Severe fever with thrombocytopenia syndrome virus induces platelet activation and apoptosis via a reactive oxygen species-dependent pathway.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) and with a high fatality rate. Thrombocytopenia is a major clinical manifestation observed in SFTS patients, but the underlying mechanism remains largely unclear. Here, we explored the effects of SFTSV infection on platelet function in vivo in severely infected SFTSV IFNar-/- mice and on mouse and human platelet function in vitro. Results showed that SFTSV-induced platelet clearance acceleration may be the main reason for thrombocytopenia. SFTSV-potentiated platelet activation and apoptosis were also observed in infected mice. Further investigation showed that SFTSV infection induced platelet reactive oxygen species (ROS) production and mitochondrial dysfunction. In vitro experiments revealed that administration of SFTSV or SFTSV glycoprotein (Gn) increased activation, apoptosis, ROS production, and mitochondrial dysfunction in separated mouse platelets, which could be effectively ameliorated by the application of antioxidants (NAC (N-acetyl-l-cysteine), SKQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) and resveratrol). In vivo experiments showed that the antioxidants partially rescued SFTSV infection-induced thrombocytopenia by improving excessive ROS production and mitochondrial dysfunction and down-regulating platelet apoptosis and activation. Furthermore, while SFTSV and Gn directly potentiated human platelet activation, it was completely abolished by antioxidants. This study revealed that SFTSV and Gn can directly trigger platelet activation and apoptosis in an ROS-MAPK-dependent manner, which may contribute to thrombocytopenia and hemorrhage during infection, but can be abolished by antioxidants.

Longitudinal analysis of immunocyte responses and inflammatory cytokine profiles in SFTSV-infected rhesus macaques.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques (Macaca mulatta) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8+ T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8+ T cells declined but showed increased activation, while both the number and activation of effector memory CD4+ T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80+/CD86+ B cells and resting memory B cells (CD27+CD21+) increased significantly. Intermediate monocytes (CD14+CD16+) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4+ T cells, B cells, CD16+CD56+ NK cells, CD14+CD16+ monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection.

Comparative study of bioactive constituents in crude and processed Glycyrrhizae radix and their respective metabolic profiles in gastrointestinal tract in vitro by HPLC-DAD and HPLC-ESI/MS analyses.

Two HPLC methods with diode array detection (HPLC-DAD) and electrospray ionization-mass spectrometry (HPLC-ESI/MS), respectively, were developed to investigate the differences of chemical constituents and their metabolism in gastrointestinal tract in vitro between two decoctions of crude and processed Glycyrrhizae radix. Total of eleven constituents (liquiritin apioside, liquiritin, licuraside, isoliquiritin, ononin, glycyrrhizin, liquiritigenin-7,4'-diglucoside, licorice saponin A3, 22ß-acetoxylglycyrrhizic acid, licorice saponin G2, and yunganoside E2) were identified in the two decoctions, whereas lower contents of these constituents were usually found in the decoction of processed Glycyrrhizae Radix. [corrected] Furthermore, these constituents were metabolized into their respective aglycons in human intestinal bacteria juice, and the metabolism ratios were all higher in processed Glycyrrhizae Radix [corrected] decoction. No change was found in artificial gastric or intestinal juice. This study revealed that the processing can alter the contents of main constituents in crude G. radix and their metabolism in gastrointestinal tract, in which intestinal bacteria play an important role in the metabolism of licorice constituents.

[A comparative study on mental health among students and adults in the earthquake-hit areas].

OBJECTIVE: To understand mental health status of the students and adults in the earthquake disaster areas, as to providing guidance on intervention for post-disaster psychological crisis. METHODS: The Self-Reporting Questionnaire (SRQ-20), an appendix of The Ministry of Health of "emergency psychological crisis intervention guiding principles", was used among 1222 victims in Wenchuan earthquake, Sichuan province. This questionnaire survey was conducted in 729 students and 493 adult victims in a randomized method. Of the 734 questionnaires distributed and received in students, 729 were validly responded with efficiency rate of 99.32%; while for adults, 496 questionnaires distributed, 496 received, 493 were valid with efficiency rate of 99.39%. RESULTS: (1) In students victims, 65% responded that they did feel "uneasy, nervous or worried", followed by "easy to be scared", "feel unhappy", "easy fatigue" and "hard to make a decision". For adult victims, 80.5% replied that they felt "uneasy, nervous or worried", followed by "feel unhappy", "easy fatigue", "difficult sleeping", "easy to be scared". (2) The average of the SRQ score of student victims was 6.58 +/- 3.99, and 6.07 +/- 4.02 for males, 7.03 +/- 3.91 for females. The average of the SRQ score of student victims was 7.36 +/- 3.98, male 6.68 +/- 3.82, female 7.99 +/- 4.03. The significant differences (t(women) = 2.985, P < 0.01; t(total) = 3.332, P < 0.01) was observed in women and the total group of students and adults. (3) The SRQ positive screening rate of students group was 46.50%, the adult group was 52.33%, SRQ >or= 7 points and SRQ < 7 sub-group of students and adults of the total score there were significant differences (t(1) = 39.771, P < 0.01; t(2) = 31.961, P < 0.01). SRQ >or= 7 sub-group of students and adult women in between there was a significant difference (t = 23.641, P < 0.01), SRQ < 7 sub-group of students and adults in general and women there were significant differences (t(1) = 3.092, P < 0.01; t(2) = 2.911, P < 0.01). (4) SRQ scores with gender and age had had a positive relation (r(SRQ total-sex) = 0.118, P = 0.000; r(SRQ total-age) = 0.103, P = 0.000). CONCLUSION: The emotional suffering symptoms of students victims and adult victims should be "nervous, unhappy, vulnerable on issues such as fatigue", the adult group had a higher symptom rate than the group of students, the mental health was more serious than that of students, as influenced by some factors including age and gender. Students, being a special population group should be paid more attention to focusing a designated behavior intervention, as a planned manner of intervention.

