Large-scale separation of alkaloids from Corydalis decumbens by pH-zone-refining centrifugal partition chromatography and their anticomplement activity.

Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids from the crude extract of Corydalis decumbens. The experiment was performed with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (5:5:3:7, v/v/v/v) where triethylamine (10 mM) was added to the stationary phase and hydrochloric acid (10 mM) to the mobile phase. From 1.6 g of the crude extract, 43 mg protopine, 189 mg (+)-egenine, and 158 mg tetrahydropalmatine were obtained with a purity of 98.2%, 94.6%, and 96.7%, respectively. Tetrahydropalmatine showed an interesting anticomplement effect with CH50 0.11 and AP50 0.25 mg/mL, respectively. In a mechanistic study, tetrahydropalmatine interacted with C1, C3, C4, and C5 components in the complement activation cascade.

Effect of Thin-Walled Radial Sheath for Large-Bore Access On Reducing Periprocedural Radial Artery Occlusion Following Complex PCI: The REDUCE-RAO Randomized Trial.

Background: Transradial artery (TRA) access for percutaneous coronary intervention (PCI) was associated with lower risks of major bleeding and vascular complications compared to transfemoral artery access. Use of large-bore ( ≥ 7-Fr) guiding catheters through TRA approach increased the likelihood of radial artery occlusion (RAO). This study aimed to investigate whether use of the thin-walled 7-Fr Glidesheath Slender, allowing PCI with large-caliber guiding catheters, is superior to standard 7-Fr Cordis sheath with respect to periprocedural RAO within 24 hours after transradial coronary intervention (TRI) in complex lesions. Methods: A prospective randomized, controlled, single-blinded (patient-blinded) trial was conducted, randomizing 504 patients with TRI for complex lesions to either 7-Fr Glidesheath Slender or conventional 7-Fr Cordis sheath. The primary outcome was defined as the incidence of periprocedural RAO with Doppler ultrasound during the first 24 hours after TRI. Results: The incidence of early RAO was 10.3% for 7-Fr Glidesheath Slender and 13.5% for conventional 7-Fr sheath (p = 0.271). The procedural success rate for Glidesheath Slender was 92.9% and for Cordis sheath was 93.7% (p = 0.722). There was no signficiant difference between treatment arms in terms of local hematoma and radial spasm, whereas use of the Glidesheath Slender was associated with significantly less pain during the procedure (numeric rating scale [NRS], 2.27 ± 0.75 vs. 2.45 ± 0.95, p = 0.017). The assessment of radial artery in ultrasound parameters after complex TRI was improved with Glidesheath Slender. Conclusions: Among patients with complex coronary lesions undergoing TRI, 7-Fr Glidesheath Slender was not superior to conventional 7-Fr in the prevention of periprocedural RAO within 24 hours following complex PCI, without reducing RAO occurrence. Clinical Trial Registration: NCT04748068.

Early radial artery occlusion following the use of a transradial 7-French sheath for complex coronary interventions in Chinese patients.

OBJECTIVES: We aimed to explore the impact of 7-Fr sheaths on the incidence of early radial artery occlusion (RAO) after transradial coronary intervention (TRI) in Chinese patients. BACKGROUND: RAO precludes future use of the vessel for vascular access. Transradial catheterization is usually performed via 5-Fr or 6-Fr catheters; 7-Fr sheath insertion enables complex coronary interventions but may increase the RAO risk. METHODS: We prospectively enrolled 130 consecutive patients undergoing complex TRI using 7-Fr sheaths. Radial artery ultrasound assessment was performed before and after TRI. Early RAO was defined as the absence of flow on ultrasound within 6-24 hr after TRI. Multivariate logistic regression was used to determine the factors related to early RAO after TRI. RESULTS: 7-Fr sheaths were mainly used for chronic total occlusion (44.6%), bifurcation (30.0%), and tortuous calcification (25.4%) lesions. All patients were successfully sheathed. Percutaneous coronary intervention (PCI) procedural success was 96.2%; 119 patients (91.5%) had preserved radial artery patency after TRI. All 11 RAO cases (8.5%) were asymptomatic. The radial artery diameter was significantly larger postoperatively (3.1 ± 0.4 mm) than preoperatively (2.6 ± 0.5 mm) (p < .001). No parameters significantly differed between patients with and without RAO. TRI history was the only independent risk factor of early RAO (odds ratio: 6.047, 95% confidence interval: 1.100-33.253, p = .039). CONCLUSIONS: 7-Fr sheath use after transradial access for complex PCI is feasible and safe. Evaluating the radial artery within 24 hr after TRI allows timely RAO recognition, important for taking measures to maintain radial artery patency and preserve access for future TRIs.

