Exploring the potential of RhoA inhibitors to improve exercise-recoverable spinal cord injury: A systematic review and meta-analysis.

BACKGROUND: The spinal cord is one of the central nervous system. Spinal cord injury (SCI) will cause loss of physical function and dysfunction below the injury site, causing them to lose sensation and mobility, thereby reducing the quality of life of patients. Although regular rehabilitation management can reduce its severity, the current effective treatment methods are limited to the treatment of secondary injuries to SCI. The purpose of treatment should not only include the restoration of the histology of the lesion, but also should focus on the restoration of sensory and mobility and. The key to effective treatment is to reduce secondary injuries. RhoA inhibitor can improve the pathophysiological changes related to secondary injury and promote the recovery of activity ability, so it may become a clinical drug for the treatment of SCI. This article systematically analyzed the effects of RhoA inhibitors on the promotion of axon regeneration and the recovery of mobility and compared the therapeutic effects of different inhibitors on SCI and their effects on physical function recovery. METHODS: We used a meta-analysis to systematically evaluate the effects of Rho inhibitors on SCI treatment and the recovery of body function. RESULTS: 21 articles (738 animals) were identified in the literatures search. Studies were selected if they reported the therapeutic effects of RhoA/ROCK inhibitors (BA-210, EGCG, ß-elemene, C3-exoenzmye, LINGO-1-Fc, Ibuprofen, SiRhoA, iRhoA + FK506, Fasudil, p21Cip1/WAF1, HA-1007, Y-27,632 and C3bot154-182). We measure the functional recovery by BBB and BMS scores. The random effect model of weighted mean difference (WMD, 95 % confidence interval) was used to analyze the effects. The WMD of the forest graph was 2.277; 95 % CI: 1.705∼2.849, P < 0.001, suggesting that RhoA inhibitors can effectively treat SCI. In addition to EGCG, all the other agents also showed the effects on the activity recovery post-SCI (P < 0.05). CONCLUSION: ß-elemene, LINGO-1-Fc, Ibuprofen, SiRhoA, RhoA + FK506, Fasudil, p21Cip1/WAF1 and Y-27,632 have similar effects to BA-210, they can promote axon germination and nerve fiber regeneration after thoracic spinal cord injury and reduce the formation of syringomyelia and protect white matter, thereby improving locomotor recovery. RhoA inhibitors have great potential to restore motor function and provide a new trend for the treatment of SCI.

Localized retinal nerve fiber layer defects and arterial hypertension.

BACKGROUND: We examined the relationship between arterial hypertension, localized retinal nerve fiber layer defects (RNFLDs), and retinal vascular abnormalities. METHODS: The study included 359 patients with arterial hypertension and 331 individuals without hypertension as control subjects. Localized RNFLDs and retinal vascular abnormalities were assessed on fundus photographs. RESULTS: After adjusting for blood concentrations of glycosylated hemoglobin (HbA1c), high-density lipoproteins, low-density lipoproteins, and hyperlipidemia in a multivariable analysis, localized RNFLDs were, in addition to arterio-venous nicking and generalized arteriolar narrowing, significantly associated with arterial hypertension. After adjusting for body mass index, waist/hip ratio, blood concentrations of glucose, HbA1c, triglycerides, high-density lipoproteins, low-density lipoproteins, and prevalence of diabetes mellitus and hyperlipidemia, categories of arterial blood pressure (optimal/normal/highly normal; mild, moderate and severe hypertension) were significantly associated with localized RNFLDs, which were present significantly more often in hypertension grades 2 and 3, with odds ratios (ORs) of 10.01 and 6.45, respectively. The corresponding ORs for arterio-venous nicking (hypertension grades 1, 2, and 3: ORs of 2.00, 1.68, and 1.99, respectively) and generalized arteriolar narrowing (hypertension grades 1 and 3; ORs of 4.60 and 4.32, respectively) were lower than those for localized RNFLDs. CONCLUSIONS: Localized RNFLDs, in addition to retinal microvascular abnormalities such as focal and generalized arteriolar narrowing, were associated with different grades of arterial hypertension. Ophthalmoscopic examination for localized RNFLDs may be useful for the assessment of the retinal abnormalities associated with arterial hypertension and for the grading of arterial hypertension.

