目的 探索并建立非肿瘤类安宁疗护患者的综合医院-社区双向转介标准与转介服务流程.方法 通过文献回顾初步建立非肿瘤类疾病评估条目,设计李克特式量表开展信函式专家咨询,邀请权威安宁疗护服务专家进行指标评分,采用界值法、主成分分析法和专家集中判断法构建各类疾病的转介指标及标准体系.结果 通过两种量化分析方法,结合集中式咨询,最终构成了以病种为单位的安宁中心-社区非肿瘤类安宁疗护患者双向转诊评估指标体系.结论 该研究构建的转诊评估指标体系能够有效地形成全科医生和专科医生对于安宁疗护服务双向转诊的共识,提高安宁疗护服务资源的有效利用.

AIMS:The intervertebral disc is the largest avascular organ of the body. Vascularization of the disc has been typically regarded as a pathological feature of intervertebral disc degeneration (IDD). However, the underlying mechanism of vascularization in IDD is still unclear. The current study aimed to investigate the role of AF cell derived exosome (AF-exo) in the interaction with human umbilical vein endothelial cells (HUVECs) and its potential role in the regulation of vascularization in IDD.MAIN METHODS:Human AF tissues were obtained from patients with IDD and idiopathic scoliosis. The AF-exo were isolated and identified by transmission electron microscopy (TEM), nanoparticle trafficking analysis (NTA) and Western blotting. Then, the AF-exo were used for HUVECs cultures. The migration of HUVECs was observed in 2D and 3D cultures. The inflammatory phenotype of HUVECs was examined by Real-time PCR and enzyme-linked immunosorbent assay (ELISA). Additionally, apoptosis of HUVECs were analyzed by flow cytometry.KEY FINDINGS:Here, we for the first time found that AF cells could secrete AF-exo and that the AF-exo could be phagocytosed by HUVECs. Additionally, we found that degenerated AF-exo exerted pro-vascularization effect on HUVECs by promoting cell migration (in 2D and 3D cultures) and inflammatory factor expression including IL-6, TNF-α, MMP-3, MMP-13 and VEGF, whereas the application of non-degenerated AF-exo demonstrated inverse effects.SIGNIFICANCE:These results showed that AF-exo is an essential regulator mediating intercellular communication between AF cells and HUVECs, suggesting its important role in vascularization in the intervertebral disc.

Abstract Aims This study aims to investigate the current status of biventricular pacemaker and defibrillator implantation in chronic heart failure (CHF) patients with indications for primary prevention of sudden cardiac death (SCD) in China and the effects of cardiac resynchronization therapy (CRT)‐pacemaker (P) and CRT‐defibrillator (D) implantation on the clinical prognosis of CHF among patients undergoing CRT. Methods and results Overall, 798 consecutive patients who had devices implanted (implantable cardioverter defibrillator: 199, CRT‐D: 362, and CRT‐P: 237) from May 2012 to July 2013 in POSCD‐China, a multicentric prospective cohort study, were enrolled. The primary endpoint was all‐cause death, and the secondary endpoint was SCD. In total, 71.3% of patients had non‐ischaemic CHF. The mean follow‐up time was 27.7 ± 12.0 months, and death occurred in 158 cases, with 35 cases of SCD. CHF was the main cause of death (68.4%), followed by sudden death (22.2%). In the CRT‐P group, the SCD rate was 8.0%, which was much higher than that in the CRT‐D (3.3%) and implantable cardioverter defibrillator (2.0%) groups. No significant differences were identified in the all‐cause death rate between the CRT‐D and CRT‐P groups (CRT‐D vs. CRT‐P, 20.4% vs. 19.4%, P = 0.840). Conclusions In China, among CHF patients with indications for primary prevention of SCD who received device implantation, non‐ischaemic CHF was the main aetiology, and the most important cause of death was heart failure. No differences in all‐cause death were observed between the CRT‐D and CRT‐P groups, but the CRT‐D group had a lower SCD rate than the CRT‐P group.

