Extensive loss of cardiomyocytes plays a major role in heart failure development after myocardial infarction (MI). Existing pharmacological treatments targeting cardiomyocyte apoptosis have shown limited clinical efficacy, largely because the underlying molecular mechanisms are unclear and effective drug delivery systems are unavailable. Emerging evidence suggests a critical regulatory role of ubiquitin-specific peptidase 10 (USP10) in cardiomyocyte apoptosis through multiple pathways. USP10 expression and its association with cardiomyocyte apoptosis were evaluated in a murine MI model. A biomimetic nanoparticle coated with neutrophil membranes and encapsulating a USP10 overexpression plasmid (NM-NP-USP10) was developed and characterized. Subsequent investigations evaluated its biodistribution, biosafety, therapeutic efficacy, and underlying mechanisms both in vivo and in vitro. The role of AMPK signaling was examined through the application of the pharmacological inhibitor Compound C. USP10 expression was markedly downregulated in the infarcted cardiac tissue and showed a positive association with cardiomyocyte apoptosis. NM-NP-USP10 preferentially accumulated in the ischemic myocardium and exhibited favorable biosafety profiles. Moreover, treatment with NM-NP-USP10 not only attenuated cardiomyocyte apoptosis but also promoted angiogenesis in vivo. Mechanistically, NM-NP-USP10 activated the AMPK/Akt/eNOS signaling pathway. In contrast, inhibition of AMPK substantially abrogated its anti-apoptotic and pro-angiogenic effects, indicating that AMPK signaling serves as a critical mediator of USP10-induced cardioprotection. These findings identify USP10 as a protective regulator in MI and demonstrate that targeted delivery of USP10 via neutrophil membrane-coated biomimetic nanoparticles facilitates cardiac repair through AMPK-dependent anti-apoptotic and pro-angiogenic mechanisms, underscoring its potential as a therapeutic strategy for MI.
To analyze the outcome of 147 cases of type B aortic dissection with thoracic endovascular aortic repair (TEVAR). We systematically reviewed 147 patients of type B aortic dissection with stent graft deployment in zone 2 or zone 3 by TEVAR from January 2012 to December 2022. These patients were observed by computed tomography angiography after the first and third months and annually thereafter during follow-up. Statistical analysis was performed by SPSS.16. The stent graft of 107 patients was deployed in zone 3, and the stent graft of 40 patients was deployed in zone 2. Severe dissection and surgery-related complications after TEVAR occurred in 19 patients, with complications arising more frequently in zone 2 than in zone 3 (12/40 vs. 7/107, P < 0.005). Endoleak was detected in 10 (6.8 Type of Research: Single-center retrospective cohort study. Key findings: 147 patients of type B aortic dissection with stent graft deployed in zone 2 or zone 3 by TEVAR. Severe dissection and surgery-related complications after Thoracic EndoVascular Aortic Repaie (TEVAR) occurred in 19 patients, with complications arising more frequently in zone 2 than in zone 3 (12/40 vs. 7/107, P < 0.005). Endoleak was detected in 10 (6.8 Take Home Message: This study suggests that TEVAR is the major treatment to use TEVAR if the stent graft can be deployed in zone 3. However, with the higher rate of complications and re-intervention after TEVAR, for patients whose stent graft can only be deployed in zone 2, it is not recommended that TEVAR be chosen as the preferred treatment.
Acquired thrombophilia and in particular the presence of antiphospholipid antibodies (aPL) may play an important role in the development of chronic thromboembolic pulmonary hypertension (CTEPH). Young patients suffering from an episode of unprovoked pulmonary embolism (PE), or PE provoked by mild risk factors, should be tested for aPL. In case of a positive result, they should be closely followed up and lifelong anticoagulant treatment should be considered. Indeed, aPL-induced thrombophilia may favor PE recurrence with the consequence of possible CTEPH development. The aPL profiles play an important role in this pathway. Patients with PE and triple positivity (lupus anticoagulant, LAC, anti-cardiolipin, aCL, and anti-β2-glycoprotein I, aβ2GPI) are at the highest risk of recurrence and deserve maximum protection by anticoagulant treatment with warfarin.
