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Objective: To explore the primary site and pathological feature of neuroendocrine neoplasm (NEN), especially the NEN of digestive system., Methods: Clinicopathological data of NEN patients at China-Japan Friendship Hospital from January 2012 to December 2016 were retrospectively analyzed. Tumor primary sites were summarized. Association between tumor site and pathological grading in gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN) was examined., Results: There were a total of 903 cases of NEN. Sites of primary tumor included the digestive system in 699 cases(77.4%), the thorax(including lung, thymus and mediastinum) in 87 cases(9.6%), other sites in 60 cases (6.6%), unknown in 57 cases(6.3%). Among 699 GEP-NEN cases, the primary sites included the stomachin in 207 cases (29.6%), pancreas in 201 (28.8%), rectumin in 185 (26.5%), duodenum in 43(6.2%), jejunum and ileum in 18(2.6%), appendix in 15 (2.1%), gallbladder in 11(1.6%), esophagus in 10(1.4%), and the colon in 9 cases (1.3%). Pathologically, the tumor grading was neuroendocrine tumor (NET) G1 in 336 cases(48.1%), NET G2 in 203 cases (29.0%), neuroendocrine carcinoma (NEC) G3 in 139 cases (19.9%). All the esophagus NEN(10/10), most gallbladder NEN(9/11) and colon NEN(6/9) were poorly-differentiated NEC (G3), while all appendix NEN(15/15), most stomach NEN(147/207, 71.0%), pancreas NEN (156/201, 77.6%), rectum NEN (169/185, 91.4%), duodenum NEN (31/43, 72.1%), jejunum and ileum NEN(16/18, 88.9%) were well-differentiated NET G1 or G2., Conclusions: The most common primary site of NEN is the digestive system. The stomach, pancreas and rectum are most common primary sitesof GEP-NEN. Difference in pathological grading is quite greatin different primary sites of GEP-NEN. Most NENs fromesophagus, colon and gallbladder are poorly-differentiated NEC.

MAPK-activated protein kinase-5 (MK5) is a protein serine/threonine kinase that is activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. The physiological function(s) of MK5 remains unknown. Here, we examined the effect of MK5 haplodeficiency on cardiac function and myocardial remodeling. At 12 wk of age, MK5 haplodeficient mice (MK5 +/- ) were smaller than age-matched wild-type littermates (MK5 +/+ ), with similar diastolic function but reduced systolic function. Transverse aortic constriction (TAC) was used to induce chronic pressure overload in 12-wk-old male MK5 +/- and MK5 +/+ mice. Two weeks post-TAC, heart weight-to-tibia length ratios were similarly increased in MK5 +/- and MK5 +/+ hearts, as was the abundance of B-type natriuretic peptide and β-myosin heavy chain mRNA. Left ventricular ejection fraction was reduced in both MK5 +/+ and MK5 +/- mice, whereas regional peak systolic tissue velocities were reduced and isovolumetric relaxation time was prolonged in MK5 +/+ hearts but not in MK5 +/- hearts. The TAC-induced increase in collagen type 1-α 1 mRNA observed in MK5 +/+ hearts was markedly attenuated in MK5 +/- hearts. Eight weeks post-TAC, systolic function was equally impaired in MK5 +/+ and MK5 +/- mice. In contrast, the increase in E wave deceleration rate and progression of hypertrophy observed in TAC MK5 +/+ mice were attenuated in TAC MK5 +/- mice. MK5 immunoreactivity was detected in adult fibroblasts but not in myocytes. MK5 +/+ , MK5 +/- , and MK5 -/- fibroblasts all expressed α-smooth muscle actin in culture. Hence, reduced MK5 expression in cardiac fibroblasts was associated with the attenuation of both hypertrophy and development of a restrictive filling pattern during myocardial remodeling in response to chronic pressure overload. NEW & NOTEWORTHY MAPK-activated protein kinase-5 (MK5)/p38-regulated/activated protein kinase is a protein serine/threonine kinase activated by p38 MAPK and/or the atypical MAPKs ERK3 and ERK4. MK5 immunoreactivity was detected in adult ventricular fibroblasts but not in myocytes. MK5 haplodeficiency attenuated the progression of hypertrophy, reduced collagen type 1 mRNA, and protected diastolic function in response to chronic pressure overload., (Copyright © 2017 the American Physiological Society.)

