Background:Despite the availability of Anti-Retroviral Therapy(ART),the health-related quality of life(HRQoL)among HIV-positive men who have sex with men(HIVMSM)in China remains poor.This study aimed to explore the re...Background:Despite the availability of Anti-Retroviral Therapy(ART),the health-related quality of life(HRQoL)among HIV-positive men who have sex with men(HIVMSM)in China remains poor.This study aimed to explore the relationship between self-reported psychopathology and HRQoL among HIVMSM in Dalian,China.Methods:A cross-sectional study was conducted in 112 HIVMSM.Symptom check list 90(SCL 90):a measure of psychopathology and World Health Organization quality of life in HIV infection(WHOQOL-HIV-Bref):a measure of HRQoL were used.Correlation and multiple regression analysis were employed to explore the association between self-reported psychopathology and HRQoL in HIVMSM.Results:Out of the total 112 HIVMSM cases,9(8%)cases were homosexuals and 103(92%)ones were bisexuals.The participants who had low family income(P=0.001),perceived discrimination(P=0.001)and lack of regular attendance in medical follow-ups(P=0.014)reported poorer HRQoL than their counterparts.Somatization,obsession,depression,phobia and overall SCL 90 scores in self-reported psycholpathology had a negative impact on the domains of HRQoL among HIVMSM.Conclusions:Total quality of life was predicted by family income,perceived discrimination,and medical follow-up attendance.Self-reported psychopathology was negatively correlated with HRQoL in HIVMSM.The Strategies that target MSM focusing on linking and engaging HIV-positive patients in medical care is the key step to improve their HRQoL.More emphasis is needed on the newly diagnosed HIVMSM in Dalian in order to develop a more targeted intervention to prevent perceived discrimination and lack of proper medical follow-up services.Trial registration:The trial registration number does not require for this manuscript.The study is cross-sectional design that do not involve intervention at all,it is not a clinical trial.展开更多
BACKGROUND Duchenne muscular dystrophy(DMD)is a neuromuscular disorder caused by mutations in the dystrophin gene.DMD is reported to coexist with other comorbidities,although the occurrence of the triad,autism spectru...BACKGROUND Duchenne muscular dystrophy(DMD)is a neuromuscular disorder caused by mutations in the dystrophin gene.DMD is reported to coexist with other comorbidities,although the occurrence of the triad,autism spectrum disorder(ASD),and epilepsy is very rare.Indeed,only one case of the triad has currently been reported.Here,we present a detailed case report of a ten-year-old boy with DMD,ASD,and epilepsy.We also investigated the dysregulation of miRNAs in this unusual triad(represented as DMD++)compared with a healthy individual and a DMD patient(represented as DMD+)without autism.AIM To understand the differential expression of miRNAs in rare comorbid DMD cases.METHODS The Sequin Form Board test,Gesell's drawing test,multiplex ligation probe amplification,and Vineland Social Maturity Scale were applied to confirm the DMD and ASD.Total RNA was isolated from samples using TRIzol.cDNA was synthesized using the Mir-X^(TM)miRNA First-Strand Synthesis kit.qRT-PCR was performed using SYBR Advantage qPCR Premix.The results were statistically analyzed using one-way analysis of variance with Tukey's ttest.RESULTS miR-146a-5p and miR-132-5p showed significant downregulation in both patient samples.miR-199a-5p and miR-146a-3p showed no change in expression between the diseased and controls.miR-132-3p showed downregulation only in the DMD+sample(0.21±0.04).The decrease in miR-132-3p can result in failed silencing of the phosphatase and tensin homolog-mediated apoptotic pathway,leading to severe skeletal muscle atrophy.Here,the downregulation of miR-132-3p in DMD+is consistent with severe muscle loss and higher disease progression than that in DMD++.DMD++has slower disease progression,and the expression of miRNA involved in inflammatory and apoptotic responses is more similar to that of the control.CONCLUSION Our study shows marked difference in miRNA expression in this rare case of DMD with autism and epilepsy.These miRNAs also serve as regulators of several muscle regeneration,apoptosis,and inflammatory pathways.This study shows the significance of studying miRNAs in such rare cases in a larger cohort to progress in several intervention treatments utilizing miRNAs.展开更多