Objectives: This study aimed to determine whether the serial changes of the electrocardiogram is associated with regression of left ventricular hypertrophy (LVH) after Liwen procedure. Background: Clinical application of the echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA, Liwen procedure) is an innovative approach to treat hypertrophic obstructive cardiomyopathy (HOCM). Methods: We enrolled 30 consecutive patients with HOCM who had undergone Liwen procedure in our Hypertrophic Cardiomyopathy Center, from June 2016 to January 2018. Electrocardiography (ECG) and echocardiogram were performed before and after Liwen procedure, and at each follow-up (1-week, 1, 3, 6 months and 1 year). The Sokolow-Lyon index (SLi), Q wave, R wave, S wave amplitude of 12-lead ECG and interventricular septal (IVS) thickness, left ventricular mass index (LVMI) by echocardiograms were measured in each patient. The sum of the ECG QRS amplitude on each lead was calculated. The reduction of SLi and QRS amplitude were used as improvement index. Results: The ECG leads with most improvement rate of the QRS wave amplitude of all cases were V1 and V2, both at 90%. The QRS wave amplitude in V1 leads and SLi were positively correlated with IVS thickness and LVMI at baseline and 1 year after Liwen procedure, respectively. The reduction of IVS thickness, LVMI and QRS wave amplitude in leads V1 and V2 were significant at one month after ablation and the follow-up period. SLi was significantly decreased at 3 months during the observation period. Similarly, the improvement of ECG QRS wave amplitude after the Liwen procedure tracked the gradual thinning of the IVS and the changes of SLi reflected the regression of LVH. Conclusion: The QRS wave amplitude reductions in lead V1 and SLi may be good indicators for evaluating the postoperative interventricular septal remodeling of the Liwen procedure. (C) 2020 Published by Elsevier Inc.

目的 探讨医教协同下全科-专科联合慢阻肺管理模式.方法 将在某院明确诊断为慢阻肺的患者80例,分为教学组40例和对照组40例,教学组以带教全科规范化培训住院医师为纽带,培养社区师资,定期举行专业培训,提高社区全科医生识别、诊断慢阻肺的能力,指导患者随访、肺康复等,实施紧密型全-专联合的管理模式.对照组开展常规的诊疗随访工作.评价两组患者吸烟控制情况、疫苗接种情况、规范用药情况、呼吸康复开展情况的变化.结果 医教协同模式能改善全科医师对慢阻肺管理的认知,教学组的慢阻肺患者吸烟控制情况、疫苗接种情况、规范用药情况、呼吸康复开展情况较对照组有明显差异.结论 以全科住院医师规范化培训的教学为纽带,以“医教协同”的模式,建立区域化全科-专科联合体,在二级医院的专科团队指导下,可以加强全科医师对呼吸慢病管理的意识,有利于促进慢阻肺患者的规范化管理.

Critical limb ischemia (CLI) is the leading cause of lower limb amputation. Traditional treatments for CLI have limitations. Studies have shown that thrombospondin-4 (TSP4) can promote the growth of neovascularization. In this study, we observed the angiogenesis efficiency of TSP4-overexpressing BMSC transplantation in CLI treatment. The recombinant FT106-tsp4-gfp lentiviral vector plasmid was constructed and transfected into 293FT cells. Primary BMSCs were successfully infected with the tsp4 virus, and TSP4 overexpression was confirmed before TSP4-BMSCs infusion. A rat CLI model was established, and 60 CLI rats were randomly divided into the CLI, BMSC + CLI and TSP4-BMSC + CLI groups. The effect of TSP4-BMSC on angiogenesis was detected by the motor function, immunohistochemistry and immunofluorescence staining assays. Neovascular density was detected by digital subtraction angiography (DSA). Our results demonstrated that TSP4-BMSCs improved the motor function score of the CLI rats and increased MMP2, MMP9, Ang-1, VEGF and vWF protein expression in tissue of the ischaemic area. Meanwhile, new blood vessels can be observed around the ischemic area after TSP4-BMSCs treatment. Our data illustrate that TSP4-BMSCs can promote the recovery of motor function in diabetic hind limb ischaemic rats. TSP4-BMSCs have better therapeutic effects than BMSCs.

