血小板平均容积对急性非ST段抬高型心肌梗死介入治疗患者长期预后的影响

目的探讨血小板平均容积对急性非ST段抬高型心肌梗死(NSTEMI)介入治疗患者长期预后的影响。方法选取2010年1月—2014年10月在中国医科大学附属盛京医院确诊为NSTEMI且行经皮冠状动脉介入(PCI)治疗的885例患者。基于血小板平均容积(MPV)水平,将患者分为低MPV组756例(MPV<10.94 fl)和高MPV组129例(MPV≥10.94 fl)。通过单因素及多因素Cox回归分析,研究MPV对NSTEMI行PCI治疗患者预后的影响。结果平均随访30.9个月,与低MPV组比较,高MPV组全因死亡及心源性死亡率更高(P <0.05);多因素校正后Cox分析显示,高MPV是行PCI的NSTEMI患者全因死亡[H^R=1.390(95%CI:1.130,1.710),P=0.002]及心源性死亡[H^R=1.306(95%CI:1.027,1.662),P=0.030]事件的危险因素;Kaplan-Meier生存曲线显示,高MPV组不良心血管事件发生率更高,预后不佳(P<0.05)。结论 MPV是NSTEMI患者PCI术后不良预后的危险因素。

D-二聚体对急性非ST段抬高型心肌梗死患者预后的预测价值

目的评估血浆D-二聚体水平对急性非ST段抬高型心肌梗死患者预后的影响。方法前瞻队列研究,选取2015年1月—2016年12月中国医科大学附属盛京医院确诊为急性非ST段抬高型心肌梗死并进行择期经皮冠状动脉介入治疗(PCI)的患者648例。根据入院次日血浆D-二聚体水平分成两组,低D-二聚体组和高D-二聚体组。收集所有患者临床资料、冠状动脉病变情况、冠状动脉介入治疗情况,以及随访1年记录临床终点事件。通过Cox回归分析研究血浆D-二聚体水平对急性非ST段抬高型心肌梗死患者预后的影响。结果与血浆低D-二聚体水平患者比较,血浆D-二聚体水平较高患者中男性比例更低、心率更快、肌酐水平更高,并且患者全因死亡率和心源性病死率更高(P <0.05)。根据Cox分析提示,血浆中D-二聚体水平是急性非ST段抬高型心肌梗死患者预后预测因素(P <0.05)。结论血浆D-二聚体水平较高患者长期的全因死亡率及心源性病死率更高,血浆D-二聚体水平可以作为预测急性非ST段抬高型心肌梗死患者预后的危险因素。

Repeated measurement of growth-differentiation factor-15in Chinese Han patients with post-myocardial infarction chronic heart failure

Background Growth-differentiation factor-15(GDF-15)is a promising prognostic biomarker in patients with chronic heart failure (CHF).Comparatively little is known about the value of repeated measurement of GDF-15with CI-IF in Chinese Han population.This study sought to identify the clinical value of repeated measurement of GDF-15in Chinese Han patients with post-myocardial infarction CHF. Methods In total,232consecutive Chinese Hart patients with post-myocardial infarction CHF were enrolled prospectively from January 2014to June 2016.The plasma concentration of GDF-15was determined on admission and over 12months.Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE)included all-cause death,myocardial infarction and first heart failure (HF)re-hospitalization.Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored.Results The median baseline GDF-15level was 2025ng/L.Baseline GDF-15was moderately associated with baseline N-terminal pro-B type nalriuretic peptide (NT-proBNP)(coefficient 0.561,P <0.001).During a median follow-up of 20months,there were 53deaths and 100MACE.GDF-I5remained an independent predictor of all-cause death (adjusted hazard ratio 1.826per 1Ln U,95%CI: 1.037-8.360;P =0.037)and MACE (adjusted hazard ratio 2.243per I Ln U,95%CI:1.181-1.775;P <0.001)adjusted for established risk factors.Repeated measurement of GDF-15was performed in 173survivals over 12months.Increase of GDF-15over 12months was associ- ated with dilatation of left ventricle and acted as an independent predictor of subsequent all-canse death (adjusted HR =3.164,95%CI: 1.245~.041;P =0.015).In the joint model,GDF-15was also shown to be a risk factor for all-cause death (HR =2.749,95%CI: 1.667-3.831;P <0.001)and MACE (FIR =2.434,95%CI:1.425-3.443;P <0.001).Conclusions Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CI-IF post-myocardial infarction.GDF-15may influence the post-myocardial infarction CI-IF through the path physiological pathway of myocardial remodeling.

