Hypertriglyceridaemia is a very rare disorder caused by the mutations of LPL gene, with an autosomal recessive mode of inheritance. Here, we identified two unrelated Chinese patients manifested with severe hypertriglyceridaemia and acute pancreatitis. The clinical symptoms of proband 1 are more severe than proband 2. Whole exome sequencing and Sanger sequencing were performed. Functional analysis of the identified mutations has been done. Whole exome sequencing identified two pairs of variants in LPL gene in the proband 1 (c.162C>A and c.1322+1G>A) and proband 2 (c.835C>G and c.1322+1G>A). The substitution (c.162C>A) leads to the formation of a truncated (p.Cys54*) LPL protein. The substitution (c.835C>G) leads to the replacement of leucine to valine (p.Leu279Val). The splice donor site mutation (c.1322+1G>A) leads to the formation of alternative transcripts with the loss of 134 bp in exon 8 of the LPL gene. The proband 1 and his younger son also harbouring a heterozygous variant (c.553G>T; p.Gly185Cys) in APOA5 gene. The relative expression level of the mutated LPL mRNA (c.162C>A, c.835C>G and c.1322+1G>A) showed significant differences compared to wild-type LPL mRNA, suggesting that all these three mutations affect the transcription of LPL mRNA. These three mutations (c.162C>A, c.835C>G and c.1322+1G>A)showed noticeably decreased LPL activity in cell culture medium but not in cell lysates.Here, we identified three mutations in LPL gene which causes severe hypertriglyceridaemia with acute pancreatitis in Chinese patients. We also described the significance of whole exome sequencing for identifying the candidate gene and disease-causing mutation in patients with severe hypertriglyceridaemia and acute pancreatitis.

Rationale Operant self-administration (SA) is an important model of motivation to consume ethanol (EtOH), but low rates of voluntary consumption in rats are thought to necessitate water deprivation and saccharin/sucrose fading for acquisition of responding. Objectives Here, we sought to devise an effective model of SA that does not use water deprivation or saccharin/sucrose fading. Methods First, we tested if Wistar rats would acquire and maintain SA behavior of a 20% EtOH under two conditions, water deprived (WD) and not water deprived (NWD). Secondly, we tested the efficacy of our SA procedure by confirming a prior study which found that the NK1 antagonist L822429 specifically blocked stress-induced reinstatement of EtOH seeking but not SA. Finally, we assessed the effect of naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress EtOH SA in rodents. Results Lever presses (LPs) and rewards were consistent with previous reports that utilized WD and saccharin/sucrose fading. Similar to previous findings, we found that L822429 blocked stress-induced reinstatement, but not baseline SA of 20% EtOH. Moreover, naltrexone dose-dependently decreased alcohol intake and motivation to consume alcohol for rats self-administering 20 % EtOH. Conclusions Our findings provide a method for voluntary oral EtOH SA in rats that is convenient for experimenters and eliminates the potential confound of sweeteners in EtOH operant SA studies. Unlike models that use intermittent access to 20% EtOH, this method does not induce escalation, and based on pharmacological experiments, appears to be driven by the positive reinforcing effects of EtOH.

Purpose To explore the long-term oncological results of self-expanding metal stents (SEMS) as a surgical transition compared with those of simple emergency surgery. Methods A systematic review of studies involving long-term tumour outcomes comparing SEMS with emergency surgery was conducted. All studies included information on 3-year and 5-year survival rates, 3-year and 5-year disease-free survival (DFS) rates, and local and overall recurrence rates; the results were expressed as odds ratios. Results Overall, 24 articles and 2508 patients were included, including 5 randomised controlled trials, 3 prospective studies, and 16 retrospective studies. The 3-year survival rate (odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.69-1.12, P = 0.05), 5-year survival rate (OR = 0.91, 95% CI 0.70-1.17, P = 0.67), 3-year DFS rate (OR = 1.14, 95% CI 0.91-1.42, P = 0.65), 5-year DFS rate (OR = 1.35, 95% CI 0.91-2.02, P = 0.17), overall recurrence rate (OR 1.04, 95% CI 0.77-1.41, P = 0.14), and local recurrence rate (OR 1.37, 95% CI 0.84-2.23, P = 0.92) were determined. There was no significant difference between the randomised and observational studies in the subgroup analysis, and the 5-year survival rate was higher in studies with a stent placement success rate of ≥ 95%. Conclusion SEMS implantation was a viable alternative in malignant left colon obstruction as a transition to surgery; its longterm survival results, including 5-year DFS and overall survival, were equivalent to those of emergent surgery.