The research advance of risk factors and risk assessment of sudden unexpected death in epilepsy / 中华神经科杂志

Epilepsy is a common disease in nervous system, of which patients often present with spontaneous unpredictable spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is one of the most serious complications of epilepsy, and it is also the main cause of premature death of epileptic patients. Generalized tonic-clonic seizures, age and genetic factors are common risk factors of SUDEP. This article summarizes the classification of SUDEP and epidemiology, mechanism, risk factors, risk assessment and preventive methods of SUDEP to help physicians to understand the difference between SUDEP and sudden cardiac death.

Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

A four-protein metabolon assembled by a small peptide protein creates the pentacyclic carbonate ring of aldgamycins

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive

New furo3,2-hisochroman from the mangrove endophytic fungus Aspergillus sp. 085242 / 中国天然药物

Four new compounds, asperisocoumarin G (1), asperisocoumarin H (2), (±)-asperisocoumarin I [(±)-3], along with the known pergillin (4) and penicisochroman L (5) were isolated from a mangrove endophytic fungus Aspergillus sp. 085242 by further chemical investigation. The structures of the new compounds, including their absolute configurations, were established by analysis of HR-ESI-MS and NMR spectroscopic data, and ECD calculation. Asperisocoumarins G-I (1-3) were new isocoumarins belonging to the class of furo[3, 2-h]isocoumarins which are rarely found in natural sources. All of the isolated compounds were evaluated for their α-glucosidase inhibitory effects, and compounds 1 and 4 showed moderate α-glucosidase inhibitory activity, respectively. In an antimicrobial test, the racemate of 3 showed antibacterial activity against Salmonella.

Low deceleration capacity is associated with higher stroke risk in patients with paroxysmal atrial fibrillation / 中华医学杂志(英文版)

Background@#Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction; however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF.@*Methods@#The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed.@*Results@#We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years); 38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356–6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2) (2.25 ± 1.48 vs. 1.40 ± 1.34, t = -4.907, P = 0.001) and CHA2DS2-vascular disease, age 65–74 years and female category (VASc) (3.76 ± 1.95 vs. 2.71 ± 1.87, t = -4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r = -0.290, P < 0.001) and CHA2DS2-VASc scores (r = -0.263, P > 0.001).@*Conclusions@#Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.

Cardioversion efficacy of nifekalan in patients with sustained atrial fibrillation after radiofrequency ablation / 中华心血管病杂志

Objective@#To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF.@*Methods@#We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis.@*Results@#(1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation.@*Conclusions@#The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.

Low deceleration capacity is associated with higher stroke risk in patients with paroxysmal atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Deceleration capacity (DC) is a non-invasive marker for cardiac autonomic dysfunction; however, few studies have shown that the influence factors of cardiac autonomic dysfunction and the correlations between DC and stroke risk in paroxysmal atrial fibrillation (AF). We aimed to explore the influencing factors of abnormal DC and the relationships between DC and stroke risk in patients with paroxysmal AF.@*METHODS@#The study included hospitalized paroxysmal AF patients with DC measurements derived from 24-h Holter electrocardiography recordings taken between August 2015 and June 2016. Multivariable regression analysis was performed to evaluate the associations between correlated variables and abnormal DC values. The relationship between DC and ischemic stroke risk scores in patients with paroxysmal AF was analyzed.@*RESULTS@#We studied 259 hospitalized patients with paroxysmal AF (143 [55.2%] male, mean age 66.4 ± 12.0 years); 38 patients of them showed abnormal DC values. In the univariate analysis, age, hypertension, heart failure, and previous stroke/transient ischemic attack (TIA) were significantly associated with abnormal DC values. Among these factors, a history of previous stroke/TIA (odds ratio = 2.861, 95% confidence interval: 1.356-6.039) were independently associated with abnormal DC values in patients with paroxysmal AF. The abnormal DC group showed a higher stroke risk with the score of congestive heart failure, hypertension, age >75 years, diabetes mellitus, previous stroke and TIA (CHADS2) (2.25 ± 1.48 vs. 1.40 ± 1.34, t = -4.907, P = 0.001) and CHA2DS2-vascular disease, age 65-74 years and female category (VASc) (3.76 ± 1.95 vs. 2.71 ± 1.87, t = -4.847, P = 0.001) scores. Correlation analysis showed that DC was negatively correlated with CHADS2 scores (r = -0.290, P < 0.001) and CHA2DS2-VASc scores (r = -0.263, P < 0.001).@*CONCLUSIONS@#Lower DC is closely associated with previous stroke/TIA, and is also correlated negatively with higher stroke risk scores in patients with paroxysmal AF. It could be a potential indicator of stroke risk in paroxysmal AF patients.

