FcRγ deficiency improves survival in experimental sepsis by down-regulating TLR4 signaling pathway.

Fc receptor common γ signaling chain (FcRγ), a common subunit shared by Fc receptors (FcγRI, III, IV, FcαRI, and FcεRI), is an important immune regulator both in innate and adaptive immunity. Previous studies have shown that FcRγ was a potential target of inflammatory diseases, whereas the role of FcRγ in sepsis has been poorly understood. In this study, we found that deficiency of FcRγ resulted in increased survival in lipopolysaccharide (LPS)/D-galactosamine and E. coli-induced sepsis in mice. This protective effect was characterized by decreased TNF-α, IL-6, and IL-10. Further experiments in bone marrow-derived macrophages (BMDMs) in vitro also showed that FcRγ deficiency resulted in decreased production of TNF-α, IL-6, and IL-10 upon LPS stimulation. The mechanism study showed that FcRγ was physiologically associated with toll-like receptor 4 (TLR4), and tyrosine phosphorylation of FcRγ mediated TLR4 signaling pathway, followed by increased ERK phosphorylation upon LPS stimulation. Our results suggest that FcRγ might be a potential therapeutic target of sepsis.

The Public Health Burden of Rotavirus Disease in Children Younger Than Five Years and Considerations for Rotavirus Vaccine Introduction in China.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea among young children worldwide. Rotavirus vaccines have demonstrated substantial benefits in many countries that have introduced vaccine nationally. In China, where rotavirus vaccines are not available through the national immunization program, it will be important to review relevant local and global information to determine the potential value of national introduction. Therefore, we reviewed evidence of rotavirus disease burden among Chinese children younger than 5 years to help inform rotavirus vaccine introduction decisions. METHODS: We reviewed scientific literature on rotavirus disease burden in China from 1994 through 2014 in China National Knowledge Infrastructure, Wanfang and PubMed. Studies were selected if they were conducted for periods of 12 month increments, had more than 100 patients enrolled and used an accepted diagnostic test. RESULTS: Overall, 45 reports were included and indicate that rotavirus causes ~40% and ~30% of diarrhea-related hospitalizations and outpatient visits, respectively, among children younger than 5 years in China. Over 50% of rotavirus-related hospitalizations occur by age 1 year; ~90% occur by age 2 years. Regarding circulating rotavirus strains in China, there has been natural, temporal variation, but the predominant local strains are the same as those that are globally dominant. CONCLUSIONS: These findings affirm that rotavirus is a major cause of childhood diarrheal disease in China and suggest that a vaccination program with doses given early in infancy has the potential to prevent the majority of the burden of severe rotavirus disease.

A Centralized Report on Pediatric Japanese Encephalitis Cases from Beijing Children's Hospital, 2013.

Fifteen pediatric cases of suspected Japanese encephalitis (JE) were reported in Beijing Children's Hospital during the late summer of 2013. The clinical manifestations in most cases included high fever, seizures, and abnormal magnetic resonance imaging findings. Twelve of 15 cases were laboratory-confirmed as JE cases by pathogen identification. Epidemiological investigations showed that five of the 12 laboratory-confirmed patients had an incomplete JE vaccination history. Follow-up investigations after discharge indicated that seven laboratory-confirmed JE patients without JE vaccinations had relatively poor prognoses, with an average Modified Rankin Scale (MRS) score of 2.6 when compared with the other five laboratory-confirmed, JE-vaccinated patients with an average MRS score of 0.5. The observation of pediatric JE cases among those with a history of JE vaccination warrants further attention.

A new lignan glycoside from Trigonostemon heterophyllus.

Phytochemical investigation on the stems of Trigonostemonheterophyllus led to the isolation of a new lariciresinol-based lignan glycoside, trigonoheteran (1), together with a known lignan glycoside, aviculin (2). Their structures were elucidated by spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY, HMBC, and NOESY).

A new diterpene from the stems of Trigonostemon heterophyllus.

