Rab35 GTPase positively regulates endocytic recycling of cardiac KATP channels.

ATP-sensitive K+ (KATP) channel couples membrane excitability to intracellular energy metabolism. Maintaining KATP channel surface expression is key to normal insulin secretion, blood pressure and cardioprotection. However, the molecular mechanisms regulating KATP channel internalization and endocytic recycling, which directly affect the surface expression of KATP channels, are poorly understood. Here we used the cardiac KATP channel subtype, Kir6.2/SUR2A, and characterized Rab35 GTPase as a key regulator of KATP channel endocytic recycling. Electrophysiological recordings and surface biotinylation assays showed decreased KATP channel surface density with co-expression of a dominant negative Rab35 mutant (Rab35-DN), but not other recycling-related Rab GTPases, including Rab4, Rab11a and Rab11b. Immunofluorescence images revealed strong colocalization of Rab35-DN with recycling Kir6.2. Rab35-DN minimized the recycling rate of KATP channels. Rab35 also regulated KATP channel current amplitude in isolated adult cardiomyocytes by affecting its surface expression but not channel properties, which validated its physiologic relevance and the potential of pharmacologic target for treating the diseases with KATP channel trafficking defects.

Transcriptomic Analysis Identifies Complement Component 3 as a Potential Predictive Biomarker for Chemotherapy Resistance in Colorectal Cancer.

Objective: 5-fluorouracil- and oxaliplatin-based FOLFOX regimens are mainstay chemotherapeutics for colorectal cancer (CRC) but drug resistance represents a major therapeutic challenge. To improve patient survival, there is a need to identify resistance genes to better understand the mechanisms underlying chemotherapy resistance. Methods: Transcriptomic datasets were retrieved from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and combined with our own microarray data. Weighted gene co-expression network analysis (WGCNA) was used to dissect the functional networks and hub genes associated with FOLFOX resistance and cancer recurrence. We then conducted analysis of prognosis, profiling of tumor infiltrating immune cells, and pathway overrepresentation analysis to comprehensively elucidate the biological impact of the identified hub gene in CRC. Results: WGCNA analysis identified the complement component 3 (C3) gene as the only hub gene associated with both FOLFOX chemotherapy resistance and CRC recurrence after FOLFOX chemotherapy. Subsequent survival analysis confirmed that high C3 expression confers poor progression-free survival, disease-free survival, and recurrence-free survival. Further correlational analysis revealed significant negative association of C3 expression with sensitivity to oxaliplatin, but not 5-fluorouracil. Moreover, in silico analysis of tumor immune cell infiltration suggested the change of C3 expression could affect tumor microenvironment. Finally, gene set enrichment analysis (GSEA) revealed a hyperactivation of pathways contributing to invasion, metastasis, lymph node spread, and oxaliplatin resistance in CRC samples with C3 overexpression. Conclusion: Our results suggest that high C3 expression is a debilitating factor for FOLFOX chemotherapy, especially for oxaliplatin sensitivity, and C3 may represent a novel biomarker for treatment decision of CRC.

Characterization of ZmCOLD1, novel GPCR-Type G Protein genes involved in cold stress from Zea mays L. and the evolution analysis with those from other species.

Maize is one of the most vital staple crops worldwide. G proteins modulate plentiful signaling pathways, and G protein-coupled receptor-type G proteins (GPCRs) are highly conserved membrane proteins in plants. However, researches on maize G proteins and GPCRs are scarce. In this study, we identified three novel GPCR-Type G Protein (GTG) genes from chromosome 10 (Chr 10) in maize, designated as ZmCOLD1-10A, ZmCOLD1-10B and ZmCOLD1-10C. Their amino acid sequences had high similarity to TaCOLD1 from wheat and OsCOLD1 from rice. They contained the basic characteristics of GTG/COLD1 proteins, including GPCR-like topology, the conserved hydrophilic loop (HL) domain, DUF3735 (domain of unknown function 3735) domain, GTPase-activating domain, and ATP/GTP-binding domain. Subcellular localization analyses of ZmCOLD1 proteins suggested that ZmCOLD1 proteins localized on plasma membrane (PM) and endoplasmic reticulum (ER). Furthermore, amino acid sequence alignment verified the conservation of the key 187th amino acid T in maize and other wild maize-relative species. Evolutionary relationship among plants GTG/COLD1 proteins family displayed strong group-specificity. Expression analysis indicated that ZmCOLD1-10A was cold-induced and inhibited by light. Together, these results suggested that ZmCOLD1 genes had potential value to improve cold tolerance and to contribute crops growth and molecular breeding.

