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1.
Background
Hematological abnormalities often occur several days before kidney injury in patients with hemorrhagic fever with renal syndrome (HFRS). We aimed to investigate the prevalence and prognostic value of the early hematological markers in patients with HFRS caused by Hantaan virus (HTNV) infection.Methods
In a retrospective cohort study, we analyzed the case records of 112 patients with acute HTNV infection and evaluated the hematological markers for early prediction and risk stratification of HFRS patients with acute kidney injury (AKI).Results
Of 112 patients analyzed, 66 (59%) developed severe AKI, defined as either receipt of acute dialysis or increased serum creatinine ≥354 µmol/L. The prognostic accuracy of hematological markers, as quantified by the area under the receiver-operating-characteristic curve (AUC), was highest with the nadir platelet count (AUC, 0.89; 95% CI, 0.83–0.95), as compared with the admission platelet count (AUC, 0.84; 95% CI, 0.77–0.92), and the admission and peak leukocyte counts. The nadir platelet count correlated moderately with the levels of peak blood urea nitrogen (r = –0.616) and serum creatinine (r = –0.589), the length of hospital stay (r = –0.599), and the number of dialysis sessions that each patient received during hospital stay (r = –0.625). By multivariate analysis, decreased nadir platelet count remained independently associated with the development of severe AKI (odds ratio, 27.57; 95% CI, 6.96–109.16; P<0.0001).Conclusions
Thrombocytopenia, rather than leukocytosis, is independently associated with subsequent severe AKI among patients with acute HTNV infection. 相似文献2.
Feng Cui Tao Wang Ling Wang Shuxia Yang Ling Zhang Haixia Cao Yan Zhang Haodong Hu Shenyong Zhai 《PloS one》2013,8(6)
Background
Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, where human cases account for 90% of the total global cases. Zibo City is one of the most serious affected areas in Shandong Province China with the HFRS incidence increasing sharply from 2009 to 2012. However, the hotspots of HFRS in Zibo remained unclear. Thus, a spatial analysis was conducted with the aim to explore the spatial, spatial-temporal and seasonal patterns of HFRS in Zibo from 2009 to 2012, and to provide guidance for formulating regional prevention and control strategies.Methods
The study was based on the reported cases of HFRS from the National Notifiable Disease Surveillance System. Annualized incidence maps and seasonal incidence maps were produced to analyze the spatial and seasonal distribution of HFRS in Zibo City. Then spatial scan statistics and space-time scan statistics were conducted to identify clusters of HFRS.Results
There were 200 cases reported in Zibo City during the 4-year study period. One most likely cluster and one secondary cluster for high incidence of HFRS were identified by the space-time analysis. And the most likely cluster was found to exist at Yiyuan County in October to December 2012. The human infections in the fall and winter reflected a seasonal characteristic pattern of Hantaan virus (HTNV) transmission. The secondary cluster was detected at the center of Zibo in May to June 2009, presenting a seasonal characteristic of Seoul virus (SEOV) transmission.Conclusion
To control and prevent HFRS in Zibo city, the comprehensive preventive strategy should be implemented in the southern areas of Zibo in autumn and in the northern areas of Zibo in spring. 相似文献3.
Hae Ji Kang Shannon N. Bennett Laarni Sumibcay Satoru Arai Andrew G. Hope Gabor Mocz Jin-Won Song Joseph A. Cook Richard Yanagihara 《PloS one》2009,4(7)
Background
The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary.Methodology/Principal Findings
Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54–65% and 46–63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses.Conclusions
Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts. 相似文献4.
Hong Xiao Hai-Ning Liu Li-Dong Gao Cun-Rui Huang Zhou Li Xiao-Ling Lin Bi-Yun Chen Huai-Yu Tian 《PloS one》2013,8(4)
Background
The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by population dynamics of its main host, rodents. It is therefore important to better understand rodents’ characteristic in epidemic areas.Methodology/Principal Findings
We examined the potential impact of food available and climatic variability on HFRS rodent host and developed forecasting models. Monthly rodent density of HFRS host and climate data in Changsha from January 2004 to December 2011 were obtained. Monthly normalized difference vegetation index (NDVI) and temperature vegetation dryness index (TVDI) for rice paddies were extracted from MODIS data. Cross-correlation analysis were carried out to explore correlation between climatic variables and food available with monthly rodent data. We used auto-regressive integrated moving average model with explanatory variables to examine the independent contribution of climatic variables and food supply to rodent density. The results indicated that relative rodent density of HFRS host was significantly correlated with monthly mean temperatures, monthly accumulative precipitation, TVDI and NDVI with lags of 1–6 months.Conclusions/Significance
Food available plays a significant role in population fluctuations of HFRS host in Changsha. The model developed in this study has implications for HFRS control and prevention. 相似文献5.