AIM: To investigate the chemical constituents in the stems of Trigonostemon heterophyllus. METHOD: The chemical constituents were isolated by column chromatography on silica gel, Rp-18, and Sephadex LH-20, and their structures were elucidated on the basis of spectroscopic analysis. RESULTS: Three compounds were isolated and identified as a new diterpene, trigonoheterene B (1), together with two known compounds, trigonostemone (2) and trigonochinene B (3). CONCLUSION: Compound 1 is new. Compounds 2 and 3 showed antibacterial activities.

Spatiotemporal patterns of Japanese encephalitis in China, 2002-2010.

OBJECTIVE: The aim of the study is to examine the spatiotemporal pattern of Japanese Encephalitis (JE) in mainland China during 2002-2010. Specific objectives of the study were to quantify the temporal variation in incidence of JE cases, to determine if clustering of JE cases exists, to detect high risk spatiotemporal clusters of JE cases and to provide evidence-based preventive suggestions to relevant stakeholders. METHODS: Monthly JE cases at the county level in mainland China during 2002-2010 were obtained from the China Information System for Diseases Control and Prevention (CISDCP). For the purpose of the analysis, JE case counts for nine years were aggregated into four temporal periods (2002; 2003-2005; 2006; and 2007-2010). Local Indicators of Spatial Association and spatial scan statistics were performed to detect and evaluate local high risk space-time clusters. RESULTS: JE incidence showed a decreasing trend from 2002 to 2005 but peaked in 2006, then fluctuated over the study period. Spatial cluster analysis detected high value clusters, mainly located in Southwestern China. Similarly, we identified a primary spatiotemporal cluster of JE in Southwestern China between July and August, with the geographical range of JE transmission increasing over the past years. CONCLUSION: JE in China is geographically clustered and its spatial extent dynamically changed during the last nine years in mainland China. This indicates that risk factors for JE infection are likely to be spatially heterogeneous. The results may assist national and local health authorities in the development/refinement of a better preventive strategy and increase the effectiveness of public health interventions against JE transmission.

Epidemiological characteristics of Japanese encephalitis in Guizhou Province, China, 1971-2009.

OBJECTIVE: The aim of the study was to establish the contemporary epidemiological characteristics of Japanese encephalitis (JE) in Guizhou Province. METHODS: A retrospective study of National Notifiable Disease Reporting System (NNDRS) data from 1971 through 2009, was conducted to ascertain the geographical, seasonal, and age distributions of JE incidence in Guizhou Province, China. RESULTS: A total of 68 425 JE cases were reported in Guizhou from 1971-2009. The JE cases occurred sporadically in all 9 prefectures of Guizhou, mostly among residents of rural areas. Seasonal distribution of JE remained consistent over the period from 1971-2009 with the main transmission season starting from June to September and peaking in August. JE occurred mainly in children under the age of 15 years with peak incidence in the 0-6-year age group. Pearson's correlation analysis showed that JE vaccine distribution had a negative correlation with JE incidence rates during 1971-2009 (coefficient of correlation=-0.475, P<0.01). CONCLUSION: Over the period of 1971-2009, the JE incidence rate had declined dramatically in terms of geographical and age distributions due to JE vaccination to children at risk.

[Surveillance and research on acute meningitis, encephalitis syndrome in Guangxi, China].

OBJECTIVE: To estimate disease burden and epidemiological characteristics of acute meningitis/encephalitis, and provide the basis for the disease control strategy development. METHODS: A syndrome surveillance system was established in Guigang city with a population of 5 020 000. For the suspected cases, serum and CSF were collected, and bacterial culture, latex agglutination test, real-time PCR and ELISA tests were carried out. All involved cases were identified to 6 categories according to WHO case definition. RESULTS: 1424 suspected cases were evaluated in a surveillance of 30 months, yielding the incidence, mortality and mortality of 11.35/100 000 (1424/12 546 500 person years), 0.43/100 000 (54/12 546 500 person years), 3.79% (54/1424) respectively. A total of 103 and 51 cases were confirmed for JE, bacterial meningitis, with a incidence of 0.82/100 000 (103/12 546 500 person years), 0.41/100 000 (51/12 546 500 person years). 96.10% (99/103) of JE cases and 37.30% (19/51) bacterial meningitis cases occurred in < 10 years old children and < 5 years old children. A clinical misdiagnosis rate of 19.42% (20/103) and 15.69% (8/51) were observed for JE and bacterial meningitis. CONCLUSION: Acute encephalitis, meningitis syndrome can cause a higher burden of disease, of which the main components of viral encephalitis. Most of syndrome is occurred in summer and autumn, mainly reported in children of younger than 10 years old. A quite misdiagnosis would be made among meningitis and encephalitis syndrome cases.

