[Show abstract][Hide abstract] ABSTRACT: Background:
Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era.
Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted.
A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42-1.01), or long-term mortality (RR 0.79; 95% CI, 0.47-1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25-0.67).
In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.
[Show abstract][Hide abstract] ABSTRACT: Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75(NTR) death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGF:NGF and the respective receptors p75(NTR):TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs.
No preview · Article · Dec 2015 · Experimental and Molecular Pathology
[Show abstract][Hide abstract] ABSTRACT: Background:
Corticosteroids are an option in the treatment of community-acquired pneumonia (CAP). However, the benefits and adverse effects of corticosteroids, especially in severe CAP, have not been well assessed.
Pubmed, Embase, and Cochrane library databases from inception to May 2015 were searched. Randomized controlled trials (RCTs) and cohort studies that evaluated use of corticosteroids in adult patients with CAP were included. The quality of outcomes was evaluated using GRADE methodology. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled relative risks (RRs) and 95% confidence intervals(CIs).
Nine eligible RCTs (1667 patients) and six cohort studies(4095 patients), were identified. The mean corticosteroid dose and treatment duration were 30 mg/day methylprednisolone for 7 days. Corticosteroids did not have a statistically significant effect on mortality (RR, 0.72; 95% CI: 0.43-1.21; evidence rank: low) in CAP patients, and severe CAP patients (RCTs; RR, 0.72; 95% CI: 0.43-1.21; evidence rank: low; cohort studies; RR, 1.00; 95% CI, 0.86-1.17 ). Corticosteroids treatment was associated with an decreased risk of adult respiratory distress syndrome (RR, 0.21; 95% CI, 0.08-0.59), and may reduce the lengths of hospital and intensive care unit stay, the duration of intravenous antibiotic treatment, and the time to clinical stability. Corticosteroid were not associated with increased rates of adverse events.
Short-term treatment with corticosteroids is safe, and may reduce the risk of adult respiratory distress syndrome, shorten the length of the disease in CAP patients.
[Show abstract][Hide abstract] ABSTRACT: To study the CPS-II mechanism underlying the pathological process of elevated blood ammonia leading to liver injury.
An in vitro hyperammonemia hepatocyte cell model was constructed by exposure to various concentrations of NH4Cl. The subsequent changes to cellular morphology were observed by microscopy. to cell apoptosis were determined by flow cytometry, and to mRNA and protein expression of CPS-II were examined by real-time PCR and western blotting, respectively.
Exposure to NH4Cl led to dose-dependent morphological damage, apoptosis and necrosis of the hepatocytes. The apoptosis rate was significantly higher for the high-dose group than for the control (no exposure) group (24.7%+/-2.39% vs. 4.1%+/-0.78%, q =8.06, P less than 0.05). Expression of the CPS-II mRNA was significantly elevated in response to NH4Cl exposure (vs. the control group; F=191.881, P less than 0.05).The CPS-II mRNA expression level increased with increasing NH4Cl concentration (grey values: 1.040+/-0.045, 1.641+/-0.123, 2.285+/-0.167 and 3.347+/-0.124, respectively). The CPS-II protein expression level was also significantly enhanced in response to the NH4Cl exposures (CPS-II protein and internal GAPDH grey value ratios: 0.099+/-0.0130, 0.143+/-0.025, 0.161+/-0.036 and 0.223+/-0.042, respectively; t=3.825, 3.968 and 6.908, P less than 0.05).
CPS-II mRNA and protein expression levels become elevated with increase in the NH4Cl concentrations, suggesting that in addition to the urea cycle, CPS-II may play an important role in the ammonia metabolism under the condition of hyperammonemia.
No preview · Article · May 2015 · Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
[Show abstract][Hide abstract] ABSTRACT: Introduction Vitamin D deficiency is common in critically ill patients, and was reported to be associated with adverse outcomes. However, the effect of vitamin D deficiency on mortality in critically ill patients remains unclear. Methods We searched PubMed and EMBASE from the inception to July 2014 for cohort studies to assess the effect of vitamin D deficiency on the incidence of mortality in critically ill patients. Mortality-specific odds ratio (OR) with 95% confidence interval (CI) were pooled with a random- or fixed-effect models when appropriate.ResultsSeven cohort studies with a total of 4,204 participants including 1,679 cases of vitamin D deficiency were included in this meta-analysis. Vitamin D deficiency was significantly associated with an increased hospital mortality (OR 1.76; 95% CI, 1.38 to 2.24; P <0.001), with very low heterogeneity (I 2¿=¿2.3%; P =0.402). The finding of increased hospital mortality in critically ill adult patients was consistently found in every stratum of our subgroup analyses. Conclusions This meta-analysis suggests that vitamin D deficiency is associated with increased incidence of hospital mortality in critically ill adult patients.
