Study objective: To develop a self administered Chinese (mainland) version of the Short-Form Health Survey (SF-36) for use in health related quality of life measurements in China. Design: A three stage protocol was followed including translation, tests of scaling construction and scoring assumptions, validation, and normalisation. Setting: 1000 households in 18 communities of Hangzhou. Participants: 1688 respondents recruited by multi-stage mixed sampling. Main results: The assumption of equal intervals was violated for the vitality and mental health scales. The recoded item values were used to calculate scale scores. The clustering and ordering of item means was the same as that of the source and other two Chinese versions. The items in each scale had similar standard deviations except those in the physical functioning, boduily pain, social functioning scales. The item hypothesised scale correlations were identical for all except the social functioning and vitality scales. Convergent validity and discriminant validity were satisfactory for all except the social functioning scale. Cronbach's α coefficients ranged from 0.72 to 0.88 except 0.39 for the social functioning scale and 0.66 for the vitality scale. Two weeks test-retest reliability coefficients ranged from 0.66 to 0.94. Factor analysis identified two principal components explaining 56.3% of the total variance. The Chinese SF-36 could distinguish known groups. Conclusions: This study suggested that the Chinese (mainland) version of the SF-36 functioned in the general population of Hangzhou, China quite similarly to the original American population tested. Caution is recommended in the interpretation of the social functioning and vitality scales pending further studies.

SummaryThe aim of this study was to investigate the characteristics of the immune function of monocytes in different stages of the patients with acute on chronic liver failure (ACLF). Human leucocyte antigen (HLA)-DR and Toll-like receptor 4 (TLR-4) expression on monocytes in early and late stages of acute on chronic liver failure were detected by flow cytometry. The secretion function of monocytes was measured by cytometric bead array. Compared with healthy controls, the levels of HLA-DR expression on monocytes in patients with chronic hepatitis B, liver cirrhosis and acute on chronic liver failure were gradually decreased, especially in the late stage of acute on chronic liver failure (P < 0·001). TLR-4 expression on monocytes in patients with liver cirrhosis and acute on chronic liver failure were higher than the healthy controls. The concentrations of interleukin (IL)-1b, tumour necrosis factor (TNF)-a and IL-12p70 in early-stage ACLF were significantly higher compared with healthy controls and lower in late-stage ACLF (P < 0·01, 0·05). However, a significantly lower amount of IL-10 was found on monocytes in early-stage ACLF than that of late-stage ACLF and healthy controls (P < 0·01). Monocyte HLA-DR expression in patients who died was significantly lower compared with patients who survived in the early and late stages of ACLF (P < 0·01). The dynamic detection of HLA-DR expression or cytokines secreted from monocytes could contribute to the estimation of the status of the immune function of patients with acute on chronic liver failure.

Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a novel candidate of tumor suppressor that can selectively induce apoptosis experimentally in a spectrum of human cancer cells including leukemia cells. However, a recent study suggests that mda-7/IL-24 promotes the survival of chronic lymphocytic leukemia B-cells. In this study, we showed that mda-7/IL-24 was constitutively expressed in leukemia cell lines and primary acute myeloid leukemia samples. Using a conditionally replicating adenovirus expressing mda-7/IL-24 (ZD55-IL-24), we showed that enforced expression of mda-7/IL-24 in leukemia cells induced autophagy, which was triggered by the upregulation of Beclin-1. Immunofluorescence and coimmunoprecipitation studies suggested that mda-7/IL-24 protein interacts with Beclin-1. Class III PI3K/Beclin-1 complex was shown involved in the mda-7/IL-24-induced autophagy. Moreover, autophagy inhibition by phosphatidylinositol 3-kinase inhibitor, wortmannin, resulted in a reduced Beclin-1 expression and autophagosome formation associated with significantly enhanced cell death. Importantly, the combination of ZD55-IL-24 with wortmannin elicited a strongly enhanced antileukemia efficacy in established leukemia xenografts. These results suggest that mda-7/IL-24-induced autophagy in leukemia cells may provide survival advantage and mda-7/IL-24 combined with agents that disrupt autophagy is a promising new strategy for the treatment of leukemia.

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