Background The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus ...Background The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus on the induction of neutralizing antibodies. A major challenge in developing an HIV-1 vaccine is to identify immunogens and adopt delivery methods that can elicit broadly neutralizing antibodies against primary isolates of different genetic subtypes. Methods Most circulating HIV-1 isolates in China are composed of clades Thai-B, CRF_BC and CRF01_AE. In order to construct DNA vaccines against these 3 HIV-1 subtypes, DNA vaccines carrying the gp120 regions from HIV-1 isolates of GX48（AE）, GX79（AE）, NX22（BC）, GS22（BC）, HN24（Thai-B） were constructed. Expression of gp120 from these DNA vaccines was detected by Western blotting in transiently transfected 293T cells. Pilot immunizations of New Zealand white rabbits were performed using the strategy of ＂DNA prime plus protein boost＂ and the neutralizing antibody response was detected in a Tzm-bl cell based assay against different HIV-1 strains. Results Response of gp120-specific antibody was relatively low after DNA primes （mean titer=10^4.72）; however, the titer of gp120-specific antibody went up with 2 protein boosts （mean titer=10^6.81）. Above all, neutralizing antibody （Nab） titers induced by this combined approach were much better than those elicited by DNA or protein used alone （P 〈0.01）. Neutralizing activities of immunized rabbit sera against several pseudoviruses and laboratorial strains were evaluated, most rabbit sera primed with monovalent vaccine were capable of neutralizing only 1 of 5 viruses, however, sera primed with the polyvalent DNA vaccines were able to neutralize at least 2 of 5 viruses. Conclusion Polyvalent DNA prime plus protein boost is an effective immunization strategy to broaden the neutralization breadth and further research should be performed on the basis of this pilot study.展开更多
Summary What is already known about this topic?Identifying the most influential spreaders in human immunodeficiency virus(HIV)transmission networks is crucial for developing effective prevention strategies.What is add...Summary What is already known about this topic?Identifying the most influential spreaders in human immunodeficiency virus(HIV)transmission networks is crucial for developing effective prevention strategies.What is added by this report?This study identified key nodes of the HIV molecular transmission network among men who have sex with men(MSM)by utilizing linkages between sequences to reconstruct the transmission network at the molecular level.展开更多
There was no global guidance or agreement regarding when a country has an adequate system to report on the service packages among human immunodeficiency virus(HIV)key populations.This article describes an approach to ...There was no global guidance or agreement regarding when a country has an adequate system to report on the service packages among human immunodeficiency virus(HIV)key populations.This article describes an approach to categorizing the system in a country for reporting the service package among HIV key populations.The approach consists of four dimensions,namely the epidemiological significance,comprehensiveness of the service packages,geographic coverage of services,and adequacy of the monitoring system.The proposed categorization approach utilizes available information and can inform the improvement of the service delivery and monitoring systems among HIV key populations.展开更多
Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic...Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic CM patients and 98 non-diabetic CM patients from January 2008 to December 2018 in the First Affiliated Hospital of Zhejiang University were included by propensity score-matched method(1:2).Demographic characteristics,symptoms,and clinical assay parameters between the two groups were compared.Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality.Results:The mean age of diabetic patients was 58.2±13.8 years;71.4%(35/49)were more than 50 years old and 46.9%were male.No difference in symptoms was found between diabetic and non-diabetic CM patients.The Charlson comorbidity score was higher in the diabetic group(1.9 vs.0.7,P<0.001).CM patients with diabetes had higher white blood cells count(106/L,111.0(18.0–242.5)vs.50.0(10.0–140.0),P=0.034)in cerebrospinal fluid(CSF),lower CSF India ink positivity(40.8%vs.60.2%,P=0.039),and Cryptococcus culture positivity(42.9%vs.60.2%,P=0.047).The overall 10-week survival rate was 79.7%in diabetic patients vs.83.2%in non-diabetic patients(log-rank P=0.794).Conclusion:Diabetic CM patients have higher CSF glucose and Charlson comorbidity score,but lower CSF India ink and culture positivity than non-diabetic CM patients.No difference in 10-week mortality was found between patients with and without diabetes.Other comorbidities may have a greater effect on prognosis.展开更多