Prevalence and influential factors of stroke in Jiangxi Province in 2014 / 中华预防医学杂志

Objective@#To discuss the prevalence and influential factors of stroke among population in Jiangxi Province.@*Methods@#Four cities in urban areas and four counties in rural areas were selected firstly, in which two districts or townships were selected; and then three communities or villages were chosen from each district and township, respectively, using the simple random sampling (SRS) method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi Province ≥6 months were randomly selected to participate in this survey from November 2013 to August 2014. Information of population characteristics, life behavior way, individual disease history were collected through questionnaire survey, and height, weight, waist circumference, blood pressure, body fat rate, visceral fat index and so on were measured by instruments. Risk factors of stroke prevalence were analyzed by the unconditioned logistic regression analysis.@*Results@#A total of 15 269 participants (6 267 males) from 15 364 eligible participants were included in the statistical analysis. Out of which, 7 793 participants came from urban areas, and their average age was (53.04±17.91) years old. In this study, 226 stroke patients (117 males) were found among15 269 participants, including 122 urban participants and 104 rural participants, whose average age was (67.76±9.74) years old. The prevalence of stroke was 1 480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100 000 among males and females. The prevalence of people aging (45-49) years old was 413.79/100 000 (6/1 450) , while which among people aging 75 years old and above was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in Jiangxi presented an uprising tendency with age increasing (linear-by-linear association χ2=62.23, P<0.01). The research showed that when other influencing factors including gender, BMI, waist circumference, pulse-pressure difference, VAI, and sleeping time in non-working days were controlled, hypertensive patients had a higher risk of stroke than people without hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years old, people aged 65-74 years old and ≥75 years old had a higher risk of stroke, the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively, compared with people with normal body fat percentage, people whose body fat percentage on high side and people who with high body fat percentage had a higher risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18-2.56), respectively, people with sleep time >8 h had a higher risk of stroke than those with sleep time of 6-8 h.@*Conclusion@#There was a high stroke prevalence among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep duration were associated with stroke prevalence. Corresponding measures for high-risk population and risk factors should be strengthened to prevent and control the stroke.

Homocysteine induces calcium overload in neonatal rat atrial cells through activation of sodium current and CaMKⅡδ / 中华心血管病杂志

