Plasma levels of high mobility group box 1 increase in patients with posttraumatic stress disorder after severe blunt chest trauma: a prospective cohort study.

BACKGROUND: High-mobility group box 1 (HMGB1), a key late mediator of systemic inflammation, is a potentially useful biomarker for predicting outcome in patients with severe blunt chest trauma. The purpose of this study was to define the relationship between plasma levels of HMGB1 and posttraumatic stress disorder (PTSD) in patients with severe blunt chest trauma. METHODS: All patients with severe blunt chest trauma (abbreviated injury score ≥3) who were admitted to traumatic surgery department and ultimately survived to follow-up at 6 mo were eligible for the study. HMGB1 was sampled every other day from day 1-day 7 after admission, and plasma concentrations of HMGB1 were measured by a quantitative enzyme-linked immunosorbent assay test. Multivariate regression analysis was used to define the independent contribution of possible risk factors selected by univariate analysis. RESULTS: PTSD was identified in 43 patients including acute PTSD (n = 21), chronic PTSD (n = 18), and delayed-onset PTSD (n = 4) after 6-mo follow-up, in whom significant higher plasma levels of HMGB1 on days three, five, and seven after blunt chest trauma were noted compared with those seen in patients without PTSD (n = 10). Multivariate logistic analysis showed that transfusion, injury severity score, and HMGB1 levels at day 7 were the valuable risk factors for PTSD. CONCLUSIONS: In blunt chest trauma, plasma HMGB1 levels were significantly higher in patients with PTSD compared with patients with non-PTSD. Our data indicate that patients with high plasma levels of HMGB1 may be more prone to develop PTSD including acute and chronic PTSD.

Gene therapy for vein graft failure.

The main pathologenesis of vein graft restenosis is neointimal hyperplasia associated with vascular smooth muscle cell migration and proliferation. Gene therapy offers a novel treatment method for reducing or delaying early thrombosis, intimal hyperplasia, and late atherosclerosis. In this review, we will (1) describe sequential pathologies of vein graft disease; (2) summarize the applications of gene therapy in vein graft restenosis; and (3) discuss novel gene therapy for vein graft failure.

[Risk factors of mortality in severe chest trauma patients].

OBJECTIVE: To investigate the risk factors of mortality in patients with severe chest trauma (SCT). METHODS: The clinical data of 777 SCT [abbreviated injury scale (AIS) ≥3] patients who were treated in the Chongqing Emergency Medical Center from January 2006 to April 2009 were retrospectively reviewed. Stepwise logistic regression analysis was used to explore 15 possible mortality-related risk factors. RESULTS: Seven factors were found to be correlated with the mortality of SCT: age, hemorrhagic shock, multiple organ dysfunction syndrome (MODS), pulmonary infection, abdominal organ injury, Glasgow coma scale (GCS) score, and thorax AIS score. Among them five factors were the independent factors that might increase the mortality of SCT: hemorrhagic shock (B=1.710, OR=1.291, P=0.001), MODS (B=3.453, OR=1.028, P<0.001), pulmonary infection (B=2.396, OR=10.941, P<0.001), abdominal organ injury (B=1.542, OR=1.210, P=0.005), and thorax AIS score ≥4 (B=0.487, OR=1.622, P<0.001). Two factors showed protective effects: age ≤60 years (B=-0.035, OR=0.962, P=0.01) and GCS score ≥12 (B=-0.635, OR=0.320, P<0.001). CONCLUSIONS: Age, disease severity, and complications (hemorrhagic shock, MODS, and pulmonary infection) are independent risk factors of the mortality of SCT. Effective treatment programs targeting these risk factors may improve the outcomes of SCT patients.

[Prevalence and mortality of severe chest trauma in Three Gorges Area of China].

OBJECTIVE: To analyze the epidemiological features of severe chest trauma (SCT) and investigate the risk factor of its mortality in the Three Gorges Area of China. METHODS: The clinical data of 1834 SCT patients who were admitted in three hospitals in this area from January 1990 to December 2009 were retrospectively reviewed. Th epidemiological features of SCT were analyzed using a database. Stepwise logistic regression analysis was used to analyze 15 possible risk factors affecting mortality. RESULTS: The morbidity rates of blunt trauma (68.5% vs. 74.7%,p=0.006) and sharp instrument injury (12.2% vs. 15.9%,p=0.039) showed significant differences before and after 2000. The pre-hospital time [(3.45±2.38)h vs. (2.20±4.39)h,p<0.01] and transfer rate (32.39% vs. 36.80%,p=0.01) significantly improved. The thoracic Abbreviated Injury Scale (AIS)(3.56±0.71vs. 3.43±0.58,p<0.01)score and Revised Trauma Score (RTS)(7.14±2.18 vs. 6.93±1.07,p<0.01) significantly increased. Treatment for pulmonary infection (12.63±4.79 vs. 17.16±6.41,p=0.019) and hemorrhagic shock (2.4±0.75 vs. 3.4±1.34,p=0.008 )was significantly improved. The leading cause of death was hypovolemic shock (59.41%). The independent rik factors of death among these SCT patients included: hemorrhagic shock (B=1.710,OR=1.291,p=0.001), multiple organ dysfunction syndrome (B=3.453,OR=1.028,p<0.001), pulmonary infection(B=2.396,OR=10.941,p<0.001), abdominal organ injury(B=1.542,OR=1.210,p=0.005), and thorax AIS(B=0.487,OR=1.622,p<0.001). CONCLUSIONS: The prevalence of SCT shows an increasing trend in the Three Gorges Area in recent years, but with a decreased rate of complications and improved treatment. Age, complications, thorax AIS, and GCS are useful prognostic indicators.