Objective: To study subtype classification of gastric neuroendocrine neoplasm (NEN) and their clinicopathological characteristics in order to provide reference for clinical practice., Methods: Clinicopathological data of 241 gastric NEN patients (174 cases from China-Japan Friendship Hospital and 67 cases from The First Affiliated Hospital of Sun Yat-Sen University) between January 2011 and June 2016 were retrospectively summarized. According to serum gastrin, 24-hour intragastric pH monitoring and pathological grade, patients with gastric NEN were divided into 4 types: type I( (hypergastrinemia and achlorhydria, related to autoimmune chronic atrophic gastritis), type II( [hypergastrinemia and Zollinger-Ellison syndrome, related to gastrinoma or multiple endocrine neoplasia type I( (MEN-I()], type III( (sporadic disease with normal serum gastrin level), and type IIII( [poorly differentiated gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC)]. Clinicopathological features, treatment and prognosis of 4 types were analyzed., Results: Of 241 gastric NEN cases, there were 86 cases (35.7%) in type I(, 7 cases (2.9%) in type II(, 61 cases (25.3%) in type III( and 87 cases(36.1%) in type IIII(. Among 86 cases of type I( gastric NEN, 73 cases (84.9%) were multiple lesions,tumor size of 66 cases (76.7%) was less than 1 cm, all the 86 cases were polypoid or granular lesions. 2 cases(2.3%)presented distant metastasis, 69 cases (80.2%) had pathological grading as NET G1; most of them received endoscopic surgery treatment and follow-up; somatostatin analogs(SSA) was used in patients with multiple lesions and repeated recurrence after endoscopic treatment. Among 7 cases of type II(, 4 cases were gastrinoma, 3 cases MEN-I(; 5 cases presented distant metastasis; treatment included surgery, SSA and proton pump inhibitor (PPI) therapy. Among 61 cases of type III( gastric NEN, 49 cases(80.3%) were single lesion,tumor size of 25 cases(41.0%) was more than 2 cm, 29 cases(47.5%) had lymph node metastasis or distant metastasis; treatment included endoscopic resection, surgery or SSA therapy according to the tumor staging. Among 87 patients of type IIII( gastric NEN, 74 cases(85.0%) had single lesion,tumor size of 51 cases (58.6%) was more than 2 cm; lesions were found in gastric cardia in 35 cases (40.2%); 65 cases (74.7%) had lymph node metastasis or distant metastasis; treatment included chemotherapy, or surgery plus chemotherapy. At the end of follow-up(June 30, 2016), 58 patients were dead, including 1 case of type I(, 12 cases of type III( and 45 cases of type IIII(. The overall survival rate of all the patients was 74.2%, and was 98.8%, 100%, 79.3%, 39.2% of types I(, II(, III(, IIII( respectively. The overall survival rate between type III( and type IIII( gastric NEN was significantly different(P = 0.000)., Conclusions: Subtype classification of gastric NEN is very significant for making therapeutic decisions and prognostic evaluation. Patients of type I( or type II( gastric NEN have good prognosis,while those of type III( and type IIII( have poor prognosis, and those of type IIII( have the worst prognosis.

While heart rate reduction (HRR) is a target for the management of patients with heart disease, contradictory results were reported using ivabradine, which selectively inhibits the pacemaker I f current, vs. β-blockers like metoprolol. This study aimed at testing whether similar HRR with ivabradine vs. metoprolol differentially modulates cardiac energy substrate metabolism, a factor determinant for cardiac function, in a mouse model of dyslipidemia (hApoB +/+ ;LDLR -/- ). Following a longitudinal study design, we used 3- and 6-mo-old mice, untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was evaluated in vivo and ex vivo in working hearts perfused with 13 C-labeled substrates to assess substrate fluxes through energy metabolic pathways. Compared with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly higher stroke volume values and glycolysis vs. their metoprolol-treated counterparts ex vivo, values for the ivabradine group being often not significantly different from 3-mo-old mice. Further analyses highlighted additional significant cardiac alterations with disease progression, namely in the total tissue level of proteins modified by O-linked N-acetylglucosamine (O-GlcNAc), whose formation is governed by glucose metabolism via the hexosamine biosynthetic pathway, which showed a similar pattern with ivabradine vs. metoprolol treatment. Collectively, our results emphasize the implication of alterations in cardiac glucose metabolism and signaling linked to disease progression in our mouse model. Despite similar HRR, ivabradine, but not metoprolol, preserved cardiac function and glucose metabolism during disease progression., (Copyright © 2016 the American Physiological Society.)

Background: Amiodarone is commonly used in the acute care setting. However the acute hemodynamic and echocardiographic effect of intravenous amiodarone administered intraoperatively on right ventricular (RV) systolic and diastolic function using transesophageal echocardiography (TEE) has not been described., Methods: The study design was a randomized controlled trial in elective cardiac surgical patients undergoing valvular surgery. Patients received an intravenous loading dose of 300 mg of either amiodarone or placebo in the operating room, followed by an infusion of 15 mg/kg for two days. Hemodynamic profiles, echocardiographic measurement of RV and left ventricular (LV) dimensions, Doppler interrogation of tricuspid and mitral valve, hepatic and pulmonary venous flow combined with tissue Doppler imaging of the tricuspid and mitral valve annulus were obtained before and after bolus., Results: Although more patients in the placebo group had chronic obstructive lung disease (14 vs 6, p=0.05) and diabetes (14 vs 5; p=0.0244), there was no difference in terms of baseline hemodynamic, 2D and Doppler variables. After bolus, a significant increase in pulmonary artery pressure, central venous pressure and pulmonary vascular resistance index (p<0.05) was observed in the amiodarone group with reduction in systolic to diastolic (S/D) ratio of the hepatic (p=0.0247) and pulmonary venous (p=0.0052) velocity., Conclusion: Acute administration of amiodarone is associated with alteration in RV diastolic properties and has minimal negative inotropic effect on RV systolic function in cardiac surgical patients with valvular disease., (© The European Society of Cardiology 2014.)