Haitao Yu Wei Jiang Hong Du Yuan Xing Guangzhen Bai Ye Zhang Yu Li Hong Jiang Ying Zhang Jiuping Wang Pingzhong Wang Xuefan Bai 《PloS one》2014,9(4)
Background
Hantaan virus (HTNV) infection causes a severe form of HFRS(hemorrhagic fever with renal syndrome)in Asia. Although HTNV has been isolated for nearly forty years, the pathogenesis of HFRS is still unknown, and little is known regarding the signaling pathway that is activated by the virus.Methodology/Principal Findings
Cardamonin was selected as a NF-κB inhibitor, and indirect immunofluorescence assays were used to detect the effect of cardamonin on HTNV-infected HUVECs. The effect of cardamonin on the HTNV-induced phosphorylation of Akt and DNA-binding activity of NF-κB were determined using Western blot analysis and electrophoretic mobility shift assays (EMSAs), respectively. Then, flow cytometric and quantitative real-time PCR analyses were performed to quantify the expression levels of the adhesion molecules ICAM-1 and VCAM-1, and the concentrations of IL-6, IL-8, and CCL5 in HUVEC supernatants were examined using ELISA. The results showed that cardamonin did not effect the proliferation of HUVECs or the replication of HTNV in HUVECs. Instead, cardamonin inhibited the phosphorylation of Akt and nuclear transduction of NF-κB and further reduced the expression of the adhesion molecules ICAM-1 and VCAM-1 in HTNV-infected HUVECs. Cardamonin also inhibited the secretion of IL-6 and CCL5, but not IL-8.Conclusion/Significance
HTNV replication may not be dependent upon the ability of the virus to activate NF-κB in HUVECs. The Akt/NF-κB pathways may be involved in the pathogenesis of HFRS; therefore, cardamonin may serve as a potential beneficial agent for HFRS therapy. 相似文献6.
Hong Xiao Huai-Yu Tian Bernard Cazelles Xiu-Jun Li Shi-Lu Tong Li-Dong Gao Jian-Xin Qin Xiao-Ling Lin Hai-Ning Liu Xi-Xing Zhang 《PLoS neglected tropical diseases》2013,7(6)
Background
The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by environmental determinants. This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome (HFRS) for the period of 1991–2010 in Changsha, China.Methods and Findings
Wavelet analyses were performed by using monthly reported time series data of HFRS cases to detect and quantify the periodicity of HFRS. A generalized linear model with a Poisson distribution and a log link model were used to quantify the relationship between climate and HFRS cases, highlighting the importance of moisture conditions. There was a continuous annual oscillation mode and multi-annual cycle around 3–4 years from 1994 to 1999. There was a significant association of HFRS incidence with moisture conditions and the Multivariate El Niño–Southern Oscillation Index (MEI). Particularly, atmospheric moisture has a significant effect on the propagation of HFRS; annual incidence of HFRS was positively correlated with annual precipitation and annual mean absolute humidity.Conclusions
The final model had good accuracy in forecasting the occurrence of HFRS and moisture condition can be used in disease surveillance and risk management to provide early warning of potential epidemics of this disease. 相似文献7.
Popugaeva E Witkowski PT Schlegel M Ulrich RG Auste B Rang A Krüger DH Klempa B 《PloS one》2012,7(4):e35587
Background
Dobrava-Belgrade virus (DOBV) is a European hantavirus causing hemorrhagic fever with renal syndrome (HFRS) in humans with fatality rates of up to 12%. DOBV-associated clinical cases typically occur also in the northern part of Germany where the virus is carried by the striped field mouse (Apodemus agrarius). However, the causative agent responsible for human illness has not been previously isolated.Methodology/Principal Findings
Here we report on characterization of a novel cell culture isolate from Germany obtained from a lung tissue of “spillover” infected yellow necked mouse (A. flavicollis) trapped near the city of Greifswald. Phylogenetic analyses demonstrated close clustering of the new strain, designated Greifswald/Aa (GRW/Aa) with the nucleotide sequence obtained from a northern German HFRS patient. The virus was effectively blocked by specific antibodies directed against β3 integrins and Decay Accelerating Factor (DAF) indicating that the virus uses same receptors as the highly pathogenic Hantaan virus (HTNV). In addition, activation of selected innate immunity markers as interferon β and λ and antiviral protein MxA after viral infection of A549 cells was investigated and showed that the virus modulates the first-line antiviral response in a similar way as HTNV.Conclusions/Significance
In summary, our study reveals novel data on DOBV receptor usage and innate immunity induction in relationship to virus pathogenicity and underlines the potency of German DOBV strains to act as human pathogen. 相似文献8.
