Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion / 药学学报

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Mechanism of Buyang Huanwu Decoction in protecting ischemic myocardium by regulating platelet autophagy in rats with acute myocardial infarction / 中国中药杂志

This study explored the effects of Buyang Huanwu Decoction(BYHWD) on platelet activation and differential gene expression after acute myocardial infarction(AMI). SD rats were randomly divided into a sham-operated group, a model group, a positive drug(aspirin) group, and a BYHWD group. Pre-treatment was conducted for 14 days with a daily oral dose of 1.6 g·kg~(-1) BYHWD and 0.1 g·kg~(-1) aspirin. The AMI model was established using the high ligation of the left anterior descending coronary artery method. The detection indicators included myocardial infarct size, heart function, myocardial tissue pathology, peripheral blood flow perfusion, platelet aggregation rate, platelet membrane glycoprotein CD62p expression, platelet transcriptomics, and differential gene expression. The results showed that compared with the sham-operated group, the model group showed reduced ejection fraction and cardiac output, decreased peripheral blood flow, and increased platelet aggregation rate and CD62p expression, and activated platelets. At the same time, TXB_2 content increased and 6-keto-PGF1α content decreased in serum. Compared with the model group, BYHWD increased ejection fraction and cardiac output, improved blood circulation in the foot and tail regions and cardiomyocytes arrangement, reduced myocardial infarct size and inflammatory infiltration, down-regulated platelet aggregation rate and CD62p expression, reduced serum TXB_2 content, and increased 6-keto-PGF1α content. Platelet transcriptome sequencing results revealed that BYHWD regulated mTOR-autophagy pathway-related genes in platelets. The differential gene expression levels were detected using real-time quantitative PCR. BYHWD up-regulated mTOR, down-regulated autophagy-related FUNDC1 and PINK genes, and up-regulated p62 gene expression. The results demonstrated that BYHWD could regulate platelet activation, improve blood circulation, and protect ischemic myocardium in AMI rats, and its mechanism is related to the regulation of the mTOR-autophagy pathway in platelets.

Research progress of pharmacological effects and clinical application of Trollius chinensis / 中国药房

Trollius chinensis has a wide range of pharmacological effects ，including anti-oxidative ，antibacterial，antiviral， anti-inflammatory，anti-tumor，anti-aging，antipyretic and analgesic effects ，relieving cough and removing phlegm ，viscera protection，and so on. Flavonoids and phenolic acids are the main medicinal components of it ，especially three monomers have a wide range of efficacy and have been studied more ，such as orientin ，vitexin and 2″-O-galactopyranosyl orientin. T. chinensis is mostly used in clinical practice in the form of Chinese patent medicines ，such as Jinlianhua granules ，Jinlianhua capsules ， Jinlianhua tablets and Jinlianhua oral liquid. These medicines are used to treatment of upper respiratory tract infection ，pharyngitis， tonsillitis，periodontitis，mumps，oral ulcer ，and hand-foot-mouth disease. They are usually used by combining with Western medicine. Due to its definite curative effect and less adverse drug reactions ，T. chinensis related preparations are more suitable for pediatric population ，and they can be used for the treatment of upper respiratory tract infection in children ，acute suppurative tonsillitis in children ，epidemic mumps in children ，hand-foot-mouth disease in children ，which is also one of its drug characteristics. This paper review the relevant literatures in recent 20 years from the respective of pharmacological effects and clinical applicationin order to provide reference for further promoting rational clinical application of T. chinensis and new drug research and development.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology / 亚洲男科学杂志(英文版)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

Factors influencing protective behaviours during haze episodes in Singapore: A population-based study

