The effect of insulin-like growth factor (IGF) on tumor necrosis factor (TNF)-induced cell killing was determined for mouse BALB/c3T3 fibroblasts in vitro. Cells maintained in 0.5% fetal bovine serum (FBS) were killed by TNF within 6 h in a concentration-dependent manner, an effect that was prevented by IGF-I. TNF-induced cytotoxicity of 3T3 cells that overexpress the human IGF-I receptor (p6 cells) was prevented by IGF-I alone in the absence of serum. TNF-induced cell death was associated with the morphologic features of apoptosis and the release of low-molecular-weight DNA, both of which were prevented by IGF-I. Neither epidermal growth factor (EGF) nor platelet-derived growth factor (PDGF) protected p6 cells from TNF-induced apoptosis. The specific protective action of the IGF-I receptor was demonstrated further by the marked sensitivity to TNF of embryo fibroblasts derived from mice with targeted disruption of the IGF-I receptor (R-cells) but not of fibroblasts derived from wild-type littermates or R-cells transfected with the cDNA for the human IGF-I receptor. Cycloheximide or actinomycin D markedly reduced the protection offered by IGF-I. IGF-I protection of BALB/c3T3 cells persisted for up to 5 days in the presence of PDGF and EGF, whereas IGF-I lost its effectiveness after 2 days in the absence of growth factors. IGF-I did not prevent TNF-induced release of arachidonic acid. The results demonstrate a specific role for the IGF-I receptor in the protection against TNF cytotoxicity. This action of the IGF-I receptor is mediated by protective cytosolic proteins that exhibit a high rate of turnover and whose levels are regulated principally by factors within serum other than IGF-I.

Acute kidney injury (AKI) is a serious complication in the intensive care unit (ICU), which may increase the mortality of critically ill patients. The red blood cell distribution width (RDW) has proved useful as a predictor of short-term prognosis in critically ill patients with AKI. However, it remains unknown whether RDW has a prognostic value of long-term all-cause mortality in these patients. The data of 18279 critically ill patients with AKI at first-time hospital admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The tertiles of the RDW values were used to divide subjects into three groups, namely RDW < 13.6% for the low RDW group, 13.6% ≤ RDW < 15.2% for the middle RDW group and RDW ≥ 15.2% for the high RDW group. Demographic data, mortality, 4-year survival time and severity scale scores were compared among groups. The Kaplan-Meier analysis and the Cox regression analysis were performed to assess the impact of RDW on all-cause mortality in AKI patients. The receiver operating characteristic (ROC) curve analysis was done to evaluate the prognostic value of RDW on the long-term outcome of critically ill patients with AKI. The median age of the enrolled subjects was 65.6 years. AKI patients with a higher RDW value had significantly shorter survival time and higher death rate. By the Kaplan-Meier analysis, patients in the higher RDW group presented significantly shorter survival time and higher death rate. The Cox regression model indicated RDW as an independent risk factor of all-cause mortality of AKI patients (HR 1.219, 95% CI, 1.211 to 1.228). By the ROC analysis, RDW appeared more efficient in predicting long-term prognosis as compared with conventional severity scales. The AUC of RDW (95% CI, 0.712 to 0.725) was significantly higher than other severity scale scores. In conclusion, RDW is positively correlated to survival time of 4-year follow-up in critically ill patients with AKI, and RDW is an independent prognostic factor of longterm outcomes of these patients. Acute kidney injury (AKI) is one of the most common complications in critically ill patients, which results in poor prognosis and high risk of death 1. Approximately 57% of patients in the intensive care unit (ICU) were complicated with AKI, and up to 27% died consequently during hospitalization 2. When AKI occurs concomitantly with other severe organ dysfunctions like myocardial infarction or sepsis, the mortality rate is further increased to 45% to 60% 3 .

These results support the performance of a phase II randomized controlled trial with pCK-HGF-X7.

In the past decades, carotid angioplasty and stenting (CAS) has been developed into a credible option for the patients with carotid stenosis. However, restenosis remains a severe and unsolved issue after CAS treatment. Restenosis is characterized by neointimal hyperplasia, which is partially caused by vascular smooth muscle cells (VSMC) proliferation. However, the molecular mechanism involved in the restenosis is still unclear. In this study, we demonstrated a functional crosstalk between two TGF-β superfamily signaling pathway members, Smad3 and BMPR2, in VSMC proliferation. Smad3 plays an important role in the TGF-β/Smad3 signaling pathway, and is significantly up-regulated in the carotid artery with restenosis to promote VSMC proliferation. In contrast, BMP receptor II (BMPR2), an inhibitor of VSMC proliferation is down-regulated in carotid restenosis. We further found that BMPR2 down-regulation is mediated by miR-17~92 cluster, which is transcriptionally regulated by Smad3. Thus, Smad3 up-regulation and Smad3/miR-17~92 cluster -dependent BMPR2 down-regulation are likely to promote VSMC proliferation and restenosis. Taken together, our results may provide novel clues for early diagnosis of carotid restenosis and developing new therapeutic strategy.

In order to improve the delivery of basic public health services, it is necessary for Beijing Municipal Government to supply clear and detailed protocols, increase funding and increase the number of skilled practitioners in the community health services.