[Evaluation of the effect of quality control circle activities on improving the nursing quality of patients with periodontitis].

PURPOSE: To study the effect of quality control circle activity on improving nursing quality of patients with periodontitis. METHODS: One hundred and twenty patients with periodontitis admitted to our hospital from January 2016 to December 2017 were selected and divided into experimental group and control group according to the principle of random control, with 60 patients in each group. Patients in both groups received supragingival scaling, subgingival scaling and related symptomatic treatment, patients in the experimental group conducted nursing under the guidance of quality control circle, while patients in the control group received routine nursing. Satisfaction degree, therapeutic effect and gingival index, probe depth, gingival sulcus bleeding index, plaque index and periodontal attachment levels were recorded and compared between the two groups using SPSS 19.0 software package. RESULTS: After quality control circle to guide nursing, the patients' satisfaction (P=0.003) and the total effective rate of treatment was significantly higher than the control group(P=0.002), the incidence of oral health problems in the experimental group was significantly lower than the control group(P=0.037), PD, GI, SBI, PLI and AL levels in the experimental group were significantly lower than the control group(P=0.000). In addition to the tangible achievements，intangible results, such as quality control circles harmonious degree of nursing, sense of responsibility, communication, and problem solving ability, cohesion and quality control methods are improved distinctly in the experimental group. CONCLUSIONS: Quality control circle activity can improve nursing quality of patients with periodontitis.

Retraction Note: Cardiac structural remodeling in hypertensive cardiomyopathy.

The authors are retracting this article [1]. In their recent work the authors have found that the degree of fibrosis in the different walls of the left atrium in pigs with hypertensive cardiomyopathy is the same. Sirius Red staining (another method to test for fibrosis) showed that there was no difference between the different walls. The authors are unable to explain this inconsistency. All authors agree with this retraction.

Apolipoprotein A1 polymorphisms and risk of coronary artery disease: a meta-analysis.

INTRODUCTION: It has been reported that APOA1 -75G/A polymorphism might be associated with susceptibility to coronary artery disease (CAD). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between APOA1-75G/A polymorphism and the risk of CAD. MATERIAL AND METHODS: A systematic search of studies on the association of single nucleotide polymorphisms (SNP) with susceptibility to CAD was conducted. A total of 9 case-control studies (1864 cases and 1196 controls) on the APOA1-75G/A polymorphism were included. RESULTS: We observed no statistically significant association between APOA1 -75G/A polymorphism and risk of CAD under the dominant genetic model (AA + AG vs. GG: OR = 1.03, 95% CI: 0.65-1.66), allelic contrast (A vs. G: OR = 0.88, 95% CI: 0.58-1.32), heterozygote model (AG vs. GG: OR = 1.24, 95% CI: 0.81-1.89) or homozygote model (AA vs. GG: OR = 0.52, 95% CI: 0.26-1.05). Significant heterogeneity between individual studies appears in all five models, but a strong association under the recessive genetic model (AA vs. AG + GG: OR = 0.51, 95% CI: 0.28-0.92). In the subgroup analysis by Hardy-Weinberg equilibrium (HWE; the presence or absence of HWE in controls), significantly decreased CAD risk and no significant heterogeneity were observed among controls consistent with HWE. Overall, the APOA1 A allele is one of the protective factors of CAD. A stronger association between APOA1-75G/A polymorphisms and CAD risk was present in the studies consistent with HWE. CONCLUSIONS: The minor allele of the APOA1-75G/A polymorphism is a protective factor for CAD, especially in the studies consistent with HWE.

