治疆“心药”:“四个认同”

强化"四个认同"教育是推进新疆社会稳定和长治久安的治疆"心药"。新疆应当高度重视"四个认同"教育,切实加强思想政治工作,发挥以现代文化为引领,把社会主义核心价值体系作为少数民族地区思想文化建设的基础和灵魂,确立"文化育民"的正确导向,自觉维护、不断巩固"四个认同",使之成为教化社会、引导群众、教育人民、凝聚人心的核心思想,成为维护社会和谐、实现长治久安的精神长城。

用“心药”,让教育“无痕”

孙子兵法说:攻城为下,攻心为上。这是一条至高无上的原则,也是一切兵法的核心思想。我认为,这也是一切学生工作的核心思想。

Population pharmacokinetics of paeoniflorin in guanxin Ⅱ prescription

To evaluate the effect of components in Guanxin Ⅱ prescription on the pharmacokinetic profiles of paeoniflorin. Plasma concentration of Paeoniflorin in rats after intravenous injection of Paronia Pall Extract （PPE） and oral administration of PPE and three types of decoctions in Guanxin Ⅱ prescription, respectively, were determined by HPLC analyses. NONMEM （nonlinear mixed-effect modeling） method was used to analyze full set of pharmacokinetic data directly. A two-compartment model with first-order degradation in absorption compartment was employed for the data analysis. The mean of population parameters, CL1, V1, CL2, V2, Ka0, and Kal, were measured to be 0.509 L/h, 0.104 L, 0.113 L/h, 0.123 L, 0.135/h, and 0.0135/h, respectively. Inter-individual variabilities were estimated and dose formulation （DF） was identified as a significant covariate of Ka 1, Ka0, and V1. It is concluded that the pharmacokinetic behaviors of paeoniflorin in rats can alter with different dose formulations.

Development of Cardiovascular Drugs Based on Isoquinoline Compounds from Chinese Medicinal Materials

By using active principles of Chinese medicinal materials as lead compounds soquinoline derivatives have been designed and synthesized.Their chemical structures include bisbenzylisoquinoline,benzyl-isoquinoline and protoberberine.Their cardiovascular effects were studied involving α-adrenoceptor,adenosine A_1,A_2 and DPH-calcium channel radioreceptor assays.In addition,calmodulin inhibiting,calcium antagonistic potassium channel blocking and antiplatelet aggre- gation activities were also performed.It was found that compound VI_(19) was a new potassium channe blocker with α-adrenoceptor antagonism,compound V_9,and V_(21) lowered blood pressure on various animal models with negative chronotropic action,compound VI_(13)possessed antiarrhythmic and antifi- brillation action,and it may be a candidate tot clinic evaluation.The structure-activity relationships deduced may provide a theoretical basis for further development of new agents.

Effects of IQ_23 on the Repolarization and Both Components of the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytcs

Using patch clamp whole cell recording techiques, we examined the effects ofIQ_23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential (AP) andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ_23 at 10, 30and 100 μmol ·L_-1 slowed the repolarization in AP dose-dependently. The APD_90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca^2+. In voltageclamp mode, IQ_23 effectively blocked both the components of the delayed rectifier potassium current(I_k), i.e., I_ks and I_kr. At concentrations of 30 and 100 μmol· L^-1, IQ_23 suppressed I_ks by 21% and 26%and suppressed I_kr by 67% and 86% respectively. But even at 100 μmol·L^-1, IQ_23 had little effect onthe inward rectifier potassium current (I_k1). It is concluded: 1. IQ_23 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca^2+; 2.IQ_23 blocks both I_ks and Ikr in the ventricular myocytes without obvious specificities between them.

Alginate-Coated Fe3O4 Hollow Microspheres for Drug Delivery

Novel hollow Fe3O4 nanoparticles for drug delivery were synthesized via a one-step template- free approach. These nanoparticles were obtained by modifing the Fe3O4 nanoparticles with 3-aminopropyltrimethoxy silane, and then grafting alginate onto the surface of amine magnetic. The hollow structure of Fe3O4 spheres was characterized by TEM, XRD, and XPS. The M-H hysteresis loop indicated that the magnetic spheres exhibit snperparamagnetic characteristics at room temperature. Daunorubicin acting as a model drug was loaded into the carrier, and the maximum percent of envelop and load were 28.4% and 14.2% respectively. The drug controlled releasing behaviors of the carriers were compared in different pH media.

