Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient outco...Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient outcomes.Advances in real-time polymerase chain reaction(PCR)technology have been instrumental in facilitating their inclusion in NBS programs.Methods We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles(TRECs),kappadeleting recombination excision circles(KRECs),and the absence of the survival motor neuron(SMN)1 gene in dried blood spots from 103,240 newborns in Zhejiang Province,China,between July 2021 and December 2022.Results Of all the samples,122 were requested further evaluation.After fow cytometry evaluation and/or genetic diagnostics,we identifed one patient with SCID,two patients with XLA,nine patients with SMA[one of whom also had Wiskott–Aldrich Syndrome(WAS)],and eight patients with other medical conditions.The positive predictive values(PPVs)of NBS for SCID,XLA,and SMA were 2.44%,2.78%,and 100%,respectively.The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID,1 in 51,620 for XLA,and 1 in 11,471 for SMA.Conclusion This study represents the frst large-scale screening in China's Mainland using a TREC/KREC/SMN1 multiplex assay,providing valuable epidemiological data.Our fndings suggest that this multiplex assay is an efective screening method for SCID,XLA,and SMA,potentially supporting the universal implementation of NBS programs across China.展开更多
Chronic kidney disease （CKD） is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in...Chronic kidney disease （CKD） is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus （HIV） infection are the major causes of CKD. HIV-associated nephropathy （HIVAN） is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits （including genetic hits） underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.展开更多
Acute kidney injury （AKI） is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities...Acute kidney injury （AKI） is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodefciency virus （HIV） acquired immune defciency syndrome （AIDS）. This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including： Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI.展开更多
Background Epilepsy secondary to acquired immunodeficiency syndrome(AIDS)can be challenging to manage.The potential interactions between antiretroviral drugs and antiepileptic drugs may result in the failure of both t...Background Epilepsy secondary to acquired immunodeficiency syndrome(AIDS)can be challenging to manage.The potential interactions between antiretroviral drugs and antiepileptic drugs may result in the failure of both treat-ments.Therefore,it is crucial to develop more effective strategies to enhance the clinical outcomes of patients.Case presentation We report a case of epilepsy secondary to AIDS.After administration of Bacteroides Fragilis 839(BF839),the secondary generalized tonic-clonic seizures disappeared,the frequency of complex partial seizures decreased by 70%,and the duration of each episode was shortened.Additionally,long-term diarrhea associated with antiretroviral therapy for AIDS resolved,and the syphilis serofast reaction turned negative.No serious adverse reactions were observed during the three-year follow up.Conclusions This case report suggests that the specific gut microbiota preparation could possibly improve refrac-tory epilepsy in HIV patients while also potentially alleviating adverse reactions to antiretroviral drugs and concurrent syphilis infection.Our case may provide a new perspective for the treatment of HIV infection/AIDS.展开更多
基金sponsored by the National Key Research and Development Program of China(No.2022YFC2703401).
文摘Background Newborn screening(NBS)for severe combined immunodefciency(SCID),X-linked agammaglobulinemia(XLA),and spinal muscular atrophy(SMA)enables early diagnosis and intervention,signifcantly improving patient outcomes.Advances in real-time polymerase chain reaction(PCR)technology have been instrumental in facilitating their inclusion in NBS programs.Methods We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles(TRECs),kappadeleting recombination excision circles(KRECs),and the absence of the survival motor neuron(SMN)1 gene in dried blood spots from 103,240 newborns in Zhejiang Province,China,between July 2021 and December 2022.Results Of all the samples,122 were requested further evaluation.After fow cytometry evaluation and/or genetic diagnostics,we identifed one patient with SCID,two patients with XLA,nine patients with SMA[one of whom also had Wiskott–Aldrich Syndrome(WAS)],and eight patients with other medical conditions.The positive predictive values(PPVs)of NBS for SCID,XLA,and SMA were 2.44%,2.78%,and 100%,respectively.The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID,1 in 51,620 for XLA,and 1 in 11,471 for SMA.Conclusion This study represents the frst large-scale screening in China's Mainland using a TREC/KREC/SMN1 multiplex assay,providing valuable epidemiological data.Our fndings suggest that this multiplex assay is an efective screening method for SCID,XLA,and SMA,potentially supporting the universal implementation of NBS programs across China.
基金Supported by NIH Fogarty International Center Grant,No.1D43TW008330-01A1Millennium Promise Award,Noncommunicable Chronic Diseases Leadership Training Program,NHLS Research Trust,Division of Nephrology Research Fund,University of the Witwatersrand,Johannesburg and FRC Individual grant,University of the Witwatersrand,Johannesburg
文摘Chronic kidney disease （CKD） is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus （HIV） infection are the major causes of CKD. HIV-associated nephropathy （HIVAN） is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits （including genetic hits） underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era.
文摘Acute kidney injury （AKI） is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodefciency virus （HIV） acquired immune defciency syndrome （AIDS）. This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including： Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI.
文摘Background Epilepsy secondary to acquired immunodeficiency syndrome(AIDS)can be challenging to manage.The potential interactions between antiretroviral drugs and antiepileptic drugs may result in the failure of both treat-ments.Therefore,it is crucial to develop more effective strategies to enhance the clinical outcomes of patients.Case presentation We report a case of epilepsy secondary to AIDS.After administration of Bacteroides Fragilis 839(BF839),the secondary generalized tonic-clonic seizures disappeared,the frequency of complex partial seizures decreased by 70%,and the duration of each episode was shortened.Additionally,long-term diarrhea associated with antiretroviral therapy for AIDS resolved,and the syphilis serofast reaction turned negative.No serious adverse reactions were observed during the three-year follow up.Conclusions This case report suggests that the specific gut microbiota preparation could possibly improve refrac-tory epilepsy in HIV patients while also potentially alleviating adverse reactions to antiretroviral drugs and concurrent syphilis infection.Our case may provide a new perspective for the treatment of HIV infection/AIDS.
