IGFBP-3 promotes cachexia-associated lipid loss by suppressing insulin-like growth factor/insulin signaling / 中华医学杂志(英文版)

BACKGROUND@#Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood.@*METHODS@#The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al .@*RESULTS@#In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients.@*CONCLUSION@#Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.

Analysis of pathogenic features and infection status of human parainfluenza virus type 3 among children in Hangzhou / 中华预防医学杂志

<p><b>OBJECTIVE</b>To determine the level of genetic variation of human parainfluenza virus type 3 (HPIV-3), and to describe infection and co-infection characteristics of HPIV-3 in children.</p><p><b>METHODS</b>Single respiratory samples from 856 pediatric patients with acute respiratory tract infection (ARI) in Hangzhou were collected from December 2009 to March 2013. All samples were screened for HPIV-3 by real-time RT-PCR and followed by HN sequencing and phylogenetic analysis. In all RSV positive specimens, we screened for the other pathogens, and co-infection characteristics were evaluated.</p><p><b>RESULTS</b>A total of 9.6% of 856 samples were positive for HPIV-3, the nucleotide among the strains ranged from 96.9% to 100%. All Hangzhou strains were placed in C3 subgroup based on HN gene analysis. 49% (n=41) of all HPIV-3-positive children with ARI were found to be co-infected with at least one of the other pathogen. The highest co-infection rate of HPIV-3 was with HRV (n=17). Children in the younger groups (≤12 months old) were significantly more prone to be co-infected with other pathogen (χ(2)=4.78, P=0.029). Pneumonia infection rate was significantly higher in the mono-infection group than the co-infection group (χ(2)=3.92, P=0.048).</p><p><b>CONCLUSION</b>HPIV-3 was an important pathogen in children with ARI in Hangzhou. HN gene variation rate was low, but showed a more local pattern. The co-infections with other respiratory viruses were popular. Except for pneumonia, no significant differences in other clinical presentation between the HPIV-3 mono-infection and co-infection groups were observed.</p>

Alberta stroke programme early CT score on diffusion-weighted imaging and clot burden scoring on MR angiography in the prediction of hemorrhagic transformation after thrombolysis in acute cerebral infarction / 中华放射学杂志

Objective To evaluate Alberta stroke programme early CT score on diffusion-weighted imaging (DWI-ASPECTS)and clot burden score on MR angiography (MRA-CBS)in predicting hemorrhagic transformation(HT) in acute anterior circulation cerebral infarction after thrombolysis in diffusion-weighted imaging Alberta stroke program.Methods A total of 37 consecutive patients with acute anterior circulation cerebral infarction were treated with thrombolysis.The clinical information , score of DWI-ASPECTS before thrombolysis , score of MRA-CBS before thrombolysis and images of enhanced gradient echo T 2*-weighted angiographywithin ( ESWAN) 24 hours before and after thrombolysis were all collected.The interval between onset and the two MRI scans were recorded respectively.We identified HT according to the images of ESWAN scanned after thrombolysis , and divided patients into 2 groups:with HT(14 cases) and without HT (23 cases).Differences of clinical data and imaging indicators between the two groups were compared by using Fisher′s exact test and Wilcoxon rank sum test.Logistic regression analysis was performed by taking HT as the dependent variable , and the scores of NIHSS , DWI-ASPECTS and MRA-CBS at admission were taken as independent variables.The variables which were statistically significant in logistic regression analysis were enrolled in receiver operating characteristic analysis.Results In HT group, the scores of NIHSS, DWI-ASPECTS and MRA-CBS were 15.00 ±5.30, 6.00(4.75,7.00) and 7.00(0.75,8.50) respectively.In the other group without HT, these scores were 7.00 ±4.80, 9.00(8.00,10.00)and 10.00(6.00,10.00) respectively.Compared with patients without HT , patients with HT had a higher baseline NIHSS score ( Z=-3.72,P<0.01), a lower DWI-ASPECTS (Z=-4.13,P<0.01) and a lower MRA-CBS (Z=-2.00, P<0.05).Logistic regression analysis showed that the scores of DWI-ASPECTS ( OR 0.42,95%CI 0.21-0.87,P <0.05 ) and NIHSS ( OR 1.22, 95%CI 1.00-1.48, P <0.05 ) at baseline predicted HT development independently.Receiver operating characteristic analysis showed that the optimal cut -off point of DWI-ASPECTS to predict the development of HT was≤7.Its sensitivity, specificity and area under ROC curve were 92.9%, 78.3% and 0.902 respectively ( P<0.01 ).Conclusions ASPECTS on DWI is of great value in predicting HT after thrombolysis in acute cerebral infarction.CBS on MRA can provide additional information for predicting HT.