Genotype v Japanese encephalitis virus is emerging.

Japanese encephalitis (JE) is a global public health issue that has spread widely to more than 20 countries in Asia and has extended its geographic range to the south Pacific region including Australia. JE has become the most important cause of viral encephalitis in the world. Japanese encephalitis viruses (JEV) are divided into five genotypes, based on the nucleotide sequence of the envelope (E) gene. The Muar strain, isolated from patient in Malaya in 1952, is the sole example of genotype V JEV. Here, the XZ0934 strain of JEV was isolated from Culex tritaeniorhynchus, collected in China. The complete nucleotide and amino acid sequence of XZ0934 strain have been determined. The nucleotide divergence ranged from 20.3% to 21.4% and amino acid divergence ranged from 8.4% to 10.0% when compared with the 62 known JEV isolates that belong to genotype I-IV. It reveals low similarity between XZ0934 and genotype I-IV JEVs. Phylogenetic analysis using both complete genome and structural gene nucleotide sequences demonstrates that XZ0934 belongs to genotype V. This, in turn, suggests that genotype V JEV is emerging in JEV endemic areas. Thus, increased surveillance and diagnosis of viral encephalitis caused by genotype V JEV is an issue of great concern to nations in which JEV is endemic.

[On-site assessment on the definition and classification of suspected cases in the manual of WHO Japanese Encephalitis Surveillance Standards].

OBJECTIVE: To assess the new edition of WHO Japanese Encephalitis (JE) Surveillance Standards (WHO Standards) based on syndrome surveillance data and to provide field evidence regarding the standards. METHODS: Based on syndrome surveillance data, acute encephalitis syndrome (AES) case was categorized, according to the WHO Standards. A cohort study was applied to estimate the AES definition set in the Standard and relative risk was computed to estimate the existence and intensity of statistical correlation between AES and JE cases. Percentage of attributable risk was counted to describe the coverage of AES for JE cases in the studied population. Sensitivity, specificity, Youden index and positive predictive value of AES components were calculated for the purpose of identifying the clinical values under the screening program. RESULTS: 1424 suspected cases were evaluated in the surveillance program and 1396 cases with ELISA result, of which 109 positive cases were detected. According to the "standardized" classification, a total of 706 cases in line with AES case definition, were categorized into 83 cases of JE, 425 cases of AES unknown and 198 cases of AES other agent. In the cohort study, a relative risk of 4.62 (95%CI: 2.80 - 7.63) and the percentage of attributable risk as 78.35% (95%CI: 64.25% - 86.89%) were observed. CONCLUSION: The AES definition for JE was significantly effecting on the screening programs and a strong correlation strength was observed in the study. AES syndrome could cover most of the JE cases. "Convulsions", with appreciative screening value, was recommended to be involved into the new version of the WHO Standards.

[Analysis on disease burdern of Japanese encephalitis (JE) in Gansu province].

OBJECTIVE: To evaluate the disease burden of Japanese Encephalitis (JE), and provide strategy for disease control and prevention. METHODS: Firstly, analysis the incidence, mortality and fatality rate of JE in Gansu province in 2006. Then the investigation was carried out for calculating all expenditure items of the patients, including medical cost of the hospitalization, medicines, the transport costs, and other non-medical direct cost. RESULTS: In 2006, among the 27 type A and B notifiable infectious diseases in Gansu Province, JE mortality rate was at the top 3, fatality rate was at first rank. The direct cost of JE disease was 6889 RMB per case. In 2006, the direct cost of JE cases was 1,116,000 RMB in Gansu Province. CONCLUSION: JE had the high mortality, and fatality. The fatality in adult was higher than in children. JE patients had to pay high costs. JE disease burden should not be underestimated.

BacA is indispensable for successful Mesorhizobium-Astragalus symbiosis.