INTRODUCTION@#Haze is a recurrent problem in Southeast Asia. Exposure to haze is linked to ophthalmic, respiratory and cardiovascular diseases, and mortality. In this study, we investigated the role of demographic factors, knowledge and perceived risk in influencing protective behaviours during the 2013 haze in Singapore.@*METHODS@#We evaluated 696 adults in a cross-sectional study. Participants were sampled via a 2-stage simple random sampling without replacement from a large residential district in Singapore in 2015. The questionnaire measured the participant's knowledge, perceived risk and behaviours during the Southeast Asian haze crisis in 2013. Reliability and validity of the questionnaire were assessed using comparative fit index (≥0.96) and root mean square error of approximation (≤0.05). We performed structural equation modelling to examine the relationship between the hypothesised factors and protective behaviours.@*RESULTS@#More than 95% of the individuals engaged in at least 1 form of protective behaviour. Knowledge was strongly associated with protective behaviours via direct effect (β=0.45, 95% CI 0.19-0.69, @*CONCLUSION@#Knowledge was associated with protective behaviours, suggesting the importance of public education. Efforts should target those of lower education level and smokers. The wearing of N95 masks correlates with uptake of other protective behaviours.

Mechanism of 'Invigorating Qi and Promoting Blood Circulation' Drug Pair Ginseng-Danshen on Treatment of Ischemic Heart Disease Based on Network Pharmacology / 中国结合医学杂志

OBJECTIVE@#Using network pharmacology to explore the mechanism of the 'invigorating qi and promoting blood circulation' drug pair Ginseng-Danshen (Salvia miltiorrhiza) on treatment of ischemic heart disease (IHD).@*METHODS@#The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential targets of the pair were identified. The pharmacodynamics of the pair was analyzed using network pharmacology. The targets of IHD were identified by database screening. Using protein-protein interaction network, the interaction targets of Ginseng-Danshen on IHD were constructed. A "constituent-target-disease" interaction network was constructed using Cytoscape software, Gene Ontology (GO) term enrichment analysis and biological pathway enrichment analysis were carried out, and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.@*RESULTS@#Seventeen active constituents and 53 targets were identified from ginseng, 53 active constituents and 61 targets were identified from Danshen, and 32 protein targets were shared by ginseng and Danshen. Twenty GO terms were analyzed, including cytokine receptor binding, cytokine activity, heme binding, and antioxidant activity. Sixty Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were analyzed, including phosphatidylinositol 3-kinase-serine-threonine kinase (PI3K-AKT) signaling pathway, p53 signaling pathway, interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, and the advanced glycation end product (AGE)-the receptor for AGE (RAGE) signaling pathway in diabetic complications.@*CONCLUSION@#The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody, inhibiting the production of peroxides, removing the endogenous oxygen free radicals, regulating the expression of inflammatory factors, reducing myocardial cell apoptosis and promoting vascular regeneration.

Effect of Shuangshen Ningxin Capsules on Cardiac Function and Hemodynamics in Rats with Coronary Microvascular Dysfunction / 中国实验方剂学杂志

