Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells.

The progressive death of mature neurons often results in neurodegenerative diseases. While the previous studies have mostly focused on identifying intrinsic mechanisms controlling neuronal survival, the extracellular environment also plays a critical role in regulating cell viability. Here we explore how intercellular communication contributes to the survival of retinal ganglion cells (RGCs) following the optic nerve crush (ONC). Although the direct effect of the ONC is restricted to the RGCs, we observed transcriptomic responses in other retinal cells to the injury based on the single-cell RNA-seq, with astrocytes and Müller glia having the most interactions with RGCs. By comparing the RGC subclasses showing distinct resilience to ONC-induced cell death, we found that the high-survival RGCs tend to have more ligand-receptor interactions with other retinal cells, suggesting that these RGCs are intrinsically programmed to foster more communication with their surroundings. Furthermore, we identified top 47 interactions that are stronger in the high-survival RGCs, likely representing neuroprotective interactions. We performed functional assays on one of the receptors, µ opioid receptor (Oprm1), a receptor known to play roles in regulating pain, reward, and addictive behavior. Although Oprm1 is preferentially expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), its neuroprotective effect could be transferred to multiple RGC subclasses by specific overexpressing Oprm1 in pan-RGCs in ONC, excitotoxicity, and glaucoma models. Lastly, manipulating Oprm1 activity improved visual functions and altered pupillary light response in mice. Our study provides an atlas of cell-cell interactions in both intact and post-ONC retina and an effective strategy to predict molecular mechanisms in neuroprotection, underlying the principal role played by extracellular environment in supporting neuron survival.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

The efficacy of the figure-of-eight suture technique in the treatment of tunnel bleeding of the femoral artery route after percutaneous coronary intervention or angiography.

OBJECTIVE: To evaluate the efficacy of the figure-of-eight (FOE) suture technique in the treatment of tunnel bleeding after femoral artery puncture compared with manual compression (MC). METHODS: This prospective, randomized, controlled study enrolled patients that had received transfemoral coronary artery angiography or percutaneous coronary intervention and then developed tunnel bleeding. They were randomly assigned into two groups: FOE suture group (ES group) and manual compression group (MC group). Total treatment time, performance frequency, performance time, rate of deep vein thrombosis (DVT) and in-hospital time after the procedure were compared. RESULTS: A total of 152 patients were enrolled in the study (ES group, n = 63; MC group, n = 89). Compared with the MC group, the total treatment time (mean ± SD: ES 22.3 ± 5.4 h versus MC 26.8 ± 6.8 h), performance frequency (mean ± SD: ES 2.1 ± 0.7 versus MC 2.6 ± 1.1), performance time (mean ± SD: ES 8.9 ± 2.5 min versus MC 12.3 ± 4.1 min), in-hospital time after the procedure (mean ± SD: ES 3.5 ± 1.2 days versus MC 4.8 ± 2.1 days) and DVT rate (ES 0.0% versus MC 6.7%) were significantly lower in the ES group. CONCLUSION: The FOE suture technique effectively treated tunnel bleeding after femoral artery puncture.

Management of acute perioperative myocardial infarction: a case report of concomitant acute myocardial infarction and tumor bleeding in the transverse colon.

Acute myocardial infarction complicated by bleeding colon tumor is problematic with regard to management, and appropriate balance of antiplatelet or anticoagulation therapy and hemostasis or surgery is crucial for effective treatment. Here, we present a case of concomitant acute myocardial infarction and bleeding tumor in the transverse colon, and share our experience of successfully balancing anticoagulation therapy and hemostasis.

The difference between Asian and Western in the effect of LDL-C lowering therapy on coronary atherosclerotic plaque: a meta-analysis report.

BACKGROUND: The different effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque between Western and Asian remain to be settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Sep. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. RESULTS: Twenty trials (ten in the West and ten in Asia) were identified. For Westerns, Mean lowering LDL-C by 49.4% and/or to level 61.9 mg/dL in the group of patients with baseline mean LDL-C 123.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.156 mm(3), 95% CI -0.248 ~ -0.064, p = 0.001). LDL-C lowering by rosuvastatin (mean 40 mg daily) could significantly decrease the volumes of CAP at follow up. For Asians, Mean lowering LDL-C by 36.1% and/or to level 84.0 mg/dL with baseline mean LDL-C 134.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.211 mm(3), 95% CI -0.331 ~ -0.092, p = 0.001). LDL-C lowering by rosuvastatin (mean 14.1 mg daily) and atorvastatin (mean 18.9 mg daily) could significantly decrease the volumes of CAP at follow up. CONCLUSIONS: There was a different effect of LDL-C lowering on CAP between Westerns and Asians. For regressing CAP, Asians need lower dosage of statins or lower intensity LDL-C lowering therapy than Westerns.

