Partial aortic root remodeling for root reconstruction in patients with acute type A dissection

In the present study, we reported our experience with partial aortic root remodeling for root reconstruction in patients with acute type A dissection, which involves in non-coronary sinus and/or the right coronary sinus with just one trimmed Dacron graft. Between February 2001 and May 2010, we performed partial aortic root remodeling in 40 patients, who underwent emergency surgical intervention. The dissected sinuses were excised leaving a 3-5 mm rim of the aortic wall from the attached aortic valve cusps. A short piece （4-5 cm） of collagen coated woven polyester vascular prosthesis was trimmed with one or two ＂tongues＂ to reconstruct the non-coronary sinus and/ or the right coronary sinus, but without using separated patches. Additional procedures were including hemi-arch replacement in 11 patients, and total arch replacement plus stent-elephant trunk in 20 patients. The mean follow-up time was 36.4~3.6 months. In-hospital mortality was only 5.0% （2/40）; furthermore, 3 （8.6%） patients underwent re-operation of the aortic valve and 2 （5.7%） patients died during follow-up. At the end of follow-up, trivial or no aortic regurgitation was found in 33 patients, but mild aortic regurgitation was found in 2 patients. Our data suggest that the early and mid-term results of partial aortic root remodeling were favorable, and it restored valve durability and function. Thus, the use of technique for root reconstruction in patients with acute type A dissection should be vigorously encouraged.

Discovery of a novel small inhibitor R J19 targeting to human Hsp90

Heat shock protein 90(Hsp90) can promote growth and proliferation of cancer cells by helping in folding, conformational maturation, and activation of various client proteins. Therefore, Hsp90 has been paid more attention to as an anticancer drug target. Reported Hsp90 inhibitors have several limitations such as poor solubility, limited bioavailability, and hepatotoxicity. Here, a novel small inhibitor RJ19 has been designed using fragment-based drug discovery and synthesized. Additionally, a crystal structure of Hsp90 N-RJ19 was determined by X-ray diffraction(resolution limit, 2.0 A, PDB code 4 L90). The crystal structure of Hsp90 N-RJ19 was analyzed in detail and compared with that of native Hsp90 N, Hsp90 N-ATP, and Hsp90 N-GDM,respectively. It was indicated that RJ19 interacted with Hsp90~N at the ATP-binding pocket, which suggests that RJ19 may replace nucleotides to bind with Hsp90~N to result in chaperone function failure of Hsp90. RJ19, therefore, has emerged as a promising anticancer lead compound. Rearrangement and displacement of L2 Loop in Hsp90~N-RJ 19 play a key role in the function failure, which also makes the pocket wider and longer facilitating structure modification of RJ19 later. The complex crystal structure and interaction between RJ19 and Hsp90~N provide a rational basis for the design and optimization of novel anticancer drugs.

Inhibition of central sympathetic nervous tone improves cardiomyocyte contraction by increasing the response of beta 2-adrenergic receptor in aged rats

In the present study,selective β1-adrenergic receptor antagonist CGP20712A and selective β2-adrenergic receptor antagonist ICI 118551 were administered to isolated cardiomyocytes from young （4-6 months）,aged （18-20 months）,and clonidine-pretreated aged （18-20 months） Sprague-Dawley rats.Cardiomyocyte contraction amplitude was measured to assess cardiomyocyte response to the β-adrenergic receptor agonist,isoprenaline.CGP20712A reduced cardiomyocyte contraction amplitude in young and aged groups and significantly reduced contraction amplitude in cells from young rats.ICI 118551 had no effect on cardiomyocyte contraction amplitude in young rats,but significantly decreased contraction amplitude in the aged groups,in particular in the clonidine-pretreated aged rats.Results demonstrated that reduced central sympathetic tone improved cardiomyocyte contraction in aged rats by improving the response of β2-adrenergic receptor to isoprenaline.

