ObjectiveTo investigate the association between cumulative atherogenic index of plasma （cumAIP） and the risk of new-onset nonalcoholic fatty liver disease （NAFLD） in young and middle-aged individuals. MethodsA prospective cohort study was conducted among the young and middle-aged individuals （aged 18 to <60 years） in the Kailuan study cohort who underwent physical examination in Kailuan General Hospital and its 10 affiliated hospitals in June 2006 to October 2010， and after screening based on the inclusion and exclusion criteria， 33 987 individuals were included in the observation cohort. The individuals were divided into Q1， Q2， Q3， and Q4 groups based on the quantiles of cumAIP. The Kaplan-Meier method was used to calculate the cumulative incidence rate of new-onset NAFLD in the four groups， while the log-rank test was used for comparison between groups. A multivariate Cox regression analysis was used to obtain the hazard ratio （HR） and 95% confidence interval （CI） of the risk of new-onset NAFLD in the four groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThe mean follow-up was 10.89±2.54 years， and there were 6 011 cases of new-onset NAFLD， including 995 cases in the Q1 group， 1 366 in the Q2 group， 1661 in the Q3 group， and 1 989 in the Q4 group， with an incidence density of 11.37， 16.02， 19.97， and 24.91 per thousand person-years. The log-rank test showed that there was a significant difference in cumulative incidence rate between the four groups （P<0.001）. With the presence or absence of NAFLD as the dependent variable and the quantiles of different exposure levels to cumAIP as the independent variable， the multivariate Cox regression model analysis showed that compared with the Q1 group， the Q2， Q3， and Q4 groups had an HR of 1.30 （95%CI： 1.20 — 1.41）， 1.52 （95%CI： 1.41 — 1.65）， and 1.79 （95%CI： 1.64 — 1.95）， respectively， for new-onset NAFLD， with a P_trend value of <0.001. With the presence or absence of new-onset NAFLD as the dependent variable and the cumulative exposure to AIP for 0， 2， 4， and 6 years as the independent variable， the Cox regression analysis showed that compared with cumulative exposure to AIP for 0 years， cumulative exposure to AIP for 2， 4， and 6 years had an HR of 1.24 （95%CI： 1.15 — 1.35）， 1.51 （95%CI： 1.40 — 1.64）， and 1.70 （95%CI： 1.56 — 1.84）， respectively， with a P_trend value of <0.001. A sensitivity analysis was performed after exclusion of the individuals with new-onset NAFLD within 2 years， the individuals who experienced atherosclerotic cardiovascular disease events during follow-up， and the individuals taking antihypertensive， hypoglycemic， and lipid-lowering drugs， and the results were similar to those of the main analysis. Considering the competitive relationship between all-cause death and outcome events， a competing risk analysis of death was performed， which showed that the results of risk analysis were similar to those of the main analysis. ConclusionA high level of cumAIP exposure can increase the risk of new-onset NAFLD in young and middle-aged individuals.

Objective To establish a mouse model of pregnancy pain-depression comorbidity induced by chronic unpredictable stress(CUS),complete Freund's adjuvant(CFA),and formalin,and to systematically evaluate the associated phenotypes and preliminarily explore the pathological basis of the comorbidity.Methods Eight-week-old C57BL/6J female mice were randomly strarified divided into a control group(no intervention before pregnancy)and a CUS model group(CUS intervention before pregnancy)based on sucrose preference test(SPT)data.After completing the CUS treatment,female and male mice were paired and mated.Pain was induced by injecting 50％CFA and 5％formalin in the right hind foot during pregnancy to create a model of pregnancy pain-depression comorbidity.The experiment was divided into 8 subgroups:control-blank group,CUS-blank group,control-CFA group,CUS-CFA group,control-formalin group,CUS-formalin group,control-CFA+formalin group,and CUS-CFA+formalin group,with 10 mice in each group.The mice in each group were subject to behavioral tests,including the SPT,forced swimming test,tail suspension test,and open field test before and after CUS intervention,during pregnancy,and after delivery.Pain sensitivity changes were measured using mechanical allodynia and thermal hyperalgesia tests.Mice were then euthanized.Levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in hippocampus,as well as cortisol and adrenocorticotropic hormone(ACTH)in serum,were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the control-blank group,the CUS-blank group showed a significant depression-like behavior with reduced pain threshold(P＜0.001).The control-CFA+formalin group showed a decrease in pain threshold after both CFA injection and formalin injection(P＜0.01).Compared with the control-blank and control-formalin groups,the pain threshold was significantly lower in the CUS-formalin group(P＜0.01),with a sequential decrease among the three.Compared with the control-blank and control-CFA groups,the pain threshold was significantly lower in the CUS-CFA group(P＜0.001),with a sequential decrease among the three.Compared with the control-blank and control-CFA+formalin groups,the mechanical pain threshold of mice in the CUS-CFA+formalin group was significantly lower(P＜0.001)and the thermal radiation tolerance time was shorter(P＜0.01),both with sequential decreases among the three.Compared with the control-CFA+formalin and the CUS-blank groups,the CUS-CFA+formalin group had a significantly lower percentage of sucrose preference(P＜0.001),longer immobility time during the forced swimming test(P＜0.001)and tail suspension test(P＜0.001),reduced central exploration time in the open field test(P＜0.001),reduced total exploration distance(P＜0.001),and reduced percentage of distance traveled for central exploration(P＜0.001).Compared with the control-CFA+formalin and CUS-blank groups,the serum cortisol and ACTH levels of the CUS-CFA+formalin group were significantly higher(P＜0.01),and the levels of IL-6 and TNF-α in the hippocampus were higher(P＜0.05).Conclusion The combination of CUS+CFA+formalin injections is an ideal method for establishing a C57BL/6J mouse model of pregnancy pain-depression comorbidity.The behavioral changes in model mice may be attributed to the regulation of inflammatory response in hippocampus and hormone levels in the hypothalamic-pituitary-adrenal(HPA)axis.

