Objective To investigate the correlation between glycosylated hemoglobin (HbAlc) and carotid intima-media thickness (CIMT) in non-diabetic peritoneal dialysis patients.Methods Forty-two non-diabetic peritoneal dialysis adult patients were enrolled in this study [mean age was (48.2± 12.3) years,50％ was male].CIMT was determined by carotid ultrasound.Patients were divided into two groups according to CIMT:CIMT normal group (CIMT ＜ 0.9 mm) and CIMT thickening group (CIMT≥0.9 mm).HbAlc,2-hour postprandial blood glucose (2hPBG) and other factors of the patients were analyzed with Spearman rank correlation and multiple linear regression.Results CIMT was correlated with age,2hPBG,LDL-C,TG,TC,HbA1c in non-diabetic peritoneal dialysis patients (r =0.355,0.373,0.416,0.345,0.351,0.456,all P ＜ 0.05).Multiple linear regression showed that HbA1c was the most powerful influence factor of CIMT(β =0.459).Conclusion HbA1c level is positively correlated with CIMT and may be a predictor of carotid atherosclerosis in non-diabetic peritoneal dialysis patients.

AIM:To analyze the alterations of angiotensin Ⅱ (Ang Ⅱ), connexin 43 (Cx43), angiotenisinⅡreceptor type 1 (AT1) and signaling molecules in the TGF-β1/Smad pathway in different regions of the left ventricular heart tissue for exploring whether Ang Ⅱregulates Cx43 expression via the TGF-β1/Smad signaling pathway in myocardial infarction ( MI) rats.METHODS:MI was induced in 20 male Sprague-Dawley rats by the left anterior descending coronary artery ligation.The rats were then randomized into 2 groups.In the losartan group, 20 mg· kg-1· d-1 of losartan were ad-ministered for 2 weeks.Heart functions were assessed after surgery and 2 weeks later again following the above treatments . All the rats were sacrificed and relevant molecules , including Ang Ⅱ, AT1, and Cx43 were determined thereafter in diffe-rent areas of the left ventricle .TGF-β1 and its downstream signaling molecules , including Smad 2, Smad 3 and Smad 7, were also detected .RESULTS:In losartan group , both left ventricular internal dimension diastole ( LVIDd) and left ven-tricular internal dimension systole (LVIDs) were smaller, with diminished interventricular septal thickness (IVSd) and left ventricular posterior wall depth ( LVPWd ) and distinct improvement of left ventricular ejection fraction ( LVEF ) ( P<0.05 ) .Losartan therapy exhibited a reduction of Ang Ⅱin the infarct zone and the border zone in the cardiac tissues .AT1 was obviously attenuated in the infarct zone with an enhanced expression of Cx 43, which was also elevated in the border zone and none infarct zone .TGF-β1, Smad 2 and Smad 3 were decreased in different zones of the left ventricle , while Smad 7, in contrary to the above factors , presented a converse alteration .CONCLUSION:The activation of Ang Ⅱpro-vokes downregulation of Cx 43 through TGF-β1/Smad signaling pathway in MI rats .

BACKGROUND:Our previous work has demonstrated that bone marrow mesenchymal stem cels (BMSCs) transplantation can improve the heart function of rats with myocardial infarction. However, the overal efficacy is not satisfactory. OBJECTIVE: To adopt pioglitazone as a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist combined with BMSCs transplantation therapy, thereby further improving cardiac function of rats with myocardial infarction as wel as investigating the relevant mechanisms. METHODS:Twenty Sprague-Dawley rats with myocardial infarction were induced by the left anterior descending coronary artery ligation. The animals were randomized into two groups: BMSCs and BMSCs+pioglitazone. Two weeks later, al the animals received the injection of BMSCs labeled with PKH26 in PBS into the local infarct zone, and then pioglitazone (3 mg/kg/d) was given by the oral gavage for 2 weeks in the BMSCs+pioglitazone group after the cel transplantation. After 2 weeks of cel transplantation, cardiac functions were evaluated by echocardiography. The expressions of PPAR-γ, Connexin 43 and molecules in TGF-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart using immunofluorescent staining, western blot assay and qRT-PCR. RESULTS AND CONCLUSION:There were no differences in the baseline parameters of cardiac function between the two groups. At 2 weeks after cel transplantation, the left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole and left ventricular ejection fraction were significantly improved in the BMSCs+ pioglitazone group; the expressions of PPAR-γ and Connexin 43 were distinctly increased in different zones of the left ventricle; the levels of TGF-β1, SMAD2 and SMAD3 were obviously attenuated in the infarct zone and border zone. The above-mentioned findings suggest that pioglitazone, a PPAR-γ agonist, can enhance BMSCs potential in improvingthe heart function after myocardial infarction, and PPAR-γ may elevate the expression of Connexin 43via the blockade of the TGF-β1/SMAD signaling pathway in the procedure.