Full-text · Article · Dec 2014 · Critical care (London, England)
[Show abstract][Hide abstract] ABSTRACT: Immunological dysfunction is a primary characteristic of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been shown to ameliorate the clinical signs of EAE by suppressing the production of proinflammatory cytokines IFN-γ, TNF-α and IL-17, as well as adhesive molecules. However, whether MAT is simply an immunosuppressive or an immunomodulatory reagent has not been studied. In the present study we focused on possible immunomodulatory mechanisms underlying the effects of MAT in EAE. Our results showed that administration of MAT significantly increased serum production of Th2 cytokines IL-4 and IL-5, and regulatory T cell (Treg) related cytokines IL-10, TGF-β1, as well as expression of Foxp3, a Treg transcription factor, in the spinal cord. In addition, MAT treatment significantly upregulated CNS expression of Nrf2 and HO-1, which play important roles in inhibiting oxidative stress and CNS inflammation. Together, our findings identify MAT as, not only an immunosuppressive, but also a potent immunomodulatory natural product for the treatment of EAE and which has potential as a novel therapeutic option for MS.
No preview · Article · Oct 2014 · Experimental and Molecular Pathology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The purpose of this study was to investigate the associated between serum total bilirubin (STB) levels and long-term outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).
A total of 1,273 consecutive patients were enrolled. Patients were grouped according to their baseline STB levels: Group 1 (STB < 3.4 μmol/L), Group 2 (3.4 μmol/L ≤ STB ≤ 10.3 μmol/L), Group 3 (10.3 μmol/L < STB ≤ 17.1 μmol/L), and Group 4 (STB < 17.1 μmol/L) and the rate of major adverse cardiovascular events (MACE) was determined
A total of 1,152 patients were successfully followed up (90.5%) for a mean period of 30 ± 5 months, including 187 patients experiencing a major adverse cardiovascular event (MACE: death from any cause, myocardial infarction, repeat revascularization or readmission). The MACE rate in Groups 3 and 4 was lower than in Groups 1 and 2 (P < 0.01). After adjusted the confounding factors with Cox regression analysis, the MACE rates in Groups 2-4 were still lower than in Group 1 (Group 2, RR=0.293, 95% CI 0.167-0.517, P < 0.01; Group 3, RR=0.142, 95% CI 0.065-0.312, P < 0.01; Group 4, RR=0.134, 95% CI 0.071-0.252, P < 0.01). The cumulative survival rates of Groups 3 and 4 were higher than that of Groups 1and 2 (P < 0.01).
High STB concentration is associated with lower MACE in patients with ACS after PCI.
Full-text · Article · Oct 2014 · Clinical and investigative medicine. Médecine clinique et experimentale
[Show abstract][Hide abstract] ABSTRACT: Background:
Despite the fact that recent evidence from meta-analysis of randomized trials indicates an increase in mortality, perioperative treatment with β-blockers is still widely advocated. We therefore performed a meta-analysis of cohort studies to evaluate the effects of perioperative β-blockers on mortality in patients undergoing non-cardiac surgery in the real world scenarios.
We searched PubMed and Embase from the inception to April 2014 for cohort studies, assessing the effect of perioperative β-blockers on mortality in patients undergoing non-cardiac surgery. Adjusted relative risk (RR) with 95% confidence interval (CI) was pooled using random effect models.
Eight cohort studies with a total of 470,059 participants (180,441 patients in the β-blocker group and 289,618 patients in the control group) were included in this meta-analysis. Perioperative β-blockers were not associated with a reduced risk of mortality (RR=0.88, 95% CI, 0.75 to 1.04), postoperation myocardial infarction (RR=1.30, 95% CI, 0.76 to 2.23), and postoperation stroke (RR=1.17, 95% CI, 0.53 to 2.57). However, in subgroup analysis of mortality, taking β-blockers on the day of surgery caused statistically significant increase in mortality of 91% (RR=1.91, 95% CI, 1.01 to 3.62).
In the real world scenarios, for patients undergoing non-cardiac surgery, the routine use of β-blockers does not seem to reduce the risk of death. Moreover, those who are taking β-blockers on the day of surgery may have an increased risk of postoperative mortality. However, these results should be interpreted with caution because of the significant heterogeneity across the studies.
Full-text · Article · Aug 2014 · International Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053™) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1.
No preview · Article · Aug 2014 · Journal of Huazhong University of Science and Technology
[Show abstract][Hide abstract] ABSTRACT: Objective
To discuss effect of FK506 nanospheres used at different time on the regeneration of allogeneic nerve after transplant.