[Association between the polymorphisms of cluster of differentiation 14 gene promoters and the susceptibility of multiple organ dysfunction syndrome after severe chest trauma].

OBJECTIVE: To investigate the polymorphisms of cluster of differentiation 14(CD14)gene promoters and explore whether such polymorphisms are associated with the susceptibility to multiple organ dysfunction syndrome(MODS) in Chongqing population. METHODS: The single nucleotide polymorphisms of the promoter region of CD14 gene at position -1145 and -159 were detected using polymerase chain reaction-restriction fragment length polymorphism method in 106 patients with severe chest trauma, among whom 47 were with MODS. RESULTS: Trauma patients carrying G allele tended to have a higher risk of MODS than those carrying A allele at position-1145, the MODS scores in trauma patients carrying G allele were significantly higher than those carrying A allele (P=0.217 for dominant effect and P=0.037 for recessive effect), and the MODS scores in trauma patients carrying T allele were significantly higher than those carrying C allele at position -159 (P=0.048 for dominant effect and P=0.198 for recessive effect). The genotypes of CD14 gene at positions -1145 and -159 were significantly correlated with the MODS scores (P=0.043,P=0.046). Compare with single-point mutation, simultaneous two-point mutation had significantly higher risk of MODS (Pü0.01), while the difference of MODS scores showed no statistical significance (P=0.239). CONCLUSION: The polymorphisms of CD14 gene promoters are associated with MODS after severe chest trauma in Chongqing population.

Minimally invasive direct coronary bypass compared with percutaneous coronary intervention for left anterior descending artery disease: a meta-analysis.

BACKGROUND: The clinical outcomes for left anterior descending (LAD) coronary artery lesion between minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) are still controversial. The objective was to compare safety and efficacy between MIDCAB and PCI for LAD. METHODS: Electronic databases and article references were systematically searched to access relevant studies. End points included mortality, myocardial infarction, target vessel revascularization (TVR), major adverse coronary events (MACE), angina recurrence, and stroke. RESULTS: Fourteen studies with 941 patients were finally involved in the present study. The mortality and incidence of myocardial infarction were similar in MIDCAB and PCI groups at 30 days, 6 months, and at follow-up beyond 1 year. Compared with PCI, MIDCAB decreased incidence of TVR and MACE at 6 months and beyond 1 year follow-up. MIDCAB was associated with a lower incidence of angina recurrence at 6 months compared with PCI. PCI was associated with higher risk of restenosis in target vessel. No significant difference was shown for stroke. CONCLUSION: Our meta-analysis indicates that there are no significant differences in the safety between MIDCAB and PCI in patients with LAD. However MIDCAB is superior to PCI for TVR and MACE.

MicroRNA-221 sponge therapy attenuates neointimal hyperplasia and improves blood flows in vein grafts.

BACKGROUND: Vein graft failure due to neointimal hyperplasia remains an important and unresolved problem of cardiovascular surgery. MicroRNA-221 (miR-221) has been shown to play a major role in regulating vascular smooth muscle cell (VSMC) proliferation and phenotype transformation. Thus, the purpose of this study is to determine whether adenovirus mediated miR-221 sponge gene therapy could inhibit vein graft neointimal hyperplasia. METHODS: Adenovirus encoding miR-221 sponge (Ad-miR-221-SP) was used to inhibit VSMC proliferation in vitro and neointimal formation in vivo. Expression of miRNA-221 was evaluated in cultured VSMC and in rat vein graft models following transduction with Ad-miR-221-SP, Ad-Control-SP (without miR-221 antisense binding sites), or Ad-GFP (control). To accelerate the transfer of miR-221 sponge gene to the vein grafts, 20% poloxamer F-127 gel was used to extend virus contact time and 0.25% trypsin to increase virus penetration. RESULTS: miR-221 sponges can significantly decrease the expression of miR-221 and proliferation in cultured VSMC. Cellular proliferation rates were significantly reduced in miR-221 sponge treated grafts as compared with controls at 6 weeks after bypass surgery (19.8% versus 43.6%, P=0.0028). miR-221 sponge gene transfer reduced the neointimal area (210.75 ± 24.13 versus 67.01 ± 12.02, P<0.0001), neointimal thickness (171.86 ± 27.87 versus 64.13 ± 16.23, P<0.0001) and neointima/media ratio (0.74 ± 0.21 versus 1.95 ± 0.25, P<0.0001) in vein grafts versus controls. miR-21 sponge treatment was also improved hemodynamics in vein grafts. We have further identified that p27 (Kip1) is a potential target gene of miR-221 in vein grafts. CONCLUSION: miR-221 sponge therapy can significantly reduce miR-221 activity and inhibit neointimal hyperplasia in vein grafts. Locally adventitial delivery of adenoviruses mediated miRNA sponges may be promising gene therapies to prevent vein graft failure.