Numerical investigation of effect of eccentric decoupled charge structure on blasting-induced rock damage

Eccentric decoupling blasting is commonly used in underground excavation.Determination of perimeter hole parameters(such as the blasthole diameter,spacing,and burden)based on an eccentric charge structure is vital for achieving an excellent smooth blasting effect.In this paper,the Riedel-Hiermaier-Thoma(RHT)model was employed to study rock mass damage under smooth blasting.Firstly,the parameters of the RHT model were calibrated by using the existing SHPB experiment,which were then verified by the existing blasting experiment results.Secondly,the influence of different charge structures on the blasting effect was investigated using the RHT model.The simulation results indicated that eccentric charge blasting has an obvious pressure eccentricity effect.Finally,to improve the blasting effect,the smooth blasting parameters were optimized based on an eccentric charge structure.The overbreak and underbreak phenomena were effectively controlled,and a good blasting effect was achieved with the optimized blasting parameters.

Effects of fructose-1,6-diphosphate on concentration of calcium and activities of sarcoplosnic Ca^(2+)-ATPase in cardiomyocytes of Adriamycin-treated rats

Objective: To observe the effects of fructose-1,6-diphosphate (FDP) on serum levels of cardiac troponin 1 (cTnl) and creatine kinase-MB (CK-MB), as well as the concentration of calcium in cardiomyocytes (Myo[Ca2+]) and activity of sarcoplosnic Ca2+-ATPase (SRCa2+-ATPase) in Adriamycin (ADR)-treated rats. Methods: Rats were intraperitoneally injected with ADR (2.5 mg/kg every other day for 6 times) and then with different dosages of FDP (every other day for twenty-one times). Bi-antibodies sandwich Enzyme linked immune absorption assay (ELISA) was performed to detect serum level of cTnl. CK-MB was detected by monoclonal antibody, Myo[Ca2+] was detected by fluorescent spectrophotometry and the activity of SRCa2+-ATPase was detected by inorganic phosphate method. Results: FDP (300, 600, 1200 mg/kg) significantly reduced the serum levels of cTnl and CK-MB, while at the same time decreased calcium concentration and increased SRCa2+-ATPase activity in cardiomyocytes of ADR-treated rats (P<0.01). Conclusions: FDP might alleviate the cardiotoxic effects induced by ADR through decreasing calcium level as well as increasing SRCa2+-ATPase activity in cardiomyocytes.

Effects of IQ23 on the Repolarization and Both Components of the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytcs

Using patch clamp whole cell recording techiques, we examined the effects ofIQ23, a benzyl-isoquinoline derivative with antiarrhythmic activities, on the action potential （AP） andpotassium currents in single guinea pig ventricular myocytes. The results showed that IQ23 at 10, 30and 100 μmol ·L-1 slowed the repolarization in AP dose-dependently. The APD90 were prolonged by15%, 28% and 31% respectively. This effect did not depend on the extracellular Ca2+. In voltageclamp mode, IQ23 effectively blocked both the components of the delayed rectifier potassium current（Ik）, i.e., Iks and Ikr. At concentrations of 30 and 100 μmol· L-1, IQ23 suppressed Iks by 21% and 26%and suppressed Ikr by 67% and 86% respectively. But even at 100 μmol·L-1, IQ23 had little effect onthe inward rectifier potassium current （Ik1）. It is concluded: 1. IQ23 can dose-dependently prolongAPD in the ventriculas myocytes of guinea pig, the effect does not depend on the extracellular Ca2+; 2.IQ23 blocks both Iks and Ikr in the ventricular myocytes without obvious specificities between them.

Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity

Background Xinfuli Granule （XG）, a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with dox- orubicin-induced cardiotoxicity. Methods Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin （DOX, 2.5 mg/kg per week） for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline （control group） or different dosage of XG （0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively） for six weeks. Transtho- racic echocardiography was performed to evaluate the left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.

Cardiac drug therapy--considerations in the elderly

Elderly individuals constitute a majority of patients encountered in current cardiovascular clinical practice. Management of these patients is a clinical challenge owing to a multitude of factors. Although medications such as statins have been shown to reduce cardiovascular mortality in the general population, evidence supporting the use of these drugs in patients greater than 75 years of age is sparse. Furthermore, aging associated changes in organ function and associated comorbidities influence the pharmacokinetics of multiple medications and can potentiate drug toxicity. In this article, we review the evidence behind the use of common cardiovasctdar medications in elderly patients and discuss pertinent clinical challenges.