Angiogenesis is a pathological signature of intervertebral disc degeneration (IDD). Accumulating evidence has shown that notochordal cells (NCs) play an essential role in maintaining intervertebral disc development and homeostasis with inhibitive effect on blood vessel in-growth. However, the anti-angiogenesis mechanism of NCs is still unclear. In the current study, we, for the first time, isolated NC-derived exosomes (NC-exos) and showed their increased concentration following compressive load cultures. We further found that NC-exos from 0.5 MPa compressive load cultures (0.5 MPa/NC-exos) inhibit angiogenesis via transferring high expressed microRNA (miR)-140-5p to endothelial cells and regulating the downstream Wnt/β-catenin pathway. Clinical evidence showed that exosomal miR-140-5p expression of the nucleus pulposus is negatively correlated with angiogenesis in IDD. Finally, 0.5 MPa/NC-exos were demonstrated to have a therapeutical impact on the degenerated disc with an anti-angiogenesis effect in an IDD model. Consequently, our present findings provide insights into the anti-angiogenesis mechanism of NC-exos, indicating their therapeutic potential for IDD.

BACKGROUND:A stroke caused by angiostenosis always has a poor prognosis. Bone marrow stromal cells (BMSC) are widely applied in vascular regeneration. Recently, thrombospondin-4 (TSP4) was reported to promote the regeneration of blood vessels and enhance the function of endothelial cells in angiogenesis. In this work, we observed the therapeutic effect of TSP4-overexpressing BMSCs on angiogenesis post-stroke.METHODS:We subcloned the tsp4 gene into a lentivirus expression vector system and harvested the tsp4 lentivirus using 293FT cells. Primary BMSCs were then successfully infected by the tsp4 virus, and overexpression of GFP-fused TSP4 was confirmed by both western blot and immunofluorescence. In vitro, TSP4-overexpressing BMSCs and wild-type BMSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). The expression level of TSP4, vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Wound healing, tube formation and an arterial ring test were performed to estimate the ability of TSP4-overexpressing BMSCs to promote the angiogenesis of endothelial cells. Using a rat permanent middle cerebral artery occlusion (MCAO) model, the effect of TSP4-overexpressing BMSCs on the regeneration of blood vessels was systematically tested by the neurological function score, immunohistochemistry and immunofluorescence staining assays.RESULTS:Our results demonstrated that TSP4-overexpressing BMSCs largely increased the expression of VEGF, angiopoietin-1 (Ang-1), matrix metalloprotein 9 (MMP9), matrix metalloprotein 2 (MMP2) and p-Cdc42/Rac1 in endothelial cells. TSP4-BMSC treatment notably up-regulated the TGF-β/Smad2/3 signalling pathway in HUVECs. In vivo, the TSP4-BMSC infusion improved the neurological function score of MCAO rats and expanded the expression of the von Willebrand factor (vWF), Ang-1, MMP2 and MMP9 proteins in cerebral ischemic penumbra.CONCLUSIONS:Our data illustrate that TSP4-BMSCs can promote the proliferation and migration of endothelial cells and tube formation. We found that TSP4-BMSC infusion can promote the recovery of neural function post-stroke. The tsp4 gene-modified BMSCs provides a better therapeutic effect than that of wild-type BMSCs.

