Simplified Genomic Data Revealing the Decline of Aleuritopteris grevilleoides Population Accompanied by the Uplift of Dry-Hot Valley in Yunnan, China.

Understanding the evolutionary history of endangered species is crucial for identifying the main reasons for species endangerment in the past and predicting the changing trends and evolutionary directions of their future distribution. In order to study the impact of environmental changes caused by deep valley incision after the uplift of the Qinghai-Tibet Plateau on endangered species, we collected 23 samples belonging to four populations of Aleuritopteris grevilleoides, an endangered fern endemic to the dry-hot valleys (DHV) of Yunnan. Single-nucleotide variation sites (SNPs) were obtained by the genotyping-by-sequencing (GBS) method, and approximately 8085 SNP loci were identified. Through the reconstruction and analysis of genetic diversity, population structure, population dynamics, evolution time, and ancestral geographical distribution, combined with geological historical events such as the formation of dry-hot valleys, this study explores the formation history, current situation, reasons for endangerment and scientifically sound measures for the protection of A. grevilleoides. In our study, A. grevilleoides had low genetic diversity (Obs_Het = 0.16, Exp_Het = 0.32, Pi = 0.33) and a high inbreeding coefficient (Fis = 0.45). The differentiation events were 0.18 Mya, 0.16 Mya, and 0.11 Mya in the A. grevilleoides and may have been related to the formation of terraces within the dry-hot valleys. The history of population dynamics results shows that the diversion of the river resulted in a small amount of gene flow between the two clades, accompanied by a rapid increase in the population at 0.8 Mya. After that, the effective population sizes of A. grevilleoides began to contract continuously due to topographic changes resulting from the continuous expansion of dry-hot valleys. In conclusion, we found that the environmental changes caused by geological events might be the main reason for the changing population size of A. grevilleoides.

Genome size evolution of the extant lycophytes and ferns.

Ferns and lycophytes have remarkably large genomes. However, little is known about how their genome size evolved in fern lineages. To explore the origins and evolution of chromosome numbers and genome size in ferns, we used flow cytometry to measure the genomes of 240 species (255 samples) of extant ferns and lycophytes comprising 27 families and 72 genera, of which 228 species (242 samples) represent new reports. We analyzed correlations among genome size, spore size, chromosomal features, phylogeny, and habitat type preference within a phylogenetic framework. We also applied ANOVA and multinomial logistic regression analysis to preference of habitat type and genome size. Using the phylogeny, we conducted ancestral character reconstruction for habitat types and tested whether genome size changes simultaneously with shifts in habitat preference. We found that 2C values had weak phylogenetic signal, whereas the base number of chromosomes (x) had a strong phylogenetic signal. Furthermore, our analyses revealed a positive correlation between genome size and chromosome traits, indicating that the base number of chromosomes (x), chromosome size, and polyploidization may be primary contributors to genome expansion in ferns and lycophytes. Genome sizes in different habitat types varied significantly and were significantly correlated with habitat types; specifically, multinomial logistic regression indicated that species with larger 2C values were more likely to be epiphytes. Terrestrial habitat is inferred to be ancestral for both extant ferns and lycophytes, whereas transitions to other habitat types occurred as the major clades emerged. Shifts in habitat types appear be followed by periods of genomic stability. Based on these results, we inferred that habitat type changes and multiple whole-genome duplications have contributed to the formation of large genomes of ferns and their allies during their evolutionary history.

Long noncoding RNA MEG3 silencing protects against hypoxia-induced pheochromocytoma-12 cell injury through inhibition of TIMP2 promoter methylation.

