Objective::The long QT syndrome type 2 is caused by the loss-of-function mutations in the KCNH2 gene, which encodes hERG1, the voltage-gated potassium channel. The hERG1 channels conduct rapid delayed rectifier K + currents ( IKr) in the human cardiac tissue. KCNH2 encodes 2 main isoforms—hERG1a and hERG1b, which assemble to form the homomeric or heteromeric hERG1 channels. However, the functional characteristics of the heteromeric hERG1 channels in long QT syndrome type 2 are not clear. In this study, a novel mutation in the N-terminus of hERG1a (F129I) was identified in a proband of long QT syndrome type 2. The purpose of this study was to identify the electrophysiological change of homomeric and heteromeric hERG1 channels with the F129I-hERG1a. Methods::Candidate genes were screened by direct sequencing. F129I-hERG1a was cloned in the pcDNA3.1 vector by site-directed mutagenesis. Then, the wild-type (WT) hERG1a and/or F129I-hERG1a were transiently expressed in the HEK293 cells with or without hERG1b co-expression. The expression levels of the transgenes, cellular distribution of hERG1a and hERG1b, and the electrophysiological features of the homomeric and the heteromeric hERG1 channels with the WT-hERG1a or F129I-hERG1a were analyzed using whole-cell patch-clamp electrophysiology, western blotting, and immunofluorescence techniques.Results::The proband was clinically diagnosed with long QT syndrome type 2 and carried a heterozygous mutation c.385T>A (F129I) in the KCNH2 gene. Electrophysiology study proved that the F129I substitution in hERG1a significantly decreased IKr in both the homomeric and heteromeric hERG1channels by 86% and 70%, respectively (WT-hERG1a (54.88 ± 18.74) pA/pF vs. F129I-hERG1a (7.34 ± 1.90) pA/pF, P < 0.001; WT-hERG1a/hERG1b (89.92 ± 24.51) pA/pF vs. F129I-hERG1a/hERG1b (26.54 ± 9.83) pA/pF, P < 0.001). The voltage dependence of I Kr activation (V ? and k) was not affected by the mutation in both the homomeric and heteromeric hERG1 channels. The peak current densities and the kinetic characteristics of I Kr were comparable for both WT/F129I-hERG1a and WT-hERG1a. The channel inactivation and deactivation analysis showed that F129I substitution did not affect deactivation of the homomeric hERG1a channel, but significantly accelerated the deactivation and recovery from inactivation of the heteromeric hERG1a/hERG1b channel based on the time constants of fast and slow recovery from deactivation F129I-hERG1a/hERG1b vs. WT-hERG1a/hERG1b ( P < 0.05). Western blotting and immunofluorescence labeling experiments showed that maturation and intracellular trafficking of the F129I-hERG1a protein was impaired and potentially increased the ratio of hERG1b to hERG1a in the F129I-hERG1a/hERG1b tetramer channel, thereby resulting in electrophysiological changes characteristic of the long QT syndrome type 2 pathology. Conclusions::IKr was significantly reduced in the homomeric and heteromeric hERG1 channels with F129I-hERG1a. The F129I mutation significantly accelerated the deactivation and recovery from inactivation of the heteromeric F129I-hERG1a/hERG1b channel. F129I-hERG1a exhibited impaired maturation and intracellular trafficking, thereby potentially increasing the ratio of the hERG1b to hERG1a stoichiometry in the hERG1 tetrameric channel. These changes demonstrated the importance of the heteromeric hERG1 channel in long QT syndrome type 2 pathophysiology.

Objective::The long QT syndrome type 2 is caused by the loss-of-function mutations in the KCNH2 gene, which encodes hERG1, the voltage-gated potassium channel. The hERG1 channels conduct rapid delayed rectifier K + currents ( IKr) in the human cardiac tissue. KCNH2 encodes 2 main isoforms—hERG1a and hERG1b, which assemble to form the homomeric or heteromeric hERG1 channels. However, the functional characteristics of the heteromeric hERG1 channels in long QT syndrome type 2 are not clear. In this study, a novel mutation in the N-terminus of hERG1a (F129I) was identified in a proband of long QT syndrome type 2. The purpose of this study was to identify the electrophysiological change of homomeric and heteromeric hERG1 channels with the F129I-hERG1a. Methods::Candidate genes were screened by direct sequencing. F129I-hERG1a was cloned in the pcDNA3.1 vector by site-directed mutagenesis. Then, the wild-type (WT) hERG1a and/or F129I-hERG1a were transiently expressed in the HEK293 cells with or without hERG1b co-expression. The expression levels of the transgenes, cellular distribution of hERG1a and hERG1b, and the electrophysiological features of the homomeric and the heteromeric hERG1 channels with the WT-hERG1a or F129I-hERG1a were analyzed using whole-cell patch-clamp electrophysiology, western blotting, and immunofluorescence techniques.Results::The proband was clinically diagnosed with long QT syndrome type 2 and carried a heterozygous mutation c.385T>A (F129I) in the KCNH2 gene. Electrophysiology study proved that the F129I substitution in hERG1a significantly decreased IKr in both the homomeric and heteromeric hERG1channels by 86% and 70%, respectively (WT-hERG1a (54.88 ± 18.74) pA/pF vs. F129I-hERG1a (7.34 ± 1.90) pA/pF, P < 0.001; WT-hERG1a/hERG1b (89.92 ± 24.51) pA/pF vs. F129I-hERG1a/hERG1b (26.54 ± 9.83) pA/pF, P < 0.001). The voltage dependence of I Kr activation (V ? and k) was not affected by the mutation in both the homomeric and heteromeric hERG1 channels. The peak current densities and the kinetic characteristics of I Kr were comparable for both WT/F129I-hERG1a and WT-hERG1a. The channel inactivation and deactivation analysis showed that F129I substitution did not affect deactivation of the homomeric hERG1a channel, but significantly accelerated the deactivation and recovery from inactivation of the heteromeric hERG1a/hERG1b channel based on the time constants of fast and slow recovery from deactivation F129I-hERG1a/hERG1b vs. WT-hERG1a/hERG1b ( P < 0.05). Western blotting and immunofluorescence labeling experiments showed that maturation and intracellular trafficking of the F129I-hERG1a protein was impaired and potentially increased the ratio of hERG1b to hERG1a in the F129I-hERG1a/hERG1b tetramer channel, thereby resulting in electrophysiological changes characteristic of the long QT syndrome type 2 pathology. Conclusions::IKr was significantly reduced in the homomeric and heteromeric hERG1 channels with F129I-hERG1a. The F129I mutation significantly accelerated the deactivation and recovery from inactivation of the heteromeric F129I-hERG1a/hERG1b channel. F129I-hERG1a exhibited impaired maturation and intracellular trafficking, thereby potentially increasing the ratio of the hERG1b to hERG1a stoichiometry in the hERG1 tetrameric channel. These changes demonstrated the importance of the heteromeric hERG1 channel in long QT syndrome type 2 pathophysiology.