Association between KCNE1 G38S gene polymorphism and risk of atrial fibrillation: A PRISMA-compliant meta-analysis.

BACKGROUND: Previous case-control studies on association between KCNE1 G38S polymorphism and risk of atrial fibrillation (AF) have been published but because of the conflicting results and small sample size of individual studies, the consolidated result is still controversial. OBJECTIVES: The aim of this study was to explore the relationship between KCNE1 G38S polymorphism and risk of AF. METHODS: We performed a comprehensive literature search on PubMed, Embase, OVID, Web of Science, Wan Fang, and CNKI databases up to March 10, 2017 in English and Chinese languages. Two of the authors individually extracted study data and assessed the study quality using Newcastle-Ottawa scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were combined in different genetic models for evaluation using a random-effect model or fixed-effect model according to interstudy heterogeneity. RESULTS: There were totally 14 independent case-control studies of 2810 patients and 3080 healthy controls included. Significant associations were found between KCNE1 G38S polymorphism and AF in overall population under all genetic models: allelic (OR: 1.34, 95% CI: 1.24-1.45, P < .001), homozygous (OR: 1.90, 95% CI: 1.61-2.24, P < .001), heterozygous (OR: 1.43, 95% CI: 1.21-1.68, P < .001), recessive (OR: 1.42, 95% CI: 1.20-1.69, P < .001), dominant genetic model (OR: 1.62, 95% CI: 1.39-1.89, P < .001). Subgroup analyses indicated similar association in Chinese and white. CONCLUSIONS: The G38S polymorphism in the KCNE1 gene can significantly increase the risk of AF in both Chinese and white.

Association between chemokine CXC ligand 12 gene polymorphism (rs1746048) and coronary heart disease: A MOOSE-compliant meta-analysis.

Recently a large number of investigations have implicated the association between the chemokine CXC ligand 12 gene polymorphism (rs1746048) and risk of coronary heart disease (CHD), but the results remain debatable. The aim of our study was to provide more compelling evidence for the relationship between rs1746048 and CHD risk. Studies eligible for this meta-analysis were identified through electronic search of PubMed, EMBASE, and CNKI. Two authors performed independent literature review and study quality assessment by using the Newcastle-Ottawa Scale checklist. The odds ratios (ORs) with 95% confidence intervals (CIs) were pooled in a specific genetic model to assess the association. The meta-analysis of 48,852 patients and 64,386 controls from 12 studies showed that patients with rs1746048 had 1.11 times of high risk in developing CHD (OR = 1.11; 95% CI = 1.09-1.14; P < .005; I = 35.8%). The increased risk of CHD was also found in both Asian (OR = 1.07; 95%CI = 1.02-1.12; P < .005; I = 40.6%) and Caucasian populations (OR = 1.14; 95% CI = 1.10-1.18; P < .005; I = 22.2%). The results of our meta-analysis suggested that chemokine CXC ligand 12 gene polymorphism (rs1746048) may be linked with susceptibility to CHD.

Cardiac structural remodeling in hypertensive cardiomyopathy.