Hypoxia is a common pathological process caused by insufficient oxygen. Long noncoding RNAs (lncRNAs) have been proven to participate in this pathology. Hypoxia is reported to significantly reduce the secretion of tissue inhibitor of metalloproteinase 2 (TIMP2) and TIMP2 induces pheochromocytoma-12 (PC12) cell cycle arrest. Thus, our study aimed to explore the mechanism by which lncRNA maternally expressed gene 3 (MEG3) was implicated in hypoxia-induced PC12 cell injury through TIMP2 promoter methylation. To elucidate the potential biological significance of MEG3 and the regulatory mechanism between MEG3 and TIMP2, a hypoxia-induced PC12 cell injury model was generated. The hypoxia-exposed cells were subjected to a series of overexpression plasmids and short hairpin RNAs, followed by the measurement of levels of MEG3, TIMP2, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), Bcl-2-associated X protein, B-cell lymphoma-2, and caspase-3, as well as the changes in MMP, cell proliferation, apoptosis, and cell cycle progression. On the basis of the findings, MEG3 was upregulated in hypoxia-injured PC12 cells. MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression. Moreover, PC12 cells following MEG3 silencing and TIMP2 overexpression exhibited significantly decreased levels of LDH, MDA, and ROS along with cell apoptosis, yet increased SOD and MMP levels, as well as cell cycle entry to the S phase and cell proliferation. In conclusion, MEG3 silencing suppresses hypoxia-induced PC12 cell injury by inhibiting TIMP2 promoter methylation. This study may provide novel therapeutic targets for hypoxia-induced injury.

Transcriptomic Evidence of Adaptive Evolution of the Epiphytic Fern Asplenium nidus.

Epiphytic ferns have been found to flourish after angiosperms dominated forest communities, and they play important roles in rainforest canopies. How do epiphytic ferns adapt to tropical rainforest canopy habitats? At present, we know little about the molecular mechanism underlying this adaptation. Asplenium nidus is a well-known epiphytic fern that is closely related to the terrestrial species Asplenium komarovii. Here, RNA-seq and comparative transcriptomic analyses were performed to explore the underlying basis of the adaptation of A. nidus to extreme environments. A total of 44.04 and 44.57 Mb clean reads were obtained from A. nidus and A. komarovii, respectively, and they were assembled into 89,741 and 77,912 unigenes. Functional annotation showed that 52,305 (58.28% of the total genes for A. nidus) and 45,938 (58.96% of the total genes for A. komarovii) unigenes were annotated in public databases. Genes involved in stress responses and photosynthesis were found to have undergone positive selection in A. nidus. Compared to A. komarovii, transcription factors related to stress response, leaf development, and root development were found to be considerably expanded in A. nidus, especially in the ANR1 subclade of MADS-box family genes which played roles in lateral root development. This study improves our understanding of the adaptation of A. nidus to epiphytic habitats by forming unique strategies.

Nicotinic Acetylcholine Receptor Alpha7 Subunit Mediates Vagus Nerve Stimulation-Induced Neuroprotection in Acute Permanent Cerebral Ischemia by a7nAchR/JAK2 Pathway.

BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p<0.05). In addition, VNS enhanced the levels of a7nAchR, p-JAK2, and p-STAT3 in the ischemic penumbra (p<0.05). However, inhibition of a7nAchR not only attenuated the beneficial neuroprotective effects induced by VNS, but also decreased levels of p-JAK2 and p-STAT3. Strikingly, pharmacological activation of a7nAchR can partially substitute for VNS-induced beneficial neurological protection. CONCLUSIONS These results suggest that a7nAchR is a pivotal mediator of VNS-induced neuroprotective effects on PMCAO injury, which may be related to suppressed inflammation via activation of the a7nAchR/JAK2 anti-inflammatory pathway.

Effects of add-on lipid-modifying therapy on top of background statin treatment on major cardiovascular events: A meta-analysis of randomized controlled trials.

BACKGROUND: In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes. METHODS: Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile. CONCLUSION: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.

Long-term efficacy and safety of statin treatment beyond six years: a meta-analysis of randomized controlled trials with extended follow-up.

Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of cholesterol-lowering treatment with statins in patients at high risk of vascular disease. However, large statin RCTs were usually restricted to the typical 5-6 years. Moreover, non-cardiovascular events, especially the risk of cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of statin treatment by performing a meta-analysis of statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a statin and the cholesterol level were almost identical between the original statin group and the original placebo group. Over the entire 6.7-14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85-0.96; P=0.0009), cardiovascular mortality (0.87, 0.81-0.93; P<0.0001) and major coronary events (0.79, 0.72-0.86; P<0.00001) was observed in favour of the original statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74-0.93; P=0.001), cardiovascular mortality (0.81, 0.69-0.95; P=0.01) and major coronary events (0.77, 0.63-0.95; P=0.01) was observed among initially statin-treated patients. Over the entire follow-up period, statin treatment did not increase the incidence of cancers (0.99, 0.95-1.04; P=0.79), deaths from cancers (1.00, 0.93-1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90-1.00; P=0.07). In conclusion, statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms.