AIM:To validate the association between long noncoding (lncRNA)-H19 and microRNA-199a-5p (miR-199a-5p) through the dual-luciferase reporter gene system by construction of a luciferase reporter vector containing the gene of lncRNA-H19.METHODS:The potential complementary binding sites of lncRNA-H19 and miR-199a-5p were predicted by RegRNA 2.0.The H19 gene or its mutant ( Mut) fragment was cloned into luciferase reporter vector psi-CHECK-2.Restriction enzyme analysis and sequence analysis were used to identify whether the recombinant plasmids of the H19 and H19-Mut were successfully constructed .miR-199a-5p mimics, miR-199a-5p inhibitor, miR-199a-5p mimics neg-ative control or miR-199a-5p inhibitor negative control was co-transfected into the 293T cells with the luciferase reporters containing H19 or H19-Mut.Dual-luciferase reporter assay was performed to detect the luciferase activity in different groups in order to verify the relationship between lncRNA-H19 and miR-199a-5p.RESULTS:The results of double enzyme diges-tion and DNA sequencing showed that the sequence of luciferase reporter vector was correct .The results of dual-luciferase reporter assay indicated that the H 19 reporter gene luciferase activity significantly decreased in miR-199a-5p mimics group by 49%(P<0.01), and the H19 reporter gene luciferase activity was obviously upregulated in miR-199a-5p inhibitor group compared with miR-199a-5p mimics group ( P<0.01).However, miR-199a-5p mimics, miR-199a-5p inhibitor, miR-199a-5p mimics negative control and miR-199a-5p inhibitor negative control showed no effect at H 19-Mut reporter gene.CONCLUSION:lncRNA-H19 binds to miR-199a-5p to exert an inhibitory effect at transcriptional level .

BACKGROUND:Previous studies have demonstrated that the electrophysiological stability and ventricular fibril ation threshold after myocardial infarction in rats are significantly improved in the mid-term of cardiac stem cel transplantation, but relative regulatory mechanism and pathway remain unclear. OBJECTIVE:To explore the relative molecular regulatory mechanism of cardiac stem cel s improving the electrophysiological stability and ventricular fibril ation threshold after myocardial infarction in rats. METHODS:Myocardial infarction was induced in 20 Sprague-Dawley rats by ligation of the left anterior descending coronary, which were then randomized into two groups (n=10 per group) and were subjected to the injection of cardiac stem cel s labeled with PKH26 in phosphate buffer solution (cardiac stem cel group) or the same amount of phosphate buffer solution (PBS) alone (PBS group) into the local infarct zone at 2 weeks after modeling, respectively. Six weeks later, relevant signaling molecules involved in the ANGII/AT1R/TGF-β1/SMAD/Cx43 pathway were al examined in myocardial tissues of the left ventricle and harvested blood samples. RESULTS AND CONCLUSION:Compared with the PBS group, expressions of connexin 43 in different zones of the left ventricle were significantly increased in the cardiac stem cel group (P<0.01);there was a significant reduction of the angiotensin II level in plasma and different regions of the left ventricular (P<0.05;P<0.01). Furthermore, in the cardiac stem cel group, expressions of angiotensin II type I receptor, transforming growth factor-β1, SMAD2 and SMAD3 were significantly decreased (P<0.01). Whereas SMAD7 was significantly elevated (P<0.05) in different areas of the left ventricle compared with the phosphate buffer solution group. These findings suggest that the cardiac stem cel transplantation can improve the electrophysiological stability and ventricular fibril ation threshold after myocardial infarction by enhancing the expression of connexin 43 via ANGII/AT1R/TGF-beta1/SMAD/CX43 signaling pathway.

BACKGROUND:Our previous work demonstrated that cardiac stem cel s (CSCs) transplantation could significantly improve the electrophysiological stability and ventricular fibril ation threshold in rats with myocardial infarction. OBJECTIVE:To compare the influence of CSCs and bone marrow mesenchymal stem cel s (BMSCs) transplantation on the electrophysiological stability and ventricular fibril ation threshold in rats with myocardial infarction in the short term.
METHODS:Thirty male healthy Sprague-Dawley rats were selected to make myocardial infarction models induced by the left anterior descending coronary artery ligation. Then, animals were randomly divided into three groups, CSCs group, BMSCs group and the PBS group, with 10 rats in each group. Two weeks after modeling, animals were respectively given the injection of 5×106 CSCs labeled with PKH26 in 0.1 mL PBS, 5×106 BMSCs labeled with PKH26 in 0.1 mL PBS or 0.1 mL PBS alone into the infracted anterior ventricular free wal . Two weeks after intervention, the electrophysiological characteristics and ventricular fibril ation threshold were measured respectively at the infarct zone, the infarct marginal zone and the non-infarct zone. Labeled CSCs and BMSCs were detected, and the expression of connexin-43 was examined in 5 μm cryostat sections from the infarct marginal zone of each heart.
RESULTS AND CONCLUSION:Compared with the BMSCs group and PBS group, significant differences were revealed in the correct unipolar electrograms activation recovery time dispersion (ARTcd), electrical stimulation-induced malignant ventricular arrhythmias and ventricular fibril ation threshold at the infarct zone, the infarct marginal zone and the non-infarct zone in the CSCs group (P<0.05). Obvious differences were discovered in the ARTcd, electrical stimulation-induced malignant ventricular arrhythmias and ventricular fibril ation threshold on the non-infarct area in the BMSCs group in contrast to the PBS group. Labeled CSCs or BMSCs were identified at the infarct marginal zone and expressed connexin-43. Connexin-43 was abundantly expressed in the CSCs group whereas it was rarely expressed in the BMSCs group, and even not expressed in the PBS group. These findings suggest that CSCs are superior to BMSCs in modulating the electrophysiological stability and the ventricular fibril ation threshold in the short term after transplantation, which is closely correlated with the expression of connexin-43.