Heart failure with preserved ejection fraction (HFpEF), which is a primary driver of morbidity and mortality, accounts for approximately half of all heart failure cases. Therefore, it is essential to develop preclinical animal models for HFpEF pharmacological treatment strategies. We created a porcine model of severe hypertension and hyperlipidemia by using a combination of deoxycorticosterone acetate (DOCA, 100 mg kg-1), Western diet (WD) and angiotensin II infusion. Systolic blood pressure, echocardiography and invasive pressure-volume loop were assessed at baseline, 12 weeks and 18 weeks. A detailed histological assessment was also performed to determine the cardiac structural remodeling. Compared with controls (n=10), hypertensive animals (n=10) showed markedly higher systolic blood pressure (181 vs. 86 mm Hg) at 18 weeks. Concentric remodeling, characterized by a normal chamber size with a thicker wall, was observed in hypertensive animals. Left ventricle diastolic function showed a tendency toward decline, according to the echocardiographic data. Hemodynamic data showed that the end-diastolic pressure-volume relationship was elevated without changes in the end-systolic pressure-volume relationship. Histological results revealed that the fibrotic area in hypertensive animals (P<0.05 vs. controls) and the fibrotic area in the posterior wall of hypertensive animals' left atria were larger than other sites of the left atria (P<0.05 vs. other sites). This model can mimic clinical HFpEF to some degree. We found that the posterior wall of the left atrium is more susceptible to atrial remodeling associated with hypertension compared with other regions of the left atrium.

KCNN3 SNP rs13376333 on Chromosome 1q21 Confers Increased Risk of Atrial Fibrillation.

To investigate the relationship between KCNN3 SNP (single-nucleotide polymorphism) rs13376333 and risk of atrial fibrillation (AF) and to provide evidence for prevention and treatment for AF.The PubMed, Embase, OVID, Cochrane library, CNKI, and Wan Fang databases were searched to identify studies on the relationship between KCNN3 SNP rs13376333 polymorphism and atrial fibrillation. Two authors performed independent article reviews and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist.Seven studies involving 24,339 individuals were included in the meta-analysis. The overall combined OR of rs13376333 polymorphism was observed for both lone AF (OR: 1.58 [95%CI: 1.37 to 1.82]; P < 0.001; I(2) = 47.0%) and total AF (OR: 1.33 [95%CI: 1.14 to 1.54]; P < 0.001; I(2) = 0). Further, when stratified by ethnicity, control sources, sample sizes, and genotyping method, similar results were observed in both subgroups. Sensitivity analysis revealed that the source of control was the source of the heterogeneity for lone AF. Omission of any single study had little effect on the combined risk estimate. No evidence of publication bias was found.This meta-analysis suggests that KCNN3 SNP rs13376333 polymorphism significantly increases the risk of lone AF and total AF, which suggests the rs13376333 polymorphism of the KCNN3 gene may play an important role in the pathogenesis of AF.

Association between angiotensinogen M235T polymorphism and hypertrophic cardiomyopathy.

BACKGROUND: To investigate the relationship between angiotensinogen (AGT) gene M235T polymorphism and hypertrophic cardiomyopathy (HCM) to explore the potential role of the AGT polymorphism in HCM. METHODS: PubMed, Embase, OVID, Cochrane library, CNKI, Wan Fang Database were searched to identify the studies involving AGT M235T polymorphism and HCM. Two authors performed independent literature review and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist. A random-effects model was used to calculate the overall combined risk estimates. RESULTS: Nine studies involving 887 cases and 1407 controls were included in our meta-analysis. No significant associations were found between AGT M235T polymorphism and HCM (allele model T vs M: OR = 1.17, 95% CI = 0.95-1.45; dominant model TT vs (MM/MT): OR = 1.21, 95% CI = 1.00-1.45; recessive model (TT/MT) vs MM: OR = 1.12, 95% CI = 0.87-1.45; heterozygous comparison MT vs MM: OR = 1.07, 95% CI = 0.82-1.41; homozygous comparison TT vs MM OR = 1.19, 95% CI = 0.88-1.61. In subgroup analysis, the significant difference of association between AGT M235T polymorphism and HCM existed in Asian and sporadic hypertrophic cardiomyopathy (SHCM), but no significant difference was found in Europeans and familial hypertrophic cardiomyopathy (FHCM). CONCLUSIONS: There is no association between AGT M235T polymorphism and HCM in general populations, but such a relationship exists in Asians and SHCM.