Angiotensin II receptor blocker attenuates intrarenal renin-angiotensin-system and podocyte injury in rats with myocardial infarction.

The mechanisms and mediators underlying common renal impairment after myocardial infarction (MI) are still poorly understood. The present study aimed to test the hypothesis that angiotensin II type 1 receptor blockers (ARBs) provides renoprotective effects after MI by preventing augmented intrarenal renin-angiotensin-system (RAS)-induced podocyte injury. Sprague-Dawley rats that underwent ligation of their coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9 weeks. Renal function, histology and molecular changes were assessed. The current study revealed that MI-induced glomerular podocyte injury was identified by increased immunostaining for desmin and p16(ink4a), decreased immunostaining for Wilms' tumor-1 and podocin mRNA expression, and an induced increase of blood cystatin C at both 3 and 9 weeks. These changes were associated with increased intrarenal angiotensin II levels and enhanced expressions of angiotensinogen mRNA and angiotensin II receptor mRNA and protein. These changes were also associated with decreased levels of insulin-like growth factor (IGF-1) and decreased expressions of IGF-1 receptor (IGF-1R) protein and mRNA and phosphorylated(p)-Akt protein at 9 weeks, as well as increased expressions of 8-hydroxy-2'-deoxyguanosine at both time points. Treatment with losartan significantly attenuated desmin- and p16(ink4a)-positive podocytes, restored podocin mRNA expression, and decreased blood cystatin C levels. Losartan also prevented RAS activation and oxidative stress and restored the IGF-1/IGF-1R/Akt pathway. In conclusion, ARBs prevent the progression of renal impairment after MI via podocyte protection, partially by inhibiting the activation of the local RAS with subsequent enhanced oxidative stress and an inhibited IGF-1/IGF-1R/Akt pathway.

Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: a meta-analysis of 72,128 patients.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. OBJECTIVE AND METHODS: The aim of this study was to evaluate the effect of ACEIs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ACEIs and new-onset diabetes were identified by electronic and manual searches. RESULTS: Nine RCTs with 92,404 patients (72,128 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in the ACEIs group [OR 0.80, (0.71, 0.91)], irrespective of achieved blood pressure levels at the follow-up. ACEIs therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics [OR 0.78, (0.65, 0.93)], placebo [OR 0.79, (0.64, 0.96)], or calcium channel blockers [OR 0.85, (0.73, 0.99)]. ACEIs treatment was associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.80, (0.68, 0.93)], coronary artery disease (CAD) or cardiovascular disease [OR 0.83, (0.68, 1.00)], or heart failure [OR 0.22, (0.10, 0.47)]. Among patients with impaired glucose tolerance or impaired fasting glucose, ramipril did not significantly reduce the incidence of diabetes [OR 0.91, (0.79, 1.05)], but significantly increased regression to normoglycemia. CONCLUSION: ACEIs have beneficial effects in preventing new-onset diabetes. ACEIs provide additional benefits of lowering the risk of new-onset diabetes in patients with hypertension, CAD or other cardiovascular disease.

[Comparative study of two treatment methods for acute periodontal abscess].

PURPOSE: The aim of this short-term study was to compare the clinical efficacy of 2 different methods to treat acute periodontal abscesses. METHODS: After patient selection, 100 cases of acute periodontal abscess were randomly divided into two groups. The experimental group was treated by supra- and subgingival scaling, while the control group was treated by incision and drainage. A clinical examination was carried out to record the following variables: subjective clinical variables including pain, edema, redness and swelling; objective clinical variables including gingival index(GI), bleeding index(BI), probing depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed with SPSS 19.0 software package. RESULES: Subjective clinical variables demonstrated statistically significant improvements with both methods from the first day after treatment and lasted for at least 30 days(P<0.05), but the results of experimental group showed much better than the control group 1 day and 7 days after treatment. 30 days after treatment, there was no significant difference between the two groups in pain and swelling improvement(P>0.05), but the experimental group showed more improvement in edema and redness than the control group(P<0.05).On improving objective variables, the experimental group showed significant improvement in GI,BI,PD and suppuration 1 day after treatment(P<0.05).After 7 days, all objective clinical variables in the experimental group improved significantly(P<0.05) in the control group, there were significant improvements in GI,suppuration,lymphadenopathy and tooth mobility(P<0.05) but the four variables of the experimental group showed more improvement than the control group(P<0.05).After 30 days, all objective clinical variables improved significantly in both groups as compared to baseline, but in the experimental group, improvements were more significant regarding to GI,BI,PD,suppuration and tooth mobility(P<0.05). CONCLUSION: The method of supra- and subgingival scaling was rapid and effective in treatment of acute periodontal abscesses.

