Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent unin...Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.展开更多
To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV...To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan,China,a total of 431 plasma samples were collected in Queshan county between 2003 and 2004,from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine(Azt+Ddi+Nvp).Personal information was collected by face to face interview.Viral load and genotypic drug resistance were tested.Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program(http://hivdb.stanford.edu).Overall,38.5% of treatment-naive patients had undetectable plasma viral load(VL),the rate significantly increased to 61.9% in 0 to 6 months treatment patients(mean 3 months)(P<0.005)but again significantly decrease to 38.6% in 6 to 12 months treatment patients(mean 9 months)(P<0.001)and 40.0% in patients receiving more than 12 months treatment(mean 16 months)(P<0.005).The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%,48.6%,70.8%,72.3% in treatment-na?ve,0 to 6 months treatment,6 to 12 months treatment,and treatment for greater than 12 months patients,respectively.No mutation associated with resistance to Protease inhibitor(PI)was detected in this study.Nucleoside RT inhibitor(NRTI)mutations always emerged after non-nucleoside RT inhibitor(NNRTI)mutations,and were only found in patients treated for more than 6 months,with a frequency less than 5%,with the exception of mutation T215Y(12.8%,6/47)which occurred in patients treated for more than 12 months.NNRTI mutations emerged quickly after therapy begun,and increased significantly in patients treated for more than 6 months(P<0.005),and the most frequent mutations were K103N,V106A,Y181C,G190A.There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan.The drug resistance strains were highly prevalent in antiretroviral-treated patients,and increased with the continuation of therapy,with many patients encountering virological failure after 6 months therapy.展开更多
More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but s...More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.展开更多
基金supported by USPHS grant (No. AI053108) to DanielJ.J. CarrP20 (No. RR017703)+1 种基金an unrestricted grant from Research to Prevent Blindnesssupported by NIAID training grant(No. AI007633)
文摘Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.
基金Molecular epidemiology research of HIV-1 Drug resistance in China sponsored by the 973 program (2005CB523103) Molecular epidemiology research and new technologies in HIV surveillance in China sponsored by the 863 program (2006AA02Z418).
文摘To investigate the prevalence of drug-resistance mutations,resistance to antiretroviral drugs,and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan,China,a total of 431 plasma samples were collected in Queshan county between 2003 and 2004,from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine(Azt+Ddi+Nvp).Personal information was collected by face to face interview.Viral load and genotypic drug resistance were tested.Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program(http://hivdb.stanford.edu).Overall,38.5% of treatment-naive patients had undetectable plasma viral load(VL),the rate significantly increased to 61.9% in 0 to 6 months treatment patients(mean 3 months)(P<0.005)but again significantly decrease to 38.6% in 6 to 12 months treatment patients(mean 9 months)(P<0.001)and 40.0% in patients receiving more than 12 months treatment(mean 16 months)(P<0.005).The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%,48.6%,70.8%,72.3% in treatment-na?ve,0 to 6 months treatment,6 to 12 months treatment,and treatment for greater than 12 months patients,respectively.No mutation associated with resistance to Protease inhibitor(PI)was detected in this study.Nucleoside RT inhibitor(NRTI)mutations always emerged after non-nucleoside RT inhibitor(NNRTI)mutations,and were only found in patients treated for more than 6 months,with a frequency less than 5%,with the exception of mutation T215Y(12.8%,6/47)which occurred in patients treated for more than 12 months.NNRTI mutations emerged quickly after therapy begun,and increased significantly in patients treated for more than 6 months(P<0.005),and the most frequent mutations were K103N,V106A,Y181C,G190A.There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan,Henan.The drug resistance strains were highly prevalent in antiretroviral-treated patients,and increased with the continuation of therapy,with many patients encountering virological failure after 6 months therapy.
文摘More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.
