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Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.
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@#Objective To summarize the clinical result of a combined technical system for bicuspid aortic valve (BAV) repair. Methods Patients who diagnosed as BAV and sever aortic regurgitation (AR) underwent a strategy of combined repair technics including annuloplasty, sinus plasty, leaflet plasty, sinus-tubular junction (STJ) plasty depending on anatomy pathological characteristics between October 2019 and January 2021 were enrolled. The clinical data of the patients were analyzed. Results A total of 17 patients were enrolled. There were 11 males and 6 females with an average age of 18-49 (32.4±13.6) years. Fifteen patients had typeⅠand 2 patients had typeⅡBAV according to Sievers classification. Annuloplasty was applicated in 13 patients, sinus plasty in 8 patients, leaflet plasty in 17 patients, and STJ plasty in 11 patients, respectively. The cardiopulmonary bypass (CPB) time was 95 (84, 135) min, aortic cross-clamping time was 68 (57, 112) min, and the ICU stay time was 17 (12, 25) h. After the operation, mild AR was presented in 14 patients, moderate AR in 1 patient and severe AR in 2 patients. The latter 3 patients underwent second operation under CPB, after then, 1 patient had mild AR and 2 patients had moderate AR. The follow-up time was 13.1±4.6 months. At the latest follow-up, 12 patients had mild AR and 5 patients had moderate AR, and no patient had reoperation. Conclusion A combined technical system for BAV repair can be used effectively and safely with an acceptable short and middle-term result.
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Parkinsonism is a clinical syndrome caused by many reasons, mainly manifested as bradykinesia, stiffness, static tremor and postural instability. Common disease development patterns include occult onset, gradual development, and little natural remission. However, clinically there are some Parkinsonism that will improve, naturally alleviate or "cure", called reversible parkinsonism (RP). By searching the relevant literature, RP was classified into 12 different types: drugs induced, poisoning induced, infection induced, intracranial vascular induced, structural encephalopathy related, changes in intracranial pressure related, imbalance of internal environment induced, visceral diseases related, alcohol withdrawal related, surgery related, immunization and radiotherapy induced RP. This article aims to provide clinicians with more ideas for the clinical diagnosis and treatment of parkinsonism, so as to promote clinicians to make reasonable identification and diagnosis and treatment of parkinsonism as soon as possible.
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Objective:To summarize the construction of a technics system of aortic valve repair in adult patients with aortic regurgitation(AR).Methods:From March 2013 to May 2020, aortic valve repair was performed in 79 patients. In which 43 cases underwent simple technics such as subcommissural annuloplasty, leaflet plication etc. Cases done before May, 2018 were defined as A group, yet the other 36 cases underwent a routine repair technics system including annuloplasty, sinusplasty, cuspidplasty and sinotubularplasty after then as B group. The general data and the operation procedure, also the follow-up were analyzed.Results:In group A, there were 2 cases with simple aortic valve repair and 41 cases with other intracardiac operations. In group B, 23 patients had aortic valve repair alone and 13 patients had other intracardiac operations. Group A mostly adopts the technologies of subjunctional involution and ridge suspension. In group B, flap ring molding, flap leaf molding, sinus tube joint molding and other technologies were used. Postoperative reflux was reduced to moderate or mild in most patients in group A. In group B, postoperative reflux was reduced to mild in most patients. There were 7 cases of severe reflux in group A, and 2 cases of severe reflux were worse after repair than before surgery. In group B, 8 patients had no effective repair, and 3 patients continued to have satisfactory repair after the second turnaround. Aortic regurgitation at 1 year(or the last echocardiographic follow-up) after surgery: 15 patients in group A were mild, 17 were moderate, and 4 were severe; In group B, 2 patients underwent revalve replacement within 1 year, and the remaining 29 patients were moderate and mild, 20 cases were moderate, 7 cases were moderate, and 2 cases were severe.Conclusion:In some adult moderate and severe AR cases, a routine combined repair system can be applied to increase success rate of repair, and shows a good short and mid-term result.