Cilostazol-based triple antiplatelet therapy compared to dual antiplatelet therapy in patients with coronary stent implantation: a meta-analysis of 5,821 patients.

BACKGROUND: Uncertainties still remain in terms of what kinds of patients benefit most from cilostazol-based triple antiplatelet therapy (TAT) after coronary stenting. METHODS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to investigate the effect of TAT versus dual antiplatelet therapy (DAT) in terms of major adverse cardiovascular events (MACEs) in patients undergoing coronary stenting. RESULTS: Fourteen RCTs with 5,821 patients were included in this study. TAT was associated with a significant reduction in the risk of MACEs compared to DAT [9.2 vs. 13.4%; odds ratio 0.59 (0.46, 0.76)] with consistent benefits among patients with diabetes, long lesions and small vessels. There were no significant between-group differences in the risk of cardiac death, myocardial infarction, stent thrombosis and bleeding events; however, the risk of target lesion revascularization was significantly lower in the TAT group. TAT resulted in borderline significant reduction in the risk of cardiovascular thrombotic events in unselected patients and significant decrease in patients with acute coronary syndrome [odds ratio 0.51 (0.27, 0.94)]. CONCLUSION: Under the treatment of standard DAT, the addition of cilostazol is an effective and relatively safe strategy in preventing MACEs after coronary stenting, especially for patients at high risk of restenosis or clinical events.

Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: a meta-analysis of 59,862 patients.

BACKGROUND: Angiotensin receptor blockers (ARBs) have been linked to reduced risk of new-onset diabetes, but the evidence was insufficient. OBJECTIVE AND METHODS: The aim of this study was to evaluate the effect of ARBs on the development of new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ARBs and new-onset diabetes were identified by electronic and manual searches. RESULTS: Eleven RCTs with 79,773 patients (59,862 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group [OR 0.79, (0.74, 0.84)] and various categories of ARBs subgroup. ARBs were associated with significant reduction in the risk of new-onset diabetes compared with placebo [OR 0.83, (0.78, 0.89)], beta-blocker [OR 0.73, (0.62, 0.87)], calcium channel blocker [OR 0.76, (0.68, 0.85)] and non-ARB [OR 0.57, (0.36, 0.91)]. ARBs were associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.74, (0.68, 0.81)], heart failure [OR 0.70, (0.50, 0.96)], impaired glucose tolerance [OR 0.85, (0.78, 0.92)] or cardiocerebrovascular diseases [OR 0.84, (0.72, 0.97)]. Compared with control group, incidence of new-onset diabetes was significantly reduced in ARBs group, irrespective of achieved blood pressure level. ARBs were associated with a lower incidence of new-onset diabetes in Western population [OR 0.81, (0.76, 0.85)] and Japanese population [OR 0.61, (0.48, 0.79)]. CONCLUSION: There is sufficient evidence that ARBs have beneficial effect in preventing new-onset type 2 diabetes. ARBs should be considered in patients with high risk of developing diabetes.

Effect of cilostazol on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials.