Anticomplement monoterpenoid glucosides from the root bark of Paeonia suffruticosa.

Six new (1-6) and 19 known monoterpenoid glucosides were isolated from the root bark of Paeonia suffruticosa. The monoterpenoid glucosides 1, 2, 7, 10-19, and 22 exhibited anticomplement effects with CH50 and AP50 values ranging from 0.14 to 2.67 mM and 0.25 to 3.67 mM, respectively. In a mechanistic study, suffrupaeoniflorin A (1) interacted with C1q, C3, C5, and C9, while galloylpaeoniflorin (12) and galloyloxypaeoniflorin (19) acted on C1q, C3, and C5 components in the complement activation cascade.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

Triglyceride glucose index predicts in-hospital mortality in patients with ST-segment elevation myocardial infarction who underwent primary angiography.

OBJECTIVES: To assess the correlation between triglyceride glucose (TyG) index and in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 2190 patients with STEMI who underwent primary angiography within 12 h from symptom onset were selected from the prospective, nationwide, multicenter CAMI registry. TyG index was calculated with the formula: Ln [fasting triglycerides (mmol/L) × fasting glucose (mmol/L)/2]. Patients were divided into three groups according to the tertiles of TyG index. The primary endpoint was in-hospital mortality. RESULTS: Overall, 46 patients died during hospitalization, in-hospital mortality was 1.5%, 2.2%, 2.6% for tertile 1, tertile 2, and tertile 3, respectively. However, TyG index was not significantly correlated with in-hospital mortality in single-variable logistic regression analysis. Nonetheless, after adjusting for age and sex, TyG index was significantly associated with higher mortality when regarded as a continuous variable (adjusted OR = 1.75, 95% CI: 1.16-2.63) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 2.50, 95% CI: 1.14-5.49). Furthermore, TyG index, either as a continuous variable (adjusted OR = 2.54, 95% CI: 1.42-4.54) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 3.57, 95% CI: 1.24-10.29), was an independent predictor of in-hospital mortality after adjusting for multiple confounders in multivariable logistic regression analysis. In subgroup analysis, the prognostic effect of high TyG index was more significant in patients with body mass index < 18.5 kg/m2 (P interaction = 0.006). CONCLUSIONS: This study showed that TyG index was positively correlated with in-hospital mortality in STEMI patients who underwent primary angiography, especially in underweight patients.

[Clinical experience of supplying sodium chloride for the treatment of patients with severe heart failure].

OBJECTIVE: To observe the effect and safety of supplying sodium chloride in the treatment of patients with severe heart failure. METHODS: Consecutive 51 hospitalized patients with severe heart failure and cardiac edema were included in this study. Normal diet (6 g NaCl/d) was supplied to all patients. On the basis of controlling fluid intake and treating related etiological factors as well as standard medications including furosemide for severe heart failure, patients with mild hyponatremia (serum sodium level 130 - 134 mmol/L) ate additional salted vegetables, patients with moderate hyponatremia (serum sodium level 125 - 129 mmol/L) and severe hyponatremia (serum sodium level < 125 mmol/L) ate additional salted vegetables and were received additionally intravenous 3%NaCl hypertonic saline infusion (10 ml/h) until reaching normal serum sodium level. RESULTS: On admission, 37.25% (19/51) patients had hyponatremia. During the first two weeks hospitalization period, 88.24% (45/51) patients were treated with intravenous diuretics and total incidence of hyponatremia was 64.71% (33/51), mild hyponatremia was 50.98% (26/51), middle and severe hyponatremia was 13.73% (7/51); among them, hyponatremia lasted less than 3 d in 57.58% (19/33) patients and ≥ 3 d in 42.42% (14/33) patients. Heart failure exacerbation and hypernatremia were not observed in patients receiving additional sodium chloride therapy. Hospitalization time was similar among patients with different blood natrium levels [average (16 ± 12) d]. Fifty out of 51 (98%) patients discharged from the hospital with improved heart failure symptoms and signs. CONCLUSION: Supplying additional sodium chloride could rapid correct hyponatremia in heart failure patients with or without intravenous diuretics therapy which might contribute to a favorable prognosis in hospitalized heart failure patients.