Objective@#To investigate the effect and related mechanism of homocysteine (Hcy) on calcium overload in neonatal rat atrial cells (NRICs).@*Methods@#NRICs were assigned to 9 groups after culture for 3 days: (1) control group; (2) Hcy group (0, 50, 100, 200, 500 μmol/L for 48 hours); (3) antioxidant group (NAC, 10 μmol/L for 24 hours); (4) Hcy+NAC group (500 μmol/L Hcy for 48 hours, then treated with 10 μmol/L NAC for 24 hours); (5) calcium/calmodulin dependent protein kinase Ⅱδ (CaMKⅡδ) inhibitor group (KN-93, 3 μmol/L KN-93 for 5 hours); (6) specific sodium current inhibitor group (ELE, 1 μmol/L ELE for 5 hours); (7) Hcy+KN-93 group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 for 5 hours); (8) Hcy+ELE group (500 μmol/L Hcy for 48 hours, then treated with 1 μmol/L ELE for 5 hours; (9) Hcy+KN-93+ELE group (500 μmol/L Hcy for 48 hours, then treated with 3 μmol/L KN-93 and 1 μmol/L ELE for 5 hours). Moreover, NRICs were also treated with CaMKⅡδ-siRNA lentivirus, and Nav1.5-siRNA lentivirus, negative lentivirus carrier containing green fluorescent protein (GFP) for 24 hours. The MOI values of the three groups were 10. Infection efficiency of lentivirus was determined by observing the percentage of GFP fluorescence under inverted fluorescence microscope after transfection for 24 hours, and cultured regularly with simultaneous Puro screening, then cells were grouped as Hcy+CaMKⅡδ-siRNA group, Hcy+Nav1.5-siRNA group and Hcy+negative group. The concentration of Ca2+ in NRICs ([Ca2+]i) of various groups was detected through Fluo-4/AM fluorescence probe, then 2', 7'- two chlorofluorescein diacetate (DCFH-DA) was used as a probe to detect reactive oxygen species (ROS) in NRICs by flow cytometry. The malondialdehyde (MDA) was detected by the activity of superoxide dismutase (SOD) and xanthine oxidase was detected by thiobarbituric acid colorimetry. The protein and mRNA expression level of CaMKⅡδ and Nav1.5 in NRICs were detected by Western blot and quantitative real-time PCR.@*Results@#(1) ROS, MDA and SOD were similar between NAC group and control group, ROS and MDA were significantly increased, while SOD was significantly reduced in Hcy group in a concentration-dependent manner. (2) [Ca2+]i: The level of [Ca2+]i was (155.57+7.25), (187.43+13.07), (248.98+27.22) and (307.36+15.09) nmol/L in 50, 100, 200 and 500 μmol/L Hcy groups, which was significantly higher than that in the control group ((123.18+7.24) nmol/L, P<0.01). In addition, the level of [Ca2+]i in Hcy+NAC group ((222.87+23.71)nmol/L) was significantly lower than that in Hcy 500 μmol/L group ((305.15+39.45) nmol/L, P<0.05), while [Ca2+]i level was similar between NAC group and the control group. (3) The protein expression of CaMKⅡδ and Nav1.5 was significantly upregulated in Hcy groups than in the control group. The protein expression level of CaMKⅡδ-Thr287 was significantly lower in NAC group than in Hcy 500 μmol/L group (P<0.01), however, there was no significant difference on the protein expression levels of CaMKⅡδ-Thr287 and Nav1.5 between NAC group and control group (all P>0.05). (4) The protein expression levels of CaMKⅡδ-Thr287 and the concentration of [Ca2+]i were significantly lower in Hcy+KN-93 group and Hcy+KN-93+ELE group than in Hcy 500 μmol/L group (P<0.05). [Ca2+]i concentration was significantly lower in Hcy+KN-93 group, Hcy+ELE group and KN-93+ELE+Hcy group than in Hcy 500 μmol/L group (P<0.05). (5) The mRNA and protein expression levels of CaMKⅡδ and Nav1.5 in each group infected with lentivirus: the GFP expression was ideal post lentivirus transfection for 24 hours (up to 90%), which was significantly lower in the CaMKⅡδ-siRNA group and Nav1.5-siRNA group than in the negative infection group (all P<0.05), which was similar between negative infection group and control group (P>0.05). Moreover, the mRNA and protein expression levels of CaMKⅡδ and CaMKⅡδ-Thr287 was significantly lower in Hcy+Nav1.5-siRNA group than in Hcy+negative infection group (P<0.05). The protein and mRNA levels of Nav1.5 were similar between Hcy+CaMKⅡδ-siRNA group and Hcy+negative infection group (P>0.05).@*Conclusions@#Hcy can induce calcium overload in NRICs by increasing oxidative stress, upregulating the sodium channel protein, and activating the late sodium current and phosphorylating CaMKⅡδ.