Predictors of adherence to home-based cardiac rehabilitation program among coronary artery disease outpatients in China

Background Cardiac rehabilitation (CR) has proven beneficial for patients with coronary artery disease. However, adherence to CR programs is the key to the health improvement in those patients. Identifying predictors for adherence, which is very much unknown in China, would be valuable for effective rehabilitation. This study aims to determine the adherence to home-based CR programs in Chinese coronary artery disease patients and determine predictors of adherence. Methods The current study included 1033 outpatients with coronary heart disease in the First Medical Center of Chinese PLA General Hospital in Beijing from July 2015 to June 2017. Participants were given an exercise prescription and took part in home-based exercise training lasting for 3–24 months. A questionnaire was used to evaluate the completion of the CR program, understanding of the program, motivation of the patients, and family/peer support. Results Two thirds of the patients adhered well to the home-based CR program. Elder patients (≥ 65-year-old) adhere to the program better, while men adhered better than women. Patients who used to exercise (B = 6.756, P < 0.001), understood the program (B = 0.078, P = 0.002), with stronger motivation to participate (B = 0.376, P < 0.001), and received better family support (B = 0.487, P < 0.001) also adhere better to the program. Conclusions Understanding the program, self-motivation of patients, and family support help to keep patients engaged in a home-based CR program. Improvement of family support by educating both patients and families may be helpful in improving adherence to home-based CR programs.

Treatment of severely calcified coronary artery disease by intravascular lithotripsy primary outcomes and 180-day followup from the Chinese SOLSTICE Trial

OBJECTIVE To assess the safety and effectiveness of intravascular lithotripsy(IVL)treatment for de novo coronary lesion involving severely calcified vessels in a Chinese population.METHODS The Clinical Trial of the ShOckwave Coronary IVL System Used to Treat CalcIfied Coronary ArtEries(SOLSTICE)was a prospective,single-arm,multicentre trial.According to the inclusion criteria,patients with severely calcified lesions were enrolled in the study.IVL was used to perform calcium modification prior to stent implantation.The primary safety endpoint was freedom from major adverse cardiac events(MACEs)at 30 days.The primary effectiveness endpoint was procedural success,defined as successful stent delivery with residual stenosis<50% by core lab assessment without in-hospital MACEs.The morphological changes of calcium modification were assessed by optical coherence tomography(OCT)before and after IVL treatment.RESULTS Patients(n=20)were enrolled at three sites in China.Severe calcification by core lab assessment was present in all lesions,with a mean calcium angle and thickness of 300±51°and 0.99±0.12 mm(by OCT),respectively.The 30-day MACE rate was 5%.Both primary safety and effectiveness endpoints were achieved in 95% of patients.The final in-stent diameter stenosis was 13.1%±5.7% with no patient had a residual stenosis<50%after stenting.No serious angiographic complications(severe dissection grade D or worse,perforation,abrupt closure,slow flow/no-reflow)observed at any time during the procedure.OCT imaging demonstrated visible multiplane calcium fracture in 80% of lesions with a mean stent expansion of 95.62%±13.33% at the site of maximum calcification and minimum stent area(MSA)of 5.34±1.64 mm^(2).CONCLUSIONS The initial coronary IVL experience for Chinese operators resulted in high procedural success and low angiographic complications consistent with prior IVL studies,reflecting the relative ease of use of IVL technology.