Single emulsion-solvent evaporation method (O/W) was adopted to prepare the FK506 nanospheres and the tibial nerve of rats after allogeneic transplantation. FK506 nanospheres were used in group A after operation immediately, in group B in 24 h after operation, and in group C in 3 d after operation while FK506 nanospheres were not used in group D; in the 4th, 8th and 12th week after operation respectively, general observation of transplanted nerves, histological examination, image analysis of myelinated fibers, wet-weight determination of musculi triceps surae, retrogradely labeling of neurons by the fluorescein and electrophysiological comparison of bilateral tibial nerve were carried out.
FK506 nanospheres can be degraded and absorbed quickly. The neural regenerations in group A and B were similar, which were both much better than those in group C and D. The difference was statistically significant and so was the difference between group C and D.
Drug release rate of FK506 nanospheres is accordant with the regeneration law of damaged nerves and the local application can promote the regenerations of nerves. The effect would be better if the drug is used in earlier period (within 24 h).
Preview · Article · Jun 2014 · Asian Pacific Journal of Tropical Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells.
Materials and methods:
SKOV3 ovarian cancer cells were treated with curcumin (10-60 μM) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment.
Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells.
The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.
No preview · Article · Apr 2014 · Asian Pacific journal of cancer prevention: APJCP
[Show abstract][Hide abstract] ABSTRACT: Observational data have suggested that statin therapy may reduce mortality in patients with infection and sepsis; however, results from randomized studies are contradictory and do not support the use of statins in this context. Here, we performed a meta-analysis to investigate the effects of statin therapy on mortality from infection and sepsis.
We searched electronic databases (PubMed and Embase) for articles published before November 2013. Randomized or observational studies reporting the effects of statin therapy on mortality in patients with infection or sepsis were eligible. Randomized and observational studies were separately pooled with risk ratios (RRs) and random-effects models.
We examined 5 randomized controlled trials with 867 patients and 27 observational studies with 337,648 patients. Among the randomized controlled trials, statins did not significantly decrease in-hospital mortality (RR, 0.98; 95% confidence interval (CI), 0.73 to 1.33) or 28-day mortality (RR, 0.93; 95% CI, 0.46 to 1.89). However, observational studies indicated that statins were associated with a significant decrease in mortality with adjusted data (RR, 0.65; 95% CI, 0.57 to 0.75) or unadjusted data (RR, 0.74; 95% CI, 0.59 to 0.94).
Limited evidence suggests that statins may not be associated with a significant reduction in mortality from infection and sepsis. Although meta-analysis from observational studies showed that the use of statins was associated with a survival advantage, these outcomes were limited by high heterogeneity and possible bias in the data. Therefore, we should be cautious about the use of statins in infection and sepsis.
[Show abstract][Hide abstract] ABSTRACT: The impact of pre-existing diabetes on the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in critically ill patients remains unclear. We performed a meta-analysis of cohort studies to evaluate the risk of ALI/ARDS in critically ill patients with and without pre-existing diabetes.
We searched PubMed and Embase from the inception to September 2013 for cohort studies assessing the effect of pre-existing diabetes on ALI/ARDS occurrence. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate.
Seven cohort studies with a total of 12,794 participants and 2,937 cases of pre-existing diabetes, and 2,457 cases of ALI/ARDS were included in the meta-analysis. A fixed-effects model meta-analysis showed that pre-existing diabetes was associated with a reduced risk of ALI/ARDS (OR 0.66; 95% CI, 0.55-0.80; p<0.001), with low heterogeneity among the studies (I(2) = 18.9%; p = 0.286). However, the asymmetric funnel plot and Egger's test (p = 0.007) suggested publication bias may exist.
Our meta-analysis suggests that pre-existing diabetes was associated with a decreased risk of ALI/ARDS in critically ill adult patients. However, the result should be interpreted with caution because of the potential bias and confounding in the included studies.
[Show abstract][Hide abstract] ABSTRACT: It is increasingly accepted that glutamate excitotoxicity contributes to the death of nerve cells in multiple sclerosis (MS). Matrine (MAT) is a quinolizidine alkaloid that has long been used in the treatment of hepatitis B without obvious side effects. Previous reports have shown that MAT suppresses central nervous system inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however whether MAT effectively inhibits excitotoxic molecules, such as glutamate-related factors, is still unclear. In this study, we provide data showing that MAT attenuated EAE disease severity, accompanied by downregulated glutamate and upregulated GABA levels, as well as enhanced expression of two dependent glutamate transporters (GLT-1 and GLAST). In addition, MAT treatment significantly reduced the level of the NMDA- and AMPA- glutamate receptor in EAE rats. Taken together, our data indicate that MAT treatment regulates glutamate-related molecules, and suggests that the neuroprotective role of MAT is a novel mechanism underlying its therapeutic effect in EAE.
No preview · Article · Dec 2013 · Neuroscience Letters