Stenting versus non-stenting treatment of intermediate stenosis culprit lesion in acute ST-segment elevation myocardial infarction： a multicenter random- ized clinical trial

Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction （STEMI） patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate （40%-70%） stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban （15 pg/kg） were enrolled and were randomly assigned （h 1） to stenting group （n = 201） and non-stenting group （n = 198）. In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention （PCI） with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI （thrombectomy）, but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events （MACCE）, a composite of cardiac death, non-fatal myocardial infarction （M1）, repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group （adjusted HR： 0.42, 95% Ch 0.19-0.89, P = 0.02）. The stenting group had lower non-fatal MI rate than non-stenting group, （1.5% vs. 5.5%, P = 0.03）. The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.

Aging effects on QT interval： Implications for cardiac safety of antipsychotic drugs

Objectives To explore the effect of aging on cardiac toxicity specifically the interaction of age and antipsychotic drugs to alter the QT interval. Methods The Medline databases were searched using the OvidSP platforms with the search strategy： ＂QT interval＂ or ＂QT＂ and ＂age＂ or ＂aging＂. The entry criteria were： over 10,000 apparently healthy individuals with data on both sexes; QT interval corrected for heart rate （QTc） and an expression of its variance for multiple age decades extending into the older ages. Results QTc increased in duration with increasing age. Considering a modest one SD increment in QTc in the normal population, the addition of Chlorpromazine produced a QTc on average greater than 450 ms for ages 70 years and older. Risperidone, that did not on average alter QTc, would be expected to produce a QTc of 450 ms in persons in their mid 70 years under some circumstances. QTc prolongation 〉 500 ms with antipsychotic drugs is more likely for persons with QTc initially at the 99th percentile. It may occur with Haloperidol which does not on average alter QTc. Conclusions The range of values for the QT interval in apparently normal older men or women, when combined with the range of expected QT interval changes induced by antipsychotic drugs, can readily be associated with prolonged QTc. Individuals with QTc at the 99th percentile may have serious QTc prolongation with antipsychotic drugs even those that are not usually associated with QTc prolongation.

Takotsubo triggered by acute myocardial infarction：a common but overlooked syndrome？

Takotsubo cardiomyopathy （TCM） is an acute cardiac syndrome characterized by extensive, but potentially reversible, left ventricular dysfunction in the absence of an explanatory coronary obstruction. Thus, TCM is distinct from coronary artery disease （CAD） and acute myocardial infarction （AMI）. However, substantial evidence for co-existing CAD in some TCM patients exist. Herein, we take this associa-tion one step further and present a case in which the patient simultaneously suffered from AMI and TCM, and in which we believe that a primary coronary event triggered TCM. An 88-year-old female presented with chest pain. Echocardiography revealed apical akinesia with hypercontractile bases. An occluded diagonal branch with suspected acute plaque rupture was identified on the angiogram, but could not explain the extent of akinesia. Cardiac function recovered completely. Thus, this patient adhered to current diagnostic criteria for TCM. TCM is a well-known complication for other conditions associated with somatic stress. It is therefore intuitive to assume that AMI, which also associates with somatic stress and elevated catecholamine, can cause TCM. Our case illustrates that TCM and AMI may occur simulta-neously. Although causality cannot be conclusively inferred from this association, the somatic stress associated with AMI may have caused TCM in this patient.

Science and the practice of cardiovascular medicine in the geriatric population

1 Why is the demograpy important? In the half century 2000-2050,there will be a virtual tsunami of aging in the United States.The anticipated increase in the population older than age 65 is 140%,and for the population older than age 85,389%.More than half of the current U.S.population can anticipate living to age 80,with a contemporary life expectancy at age 75 of 11 years,and at age 85 of 6 years.

Three Salts of Labdanic Acids from Andrographis paniculata (Acanthaceae)

Three salts of labdanic acids, named as magnesium andrographate, disodium andrographate and dipotassium andrographate 19-O-beta -D-glucoside were isolated from the hydrophilic extract of Andrographis paniculata Nees. (Acanthaceae), together with guanosine, uridine, 6-epihardpagide, procumbide, violanthin and apigenin 7-O-beta -D-glucoside. Their structures were determined by spectroscopic analysis and chemical transformation.

Stereoselective urinary excretion of S-(-)- and R-(+)-propranolol glucuronide following oral administration of RS-propranolol in Chinese Han subjects

AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of closes were 14.7±2.46% and 7.68±1.60% for S-(-)-and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.

Pharmacologic treatment of depression in patients with myocardial infarction

Depression is a common medical problem and is more prevalent among patients with coronary artery disease. Whether early detection and treatment of depression will enhance cardiovascular outcome is uncertain. Obviously, the safety and efficacy of the anti-depression drugs is an important link. This article reviews the patho-physiologic and behavioural links between depression and cardiovascular disease progression, the treatment of depression, and the potential benefits of anti-depressants in patients with coronary disease.