Vessel healings after stenting with different polymers in STEMI patients

Background Different stems implantation in ST-segmem elevation myocardial infarction （STEMI） patients may influence the long term prognosis by affecting vessel healings after stenting. The aim of this study was to evaluate the vessel healings after implantation of drug elming stems （DES） with biodegradable or durable polymer or of bare-metal stems （BMS） in patients with ache STEMI. Methods This study included 50 patients, who underwem follow up angiogram and optical coherence tomography （OCT） assessment about one year after percutaneous coronary intervemion （PCI） for STEMI. According to the initial stems types, these patients were classified to durable （n = 19） or biodegradable polymer sirolimus-eluting stems （n = 15）, or BMS （n = 16） groups. The conditions of stem struts coverage and malapposi- tion were analyzed with OCT technique. Results A total of 9003 struts were analyzed： 3299, 3202 and 2502 from durable or biodegradable polymer DES, or BMS, respectively. Strut coverage rate （89.0%, 94.9% and 99.3%, respectively）, malapposition presence （1.7%, 0.03% and 0 of struts, respectively） and average intimal thickness over struts （76 ± 12 μm, 161 ± 30 μm and 292 ± 29 μm, respectively） were significantly differem among different stent groups （all P 〈 0.001）. Conclusions Vessel healing status in STEMI patients is superior after implantation of biodegradable polymer DES than durable polymer DES, while both are inferior to BMS.

Depression and myocardial injury in ST-segment elevation myocardial infarction:A cardiac magnetic resonance imaging study

BACKGROUND Depression is common in patients with myocardial infarction and has been independently associated with adverse outcomes.However,the association between depression and myocardial injury on cardiac magnetic resonance(CMR)in patients with ST-segment elevation myocardial infarction(STEMI)has still not been assessed.AIM To assess the association between depression and myocardial injury on CMR in patients with STEMI.METHODS A total of 107 STEMI patients undergoing primary percutaneous coronary intervention(P-PCI)were analyzed in this prospectivecohort study.Each subject completed the Patient Health Questionnaire-9(PHQ-9)to assess the presence and severity of depressive symptoms.CMR was performed at a median of 3 d after PPCI for quantifying post-MI myocardial injury.Correlations between depression identified by the PHQ-9 and myocardial injury measured on CMR were assessed.RESULTS In this study,19 patients(17.8%)were diagnosed with major depression identified by the PHQ-9≥10.PHQ-9 was analyzed both as a continuous variable and dichotomous variable.After multivariable adjustment,the proportion of patients with large infarction size was significantly higher in the major depression group(PHQ-9≥10)(OR:4.840,95%CI:1.122–20.868,P=0.034).When the PHQ-9 was evaluated as a continuous variable,after multivariable adjustment,an increased PHQ-9 score was associated with an increased risk of large infarction size(OR:1.226,95%CI:1.073–1.401,P=0.003).CONCLUSION In patients with STEMI undergoing PCI,depression was independently associated with a large infarction size.

N-terminal pro-brain natriuretic peptide but not high-sensitivity C-reactive protein is related to severity of coronary artery stenosis in patients with acute coronary syndrome

Objective Biochemical indicators such as N-terminal pro-brain type natriuretic peptide（NT pro-BNP）and high-sensitivity Creactive protein（hsCRP）predict mortality in acute coronary syndrome（ACS）.However,little is known about the relationship of these factors with severity of coronary artery stenosis in patients with.Methods Three hundred and thirty-one subjects including 246 unstable angina pectoris patients and 85 myocardial infarction patients were recruited and classified into two groups：single-vessel disease group（1-vessel disease,n=93）and multiple-vessel disease group（≥2-vessels disease,n=238）according to selective coronary angiography.Plasma levels of NT pro-BNP and hsCRP were measured and severity of coronary stenosis was determined by Gensini score.Results NT pro-BNP but not hsCRP level was higher in patients with myocardial infarction than in patients with unstable angina pectoris.The patients with multiple-vessel disease had significantly higher NT pro-BNP level but not hsCRP compared with those with single-vessel disease.NT pro-BNP levels increased significantly as left ventricle（LV）function decreased,and only NT proBNP but not hsCRP level was related to Gensini score of severity of coronary stenosis in ACS.Conclusion NT proBNP but not hsCRP level is related to severity of coronary artery stenosis in patients in ACS.