Objective? To summarize the nursing experience for 6 patients receiving wireless pacemaker implantation. Methods? The nursing experience for 6 patients who received wireless pacemaker implantation for the first time in Beijing Anzhen Hospital, Capital Medical University from August to October 2018. The nursing highlights included preoperative nursing, operative nursing, postoperative monitoring, nursing, follow-up and education. Results? 2 of the 6 patients sustained atrial fibrillation combined with long pause, and 4 sustained atrionector lesion combined with incidental long pause. The threshold value and perception of pace-making was sound and the impedance was ideal during operation. No complication was found during and post operation. The surgical time for implanting wireless pacemakers was short and the patients' appearance was not affected. Their mental burden was relatively light. Nursing procedures were simpler than the those for traditional pacemakers. Conclusion? Wireless pacemakers reduce airbag and wire-related complications and is promising in clinical use. But nursing experience needs to be observed clinically and summarized.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective To investigate the influence of nursing care on the anxiety and depression of patients with coronary heart disease,who underwent percutaneous coronary intervention (PCI). Methods Sixty-five patients who received the coronary intervention treatment were selected and randomly divided into the intervention group (33 cases) and the control group (32 cases). The degrees of depression and anxiety in these patients were assessed by the patient Health Questionnaire-9 (PHQ-9) scale and Generalized Anxiety Disorder-7 (GAD-7) scale before and after PCI. The control group received clinical conventional nursing care. The intervention group received psychological intervention on the basis of conventional nursing. Results Before the intervention, there was no difference of PHQ-9 and GAD-7 scores between the two groups (P>0.05). However,after the intervention, the PHQ-9 and GAD-7 scores of both groups reduced significantly (P<0.05). Moreover,significant importance was found in the reduction of the two scales′ scores in the intervention group compared with the control group (P<0.05). Conclusions Psychological intervention can obviously relieve the negative emotions of patients with coronary heart disease,which is of important clinical importance to the guarantee of successful surgery and patient recovery.

Objective To determine whether Ca2+ activated Cl- current(Icl(Ca)) contributes to the functional remodeling of the failing heart.Methods Whole cell patch-clamp recording technique was employed to record the Icl(Ca) in cardiac myocytes enzymatically isolatedfrom rapidly pacing induced canine failing hearts at room temperature and compared that of the normal hearts (Nor).Results Thecurrent density of DIDS(200M)sensitive Icl(Ca) induced by intracellular Ca2+ release trigged by L-type Ca2+ current(Ica,L)wassignificantly decreased in heart failare(HE)cells compared to Nor cells.At membrane voltage of 20mV,the Icl(Ca) density was 3.02±0.54 pA/pF in Nor(n=6)vs.1.31±0.25 pA/pF in HF(n=8)cells,(P＜0.01),while the averaged Ica,L density did not show differencebetween two groups.The time constant of current decay of Icl(Ca) was similar in both types of cells.On the other hand,in intra cellularCa2+ clamped mode,where the[Ca2+];was maintained at 100nmol/L,Icl(Ca) density be increased significantly in HF cells when themembrane voltage at+30mV or higher.Conclusions Our results suggest that Icl(Ca) density was decreased in pacing induced failingheart but the channel function be enhanced.Impaired Ca2+ handing in HF cells rather than reduced,Icl(Ca) channel function itself may havecaused this abnormality.The Icl(Ca) density reduction might contribute to the prolongation of action potential in failing heart.The Icl(Ca)channel function up-rugulation is likely to cause cardiac arrhythmia by inducing a delayed after depolarization,when Ca2+ overloadoccurred in diastolic failing heart cells.