Anxiolytic-like effects of α-asarone in a mouse model of chronic pain.

α-asarone (ASR) is a major bioactive compound isolated from the rhizome of Acorus tatarinowii Schott and it has extensive biological effects. Clinically, anxiety disorder is a common comorbidity of chronic pain. However, limited information is available regarding the effects of ASR on chronic pain-related anxiety. This study aims to evaluate the anxiolytic effects of ASR in chronic pain mice. Chronic inflammatory pain was induced by hind-paw injection of complete Freund's adjuvant (CFA). Behavioral tests, western-blot analysis and whole-cell patch recordings were performed to evaluate the subsequent events. We found that ASR induced anxiolytic activities in CFA-injected mice but did not affect the nociceptive threshold. ASR administration reversed the up-regulation of GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, NR2A-containing N-methyl-D-aspartate (NMDA) receptors and down-regulation of γ-aminobutyric acid A (GABAA) receptors in the basolateral amygdala (BLA) of CFA-injected mice. Electrophysiological data revealed that ASR treatment restored the balance between excitatory and inhibitory neurotransmissions, which was disturbed in the BLA of CFA-injected mice. Moreover, ASR prevented the hyper-excitability of pyramidal neurons in the BLA of chronic pain mice. Our results suggested that the anxiolytic effects of ASR were partially due to maintaining the balance between excitatory/inhibitory transmissions and attenuating neuronal hyper-excitability of excitatory neurons in the BLA.

The platelet derived growth factor-B polymorphism is associated with risk of severe fever with thrombocytopenia syndrome in Chinese individuals.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV). We hypothesize that host genetic variations may contribute to susceptibility to SFTS. RESULTS: Compared with the rs1800818 AA genotype, AG + GG genotypes were significantly associated with increased susceptibility to SFTS (odds ratio, 1.66, 95% confidence interval = 1.28-2.16; P < 0.001). By using the ELISA assay, we observed that PDGF-BB concentration was significantly reduced in acute phase of patients than in the controls (P < 0.001) and recovered patients at 6 month (P = 0.007) and 12 month (P = 0.003). A persistently reduced PDGF-BB was also revealed from the SFTSV-infected C57BL/6J mice (P < 0.001). The rs1800818 G allele was associated with decreased serum PDGF-BB levels in SFTS patients at their early infection (P = 0.015). In accordance, the relative mRNA levels of the at-risk G allele of 1800818 were lower than those of the A allele in heterozygous cell from acute phase of SFTS patients. PDGF-B rs1800818 conferred no susceptibility to severe or fatal outcome in SFTS patients. MATERIALS AND METHODS: An initially small-scale case-control association study guided the selection of platelet derived growth factor-B (PDGF-B) rs1800818 in 1020 SFTS patients and 1353 controls. Functional analyses were conducted to verify the biological significance of rs1800818 polymorphism. CONCLUSIONS: Our findings suggest that the PDGF-B rs1800818 polymorphism might play a role in mediating the susceptibility to SFTS.

The prospective evaluation of viral loads in patients with severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV) is a potentially fatal disease that was first identified in China. Person to person transmission through contact with blood or body fluids was considered as an important infection route. OBJECTIVES: The study is designed to investigate the longitudinal viral loads following SFTSV infection and to identify factors affecting viral shedding in SFTS patients. METHODS: A prospective, observational study was performed on 208 laboratory-confirmed SFTSV infected patients in Xinyang, Henan Province. Sequential serum samples were collected on admission and during the hospitalization for quantification of SFTSV RNA by real-time RT-PCR. RESULTS: The viral RNA was undetectable in 55.6% of the patients on admission into the hospital, becoming detectable in most cases until three days and attained maximum level on six days after disease onset. This was followed by an obvious decrease thereafter, but maintained detectable for over 20 days. Viral load was independently predictable of severe disease outcome throughout the hospitalization. Viral load of >10(7)copies/mL was predictable of fatal outcome. The serum levels of PLT, WBC, LDH, AST and CK were significantly associated with viral loads level. CONCLUSIONS: The diagnosis of SFTSV infection based on PCR test should be performed at least three days after disease onset. Peaking viral loads were attained around six days after disease, posing a highest risk of human-to-human transmission.