BACKGROUND:Piglitazone, aperoxisome proliferator-activated receptor γ(PPAR-γ) agonist, has been demonstrated topromote survivalandcardiac differentiation ofexogenous bone marrow mesenchymal stem celsto improvecardiacfunction.In this study, we attempted to investigate whether pioglitazone couldinduce cardiac differentiation of endogenous bone marrow mesenchymal stem celsandimprove cardiacfunction, andmeanwhile, probed into the relevant mechanisms.
OBJECTIVE:To compare the therapeutic efficacy ofpioglitazone combined with bone marrow mesenchymal stem cel transplantation, pioglitazone alone and phosphate buffer solution(PBS)and to investigatetherelevant mechanisms.
METHODS:ThirtySprague-Dawley ratswith myocardial infarctioninducedby ligation of the left anterior descending coronary artery were randomized intocombined group (combination of bone marrow mesenchymal stem cels and pioglitazone), pioglitazone group andPBSgroup. Two weeks later, PKH26-labeled bone marrow mesenchymal stem cels inPBSorPBSalone wereinjected into the local infarct zone in the combinedgroup andthe other twogroups, respectively. Pioglitazone (3 mg/kg/d) was given by the oral gavage in the combinedand pioglitazone groups forcontinuous2weeks after cels transplantation. At 2weeks after treatment, cardiac functions were evaluated. In addition, expressions of PPAR-γ, connexin 43 and relative factors in transforming growth factor-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart.
RESULTS AND CONCLUSION:There were no differences in the baseline parameters of cardiac function between the two groups.Twoweeksafter treatment, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and left ventricular ejection fraction were significantlyimprovedin the combined groupcompared with the other two groups; the expression of PPAR-γ was significantly increased in different zones of the left ventriclein the combined andpioglitazone groups.In the combined group, there was a significantlyhigher expression of connexin 43, and the levels of transforming growth factor-β1, SMAD2 and SMAD3 were obviously attenuated in the infarctand marginal zones.However, no differences were found in the abovedeterminants between the pioglitazone andPBSgroups. To conclude, pioglitazone cannot induce the differentiation andproliferation of endogenous bone marrow mesenchymal stem cels, but pioglitazone combined with exogenous bone marrow mesenchymal stem cels can improve cardiac function post myocardial infarction.In this process,PPAR-γmight promote the connexin 43 expression inexogenous bone marrow mesenchymal stem celsviathe blockade oftransforming growth factor-β1/SMAD signaling pathway.

Objective:To evaluate the effects of different pacing modes (unipolar/bipolar) under left bundle branch pacing(LBBP) on ventricular mechanical synchrony and myocardial work using the pressure-strain loop technique.Methods:Twenty-nine patients with LBBP due to symptomatic bradycardia were collected as LBBP group in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from December 2018 to July 2020. Another 29 matched patients with right ventricular pacing (RVP) during the same period were also included as a RVP group. Each LBBP patient was programmed to different pacing modes (uni-/bio-polar) within 1 week after the operation.Under each pacing mode, the inter- and intra-ventricular mechanical synchronization were evaluated. Meanwhile, the global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by the left ventricular pressure-strain loops technique.Results:Compared with the RVP group, the mechanical synchrony in the LBBP group was significantly improved (all P<0.05). GWI, GCW, and GWE increased, while GWW decreased, and the differences were statistically significant (all P<0.05), there were no significant differences in ventricular mechanical synchronization, GWI, GCW, GWE, and GWW between unipolar and bipolar pacing in the LBBP group (all P>0.05), there were no significant differences in these parameters when increasing output voltage (all P>0.05). Conclusions:LBBP induces better mechanical synchronization and higher myocardial work efficiency than RVP. Different LBBP pacing modes do not affect ventricular mechanical synchronization and myocardial work efficiency.