Effect of xeroderma pigmentosum group D gene on proliferation of hu-man umbilical arterial smooth muscle cells induced by Ox-LDL / 中国病理生理杂志

AIM:To investigate the effects of xeroderma pigmentosum group D ( XPD) gene on the prolifera-tion of human umbilical arterial smooth muscle cells ( HUASMCs) induced by oxidized low-density lipoprotein ( Ox-LDL) . METHODS:The recombinant plasmid pEGFP-N2/XPD was transfected into HUASMCs by liposome .The cells were di-vided into blank control group , pEGFP-N2 group, pEGFP-N2/XPD group, Ox-LDL group, Ox-LDL+pEGFP-N2 group and Ox-LDL+pEGFP-N2/XPD group.The proliferation rate of the cells was detected by MTT and EdU assays .The apop-totic rate and cell cycle distribution were analyzed by flow cytometry .The protein levels of XPD, caspase-3, Bcl-2 and Bax were determined by Western blot .RESULTS:Compared with blank control group , the expression of XPD was increased in pEGFP-N2/XPD group (P<0.05).According to the results of MTT and EdU assays , the cell proliferation in pEGFP-N2/XPD group was reduced compared with blank control group (P<0.05).Compared with Ox-LDL group, the cell prolifera-tion in Ox-LDL+pEGFP-N2/XPD group was significantly inhibited (P<0.05).According to the results of flow cytome-try, the cell proportion of S phase decreased and the G 0/G1-phase cell proportion increased significantly in pEGFP-N2/XPD group and Ox-LDL+pEGFP-N2/XPD group compared with blank control group and Ox-LDL group, repectively (P<0.05).Compared with blank control group and Ox-LDL group, the protein level of Bcl-2 decreased and the protein levels of Bax and cleaved caspase-3 increased in pEGFP-N2/XPD group and Ox-LDL +pEGFP-N2/XPD group, respectively (P<0.05).CONCLUSION:XPD inhibits the proliferation of HUASMCs and promotes their apoptosis , and reduces the promoting effect of Ox-LDL on the proliferation of HUVSMCs .XPD may be the target for treatment of atherosclerosis .

Recurrent syncope related to catecholaminergic polymorphic ventricular tachycardia due to de novo RyR2-R2401H mutation / 中华心血管病杂志

Objective@#To explore the clinical and molecular genetic features of a Chinese patient with catecholaminergic polymorphic ventricular tachycardia (CPVT).@*Methods@#Clinical data including resting electrocardiography, echocardiography and treadmill exercise testing of a patient with CPVT admitted to our department in March 2013 were analyzed, and the peripheral venous blood samples of the patient and his family members and 400 ethnicity-matched healthy controls were obtained. All exons and exon-intron boundaries of the six CPVT-related genes including RYR2, CASQ2, TRDN, CALM1, KCNJ2 and ANKB were sequenced to detect the variants related to CPVT. The relationship between the genotypes and phenotypes was analyzed to direct the target therapy.@*Results@#Recurrent syncope induced either by exercise or extreme frightened fear was observed in this patient. There was no positive family history of syncope or sudden death. The resting electrocardiography and echocardiography of the patient were normal, while the exercise testing revealed bidirectional and polymorphic ventricular tachycardia. A cardiac ryanodine receptor gene mutation (R2401H) was identified in this patient, while this mutation was absent in his parents and sister and 400 controls. No variant was detected in the remaining five candidate genes. Treatment with high dose of metoprolol succinate (118.75 mg/d) was effective and patient was free of syncopal attack during the 2 years follow-up.@*Conclusion@#This is the first report on RyR2-R2401H mutation in Chinese patient with CPVT, and high dose of metoptolol is the effective therapy option for CPVT related to RyR2 mutation.