In recent years, cellular immunotherapy has served an important role in the combined treatment of hepatocellular carcinoma. The possibility of specific cell therapies for the treatment of solid tumours has been further explored following the success of chimeric antigen receptor (CAR)‑T cell therapy in the treatment of haematological tumours. The present study aimed to evaluate the specificity and efficiency of c‑MET‑targeted CAR‑NK cell immunotherapy on human liver cancer in vitro. A CAR structure that targeted and recognised a c‑MET antigen was constructed. c‑MET‑CAR was transferred into primary NK cells using lentiviral infection. c‑MET‑positive HepG2 cells were used as an in vitro study model. The cytotoxicity assay results revealed that c‑MET‑CAR‑NK cells exhibited more specific cytotoxicity for HepG2 cells with high c‑MET expression compared with the lung cancer cell line H1299, which has low levels of c‑MET expression. The results of the present study demonstrated that c‑MET may be a specific and effective target for human liver cancer cell CAR‑NK immunotherapy. Based on these results, CAR‑NK cell‑based immunotherapy may provide a potential biotherapeutic approach for liver cancer treatment in the future.

A 70-year-old woman presented with severe hypertrophic obstructive cardiomyopathy (HOCM) (maximum ventricular septum thickness of 28 mm, peak pressure gradient (PG) in the left ventricular outflow tract (LVOT) of 153 mmHg). We performed percutaneous trans-apex intra-septal radiofrequency ablation (PTAISRA) of the interventricular septum under guidance of transthoracic echocardiography. At six-months follow up, the symptoms were significantly relieved; the septal thickness was reduced to 18 mm and the peak LVOT PG reduced to 44 mmHg. This case highlights a novel use of radiofrequency ablation for the treatment of HOCM. Long-term safety and efficacy merit evaluation.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) may provide comparable protection while avoiding the disadvantage of transvenous lead, but the abnormal features of the hypertrophic cardiomyopathy (HCM) electrocardiogram (ECG) make it a challenge for S-ICD template screening. We aimed to investigate S-ICD eligibility according to the S-ICD manufacturer's surface ECG screening template in China, and further analyze its corresponding ineligible predicting factors in 12-lead suface ECG. A total of 179 HCM patients (114 males; mean age: 45 ± 14 years) underwent S-ICD screening at rest and on exercise, among which 91 patients (50.8%) were eligible for S-ICD. Among the patients who passed screening, 43 (47.3%) had 3 vectors eligibility; 64 (70.3%) screening qualified on both sides; 10 patients (11.0%) passed the screening while the electrodes located only on the left parasternal line versus 17 patients (18.7%) moved to the right line. The secondary sensing vector (Lead III) was mostly appropriate (53.6%), followed by the primary sensing vector (lead II, 53.1%) and the alternate sensing vector (Lead I, 46.9%). Higher R wave was the major cause, accounted for 70.5%, for screening failure. There existed significant difference in T wave in lead II, aVF, V5 and V6, adds R/T ratio in lead V5 and V6, between the screening success group (group A) and screening failure group (group B) at rest and on exercise. A multivariable logistic regression analysis was performed to identify that R/T ≤ 3.5 in lead V5 was the independent factor to predict the screening ineligibility, with odds ratio 3.648. S-ICD screening success is 50.8% in HCM patients, which is much lower than that in other studies. R/T ≤ 3.5 in lead V5 in 12-lead surface ECG was an independent predicting factor for screening failure.