9.
Changjun Bao Wanwan Liu Yefei Zhu Wendong Liu Jianli Hu Qi Liang Yuejia Cheng Ying Wu Rongbin Yu Minghao Zhou Hongbing Shen Feng Chen Fenyang Tang Zhihang Peng 《PloS one》2014,9(9)
Background
Hemorrhagic fever with renal syndrome (HFRS) is endemic in mainland China, accounting for 90% of total reported cases worldwide, and Jiangsu is one of the most severely affected provinces. In this study, the authors conducted GIS-based spatial analyses in order to determine the spatial distribution of the HFRS cases, identify key areas and explore risk factors for public health planning and resource allocation.Methods
Interpolation maps by inverse distance weighting were produced to detect the spatial distribution of HFRS cases in Jiangsu from 2001 to 2011. Spatio-temporal clustering was applied to identify clusters at the county level. Spatial correlation analysis was conducted to detect influencing factors of HFRS in Jiangsu.Results
HFRS cases in Jiangsu from 2001 to 2011 were mapped and the results suggested that cases in Jiangsu were not distributed randomly. Cases were mainly distributed in northeastern and southwestern Jiangsu, especially in Dafeng and Sihong counties. It was notable that prior to this study, Sihong county had rarely been reported as a high-risk area of HFRS. With the maximum spatial size of 50% of the total population and the maximum temporal size of 50% of the total population, spatio-temporal clustering showed that there was one most likely cluster (LLR = 624.52, P<0.0001, RR = 8.19) and one second-most likely cluster (LLR = 553.97, P<0.0001, RR = 8.25), and both of these clusters appeared from 2001 to 2004. Spatial correlation analysis showed that the incidence of HFRS in Jiangsu was influenced by distances to highways, railways, rivers and lakes.Conclusion
The application of GIS together with spatial interpolation, spatio-temporal clustering and spatial correlation analysis can effectively identify high-risk areas and factors influencing HFRS incidence to lay a foundation for researching its pathogenesis. 相似文献10.
Background
Without intervention, up to 25% of individuals chronically infected with hepatitis B virus (HBV) die of late complications, including cirrhosis and liver cancer. The United States, which in 1991 implemented a strategy to eliminate HBV transmission through universal immunization, is a country of low prevalence. Approximately 3,000–5,000 U.S.-acquired cases of chronic hepatitis B have occurred annually since 2001. Many more chronically infected persons migrate to the United States yearly from countries of higher prevalence. Although early identification of chronic HBV infection can reduce the likelihood of transmission and late complications, immigrants are not routinely screened for HBV infection during or after immigration.Methods
To estimate the number of imported cases of chronic hepatitis B, we multiplied country-specific prevalence estimates by the yearly number of immigrants from each country during 1974–2008.Results
During 1974–2008, 27.9 million immigrants entered the U.S. Sixty-three percent were born in countries of intermediate or high chronic hepatitis B prevalence (range 2%–31%). On average, an estimated 53,800 chronic hepatitis B cases were imported to the U.S. yearly from 2004 through 2008. The Philippines, China, and Vietnam contributed the most imported cases (13.4%, 12.5%, and 11.0%, respectively). Imported cases increased from an estimated low of 105,750 during the period 1974–1977 to a high of 268,800 in 2004–2008.Conclusions
Imported chronic hepatitis B cases account for approximately 95% of new U.S. cases. Earlier case identification and management of infected immigrants would strengthen the U.S. strategy to eliminate HBV transmission, and could delay disease progression and prevent some deaths among new Americans. 相似文献11.