Objective:To investigate the effect of Shuangshen Ningxin capsules （SSNX） on cardiac hemodynamics and cardiac function in rats with coronary microvascular dysfunction. Method:Rats were randomly divided into a sham operation group， a model group， a nicorandil group （5 mg·kg^-1）， and high- （180 mg·kg^-1）， medium- （90 mg·kg^-1）， and low-dose （45 mg·kg^-1） SSNX groups. Rats received corresponding drugs for 7 days. Two hours after the last administration， the model of coronary microvascular dysfunction was induced by left ventricular injection of embolic microspheres （40-120 μm， about 1 000 microspheres）. Twenty-four hours after modeling， left ventricular internal dimension in diastole （LVIDd）， left ventricular internal dimension in systole （LVIDs） left ventricular end-diastolic volume （LVEDV）， left ventricular end-systolic volume （LVESV）， stroke volume （SV）， cardiac output （CO）， left ventricular ejection fraction （EF）， and left ventricular shortening rate （FS） were detected by echocardiography. Cardiac catheterization was used to observe the arterial systolic blood pressure （SBP）， diastolic blood pressure （DBP）， left ventricular systolic pressure （LVSP）， left ventricular end-diastolic pressure （LVEDP）， maximum rate of increase in left ventricular pressure （LV+dp/dt_max）， and maximum rate of decrease in left ventricular pressure （LV-dp/dt_max）， and the mean arterial pressure （MAP） was calculated. Heart rate （HR） was calculated according to Ⅱ lead ECG. Biochemical analysis was carried out to detect the activities of creatine kinase （CK）， creatine kinase-MB （CK-MB）， and lactate dehydrogenase （LDH）. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum cardiac troponin T （cTnT）. Western blot was used to detect the protein expression of Caspase-3， Bcl-2， and Bax， and 2，3，5-triphenyltetrazolium chloride （TTC） staining to observe the area of myocardial infarction. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of the myocardium. Result:As revealed by echocardiography， compared with the sham operation group， the model group showed reduced SV， CO， EF， and FS （<italic>P</italic><0.01）， and increased LVIDs and LVEDV （<italic>P</italic><0.01）. Compared with the model group， the SSNX groups showed increased EF （<italic>P</italic><0.05， <italic>P</italic><0.01） and FS （<italic>P</italic><0.01）， and the high- and medium-dose SSNX groups displayed reduced LVIDs and LVESV， and increased LVEDV， SV， and CO （<italic>P</italic><0.05， <italic>P</italic><0.01）. SBP， DBP， MAP， LVSP， LV+dp/dt_max， and LV-dp/dt_max in the model group were lower than those in the sham operation group （<italic>P</italic><0.01）， while there was no significant difference in HR. SSNX improved hemodynamics of rats， and increased SBP， DBP， MAP， LVSP， LV+dp/dt_max， LV-dp/dt_max， and HR as compared with the model group （<italic>P</italic><0.05， <italic>P</italic><0.01）. The serum CK， LDH， CK-MB， and cTnT levels in the model group were higher than those in the sham operation group （<italic>P</italic><0.01）. Compared with the model group， SSNX groups reduced serum CK， LDH， CK-MB， and cTnT （<italic>P</italic><0.05，<italic> P</italic><0.01）. Compared with the sham operation group， the model group displayed increased expression of Caspase-3 protein in the myocardium （<italic>P</italic><0.01） and reduced expression of Bcl-2 protein （<italic>P</italic><0.05）. The expression of Caspase-3 protein in the myocardium of SSNX groups was lower than that in the model group， and statistical difference was observed between the low-dose SSNX group and the model group （<italic>P</italic><0.05）. Compared with the model group， the SSNX groups exhibited increased expression of Bcl-2 in the rat myocardium， and the statistical difference was observed in the high-dose SSNX group <italic>（P</italic><0.01）. As demonstrated by the TTC staining， compared with the model group， SSNX groups showed reduced areas of myocardial infarction （<italic>P</italic><0.01）. The HE staining indicated that the pathological injury in myocardial tissues of the SSNX groups was relieved as compared with that in the model group. Conclusion:SSNX can significantly enhance the cardiac function after coronary microvascular dysfunction caused by embolic microspheres， improve cardiac hemodynamics， reduce the area of myocardial infarction， and decrease CK， LDH， CK-MB， and cTnT levels. The mechanism may be related to the inhibition of cardiomyocyte apoptosis to protect the myocardium.

Network Meta-analysis of clinical efficacy of Chinese herbal injection in adjuvant treatment of unstable angina pectoris / 中国中药杂志