文摘Background:Despite the availability of Anti-Retroviral Therapy(ART),the health-related quality of life(HRQoL)among HIV-positive men who have sex with men(HIVMSM)in China remains poor.This study aimed to explore the relationship between self-reported psychopathology and HRQoL among HIVMSM in Dalian,China.Methods:A cross-sectional study was conducted in 112 HIVMSM.Symptom check list 90(SCL 90):a measure of psychopathology and World Health Organization quality of life in HIV infection(WHOQOL-HIV-Bref):a measure of HRQoL were used.Correlation and multiple regression analysis were employed to explore the association between self-reported psychopathology and HRQoL in HIVMSM.Results:Out of the total 112 HIVMSM cases,9(8%)cases were homosexuals and 103(92%)ones were bisexuals.The participants who had low family income(P=0.001),perceived discrimination(P=0.001)and lack of regular attendance in medical follow-ups(P=0.014)reported poorer HRQoL than their counterparts.Somatization,obsession,depression,phobia and overall SCL 90 scores in self-reported psycholpathology had a negative impact on the domains of HRQoL among HIVMSM.Conclusions:Total quality of life was predicted by family income,perceived discrimination,and medical follow-up attendance.Self-reported psychopathology was negatively correlated with HRQoL in HIVMSM.The Strategies that target MSM focusing on linking and engaging HIV-positive patients in medical care is the key step to improve their HRQoL.More emphasis is needed on the newly diagnosed HIVMSM in Dalian in order to develop a more targeted intervention to prevent perceived discrimination and lack of proper medical follow-up services.Trial registration:The trial registration number does not require for this manuscript.The study is cross-sectional design that do not involve intervention at all,it is not a clinical trial.
文摘BACKGROUND Duchenne muscular dystrophy(DMD)is a neuromuscular disorder caused by mutations in the dystrophin gene.DMD is reported to coexist with other comorbidities,although the occurrence of the triad,autism spectrum disorder(ASD),and epilepsy is very rare.Indeed,only one case of the triad has currently been reported.Here,we present a detailed case report of a ten-year-old boy with DMD,ASD,and epilepsy.We also investigated the dysregulation of miRNAs in this unusual triad(represented as DMD++)compared with a healthy individual and a DMD patient(represented as DMD+)without autism.AIM To understand the differential expression of miRNAs in rare comorbid DMD cases.METHODS The Sequin Form Board test,Gesell's drawing test,multiplex ligation probe amplification,and Vineland Social Maturity Scale were applied to confirm the DMD and ASD.Total RNA was isolated from samples using TRIzol.cDNA was synthesized using the Mir-X^(TM)miRNA First-Strand Synthesis kit.qRT-PCR was performed using SYBR Advantage qPCR Premix.The results were statistically analyzed using one-way analysis of variance with Tukey's ttest.RESULTS miR-146a-5p and miR-132-5p showed significant downregulation in both patient samples.miR-199a-5p and miR-146a-3p showed no change in expression between the diseased and controls.miR-132-3p showed downregulation only in the DMD+sample(0.21±0.04).The decrease in miR-132-3p can result in failed silencing of the phosphatase and tensin homolog-mediated apoptotic pathway,leading to severe skeletal muscle atrophy.Here,the downregulation of miR-132-3p in DMD+is consistent with severe muscle loss and higher disease progression than that in DMD++.DMD++has slower disease progression,and the expression of miRNA involved in inflammatory and apoptotic responses is more similar to that of the control.CONCLUSION Our study shows marked difference in miRNA expression in this rare case of DMD with autism and epilepsy.These miRNAs also serve as regulators of several muscle regeneration,apoptosis,and inflammatory pathways.This study shows the significance of studying miRNAs in such rare cases in a larger cohort to progress in several intervention treatments utilizing miRNAs.
基金This work was supported by the grants from the China 973 Project （No. 2006CB504206） and the Natural Science Foundation of China （No. 30700706）. In addition, this work was supported by a funding from Jiangsu Provincial Key Infectious Diseases Laboratory.