Li-Qun Fang Xian-Jun Wang Song Liang Yan-Li Li Shao-Xia Song Wen-Yi Zhang Quan Qian Ya-Pin Li Lan Wei Zhi-Qiang Wang Hong Yang Wu-Chun Cao 《PLoS neglected tropical diseases》2010,4(8)
Background
Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantaviruses. It is endemic in all 31 provinces, autonomous regions, and metropolitan areas in mainland China where human cases account for 90% of the total global cases. Shandong Province is among the most serious endemic areas. HFRS cases in Shandong Province were first reported in Yutai County in 1968. Since then, the disease has spread across the province, and as of 2005, all 111 counties were reported to have local human infections. However, causes underlying such rapid spread and wide distribution remain less well understood.Methods and Findings
Here we report a spatiotemporal analysis of human HFRS cases in Shandong using data spanning 1973 to 2005. Seasonal incidence maps and velocity vector maps were produced to analyze the spread of HFRS over time in Shandong Province, and a panel data analysis was conducted to explore the association between HFRS incidence and climatic factors. Results show a rapid spread of HFRS from its epicenter in Rizhao, Linyi, Weifang Regions in southern Shandong to north, east, and west parts of the province. Based on seasonal shifts of epidemics, three epidemic phases were identified over the 33-year period. The first phase occurred between 1973 and 1982 during which the foci of HFRS was located in the south Shandong and the epidemic peak occurred in the fall and winter, presenting a seasonal characteristic of Hantaan virus (HTNV) transmission. The second phase between 1983 and 1985 was characterized by northward and westward spread of HFRS foci, and increases in incidence of HFRS in both fall-winter and spring seasons. The human infections in the spring reflected a characteristic pattern of Seoul virus (SEOV) transmission. The third phase between 1986 and 2005 was characterized by the northeast spread of the HFRS foci until it covered all counties, and the HFRS incidence in the fall-winter season decreased while it remained high in the spring. In addition, our findings suggest that precipitation, humidity, and temperature are major environmental variables that are associated with the seasonal variation of HFRS incidence in Shandong Province.Conclusions
The spread of HFRS in Shandong Province may have been accompanied by seasonal shifts of HTNV-dominated transmission to SEOV-dominated transmission over the past three decades. The variations in HFRS incidence were significantly associated with local precipitation, humidity, and temperature. 相似文献12.
Hai-Ning Liu Li-Dong Gao Gerardo Chowell Shi-Xiong Hu Xiao-Ling Lin Xiu-Jun Li Gui-Hua Ma Ru Huang Hui-Suo Yang Huaiyu Tian Hong Xiao 《PloS one》2014,9(9)
Background
Hemorrhagic fever with renal syndrome (HFRS), a rodent-borne infectious disease, is one of the most serious public health threats in China. Increasing our understanding of the spatial and temporal patterns of HFRS infections could guide local prevention and control strategies.Methodology/Principal Findings
We employed statistical models to analyze HFRS case data together with environmental data from the Dongting Lake district during 2005–2010. Specifically, time-specific ecologic niche models (ENMs) were used to quantify and identify risk factors associated with HFRS transmission as well as forecast seasonal variation in risk across geographic areas. Results showed that the Maximum Entropy model provided the best predictive ability (AUC = 0.755). Time-specific Maximum Entropy models showed that the potential risk areas of HFRS significantly varied across seasons. High-risk areas were mainly found in the southeastern and southwestern areas of the Dongting Lake district. Our findings based on models focused on the spring and winter seasons showed particularly good performance. The potential risk areas were smaller in March, May and August compared with those identified for June, July and October to December. Both normalized difference vegetation index (NDVI) and land use types were found to be the dominant risk factors.Conclusions/Significance
Our findings indicate that time-specific ENMs provide a useful tool to forecast the spatial and temporal risk of HFRS. 相似文献13.
Sajid Shahul Michele R. Hacker Victor Novack Ariel Mueller Shahzad Shaefi Bilal Mahmood Syed Haider Ali Daniel Talmor 《PloS one》2014,9(9)
Importance
The association between hospital volume and inpatient mortality for severe sepsis is unclear.Objective
To assess the effect of severe sepsis case volume and inpatient mortality.Design Setting and Participants
Retrospective cohort study from 646,988 patient discharges with severe sepsis from 3,487 hospitals in the Nationwide Inpatient Sample from 2002 to 2011.Exposures
The exposure of interest was the mean yearly sepsis case volume per hospital divided into tertiles.Main Outcomes and Measures
Inpatient mortality.Results
Compared with the highest tertile of severe sepsis volume (>60 cases per year), the odds ratio for inpatient mortality among persons admitted to hospitals in the lowest tertile (≤10 severe sepsis cases per year) was 1.188 (95% CI: 1.074–1.315), while the odds ratio was 1.090 (95% CI: 1.031–1.152) for patients admitted to hospitals in the middle tertile. Similarly, improved survival was seen across the tertiles with an adjusted inpatient mortality incidence of 35.81 (95% CI: 33.64–38.03) for hospitals with the lowest volume of severe sepsis cases and a drop to 32.07 (95% CI: 31.51–32.64) for hospitals with the highest volume.Conclusions and Relevance
We demonstrate an association between a higher severe sepsis case volume and decreased mortality. The need for a systems-based approach for improved outcomes may require a high volume of severely septic patients. 相似文献14.