NMDA receptor and its role in cardiovascular diseases / 中南大学学报(医学版)

Cardiovascular disease is the main threat to human health,which is one of the important causes of death in worldwide.N-methyl-D-aspartate receptor (NMDAR) is one of crucial ionic glutamate receptors.The physiology and pharmacology function of the composition of NMDAR are very complicated.Researches have shown that NMDAR with a high permeability to calcium and a unique feature of controlling numerous calcium-dependent processes.NMDAR affects the occurrence and development of cardiovascular disease such as hypertension,arrhythmia,myocardial infarction.

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

Objective To explore the effect and mechanism of angiotensin II receptor blockers – Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level. Results The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P < 0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (P < 0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arrhythmia between MI group and SO group (P < 0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P < 0.05). There was the significant difference in the overall score between MI + Irbesartan group and MI group (P < 0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P < 0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Filamentous fungal sesterterpenoids and their synthases / 生物工程学报

Although the number of sesterterpenoids is fewer than other terpenoids reported, they have presented a wide range of biological activities and medicinal value. Reported filamentous fungal sesterterpene synthases are special on bifunctional two catalytically independent domains: prenyltransferase and terpene cyclase, but less specific on substrates selection and diverse ways of cyclization. This article reviews the research advances in filamentous fungal sesterterpenoids and their synthases, especially describes filamentous fungal sesterterpenoids and the structure and function characteristics of sesterterpene synthase.

Atrial remodeling and atrial fibrillation:recent advances and translational perspectives / 中华老年医学杂志

Atrial fibrillation (AF) is the most common clinical arrhythmia.Atrial electrical remodeling and structural remodeling are the important mechanisms for AF.The intracellular Ca2+ handling abnormalities play an important role in the induction of triggered ectopic activity and in the activation of Ca2+-related cell signaling which mediates fibrillatory remodeling.In addition,the importance of microRNAs,which are a new class of small noncoding sequences that regulate gene expression,has been found in both electrical and structural remodeling.The new discovery of AF mechanisms are helpful to exploring the effective treatment for AF,showing good prospects for the use of translational perspectives.

Effect of livin-modified BM-MSCs transplantation on cardiac function fol-lowing acute myocardial infarction in a rat model / 中国病理生理杂志

[ ABSTRACT] AIM:To study the effect of livin gene-modified bone marrow mesenchymal stem cells ( BM-MSCs) transplantation on the cardiac function following acute myocardial infarction in a rat model and the expression of livin , caspase-3, caspase-7 and caspase-9 in the livin gene-modified BM-MSCs.METHODS: The MSCs were obtained by the whole bone marrow culture method , and the apoptosis of the MSCs after infection with adenovirus vector carrying enhanced green fluorescent protein ( EGFP) gene and livin recombinant vector ( rAd-livin) were detected by flow cytometry .The ex-pression of livin, caspase-3, caspase-7 and caspase-9 was detected by Western blot .After permanent left anterior descend-ing artery occlusion , the rats were randomized to receive intramyocardial injection of DMEM without cells ( vehicle group ) , or containing MSCs ( MSCs group ) , MSCs ( EGFP ) ( rAd-control/MSCs group ) or MSCs ( livin ) ( rAd-livin/MSCs group).Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum in-creased rate of left ventricular pressure ( -dp/dtmax ) and the maximum decline rate of left ventricular pressure ( +dp/dtmax ) were recorded for evaluating the cardiac functions .RESULTS: The apoptosis of rAd-livin/MSCs was significantly decreased as compared with MSCs and rAd-control/MSCs (P<0.05).Meanwhile, the expression of caspase-3, caspase-7 and caspase-9 was significantly downregulated as compared with the other 2 groups ( P<0.05 ) .The cardiac function in rAd-livin/MSCs group was significantly improved as compared with DMEM group , and those in the other 2 groups got the similar results, but the function in rAd-livin/MSCs group was better improved .Meanwhile, the number of surviving cells in rAd-livin/MSCs group was significantly improved as compared with the other 2 groups .CONCLUSION:The apoptosis of MSCs is decreased after rAd-livin transfection, and the expression of caspase-3, caspase-7 and caspase-9 is also significant-ly downregulated while the expression of livin is significantly upregulated .Transplantation of livin-modified BM-MSCs by lentiviral vector results in better prognosis for treating myocardial infarction by enhancing cell survival .