Candidatus Rickettsia tarasevichiae Infection in Eastern Central China: A Case Series.

BACKGROUND: Human infection with Candidatus Rickettsia tarasevichiae (CRT) was first reported in northeastern China in 2012. OBJECTIVE: To describe the clinical spectrum and laboratory findings of patients infected with CRT in eastern central China. DESIGN: Case series. SETTING: A sentinel hospital for severe fever with thrombocytopenia syndrome (SFTS) in eastern central China in 2014. PARTICIPANTS: Hospitalized patients with SFTS-like illness. MEASUREMENTS: Molecular and serologic tests were performed to diagnose CRT infection. Data about clinical manifestations and laboratory findings were retrieved from medical records. RESULTS: 56 of 733 assessed patients had CRT based on polymerase chain reaction and sequencing. All patients presented with nonspecific manifestations, including fever (96%), malaise (88%), myalgia (57%), cough (25%), and dizziness (14%). Only 2 patients had rash. Further, 16% had eschar, 29% had lymphadenopathy, 100% had gastrointestinal symptoms, 34% had neurologic symptoms, 43% had hemorrhagic manifestations, and 23% had signs of plasma leakage. Thrombocytopenia was observed in 70%, leukopenia in 59%; lymphopenia in 45%; and elevated levels of lactate dehydrogenase in 82%, aspartate aminotransferase in 70%, alanine aminotransferase in 54%, and creatinine kinase in 46%. Co-infection with SFTS virus was documented in 66% patients, and 8 of the 56 patients died. LIMITATIONS: Patients with CRT were not treated for infection because they were retrospectively identified. This was not a population-based study, and the results cannot be generalized to all patients with CRT. CONCLUSION: Candidatus R tarasevichiae infection should be considered in the differential diagnosis of febrile patients with SFTS-like illness in endemic areas. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Common adverse events associated with ribavirin therapy for Severe Fever with Thrombocytopenia Syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is associated with high mortality rate, for which antiviral therapy with ribavirin was recommended. Based on our previous study, no visible effect of ribavirin therapy in improving clinical outcome was observed. Here we have accumulated the sample size to 634, and by performing prospective observation on the clinical progress and laboratory parameters, we found a significantly higher incidence of anemia and hyperamylasemia in patients who received ribavirin therapy in comparison with those who received no therapy. Generalized estimating equation model disclosed a significant effect on hemoglobin reduction and blood amylase augmentation from ribavirin administration. The occurrence of anemia and hyperamylasemia was associated with SFTS patients receiving ribavirin therapy, which might be adverse event of this drug administration. The recommendation of ribavirin for treating SFTS should be applied with caution.

Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis.

BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. Until recently, SFTSV-associated encephalitis remained largely uninvestigated. METHODS: We made clinical investigation on SFTS patients who experienced encephalitis in one reference hospital in Henan Province from 2011 to 2013 to identify the risk factors for encephalitis occurrence and their fatal outcome development. RESULTS: Altogether 538 SFTS patients were included and 19.1% of them developed encephalitis. Fatal outcome occurred in 44.7% of the encephalitis patients. The risk factors associated with encephalitis occurrence and death included older age, longer delay between disease onset and hospital admission, pre-existing diabetes and myalgias, as well as the laboratory evaluations of higher virus load on admission, decreased WBC, PLT count, lymphocyte percentage and ALB, elevated neutrophils percentage, AST, ALT, LDH, CK, ALP, GGT, BUN and CREA. These parameters could be used as potential predictors referring to severe SFTS cases. One SFTSV strain was isolated from cerebrospinal fluid sample. Cytokine/chemokine assay revealed that blood EOTAXIN, IFN-γ, IL-15, IL-6, IP-10, TNF-α were remarkably elevated before clinical deterioration in the confirmed encephalitis patient. CONCLUSIONS: SFTSV is capable of infecting the central nervous system and screening for SFTSV in encephalitis of unknown reason should be performed in SFTS endemic regions. The encephalitis occurrence and fatal outcome could be potentially predicted by clinical and laboratory evaluations.