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Objective:To evaluate the mid-term outcomes of patients with rheumatic heart disease who underwent aortic valve repair surgery in a prospective cohort.Methods:From January 2016 to December 2020, a total of 54 patients with rheumatic heart disease underwent aortic valve repair surgery in Beijing Anzhen Hospital, with an average age of (50.61±13.29) years, including 29 females (53.7%). There were 31 patients (57.4%) had pure aortic insufficiency, 2 patients (3.7%) had pure aortic stenosis and 21 patients (38.9%) had mixed lesion. During the same period, 43 patients (80.0%) underwent mitral valve surgery, 36 patients (66.7%) underwent tricuspid valve surgery, and 20 patients (37.0%) underwent atrial fibrillation radiofrequency ablation.The follow-up period was from 1 month to 61 months (median follow-up was 25 months). Paired rank-sum test was used to compare the differences in continuous variables among subjects, and Kaplan- Meier method was used to analyze the clinical outcomes during the follow-up period. Results:Proportion of moderate and severe aortic regurgitation Preoperatively was higher than that of discharge data, aortic valve orifice maximum velocity and left ventricular end-diastolic diameter were significantly lower than discharge data (all P<0.05). The 5-year survival rate was (96.1±2.7)% (2 patients died). The 5-year freedom from reoperation after aortic valve repair was (89.5±4.5)%(5 patients underwent redo surgery). The 5-year freedom from valvular-related complications was (91.3±4.2)%(3 patients suffered from complications). Conclusion:Aortic valve repair surgery for rheumatic aortic valve disease is feasible and has excellent early and mid-term results, it can be a reliable treatment option.
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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.
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Humans , Angina Pectoris , Angina, Unstable/drug therapy , China , Drugs, Chinese Herbal , Network Meta-Analysis , Treatment OutcomeABSTRACT
Transcatheter aortic valve replacement is a new method for the treatment of patients with symptomatic aortic stenosis and high surgical risk.With the development of technology, this method has been widely used in the world.The current research shows that the short and medium-term curative effect is worthy of affirmation.Due to clinical experience, more and more surgical approaches have been proposed.This article reviews the advantages and disadvantages, clinical research, application progress and problems of transcardiac and transcatheter aortic valve replacement.
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Objective@#To explore the characteristics of pain sensitivity of autism spectrum disorder (ASD), and to provide reference for clinical comprehensive intervention of ASD.@*Methods@#A case-control study was conducted to investigate the characteristics of pain sensitivity in 142 ASD children and 142 normal children using the items related to pain sensitivity in the Autism Treatment Evaluation Checklist (ATEC). In addition, two recognized ASD model mice (BTBR mice and model mice induced by VPA) were selected as experimental group. The thermal pain threshold and mechanical pain threshold of BTBR mice were measured by electroshock seizure threshold and Von Frey filament test, and the differences of pain characteristics between BTBR mice and control mice were compared, the thermal pain threshold of model mice induced by VPA (VPA rats) was measured by electroshock seizure threshold, and the differences between BTBR mice and control mice (Con) were compared.@*Results@#There was significant difference in pain sensitivity between ASD group and control group (χ 2=0.81，P<0.05), and the sensitivity of ASD children to pain was significantly lower than that of normal control children. The pain sensitivity of BTBR mice and C57BL/6 mice on the 42 nd day after birth was measured. The T-test analysis showed that the time taken for BTBR and C57BL/6 mice to retract their feet on the 42 nd day after birth (3.62±0.38,3.02±0.33)s (t=3.28,P<0.01), and the mechanical pain threshold (9.75±3.58,0.55±0.93)s (t=7.44,P<0.01). The detection of thermal stinging pain in VPA rats and con rats on the 9 th, 11 th, 13 th and 15 th day after birth was detected. The results of t test were as follows:P9(11.34±1.38,9.81±1.64)g, P11(11.37±1.98,9.36±1.11)g, P13(11.53±1.38,9.51±1.01)g and P15(12.05±2.91,8.74±1.60)g (t=-2.79,-2.25,3.95,3.95,P<0.05).@*Conclusion@#Compared with normal control children, ASD children show insensitivity to pain which is further supported by two types of animal models for ASD.