The Effectand Mechanism of Forsinopril on Ventricular Hypertrophy of SHR and Left Ventricular Pressure overloading Rat

The effects and mechanism of long term angiotensin converting enzyme inhibitor (ACEI) Forsinopril on left ventricular hypertrophy of spontaneous hypertension rat (SHR) and left ventricular pressure overloading rat were studied. The left ventricular index (left ventricle weight/body weight) was used to evaluate left ventricular hypertrophy and the in situ hybridization to investigate the TGF β1 gene expression in left ventricle. The results showed that Forsinopril significantly decreased the left ventricular index of both SHR and left ventricle pressure overloading rat. Forsinopril reduced the integral photic density of TGF β1 gene statement from 2.836±0.314 to 1.91±0.217 ( P <0.01, n =8 ) of SHR rat and from 3.071±0.456 to 2.376±0.379 ( P <0.01, n =8) of left ventricular pressure overloading rat respectively. It was concluded that Forsinopril could prevent the occurrence of left ventricular hypertrophy and reduce the TGF-β1 gene expression in left ventricle of both SHR and left ventricular pressure overloading rat significantly.

Treatment of etoposide capsule combined with cisplatin or carboplatin in elderly patients with small cell lung cancer

We aimed to explore the efficacy and safety of etoposide capsule combined with cisplatin or carboplatin in the treatment of elderly patients with small cell lung cancer （SCLC）. Methods： From October 2011 to November 2013, 32 elderly patients （71-79 years old） with histopathologically confirmed SCLC in General Hospital of Shenyang Military Region （China） were enrolled in the research. The patients were administrated with lastet capsule 150-175 mg, dl-5, combined with cisplatin 20 mg/m^2 dl-3 or carbopiatin AUC = 5, applied over 2 days. Twenty-one days were 1 treatment cycle. Results：After treatments, 2 cases acquired complete response （CR）, 19 cases acquired partial response （PR）, 8 cases acquired stable disease （SD）, and 3 cases had progression of disease （PD）. The objective response rate was 65.6% （21/32）, disease control rate was 90.6% （29/32）. The median time of progression-free survival （PFS） was 6.9 months, the median survival time was 14.0 months, and 1 year survival rate was 62.4%. The main adverse reactions of 1/11 leukopenia and gastrointestinal reaction were observed. Conclusion： Etoposide capsule combined with cisplatin or carboplatin therapy have curative effect and good tolerance in elderly patients with SCLC.

Neuregulin-1 therapy improved cardiac function and reduced ANPmRNA expression in post myocardial infarction rats with cardiac dysfunction

Objective To observe the influence of neuregulin-1 on the cardiac function of post-myocardial infarction rats.Methods Left ventricular MI was created in Sprague-Dawley rats by ligation of the left anterior descending coronary.Six months after the operation,rats were evaluated with echocardiology methods.36 rats that had an infarct area and a EF around 60%were randomized into 3 groups:MI group(n=12)were injected a blank vehicle fluid intravenously for 5 days,after which they continued to be raised on standard food and water for 30 days.MI+NRG group(n=12),received NRG-110μg·kg-^(1) intravenously for 5 days,after which they continued to be raised on standard food and water for 30 days.MI+Capt group(n=12)received captopril orally(dissolved in their drinking water 2g/L)for 30days,after which tap water substituted the solution for 5 days.Final echocardiographic and hemodynamic measurements were made at the end of 1 month of therapy.Total RNA was extracted from frozen left ventricular tissues,and was reverse transcribed into firststrand PCR was performed with primers for BNP、ANP.Results Rats treated with neuregulin had a smaller LVDs(P=0.014),a betterLVEF(P=0.004),and a tendency towards less lung perfusion than untreated rats.Neuregulin decreased the expression of ANP mRNA in the ventricle(P=0.025).Conclusion Neuregulin markedly improved the cardiac function of rats that survived myocardial infarction,and decreased the expression of ANP mRNA in the ventricle.

Efficiency and safety of trastuzumab plus chemotherapy in Her-2 overexpressing metastatic breast cancer patients

Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The primary endpoint was overall response rate （ORR） and the second endpoint was clinical benefit rate （CBR） and toxcities. Methods： Estrogen recep- tor （ER） （-）, progesterone receptor （PR） （-）, Her-2 （＋＋＋） patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group （H group） and 75 of them were assigned to the Control group （C group）. They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results： Response rate （RR） of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant （P 〈 0.05）. CBR of the two groups were 76.4% （H group） and 64.0% （C group）, had significant difference （P 〈 0.05）. Complete response rate （CRR） of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups （P = 0.055）. Grade 3-4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy （17.6%） and 4 patients with chemotherapy （5.4%）, with no statistical significance （P = 0.054）. In the subgroup of antharcycline-containing regimens, Grade 1-4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracyciine contained chemotherapy （H ＋ ACCT arm; 40.9%, g/22）], and 4 patients in the antharcycline- containing chemotherapy arm （ACCT arm; 12.5%, 4/32）. There was statistical significant difference between the two arms （P 〈 0.05）. Grade 3--4 cardiac toxicity, the occurance rates were 18.1% （4/22） in H ＋ ACCT arm and 6.3% （2/32） in ACCT arm, and there was no significant statistical difference （P = 0.352）. Grade 3-4 granulocytopenia in the H group and C group were 27.5% （14/51） and 26.7% （20/75）, with no significant difference （P = 0.922）. Conclusion： The efficiency of trastuzumab combining with chemotherapy using as first line regimen in Her-2 overexpressing MBC patients were exact. However, the long-term cardiac toxicity can be hidden troubles of trastuzumab using.

Neoadjuvant chemotherapy for triple-negative breast cancer:a meta-analysis with 7168 cases

Objective:The pathological complete response(pCR) rates of neoadjuvant chemotherapy(NAC) in triple-negative breast cancer(TNBC) was reported higher than that in non-TNBC but ranged from 12% to 48%. pCR was reported to be a predictor of long overall survival and exact pCR rate of NAC in TNBC would give us some hints on how to improve outcomes of TNBC patients. The meta-analysis was conducted to estimate the pCR rate of NAC for TNBC through contrasting the pCR rates of TNBC and non-TNBC tumors in NAC. Methods: Studies were selected from the PubMed database and Cochrane Collaboration Library. pCR rates were collected in groups of TNBC and non-TNBC tumors. Review Manager 4.2 was used to perform forest plots and funnel plots. Results: The analysis included 22 studies with 7168 patients, the aggregate pCR rate was 29.5% in TNBC group, which was 17.7% higher than non-TNBC. The summary relative risk(RR) for pCR rate of TNBC group with that of non-TNBC group was 2.55. No obvious statistical heterogeneity and publication bias was detected. Conclusion: This meta-analysis demonstrated that NAC showed a higher pCR rate in TNBC than non-TNBC.

Complete revascularization reduces adverse outcomes in patients with multivessel coronary artery disease

AIM To investigate the infuence of complete and incomplete revascularization （ICR） in patients with multivessel coro-nary artery disease undergoing coronary artery bypass or percutaneous coronary intervention.METHODS We searched PubMed using the keywords “complete revascularization”, “incomplete revascularization”, “cor-onary artery bypass”, and “percutaneous coronary intervention”. We selected randomized controlled studies （RCT） and observational studies only for review. The main outcomes of interest were mortality, myocardial infarction （MI） and repeat revascularization. We identified further studies by hand searching relevant publications and included those that met with the inclusion criteria in our fnal analysis and performed a systematic review.RESULTSTen studies were identified, including 13327 patients of whom, 8053 received complete revascularization and 5274 received ICR. Relative to ICR, CR was associated with lower mortality （RR： 0.755, 95%CI： 0.66 to 0.864, P = 0.765, I2 = 0.0%）, lower rates of MI （RR： 0.759, 95%CI： 0.615 to 0.937, P = 0.091, I2 = 45.1%）, lower rates of MACCE （RR： 0.731, 95%CI： 0.668 to 0.8, P = 0.453, I2 = 0.0%） and reduced rates of repeat coronary revascularization （RR： 0.691, 95%CI： 0.541 to 0.883, P = 0.0, I2 = 88.3%）.CONCLUSIONCR is associated with lower rates of adverse outcomes. CR can be used as a standard in the choice of any particular revascularization strategy.

Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction

BACKGROUND Nocturnal hypertension is reported as a risk factor for cardiovascular disease.This study aimed to explore the potential association between nocturnal hypertension and heart failure(HF)rehospitalization in patients with HF with preserved ejection fraction(HFpEF).METHODS A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study.Cox regression analysis was used to reveal the potential association between nighttime blood pressure(BP)levels,nocturnal hypertension and nocturnal BP patterns and HF rehospitalization.Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups.RESULTS There were 537 patients with HFpEF were included in the final analysis.The mean age of the study population was 77.14±8.68 years,and 41.2% of patients were men.After a median follow-up duration of 10.93(4.19–21.13)months,176 patients(32.7%)with HFpEF were readmitted for HF.Cox regression analysis had revealed that nighttime systolic BP level[hazards ratio(HR)=1.018,95%CI:1.008–1.028,P=0.001],nighttime diastolic BP level(HR=1.024,95%CI:1.007–1.042,P=0.007),nocturnal hypertension(HR=1.688,95%CI:1.229–2.317,P=0.001)were associated with HF rehospitalization.Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate(log-rank P<0.001).Furthermore,patients with a riser pattern had a higher risk of HF rehospitalization(HR=1.828,95%CI:1.055–3.166,P=0.031)and lower eventfree survival rate(log-rank P=0.003)than those with a dipper pattern.These findings were also confirmed in patients with HFpEF and hyperuricemia.CONCLUSIONS Nighttime BP levels,nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF,and prominently in patients with HFpEF and hyperuricemia.Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

Troponin I biomarker as a strong prognostic factor for predicting COVID-19 mortality:A systematic review

BACKGROUND The increase in circulating Troponin-I in the blood of patients suffering coronavirus disease 2019(COVID-19)can be a strong prognostic factor for predicting disease poorer outcome.AIM To review the literatures to approve this claim systematically.METHODS Two blinded reviewers independently screened the titles and abstracts of the manuscripts using the keywords and deeply searching the databanks including PubMed,Scopus,Google Scholar,and Web of knowledge,followed by profoundly appraisement of the full texts to assess the inclusion appropriateness.RESULTS The manuscripts entered into our final assessment were categorized as the two groups including 10 manuscripts describing and comparing death and diseaserelated complications between the subgroups of patients with raised serum troponin level and those with normal ranges of this biomarker and 7 manuscripts comparing the mean level of serum troponin concentration across the survived and non-survived groups.Comparing outcome of COVID-19 disease in the groups with raised troponin level and normal level of this markers showed increased the likelihood of death[hazard ratio(HR)=4.967,P<0.001],acute respiratory distress syndrome(HR=5.914,P<0.001),acute kidney injury(HR=3.849,P<0.001),and intensive care unit(ICU)admission(HR=3.780,P<0.001)following raise of troponin.The pooled analysis showed significantly higher concentration of this marker in the survived group compared to non-survived group(weighted mean differences of 22.278,95%CI:15.647 to 28.927,P<0.001).CONCLUSION Raising troponin-I on admission can be linked to the increase risk for in-hospital death,acute respiratory distress syndrome,kidney injury,and ICU admission by 4.9,5.9,3.8,and 3.7 times as compared to those with initial normal troponin-I concentration.Thus,raising baseline value of troponin-I can be used as a prognostic factor for poor outcome of COVID-19.

Development of Heart Rate Variaty in the Early and Rehabilitation Phase of AMI

Heart rate variaty (HRV) of 85cases with AMI was observed in the early phase after onset and rehabilitation phase at first month and sixth month, and was contrasted with six time threshold indices of 111 cases with coronary heart disease and that of 35 normal control. We found the HRV of AMI was apperantly lower in the acute phase than that of coronary heart disease and normal controls. HRV recovered gradually with inclining to be stable after half a year, but it was still lower than that of controls. Low HRV in early phase of AMI suggested the poor prognosis.

Endothelial extracellular vesicles induce acute lung injury via follistatin-like protein 1