Percutaneous coronary intervention in the elderly with ST-segment elevation myocardial infarction.

As a result of increased life expectancy, octogenarians constitute an increasing proportion of patients admitted to hospital for ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention is currently the treatment of choice for octogenarians presenting with STEMI. The recent literature on this topic has yielded controversial results, even though advances in drug-eluting stents and new types of antithrombotic agents are improving the management of STEMI and postoperative care. In this paper, we review the current status of percutaneous coronary intervention in the elderly with STEMI, including the reasons for their high mortality and morbidity, predictors of mortality, and strategies to improve outcomes.

Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound.

BACKGROUND: Conflicting results currently exist on the effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque, and the target level of LDL-C resulting in the regression of the coronary atherosclerotic plaques has not been settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Jan. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. Data concerning the study design, patient characteristics, and outcomes were extracted. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. SMD were calculated using fixed or random effects models. RESULTS: Twenty trials including 5910 patients with coronary heart disease were identified. Mean lowering LDL-C by 45.4% and to level 66.8 mg/dL in the group of patients with baseline mean LDL-C 123.7 mg/dL, mean lowering LDL-C by 48.8% and to level 60.6 mg/dL in the group of patients with baseline mean LDL-C 120 mg/dL, and mean lowering LDL-C by 40.4% and to level 77.8 mg/dL in the group of patients with baseline mean LDL-C 132.4 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.108 mm3, 95% CI -0.176 ~ -0.040, p = 0.002; SMD -0.156 mm3, 95% CI -0.235 ~ -0.078, p = 0.000; SMD -0.123 mm3, 95% CI -0.199 ~ -0.048, p = 0.001; respectively). LDL-C lowering by rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could significantly decrease the volumes of CAP at follow up (SMD -0.162 mm3, 95% CI: -0.234 ~ -0.081, p = 0.000; SMD -0.101, 95% CI: -0.184 ~ -0.019, p = 0.016; respectively). The mean duration of follow up was from 17 ~ 21 months. CONCLUSIONS: Intensive lowering LDL-C (rosuvastatin mean 33 mg daily and atorvastatin mean 60 mg daily) with >17 months of duration could lead to the regression of CAP, LDL-C level should be reduced by >40% or to a target level <78 mg/dL for regressing CAP.

Bosentan ameliorates the expression of fibrotic related growth factors and collagen-1 in diabetic mice.

OBJECTIVE: To investigate the potential beneficial effect of bosentan in ameliorating fibrotic agents in diabetic mice. METHODS: Male 6-week old C57BL/6 mice were divided into 3 groups (N=20): Control group, diabetes mellitus (DM) group and DM-B group (diabetes with bosentan group). Streptozotocin (STZ) was injected as 200 mg/Kg for single dose, i.p. (intraperitoneal injection). Fasting blood glucose (FBG) was measured at 0-, 1-, 2-week after STZ injection to confirm that diabetes was induced in the mice. Bosentan (100mg/Kg) and placebo was given i.g. (intragastric administration) once a day immediately after STZ injection for 18 weeks. The mRNA expression of tissue growth factor beta (TGF-b), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and collagen-1 were evaluated by RT-PCR and real-time PCR. Differences in the data between the groups were compared by Student t-test for independent samples. RESULTS: After 18 weeks of diabetic situation, FBG of DM-B mice was significantly higher than that of control mice and was similar with that of DM mice (DM mice vs. control mice, p<0.001; DM-B vs. control mice, p<0.001; DM mice vs. DM-B mice, p>0.05). The cardiac VEGF mRNA (a potent angiogenic factor) level in DM-B mice was significantly higher than DM mice (p<0.01). The heart of DM-B mice also showed lower expression of fibrotic genes (TGF-b, CTGF and collagen-1) than DM mice (p<0.01). CONCLUSION: These findings indicate the potential usefulness of an ET receptor antagonist bosentan in the amelioration of fibrotic agents, which may promote tissue fibrosis. This may provide a promising therapeutical strategy for diabetic cardiac fibrosis.

Progressive deterioration of left ventricular function in a patient with a normal coronary angiogram.

Cardiac ischemia with a normal coronary angiogram can be caused by coronary microvascular dysfunction. A favorable prognosis, with excellent long-term clinical outcome, without major acute coronary events, has been consistently reported in these patients. We report a patient with a normal coronary angiogram and 3 episodes of myocardial infarctions, where the formation of a ventricular aneurysm and progressive deterioration of left ventricular function was documented, and hypoperfusion of the myocardium was confirmed by cardiovascular magnetic resonance imaging. This case suggests that myocardial ischemia caused by coronary microvascular dysfunction could have a poor prognosis. Whether this case represents a special clinical condition which is between the cardiac syndrome X and coronary artery disease remains to be investigated.

Effect of haemoglobin concentration on the clinical outcomes in patients with acute myocardial infarction and the factors related to haemoglobin.