To the Editor: A 20-year-old unmarried young male was hospitalized for 1 week due to an unexpected finding of heart enlargement at his regular physical examination. His parents and two sisters presented no abnormal findings in electrocardiogram (ECG) and echocardiography (Echo) examinations. He had an uncle with unexplained sudden death at the age of 47 years. The patient had no history of drug abuse, smoking, heavy alcohol consumption, or illicit drug use. Blood tests showed elevated pro-brain natriuretic peptide (2292 pg/ml, normal range: <125 pg/ml), creatine kinase-muscle/brain mass (10.3 ng/ml, normal range: 0.3–4.0 ng/ml), alanine transaminase (194 U/L, normal range: 9–50 U/L), and aspartate aminotransferase (271 U/L, normal range: 15–40 U/L), while other blood test results were within normal range. The 12-lead surface ECG revealed atrial rhythm with 2:1 atrial ventricular block (AVB) and Type B Wolff-Parkinson-White syndrome (WPW), ventricular rate of 43 beats/min left ventricular (LV) hypertrophy with strain, and interventricular block. A previous ECG had been taken at another hospital about 1 week ago and also showed atrial rhythm and Type B WPW, but the ventricular rate was 72 beats/min (A:V = 1:1) at that time. The Echo indicated heart enlargement (left atrium [LA] 47 mm, right atrium [RA] 43 mm, LV 61 mm × 68 mm × 86 mm, and right ventricular [RV] 33 mm), diffused thickening of interventricular septum and LV walls up to 18 mm and decreased movement, low LV ejection fraction (LVEF; 40%), and mild mitral and tricuspid regurgitation. X-ray showed LV enlargement with a cardiothoracic ratio of 0.64. Then, the patient underwent an electrophysiological study (EPS) to verify the arrhythmias. Before the programmed stimulation examination, the intracardiac electrogram showed alternate II° I and II° II AVB. During the coronary sinus (CS5,6) stimulation with a parameter of S1 = 600/500/450 ms, artrioventricular (AV) was maintained at 2:1 conduction, HV was stable for 28 ms, but AH became increasingly longer. With a parameter of S1 = 400 ms, AV conduction rate was changed at 2:1–4:1; however, HV was maintained at 28 ms. When RV was stimulated with 600 ms, VA retrograde blocked. The patient's EPS showed evidence of preexcitation and AVB, exhibited an unusual pattern of high-grade (2:1–4:1) AVB when stimulated CS with S1 = 400 ms. The highly unusual pattern of high-grade AVB with an accessory pathway may be simply explained by a block that has occurred in the proximal AV node because these accessory pathways lie directly and distally to the AV node. The EPS results indicated that AV conduction over the bypass was partly impaired because when potential H occurred, potential V was always present. Otherwise, even if complete AV nodal block was present, routine AV bypass conduction would become fully manifest and support 1:1 AV conduction. Radiofrequency catheter ablation of the bypass was not attempted because it failed to induce sustained tachycardia arrhythmia. The patient had strong indications for a ventricular pacing therapy because of existence of II° II AVB and with the addition of his heart dysfunction, cardiac resynchronization therapy (CRT) was the best option for him. Because the risk of sudden cardiac death (SCD) at 5 years was 3.18%, 2014 European Society of Cardiology (ESC) recommendation[1] of implantable cardiac defibrillation (ICD) was generally not indicated. To further optimize the procedure and ensure optimal treatment results, we performed the CRT with a guidance by three-dimensional (3D) electroanatomic mapping (EAM) and anchored the LV lead to the latest activated region. The outer straight sheath was anchored to the CS by means of decapolar CS electrode (Johnson, USA). CS angiography results showed that the anterolateral vein (ALV), lateral vein, and posterolateral vein (PLV), and the latter was thicker than the first two [Figure 1a]. Then, we conducted a CS vein mapping procedure with the LV lead 4296 (Medtronic, USA), which was connected to Ensite Navx (Abbott, USA) via a crossover clamp. We placed the lead in the great vein, ALV, lateral vein, and PLV along with a Runthrough NS wire (Terumo, Japan). The reference line was set as the summit of QRS for the surface ECG, and electrical delay was measured in milliseconds between the reference line on the surface ECG and the onset on the bipolar intracardiac electrogram. We collected the activation potential (reflected by the activation time) point by point when pulling back the lead and determined that the purple area was the latest activated region while the white one was the earliest. At the end, it is easy to detect the latest activated region where the lead could actually be reached [Figure 1b]. Candidate pacing sites were tested for phrenic nerve stimulation (PNS) by 10 V unipolar pacing on the tip of the lead. Finally, the lead was located at the end of the PLV, where the parameters were good, and no PNS [Figure 1c]. Post-ECG showed atrial rhythm, VAT pacing mode.Figure 1: (a) Coronary angiography image; (b) three-dimensional EAM results (AP and LAO position): the latest activated region was also located at the end of the posterolateral vein, and the LV lead was located in the outer one branch. (c) Final X-ray images, LAO position. GV: Great vein; ALV: Anterolateral vein; LV: Left ventricular; PLV: Posterolateral vein; EAM: Electroanatomic mapping; AP: Anteroposterior; LAO: Left anterior oblique.The patient underwent CRT-pacemaker (CRT-P) implantation without complications, was also prescribed a standardized β-blocker/angiotensin receptor blocker (ARB)/spironolactone, and was advised to avoid high-intensity physical activity. To determine the potential genetic source of the patient's clinical presentation, one month after the treatment, we performed gene analysis of blood. The exons of hypertrophic cardiomyopathy (HCM)-related genes were amplified and sequenced by targeted exome capture on an Illumina/SolexaHiSeq 2000 sequencer. It was revealed that the patient has a heterozygous lysosome-associated membrane protein 2 (LAMP2) gene mutation caused by a G>A transition in base 928 of exon 7, and a mutation in the MYBPC3 gene caused by G>A transition in base 122 of exon 2, supporting the diagnosis of Danon disease. Gastrocnemius muscle biopsy showed myocyte vacuolization, and periodic acid–Schiff