Cardiopulmonary bypass has been speculated to elicit systemic inflammation to initiate acute lung injury(ALI), including acute respiratory distress syndrome(ARDS), in patients after cardiac surgery. We previously found that post-operative patients showed an increase in endothelial cell-derived extracellular vesicles(eEVs) with components of coagulation and acute inflammatory responses. However, the mechanism underlying the onset of ALI owing to the release of e EVs after cardiopulmonary bypass, remains unclear. Plasma plasminogenactivated inhibitor-1(PAI-1) and eEV levels were measured in patients with cardiopulmonary bypass. Endothelial cells and mice(C57BL/6,Toll-like receptor 4 knockout(TLR4^(-/-))) and inducible nitric oxide synthase knockout(iNOS^(-/-)) were challenged with eEVs isolated from PAI-1-stimulated endothelial cells. Plasma PAI-1 and eEVs were remarkably enhanced after cardiopulmonary bypass. Plasma PAI-1 elevation was positively correlated with the increase in eEVs. The increase in plasma PAI-1 and eEV levels was associated with post-operative ARDS. The eEVs derived from PAI-1-stimulated endothelial cells could recognize TLR4 to stimulate a downstream signaling cascade identified as the Janus kinase 2/3(JAK2/3)-signal transducer and activator of transcription 3(STAT3)-interferon regulatory factor 1(IRF-1)pathway, along with i NOS induction, and cytokine/chemokine production in vascular endothelial cells and C57BL/6 mice, ultimately contributing to ALI. ALI could be attenuated by JAK2/3 or STAT3 inhibitors(AG490 or S3I-201, respectively), and was relieved in TLR4-/-and iNOS-/-mice. eEVs activate the TLR4/JAK3/STAT3/IRF-1 signaling pathway to induce ALI/ARDS by delivering follistatin-like protein 1(FSTL1), and FSTL1 knockdown in eEVs alleviates eEV-induced ALI/ARDS. Our data thus demonstrate that cardiopulmonary bypass may increase plasma PAI-1 levels to induce FSTL1-enriched eEVs, which target the TLR4-mediated JAK2/3/STAT3/IRF-1 signaling cascade and form a positive feedback loop, leading to ALI/ARDS after cardiac surgery. Our findings provide new insight into the molecular mechanisms and therapeutic targets for ALI/ARDS after cardiac surgery.

High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs angiogenesis.Autophagy plays a critical role in angiogenesis,and HDL regulates autophagy.However,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting autophagy.Endothelial cells(ECs)were treated with n HDL and d HDL with or without an autophagy inhibitor.Autophagy,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube formation.We found that autophagy-related protein 5(ATG5)was a direct target of miR-181a-5p.ATG5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d HDL.ATG5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 mice.ATG5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)mice.Taken together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted angiogenesis.In contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)generation.Our findings reveal a novel mechanism by which HDL affects angiogenesis by regulating autophagy and provide a therapeutic target for d HDL-impaired angiogenesis.

Efficacy of Dual Antiplatelet Therapy Combined with Naoxintong Capsules(脑心通胶囊) Following Coronary Microembolization Induced by Homologous Microthrombi in Rats

Objective： To evaluate the efficacy of dual antiplatelet therapy combined with Naoxintong Capsule （脑心通胶囊, NXTC） in a rat model of coronary microembolization （CME）. Methods： A total of 95 rats were randomly divided into 6 groups： control, sham-operation, CME model, NXTC, dual antiplatelet （clopidogrel and aspirin） intervention （DA）, and NXTC combined with DA （NDA） groups. The complete data in 69 rats were obtained. The number of CME, myocardial apoptosis rate, bleeding time, clotting time, and adensosine diphosphate （ADP）-induced platelet aggregation were assessed. Results： Compared with the CME group, the number of CME and myocardial apoptosis rates were significantly decreased in the NXTC, DA, and NDA groups （P〈0.01）. Compared with other intervention groups, the number of CME and myocardial apoptosis rates were the least in the NDA group （P〈0.01）, and the incidence of surgical bleeding was the highest in the DA group （P〈0.01）. Compared with the CME group, ADP-induced maximum platelet aggregation rate was significantly inhibited in the NXTC, DA, and NDA groups （P〈0.01）, both bleeding time and clotting time were significantly increased in the NXTC, DA, and NDA groups （P〈0.01）, while the above parameters were the highest in the DA group （P〈0.05）. Conclusion： The combination therapy of NXTC and DA enhanced the anti-CME effect of either therapy alone and reduced the risk of the DA therapy-associated bleeding, demonstrating an improved benefit/ risk ratio in the rat model of CME.