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

OBJECTIVE@#To explore the effect and mechanism of angiotensin II receptor blockers - Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia.@*METHODS@#Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level.@*RESULTS@#The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P < 0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (P < 0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arrhythmia between MI group and SO group (P < 0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P < 0.05). There was the significant difference in the overall score between MI + Irbesartan group and MI group (P < 0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P < 0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan.@*CONCLUSIONS@#Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Preparation of Neochlorogenic Acid Reference Substances by Medium-low-pressure Preparative Chromatography / 世界科学技术-中医药现代化

This study was aimed to establish a separation method for neochlorogenic acid reference substances from Lonicera japonica. Refined neochlorogenic acid inL. japonica water extract was separated and concentrated by HPD200A macroporous resin, which was isolated and purified by medium-low-pressure preparative chromatography and determined by HPLC. The structure was identified by various spectroscopic data including ESI-MS,1H-NMR and13C-NMR. The results showed that the optimal purification technology conditions were as follows: washed with 5BV of water, collected elution, concentration, drying; neochlorogenic acid crude products were eluted with acetonitrile-0.5% formic acid solution (10:90) with the flow rate of 20 mL·min-1; and the detection wavelength was 326 nm. The contents of the prepared neochlorogenic acid reached to 98.86% and the yield was 89.1%. It was concluded that the method was effective for the preparation of neochlorogenic acid with high purity. It can be used to prepare the reference substances for quantitative analysis and content determination of Chinese materia medica.

Determination of Amino Acids inQihong Maitong Injection through Pre-column Derivatization HPLC / 世界科学技术-中医药现代化

In this article, an HPLC method for the contents determination of amino acids in Qihong Maitong injection was reported. In detailed, OPA-Fmoc pre-column derivatization was adopted, and related HPLC methods to determine the contents of amino acids was established. Linear relationship was well constructed for 17 amino acids through the method mentioned above. Briefly speaking, the optimized method was accurate and reproducible, and suitable for the determination of amino acids in Qihong Maitong injection and corresponding quality control.

Effect of Cold Stress on Connexin43 Protein Expression With Drug Intervention in Neonatal Rats’ Myocardial Cells / 中国循环杂志

Objective: To study the effects of acute cold stress on connexin43 (Cx43) protein expression with drug intervention, and cell to cell conduction with its mechanism in neonatal rats’ myocardial cells. Methods: The primary neonatal rats’ myocardial cell culture was conducted in 4 groups. Group① , the cells were normally cultured, Group②, the cells were cultured at 4℃, Group③, the cells were cultured at 0℃and Group④, the anti-arrhythmia peptide (AAP 10) was added in Group②and Group③. The apoptosis rate of myocardial cells was evaluated by lfow cytometry assay, mRNA and protein expressions of CX43 were examined by RT-PCR and Western blot analysis, and CX43 phosphorylation product (P-CX43) was detected. Results: Compared with normally cultured cells, the myocardial cell apoptosis rate was obviously increased by acute cold stress at 4℃and 0℃with time extension. The mRNA expression of Cx43 was decreased at varying degrees at 4℃and 0℃stimulation, the protein expression of Cx43 was decreased at varying degrees at 4℃and 0℃stimulation with time extension, and P-Cx43 level was decreased. While the APP 10 intervention may obviously elevate the protein levels of Cx43 and P-Cx43. Conclusion: Acute cold stress could reduce the protein expression of CX43 and P-CX43, while APP 10 intervention may elevate such expression and improve the cell to cell conduction in neonatal rats’ myocardial cells.