Benefits and Risks of Prolonged Duration Dual Antiplatelet Therapy (Clopidogrel and Aspirin) After Percutaneous Coronary Intervention in High-Risk Patients With Diabetes Mellitus.

The efficacy and safety of prolonged (>1-year) dual antiplatelet therapy (DAPT) duration in high-risk patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) remain unknown. All patients undergoing PCI at Fuwai hospital between January 2013 and December 2013 were prospectively enrolled into the Fuwai PCI registry. A total of 3,696 high-risk diabetics patients with at least one additional atherothrombotic risk factor were screened for inclusion. The primary efficacy outcome was the composite of all-cause mortality, myocardial infarction, or stroke. The median follow-up duration was 887 days. 69.8% of DM patients were on DAPT at 1 year without discontinuation. Based on multivariate Cox regression model and inverse probability of treatment weighting (IPTW) analysis, long-term (>1-year) DAPT reduced the risk of primary efficacy outcome (1.7% vs 4.1%; adjusted hazard ratio [adjHR]: 0.382, 95% confidence interval [CI]: 0.252 to 0.577; IPTW-HR: 0.362 [0.241 to 0.542]), as well as cardiovascular death and definite/probable stent thrombosis, compared with short-course (≤1-year) DAPT. Risk of the safety end point of clinically relevant bleeding (adjHR: 0.920 [0.467 to 1.816]; IPTW-HR: 0.969 [0.486 to 1.932]) was comparable between longer DAPT and shorter DAPT. A lower number of net clinical benefit adverse outcomes was observed with >1-year DAPT versus ≤1-year DAPT (adjHR: 0.471 [0.331 to 0.671]; IPTW-HR: 0.462 [0.327 to 0.652]), which appeared increasingly favorable in those with multiple atherothrombotic risk characteristics. In high-risk patients with DM receiving PCI who were event free at 1 year, DAPT prolongation resulted in significant reduction in the risk of ischemic events not offset by increase of clinically meaningful bleeding events, thereby achieving a net clinical benefit. Extending DAPT beyond the period mandated by guidelines seems reasonable in high-risk DM patients not deemed at high bleeding risk.

Optimal Strategy for Antiplatelet Therapy After Coronary Drug-Eluting Stent Implantation in High-Risk "TWILIGHT-like" Patients With Diabetes Mellitus.

Background: Patients with diabetes mellitus (DM) are known to be at high-risk for both ischemic and bleeding complications post-percutaneous coronary intervention (PCI). The ischemic benefit vs. bleeding risk associated with extended dual antiplatelet therapy (DAPT) in high-risk "TWILIGHT-like" patients with diabetes mellitus after PCI has not been established. Methods: All consecutive high-risk patients fulfilling the "TWILIGHT-like" criteria undergoing PCI from January 2013 through December 2013 were identified from the prospective Fuwai PCI Registry. High-risk "TWILIGHT-like" patients were defined by at least one clinical and one angiographic feature based on the TWILIGHT trial selection criteria. The present analysis evaluated 3,425 diabetic patients with concomitant high-risk angiographic features who were event-free at 1 year after PCI. Median follow-up was 2.4 years. The primary effectiveness endpoint was a composite of death, myocardial infarction, or stroke (termed major adverse cardiac and cerebrovascular events), and primary safety endpoint was clinically relevant bleeding according to the Bleeding Academic Research Consortium types 2, 3, or 5. Results: On inverse probability of treatment weighting (IPTW) analysis, prolonged-term (>1-year) DAPT with aspirin and clopidogrel decreased the risk of primary effectiveness endpoint compared with shorter ( ≤ 1-year) DAPT [1.8 vs. 4.3%; hazard ratio (HR)IPTW: 0.381; 95% confidence interval (CI): 0.252-0.576; P < 0.001] and reduced cardiovascular death [0.1% vs. 1.8%; HRIPTW: 0.056 (0.016-0.193)]. Prolonged DAPT was also associated with a reduced risk of definite/probable stent thrombosis [0.2 vs. 0.7%; HRIPTW: 0.258 (0.083-0.802)] and non-significantly lower rate of myocardial infarction [0.5 vs. 0.8%; HRIPTW: 0.676 (0.275-1.661)]. There was no significant difference between groups in clinically relevant bleeding [1.1 vs. 1.1%; HRIPTW: 1.078 (0.519-2.241); P = 0.840). Similar results were observed in multivariable Cox proportional hazards regression model. Conclusion: Among high-risk PCI patients with diabetes mellitus without an adverse event through 1 year, extending DAPT >1-year significantly reduced the risk of major adverse cardiac and cerebrovascular events without an increase in clinically relevant bleeding, suggesting that such high-risk diabetic patients may be good candidates for long-term DAPT.