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The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.
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Humans , Blood Platelets , Coronary Disease , Medicine, Chinese Traditional , Platelet Activation , SyndromeABSTRACT
The published literature of insomnia in the elderly treated with acupuncture was retrieved in CNKI, Wanfang and VIP from the date of establishment to December 31, 2019. Association rule analysis and cluster analysis were used to summarize the acupoint selection rules of insomnia in the elderly treated with acupuncture. A total of 37 articles were included, involving 60 acupuncture prescriptions. The most commonly used acupoints were Sanyinjiao (SP 6), Shenmen (HT 7), Anmian (Extra), Baihui (GV 20), Sishencong (EX-HN 1), Neiguan (PC 6), Xinshu (BL 15) and Taixi (KI 3). The most commonly used acupoint combinations were Sanyinjiao (SP 6)-Anmian (Extra)-Baihui (GV 20)-Sishencong (EX-HN 1)-Shenting (GV 24)-Shenmen (HT 7)-Xinshu(BL 15), Xinshu(BL 15)-Pishu (BL 20)-Shenshu (BL 23)-Shenting (GV 24), Zhaohai (KI 6)-Shenmai (BL 62), Taichong (LR 3)-Ganshu (BL 18), Daling (PC 7)-Taixi (KI 3), Neiguan (PC 6)- Zusanli (ST 36) and Guanyuan (CV 4)-Qihai (CV 6)-Zhongwan (CV 12). On the basis of acupoint selection according to disease differentiation, the acupoint selection rules and characteristics of insomnia in the elderly treated with acupuncture are regulating and supplementing the spleen and kidney and treating according to spleen-kidney.
Subject(s)
Aged , Humans , Acupuncture Points , Acupuncture Therapy , Cell Differentiation , Publications , Sleep Initiation and Maintenance Disorders/therapyABSTRACT
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.
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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<sup>-1</sup>）， and high- （180 mg·kg<sup>-1</sup>）， medium- （90 mg·kg<sup>-1</sup>）， and low-dose （45 mg·kg<sup>-1</sup>） 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<sub>max</sub>）， and maximum rate of decrease in left ventricular pressure （LV-dp/dt<sub>max</sub>）， 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<sub>max</sub>， and LV-dp/dt<sub>max</sub> 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<sub>max</sub>， LV-dp/dt<sub>max</sub>， 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.
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Objective:To study the effect of Shuangshen Xionglian （SSXL） granules on vasculopathy and phosphatidylinositol 3 kinase （PI3K）/serine threonine kinase （Akt）/nitrogen oxide synthase （eNOS） signal in hyperhomocysteinemia chronic kidney disease rats. Method:Rats were randomly divided into 5 groups： sham operation group， model group， and high， medium and low-dose （8， 4， 2 g·kg-1） SSXL groups. The model of hyperhomocysteinemia chronic kidney disease in rats was established with high methionine feed combined with 5/6 nephrectomy. After 5/6 nephrectomy， continuous intragastric administration lasted for four weeks. Arterial blood pressure was measured at the 4th and 8th weeks after operation. At the end of the 8th week after the operation， blood was collected to determine serum creatinine， urea nitrogen， homocysteine （Hcy）， methionine and blood lipid. Western blot was used to detect the expressions of PI3K/Akt/eNOS pathway-related proteins， such as p-p85， p-Akt and p-Ser177 in thoracic aorta， and serum NO and eNOS were measured. The changes of endothelium-dependent relaxation and non-endothelium-dependent relaxation were measured by the method of isolated thoracic aorta ring. Pathological htoxylin eosin （HE） staining was used to observe the changes of renal tissue and thoracic aorta. Result:At the 8th week of the experiment， compared with the sham operation group， arterial systolic blood pressure， serum urea nitrogen， creatinine， Hcy， methionine， total cholesterol and low-density lipoprotein of the model group were significantly