Traditional right ventricular pacing is non-physiological pacing, can lead to ventricular electrical and mechanical dyssynchmnization, which increases the risk of heart failure and atrial fibrillation. His-Purkinje system pacing is the hot research of physiological pacing method. The high thresholds and difficult implantation of his bundle pacing limits its application and popularization. In recent years, domestic scholars have proposed left bundle branch area pacing. Many studies have confirmed the safety and feasibility of left bundle branch area pacing. Left bundle branch pacing transmit down the conduction system, which can effectively achieve ventricular electrical and mechanical synchrony, At the same time, it also has many others advantages, such as good and stable electrical parameters, significantly improved cardiac function, and pacing across blocked parts. It will become the main development direction of physiological pacing in the future. This article aims to review the origin, standard and classification, advantages and limitations of left bundle branch area pacing.

BACKGROUND:Calcium channel abnormalities can damage myocardium. Heroin can directly affect calcium ion channel, and alter myocardial structure.
OBJECTIVE:To study the changes of heroin-induced myocardial ultrastructure, L-type calcium channel current and action potential of myocardial cel s after rat cardiac arrhythmia.
METHODS:Sprague-Dawley rats were randomly divided into control group and model group. In the model group, rats were administered heroin at initial dose of 5 mg/kg?d. The daily dose escalation method was used (increasing dose:2.5 mg/kg?d) to replicate rat models of heroin addiction. At 20 days, models of heroin addiction were successful y established. At 30 days after increasing the dose, rat models of heroin addiction-induced arrhythmias were further established.
RESULTS AND CONCLUSION:Compared with the control group, the electron microscopy demonstrated that myocardial structure changes mainly presented nuclear membrane shrinkage, nuclear condensation, nuclei became smal , chromatin assembled into blocks, mitochondria disordered and disappeared, sarcomeres disordered, focal fracture, and unclear myofilament in rat models of heroin addiction. Electric current-voltage curve of myocardial cel L-type calcium channel current showed the increasing trends. The 90%repolarization action potential was significantly shortened. These data indicated that heroin can directly lead to the pathological change of myocardial structure. Calcium channel current change is one of the main reasons for myocardial injury.

Abstract BACKGROUND:Caspase-8 plays an important role in starting the process of cel apoptosis, and diacetylmorphine can induce neuronal apoptosis. The relationship between the apoptosis of cerebelar granule neurons cels induced by diacetylmorphine and caspase-8 has not been reported. OBJECTIVE:To investigate the effect of caspase-8 on diacetylmorphine-induced neuronal apoptosis. METHODS:Cerebelar granule neurons from Sprague-Dawley rats aged 7 days were culturedin vitro. At 7 days, the cels were cultured with different dosage of diacetylmorphine (10, 40, 80, 100, 120 mg/L) and SP600125 for 24 hours, and were divided into control group, 80 mg/L diacetylmorphine group, diacetylmorphine+SP600125 group. Cel morphology was observed by Hoechst 33258 fluorescent staining, and cel apoptosis rate was measured by flow cytometry. Immunofluorescence staining, RT-PCR and western blot assay were used to detect caspase-8 mRNA and protein expression. RESULTS AND CONCLUSION:(1) After different dosage of diacetylmorphine was used to induce neuronal apoptosis, dark blue translucent apoptotic bodies were found in apoptotic cels, appearing with nucleus condensation, cohesion and fracture, and the apoptosis rate presented an increasing trend with increasing of drug dosage (P < 0.05). (2) Compared with the control group, caspase-8 mRNA and protein expression was remarkable under the intervention of 80 mg/L diacetylmorphine(P < 0.05); caspase-8 mRNA expression exhibited an increasing trend with increasing dosage of diacetylmorphine (P < 0.05), while caspase-8 mRNA and protein expression in the diacetylmorphine+SP600125 group was significantly lower than that in the 80 mg/L diacetylmorphine group (P < 0.05). These findings indicate that caspase-8 is involved in the process of diacetylmorphine-induced neuronal apoptosis, and meanwhile, it is also an important candidate of pro-apoptotic factors in the c-jun N-terminal kinase signaling pathway.

