重症禽流感病毒A(H5N1)感染的细胞毒疗法

据文献报道,禽流感病毒AH5N1亚型感染的死亡率仍然很高,现在WHO报道的数据是大约50%。事后分析发现,感染患者的噬血细胞现象与噬血细胞性淋巴组织增生症(HLH)患者相似。这种噬血细胞现象可能是H5N1感染后的一个显著特征。在临床表现方面,H5N1感染与HLH也有相似,比如血细胞减少以及急性脑炎。据报道,其他重症病毒感染且有可能并发继发性HLH、重症EB病毒相关噬血细胞性淋巴组织增生症(Epstein-Barrvirus-associatedhemophagocyticlymphohistiocytosis,EBV-H的LH)患者,若早期即开始给予特异性的HLH治疗(包括细胞毒药物和促进凋亡的药物),存活率会由50%升至90%。由于生存率有如此明显的升高,特异性的HLH治疗(包括细胞毒药物治疗)可被作为重症禽流感病毒A感染并发继发性HLH患者的治疗方法。     

Ethnic-specific splicing mutation of the carnitine-acylcarnitine translocase gene in a Chinese neonate presenting with sudden unexpected death

Carnitine-acylcarnitine translocase (CACT) deficiency (OMIM 212138 ) is an autosomal recessive disease caused by mutations of the SLC25A20 gene [ solute carrier family 25 ( carnitine/acylcarnitine translocase ),member 20 ]. The gene has an open reading frame of 903 bp, mapped to chromosome 3p21.31 by in situ hybridization, and encodes a protein having three repeated homologous domains, each about 100 amino acids in length--a characteristic feature of mitochondrial transport proteins. CACT is essential in long-chain fatty acid oxidation because CACT is located in the inner side of the inner mitochondrial membrane, shuttling longchain acylcarnitines in the intermembranous space against carnitine in the mitochondrial matrix. The first patient with CACT deficiency reported in the United States,and the first patient reported in the United Kingdom are both of mixed ethnicity with one of the parents being Chinese. Intriguingly, there is no single case of CACT deficiency reported in Chinese populations, suggesting that this disease may be underdiagnosed in Chinese populations. In this study, we have confirmed that CACT deficiency can be a cause of sudden neonatal death in Chinese.     

Cytotoxic therapy for severe avian influenza A (H5N1) infection

The mortality rate in documented avian influenza A virus subtype H5N1 infection is still high, which is currently reported by WHO at about 50%. Post-mortem analyses in affected patients have revealed haemophagocytosis similar to that found in patients with haemophagocytic lymphohistiocytosis (HLH); such haemophagocytosis could be a very prominent post-mortem feature in H5N1 infection. There are also clinical similarities between H5N1 infection and HLH, such as massive hypercytokinaemia, cytopenia, and acute encephalitis. Importantly, patients with another severe viral infection that may be complicated by secondary HLH, severe Epstein-Barr-virus-associated HLH, have significantly better survival if specific HLH therapy (including the cytotoxic and pro-apoptotic drug etoposide) is initiated early, with survival reported to rise from about 50% to 90%. With this notable improvement in survival, specific HLH treatment, including cytotoxic therapy, could be considered in patients with severe avian influenza A infection complicated by secondary HLH.     

Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

PurposeAgonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer.Materials and MethodsThe abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell.ResultsWe observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA.ConclusionThe abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.     

Normative data for triceps and subscapular skinfold thicknesses of Chinese infants

Skinfold thickness is a validated parameter of subcutaneous fat accumulation. Data on triceps and subscapular skinfold thicknesses were collected from 10 043 (5318 males, 4725 females) singletons at 12 hospitals with gestation 31-42 wk. The LMS method using maximum penalized likelihood was used to perform model fitting of the anthropometric centiles for these parameters. Both triceps and subscapular skinfold thicknesses were greater in girls than in boys. Racial differences were found when comparing with other populations. The triceps subscapular skinfold thicknesses of Chinese infants were significantly lower than those of US white infants but larger than those of African-American infants, Israeli infants, Spanish infants and Indian infants.

Conclusion: This study provides the first set of references for the triceps and subscapular skinfold thicknesses of Chinese infants by gestation and gender. These data are helpful in determining the nutritional status of infants at birth and in assessing the postnatal growth of Chinese infants.