staining (Wuhan Servicebio Technology CO., LTD) revealed diffuse glycogen deposition. Genotyping results of family members (his parents and two sisters) were also negative for LAMP2 mutations, indicating that the patient has a de novo LAMP2 mutation. Three months after the procedure, an Echo examination showed that his heart had become smaller (LA 43 mm, RA 38 mm, LV 61 mm × 65 mm × 87 mm, and RV 28 mm), and LVEF increased slightly to 41%. After another 3 months (6 months post-procedure), the LVEF was still maintained at 40%. The programmed results showed that all parameters from the three leads were good, and no malignant events, except several preatrial contractions. Based on the poor progression of Danon disease, CRT is the only bridge treatment to prevent worsening of heart function, and we again communicated with his parents about heart transplantation and the lifetime sequelae. With the exception of adding 3D mapping with the LV lead (no extra charges), CRT implantation was conducted as the conventional procedure, so it was approved by the hospital's ethics committee and deemed not require formal informed consent. Danon disease is an X-linked dominant inherited disorder, which is caused by deficiency of the LAMP2, resulting in glycogen deposition in myocardial, skeletal, and brain cells. Clinical manifestation include cardiomyopathy, conduction abnormalities, skeletal myopathy, and intellectual disability.[2] It manifests predominantly in males at an earlier age with more severe symptoms than that of females.[3] Genetic testing has a direct impact on clinical diagnosis, treatment, and prognosis in a range of inherited arrhythmia syndromes and cardiomyopathies and should be considered in such cases.[4] We think that presentation of the classic syndrome should prompt the clinician to investigate for Danon disease, which can be definitively diagnosed by genetic testing and muscle biopsy. As mentioned above, although lacking skeletal myopathy and intellectual disorders, the patient fit other indications for Danon disease, specifically the genetic testing and muscle biopsy results. ECG showed atrial rhythm, Type B WPW, alternate II° I and II° II AVB. Based on our previous EPS results, there was a fasciculoventricular pathway. Since such a bypass could not cause tachycardia, there was no need to ablate it. Furthermore, the patient had a strong indication of ventricular pacing, in view of LV dysfunction, so CRT was suggested. The risk of SCD at 5 years was 3.18%; ESC recommendation was that ICD is generally not indicated. On the other hand, SCD is the most common ultimate clinical cause in such patients if left untreated. Unfortunately, ICD therapy does not always prevent SCD or terminate lethal ventricular tachyarrhythmias in Danon disease. Therefore, no matter which type of cardiomyopathy or the severity of heart failure, timely evaluation for a heart transplant is strongly recommended. In view of the need to maintain LV function, the ineffectiveness of defibrillation, the financial load of ICD, and parental support, the patient received CRT-P to preserve cardiac function and as a short-run bridge therapy for heart transplantation. Long-term pharmacologic therapy is only experimental due to the lack of clinical trials on β-blockers, angiotensin-converting enzyme inhibitor/ARB, and spironolactone. Superior CRT outcome occurs when the LV lead position coincides with the region of latest mechanical contraction. Studies have revealed that a greater delay in time from the onset of the QRS complex to the local sensed LV lead EGM (Q-LV) is associated with a greater possibility of benefit from CRT.[56] The conventional anatomical LV lead placement strategy does not verify vein targeting with maximal electrical delay in many CRT patients, resulted in CRT nonresponse influencing long-term survival rate and quality of life. Rad et al.[7] reported that conducting CS 3D electrical mapping with a guidewire for LV lead placement in the latest activated region and avoidance of PNS improves the outcome of CRT, particularly in patients with multiple selectable target veins. It is suggested that CS 3D mapping can be used at the time of CRT implantation to assess LV electrical activation pattern and guide LV lead placement to the latest activated region lack PNS. We mapped directly the activation time of CS point by point with the LV lead, which was anchored to the latest activated region free of PNS. This method is more accurate and practical since the region guidewire, but not the LV lead, could reach. The patient was pacing dependent because of the presence of II° II AVB, so CRT was vital to maintain LV function. Since the ALV and lateral vein were thinner and there were three branches in PLV, we made an attempt to affirm whether the LV lead could anchor in ALV or lateral vein, but the lead failed to go forward sufficiently because of narrowness and early activation mapping. We then made sure which branch of PLV was the latest activated region with no PNS. At last, we located the lead 4296 in the outer branch of PLV. Six months later, his heart function was preserved with no serious adverse events. As a result, early detection and treatment in addition to family screening are necessary components in the management of the disease. This case report validates the importance of genetic testing and muscular biopsy in the assessment of patients with undiagnosed hypertrophic cardiomyopathy and conduction disorders. Furthermore, for those with an indication of ventricular pacing combined with LV dysfunction, CS EAM guidance for CRT may be a better choice to anchor the LV lead to the latest activation target vein and lack of PNS easily. There are some limitations of this procedure. First, we had only a standard bipolar LV lead available instead of a quadrupolar LV lead, or MPP, which could further optimize the pacing polarity. Second, the available target veins were limited for this patient, but may provide a new method to guide optimization of CRT implantation in the future. Third is the lack of cardiomyocyte biopsy due to parental decision. Fourth, failure to CRT with defibrillator implantation versus palliative CRT was partly ascribed to economic reasons. The last constraints were short visits and long intervals between follow-up visits. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

