Humans ; Liver Failure ; Lymphohistiocytosis, Hemophagocytic

Objective To investigate residual hearing of children with sensorineural hearing loss in whom wave V was not found in ABR testing and to emphasize the importance of behavioral audiometry in determining the residual hearing.Methods Residual hearing obtained by behavioral audiometry of 101 children with SNHL was studied in relation to the absence of wave V in both click-ABR and tone burst-ABR tests.Results All children have residual hearing of different degrees at different frequencies.There appeared to be a higher percentage of lowfrequency residual hearing than middle and high frequencies.Also,the residual hearing at low frequencies appeared to be better than those in the middle and high frequencies.Average residual hearing thresholds in the right ears from 500 to 4 000 Hz were 106.81±7.13,110.00±7.90,111.78±5.22,112.06±7.08 dB HL and those in the left ears were 98.01±3.98,111.30±7.18,112.06±7.08,108.33±7.23 dB HL.Conclusion The absence of wave V in ABR does not mean total deafness.For those children with no wave V in ABR,behavioral audiometry must be conducted to determine children's behavioral hearing thresholds in order to know their residual hearing.

Objective:To explore the effect of D393E mutation on its intracerebral neurovirulence in mice after infectious clone of the chimeric Japanese encephalitis virus (JEV)/Zika virus (ZIKV) containing envelope protein D393E mutant was built and the virus was rescued.Methods:The full-length cDNA plasmid of JEV/ZIKV chimeric virus containing D393E mutation in the envelope protein was built by SOE PCR and gene cloning technology. The linearized fragment of the plasmid was used for in vitro transcription to obtain viral RNA, followed by electrotransfection into BHK-21 cells to rescue the mutant virus JEV/ZIKV(D393E). The plaque size and growth characteristics of JEV/ZIKV (D393E) and JEV/ZIKV were compared after BHK-21 cells were inoculated with the viruses. The intracerebral neurovirulence of the viruses was calculated after the viruses were inoculated in mice intracerebrally (i.c.).Results:Restriction enzyme digestion evaluation confirmed that the infectious clone of mutant virus was correctly built. The plaque assay demonstrated that the plaque diameter of JEV/ZIKV (D393E) was about 0.7±0.2 mm, which was smaller than that of JEV/ZIKV (1.3±0.2 mm). The LD 50 value of the mutant was 31.51 PFU when injected in mice via i. c. route, which was greater than 2.21 PFU of JEV/ZIKV. Conclusions:The D393E mutation of ZIKV envelope protein in JEV/ZIKA chimeric virus decreases the neurovirulence of the virus in mice.

Objective:To construct the chimeric virus ChimZIKV of Japanese encephalitis virus and Zika virus and evaluate whether the chimeric virus can be developed into a candidate vaccine strain against Zika virus.Methods:The infectious clone of chimeric virus ChimZIKV was constructed by replacement the prM/E of Japanese encephalitis virus vaccine strain with that of Zika virus. RNA of chimeric virus ChimZIKV had been transcribed in vitro and was electro-transfected into BHK-21 cells to rescue chimeric virus. Afterward, the chimeric virus was identified by plaque assay, immunofluorescence and gene sequencing. The growth was shown by the growth curve. The neurobirulence, viremia, neutralizing antibody production and immune protective effect of chimeric virus were tested by animal experiments.Results:The result of restriction enzyme digestion showed that the infectious clone of chimeric virus was successfully constructed, and the immunofluorescence assay and sequencing showed that chimeric virus ChimZIKV was successfully rescued. The cell proliferation activity test showed that the cell proliferation activity of the chimeric virus infected group was higher than that of the infected group. The result of animal experiments showed that chimeric virus showed very low neurovirulence to mice and suckling mice, and the result of viremia showed that chimeric virus had no obvious viremia in mice. Plaque reduction neutralization test (PRNT) showed 100% positive conversion of neutralizing antibody in sera of immunized mice, and the highest neutralizing antibody titer (GMT=85) was seen in the third week. The immune protection experiment showed that the protection rate against JE/ZIKV(MR766) was 30%.Conclusions:This study showed that the chimeric virus ChimZIKV is immunogenic and with low neurovirulence, and it may be further developed as a candidate vaccine strain against Zika virus.

Objective: To evaluate the incidence, and the characteristics of organ failure in relationship to prognosis in hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) patients using chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score for judgments of clinical treatment and prognosis. Methods: Clinical data of 316 patients who were diagnosed as HBV-ACLF during hospitalization from February 2015 to February 2016 were retrospectively analyzed. Intrahepatic and extrahepatic organ failures were assessed according to CLIF-SOFA score, and the relationship between clinical characteristics and prognosis was analyzed. Continuity variables were analyzed by analysis of variance, or Kruskal-Wallis H test. Comparison of the categorical data were done using χ ² or Fisher's exact test, and the predictive efficacy of various prognostic scores was compared using the area under the receiver operating characteristic curve (AUROC) and Z-test. Results: Of 316 cases (87.3% men) of HBV-ACLF, the mean age was (45 ± 11) years old. 78.8% of patients with underlying liver disease had hepatitis B virus induced cirrhosis. Mortality rates in patients without liver transplantation at 28 days, 90 days and 180 days were 20.5% (63/307), 36.7% (110/300) and 39.2% (116/296), respectively. According to the CLIF-SOFA score, 89.9% (284 patients) had organ failure at baseline, of which 97.5% had liver failure (Total bilirubin ≥ 12 mg/dl) and only 2.5% had coagulation, kidney, circulation or respiratory failure without liver failure. Besides liver failure, the incidence of extrahepatic organ failure was coagulation (23.1%), kidney (5.7%), brain (3.8%), circulation (1.3%) and respiratory failure (0.3%). With increasing number of organ failure, the mortality rate of two and three or more organ failures were 69.6% and 69.2%, respectively, which was significantly higher than that of single organ failure and non-organ failure patients (27% and 6.9%, respectively; P < 0.001). Liver failure with coagulation failure (International normalized ratio≥2.5 or platelet count≤20×10⁹/L) had worst prognosis with a mortality rate of up to 75% at 90 days. Conclusion According to the CLIF-SOFA score, the main organ failure in patients with HBV-ACLF in China is liver failure. The mortality rate in patients with two or more organ failures is as high as 70% within 3 months. Therefore, timely manner liver transplantation should be considered.