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis.

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models.

Transforming growth factor beta-1 (TGFß1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease. We performed RNA-sequencing of TGFß1-stimulated human aortic or arterial VSMCs which revealed large and consistent upregulation of Interleukin 11 (IL11). IL11 has an unknown function in VSMCs, which highly express the IL11 receptor alpha, suggestive of an autocrine loop. In vitro, IL11 activated ERK signaling, but inhibited STAT3 activity, and caused VSMC phenotypic switching to a similar extent as TGFß1 or angiotensin II (ANGII) stimulation. Genetic or therapeutic inhibition of IL11 signaling reduced TGFß1- or ANGII-induced VSMC phenotypic switching, placing IL11 activity downstream of these factors. Aortas of mice with Myh11-driven IL11 expression were remodeled and had reduced contractile but increased matrix and inflammatory genes expression. In two models of arterial pressure loading, IL11 was upregulated in the aorta and neutralizing IL11 antibodies reduced remodeling along with matrix and pro-inflammatory gene expression. These data show that IL11 plays an important role in VSMC phenotype switching, vascular inflammation and aortic pathobiology.

[MMP-9 gene -1562C/T polymorphism in aortic dissection in Chinese hypertensive patients].

OBJECTIVE: To investigate the association of matrix metalloproteinase 9 (MMP-9) gene -1562C/T polymorphism with the pathogenesis and site involved range of aortic dissection in Chinese population. METHODS: 142 hypertensive patients with aortic dissection and 130 hypertensive patients without aortic dissection were enrolled. Genomic DNAs were extracted from peripheral blood leucocytes. MMP-9 gene -1562C/T polymorphism was determined with PCR-RFLP. MMP-9 gene -1562C/T genotype and allele frequency were compared between hypertensive patients with aortic dissection and without. In addition, associations of MMP-9 gene -1562C/T polymorphism with clinical aspects were analyzed in hypertensive patients with aortic dissection. RESULTS: There was a significant difference in the T allele frequency of the C-1562T MMP-9 polymorphism between the two groups, with more T allele (17.6%) observed in hypertensive patients with aortic dissection as compared with these without (11.2%) (P = 0.033). The genotype distribution for the MMP-9 -1562C/T polymorphism in hypertensive patients with aortic dissection (-1562CC: 69.0%; -1562 CT: 26.8%; -1562TT: 4.2%) and those without (-1562CC: 79.2%; -1562CT: 19.2%; -1562TT: 1.6%; P = 0.118) showed no remarkable difference, but hypertensive patients with aortic dissection possessing T allele showed a higher odds ratio for involving ascending aorta (OR = 2.063, 95% CI = 0.998 - 4.264, P = 0.049) as compared with those without T allele. CONCLUSIONS: The T variant of MMP-9 gene -1562C/T polymorphism was significantly associated with aortic dissection in hypertensive patients and may represent an important genetic component contributing to aortic dissection susceptibility. Furthermore, hypertensive patients with aortic dissection possessing MMP-9 gene -1562T allele are more prone to involvement of ascending aorta.

A functional variant in the coding region of CAMTA2 is associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription.