[Influence of age on median lethal burn area of burn patients].

OBJECTIVE: To discuss the influence of age on the LA50 (the burn area lethal to 50% of patients) of burn patients. METHODS: (1) Twenty-three thousand and seventy-three burn patients hospitalized in our center from December 1958 to December 2004 were enrolled, and they were divided into 25 age groups. LA50 values of total and full-thickness burn areas of patients in each age group were computed with probit regression method with Probit analysis of SPSS 11.0. (2) Those age groups with similar LA50 values were merged into one age group; thus 4 new age groups were formed. LA50 and its 95% confidence interval (CI) of total and full-thickness burn areas of patients in each age group were computed respectively. (3) All the patients were divided into group A (admitted from 1 December 1958 to 31 December 1983) and group B (admitted from 1 January 1984 to 31 December 2004) according to the admission time. LA50 and its 95% CI of total and full-thickness burn areas of patients in each age group of groups A and B were computed respectively. RESULTS: (1) LA50 values of total and full-thickness burn areas of patients among the 25 age groups were low in age groups younger than or equal to 5 years, which increased in age groups older than 5 years, distinctly higher in age groups older than 15 years, and they became lower in age groups older than 60 years. (2) LA50 values of total and full-thickness burn areas of patients in the 4 merged age groups were lowest in age groups older than 60 years (50.90% TBSA) and younger than or equal to 5 years (35.81% TBSA), and highest in age group older than 15 years and younger than or equal to 60 years (89.38% and 59.22% TBSA). There were statistically significant differences in LA50 of total and full-thickness burn areas of patients among 4 merged age groups [with 95% CI values of LA50 of total burn areas of patients in age groups ranging from young to old respectively (56.87 to 64.69)%, (64.46 to 74.36)%, (85.89 to 93.37)%, (44.55 to 60.73)% TBSA; with 95% CI values of LA50 of full-thickness burn areas of patients in age groups from young to old respectively (32.67 to 39.69)%, (40.86 to 50.41)%, (55.27 to 63.85)%, (32.46 to 54.86)% TBSA]. (3) LA50 values of total and full-thickness burn areas of patients in group B (98.94% and 73.23% TBSA) were significantly higher than those in group A (69.61% and 39.79% TBSA). There were differences in LA50 values of patients among different age groups in both group A and group B. The variation trend of LA50 values of patients among the 4 age groups in groups A and B was almost the same. Except for LA50 of total burn areas of patients in age group older than 5 years and younger than or equal to 15 years and LA50 of full-thickness burn areas of patients in age group older than 60 years, there were statistically significant differences in the LA50 of total and full-thickness burn areas of the other patients between group A and group B [with 95% CI of LA50 of total burn areas of patients of younger than or equal to 5 years, older than 15 years and younger than or equal to 60 years, and older than 60 years respectively (48.38 to 56.07)% and (68.68 to 81.35)% TBSA, (75.91 to 84.89)% and (97.09 to 110.45)% TBSA, (30.08 to 45.08)% and (60.67 to 102.69)% TBSA; with 95% CI of LA50 of full-thickness burn areas of patients of younger than or equal to 5 years, older than 5 years and younger than or equal to 15 years, older than 15 years and younger than or equal to 60 years respectively (27.48 to 34.69)% and (42.09 to 54.03)% TBSA, (34.78 to 46.43)% and (49.62 to 69.47)% TBSA, (43.98 to 51.77)% and (66.43 to 77.99)% TBSA]. CONCLUSIONS: Age is one of the important factors that influence the LA50 of burn patients. LA50 in different age groups increases with the development of medical technology; however, the influence of age on LA50 is not visibly changed by the advance of treatment.