[Reliability and validity of the self-reporting questionnaire for assessing mental health applied in Wenchuan earthquake].

OBJECTIVE: To detect the reliability and validity of the self-reporting questionnaire (SRQ-20), and to make a rapid assessment on mental health among victims in sudden crisis. METHODS: The SRQ-20 which is on appendix of the Ministry of Health adopted as "emergency psychological crisis intervention guiding principles" was administrated among 1222 victims in Wenchuan earthquake. The reliability of the questionnaire was tested by split-half coefficient and Cronbach's alpha coefficient; the validity was tested by means of principal component factor analysis. RESULTS: The self-reporting questionnaire and split-half coefficient was 0.748, each item of Cronbach's alpha in the reliability coefficient was between in 0.778 to 0.789, overall Cronbach's alpha in the reliability coefficient was 0.792. There were five main components in principal component factor analysis: lacking of power, somatization/biological symptoms, depression thought, emotions and awareness. CONCLUSION: The self-reporting questionnaire (SRQ-20) should have good reliability, and validity, and China's psychological crisis intervention in processing assessment of the mental health should be a fast, accurate and effective screening tool.

Epidemiological survey of Tourette syndrome in children and adolescents in Wenzhou of P.R. China.

An epidemiological survey on Tourette syndrome (TS) in a developing country is relatively scarce. This study was conducted to investigate the prevalence and distribution of TS in children and juveniles aged 7-16 years in Wenzhou of P.R. China. A total of 9742 children and adolescents were included in this survey. Cross-sectional study with stratified-cluster sampling method was used. The prevalence of TS among school-age children was estimated to be an average of 0.43%. The ratio of male to female was 10.6 to 1 (0.74% for males and 0.07% for females). Pupils in the age range of 7-16 years are more likely to have comorbid disorders. The mean age at onset of TS was 7.7+/-2.7 years, with 45.2% of them at the age of 6-7. The rate of delayed diagnosis, misdiagnosis and misclassification of the syndrome were 78.6, 42.9 and 23.8%, respectively. This survey supports that TS is a common disease prevalent amongst children and juveniles in Wenzhou area of P.R. China, and its incidence was correlated with age and sex and often misdiagnosed and misclassified.

[Study on the prevalence of tic disorders in schoolchildren aged 7-16 years old in Wenzhou].

OBJECTIVE: To study the epidemiological features of tic disorders (TD) among schoolchildren in Wenzhou area. METHODS: Stratified cluster sampling was carried out to investigate TD in 9742 schoolchildren aged 7 to 16 years old in Wenzhou. RESULTS: The average prevalence rate of TD among school-age children was 104/10 000 (166/10 000 for males, 29/10 000 for females). There was a significantly higher prevalence rate for males than that for females (chi(2) = 43.96, P < 0.001, prevalence ratio = 5.7, prevalence ratio 95% CI: 3.20 - 10.30). The prevalence rates of clinical subtypes in males was significantly higher than that of females while pupils was significantly higher than that in high school students (chi(2) = 11.33, P < 0.01, prevalence ratio = 2.2, prevalence ratio 95% CI: 1.37 - 3.43). Prevalence rate of transient tic disorders (TTD), chronic motor vocal tic disorder (CMVTD), tourette syndrome (TS) were 34/10 000, 27/10 000 and 43/10 000 respectively with the highest among 9-10 years old group. The mean onset age of TD was 8.5 +/- 2.8 years. The peak of onset was among 6-10 year olds. The rate of delayed diagnosis of the disorders was 69.3% and the median in delayed diagnosis was 1.0 year. CONCLUSION: TD is a common disease with high rate of misdiagnoses among schoolchildren in Wenzhou area. Physicians and population should be trained to identify the syndromes and to practice correct diagnosis and effective treatment as early as possible.

[Study on the prevalence of Tourette syndrome in children and juveniles aged 7-16 years in Wenzhou area].

OBJECTIVE: To study the prevalence and distribution of Tourette syndrome (TS). METHODS: Nine thousand, seven hundred and forty-two children and juveniles aged 7 - 16 years in Wenzhou were studied, using cluster random sampling method. RESULTS: The prevalence of TS among school-age children was estimated to be 0.43% (0.74% for males and 0.07% for females). The prevalence of male children and juveniles was higher than that of female children and juveniles (chi(2) = 25.09, P < 0.001, prevalence ratio = 10.95, prevalence ratio 95% CI: 3.38 - 35.46). The highest prevalence of TS was between 9 - 10 years old. The mean age at onset of TS was 7.7 +/- 2.7 years, with 45.2% of them among 6 - 7 year olds. The rate of delayed diagnosis and rates of misdiagnosis and misclassification of the syndromes were 78.6%, 42.9% and 23.8%, respectively. CONCLUSION: Tourette syndrome had been a common disease of children and juveniles in Wenzhou area. The disease was correlated with age and sex, often misdiagnosed and misclassified. Physicians and as well as general publics should be trained to identify the cases.