OBJECTIVE: The calmodulin-binding transcription activator 2 (CAMTA2) promotes transcription of genes involved in cardiac hypertrophy through its interaction with Nkx2.5 and is an indispensable transcription coactivator for cardiac hypertrophy. We hypothesized that variants in the coding region of CAMTA2 would affect its function and confer a risk of cardiac hypertrophy. METHODS: The effects of the variant rs238234 on the activity of the atrial natriuretic factor promoter and on the cardiomyocytes hypertrophy were assessed in the H9C2 cell line and primary neonatal rat cardiomyocytes, respectively. Furthermore, the association of this variant with left ventricular hypertrophy (LVH) was tested in hypertensive patients with and without hypertrophy (N = 325 and 697), and this analysis was replicated in an independent population of 987 hypertensive patients without hypertrophy and 463 hypertensive patients with hypertrophy. RESULTS: We found that the G allele of rs238234 activated the atrial natriuretic factor promoter more strongly than the C allele. The cell size of cardiomyocytes was larger in the presence of the Ad-CAMTA2 G allele, and the G allele was associated with significantly increased susceptibility to LVH in hypertensive [odds ratio (OR), 1.29; P = 0.009]. In the discovery cohort, after adjusting for age and sex, the GG genotype was significantly associated with increased LVH risk (OR, 1.75; P = 0.015). There was little attenuation of the ORs (1.62; P < 0.05) when adjusting for BMI, heart rate, blood pressure, smoking, and drinking and further adjusting all covariates including lipid levels and other major risk factors. However, the GC genotype did not show any association with LVH using three regressive models. Replication in the second study yielded similar results. CONCLUSION: Our results provide evidence that the rs238234 GG genotype in the coding region of CAMTA2 may increase the risk of LVH by affecting the activation of Nkx2.5-dependent transcription.

Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma.

Protein phosphatase 2A (PP2A) is a heterotrimeric protein phosphatase consisting of a 36-kD catalytic C subunit (PP2Ac). This study aimed to explore the prognostic and biological significance of PP2Ac in human hepatocellular carcinoma (HCC). High PP2Ac expression was significantly (P < 0.01) associated with serum hepatitis B surface antigen positivity, serum hepatitis B e antigen positivity, liver cirrhosis, moderate to poor differentiation grade, advanced disease stage, intrahepatic metastasis, and early recurrence in HCC. Multivariate analysis revealed PP2Ac as an independent prognostic factor for overall survival. Enforced expression of hepatitis B virus X protein (HBx) and its carboxyl-terminal truncated isoform induced PP2Ac expression in HCC cells. Co-immunoprecipitation assay revealed a direct interaction between PP2Ac and HBx. Small interfering RNA-mediated knockdown of PP2Ac significantly inhibited in vitro cell proliferation, colony formation, migration, and invasion and reduced tumor growth in an xenograft mouse model. In contrast, overexpression of PP2Ac promoted HCC cell proliferation, colony formation, and tumorigenesis. Additionally, silencing of PP2Ac impaired the growth-promoting effects on HepG2 HCC cells elicited by overexpression of carboxyl-terminal truncated HBx. Gene expression profiling analysis showed that PP2Ac downregulation modulated the expression of numerous genes involved in cell cycle and apoptosis regulation. Collectively, PP2Ac upregulation has a poor prognostic impact on the overall survival of HCC patients and contributes to the aggressiveness of HCC. PP2Ac may represent a potential therapeutic target for HCC.

[The effect long-term administration of a selective beta1 blocker bisoprolol on glucose metabolism in patients with essential hypertensive and type 2 diabetes mellitus].

