Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In th...Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis,intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8?T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8?T cells are involved in the pathogenesis of RE.展开更多
Rasmussen's encephalitis(RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually ...Rasmussen's encephalitis(RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus(EBV) antigens as well as of Toll-like receptor 3(TLR3), TLR9, and downstream adapter TIRdomain-containing adapter-inducing interferon-β(TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry(IHC). In the RE group, EBV antigens were detected in 53% of individuals at various expression levels. In contrast, there was no detectable EBV antigen expression in control brain tissues. Moreover, we found marked increases in the expression of TLR3, TLR9, and TRIF in the brain tissues of RE patients compared with levels in the control group. Furthermore, among RE cases, EBV expression and high TLR3 expression were associated with more severe brain atrophy. Our results suggest that the elevated expression of EBV and TLRs may be involved in RE occurrence through the activation of downstream molecules.展开更多
The incidence of Japanese encephalitis(JE)has significantly decreased in China due to JE vaccines.In this study,we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against...The incidence of Japanese encephalitis(JE)has significantly decreased in China due to JE vaccines.In this study,we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus(JEV)to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children.A total of 300 serum samples were collected from vaccinated children aged 3-10 years in Zhaotong,Yunnan,China.The seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization test.The highest seropositivity of 82%was observed in vaccinated children during the first 0.5-1.5 years after booster vaccination.Then,the seropositivity began to decline and remained lower than the original level observed in the 0.5-1.5-year group.An association was found between the waning of seroprevalence and elapsed time of the post-booster vaccination.Similarly,the neutralizing antibody(nAb)titres gradually decreased over time,and the levels showed a positive correlation with the protective efficacy in mice.This finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE vaccine.Our results provide data that clarify the persistence and waning of antibodies to JEV,which may help elucidate the pathogenesis of JE.展开更多
Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4...Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.展开更多
An emerging mosquito-borne arbovirus named Zika virus(ZIKV), of the family Flaviviridae and genus Flavivirus, is becoming a global health threat. ZIKV infection was long neglected due to its sporadic nature and mild s...An emerging mosquito-borne arbovirus named Zika virus(ZIKV), of the family Flaviviridae and genus Flavivirus, is becoming a global health threat. ZIKV infection was long neglected due to its sporadic nature and mild symptoms. However, recently, with its rapid spread from Asia to the Americas, affecting more than 30 countries, accumulating evidences have demonstrated a close association between infant microcephaly and Zika infection in pregnant women. Here, we reviewed the virological, epidemiological, and clinical essentials of ZIKV infection.展开更多
Dear Editor,Glioma is the most common primary central nervous system(CNS)tumors in human.Gliomas are classified into low-grade glioma(LGG,grades I–II)and high-grade glioma(HGG,grades III–IV)according to the World He...Dear Editor,Glioma is the most common primary central nervous system(CNS)tumors in human.Gliomas are classified into low-grade glioma(LGG,grades I–II)and high-grade glioma(HGG,grades III–IV)according to the World Health Organization classification guidelines(Louis et al.2007).Comparing to the LGG,the HGG becomes more aggressive and has a poorer median overall survival.At present,glioma is mainly treated by radiotherapy,chemotherapy and surgical resection,but the effect is not ideal,especially for the glioblastoma(GBM),which is the most malignant type of gliomas and is resistant to current therapy protocols.There are several theories about the pathogenesis of glioma,such as radiation(Ohgaki and Kleihues 2005)。展开更多
The riserless mud recovery(RMR)system abandons the riser used in conventional offshore drilling,and the drill string above the seabed is directly exposed to seawater,resulting in convective heat transfer from the dril...The riserless mud recovery(RMR)system abandons the riser used in conventional offshore drilling,and the drill string above the seabed is directly exposed to seawater,resulting in convective heat transfer from the drilling fluid in the drill string to seawater.Therefore,the wellbore temperature distribution in the RMR system is quite different from the conventional offshore drilling.In this paper,based on the heat transfer characteristics of the RMR system,a mathematical model of the thermal field of the RMR system is established.The data used in this paper come from a vertical well in the South China Sea.Computational Fluid Dynamics(CFD)software is used to simulate the temperature distribution in drill string at different seawater depths and different formation depths in this paper,and the simulation results are compared with the calculation results of the mathematical model,so as to verify the feasibility of the mathematical model established in this paper.Combined with the calculation results of the mathematical model,this paper also explores the effect of different discharge capacity and different injection temperature of drilling fluid on the wellbore temperature change.展开更多