为了实现三相LCL型并网逆变器的电流追踪,提出了一种分数阶滑模控制方案.首先建立三相LCL并网逆变器在d-q坐标系下的数学模型,然后根据滑模控制理论对逆变器进行控制器设计.针对传统滑模控制中的抖振现象引入分数阶理论,确定分数阶滑模面和分数阶滑模趋近律,利用分数阶微分算子抑制系统抖振.最后在MATLAB/Simulink仿真软件中进行仿真验证,仿真结果表明,分数阶滑模控制有效抑制了传统滑模控制中的抖振现象,提高了控制系统的响应速度和跟踪精度,具有更好的动态性能和鲁棒性.

To the Editor: Radiofrequency catheter ablation (RFCA) is the first‐line therapy for symptomatic paroxysmal supraventricular tachycardia. However, several life‐threatening complications remain underestimated. Herein, we report an atypical case of RFCA complicated by acute pulmonary embolism (PE), an extremely rare but potentially fatal complication. After 3 months of anticoagulation therapy, PE was treated successfully.

We reported a case that left ventricular (LV) lead with retained guidewire was used 6 years ago, but the LV lead was broken during 6 years of follow-up. Although the retained guidewire technique has already been abandoned, the long-term safety of retained guidewire lead appears to be an even greater concern.