The present study evaluated the curative efficacy of Chinese herbal injection on unstable angina pectoris( UAP) by network Meta-analysis. The databases,including Pub Med,Cochrane Library,Web of Science,CNKI,CBM,VIP and Wanfang were searched for randomized controlled trial( RCT) of Chinese herbal injection in the treatment of UAP. All researchers independently screened the articles,extracted the data and evaluated the quality. Open BUGS and Stata were employed for the analysis of the trials that met the quality standards. Fifty-eight studies were finally included in this study,involving 20 intervention measures. In terms of the effective rate,16 injections such as Dengzhan Xixin Injection,Xuesaitong Injection and Danshen Injection combined with western medicine exhibited significant efficacy. In terms of ECG,Puerarin Injection,Ginkgo Leaf Extract and Dipyridamole Injection( GDI),Breviscapine Injection combined with western medicine were superior to western medicine. In terms of the reduction of the angina attack times,Sodium Tanshinone ⅡASulfonate Injection,GDI and Dazhu Hongjingtian Injection combined with western medicine showed better effects than western medicine. In terms of shortening the angina duration,Shenmai Injection combined with western medicine was superior to western medicine. As revealed by the results,Dengzhan Xixin Injection,Xuesaitong Injection,Danshen Injection,Breviscapine Injection,Danshen Ligustrazine Injection combined with western medicine displayed prominent curative efficacy,which were recommended for clinical application. Meanwhile,appropriate intervention measures should be selected according to individual conditions. Limited by the quality of the included trials,the conclusions still need to be further verified.

Effect of Shuangshen Ningxin Capsule in Alleviating Myocardial Ischemia/Reperfusion Injury in Rats by Regulating Mitochondrial ATP-sensitive Potassium Channel / 中国实验方剂学杂志

Objective:To observe the effect of Shuangshen Ningxin capsule in alleviating myocardial ischemia/reperfusion injury in rats by regulating mitochondrial adenosine triphosphate（ATP）-sensitive potassium channels.Method:A total of 56 adult male Sprague-Dawley rats were randomly divided into sham-operated control group (sham), model group (model), Shuangshen Ningxin group (SSNX, 90 mg·kg-1).Shuangshen Ningxin and mitochondrial ATP-sensitive potassium channel (MitoKATP) channel inhibitor group 5-hydroxyl-acid group (SSNX+5-HD, 5 mg·kg-1), with 14 rats in each group. Except the sham operation group, the other three groups received occlusion of left anterior descending coronary artery (LAD) for 45 min, and were sacrificed 3 h after reperfusion. Myocardial ischemia and infarct size were observed by TSC Evans blue staining, and myocardial tissue damage degree was observed by hematoxylin-eosin(HE) staining. The kit was used to measure serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The ultrastructural changes of mitochondria and mitochondrial autophagy were observed under transmission electron microscope. The changes of mitochondrial membrane potential in cardiomyocytes were detected by fluorescent probe.Result:Compared with the sham group, myocardial infarct size and myocardial ischemic area percentage in the model group were significantly increased, myocardial tissue arrangement was disordered and loose, individual myocardial fibers were broken, cardiomyocytes were necrotic, and serum CK, CK-MB, LDH activities were significantly increased (P<0.01). Mitochondrial membrane potential was significantly decreased (P<0.01), and mitochondrial structure was destroyed by transmission electron microscopy. Compared with the model group, the myocardial tissue of the SSNX group was arranged orderly, and a small amount of cell edema was mildly degenerated. The percentage of myocardial infarct size and myocardial ischemic area was significantly decreased, serum CK, CK-MB, and LDH activities were significantly decreased (P<0.01), while mitochondrial membrane potential increased (P<0.01). Compared with the model group, the SSNX+5-HD group had mild myocardial tissue disorder and mild degeneration of cell edema in some areas, the percentage of myocardial infarct size and myocardial ischemic area was significantly reduced, serum CK, CK-MB, and LDH activities were significantly decreased (P<0.01), and mitochondrial membrane potential increased (P<0.01). Compared with SSNX group, SSNX+5-HD group had significant increase in serum CK, CK-MB and LDH activities (P<0.01), significant increase in the percentage of myocardial infarct size and myocardial ischemic area, and mitochondrial membrane potential Reduced (P<0.05).Conclusion:SSNX protects rat myocardial ischemia-reperfusion injury by opening mitochondrial ATP-sensitive potassium channel.