Preliminary histological and biomechanical study about the timing of surgical repair for acute rotator cuff tears in rabbits / 中华外科杂志

<p><b>OBJECTIVES</b>To establish the animal model of acute rotator cuff tear in rabbits, and study the effect of timing of surgical repair on healing of tendon-bone interface, formation and distribution of collagens in the supraspinatus tendon insertion and biomechanical properties of supraspinatus.</p><p><b>METHODS</b>Supraspinatus tenotomy was performed in the right shoulder of 90 skeletally matured male New Zealand white rabbits to establish the animal model of acute rotator cuff tear. The rabbits were randomly divided into 3 groups : group of early repair, repaired at 1 week after tenotomy; group of late repair, repaired at 4 weeks after tenotomy; and group without repair, used as control. At 2 weeks, 4 weeks and 8 weeks after repair, healing of tendon-bone interface was observed by HE staining. Collagens were observed by Sirius Red F 3B (SR) in saturated carbazotic acid staining. The areas of type I and III collagens were measured by using imaging analysis software and the ratio of type I and III collagens were calculated. Failure loads of supraspinatus on both sides were measured. The percentage of failure loads of the surgical side was calculated and contralateral supraspinatus were uninjured.</p><p><b>RESULTS</b>There was no obvious fatty infiltration and muscle atrophy in supraspinatus in all groups. At 8 weeks, the formation of a new enthesis of supraspinatus in groups of early and late repair were observed. In groups of early and late repair, the ratio of areas of type I and III collagens at 8 weeks (2.02 ± 0.77 and 2.06 ± 0.58) was larger than that at 2 weeks (1.10 ± 0.24 and 1.14 ± 0.50, t = 3.082, 3.655, P < 0.01). At 2, 4 and 8 weeks, the percentages of failure loads of the surgical side and uninjured contralateral supraspinatus in group of early repair(38% ± 11%, 66% ± 7%, 89% ± 4%) and group of late repair (41% ± 16%, 63% ± 7%, 89% ± 9%) were both higher than that in group without repair (14% ± 6%, 32% ± 4%, 56% ± 12%); the differences were all statistically significant (group of early repair: t = 3.311, 8.549, 5.719; group of late repair: t = 3.713, 8.063, 6.044; P < 0.01). The percentage of failure loads of the surgical side and uninjured contralateral supraspinatus at 8 weeks was higher than those at 4 weeks (t = 3.878 - 4.613, P < 0.01) and 2 weeks (t = 7.158 - 10.024, P < 0.01) in all groups.</p><p><b>CONCLUSIONS</b>Surgical repair within 4 weeks of acute rotator cuff tear lead to formation of a new enthesis of supraspinatus, improvement of both ratio of type I collagen in the supraspinatus tendon insertion and biomechanical properties of supraspinatus.</p>

[Comparison of the therapeutical effectiveness between paper splint adduction fixation and plaster abduction fixation in Bennett fracture].

OBJECTIVE: To study and compare the difference on the therapeutical effectiveness between paper splint adduction fixation and plaster abduction fixation in Bennett fracture. METHODS: In the study, seventy outpatient were selected from October 2005 to April 2007, and devided into two groups randomly involving experiment group (35 cases with paper splint adduction fixation) and control group (35 cases with plaster abduction fixation). After the fracture clinical healed and removed fixation, the patients had been followed up 6 months. At the 6th, 8th, 12th, 16th, 20th, 24th week after fracture, the fracture hand had been scored and compared according to Gabriele's score system. RESULTS: At the 8th, 12th, 16th and 20th week, the excellent rate of experiment group was higher than control group, there was significant difference (P<0.05) At 6th week and 24th week there was no significant difference (P>0.05). At 8th, 12th, 16th, 20th and 24th week, the functional score of experiment group was higher than control group, there was significant difference (P<0.05); At 6th week there was no significant difference (P>0.05). CONCLUSION: The paper splint adduction fixation could promote recovery of the hand function in Bennett fracture. In addition, the paper splint adduction fixation is comfortable to recipient. It could be spreaded in clinic as a effective fixation method.