摘Background： SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive （AR） Charcot-Marie-Tooth （CMT） disease type 1, autosomal dominant （AD）-CMTI, and AD-CMT2, respectively. Pathogenic variants in these three genes were not well documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2, PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT families. Methods： A total of 315 probands from 315 unrelated Chinese CMT families were recruited from the Department of Neurology of Third Xiangya Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84 AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMTI probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using polymerase chain reaction and Sanger sequencing. All these patients were out of 315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of pathogenic variants of PMP22, MFN2, MPZ, GJB 1, GDAP1, HSPB1, HSPB8, EGR2, NEFL. and RABT. Candidate variants were analyzed based on the standards and guidelines of American College of Medical Genetics and Genomics （ACMG）. Clinical features were reevaluated. Results： We identified three novel heterozygous variants such as p.L95V （c.283C〉G）, p.L 1048P （c.3143T〉C）, and p.V 1105 M （c.3313G〉A） of SH3TC2 gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in silico and screening in the healthy control revealed that the three SH3TC2 variants were likely pathogenic, no second allele variants were discovered. According to the standards and guidelines of ACMG, the heterozygous SH3TC2 variants such as p.L95V, p.LI048P, and p.V1105M were considered to be of uncertain significance. Conclusions： SH3TC2, PMP2, and BSCL2 pathogenic variants might be rare in Chinese CMT patients. Further studies to confirm our findings are needed.
基金supported by the National Basic Research Program of China(No.2022YFA1603701)the National Natural Science Foundation of China(No.82341044)the Beijing Natural Science Foundation(No.L212015).
文摘Memory catalysis and conventional Fenton reactions are intended to counteract prevailing energy and environmental crises;however,poor performance and the need for UV irradiation question their sustain-ability.Herein,we demonstrate defect-engineered,dual Z-scheme MoS_(2)/WO_(3-x)/Ag_(2)S exhibiting enhanced photo-Fenton(PFR),night-Fenton(NFR),and photocatalytic activities(PR)against tetracycline(TC)and Rhodamine B(RhB).Defects enable the catalyst to store ample electrons just like metals,which play a vi-tal role by exciting H2 O2 during Fenton reactions.It removed 91.54%,76.43%,and 83.39%TC(40 mg L^(-1))in 100 min and registered degradation rate constants of 0.05379,0.02858,and 0.04133 min^(-1)against RhB(20 mg L^(-1))during PFR,NFR,and PR respectively.The total organic carbon(TOC)removal rates reached 58.56%and 60.88%during TC and RhB degradations in PFR,respectively.Solid and Liquid EPR analy-sis shows it can excite H_(2)O_(2)to carry Fenton reactions with and without light.It demonstrates wide pH adaptability and tremendous potential to simultaneously counter energy and environmental crises.