Relationship between serum vasoactive factors and plaque morphology in patients with non-ST-segment elevated acute coronary syndrome.

BACKGROUND: Vasoactive factors have been reported to correlate with vulnerable plaque and acute coronary syndrome (ACS). This study aimed to investigate the relationship between vasoactive factors and plaque morphology in patients suffering from non-ST-segment elevated ACS. METHODS: From April 2007 to April 2009, 124 consecutive patients suffering from non-ST-segment elevated ACS who had received coronary angiography (CAG) and intravascular ultrasound (IVUS) in the People's Liberation Army General Hospital and Beijing Anzhen Hospital were enrolled in this study. Three serum vasoactive factors, plasma soluble vascular endothelial growth factor receptor-1 (sFlt-1), placental growth factor (PLGF) and interleukin-18 (IL-18), were measured by enzyme-linked-immunosorbent serologic assay of the patients. The levels of vasoactive factors were compared between vulnerable plaque group and stable plaque group, and between unstable angina pectoris (UAP) group and non-ST-segment elevation acute myocardial infarction (NSTE-AMI) group. The relationship between the plaque morphology and levels of vasoactive factors was analyzed. RESULTS: The levels of vasoactive factors were similar between the UAP group (69 patients) and NSTE-AMI group (55 patients). The levels of sFlt-1 and PLGF in the vulnerable plaque group were significantly higher than those in the stable plaque group. The level of IL-18 was correlated positively with plaque morphology. Multivariate Logistic regression analysis showed that the level of PLGF was an independent risk factor for vulnerable plaque (OR=2.115, 95% CI 1.415-5.758, P=0.018). Using the ROC curve, PLGF was a significant factor for the diagnosis of vulnerable plaque (the diagnostic point was 26.3 ng/L, the proportion of square area under the ROC curve was 0.799, 95%CI 0.758-0.839, P<0.001; the sensitivity of PLGF under the ROC curve was 86%, and the specificity 63%). CONCLUSION: Both IL-18 and PLGF are biomarkers for vulnerable plaques and helpful to predict vulnerable plaque.

[Influence of pravastatin on blood lipids and serum high sensitive C-reactive protein in patients undergoing conventional coronary artery bypass grafting under on-pump: a clinical study of 81 cases].

OBJECTIVE: To investigate the effect of pravastatin on blood lipids and serum high sensitive C-reactive protein (HsCRP) in patients undergoing conventional coronary artery bypass grafting under on-pump bypass (CCABG). METHODS: Eighty-one patients underwent CCABG. Among which 40 took orally pravastatin 20 mg once daily to at least 28 days after operation, and 41 were used as control group. The serum levels of total cholesterol (TC), triglyceride (TG), HDL-C cholesterol (HDL-C), LDL-C cholesterol (LDL-C), and HsCRP were monitored before and 24 h, 72 h, 7 days, 10 days, 14 days, and 28 days postoperatively. RESULTS: In the control group the levels of different blood lipids after operation remarkably decreased after operation compared with those before operation (all P < 0.05), reached the lowest levels 24 h after operation, then gradually increased, however, still lower than those before operation (all P < 0.05), and recovered to the baseline level 28 hours after operation; and the HsCRP level increased 24 h after operation and peaked 72 h after, then gradually decreased, and recovered to the baseline level 28 days after operation. In the pravastatin group the TC level reached its lowest level 24 h after operation, then gradually increased, however, still lower than that before operation, and recovered to the baseline level 28 days after operation; and the TG level reached the lowest level 24 h after operation (P < 0.05), and then gradually increased 3 d after operation (P > 0.05). The TC, TG, and LDL-C levels 7, 10, 14, and 28 d after operation of the pravastatin group were all significantly lower than those of the control group (all P < 0.05). The HsCRP levels at different time points of the pravastatin group were all significantly lower than those of the control group (all P < 0.05). CONCLUSION: The use of pravastatin in the early stage of CCABG is safe and can decrease systemic inflammatory reaction.

[Change of N-terminal pro-brain natriuretic peptide and big endothelin in patients undergoing coronary artery bypass grafting].