Research progress of traditional Chinese medicine in regulating autophagy and ischemic heart disease / 中国中药杂志

Ischemic heart disease(IHD) is a common and frequently-occurring disease that causes serious harm to human health. Autophagy is a life process that maintains cell homeostasis by degrading macromolecules such as damaged organelles in cells. In the process of ischemic heart disease development, on the one hand, cardiomyocytes degrade macromolecules such as damaged organelles by autophagy to provide material basis for energy synthesis and maintain cell homeostasis; on the other hand, over-activated autophagy can also increase cardiomyocyte death. Ischemic heart disease has a complex pathological mechanism, and the occurrence of autophagy is closely related to the survival or death of myocardial cells, so the regulation of autophagy may be an important therapeutic target for ischemic heart disease. Traditional Chinese medicine(TCM) with obvious effects, unique advantages and great potential has been widely used in the treatment of ischemic heart disease. In recent years, more and more studies have found that TCM can protect myocardium by regulating autophagy of cardiomyocytes. In this review, we summarized recent studies on the regulation of autophagy in myocardial cells by traditional Chinese medicine in ischemic heart disease. The pharmacological mechanism of Chinese medicinein regulating autophagy to protect cardiomyocytes was reviewed through different ways(promoting or inhibiting autophagy) from three levels, i.e. active ingredient, as well as drug pair and compound. The specific mechanism of Chinese medicine in regulating autophagy to protect ischemic heart disease was explored to provide references or new ideas for clinical treatment and drug development of ischemic heart disease.

Salvianolic acid B regulates mitochondrial autophagy mediated by NIX to protect H9c2 cardiomyocytes from hypoxia/reoxygenation injury / 中国中药杂志

The aim of this paper was to investigate whether the mechanism of salvianolic acid B in protecting H9 c2 cardiomyocytes from hypoxia/reoxygenation injury is related to the regulation of mitochondrial autophagy mediated by NIX. H9 c2 cardiomyocytes were cultured in vitro and divided into normal group, model group and salvianolic acid B group(50 μmol·L~(-1)). Hypoxia/reoxygenation injury model was established by hypoxia for 4 h and reoxygenation for 2 h. In normal group, high glucose DMEM medium was used for culture. Those in model group were cultured with DMEM medium without glucose and oxygen, and no drugs for hypoxia and reoxyge-nation. In salvianolic acid B group, salvianolic acid B prepared by glucose-free DMEM medium was added during hypoxia, and the other process was as same as the model group. The cell viability was evaluated by CCK-8 assay. The leakage of lactate dehydrogenase(LDH) was detected by microplate method. The levels of intracellular reactive oxygen species(ROS) and mitochondrial membrane potential(ΔΨm) were measured by chemical fluorescence method. The level of intracellular adenosine triphosphate(ATP) was mea-sured by fluorescein enzyme method. The autophagy related proteins LC3-Ⅰ, LC3-Ⅱ, apoptosis related protein cleaved caspase-3 and mitochondrial autophagy receptor protein NIX were detected by Western blot. As compared with the normal group, the activity of H9 c2 cardiomyocytes and ATP level were decreased(P<0.05); LDH leakage and ROS production were increased(P<0.01); ΔΨm was decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio, cleaved caspase-3 and NIX protein expression levels were increased(all P<0.05) in the model group. As compared with the model group, the activity of cells and ΔΨm were significantly increased(P<0.01); ATP level was increased(P<0.05); LDH leakage and ROS generation were decreased(P<0.01); LC3-Ⅱ/LC3-Ⅰ ratio was decreased(P<0.01); cleaved caspase-3 and NIX expression levels were decreased(P<0.05) in the salvianolic acid B group. The protective effect of salvianolic acid B on hypoxia/reoxygenation injury of H9 c2 cardiomyocytes may be associated with inhibiting mitochondrial auto-phagy. The specific mechanism may be related to inhibiting the activation of mitochondrial autophagy mediated by NIX, increasing ΔΨm, reducing ROS production, reducing the expression of cleaved caspase-3, LC3-Ⅱ, and increasing cell viability.