Myeloid-derived suppressor cells(MDSCs)are well known for their capacity to suppress antitumor T-cell responses,but their effects on B-cell function and antibody production remain unclear.Here,we found that MDSCs that...Myeloid-derived suppressor cells(MDSCs)are well known for their capacity to suppress antitumor T-cell responses,but their effects on B-cell function and antibody production remain unclear.Here,we found that MDSCs that accumulated around the germinal center in the spleen of tumor-bearing mice co-located with B cells.In the presence of MDSCs,the antibody reaction to a surrogate antigen was significantly enhanced in mice,especially the immunoglobulin(Ig)A subtype.Co-culture with MDSCs promoted both proliferation and differentiation of B cells into IgA-producing plasma cells in vitro.Interestingly,the cross talk between MDSCs and B cells required cell-cell contact.MDSCs from tumor necrosis factor receptor(TNFR)2^(−/−)mice,but not from TNFR1^(−/−)mice,failed to promote B-cell responses.Further investigation suggested that interleukin-10 and transforming growth factor-β1 were crucial for the MDSC-mediated promotion of IgA responses.These results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.展开更多
基金supported by the National Natural Science Foundation of China(81701992,81471957,and 81671971)the Beijing Municipal Natural Science Foundation(7144217)+2 种基金the Capital Applied Clinic Research Programs of Science and Technology(Z131107002213171)the Beijing Rising-star Plan of Science and Technology(Z141107001814042)Scientific Research Common Program of Beijing Municipal Commission of Education(KM201610025001)
文摘Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis,intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8?T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8?T cells are involved in the pathogenesis of RE.
基金the National Natural Science Foundation of China (81471957, 81571275, 81671971, and 81701992)the Beijing Municipal Natural Science Foundation (7144217)the Scientific Research Common Program of Beijing Municipal Commission of Education (KM201610025001)
文摘Rasmussen's encephalitis(RE) is a rare pediatric neurological disorder, the etiology of which remains unclear. It has been speculated that the immunopathogenesis of RE involves damage to neurons, which eventually leads to the occurrence of RE. Viral infection may be a critical factor in triggering RE immunopathogenesis. In this study, we analyzed the expression of Epstein-Barr virus(EBV) antigens as well as of Toll-like receptor 3(TLR3), TLR9, and downstream adapter TIRdomain-containing adapter-inducing interferon-β(TRIF) in the brain tissues of 26 patients with RE and 16 control individuals using immunohistochemistry(IHC). In the RE group, EBV antigens were detected in 53% of individuals at various expression levels. In contrast, there was no detectable EBV antigen expression in control brain tissues. Moreover, we found marked increases in the expression of TLR3, TLR9, and TRIF in the brain tissues of RE patients compared with levels in the control group. Furthermore, among RE cases, EBV expression and high TLR3 expression were associated with more severe brain atrophy. Our results suggest that the elevated expression of EBV and TLRs may be involved in RE occurrence through the activation of downstream molecules.
基金supported by grants from the National Natural Science Foundation of China (81471957, 81772172, 81671971, U1602223 and 81871641)a grant from the Open Research Projects of Key Laboratory of Beijing Ditan Hospital, Capital Medical University (DTKF201705)
文摘The incidence of Japanese encephalitis(JE)has significantly decreased in China due to JE vaccines.In this study,we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus(JEV)to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children.A total of 300 serum samples were collected from vaccinated children aged 3-10 years in Zhaotong,Yunnan,China.The seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization test.The highest seropositivity of 82%was observed in vaccinated children during the first 0.5-1.5 years after booster vaccination.Then,the seropositivity began to decline and remained lower than the original level observed in the 0.5-1.5-year group.An association was found between the waning of seroprevalence and elapsed time of the post-booster vaccination.Similarly,the neutralizing antibody(nAb)titres gradually decreased over time,and the levels showed a positive correlation with the protective efficacy in mice.This finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE vaccine.Our results provide data that clarify the persistence and waning of antibodies to JEV,which may help elucidate the pathogenesis of JE.