OBJECTIVE: To investigate the effects of bisoprolol on glucose metabolism and blood pressure in essential hypertensive patients with type 2 diabetes mellitus. METHODS: A total of 92 hypertensive patients with type 2 diabetes on stable antidiabetic therapy with HbAlc less than 7% were recruited. In a randomized, open trial the patients were treated for 12 weeks with bisoprolol or captopril following a 1-week placebo run-in period, the main parameters measured were HbA1c, fasting blood glucose and 2-hour postprandial glucose following a standard dinner as well as systolic and diastolic blood pressure. RESULTS: There were no differences in HbA1 [(6.0 +/- 0.8)% vs (6.2 +/- 0.8)%, P > 0.05], fasting glucose [(7.0 +/- 1.8) mmol/L vs (7.0 +/- 1.9) mmol/L, P > 0.05], 2-hour postprandial blood glucose [(10.7 +/- 2.5) mmol/L vs (11.2 +/- 3.4) mmol/L, P > 0.05], systolic blood pressure [(147.3 +/- 9.7) mm Hg (1 mm Hg = 0.133 kPa) vs (146.2 +/- 8.3) mm Hg, P > 0.05] and diastolic blood pressure (88.3 +/- 8.9 mm Hg vs 87.8 +/- 7.9 mm Hg, P > 0.05) between the bisoprolol and captopril group before treatment. After administration of bisoprolol or captopril, there were still no differences between these two groups in HbA1c [(5.7 +/- 0.9)% vs (5.7 +/- 1.1)%, P > 0.05], fasting blood glucose [(6.8 +/- 1.6) mmol/L vs (6.4 +/- 2.1) mmol/L, P > 0.05], 2-hour postprandial glucose [(10.0 +/- 2.9) mmol/L vs (10.2 +/- +/- 2.9)mmol/L, P > 0.05], systolic blood pressure [(124.8 +/- 10.6) mm Hg vs (126.6 +/- 7.8) mm Hg, P > 0.05] and diastolic blood pressure [(74.5 +/- 7.7) mm Hg vs (77.6 +/- 7.6) mm Hg, P = 0.05]. CONCLUSIONS: Based on these results, bisoprolol appears to be a beta1-selective blocker possessing a satisfactory antihypertensive effect without any adverse effects on glucose metabolism and is therefore a choice for treating hypertensive patients with type 2 diabetes mellitus.

Arsenic trioxide-induced hela cell death is partially prevented by K+ channel blockers.

AIM: To investigate the effects of K+ channel blockers on arsenic trioxide-induced HeLa cell death. METHODS: Viability of HeLa cells was assessed by mitochondrial dehydrogenase activity using colorimetric MTT assay and the voltage-dependent K+ currents were recorded by using patch-clamp technique. RESULTS: Exposure of As2O3 (5 micromol x L(-1)) for 24 h caused marked HeLa cell death. The rest living cells after As2O3 24 h-incubation showed significant increase of K+ currents densities. At +80 mV, the densities of K+ currents (61 +/- 18) pA/10 pF (n = 8) in As2O3 24 h-incubation group were significantly more than that in the control group (38 +/- 10) pA/10 pF (n = 8, P < 0.05). The HeLa cells were prevented partially from As2O3-induced cell death by co-application for 24 h with typical voltage-dependent K+ channel blockers, 4-aminopyridine (3 mmol x L(-1)) or tetraethylammonium (5 mmol x L(-1)). 4-Aminopyridine (3 mmol x L(-1)) or tetraethylammonium (5 mmol x L(-1)) did not show any toxic effects on HeLa cells. CONCLUSION: Chronic treatment with As2O3 increased voltage-dependent K+ currents in HeLa cells and the cell death induced by As2O3 was reduced partially by voltage-dependent K+ channel blockers, 4-aminopyridine or tetraethylammonium.

microRNA-622 acts as a tumor suppressor in hepatocellular carcinoma.

microRNAs (miRNAs) are important regulators of tumor development and progression. In this study, we aimed to explore the expression and role of miR-622 in hepatocellular carcinoma (HCC). We found that miR-622 was significantly downregulated in human HCC specimens compared to adjacent noncancerous liver tissues. miR-622 downregulation was significantly associated with aggressive parameters and poor prognosis in HCC. Enforced expression of miR-622 significantly decreased the proliferation and colony formation and induced apoptosis of HCC cells. In vivo studies demonstrated that miR-622 overexpression retarded the growth of HCC xenograft tumors. Bioinformatic analysis and luciferase reporter assays revealed that miR-622 directly targeted the 3'-untranslated region (UTR) of mitogen-activated protein 4 kinase 4 (MAP4K4) mRNA. Ectopic expression of miR-622 led to a significant reduction of MAP4K4 expression in HCC cells and xenograft tumors. Overexpression of MAP4K4 partially restored cell proliferation and colony formation and reversed the induction of apoptosis in miR-622-overexpressing HCC cells. Inhibition of JNK and NF-κB signaling phenocopied the anticancer effects of miR-622 on HCC cells. Taken together, miR-622 acts as a tumor suppressor in HCC and restoration of miR-622 may provide therapeutic benefits in the treatment of HCC.