Junning Wang Weijuan Guo Hong Du Haitao Yu Wei Jiang Ting Zhu Xuefan Bai Pingzhong Wang 《PloS one》2014,9(11)
Background
Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163). The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.Methods
Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.Results
The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.Conclusion
sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further. 相似文献15.
Zuo SQ Fang LQ Zhan L Zhang PH Jiang JF Wang LP Ma JQ Wang BC Wang RM Wu XM Yang H Cao ZW Cao WC 《PLoS neglected tropical diseases》2011,5(1):e945
Background
Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, and has extended from rural areas to cities recently. Beijing metropolis is a novel affected region, where the HFRS incidence seems to be diverse from place to place.Methodology/Principal Findings
The spatial scan analysis based on geographical information system (GIS) identified three geo-spatial “hotspots” of HFRS in Beijing when the passive surveillance data from 2004 to 2006 were used. The Relative Risk (RR) of the three “hotspots” was 5.45, 3.57 and 3.30, respectively. The Phylogenetic analysis based on entire coding region sequence of S segment and partial L segment sequence of Seoul virus (SEOV) revealed that the SEOV strains circulating in Beijing could be classified into at least three lineages regardless of their host origins. Two potential recombination events that happened in lineage #1 were detected and supported by comparative phylogenetic analysis. The SEOV strains in different lineages and strains with distinct special amino acid substitutions for N protein were partially associated with different spatial clustered areas of HFRS.Conclusion/Significance
Hotspots of HFRS were found in Beijing, a novel endemic region, where intervention should be enhanced. Our data suggested that the genetic variation and recombination of SEOV strains was related to the high risk areas of HFRS, which merited further investigation. 相似文献16.
17.
Ying Ma Jiuping Wang Bin Yuan Meiliang Wang Yun Zhang Zhuwei Xu Chunmei Zhang Yusi Zhang Bei Liu Jing Yi Kun Yang Angang Yang Ran Zhuang Boquan Jin 《PLoS neglected tropical diseases》2013,7(2)
Background
Hantaan virus (HTNV) infection in humans is a serious public health concern in Asia. A potent T cell activation peptide vaccine from HTNV structure protein represents a promising immunotherapy for disease control. However, the T cell epitopes of the HTNV restricted by the HLA alleles and the role of epitope-specific T cell response after HTNV infection remain largely unexplored.Methodology/Principal Findings
Five well-conserved novel CD8+ T-cell epitopes of the HTNV nucleoprotein restricted by the most popular HLA alleles in Chinese Han population were defined with interferon-γ enzyme-linked immunospot assay in 37 patients infected with HTNV during hospitalization. Two epitopes aa129–aa137 and aa131–aa139 restricted by HLA-A2 and B35, respectively, were selected to evaluate the epitope-specific CD8+ T-cell response. HLA-peptide pentamer complex staining showed that the frequency of single epitope-specific CD8+ T cell could be detected in patients (95% confidence interval for aa129–aa137: 0.080%–0.208%; for aa131–aa139: 0.030%–0.094%). The frequency of epitope-specific pentamer+ CD8+ T-cell response was much higher in mild/moderate patients than in severe/critical ones at the acute stage of the disease. Moreover, the frequency of epitope-specific CD8+ T cells at acute stage was inversely associated with the peak level of serum creatinine and was positively associated with the nadir platelet counts during the hospitalization. The intracellular cytokine staining and the proliferation assay showed that the effective epitope-specific CD8+ T cells were characterized with the production of interferon-γ, expression of CD69 and the strong capacity of proliferation.Conclusion/Significance
The novel HLA class I restricted HTNV nucleoprotein epitopes-specific CD8+ T-cell responses would be closely related with the progression and the severity of the disease, which could provide the first step toward effective peptide vaccine development against HTNV infection in humans. 相似文献18.