High mobility group box 1 gene polymorphism is associated with the risk of postoperative atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary cause of postoperative atrial fibrillation (POAF). The objective of this study was to determine the relationships between rs2249825 (C/G) polymorphism in high-mobility group box protein 1 (HMGB1) and POAF in patients who underwent coronary artery bypass grafting (CABG) under CPB. METHODS: A prospective cohort study was carried out between February 2011 and January 2014. Patients who had no history of atrial fibrillation undergoing CABG with CPB were recruited in this study, and were matched based on preoperative characteristics. Blood samples were obtained before, and at 4, and 24 h after CPB. HMGB1 level was measured by enzyme immunoassay. Patients were genotyped for single nucleotide polymorphisms of HMGB1 (rs2249825). Patients were genotyped for single nucleotide polymorphisms of HMGB1 (rs2249825) using pyrosequencing method. The primary clinical end point was the incidence of POAF after surgery. RESULTS: After matching, a total of 128 patients undergoing elective CABG with CPB were eligible for analysis. Plasma HMGB1 concentrations were increased 4 h after CPB (p <0.0001) and were still increased at 24 h (p <0.0001). The frequencies of CC, CG, GG genotypes were 21 (56.8 %), 29 (37.8 %), and 2 (5.4 %) in patients with POAF and 81.3, 16.5, and 2.2 % in patients without POAF (p = 0.016). CG + GG genotype was associated with high HMGB1 levels compared with the genotype CC at 4 h (p = 0.023), and 24 h (p = 0.015) after CPB. Multivariate analysis showed that age older than 60 years (OR = 1.40; 95 % CI: 1.03 to 1.89; p = 0.021) and allele G of polymorphisms (OR = 1.61; 95 % CI: 1.08 to 2.04; p = 0.034) were independent risk factors for POAF. CONCLUSIONS: The HMGB1 rs2249825 was associated with the susceptibility to POAF after CABG with CPB in a Chinese Han population.

[Clinic research on heroin de-addiction effects of acupuncture and its potentiality of preventing relapse].

OBJECTIVE: To compare the effects of de-addiction with the therapy of acupuncture, acupuncture plus opium, opium plus buprenorphine and opium plus Han's instrument for de-addiction and to study the effects of the four therapeutic methods on the protracted withdrawal syndrome and craving. METHODS: The effects of de-addiction were assessed with the opiate withdrawal scale and the craving degree with visual analogue scale (VAS). RESULTS: The dominance of acupuncture treatment for withdrawal syndrome appeared to be after the 6th day, and the dominance for controlling craving showed after the 8th day, moreover, there were little side effects. CONCLUSION: Acupuncture treatment had the potentiality of preventing relapse and could be used for treating the protracted withdrawal syndrome and psychic dependence during the period between the stages of abstinence and rehabilitation.

High plasma levels of high mobility group box 1 is associated with the risk of sepsis in severe blunt chest trauma patients: a prospective cohort study.

BACKGROUND: High mobility group box 1 (HMGB1) is a late mediator of systemic inflammation. Extracellular HMGB1 play a central pathogenic role in critical illness. The purpose of the study was to investigate the association between plasma HMGB1 concentrations and the risk of poor outcomes in patients with severe blunt chest trauma. METHODS: The plasma concentrations of HMGB1 in patients with severe blunt chest trauma (AIS ≥ 3) were measured by a quantitative enzyme-linked immunosorbent assay at four time points during seven days after admission, and the dynamic release patterns were monitored. The biomarker levels were compared between patients with sepsis and non-sepsis, and between patients with multiple organ dysfunction syndrome (MODS) and non-MODS. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The short-form 36 was used to evaluate the quality of life of patients at 12 months after injury. RESULTS: Plasma HMGB1 levels were significantly higher both in sepsis and MODS group on post-trauma day 3, 5, and 7 compared with the non-sepsis and non-MODS groups, respectively. Multivariate analysis showed that HMGB1 levels and ISS were independent risk factors for sepsis and MODS in patients with severe blunt chest trauma. CONCLUSIONS: Plasma HMGB1 levels were significantly elevated in patients with severe blunt chest trauma. HMGB1 levels were associated with the risk of poor outcome in patients with severe blunt chest trauma. Daily HMGB1 levels measurements is a potential useful tool in the early identification of post-trauma complications. Further studies are needed to determine whether HMGB1 intervention could prevent the development of sepsis and MODS in patients with severe blunt chest trauma.