Comparison of Aspirin and Naoxintong Capsule(脑心通胶囊)with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase

Objective： To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule（脑心通胶囊, NXT） and aspirin with adjusted-dose warfarin in Chinese elderly patients（over 65 years） with nonvalvular atrial fibrillation（NVAF） and genetic variants of vitamin K epoxide reductase（VKORC1）, who are at high-risk of thromboembolism. Methods： A total of 151 patients, with NVAF and AA genotype of VKORC1-1639（a sensitive genotype to warfarin） and a CHA2 DS2-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin（100 mg/day） and NXT（1.6 g thrice a day） or adjusted-dose warfarin [international normalized ratio 2.0–3.0）. The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Results： Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding（secondary event） in the combination therapy group was lower than that in the adjusted-dose warfarin group（0% vs. 7.9%, odds ratio： 0.921, 95% confidence interval： 0.862–0.984, P=0.028）. Conclusions： Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin.（No. ChiC TR-TRC-13003596）

DYNAMIC ANALYSIS OF FLUID-STRUCTURE INTERACTION OF ENDOLYMPH AND CUPULA IN THE LATERAL SEMICIRCULAR CANAL OF INNER EAR

The semicircular canals, composed of lateral, anterior and posterior canals in the inner ear, are the sensors of equilibrium during head rotation movements in the three-dimensional space. Semicircular canals are filled with endolymph confined by the cupula. The study of the relationship between endolymph flow and cupular deformation is important in revealing the semicircular canals biomechanical behavior. To date, there are few studies focusing on the transient endolymph flow and cupular deformation in response to a head rotation motion. The lateral semicircular canal is mainly responsible for the sense of the horizontal rotation movement. In order to figure out the intricate dynamics in the lateral semicircular canal during the head rotation motion, the time evolutions of both endolymph flow and cupular deformation are analyzed in this article by using a fully coupled fluid-structure interaction model. It is shown that the cupular deformation provides cues for understanding the physiology of sensing the head rotation.

Integrative Medicine on Optimizing Clopidogrel and Aspirin Therapy

This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2 C19 gene mutation(CYP2 C19*2 and CYP2 C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention(PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation(AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments(e.g., clopidogrel, CYP2 C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines,Naoxintong Capsule(脑心通胶囊, NXT)] to treat CYP2 C19 gene mutation patients following PCI can be effective.Aspirin combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.

A Randomized Controlled Trial of Adjunctive Bunchang Naoxintong Capsule (步长脑心通胶囊) Versus Maintenance Dose Clopidogrel in Patients with CYP2C19*2 Polymorphism

Objective：To determine the impact of adjunctive Buchang Naoxintong Capsule（步心脑心通胶囊,NXT） on dual antiplatelet therapy in patients with cytochrome P450 2C19＊2（CYP2C19＊2） polymorphism undergoing percutaneous coronary intervention（PCI）.Methods：Ninety patients with CYP2C19＊2 polymorphism were enrolled,and their genotypes were confirmed by polymerase chain reaction（PCR）.The patients were randomly assigned to receive either adjunctive NXT（triple group,45 cases） or dual antiplatelet therapy（dual group,45 cases） using a computer-generated randomization sequence and sealed envelopes.Platelet function was assessed at baseline and 7 days after treatment with conventional aggregometry.Subsequent major adverse cardiovascular events（MACE,including sudden cardiac arrest and acute coronary syndrome） were recorded during a 12-month followup.Results：Baseline platelet function measurements were similar in both groups.After 7 days,percent inhibitions of maximum platelet aggregation and late platelet aggregation were significantly greater in the triple versus dual group（42.3%±16.0%vs.20.8%±15.2%,P〈0.01,and 54.7%±18.3%vs.21.5%±29.2%,P〈0.01,respectively）.During the 12-month follow-up,the rate of subsequent MACE（6/45） was significantly lower in the triple group compared with the dual group（14/45;P〈0.05）.Conclusion：Adjunctive NXT to maintenance dose clopidogrel（75 g） could enhance the antiplatelet effect and decrease subsequent MACE in patients with the CYP2C19＇2polymorphism undergoing PCI.

Evidence-based medicine in China

Evidence-based medicine (EBM) has been promoted in China for the past 2 decades and has had a great in-fluence on the field of medicine. Medical students, practitioners, and policy makers have employed evidence from well-designed and well-conducted studies to optimize decision-making. This article summarizes the recent progress in EBM in China. Development of EBM in remote areas of China Ten years ago, many remote areas, such as Tibet, Xinjiang, the western edge of Yunnan Province, the northeast edge of Guizhou Province, and Western Sichuan Plateau, suffered from deep medical and social problems. There was a wide disparity in access to physicians practicing EBM between rural areas and big cities at that time.