Objective To investigate the changes of serum creatine kinase (CK),creatine kinase isoenzyme (CK-MB),cardiac troponin I(cTnI)and electrocardiogram (ECG) before and after the treatment of pneumo-nia in children.Methods From December 2014 to December 2016,95 children with pneumonia were selected as the study group,and 48 healthy subjects who underwent the healthy assessment from December 2014 to January 2016 were selected as the control group.All children with pneumonia were treated after admission.2 mL of venous blood were collected from each research subject after the admission and patients in study group after treatment,serum was seperated,and levels of CK,CK-MB,cTnI were measured and the ECG record was conducted.Results The serum levels of CK,CK-MB and cTnI in the study group were higher than those in the control group (P<0.05);the incidences of ST segment elevation or depression,atrial premature beat,ven-tricular premature beat,sinus tachycardia and sinus bradycardia in the study group were higher than those in the control group,and the differences were statistically significant (P<0.05);the serum levels of CK,CK-MB and cTnI in the study group were lower than those before treatment,and the difference was statistically signif-icant (P<0.05);the incidences of atrial premature beat,ventricular premature beat,sinus tachycardia and si-nus bradycardia in the study group after treatment were lower than those before treatment,and the difference was statistically significant (P<0.05);the incidence of ST segment elevation or depression after treatment in the study group was lower than that before treatment,and there was no significant difference (P>0.05).Con-clusion The serum levels of CK,CK-MB,cTnI and ECG were obviously abnormal in children with pneumoni-a.After treatment,serum CK,CK-MB and cTnI levels can be reduced and ECG abnormalities can be ameliora-ted.

Objective:To analyze the molecular characteristics of hemagglutinin-neuraminidase (HN) gene of human parainfluenza virus type 3 (HPIV3) among the cases with acute respiratory tract infection (ARI) in Henan Province.Methods:Nasal/throat swab samples collected from patients with severe acute respiratory tract infection (SARI) in Luohe and patients with influenza-like illness (ILI) in Zhengzhou were used in this study. HPIV nucleic acids in the samples were detected using real-time fluorescent PCR. HPIV3-positive samples were subjected to RT-PCR for the amplification of HN genes and the sequences were analyzed with Sanger method. CExpress and MEGA7.0 software were used for sequences editing, evolution tree construction and gene sequence analysis.Results:A total of 374 throat swab samples collected form ARI cases in Luohe and Zhengzhou were tested and 20 (5.3%) of them were positive for HPIV3. Eighteen HPIV3 HN gene sequences were successfully amplified and all belonged to C3 subgroups, including 16 sequences of C3f genotype and two sequences of C3a genotype. The 18 HN gene sequences shared the homology of 97.6%-100.0% in nucleotide and 99.3%-100.0% in amino acid, but the differences between them and the prototype strain Wash/47885/57 were significant. There were 12 amino acid mutations shared by them, including four function-related mutations (H295Y, I391V, D556N and I53T). There were no significant differences in the nucleotide or amino acid sequences as compared with the epidemic strain of China/BCH4210A/2014.Conclusions:The C3f and C3a branches of HPIV3 were the epidemic genotypes in Henan Province in recent years and a local circulating prevalence might be established. Continuous and in-depth monitoring of HPIV3 C3 subtype would be of great significance for the prevention and control of HPIV3-associated diseases.

Objective: To investigate the effect of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) on the mitochondrial mass in rat adrenal pheochromocytoma (PC12) cells and the potential mechanisms. Methods: Highly differentiated PC12 cells were divided into control, 1, 10 or 20 μmol/L PBDE-47-treated groups and cultured for 24 h. Transmission electron microscopy was employed to observe the changes in mitochondrial morphology and quantity in PC12 cells. Flow cytometry was used to measure the fluorescence intensity of Nonyl Acridine Orange (NAO) , a fluorescent indicator of mitochondrial membrane cardiolipin, to reflect mitochondria mass. Western blotting was used to determine the expression levels of Mitofusion 1 (Mfn1) and Fission 1 (Fis1) proteins. To further explore the role of abnormal mitochondrial fusion and fission in PBDE-47-induced mitochondrial mass changes, PC12 cells were divided into control group, 5 μmol/L M1 treatment group, 20 μmol/L PBDE-47 treatment group and 5 μmol/L M1+20 μmol/L PBDE-47 combined treatment group and cultured for 24 h, then the fluorescence intensity of NAO and expression levels of Mfn1 and Fis1 proteins were detected. Results: The control group showed numerous mitochondria with normal morphology, while the number of mitochondria decreased after PBDE-47 treatment. Especially, the disappeared cristae, swelling and vacuoles of mitochondria and decreased fluorescence intensity of NAO (P<0.05) were observed in 10 and 20 μmol/L PBDE-47-treated groups. Meanwhile, the expression levels of Mfn1 and Fis1 proteins in the 10 and 20 μmol/L PBDE-47-treated groups were significantly decreased compared with control group (P<0.05) . However, 5 μmol/L M1 co-treatment with 20 μmol/L PBDE-47 significantly increased the levels of Mfn1 and Fis1 proteins and fluorescence intensity of NAO compared with the 20 μmol/L PBDE-47 group (P<0.05) . Conclusion PBDE-47 can inhibit the mitochondrial fusion and fission process, thus leading to damage of mitochondria mass in PC12 cells.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*