BACKGROUND: The impact of haemoglobin concentrations on clinical outcomes is still a controversial issue. To determine the association between haemoglobin concentrations on admission and clinical outcomes and the related factors, this study was performed in a Chinese hospital. FINDINGS: We conducted a retrospective study on 1394 Chinese patients with acute myocardial infarction. Patients were categorized according to the haemoglobin concentration on admission, and data were evaluated to determine whether there was an association between the haemoglobin concentrations on admission and 30-day in-hospital MACEs (major cardiovascular events). Patients with hemoglobin values between 141 and 150 g/L were used as the reference, the MACEs increased as hemoglobin concentrations fell below 140 g/L or rose > 150 g/L, with an adjusted OR (odds ratio) of 5.96[95% CI (confidence interval) 2.00 to 17.68, p = 0.0013], 4.39(1.37 to 14.08, p = 0.0128), 3.99(1.46 to 10.92, p = 0.0071), 3.19(1.27 to 8.05, p = 0.0139), 2.37(0.94 to 6.01, p = 0.0687), 2.11(0.66 to 6.74, p = 0.2065), 2.01(0.60 to 6.68, p = 0.2559) in patients with haemoglobin concentrations <100 g/L, 101-110 g/L, 111-120 g/L, 121-130 g/L, 131-140 g/L, 151-160 g/L, and >160 g/L respectively. Partial correlation analysis showed that age, albumin and creatinine were significantly associated with hemoglobin concentration. CONCLUSIONS: Our results demonstrated that haemoglobin concentration affected MACEs in patients with acute myocardial infarction, and that haemoglobin concentration was associated with age, albumin and creatinine.

Endothelin-1 receptor blockade induces upregulation of renin-angiotensin-aldosterone system expression in terms of blood pressure regulation.

OBJECTIVE: To compare the level of expression of the renin-angiotensin-aldosterone system (RAAS) in mice with or without the endothelin-1 receptor antagonist bosentan and to examine the potential value in blood pressure regulation. MATERIALS AND METHODS: Bosentan (10 mg/kg/d) and placebo were given to two groups of male C57BL/6 mice (n=5) from ages 6 to 12 weeks. The mRNAs of liver, kidney and lung were isolated for Northern blot analysis. A further 15 male C57BL/6 mice were divided into three groups (n=5): mice in group A were given the angiotensin II type 1 receptor blocker valsartan (10 mg/kg/d); mice in group B were given bosentan (10 mg/kg/d); and mice in group C were given both valsartan and bosentan (10 mg/ kg/d for each drug). All mice were administered the drugs from 6 to 12 weeks of age and had their systolic blood pressure (SBP) measured at the end of the drug treatments. RESULTS: Northern blot analysis demonstrated that the expression levels of angiotensinogen in liver (p=0.0126), renin in kidney (p=0.002), and angiotensin-converting enzyme in lung (p=0.0041) were upregulated in mice treated with bosentan. No difference in SBP was found among the groups before drug administration. Six weeks after monotherapy with valsartan, SBP was slightly lowered (126+/-2 vs. 122+/-3 mmHg, p=0.0381). Monotherapy with bosentan also had a small effect on SBP (126+/-2 vs. 122+/-3 mmHg, p=0.0381), whereas dual blockade with valsartan and bosentan significantly lowered SBP (127+/-3 vs. 103+/-3 mmHg, p<0.001). CONCLUSIONS: We conclude that RAAS components are upregulated under endothelin blockade. Dual blockade of the RAAS and endothelin system is beneficial for blood pressure control.

A sewing needle in liver: a case report and review of the literature.

INTRODUCTION: Hepatic foreign bodies are quite rare. A sewing needle as a hepatic foreign body in an old woman is very rare and the managements have been varied. CASE PRESENTATION: An old woman was incidentally found to have a sewing needle in her liver on abdominal X-ray. The sewing needle was kept stable in her liver after two years of follow-up. Eleven cases of sewing needle in the liver were reviewed. CONCLUSION: Sewing needle as a foreign body in the liver is rare. In general, the sewing needle should be removed through laparotomy or laparoscopy, but a stable and uncomplicated sewing needle in the liver need not be removed.

Pyrogen reaction and conversion of sustained ventricular tachycardia to sinus rhythm: two case reports.

INTRODUCTION: Pyrogen reaction is a side effect of intravenous infusion of solution on body; sustained ventricular tachycardia is a serious arrhythmia, no relationship between them has been reported before. CASE PRESENTATION: Two patients with sustained ventricular tachycardia refractory to lidocaine happened to have pyrogen reaction. The sustained ventricular tachycardia was converted to sinus rhythm after the pyrogen reaction. CONCLUSION: The conversion of sustained ventricular tachycardia might be related to pyrogen reaction. The effects of pyrogen reaction on sustained ventricular tachycardia need further research.