Lipid-lowering Activity and Mechanism of Allii Sativi Bulbus / 中国实验方剂学杂志

Preliminary results have been achieved in the prevention and treatment of cardiovascular disease (CVD) in China, but the number of CVD patients will continue to grow rapidly in the next 10 years. Generally speaking, the prevalence and mortality of CVD in China are still on the rise. CVD has worsened and become a major public health problem. It is urgent to prevent CVD. Therefore, the development of safe, effective and inexpensive drugs for the prevention and treatment of CVD is a livelihood project of great significance. Allii Sativi Bulbus, as a commonly used medicinal and edible herbal medicine, has rich resources and a long history of application. Since the 1980s, many studies on Allii Sativi Bulbus have been carried out by global scholars. The results show that Allii Sativi Bulbus has the effects in reducing blood lipid, preventing atherosclerosis, lowering blood pressure, resisting myocardial ischemia and treating other cardiovascular diseases, with many pharmacological activities such as anti-tumor, anti-bacterial, anti-inflammatory, insecticidal, regulating immunity, anti-oxidation, free radical scavenging activities. Focusing on the regulation of blood lipid metabolism by Allii Sativi Bulbus, the latest literatures at home and abroad have been consulted. Both basic research and clinical trials have shown that Allii Sativi Bulbus has a good hypolipidemic effect. Its mechanism is mainly related to the inhibition of key enzymes in the process of lipid synthesis and related factors regulating lipid metabolism. In this paper, the hypolipidemic effect and molecular mechanism of garlic were reviewed to define its research trends and problems, and provide reference for further research and clinical application of Allii Sativi Bulbus.

Protective Effect of Traditional Chinese Medicine on Ischemic Myocardium by Mitochondrial Autophagy / 中国实验方剂学杂志

Ischemic heart disease is one of the most deadly diseases in the world, and new therapies and preventive measures are urgently needed. In general, cardiomyocytes rely on adenosine triphosphate(ATP) produced by mitochondrial oxidative phosphorylation to maintain their systolic and ion pump functions. Autophagy is a procedural degradation mechanism widely present in eukaryotic cells. It is a self-defense mechanism and self-repair process of the body tissues. It is also a way of apoptosis and a basic phenomenon to maintain the energy balance of human cells. Mitochondrial autophagy is a type of selective autophagy in cells. In fact, damaged mitochondria selectively remove damaged proteins and organelles with autophagy to maintain intracellular homeostasis. Mitochondrial autophagy is important for maintaining the homeostasis of cardiomyocytes. With the deepening of modern biological research, more and more traditional Chinese medicines(TCM) or their extracts have been proven to alleviate myocardial cell damage after ischemia/reperfusion through autophagy or regulation of mitochondrial function. This further inspires TCM workers to find effective treatment measures by targeting mitochondria. Under the above background, this paper reviews the effects of mitochondrial autophagy on ischemic heart disease and the intervention studies of TCM in this field.