A homologue of Sinorhizobium meliloti bacA was isolated from Mesorhizobium huakuii 7653R, which is capable of fixing atmospheric nitrogen in symbiotic association with leguminous Astragalus sinicus (Chinese milk vetch). Inactivation of the bacA gene abolished the ability of M. huakuii 7653R to establish a successful symbiosis with its host plant. Simultaneously, compared with wild-type M. huakuii 7653R, the bacA mutant was more sensitive to cell envelope-disrupting agents (acidic solution, ethanol, SDS, and crystal violet). Mass spectrometry analysis revealed that the very-long-chain fatty acid (27-OHC-28:0 and 29-OHC-30:0) contents of lipid A was reduced in the M. huakuii 7653R bacA mutant. Taken together, our data suggest that the cell envelope was altered in the M. huakuii 7653R bacA mutant, which might deteriorate bacterial adaption to acute environmental changes encountered in host cells and ultimately result in the failure of Mesorhizobium-legume symbiosis.

[Meta-analysis on serological effect of the primary vaccination for Japanese encephalitis of the literatures].

OBJECTIVES: To summary and compare the different seroconversion rates after the primary vaccination for the Japanese encephalitis (JE), and to evaluate the serological effect of 3 kinds of JE vaccines. METHOD: Searching "CHKD", "Wanfang" database and "EMCC" databases, the studies of the immunogenicity after the primary JEV vaccination, all randomized controlled trials or non-randomized controlled trials were included, and statistical analysis were made by RevMan 4.2.10 software. RESULTS: A total of 12 literatures were included, 7 studies had control groups. The seroconversion rates after the primary vaccination, JEV-L, JEV-I (Vero) and JEV-I (PHK), were 86% (95% CI: 80%-91%), 83% (95% CI: 72% -94%) and 64% (95% CI: 58%-69%) respectively. Comparing the seroconversion rates of the 3 kinds of vaccines after primary immunization, the rate of JEV-I (Vero) was significantly higher than the rate of JEV-I (PHK), other comparisons were no significant difference. CONCLUSION: The serological effects of JEV-L and JEV-I (Vero) after the primary vaccination were higher than that of JEV-I (PHK).

[Study progress on serogroup B meningococcal vaccine].

Meningococcal disease, caused by Neisseria meningitidis (Nm), is still one serious threatening infectious disease with high mortality. Vaccination is available for prevention and control of such disease. Based on the chemical structure of capsule polysaccharide, Nm strains were classified into 13 serogroups. Meningococcal polysaccharide vaccines and polysaccharide conjugated protein vaccine against serogroup A, C, W135 and Y were efficacious and have been widely used. Because of poor immunogenicity and the structurally homologous with neural cell, capsule polysaccharide of serogroup B Nm can not be used as vaccine candidate. In last several decades, B group vaccines develoment focused on the proteins research. Based on the out membrane protein and reverse vaccinology technology, progress of B group vaccine were accelerated. Several meningococcal B vaccine showed favorable immunogenicity and efficacity. Some B vaccines have been licensed and widely used.

[Testing of antibodies against serogroup C Neisseria meningitidis by serum bactericidal assay in healthy population, Liaoning province].

OBJECTIVE: To test the serum antibodies from healthy population by Serum Bactericidal Assay (SBA), in order to evaluate the level of protective antibodies against serogroup C Neisseria meningitidis in Liaoning province. METHODS: 240 serum samples were selected from eight age-group randomly. Serogroup C vaccine candidate strain (C11) and the prevail serogroup C strain (053442) were used for SBA. RESULTS: 48.33% of 240 serum samples were positive (titer > or = 1:2) to C11 vaccine strain. Protective rate of SBA was 35.83% (titer > or = 1:8), in which, > or = 6 years old were 13.33%, 7-19 years old was 61.67%, 20-39 years old were 46.67% and > or = 40 years old were 63.33%. Rate of SBA to 053442 was lower than that to C11 in the group over 15 years old by statistic analysis. CONCLUSION: Population under 6 years old showed lower SBA capacities. With the implemention of Expanded Program on Immunization, children under 3 years old should be considered how to give them meningococcal vaccine in order to improve the titer of antibodies against Neisseria meningitidis serogroup C.