Use of antiarrhythmic drugs in elderly patients

Human aging is a global issue with important implications for current and future incidence and prevalence of health conditions and disability. Cardiac arrhythmias, including atrial fibrillation, sudden cardiac death, and bradycardia requiring pacemaker placement, all increase exponentially after the age of 60. It is important to distinguish between the normal, physiological consequences of aging on cardiac electrophysiology and the abnormal, pathological alterations. The age-related cardiac changes include ventricular hypertrophy, senile amyloidosis, cardiac valvular degenerative changes and annular calcification, fibrous infiltration of the conduction system, and loss of natural pacemaker cells and these changes could have a profound effect on the development of arrhythmias. The age-related cardiac electrophysiological changes include up- and down-regulation of specific ion channel expression and intmcellular Ca2＋ overload which promote the development of cardiac arrhythmias. As ion channels are the substrates of antiarrhythmic drugs, it follows that the pharmacokinetics and pharmacodynamics of these drugs will also change with age. Aging alters the absorption, distribution, metabolism, and elimination of antiarrhythmic drugs, so liver and kidney function must be monitored to avoid potential adverse drug effects, and antiarrhythmic dosing may need to be adjusted for age. Elderly patients are also more susceptible to the side effects of many antiarrhytbanics, including bradycardia, orthostatic hypotension, urinary retention, and falls. Moreover, the choice of antiarrhythmic drugs in the elderly patient is frequently complicated by the presence of co-morbid conditions and by polypharmacy, and the astute physician must pay careful attention to potential drug-drug interactions. Finally, it is important to remember that the use of antiarrhythmic drugs in elderly patients must be individualized and tailored to each patient＇s physiology, disease processes, and medication regimen.

Ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris based on data mining

Objective To explore ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris, and to provide new ideas for the clinical treatment.Methods With “angina pectoris” as the key word, ancient books prescriptions and Chinese patent medicines related to angina pectoris were collected from China National Knowledge Infrastructure(CNKI), Traditional Chinese Medicine Database System, Chinese Medicine Prescription Database, New National Proprietary Chinese Medicine(2 nd edition), and Chinese Pharmacopoeia(2020 edition) from January 1, 2015 to December 31, 2021. Core highfrequency aromatic Chinese medicines were defined, and their potential medication rules were analyzed and summarized. Microsoft Access 2010 was used for data management. Data analysis software, including Excel and IBM SPSS Modeler 18.0 were used for drug association rule analysis, and Cytoscape 3.7.2 for visual display.Results There were 67 ancient books prescriptions and 258 Chinese patent medicines containing aromatic Chinese medicines treating angina pectoris collected from relevant databases. In ancient books prescriptions, there were nine aromatic Chinese medicines with the frequency ≥10, and the most commonly used medicine was Danggui(Angelicae Sinensis Radix), followed by Chenpi(Citri Reticulatae Pericarpium). There were 33 aromatic Chinese medicines with the frequency ≥10 in Chinese patent medicines, and the most commonly used medicine was Danshen(Salviae Miltiorrhizae Radix et Rhizoma), followed by Chuanxiong(Chuanxiong Rhizoma) and Sanqi(Notoginseng Radix et Rhizoma). In ancient books prescriptions, the medicines mainly belonged to intenal-warming medicines, Qi-regulating medicines, and blood circulation promoting and blood stasis removing medicines.There were eight medicine pairs with confidence equal to 100% in ancient books prescriptions, the most frequently used pairs were Chuanxiong(Chuanxiong Rhizoma) +Danggui(Angelicae Sinensis Radix), and Xiangfu(Cyperi Rhizoma) + Chenpi(Citri Reticulatae Pericarpium). In Chinese patent medicines, the aromatic Chinese medicine Chuanxiong(Chuanxiong Rhizoma) could be combined with many other Chinese medicines, among which the Confidence and Support of Chuanxiong(Chuanxiong Rhizoma) + Danshen(Salviae Miltiorrhizae Radix et Rhizoma) were at a high level.Conclusion Aromatic Chinese medicines for the treatment of angina pectoris of coronary heart disease are mainly warm, and the flavors are mainly pungent, sweet, and bitter. They mainly access to the liver, gallbladder, and pericardium meridians. The treatment of angina pectoris of coronary heart disease mainly focuses on warming heart pulse, and promoting blood circulation and removing blood stasis.