Glycemic and blood pressure control in older patients with hypertension and diabetes： association with carotid atherosclerosis

Backgroud Numerous studies have confirmed the effectiveness of slowing the progression of atherosclerosis by blood pressure （Bp） control in patients with hypertension and several studies also showed the efficacy of intensive glycemic control in decreasing progression of carotid intima-media thickness （CIMT） in patients with type 1 and type 2 diabetes. However, few studies have compared the relative importance of glycemic w＇. Bp control in patients with diabetes and hypertension. We aimed to investigate the association between Bp and glycemic control and subclinical carotid atherosclerosis in older patients with hypertension and type 2 diabetes. Methods In a cross-sectional study, B-mode high-resolution ultrasonography of the carotid artery was performed in 670 subjects （508 males and 162 females） aged 60 years or over who had self-reported hypertension and diabetes but no history of coronary heart disease or stroke. Subjects were categorized by their systolic blood pressure： tight control, 〈 130 mmHg; usual control, 130-139 mmHg; or uncontrolled, 〉 140 mmHg, and by their hemoglobin Alc （HbAlc） level： tight control, 〈 6.5%; usual control, 6.5%-7.5%; or uncontrolled, 〉 7.5%, respectively. Results The mean CIMT was 8.20 ±0.11 mm, and carotid plaque was found in 52.5% （352/670） subjects. Overall, 62.1% of the subjects had subclinical carotid atherosclerosis, defined as having either carotid plaque or elevated CIMT （≥ 1.1 ram）. The mean CIMT was significantly different between Bp control categories （7.60 ± 0.09 mm, 7.90 ±0.08 mm, and 8.60 ± 0.12 mm, respectively, P = 0.03） but not between glycemic control categories （8.20± 0.10 mm, 8.1 ±0.08 mm, and 8.40 ± 0.14 ram, respectively, P = 0.13） using ANCOVA analysis. Multivariable logistic regression adjusting for potential confounding factors showed that usual or uncontrolled Bp control were associated with having carotid plaque （OR = 1.08 and OR=1.42, respectively）, or elevated CIMT [Odd ratio （OR） = 1.17, 95% confidence interval （CI） 1.04-2.24, and OR = 1.54, 95% CI 1.36-2.96, respectively compared to tight Bp control; but did not show glycemic control as independent predictor of either having carotid plaque or elevated CIMT. Conclusions In older patients with hypertension and diabetes, blood pressure control, but not glycemic control is associated with subclinical carotid atherosclerosis.

Incidence,predictors,and prognosis of thrombocytopenia among patients undergoing intra-aortic balloon pumping in the intensive care unit:a propensity score analysis

OBJECTIVE To explore the incidence,predictors,and prognosis of intra-aortic balloon pumping(IABP)-related thrombocytopenia in critically ill patients.METHODS This multi-center study used the eICU Collaborative Research Database V1.2,comprising data on>130,000 patients from multiple intensive care units(ICUs)in America between 2014 and 2015.A total of 710 patients undergoing IABP were included.Thrombocytopenia was defined as a drop in platelet count>50%from baseline.From the cohort,167 patients who developed thrombocytopenia were matched 1:1 with 167 patients who did not,after propensity score(PS)matching.The associations between IABP-related thrombocytopenia and clinical outcomes were examined by multivariable logistic regression.RESULTS Among 710 patients undergoing IABP,249 patients(35.07%)developed thrombocytopenia.The APACHE IVa score was a predictor of thrombocytopenia[adjusted odds ratio(OR)=1.09,95%confidence interval(CI):1.02−1.15].After 1:1 PS matching,in-hospital mortality(adjusted OR=0.76,95%CI:0.37−1.56)and in-ICU mortality(adjusted OR=0.74,95%CI:0.34−1.63)were similar between the thrombocytopenia and non-thrombocytopenia groups.However,major bleeding occurred more frequently in the thrombocytopenia group(adjusted OR=2.54,95%CI:1.54−4.17).In-hospital length of stay(LOS)and in-ICU LOS were significantly longer in patients who developed thrombocytopenia than in those who did not(9.71 vs.7.36,P<0.001;5.13 vs.2.83,P<0.001).CONCLUSIONS Among patients undergoing IABP in the ICUs,thrombocytopenia was not associated with a difference in inhospital mortality or in-ICU mortality;however,thrombocytopenia was significantly associated with a greater risk of major bleeding and increased in-ICU and in-hospital LOS.

Hyperpolarization activated cation current (If) in cardiac myocytes from pulmonary vein sleeves in the canine with atrial fibrillation

Objective To investigate the characteristics of ectopic automaticity and cation current (If) of cardiac myocytes from pulmonary vein sleeves (PVs) in canines with atrial fibrillation. Methods The canines (8–10 years old) were subjected to long-term, rapid atrial pacing (RAP) for 10 weeks, which induced the atrial fibrillation model. Disassociation of PVs of canines yielded single cardiac myocytes from a Landengorff column. Action potential, If and hyperpolarisation activated cyclic nucleotide-gated (HCN) currents were measured with the patch-clamp technique. Results Compared with the control group, cardiac myocytes from the RAP canine PVs had spontaneous diastolic depolarization, shorter action potential duration, and larger If densities. In the group of RAP cells, the half maximal activation potential (V1/2) was found to be less negative (��105.5 ±5.2 mV) compared to control cells (��87.3 ±4.9 mV). Current densities of If were increased significantly by β-adrenergic receptor stimulation with isoproterenol and caused an acceleration of current activation. In contrast, If currents in the RAP were reduced by carvedilol, a selective beta-adrenergic receptor. Another important finding is that HCN4-based channels may make a significant contribution to If in PVs cells, but not HCN2. Meanwhile, HCN4 current significantly increases in canine PVs cardiac myocytes with RAP. Conclusions The spontaneous action potential and larger If currentwere observed in the PVs cardiac myocytes using RAP, whichmay contribute tomore ectopic activity events to trigger and maintain atrial fibrillation.

Mutational analysis of KCNJll in Chinese elderly essential hypertensive patients

Objective To compare the distribution ofKCNJll polymorphisms between elderly Chinese population with and without hypertension. Methods We examined the mutation of KCNJll gene by directly sequencing. Data for the present study were obtained from 250 hypertensive subjects （60 to 83 years old） as well as 250 normotensive subjects （60 to 86 years old）. Results We found nine different mutations in KCNJ11, including six novel mutations （1131M, L1471, L147V, L147L, Q235H, G245C）. None of the novel mutations were found in the normotensive subjects, and all the residues were conserved in other species. These sequence variants in Chinese population indicate the diversity of the human library and the complexity of hypertension. Conclusions The consistent finding of our present study provided a basis for the development of new strategies to diagnosis and treat hypertension in the elderly.

CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders.Trefoil factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood.Here,we found that the upregulated TFF3 in CRC predicted a worse overall survival rate.TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis.CD147,a membrane protein,was identified as a binding partner for TFF3.Via binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and invasion.PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC progression.Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression.The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor.Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice.Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.