[Analysis on data from the clinical acute viral encephalitis surveillance system in three prefectures in Shaanxi during 2005 - 2006].

OBJECTIVE: To describe the epidemiological features of viral encephalitis and burden of Japanese encephalitis (JE), and to identify potential strategies for effective JE control measures, using data from the Viral Encephalitis Surveillance Program (VESP) launched in Ankang, Baoji, and Weinan prefectures, Shaanxi province. METHODS: Data was gathered from sentinel hospitals reporting system on all the viral encephalitis (VE) cases identified between June 2005 and May 2007. County Center for Disease Control and Prevention (CDC) investigated the cases, drawing blood and cerebrospinal fluid (CSF) samples from the hospitals, and testing IgM antibody against JE using ELISA. We used Epi Data and Excel for data entry and analysis. RESULTS: A total of 1097 VEs were reported and 1053 (96.0%) had blood or CSF samples collected and tested for IgM antibody against JE. Three hundred and eleven cases (29.5%) showed JE antibody positive (JE confirmed case). Among the JE confirmed cases, numbers of those under 15 year of age accounted for 33.7%, 43.9% and 88.3% in Baoji, Weinan and Ankang prefectures respectively. The rest were mainly children aged 5-14 years old (53.3%). Toddlers,farmers and children accounted for 85.2% in JE confirmed cases. About half of other VE cases (51.0%) were students of all age. Data an investigation on 398 reported VE cases at discharge, showed that 67.1% of JE confirmed cases recovered while 83.7% of the other VE cases fully recovered. The case fatality rates were 9.2% for JE confirmed cases and 3.1% for other VE cases. 578 cases were followed up at 90-days after discharge, 69.6% of JE confirmed cases and 90.2% of other VE cases recovered, with case fatality rates were 13.6% and 3.6% for JE confirmed cases and for other VE cases, respectively. The sequelae rates were 10.0% for JE confirmed cases and 4.5% for other VE cases. CONCLUSION: The peak of the VE season was the same as that of JE. There were 45.6% of reported JE cases with negative JE IgM, suggesting that it is necessary to carry out laboratory testing for clinical diagnosis cases. The fact that high risk population was different at prefectures levels suggested that more attention be paid in JE control and prevention.

[Molecular typing of Neisseria meningitidis serogroup C strains with pulsed field gel electrophoresis in China].

OBJECTIVE: To study the characteristics of epidemiology and molecular typing on Neisseria meningitidis serogroup C strains associated with outbreaks of Anhui province and sporadic cases in China, using pulsed field gel electrophoresis (PFGE). METHODS: 212 Neisseria meningitidis serogroup C strains were isolated from invasive meningococcal cases, close contacts and healthy carriers, including 48 strains from Anhui province with 38 strains associated with serogroup C outbreaks. PFGE were performed by genomic DNA digestion with Nhe I restriction enzyme. The results of PFGE were analyzed by BioNumerics software (Version 4.0, Applied Maths BVBA, Belgium). RESULTS: A total number of 212 Neisseria meningitidis serogroup C isolates were typed by 43 patterns, named AH1 to AH43. In China, AH1 pattern was the major PFGE pattern with 69.3% (n = 147) of all strains, distributed in 11 provinces. Three types of PFGE patterns (AH1 to AH3) were found in 48 strains from Anhui province, in which, 93.8% (n = 45) belonged to AH1. 97.4% (n = 37) of 38 strains associated with serogroup C outbreaks in Anhui province showed AH1 pattern. A total of 53 serogroup C strains were isolated from invasive meningococcal cases with 67.9% (36/53) of AH pattern. 71.9% (87/121) of serogroup C strains isolated from contacts of invasive meningococcal cases was AH1 pattern and 63.2% (24/38) of the strains from healthy carriers showed AH1 pattern. CONCLUSION: By PFGE typing and analysis, AH1 pattern of Neisseria meningitidis serogroup C strains was proved to be the main clone which causing the outbreaks in Anhui province and might be responsible for the sporadic serogroup C meningococcal disease epidemics else where in the country.