increased. Four weeks later after administration， arterial systolic blood pressure， serum urea nitrogen， Hcy， methionine， serum total cholesterol and serum low-density lipoprotein were significantly reduced in each dose group （P<0.05， P<0.01）. The creatinine in the SSXL 8， 4 g·kg-1 group was significantly reduced （P<0.05）. The nitric oxide content of SSXL in each dose groups were increased compared with that in the model group （P<0.05， P<0.01）， and the serum eNOS activity of the SSXL in the SSXL 8 g·kg-1 group was significantly increased compared with that in the model group （P<0.05）. The endothelium dependent and non-endothelium dependent vasodilation of thoracic aortic rings in the model group were significantly damaged. The cumulative concentration of acetylcholine （1×10-5.5~1×10-4 mmo1·L-1） in the SSXL 8 g·kg-1 group was significantly improved （P<0.05， P<0.01）. The diastolic degree of the vascular ring in the SSXL 8 g·kg-1 group was significantly higher than that in the model group （P<0.05）. Western blot results showed that the expressions of p-85， p-Akt and p-Ser177 in blood vessels increased in the sham group compared with those in the model group （P<0.01）. Compared with the model group， the phosphorylation level of this pathway was increased in the SSXL groups， and the expressions of p-Akt and p-Ser177 in the SSXL 8 g·kg-1 group were significantly increased （P<0.05）. The pathological results showed that the pathological changes of thoracic aorta and renal tissue in the dosages of SSXL were significantly reduced compared with those in the model group. Conclusion:SSXL granules can improve hyperhomocysteine and dyslipidemia in rats of chronic kidney disease with hyperhomocysteine， reduce serum creatinine， urea nitrogen levels and arterial systolic blood pressure， and improve vascular morphology and diastolic function， which may be related to the regulation of the PI3K/Akt/eNOS signaling pathway.
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@#Objective To analyze the protective mechanism of spinal cord ischemia-reperfusion injury mediated by N-methyl-D-aspartate (NMDA) receptor. Methods A total of 42 SD rats were randomly assigned to 4 groups: a non-blocking group (n=6), a saline group (n=12), a NMDA receptor blocker K-1024 (25 mg/kg) group (n=12) and a voltage-gated Ca2+ channel blocker nimodipine (0.5 mg/kg) group (n=12). The medications were injected intraperitoneally 30 min before ischemia. The neural function was evaluated. The neuronal histologic change of spinal cord lumbar region, the release of neurotransmitter amino acids and expression of spinal cord neuronal nitric oxide synthase (nNOS) were compared. Results At 8 h after reperfusion, the behavioral score of the K-1024 group was 2.00±0.00 points, which was statistically different from those of the saline group (5.83±0.41 points) and the nimodipine group (5.00±1.00 points, P<0.05). Compared with the saline group and nimodipine group, K-1024 group had more normal motor neurons (P<0.05). There was no significant difference in glutamic acid concentration in each group at 10 min after ischemia (P=0.731). The nNOS protein expression in the K-1024 group was significantly down-regulated compared with the saline group (P<0.01). After 8 h of reperfusion, the expression of nNOS protein in the K-1024 group was significantly up-regulated compared with the saline group (P<0.05). Conclusion K-1024 plays a protective role in spinal cord ischemia by inhibiting NMDA receptor and down-regulating nNOS protein expression; during the reperfusion, K-1024 has a satisfactory protective effect on spinal cord function, structure and biological activity of nerve cells.
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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.
Subject(s)
Humans , Autophagy , Medicine, Chinese Traditional , Myocardial Ischemia , Myocardium , Myocytes, CardiacABSTRACT
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.