The role of Fas in the progression of ischemic heart failure: prohypertrophy or proapoptosis.

During myocardial ischemia, cardiomyocytes can undergo apoptosis or compensatory hypertrophy. Fas expression is upregulated in the myocardial ischemia and is coupled to both apoptosis and hypertrophy of cardiomyocytes. The role of Fas in apoptosis induction or cardiomyocyte hypertrophy during ischemic conditions is, however, still unclear. Some reports suggested that Fas might induce myocardial hypertrophy. Apoptosis of ischemic cardiomyocytes and Fas expression in the nonischemic cardiomyocytes occurs during the early stage of ischemic heart failure. Hypertrophic cardiomyocytes easily undergo apoptosis in response to ischemia, after which apoptotic cardiomyocytes are replaced by fibrous tissue. In the late stage of ischemic heart failure, hypertrophy, apoptosis, and fibrosis are thought to accelerate each other and might thus form a vicious circle that eventually results in heart failure. In this review, we summarize recent advances in the understanding of the role of Fas in remodeling ischemic myocardial tissues.

Subacute stent thrombosis happening at discharge.

We present the two cases of men who were admitted to our hospital with effort angina and three vessels lesions. The symptoms were alleviated after three sirolimus-eluting stents implantation. But on the scheduled discharge day when the patients were on therapy of clopidogrel, in combination with aspirin or anticogulation, subacute stent thrombosis (SST) happened and led to patients' death.

[Relationship between the expression of Fas, bcl-2 and apoptosis of cardiomyocytes in experimental myocardial ischemia in rats].

OBJECTIVE: To explore the relationship between expression of Fas, bcl-2 and apoptosis of cardiomyocytes in myocardial ischemia in rats. METHODS: Myocardial ischemia was experimentally induced by ligating the left coronary artery. The rate were killed from 10 minutes to 7 days after the operation. Apoptotic myocardial cells were detected by TUNEL method. The expression of Fas and bcl-2 was studied by ABC immunohistochemistry. RESULTS: Cardiomyocytic apoptosis appeared from 3 to 36 hours after ischemia. This phenomenon however could not be detected by TUNEL method 7 days after ischemia. The expression of Fas could be detected by ABC immunohistochemistry from 3 hours to 7 days after ischemia, and the expression of bcl-2 from 10 minutes to 7 days. Cardiomyocytic apoptosis and Fas / bcl-2 expression appeared in different regions of myocardium: apoptosis in the ischemic regions, while Fas and bcl-2 expression in regions without obvious ischemia. CONCLUSION: In rats, Fas and bcl-2 may not directly regulate apoptosis of cardiomyocytes in case of myocardial ischemia.

[Effects of Ca2+ antagonist on cardiomyocytic apoptosis after experimental myocardial infarction].

OBJECTIVE: To explore the effects of Ca(2+) antagonist on apoptosis of cardiomyocytes after myocardial ischemia. METHODS: The model of myocardial infarction was made by ligating left coronary artery in SD rats. In experimental group, the rats were administrated with Adalat through oral cavity (1 mg/kg) before operation and through peritoneal cavity (0.4 mg/kg 3 hours after operation. In ischemic control group the rats were injected with placebo and in normal control group the rats were treated with sham operation (no ligating left coronary artery) and placebo. The rats were killed 6 hours after operation, with their left ventricular function had been measured. Apoptotic myocardial cells were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) method, Fas and Bcl-2 proteins by the ABC immunohistochemistry method. Apoptosis indexes were calculated under high magnification field of microscopy. RESULTS: The systolic pressure, end-diastolic pressure and dp/dt of left ventricle in experiment group were not significant different from those in the ischemic control group, they were 76.7+/-7.5/8.0+/-6.1 mm Hg vs. 74.9+/-11.1/11.6+/-8.3 mm Hg (P>0.05) and (777.3+/-128.6)mm Hg/s vs. (761.8+/-136.4)mm Hg/s (P>0.05) respectively; but those in both the experimental group and the ischemic control group were lower than those in the normal control group, they were 94.9+/-7.5/2.8+/-3.2 mm Hg (P<0.001) and (1131.5+/-112.8)mm Hg/s(P<0.001). There were a lot of positive myocytes with TUNEL stain in the ischemic region of left ventricle in both the experimental and the ischemic control group, apoptosis index in the experimental group was lower than that in the ischemic control group (0.201+/-0.053 vs. 0.261+/-0.045, P<0.05). The positive myocytes of Fas and Bcl-2 protein appeared in the region surrounding ischemic myocytes. There were no positive myocytes with the three types of stain in normal control group. CONCLUSION: Ischemia could induce apoptosis of myocytes and expression of Fas and Bcl-2 gene; Ca(2+) antagonist could protect myocytes from apoptosis.