Yusi Zhang Chunmei Zhang Ran Zhuang Ying Ma Yun Zhang Jing Yi Angang Yang Boquan Jin 《PLoS neglected tropical diseases》2015,9(2)
Background
Hantaan virus (HTNV) causes a severe lethal haemorrhagic fever with renal syndrome (HFRS) in humans. Despite a limited understanding of the pathogenesis of HFRS, the importance of the abundant production of pro-inflammatory cytokines has been widely recognized. Interleukin 33 (IL-33) has been demonstrated to play an important role in physiological and pathological immune responses. After binding to its receptor ST2L, IL-33 stimulates the Th2-type immune response and promotes cytokine production. Depending on the disease model, IL-33 either protects against infection or exacerbates inflammatory disease, but it is unknown how the IL-33/ST2 axis regulates the immune response during HTNV infection.Methodology/Principal Findings
Blood samples were collected from 23 hospitalized patients and 28 healthy controls. The levels of IL-33 and soluble ST2 (sST2) in plasma were quantified by ELISA, and the relationship between IL-33, sST2 and the disease severity was analyzed. The role of IL-33/sST2 axis in the production of pro-inflammatory cytokines was studied on HTNV-infected endothelial cells. The results showed that the plasma IL-33 and sST2 were significantly higher in patients than in healthy controls. Spearman analysis showed that elevated IL-33 and sST2 levels were positively correlated with white blood cell count and viral load, while negatively correlated with platelet count. Furthermore, we found that IL-33 enhanced the production of pro-inflammatory cytokines in HTNV-infected endothelial cells through NF-κB pathway and that this process was inhibited by the recombinant sST2.Conclusion/Significance
Our results indicate that the IL-33 acts as an initiator of the “cytokine storm” during HTNV infection, while sST2 can inhibit this process. Our findings could provide a promising immunotherapeutic target for the disease control. 相似文献19.
Chuncheng Lu Miaofei Xu Ying Wang Yufeng Qin Guizhen Du Wei Wu Xiumei Han Chao Ji Yanli Yang Aihua Gu Yankai Xia Ling Song Shoulin Wang Xinru Wang 《PloS one》2013,8(1)
Background
The meiotic program initiation pathway genes (CYP26B1, NANOS1 and STRA8) have been proposed to play key roles in spermatogenesis.Objective
To elucidate the exact role of the genetic variants of the meiosis initiation genes in spermatogenesis, we genotyped the potential functional genetic variants of CYP26B1, NANOS1 and STRA8 genes, and evaluated their effects on spermatogenesis in our study population.Design, Setting, and Participants
In this study, all subjects were volunteers from the affiliated hospitals of Nanjing Medical University between March 2004 and July 2009 (NJMU Infertile Study). Total 719 idiopathic infertile cases were recruited and divided into three groups according to WHO semen parameters: 201 azoospermia patients (no sperm in the ejaculate even after centrifugation), 155 oligozoospermia patients (sperm counts <20×106/ml) and 363 infertility/normozoospermia subjects (sperm counts >20×106/ml). The control group consisted of 383 subjects with normal semen parameters, all of which had fathered at least one child without assisted reproductive technologies.Measurements
Eight single nucleotide polymorphisms (SNPs) in CYP26B1, NANOS1 and STRA8 genes were determined by TaqMan allelic discrimination assay in 719 idiopathic infertile men and 383 healthy controls.Results and Limitations
The genetic variant rs10269148 of STRA8 gene showed higher risk of spermatogenic impairment in the groups of abnormospermia (including azoospermia subgroup and oligozoospermia subgroup) and azoospermia than the controls with odds ratios and 95% confidence intervals of 2.52 (1.29–4.94) and 2.92 (1.41–6.06), respectively (P = 0.006, 0.002 respective). Notably, larger sample size studies and in vivo or in vitro functional studies are needed to substantiate the biological roles of these variants.Conclusions
Our results provided epidemiological evidence supporting the involvement of genetic polymorphisms of the meiotic program initiation genes in modifying the risk of azoospermia and oligozoospermia in a Han-Chinese population. 相似文献20.
Endothelial Protein C Receptor Gene Variants Not Associated with Severe Malaria in Ghanaian Children
Kathrin Schuldt Christa Ehmen Jennifer Evans Juergen May Daniel Ansong Juergen Sievertsen Birgit Muntau Gerd Ruge Tsiri Agbenyega Rolf D. Horstmann 《PloS one》2014,9(12)