Objective To study the effect of parecoxib sodium on tumor microenvironment in patients undergoing laparoscopic radical resection of rectal cancer.Methods Sixty patients undergoing laparoscopic surgery for radical rectal cancer resection were randomized into test group and control group(n=30).The patients in test control group received intravenous injections of 40 mg parecoxib sodium at the time of anesthesia induction,immediately after and at 12 h after the surgery,and those in the control group were injected with an equal volume of physiological saline at the same time points.Plasma levels of IL-6,TNF-α,and CXCL8 of the patients were measured using ELISA,and expressions of CXCL8,CXCR1,and CXCR2 in the peripheral blood mononuclear cells(PBMCs)were detected with Western blotting.Postoperative VAS scores and gastrointestinal reactions and disease regression at 6 months after the operation were recorded.Results Compared with the control patients,the patients in the test group showed significantly reduced plasma levels of IL-6,TNF-α,and CXCL8(P<0.05)and milder elevations of CXCL8,CXCR1,and CXCR2 proteins in PBMCs(P<0.05)with significantly lower VAS scores at 12 h and 24 h after the operation(P<0.05)and lower postoperative incidence of adverse gastrointestinal reactions(P<0.05).At 6 months after the operation,the number of patients with metastasis or tumor recurrence was significantly smaller in the test group than in the control group(P>0.05).Conclusion Parecoxib sodium can improve the inflammatory microenvironment to promote patient recovery after laparoscopic radical resection of rectal cancer possibly through a mechanism that down-regulates CXCL8-CXCR1/2 expressions in the PBMCs.

Objective To study the effect of parecoxib sodium on tumor microenvironment in patients undergoing laparoscopic radical resection of rectal cancer.Methods Sixty patients undergoing laparoscopic surgery for radical rectal cancer resection were randomized into test group and control group(n=30).The patients in test control group received intravenous injections of 40 mg parecoxib sodium at the time of anesthesia induction,immediately after and at 12 h after the surgery,and those in the control group were injected with an equal volume of physiological saline at the same time points.Plasma levels of IL-6,TNF-α,and CXCL8 of the patients were measured using ELISA,and expressions of CXCL8,CXCR1,and CXCR2 in the peripheral blood mononuclear cells(PBMCs)were detected with Western blotting.Postoperative VAS scores and gastrointestinal reactions and disease regression at 6 months after the operation were recorded.Results Compared with the control patients,the patients in the test group showed significantly reduced plasma levels of IL-6,TNF-α,and CXCL8(P<0.05)and milder elevations of CXCL8,CXCR1,and CXCR2 proteins in PBMCs(P<0.05)with significantly lower VAS scores at 12 h and 24 h after the operation(P<0.05)and lower postoperative incidence of adverse gastrointestinal reactions(P<0.05).At 6 months after the operation,the number of patients with metastasis or tumor recurrence was significantly smaller in the test group than in the control group(P>0.05).Conclusion Parecoxib sodium can improve the inflammatory microenvironment to promote patient recovery after laparoscopic radical resection of rectal cancer possibly through a mechanism that down-regulates CXCL8-CXCR1/2 expressions in the PBMCs.

Objective:To investigate the effect of acute mixed hyperlipidemia on acute myocardial infarct size and the potential mechanism.Methods: Fifty-three Sprague-Dawley(SD) rats were divided into three groups: the control group(n=15) was injected with 1.0 mL 0.9% sodium chloride,the low dose group(n=17) and high dose group(n=21) were injected with 0.5 mL and 1.0 mL 10% Triton WR-1339 solution respectively.Acute myocardial infarction was produced 24 hours after the injection.Serum lipid and the activity of lipoprotein-associated phospholipase A2(Lp-PLA2) were measured before and 24 hours after the injection.Rats were killed 24 hours after ligation and their hearts were excised to evaluate the myocardial infarct size.Results: Serum total cholesterol(TC) and trig1ycerides(TG) concentrations were(6.92?1.48) mmol/L and(11.76?2.76) mmol/L in the low dose group 24 hours after injection,(11.91?0.87) mmol/L and(33.97?5.85) mmol/L in the high dose group,and both increased significantly compared with the baseline.Also serum low density lipoprotein cholesterol(LDL-C) concentration increased(P0.05).Myocardial infarct size was significantly(P