New Phenolic Glycoside from Aerial Part of Allium sativum / 中国实验方剂学杂志

Objective: To study the chemical constituents from the aerial part of Allium sativum. Method: The aerial part of A. sativum was treated by heating reflux extraction with 70% ethanol. The combined extracting solution was treated with decompressed recovery solvent to obtain the total extract. The total extract's thick paste was suspended with an appropriate amount of distilled water, and then extracted with petroleum ether, ethyl acetate and water-saturated n-butyl alcohol to obtain petroleum ether extraction fraction, ethyl acetate extraction fraction and n-butyl alcohol extraction fraction. The n-butyl alcohol extraction fraction was isolated and purified by positive phase silica gel column chromatography, ODS column chromatography and preparative HPLC,etc. The structures of the chemical constituents were elucidated by means of physicochemical properties and spectroscopic analysis, and spectral data, like 1H-NMR, 13 C-NMR, DEPT, HMBC and HR-ESI-MS. Result: Seven compounds were isolated and identified as 2-methoxy-phenol-1-O-α-L-arabinopyranosyl-(1→6)-β-D-glucopyranoside(1),phenyl-ethanol-4-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside(2),trans-resveratrol 3-O-β-D-glucopyranoside(3),stigmasterol(4),β-sitosterol(5),stigmasterol-3-O-β-D-glucopyranoside(6) and daucosterol(7). Conclusion: Compound 1 is a new phenolic glycoside named dasuanxinoside J,and compounds 2-7 are isolated from A. sativum for the first time.

Protective effect of safflower yellow injection against rat MIRI by TLR-NF-κB inflammatory pathway / 中国中药杂志

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.

Advance in Transcranial Direct Current Stimulation for Aphasic Rehabilitation (review) / 中国康复理论与实践

Transcranial direct current stimulation (tDCS) was applied in rehabilitation of aphasia effectively. Based on the three hy-potheses on aphasic rehabilitation, it is needed to consider the stage, location and the extent of brain damage in the left hemisphere of aphasia patients. If the core language functional areas are not damaged, tDCS can be used to either acti-vate the left hemisphere to enhance the activity of perilesional areas, or to inhibit the right hemisphere to weaken the in-hibitory effect from the right one. In contrast, if the core language functional areas are damaged, tDCS should be used to activate the right hemisphere to compensate the left core language functional areas impaired. The integrity of white mat-ter fiber tracts also affects the efficacy of tDCS. By exciting or inhibiting the cortex, tDCS can enhance the cerebral con-nectivity, and mediate its neural processing, to improve word- retrieval deficit, articulatory disturbance and discourse skill in daily living. The benefit from tDCS may be long-term and generalizated, which needs more researches.

Apnoeic and Hypopnoeic Load in Obstructive Sleep Apnoea: Correlation with Epworth Sleepiness Scale

<p><b>INTRODUCTION</b>Patients with obstructive sleep apnoea (OSA) often present with excessive daytime sleepiness (EDS) as measured by the Epworth Sleepiness Scale (ESS). However, the relationship between EDS and OSA severity as measured by the apnoea-hypopnoea index (AHI) remains inconsistent. We hypothesise that this may be due to the usage and equal weightage of apnoea and hypopnoea events used in determining AHI and that apnoea and hypopnoea load as measured by their total durations may be a better metric to use. We sought to investigate if apnoea or hypopnoea load can display better correlation with ESS.</p><p><b>MATERIALS AND METHODS</b>Retrospective analysis of 821 patients with AHI ≥5, who underwent in-laboratory polysomnogram for suspected OSA from January 2015-December 2015, was performed. Objective factors on polysomnogram were correlated with ESS.</p><p><b>RESULTS</b>ESS was correlated with age (r = -0.148, <0.001), number of apnoeas (r = 0.096, = 0.006), apnoea load (r = 0.102, = 0.003), apnoea index (r = 0.075, = 0.032), number of desaturations (r = 0.081, = 0.020), minimum SpO (r = -0.071, = 0.041), time SpO <85% (r = 0.075, = 0.031) and REM sleep duration (r = 0.099, = 0.004). Linear regression analysis found age ( <0.001), apnoea load ( = 0.005), REM ( = 0.021) and stage 1 sleep duration ( = 0.042) as independent factors correlated to ESS. The apnoea load calculated using duration in apnoea correlate with ESS in patients with severe OSA by AHI criteria compared to the mild category.</p><p><b>CONCLUSION</b>AHI does not correlate with ESS. Younger age, longer apnoea, stage 1 and REM sleep were independently related to higher ESS though the correlations were weak. Apnoea load should be taken into account when determining OSA severity.</p>