BACKGROUND: It has been well established that cilostazol has anti-proliferative effect against in-stent restenosis. However, it remains unclear whether cilostazol can prevent the progression of carotid atherosclerosis. METHODS AND RESULTS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of cilostazol on the progression of carotid intima-media thickness (IMT). Five RCTs with 698 patients [597 subjects with type 2 diabetes mellitus (T2DM)] were included in this study. Cilostazol was associated with a significant reduction in the progression of carotid IMT (WMD, -0.08mm, 95% CI -0.13, -0.04; P=0.00003). Subgroup analysis shows that cilostazol monotherapy or addition to dual antiplatelet therapy (aspirin and clopidogrel) was superior to placebo (WMD, -0.04mm, 95% CI -0.05, -0.03; P<0.00001), no antiplatelet medication (WMD, -0.12mm, 95% CI -0.21, -0.03; P=0.008), aspirin monotherapy (WMD, -0.06mm, 95% CI -0.12, 0.00; P=0.04) or dual antiplatelet therapy (WMD, -0.16mm, 95% CI -0.30, -0.02; P=0.03) in preventing the progression of carotid IMT. Cilostazol resulted in a significant decrease in total cholesterol (WMD -8.47mg/dl, 95% CI -14.18, -2.75; P=0.004) and LDL-C (WMD -8.25mg/dl, 95% CI -14.15, -2.36; P=0.006) and favorable trends in reducing triglyceride (WMD -15.83mg/dl, 95% CI -32.14, 0.48; P=0.06). CONCLUSION: It suggests that cilostazol may have beneficial effects in preventing the progression of carotid atherosclerosis and improving pro-atherogenic lipid profile, especially in patients with T2DM. Whether the anti-atherosclerotic effect of cilostazol is independent of improving pro-atherogenic dyslipidemia is worth further investigation.

Effect of alpha-glucosidase inhibitors on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials.

BACKGROUND: It remains unclear whether lowering postprandial glucose by alpha-glucosidase inhibitors (alpha-GIs) can prevent the progression of carotid intima-media thickness (IMT). METHODS AND RESULTS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to evaluate the effect of alpha-GIs on the progression of carotid IMT. Five RCTs with 411 patients were included in this study. Alpha-GIs therapy was associated with a significant reduction in the annual progression of carotid IMT (WMD, -0.06 mm/year, 95% CI -0.11, -0.01; P=0.02) and the progression in carotid IMT at the end of follow-up (WMD, -0.07 mm, 95% CI -0.12, -0.02; P=0.003). In subgroup analysis, alpha-GIs therapy was associated with a significant reduction in the annual progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM) (WMD, -0.08 mm/year, 95% CI -0.10, -0.06; P<0.00001), and in the progression of carotid IMT in patients with impaired glucose tolerance (IGT) at the end of follow-up (WMD, -0.03 mm, 95% CI -0.05, -0.01; P=0.01). Alpha-GIs treatment was associated with significant increase in HDL-C (WMD 1.56 mg/dl, 95% CI 0.09, 3.03; P=0.04) and decrease in basal immunoreactive insulin as well as had favorable trends towards reducing HbA1c, triglyceride and diastolic blood pressure. CONCLUSION: It suggests that alpha-GIs therapy may be an effective strategy in preventing the progression of carotid IMT in patients with IGT or T2DM. It partially contributes to the improvement in atherogenic metabolic parameters induced by alpha-GIs. More studies, especially large multi-centre RCTs, are still warranted to further clarify the anti-atherosclerotic effect of alpha-GIs.

Glucometabolic state in Chinese patients undergoing elective coronary angiography.

AIM: The aim of this study is to characterize the glucometabolic state of patients undergoing elective coronary angiography (CA) in a subpopulation in China. METHODS AND RESULTS: This study recruited 896 patients undergoing elective CA for the evaluation of suspected coronary artery disease (CAD). Oral glucose tolerance tests (OGTTs) performed in patients without previously known diabetes revealed that 173 (19.2%) had newly diagnosed diabetes and 281 (31.5%) had impaired glucose regulation. The prevalence of abnormal glucose metabolism (AGM) was significant difference among three groups of CA diagnosis, including normal coronary, nonsignificant stenosis and CAD. Overall, the proportion of patients with type 2 diabetes increased from 22.0% at baseline to 41.2% post-OGTT analysis. In total, 270 (59.5%) patients with AGM would have remained undetected if OGTTs had not been performed. Patients with CAD, hypertension, dyslipidemia, obesity and high C-reactive protein levels were at high risk of AGM. CONCLUSIONS: AGM is common and underestimated by FPG testing alone in patients undergoing elective CA. OGTTs should be routinely performed to assess the glucometabolic state of patients undergoing elective CA, especially in patients with high risks of AGM. Detecting the state of AGM in CA individuals may provide strategies to reduce the progression of AGM and associated complications.

Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials.