2771 To the Editor: Dilated cardiomyopathy (DCM) is characterized by ventricular chamber enlargement and systolic dysfunction. DCM is identified when complicated by severe clinical symptoms and disability and ultimately leads to progressive heart failure (HF) and a decline in left ventricular (LV) contractile function, ventricular and supraventricular arrhythmias, conduction system abnormalities, thromboembolism, and sudden heart failure‐related death. Overactivation of renin‐angiotensin‐aldosterone systems (RAAS) is one of the key detrimental mechanisms of DCM progression and is associated with poor prognosis. Despite considerable advances in neurohumoral modulation therapy including angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), mortality and morbidity among DCM patients remains high.

Multidrug resistance (MDR) and targeted therapies present major challenges in tumor chemotherapy. Nanoparticles (NPs) hold promise for use in cancer theranostics due to their advantages in terms of tumor-targeted cytotoxicity and imaging. In this study, we developed N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC)/alginate-encapsulated Fe3O4 magnetic NPs (HTCC-MNPs) and applied them to MDR gastric cancer both in vivo and in vitro. HTCC-MNPs were fabricated from sodium alginate (ALG), Fe3O4 and HTCC using an ionic gelation method. The sizes and physical characteristics of the NPs were determined using dynamic light scattering, transmission electron microscopy (TEM) and zeta potential analysis. The HTCC-MNPs exhibited excellent water solubility and biocompatibility as well as significantly reduced cell viability in the drug-resistant cancer cell line SGC7901/ADR, but not in normal gastric cells (P < 0.05). An analysis of LC3 expression demonstrated the involvement of autophagy in HTCC-MNP cytotoxicity. Additionally, apoptosis was verified using a DNA content assay. HTCC-MNPs led to mitochondrial membrane potential loss, decreased ATP production and excessive reactive oxygen species (ROS) generation compared to a control group (P < 0.05). Magnetic resonance imaging showed enrichment of HTCC-MNPs in tumor-bearing mice. In vivo bioluminescence imaging and tumor volume measurements revealed that HTCC-MNPs markedly inhibited in vivo tumor growth (P < 0.05). In conclusion, HTCC-MNPs significantly inhibited MDR gastric tumor growth and reduced tumor volume via the induction of cellular autophagy and apoptosis, which was attributed to mitochondrial dysfunction and excessive ROS accumulation.

BACKGROUND:Reverse-mode of the Na(+)/Ca(2+) exchanger (NCX) stimulation provides cardioprotective effects for the ischemic/reperfused heart during ischemic preconditioning (IP). This study was designed to test the hypothesis that pretreatment with an inhibitor of cardiac delayed-rectifying K(+) channel (IKr), E4031, increases reverse-mode of NCX activity, and triggers preconditioning against infarct size (IS) and arrhythmias caused by ischemia/reperfusion injury through mitoKCa channels.MATERIALS AND METHODS:In the isolated perfused rat heart, myocardial ischemia/reperfusion injury was created by occlusion of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Two cycles of coronary occlusion for 5 min and reperfusion were performed, or pretreatment with E4031 or sevoflurane (Sevo) before the 30 min occlusion with the reversed-mode of NCX inhibitor (KB-R7943) or not.RESULTS:E4031 or Sevo preconditioning not only markedly decreased IS but also reduced arrhythmias, which was significantly blunted by KB-R7943. Furthermore, these effects of E4031 preconditioning on IS and arrhythmias were abolished by inhibition of the mitoKCa channels. Similarly, pretreatment with NS1619, an opener of the mitoKCa channels, for 10 min before occlusion reduced both the infarct size and arrhythmias caused by ischemia/reperfusion. However, these effects weren't affected by blockade of the NCX with KB-R7943.CONCLUSION:Taken together, these preliminary results conclude that pretreatment with E4031 reduces infarct size and produces anti-arrhythmic effect via stimulating the reverse-mode NCX, and that the mitoKCa channels mediate the protective effects.