Therapeutic effect of subtotal parathyroidectomy for 72 uremic patients with secondary hyperparathyroidism / 中国现代普通外科进展

Objective:To retrospectively analyze the therapeutic effect of subtotal parathyroidectomy (sT-PTX) on uremic patients with secondary hyperparathyroidism (SHPT).Methods:Seventy two SHPT patients treated with sT-PTX in our hospital were enrolled in this study.Serum parathyroid hormone(PTH),calcium(Ca) and phosphorus(P) obtained in the preoperative,postoperative and followup periods were collected and compared.Their symptoms,postoperative complications and relapse were recorded.Results:(1)sT-PTX operation performed successfully in 70/72 patients(97.2％).(2)After sT-PTX,bone pain and itching improved rapidly,with the improvement of nutritional status,Partial patients with renal hypertension were remitted compared with preoperative.Thirteen cases can walk without wheelchair after sT-PTX.(3)Serum PTH,Ca,and P decreased significantly after sT-PTX for one week,one month and 6 months as compared with those before sT-PTX(P＜0.05).(4)Postoperative hypocalcemia was frequently seen(53/72,53.6％) but could be effectively controlled by intravenous calcium infusion.(5)SHPT recurred in the 6 months after sT-PTX in 4 cases (5.7％).Conclusions:T-PTX can effectively decrease PTH level and improve symptoms,and is a safe measure for the treatment of uremic patients with SHPT.

Hydrophilic Interaction Liquid Chromatography Coupled with Mass Spectrometry for Serum Metabolomics Analysis of Bladder Cancer / 分析化学

Bladder cancer ( BC) is a fatal malignancy with considerable mortality, and can cause a serious threat to human health. The successful treatment of bladder cancer relies mainly on early detection. Biomarkers are vital to early diagnosis of bladder cancer, and metabonomics play an important role in biomarkers finding. In this study, we used 69 polar metabolites to select the appropriate separation system and develop the zwitterionic hydrophilic chromatography/mass spectrometry ( ZIC-HILIC/MS ) method. In this method, 50 representative compounds had broad linear ranges between 2-6 orders of magnitude. Moreover the limit of detection of the method was below ng/mL levels. The analysis for six serum samples prepared in parallel showed that this method had good reproducibility, and the RSDs of more than 85% metabolites were less than 30%. Based on this method, it was found that 35 metabolites had significant differences in BC group and healthy control. After screening and validation, the combination of chenodeoxycholic acid, eicosenoic acid, GPC, dodecenoic acid and cystine was a potential biomarker to distinguish BC and normal group. These results indicated that the ZIC-HILIC/MS method could detect diverse metabolites for metabolomic analysis purpose with good reproducibility and stability.

A study of risk factors and predictive factors in intraoperative floppy iris syndrome during phacoemulsification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To determine the incidence of intraoperative floppy iris syndrome (IFIS) in patients undergoing phacoemulsification in a Chinese hospital,and to assess new risk factors and predictive factors for IFIS.METHODS:A prospective,observational case series.In the consecutive cataract surgeries performed in one year,the medicine administration,pupil size (PS)before and after mydriasis,and signs of IFIS were recorded.RESULTS:Totally 807 patients (1068 eyes) underwent cataract surgeries.Among the 1068 eyes,signs of IFIS were noted in 34 eyes.Strong positive correlations were showed between finasteride (6.4％,OR =5.885),tamsulosin (25％,OR=21.578),reserpine (16.7％,OR=12.947),clozapine (66.7％,OR=139.467),post-panretinal photocoagulation (14.3％,OR =10.789) and IFIS.Pupil size was inversely related to IFIS incidence (P＜0.001).A dilated pupil smaller than 7.25mm could predict iFiS (P＜0.001).CONCLUSION:The incidence rate of IFIS was 3.18％.Reserpine,clozapine and post-panretinal photocoagulation emerged as new risk factors for IFIS.A small dilated pupil may imply IFIS occurrence.