Correlation between Acute Coronary Syndrome Classification and Multi-detector CT Characterization of Plaque

Objective To determine if multi-detector CT （MDCT） characterization of plaque is correlated with the classification of acute coronary syndrome （ACS）. Methods Altogether 1900 patients were examined by MDCT from December 2007 to May 2009, of whom 95 patients fulfilled the criteria of ACS. Those patients were divided into the discrete plaque group （n=61） and diffuse plaque group （n=34） based on the findings in MDCT. The clinical diagnosis of ACS and CT results were analyzed, including segment stenosis score, segment involvement score, 3-vessel plaque score, left main score, calcification score, and remodeling index. The incidences of major adverse cardiac events in follow-up period were also recorded. Results The patients of the diffuse plaque group were older than those of the discrete plaque group （P〈0.0001）. The diffuse plaque group presented more cases of hypertension, peripheral artery disease, diabetes, and heart failure than discrete plaque group （all P〈0.05）. All the 5 patients with ST-segment elevation myocardial infarction were found in discrete plaque group. The segment stenosis score of the discrete plaque group was lower than that of the diffuse plaque group （5.15±3.55 vs. 14.91±5.37, P〈0.001）. The other four scores demonstrated signiflcant inter-group difference as well （all P〈0.05）. The remodeling index of the discrete plaque group was higher （1. 12±0.16 vs. 0.97±0.20, P〈0.05）. Follow-up data showed that major adverse cardiac events occurred more frequently in diffuse plaque group than in discrete group （29.41% vs. 11.48%, P=0.0288）. Conclusions Characteristics of discrete and diffuse plaques may be significantly different among different classes of ACS. The diffuse plaque may present higher risk, correlated to higher mortality. The diagnosis of discrete and diffuse plaques by MDCT would provide a new insight into the prognosis and treatment of ACS.

Unlocking T cell exhaustion:Insights and implications for CAR-T cell therapy

Chimeric antigen receptor T(CAR-T)cell therapy as a form of adoptive cell therapy(ACT)has shown significant promise in cancer treatment,demonstrated by the FDA-approved CAR-T cell therapies targeting CD19 or B cell maturation antigen(BCMA)for hematological malignancies,albeit with moderate outcomes in solid tumors.However,despite these advancements,the efficacy of CAR-T therapy is often compromised by T cell exhaustion,a phenomenon that impedes the persistence and effector function of CAR-T cells,leading to a relapse rate of up to 75%in patients treated with CD19 or CD22 CAR-T cells for hematological malignancies.Strategies to overcome CAR-T exhaustion employ state-of-the-art genomic engineering tools and single-cell sequencing technologies.In this review,we provide a comprehensive understanding of the latest mechanistic insights into T cell exhaustion and their implications for the current efforts to optimize CAR-T cell therapy.These insights,combined with lessons learned from benchmarking CAR-T based products in recent clinical trials,aim to address the challenges posed by T cell exhaustion,potentially setting the stage for the development of tailored next-generation approaches to cancer treatment.

Improving antitumor immunity using antiangiogenic agents:Mechanistic insights,current progress,and clinical challenges

Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy can ultimately relapse and progress.Thus,some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy.Recently,multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response;thus,vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes.A successful antitumor immune response requires an intact“Cancer-Immunity Cycle,”including T cell priming and activation,immune cell recruitment,and recognition and killing of cancer cells.Angiogenic inducers,especially vascular endothelial growth factor(VEGF),can interfere with activation,infiltration,and function of T cells,thus breaking the“Cancer-Immunity Cycle.”Together with immunostimulation-regulated tumor vessel remodeling,VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors.Following the successes of recent landmark phase III clinical trials,therapies combining immune checkpoint inhibitors(ICIs)with antiangiogenic agents have become first-line treatments for multiple solid tumors,whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies.In this review,we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies.Then,we discussed recent progress in randomized clinical trials.ICI-containing combinations were the focus of this review because of their recent successes,but combinations containing other immunotherapies were also discussed.Finally,we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate collaboration within the research community.