BACKGROUND:Myocarditis is a cardiomyopathy associated with the inflammatory response. Rosuvastatin (RS) demonstrates cardioprotective effect in the clinical setting, although its cellular and molecular mechanisms in ameliorating myocarditis are largely unknown. MG53 (muscle-specific E3 ligase Mitsugumin 53), a newly identified striated muscle-specific protein, is involved in skeletal muscle membrane repair. We aimed to explore whether RS mediated the repair of cardiomyocytes in an MG53-dependent manner.METHODS:The RS-induced upregulation of MG53 was determined using RT-qPCR and western blotting. A lipopolysaccharide (LPS)-induced cell inflammatory model was constructed using rat cardiac muscle cell H9C2. Inflammatory injury was evaluated according to the alterations of cell viability, mitochondrial membrane potential, cell apoptosis, and expression of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1). Small interfering RNAs (siRNAs) were used to silence MG53. The cardioprotective effect of RS and the inhibition of this protection by MG53 silence were evaluated in the forementioned in vitro model. The underlying mechanism was finally investigated using western blotting to detected the expressions of apoptotic markers (Bcl-2, Bax, Cleaved caspase-9, Cleaved caspase-3), cell cycle regulatory factors (Cyclin A, Cyclin E1, Cyclin D1, CDK2), and components involved in NF-κB signaling pathway (p-IκBa, Iκba, p-p65, p65).RESULTS:RS ameliorated LPS-induced inflammatory injury. RS upregulated the expression of MG53. MG53 was crucial for the RS-mediated repair response in vitro. Ablation of MG53 inhibited the RS-mediated protective effect. Furthermore, RS and MG53 interact in multiple signaling pathways to modulate recovery.CONCLUSION:RS exerts cardioprotective effect in an MG53-dependent manner. MG53 may serve as a novel drug target for myocarditis treatment.
背景:当前市售可吸收止血材料对于动脉性出血的止血性能尚未达到临床理想效果.目的:研究复合大孔聚多糖止血材料在小动脉出血创伤中的止血效果.方法:通过离断兔股动脉建立小动脉出血模型,随机分为2组,实验组(n=10)采用课题组自主研发的复合大孔聚多糖止血材料,对照组(n=7)应用市售复合微孔聚多糖止血粉.术后记录两组止血成功率与出血量,动态检测血常规及肝肾功能指标检测,并通过苏木精-伊红染色观察伤口组织.结果与结论:①实验组的止血成功率高于对照组(90%,43%,P < 0.05),两组术中出血量比较差异无显著性意义(P > 0.05);②术后180 d内的血常规及肝肾功能指标检测结果显示,两组各指标变化趋势基本一致,并且两种止血材料均未造成明显的肝肾功能障碍,也未在降解吸收过程中发生化脓、炎症等情况;③术后90 d的伤口组织苏木精-红染色显示,实验组组织染色均匀,肌纤维形态结构正常、分界清晰、排列规则,间质未见明显异常,伤口处未见瘢痕等存在;对照组同样组织染色均匀,肌纤维形态结构正常、分界清晰、排列规则,间质未见明显异常,但局部出现较多瘢痕;④结果表明,复合大孔聚多糖止血材料的止血有效性高于市售复合微孔聚多糖止血粉,其安全性与市售复合微孔聚多糖止血粉相比非劣效,可用于体内止血.