文摘Background The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus on the induction of neutralizing antibodies. A major challenge in developing an HIV-1 vaccine is to identify immunogens and adopt delivery methods that can elicit broadly neutralizing antibodies against primary isolates of different genetic subtypes. Methods Most circulating HIV-1 isolates in China are composed of clades Thai-B, CRF_BC and CRF01_AE. In order to construct DNA vaccines against these 3 HIV-1 subtypes, DNA vaccines carrying the gp120 regions from HIV-1 isolates of GX48（AE）, GX79（AE）, NX22（BC）, GS22（BC）, HN24（Thai-B） were constructed. Expression of gp120 from these DNA vaccines was detected by Western blotting in transiently transfected 293T cells. Pilot immunizations of New Zealand white rabbits were performed using the strategy of ＂DNA prime plus protein boost＂ and the neutralizing antibody response was detected in a Tzm-bl cell based assay against different HIV-1 strains. Results Response of gp120-specific antibody was relatively low after DNA primes （mean titer=10^4.72）; however, the titer of gp120-specific antibody went up with 2 protein boosts （mean titer=10^6.81）. Above all, neutralizing antibody （Nab） titers induced by this combined approach were much better than those elicited by DNA or protein used alone （P 〈0.01）. Neutralizing activities of immunized rabbit sera against several pseudoviruses and laboratorial strains were evaluated, most rabbit sera primed with monovalent vaccine were capable of neutralizing only 1 of 5 viruses, however, sera primed with the polyvalent DNA vaccines were able to neutralize at least 2 of 5 viruses. Conclusion Polyvalent DNA prime plus protein boost is an effective immunization strategy to broaden the neutralization breadth and further research should be performed on the basis of this pilot study.
基金Supported by the National Natural Science Foundation of China(NSFC)(No.71473234 and 71573239).
文摘Summary What is already known about this topic?Identifying the most influential spreaders in human immunodeficiency virus(HIV)transmission networks is crucial for developing effective prevention strategies.What is added by this report?This study identified key nodes of the HIV molecular transmission network among men who have sex with men(MSM)by utilizing linkages between sequences to reconstruct the transmission network at the molecular level.
文摘There was no global guidance or agreement regarding when a country has an adequate system to report on the service packages among human immunodeficiency virus(HIV)key populations.This article describes an approach to categorizing the system in a country for reporting the service package among HIV key populations.The approach consists of four dimensions,namely the epidemiological significance,comprehensiveness of the service packages,geographic coverage of services,and adequacy of the monitoring system.The proposed categorization approach utilizes available information and can inform the improvement of the service delivery and monitoring systems among HIV key populations.
基金This work was supported by the National Science and Technology Major Project of China during the 13th Five-year plan period(2018ZX10302104)Independent Research Foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,the First Affiliated Hospital,School of Medicine,Zhejiang University(2020ZZ19).
文摘Background:Diabetes is a risk factor for acquisition of cryptococcal meningitis(CM).However,the effects of diabetes on outcomes of CM patient have not been fully studied.Methods:In this retrospective study,49 diabetic CM patients and 98 non-diabetic CM patients from January 2008 to December 2018 in the First Affiliated Hospital of Zhejiang University were included by propensity score-matched method(1:2).Demographic characteristics,symptoms,and clinical assay parameters between the two groups were compared.Kaplan-Meier analysis and Cox proportional hazards model were used to assess factors associated with 10-week mortality.Results:The mean age of diabetic patients was 58.2±13.8 years;71.4%(35/49)were more than 50 years old and 46.9%were male.No difference in symptoms was found between diabetic and non-diabetic CM patients.The Charlson comorbidity score was higher in the diabetic group(1.9 vs.0.7,P<0.001).CM patients with diabetes had higher white blood cells count(106/L,111.0(18.0–242.5)vs.50.0(10.0–140.0),P=0.034)in cerebrospinal fluid(CSF),lower CSF India ink positivity(40.8%vs.60.2%,P=0.039),and Cryptococcus culture positivity(42.9%vs.60.2%,P=0.047).The overall 10-week survival rate was 79.7%in diabetic patients vs.83.2%in non-diabetic patients(log-rank P=0.794).Conclusion:Diabetic CM patients have higher CSF glucose and Charlson comorbidity score,but lower CSF India ink and culture positivity than non-diabetic CM patients.No difference in 10-week mortality was found between patients with and without diabetes.Other comorbidities may have a greater effect on prognosis.