Subject(s)
Humans , Apoptosis , Autophagy , Benzofurans , Cell Hypoxia , Cell Survival , Hypoxia , Myocytes, CardiacABSTRACT
Nearly 70% of breast cancer (BC) is hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and endocrine therapy is the mainstay of treatment for this subtype. However, intrinsic or acquired endocrine resistance can occur during the endocrine treatment. Based on insights of endocrine resistance mechanisms, a number of targeted therapies have been and continue to be developed. With regard to HR-positive, HER2-negative advanced BC, aromatase inhibitor (AI) is superior to tamoxifen, and fulvestrant is a better option for patients previously exposed to endocrine therapy. Targeted drugs, such as cyclin-dependent kinases (CDK) 4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, phosphoinositide-3-kinase (PI3K) inhibitors, and histone deacetylase (HDAC) inhibitors, play a significant role in the present and show a promising future. With the application of CDK4/6 inhibitors becoming common, mechanisms of acquired resistance to them should also be taken into consideration.
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OBJECTIVE@#To observe the clinical effect of acupuncture by stages on secondary dysmenorrhea of adenomyosis through prospective case-series study.@*METHODS@#A total of 36 cases of adenomyosis patients with moderate-to-severe dysmenorrhea were treated with acupuncture by stages. The acupoints of Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32) and Shiqizhui (EX-B 8) were selected and acupuncture was given once a day during menstrual period; the acupoints of Guanyuan (CV 4), Zigong (EX-CA1), Sanyinjiao (SP 6) and Zusanli (ST 36) ect. were selected and acupuncture was given twice per week during non-menstrual period. All the treatment was given for three menstrual cycles. The visual analogue scale (VAS), Cox menstrual symptom scale (CMSS), Endometriosis Health Profile-5 (EHP-5) scores and the menstrual blood volume of pictorial blood loss assessment chart (PBAC) were observed before treatment and at the 1st, 2nd and 3rd menstrual cycle into treatment. Before treatment and at the 3rd menstrual cycle into treatment, the volume of uterus was measured by transvaginal ultrasound and the correlation among the quality of life, the severity of pain and symptoms was analyzed.@*RESULTS@#The VAS, CMSS and EHP-5 scores at the 1st, 2nd and 3rd menstrual cycle into treatment were lower than those before treatment (0.05). Compared before treatment, at the 1st, 2nd and 3rd menstrual cycle into treatment, the PBAC scores were reduced in patients with PBAC>100 points (<0.01). Compared between 2nd and 1st menstrual cycle into treatment, between 3rd and 2nd menstrual cycle into treatment, the VAS, CMSS scores were all decreased (<0.01, <0.05). There was a significant positive correlation between the severity score of CMSS and EHP-5 at the corresponding time points of the 1st, 2nd and 3rd menstrual cycle into treatment (<0.01).@*CONCLUSION@#The acupuncture by stages has significant analgesic effect in patients with secondary dysmenorrhea of adenomyosis, and has the advantages of relieving the menstruation-related symptoms, regulating menstrual blood volume and improving the quality of life.
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Objective@#Mitral valve replacement is more frequently performed in elder patients with rheumatic valve diseases. Mitral valve repair may be feasible in young patients with suitable anatomy in rheumatic mitral valve disease, but still controversial in elder patients. Our study was to compare mitral repair to bioprosthetic replacement in patients aged 60 years or older.@*Methods@#Eighty two patients(age ≥60 years) underwent mitral valve surgery(mitral repair or bioprosthetic replacement)in our single institution from January 2014 to January 2016 were reviewed, including 25 cases of repair(MVP) and 57 cases of bioprosthetic replacement(MVR). 5 years follow-up oganalysis.@*Results@#Mean age in MVP and MVR was 64.43 years and 67.28 years, respectively. There were no statistically differences in extracorporeal circulation time(P=0.99) and aorta blocking time(P=0.88); the operative mortality rate in MVR was 5.3% while none in MVP(P=0.24). During follow-up 6 deaths happened in MVR, 4 of them died from MACE while the other 2 died from other causes. There was no death in MVP(P=0.17). No redo or other complications were found during follow-up.@*Conclusion@#In patients aged 60 years or older with rheumatic mitral valve disease, mitral repair is associated with a same perioperative and mid-term result compared with bioprosthetic replacement. Rheumatic mitral valves could be repaired in elderly patients.
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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.