Aims: Myocarditis is an inflammation of the heart muscle, due to infectious, toxic or autoimmune causes. Literature reported controversial results in relation to the effect of immunosuppression (IS)/immunomodulation (IM). We aimed at assessing the effect of IS/IM by meta analysis. Methods and results: Using the P.R.I.S.M.A. approach, two researchers searched for relevant studies on PubMed, Embase, and the Central Registry of Controlled Trials of the Cochrane Library. Proposed MeSH terms were: "immunotherapy OR immune therapy OR immune modeling OR Immunosuppressive Agents" AND "combination OR combined with OR plus" AND "myocarditis OR cardiomyopathies OR inflammatory cardiomyopathy". The language was restricted to English. Reference lists of included articles and those relevant to the topic were hand searched for the identification of additional, potentially relevant articles. The cutoff date was from 1987 until 30th Nov 2019. Reported survival or mortality events or change of left ventricular ejection fraction (LVEF) after IS/IT were primary outcomes of the study; in addition, improvement of New York Heart Association class, followup biopsy (Bx) findings, viral genome clearance on Bx and recurrence of myocarditis were recorded if reported. Statistical analysis was conducted using Review Manager 5.3; 5452 studies were screened, of these 73 were assessed for eligibility, including 8 randomized control studies, 26 retrospective studies, 2 prospective studies and 1 case control study, 34 case reports and 2 case series. In prospective studies, the difference in mortality between the IS and control groups tended to be lower in the combined IS groups (12.5% vs. 18.2%) (95% CI of odds ratio 0.7(0.3, 1.64)) and the pooled difference of the increase of LVEF between the IS and control groups tended to be higher in the combined IS groups (95% CI 7.26 (2.29, 16.81)). In retrospective studies, the difference of survival between the IS and control group was significantly in favor of IS (95%CI Hazard ratio 0.82 (0.69, 0.96)). Conclusions. A tailored IS may be considered in myocarditis, depending on the phase of the disease, and the type of underlying autoimmune or immune-mediated form.
Thrombotic Antiphospholipid Syndrome (APS) is a condition affecting young individuals in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL). An extensive body of literature has covered the most common clinical presentation of the syndrome, venous thromboembolism. Arterial thrombosis in APS, a lesser clinical expression, is less studied. This review will concentrate on the body of literature concerning pathogenesis, clinical presentation and management of arterial thrombosis in APS.
Myocarditis is an inflammation of the heart muscle, due to infectious, toxic or autoimmune causes. Literature reported controversial results in relation to the effect of immunosuppression (IS)/immunomodulation (IM). We aimed at assessing the effect of IS/IM by meta analysis. Using the P.R.I.S.M.A. approach, two researchers searched for relevant studies on PubMed, Embase, and the Central Registry of Controlled Trials of the Cochrane Library. Proposed MeSH terms were: “immunotherapy OR immune therapy OR immune modeling OR Immunosuppressive Agents” AND “combination OR combined with OR plus” AND “myocarditis OR cardiomyopathies OR inflammatory cardiomyopathy”. The language was restricted to English. Reference lists of included articles and those relevant to the topic were hand searched for the identification of additional, potentially relevant articles. The cutoff date was from 1987 until 30th Nov 2019. Reported survival or mortality events or change of left ventricular ejection fraction (LVEF) after IS/IT were primary outcomes of the study; in addition, improvement of New York Heart Association class, follow-up biopsy (Bx) findings, viral genome clearance on Bx and recurrence of myocarditis were recorded if reported. Statistical analysis was conducted using Review Manager 5.3; 5452 studies were screened, of these 73 were assessed for eligibility, including 8 randomized control studies, 26 retrospective studies, 2 prospective studies and 1 case control study, 34 case reports and 2 case series. In prospective studies, the difference in mortality between the IS and control groups tended to be lower in the combined IS groups (12.5% vs. 18.2%) (95% CI of odds ratio 0.7(0.3, 1.64)) and the pooled difference of the increase of LVEF between the IS and control groups tended to be higher in the combined IS groups (95% CI 7.26 (−2.29, 16.81)). In retrospective studies, the difference of survival between the IS and control group was significantly in favor of IS (95%CI Hazard ratio 0.82(0.69, 0.96)). Conclusions. A tailored IS may be considered in myocarditis, depending on the phase of the disease, and the type of underlying autoimmune or immune-mediated form.