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

A pilot study on diagnosis of coronary artery disease using computed tomography first-pass myocardial perfusion imaging at rest

Background:Although computed tomography coronary angiography (CTCA) can identify coronary stenosis,little data exists on the ability of multislice computed tomography (MSCT) to detect myocardial perfusion defects at rest.Methods:In 33 patients with diagnosed or suspected coronary artery disease (CAD),CTCA using retrospective electrocardiography (ECG) gating at rest and invasive coronary angiography (ICA) was performed.The 2D myocardial images were reconstructed in diastolic and systolic phases using the same raw data for CTCA.CT values of the myocardium were used as an estimate of myocardial enhancement,which were shown by color mapping.Myocardial ischemia was defined as a pattern of transient endocardial hypo-enhancement at systole and normal enhancement at diastole.The results of ICA were taken as the reference standard.Results:When a diameter reduction of more than 50% in ICA was used as diagnostic criteria of CAD,the sensitivity,specificity,positive predictive value (PPV),and negative predictive value (NPV) of CT first-pass myocardial perfusion imaging (MPI) at rest were 0.85,0.67,0.92,and 0.50 per patient,respectively,and 0.58,0.93,0.85,and 0.76 per vessel,respectively.Conclusions:CT first-pass MPI at rest could detect CAD patients,which could become a practical and convenient way to detect ischemia,consequently offering the ability for MSCT to act as a "one stop shop" for the diagnosis of CAD.

Covalent organic frameworks for optical applications

Linking molecules into extended crystalline networks to construct covalent organic frameworks(COFs)added in variety to the readily thriving research on moleculebased solid-state materials,featured by classic polymers and molecular crystals.Compared to the development of COFs for gas separation,energy storage,and conversion,where the porosity feature of COFs is utilized,the optical applications,such as fluorescence,white light emission,and photodynamic therapy,involving the molecular and crystalline feature of COFs,are much less explored.In this review,we focused on the optical properties of COFs,and how do these macroscopic properties correlate with the microscopic structure of COFs.Other than the influence from organic functional groups in previous reviews on COFs,here,three critical structure factors,the connection,orientation,and alignment of the molecular building blocks,are outlined and associated with the optical properties of COFs.We also analyze the properties of COFs from both energy and dynamic aspects in an attempt to provide further insight into the possible underlying mechanism.At the end of this review,we also discuss the remaining challenges and future directions for the design of COFs for optical applications,and unveil the potential of COFs toward this direction.

Implantable versatile oxidized bacterial cellulose membrane for postoperative HNSCC treatment via photothermal-boosted immunotherapy

The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.

Inspired heat shock protein alleviating prodrug enforces immunogenic photodynamic therapy by eliciting pyroptosis

Despite immunotherapy involving immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,the clinical efficacy is limited due to ICI resistance.Pyroptosis is a gasdermin-mediated programmed cell death that enhances responses to ICIs.However,nontargeted elicitation of pyroptosis may induce systemic side effects and toxicity.Therefore,we reasonably design and construct a tumor-specific prodrug that combines the heat shock protein 90 inhibitor tanespimycin(17-AAG)with the photosensitizer chlorin e6(Ce6)to induce pyroptosis,by utilizing the high glutathione level in the tumor microenvironment.The released Ce6 and 17-AAG produce reactive oxygen species by laser triggering,which induces gasdermin E-mediated pyroptosis.Furthermore,17-AAG reduces myeloid-derived suppressor cells and sensitizes tumors to anti-programmed death^(-1)(PD-1)therapy.Thus,our prodrug strategy achieves tumor-targeted pyroptosis to suppress tumor growth,thereby improving the response to anti-PD-1 therapy and extending the survival of 4T1 breast tumor-bearing mice.Consequently,this pyroptosis-based prodrug represents a novel strategy for enforcing immunogenic photodynamic therapy.