AIMS: To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) on diabetic peripheral neuropathy (DPN). METHODS: Randomized controlled trials (RCTs) comparing TENS with routine care, pharmacological interventions or placebo devices on patients with symptomatic DPN, were identified by electronic and manual searches. Studies were selected and available data were extracted independently by two investigators. Meta-analysis was performed by RevMan 4.2.8 software. RESULTS: Three RCTs involving 78 patients were included in this study. The reductions in mean pain score were significantly greater in TENS group than in placebo TENS group in 4 weeks and 6 weeks follow-up [4 weeks, SMD-5.37, 95% CI (-6.97, -3.77); 6 weeks, SMD-1.01, 95% CI (-2.01, -0.01)], but not in 12 weeks follow-up [SMD-1.65, 95% CI (-4.02, 0.73)]. TENS therapy was associated with significantly subjective improvement in overall neuropathic symptoms in 12 weeks follow-up [WMD-0.18, 95% CI (-0.32, -0.051)]. No TENS-related adverse events were registered in TENS group. CONCLUSIONS: TENS therapy may be an effective and safe strategy in treatment of symptomatic DPN. Due to small sample and short-term treatment duration, large multi-centre RCTs are needed to further evaluate the long-term effect of TENS on DPN.

Effect of thiazolidinediones on in-stent restenosis in patients after coronary stenting: a meta-analysis of randomized controlled trials.

BACKGROUND: Recent experimental studies have demonstrated that thiazolidinediones (TZDs) therapy inhibits proliferation and migration of vascular smooth muscle cells, accelerates endothelium reparation and attenuates neointimal hyperplasia. It implies that TZDs therapy may have beneficial effects on in-stent restenosis (ISR). Several small-sample clinical trials have evaluated the effect of TZDs therapy on ISR, however, the results were inconsistent across trials. METHODS AND RESULTS: We performed a meta-analysis of all relevant randomized controlled trials to evaluate the effect of TZDs therapy on in-stent restenosis in patients undergoing coronary stenting. Eight trials involving 366 patients were included in this study. TZDs therapy was associated with a significant reduction in the risk of ISR in both diabetic (RR 0.37, 95% CI 0.23-0.59; P<0.0001) and non-diabetic patients (RR 0.16, 95% CI 0.05-0.45; P=0.0006). TZDs therapy was associated with a significant reduction in late lumen loss (WMD -0.54 mm, 95% CI -0.87 mm, -0.22 mm; P=0.001), percent diameter stenosis (WMD -15.7%, 95% CI -19.4%, -12.0%; P<0.00001), neointimal area/volume (SMD -0.76, 95% CI -1.13, -0.39; P<0.0001) and target lesion revascularization (RR 0.32, 95% CI 0.18-0.57; P=0.0001). CONCLUSIONS: Our study suggests that TZDs therapy is an effective strategy in preventing ISR in both diabetic and non-diabetic patients undergoing coronary stenting. More studies, especially large multi-centre RCTs, are still warranted to further clarify the anti-restenotic effect of TZDs therapy.

Effect of peroxisome proliferator-activated receptor gamma ligand. Rosiglitazone on left ventricular remodeling in rats with myocardial infarction.

BACKGROUND: Recent studies have demonstrated that PPARgamma ligands have anti-inflammatory effect which is involved in ventricular remodeling. So we hypothesized that PPARgamma ligand may have beneficial effects on post-infarct ventricular remodeling. METHODS: Experimental myocardial infarction (MI) was induced in SD rats by ligation of the left coronary artery. Twenty-four hours after surgery, survival rats were randomly divided into MI group and Rosiglitazone (MI+Ros) group which would take rosiglitazone 3 mg/kg day for 8 weeks. After 8 weeks treatment, left ventricular hemodynamics were measured and organs were weighed. Myocardial collagen analysis was determined in Van Gieson staining by quantitative morphometry. Myocardial angiotensin II and aldosterone were detected by radioimmunoassay. Myocardial AT1 and AT2 mRNA expression were determined by RT-PCR. RESULTS: Only 1 rat in MI group died of anesthesia at the 8th week. Rosiglitazone treatment could improve left ventricular +/-dp/dt(max), collagen volume fraction and perivascular circumferential area; reduce lung/body mass ratio and liver/body mass ratio; inhibit myocardial angiotensin II and aldosterone; and had no significant effects on myocardial AT1 and AT2 mRNA. Plasma insulin and blood glucose were comparable between two groups. CONCLUSIONS: PPARgamma ligand has neutral effect on mortality and beneficial effect on post-infarct ventricular remodeling, partly by suppressing myocardial angiotensin II and aldosterone, irrespective of plasma insulin and blood glucose level.