Acidification alters antiarrhythmic drug blockade of the ether-a-go-go-related Gene (HERG) Channels.

Acidosis is one of the important deleterious factors during myocardial ischaemia and reperfusion. The ether-a-go-go-related gene, HERG, is a primary target for blockade by many drugs including dofetilide, quinidine and azimilide. While most drugs lose their efficacy against arrhythmias associated with myocardial ischaemia and reperfusion, dofetilide remains effective. The unique ability of dofetilide to terminate ischaemia-induced arrhythmias is not yet fully explained. The aim of the present study is to elucidate the acidification modulation of antiarrhythmic drugs blockade of HERG channels. The human gene HERG encoding K+ channels were expressed in Xenopus oocytes, and Whole-cell macroscopic currents of Xenopus oocytes were recorded with conventional two-electrode techniques. The inhibitory effects of dofetilide (0.25 microM) were significantly enhanced with decreasing pH (from 7.5 to 6.5). The percent block of dofetilide under pH 6.5 at 0 mV was 69+/-6.1% versus 54+/-3.0% under pH 7.5 (n=7, P<0.05). The IC50 values, determined by the Hill equation with the currents recorded at 0 mV, were decreased by approximately half from 192+/-23 nM with pH 7.5 to 93+/-15 nM with pH 6.5 (P<0.01). Acidification weakened the inhibitory effects of quinidine and azimilide on HERG channels. At 0 mV, the percent block of quinidine (10 microM) under pH 6.5 was 24+/-2.8% versus 62.5+/-9.0% under pH 7.5 (n=4, P<0.01), The percent block of azimilide (10 microM) under pH 6.5 was similar to that under pH 7.5 (n=6). Acidification markedly potentiated dofetilide blockade of the HERG channels but weakened the inhibitory effects of quinidine and azimilide.

Undifferentiated liver embryonal sarcoma in adults: a report of four cases and literature review.

AIM: To evaluate the undifferentiated embryonal sarcoma of liver (UESL) in adults in order to improve its diagnosis and treatment. METHODS: Four primary and one recurrent cases of UESL were clinicopathologically evaluated and immunohistochemically investigated with a panel of antibodies using the EnVision+ system. Relevant literature about UESL in adults was reviewed. RESULTS: Three males and one female were enrolled in this study. Their chief complaints were abdominal pain, weight loss, or fever. Laboratory tests, imaging and pathological features of UESL in adults were similar to those in children. Immunohistochemistry showed evidence of widely divergent differentiation into mesenchymal and epithelial phenotypes. The survival time of patients who underwent complete tumor resection followed by adjuvant transcatheter arterial chemoembolization (TACE) was significantly longer than that of those who underwent surgical treatment alone. CONCLUSION: UESL in adults may undergo pluripotential differentiation and its diagnosis should be made based on its morphological and immunohistochemical features. Complete tumor resection after adjuvant TACE may improve the survival time of such patients.

Primary mixed germ cell tumor of the liver with sarcomatous components.

Germ cell tumor (GCT) of the liver is extremely rare. Here, we describe a case of hepatic mixed GCT with significant sarcomatous components and elevated serum alpha-fetoprotein (AFP) in a 34-year-old man. Histopathologically, the tumor was composed of two GCTs components: yolk sac tumor and immature teratoma. The predominant components of immature teratoma consisted of several types of tissue that represented different germinal layers (endoderm, mesoderm and ectoderm) and showed varying degrees of differentiation with significant sarcomatous components. The yolk sac component showed positivity for AFP and cytokeratin (AE1/AE3). The immature teratoma components showed positivity for varying differentiation markers. Interphase cytogenetic analysis revealed that the yolk sac tumor and immature teratoma were positive for i(12p) and 12p over-representation. In particular, the rhabdomyoblastic components also showed typical i(12p) and 12p overrepresentation. This suggested that sarcomatous components may be associated with dedifferentiation or malignant transformation of certain mesenchymal components within teratoma.