Living donor liver transplantation (LDLT) has emerged as an alternative to deceased donor liver transplantation (DDLT) because of the increasing number of patients waiting for liver transplantation (LT). However, whether it can achieve operative outcomes similar to those achieved with DDLT for adult patients remains controversial. We conducted this metaanalysis to compare the operative outcomes of LDLT and DDLT recipients. A literature search was performed to identify clinical controlled studies comparing LDLT and DDLT that were published before October 2013. Four perioperative outcomes [duration of the recipient operation (DRO), red blood cell (RBC) transfusion requirement, length of the hospital stay, and cold ischemia time (CIT)] and 5 postoperative complication outcomes (biliary complications, vascular complications, intraabdominal bleeding, perioperative death, and retransplantation) were the main outcomes assessed. Nineteen studies with a total of 5450 patients were included in the meta-analysis. In comparison with DDLT, LDLT was associated with a significantly longer DRO and a shorter CIT. We found that biliary complications [odds ratio (OR) 5 3.08, 95% confidence interval (CI) 5 1.97-4.81, P < 0.001], vascular complications (OR 5 2.16, 95% CI 5 1.32-3.54, P 5 0.002), and retransplantation (OR 5 1.76, 95% CI 5 1.09-2.83, P 5 0.02) occurred more frequently for LDLT recipients, and the subgroup analysis indicated that the biliary complication rate decreased dramatically with greater LDLT experience. No significant difference was observed in RBC transfusion requirements, the lengths of hospital stays, intra-abdominal bleeding rates, or perioperative mortality between LDLT and DDLT recipients. In conclusion, LDLT is associated with a higher rate of surgical complications after transplantation. A reduction of postoperative complication rates can be achieved as centers gain greater experience with LDLT. However, LDLT is still an excellent alternative to DDLT because it facilitates access to LT.

Angiogenesis is a complex cellular process involving multiple regulatory growth factors and growth factor receptors. Among them, the ligands for the endothelial-specific tunica intima endothelial receptor tyrosine kinase 2 (Tie2) receptor kinase, angiopoietin-1 (Ang1) and Ang2, play essential roles in balancing vessel stability and regression during both developmental and tumorinduced angiogenesis. Despite possessing a high degree of sequence identity, Ang1 and Ang2 have distinct functional roles and cellsignaling characteristics. Here, we present the crystal structures of Ang1 both unbound and in complex with the Tie2 ectodomain.Comparison of the Ang1-containing structures with their Ang2-containing counterparts provide insight into the mechanism of receptor activation and reveal molecular surfaces important for interactions with Tie2 coreceptors and associated signaling proteins. Using structure-based mutagenesis, we identify a loop within the angiopoietin P domain, adjacent to the receptor-binding interface, which confers the specific agonist/antagonist properties of the molecule. We demonstrate using cell-based assays that an Ang2 chimera containing the Ang1 loop sequence behaves functionally similarly to Ang1 as a constitutive Tie2 agonist, able to efficiently dissociate the inhibitory Tie1/Tie2 complex and elicit Tie2 clustering and downstream signaling. cellular signaling | Tie receptor tyrosine kinase | X-ray crystallography P roper development of the cardiovascular system involves two highly integrated and dynamic processes: vasculogenesis and angiogenesis (1). Vasculogenesis involves the in situ differentiation of endothelial cells from precursor angioblasts and results in their subsequent migration and proliferation, leading to the formation of the endocardium of the heart, as well as the major primitive blood vessels (2-6). Angiogenesis occurs following vasculogenesis and results in the remodeling and extension of the endothelial tubes into the adult microvasculature, as well as in the growth and expansion of vessels into organs including the kidney and brain. Endothelial cells lining these newly formed vessels are surrounded by support cells, such as smooth muscle cells and pericytes, which serve to regulate blood flow and provide survival signals (7). Angiogenesis predominantly takes place during embryonic development, although it also recurs during wound repair in adulthood. Its role is essential for tumor development, as well as metastasis and, therefore, represents a viable target for therapeutic intervention (8).The angiopoietins are a small set of growth factor ligands for the tunica intima endothelial receptor tyrosine kinase 2 (Tie2) endothelial-specific receptor tyrosine kinase and are critical for both development and pathological angiogenesis (9-11). The prototypic family member, angiopoietin-1 (Ang1), is a Tie2 agonist, whereas the highly homologous Ang2 is a context-dependent agonist/antagonist. All angiopoietin family members, Ang1 to -4, contain an amino-terminal "superclustering" and...

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Genetic associations for keratoconus could be useful for understanding disease pathogenesis and discovering biomarkers for early detection of the disease. We conducted a systematic review and meta-analysis to summarize all reported genetic associations for the disease. We searched in the MEDLINE, Embase, Web of Science, and HuGENET databases for genetic studies of keratoconus published from 1950 to June 2016. The summary odds ratio and 95% confidence intervals of all polymorphisms were estimated using the random-effect model. Among 639 reports that were retrieved, 24 fulfilled required criteria as eligible studies for meta-analysis, involving a total of 53 polymorphisms in 28 genes/loci. Results of our meta-analysis lead to the prioritization of 8 single-nucleotide polymorphisms (SNPs) in 6 genes/loci for keratoconus in Whites. Of them 5 genes/loci were originally detected in genome-wide association studies, including FOXO1 (rs2721051, P = 5.6 × 10−11), RXRA-COL5A1 (rs1536482, P = 2.5 × 10−9), FNDC3B (rs4894535, P = 1.4 × 10−8), IMMP2L (rs757219, P = 6.1 × 10−7; rs214884, P = 2.3 × 10−5), and BANP-ZNF469 (rs9938149, P = 1.3 × 10−5). The gene COL4A4 (rs2229813, P = 1.3 × 10−12; rs2228557, P = 4.5 × 10−7) was identified in previous candidate gene studies. We also found SNPs in 10 genes/loci that had a summary P value < 0.05. Sensitivity analysis indicated that the results were robust. Replication studies and understanding the roles of these genes in keratoconus are warranted.