Clinical study of amiodarone-associated torsade de pointes in Chinese people.

OBJECTS: Amiodarone-associated torsade de pointes (Tdp) has been reported increasingly in China in recent years. In this study, we made clinical analysis of amiodarone-associated Tdp in Chinese people. METHODS: Two major Chinese medical databases were searched to identify articles published during the last 26 years that presented data on amiodarone-associated proarrhythmic events. The articles were divided into two categories: case reports and observational studies. RESULTS: Fifty-two Chinese-language case reports with 98 patients and 2 patients registered in our hospital, total 100 patients about amiodarone-associated Tdp, were enrolled in the study. Amiodarone-associated Tdp occurred more frequently in females (68.0%, 68/100). The major primary disease of females was rheumatic heart disease (40.7%, 24/59), while that of males was coronary heart disease (45.8%, 11/24). In most patients, Tdp occurred repeatedly and terminated in 24-48 hours. Some Tdp worsen to ventricular fibrillation and caused 19 patients' death (mortality rate 21.8%, 19/87). Known predisposing factors to the development of Tdp, such as heart failure, hypokalemia, drugs combination, and bradyarrhythmia, existed in many cases. Tdp also occurred in six patients (4 females, 2 males) without any known predisposing factors except QTc interval prolongation. Fourteen observational studies each reported data from at least 100 patients who were treated with amiodarone for at least 1 month. Of 2,354 patients included in these studies, 455 patients exposed to amiodarone were reported to have proarrhythmic events (an overall incidence of 19.3%), while only 4 patients were reported to have Tdp or ventricular fibrillation (an incidence of 0.17%). CONCLUSIONS: In conclusion, approximately one-fifth of the patients have amiodarone-induced proarrhythmic events, while the incidence of Tdp or ventricular fibrillation is remarkably low. Amiodarone-associated Tdp occurred more frequently in Chinese females. Known predisposing factors for occurrence of Tdp prevailed in Chinese patients. QTc interval prolongation may be an independent risk factor of amiodarone-associated Tdp.

[Effects of IGF-I and BMP-2 combined application on promoting proliferation, differentiation and calcification of MC 3T3-E1 and NIH 3T3 cells].

OBJECTIVE: To demonstrate the effects of recombinant human insulin-like growth factor-I (rhIGF-I) and/or recombinant human bone morphogenetic protein-2 (rhBMP-2) on proliferation, differentiation and calcification of MC 3T3-E1 cells and NIH 3T3 cells. METHODS: Mouse osteoblast-like cell line MC 3T3-E1 and mouse fibroblast cell line NIH 3T3 were treated with different dosages of rhIGF-I or rhBMP-2 and rhIGF-I plus rhBMP-2. Cell proliferation was measured by methylthiazol tetrazolium (MTT)method and flow cytometry. Cell differentiation was examined by using alkaline phosphatase(ALP)measurement kit. Radioimmunoassay was applied to detect levels of osteocalcin (OC) secreted by cultured cells. Von kossa staining method was used to study the calcification effects. RESULTS: MC 3T3-E1 cells treated with 1-50 ng/ml rhIGF-I and NIH 3T3 cells treated with 5-75 ng/ml rhIGF-I showed marked effects of promoting proliferation (P<0.01), increasing the percentages of S-phase cells, decreasing the percentages of G1-phase cells and increasing activities of cellular ALP and percentages of calcification area (P<0.05). 10-100 ng/ml rhBMP-2 was also able to promote proliferation (P<0.01), increase the percentages of S-phase cells, decrease the percentages of G1-phase cells and enhancing cellular ALP activities and percentages of calcification area for both the two cells (P>0.05). CONCLUSION: rhIGF-I and rhBMP-2 have synergistical effects on promoting cell proliferation, early cell differentiation and calcification depending on the used dosages, but no significant effects on promoting advanced cell differentiation.