OBJECTIVE: To examine the change in N-terminal pro-brain natriuretic peptide (Nt-proBNP) and big endothelin (big ET) in patients undergoing coronary artery bypass grafting (CABG), and to evaluate their value in predicting postoperative mortality and complication. METHODS: Forty-seven patients undergoing coronary artery bypass grafting under on-pump (CCABG) and 43 patients undergoing off-pump bypass (OPCAB) were included for study. The levels of Nt-proBNP and big ET were determined before and 24 hours after operation in all patients. RESULTS: (1)There were no differences between two groups. The serum levels of Nt-proBNP and big ET increased significantly 24 hours after operation. Compared with those before operation, Nt-proBNP [(1 083.5 +/- 717.9) pmol/L] in CCABG group was increased [(1 579.2 +/- 719.7)pmol/L, t = -4.30, P<0.01], big ET was increased from (1.10 +/- 1.82 ) pmol/L to (1.68 +/- 1.73)pmol/L(t = -5.35, P<0.01) 24 hours after operation; Nt-proBNP [(999.6 +/- 843.6) pmol/L] in OPCAB group was increased [(1 460.8+/-830.0) pmol/L, t = -4.20, P<0.01], big ET was increased from (1.35 +/- 1.65) pmol/L to (1.73 +/- 1.50) pmol/L (t = -2.46, P=0.018) 24 hours after operation. (2)The level of Nt-proBNP before operation was showed to be negatively correlated with left ventricular ejection fraction (LVEF) (r = -0.43, P<0.001). (3)By univariate and multivariate Logistic regression analysis, the association of clinical variable with postoperative complication was assessed. Multivariable predictors, including the level of LVEF (OR = 1.045, 95%CI:0.999-1.092, P = 0.050) and Nt-proBNP 24 hours after operation (OR = 0.990, 95%CI:0.999-1.000, P = 0.014), were significantly associated with a higher postoperative mortality, lower cardiac output, and higher incidence of myocardial infarction and congestive heart failure. Receiver operating characteristic curves (ROC) for Nt-proBNP 24 hours after operation was valid for the prediction of postoperative complication, and the area under the curve was 0.698 (95% CI:0.585-0.811, P<0.003), sensitivity and specificity were 88.9% and 57.1%, respectively. CONCLUSION: Significant increase in Nt-proBNP and ET is found after CABG. BNP and LVEF are showed to be risk factors for postoperative complications in patients undergoing CABG.

[Comparative studies of the blood lipids and apolipoproteins A1 and B in patients underwent coronary artery bypass grafting under on-pump and off-pump bypass].

OBJECTIVE: To compare the influences of coronary artery bypass grafting under on-pump (CCABG) and off-pump bypass (OPCAB) on blood lipids and Apolipoproteins A(1) and B. METHODS: 41 patients underwent CCABG and 38 patients OPCAB. The serum levels of total cholesterol (TC), triglycerides (TG), HDL-C cholesterol (HDL-C), LDL-C cholesterol (LDL-C) and Apolipoproteins A(1) and B were monitored before and 24 h, 72 h, 7 d, 10 d, 14 d, 28 d after operation in all patients. None of them received lipid-lowering drug during the test. RESULTS: (1) There were no difference between two groups. The serum levels of TC, LDL-C decreased significantly in 24 h, 72 h, 7d, 10 d, 14 d after operation (P < 0.001). The level in 24 h was the lowest, then began increasing; until 28 days after operation the serum levels of TC, LDL-C exceeded preoperative baseline level (P < 0.05). (2) the level of TG and HDL-C in 24 h was the lowest (P < 0.001), then began increasing (P > 0.05). Until 28 days after operation the serum levels of TG exceeded preoperative baseline level (P < 0.05). (3) the serum levels of ApoA(1) decreased significantly in 24 h, 72 h, 7 day, 10 day, 14 day after operation (P < 0.001). The level in 24 h was the lowest, and lasted until 28 days after operation (P > 0.05); the serum levels of ApoB in 24 h was the lowest, then began increasing (P > 0.05). CONCLUSIONS: There presents significant influence on blood lipids and Apolipoproteins A(1) and B after CABG, and initiate lipid (s)-lowering therapy as soon as possible.