基金supported by the National Natural Science Foundation of China (81772172, 81471957, 81671971, U1602223)
文摘Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.
基金supported by the National Natural Science Foundations of China(81471957,81271839,81372935,81301435,and 81401676)
文摘An emerging mosquito-borne arbovirus named Zika virus(ZIKV), of the family Flaviviridae and genus Flavivirus, is becoming a global health threat. ZIKV infection was long neglected due to its sporadic nature and mild symptoms. However, recently, with its rapid spread from Asia to the Americas, affecting more than 30 countries, accumulating evidences have demonstrated a close association between infant microcephaly and Zika infection in pregnant women. Here, we reviewed the virological, epidemiological, and clinical essentials of ZIKV infection.
基金supported by the following funds:the National Natural Science Foundation of China(81671971,81871641 and 81701992)the Beijing Natural Science Foundation ProgramScientific Research Key Program of Beijing Municipal Commission of Education(KZ201810025035)。
文摘Dear Editor,Glioma is the most common primary central nervous system(CNS)tumors in human.Gliomas are classified into low-grade glioma(LGG,grades I–II)and high-grade glioma(HGG,grades III–IV)according to the World Health Organization classification guidelines(Louis et al.2007).Comparing to the LGG,the HGG becomes more aggressive and has a poorer median overall survival.At present,glioma is mainly treated by radiotherapy,chemotherapy and surgical resection,but the effect is not ideal,especially for the glioblastoma(GBM),which is the most malignant type of gliomas and is resistant to current therapy protocols.There are several theories about the pathogenesis of glioma,such as radiation(Ohgaki and Kleihues 2005)。
基金The financial support from the Natural Science Foundation of China(NSFC)(No.51274168)the National Key R&D Program of China(No.2018YFC0310202)is gratefully acknowledged。
文摘The riserless mud recovery(RMR)system abandons the riser used in conventional offshore drilling,and the drill string above the seabed is directly exposed to seawater,resulting in convective heat transfer from the drilling fluid in the drill string to seawater.Therefore,the wellbore temperature distribution in the RMR system is quite different from the conventional offshore drilling.In this paper,based on the heat transfer characteristics of the RMR system,a mathematical model of the thermal field of the RMR system is established.The data used in this paper come from a vertical well in the South China Sea.Computational Fluid Dynamics(CFD)software is used to simulate the temperature distribution in drill string at different seawater depths and different formation depths in this paper,and the simulation results are compared with the calculation results of the mathematical model,so as to verify the feasibility of the mathematical model established in this paper.Combined with the calculation results of the mathematical model,this paper also explores the effect of different discharge capacity and different injection temperature of drilling fluid on the wellbore temperature change.
基金supported by the Ministry of Science and Technology of China(2012CB917103,2012CB934003)the National Natural Science Foundation of China(91229203)the German Research Foundation(DFG 749-6/1 and SFB 633)。
文摘Myeloid-derived suppressor cells(MDSCs)are well known for their capacity to suppress antitumor T-cell responses,but their effects on B-cell function and antibody production remain unclear.Here,we found that MDSCs that accumulated around the germinal center in the spleen of tumor-bearing mice co-located with B cells.In the presence of MDSCs,the antibody reaction to a surrogate antigen was significantly enhanced in mice,especially the immunoglobulin(Ig)A subtype.Co-culture with MDSCs promoted both proliferation and differentiation of B cells into IgA-producing plasma cells in vitro.Interestingly,the cross talk between MDSCs and B cells required cell-cell contact.MDSCs from tumor necrosis factor receptor(TNFR)2^(−/−)mice,but not from TNFR1^(−/−)mice,failed to promote B-cell responses.Further investigation suggested that interleukin-10 and transforming growth factor-β1 were crucial for the MDSC-mediated promotion of IgA responses.These results demonstrate a novel mechanism of MDSC-mediated immune regulation during tumor growth.