Objective:To compare the early and mid-term results of thoracic endovascular aortic repair (TEVAR) with covered stent and simple medication in treating uncomplicated acute type B aortic dissection (ATBAD).Methods:The clinical data of 203 patients (118 males and 85 females) with uncomplicated ATBAD admitted to the First Affiliated Hospital of Xiamen University from January 2012 to December 2018 were collected and analyzed. The patients were divided into two groups based on the ways of treatment: simple medication group (Med group, 67 cases) and TEVAR group (136 cases). The operative and follow-up data of the patients in two groups were analyzed to evaluate the incidence rate of postoperative complications and the reintervention rate.Results:The follow-up time was (3.7±1.8) years (range: 3-84 months). During the follow-up period, the overall incidence rate of complications was 15.3% (31/203), the reintervention rate was 10.3% (21/203), and the mortality rate was 6.4%(13/203). The incidence rate of aortic-related complications (26.9% vs. 9.6%; P<0.05), the reintervention rate(19.4% vs. 6.6%; P<0.05), and the mortality rate (13.4% vs. 2.9%; P<0.05) in the TEVAR group were significantly lower than those in the Med group, and the differences were statistically significant. Compared with the Med group, the TEVAR group did not show a higher incidence of aortic dissection rupture (7.5% vs. 1.5%; P<0.05) and retrograde type A aortic dissection (4.5% vs. 1.5%; P>0.05). Conclusion:For the treatment of uncomplicated ATBAD, TEVAR is effective and safe. Compared with simple medication, TEVAR can achieve better early and mid-term results in treating uncomplicated ATBAD.
目的 分析覆膜支架腔内修复术(TEVAR)中支架锚定于Zones 2或Zone 3的并发症发生情况.方法 回顾性分析2013年6月至2018年7月117例Stanford B型主动脉夹层患者行TEVAR的治疗及随访资料(出院随访期间意外死亡除外),随访期间,患者均行主动脉CT血管造影检查,了解覆膜支架位置、远端真假腔血栓化程度、主动脉重要分支血流灌注情况、有无内瘘、是否新发主动脉夹层及其他的并发症.结果 术中所有覆膜支架释放成功,27例支架锚定于Zone 2,90例支架锚定于Zone 3.117例随访患者中有14例发生并发症,其中Zone 2发生8例,Zone 3发生6例.随访发现内瘘发生率为6.84%,Ⅰa型内瘘3例,锚定于Zone 2的2例,Zone 3的1例;Ⅰb型内瘘1例,锚定于Zone 3;Ⅱ型内瘘3例,锚定于Zone 2的2例,Zone 3的1例;Ⅳ型内瘘1例,锚定于Zone 3.8例患者接受再次手术干预治疗,包括Zone 2的5例(其中2例行腔内修复术,3例行开放手术)和Zone 3的3例(其中2例行腔内修复术,1例行开放手术).结论 TEVAR治疗Stanford B型主动脉夹层患者将支架锚定于Zone 2,随访期间并发症发生率较高,因此对于支架只能锚定于Zone 2的患者需谨慎选择TEVAR治疗.
Objective:To analyze the effects of thoracic endovascular aortic repair (TEVAR) with stents deployed in different landing zones on early to mid-term results in patients with type B aortic dissection.Methods:The data of 147 patients with type B aortic dissection receiving TEVAR in the First Affiliated Hospital of Xiamen University from January 2012 to December 2017 were reviewed retrospectively. All of the patients were divided into two groups based on the distance between proximal entry tear and left subclavian artery: (1) ≤2 cm, the stent was deployed in Zone 2 (Zone 2 group, 40 cases); (2) >2 cm, the stent was deployed in Zone 3 (Zone 3 group, 107 cases). CTA data of the two groups at 1-, 3-month and annually thereafter were analyzed to assess the postoperative complication rates (mainly the incidences of endoleak) and reintervention rates.Results:The age of the Zone 2 group was younger than that of the Zone 3 group [(57±9.3)years vs (61±10)years, t=2.04, P=0.04]. The follow-up period was (37.8±20.5) months (range: 6-77 months). In total, there were 18 cases presented with postoperative complications during follow-up, and the complication rate of Zone 2 group was higher than that of Zone 3 group [27.5% (11/40) vs 6.54% (7/107), χ2=11.90, P=0.001]. A total of 10 cases appeared with endoleak, and the incidence of endoleak in the Zone 2 group was higher than that in the Zone 3 group [15%(6/40) vs 3.74%(4/107), χ2=5.82, P=0.025]. A total of 12 patients were treated with reintervention, and the reintervention rate of Zone 2 group was higher than that of Zone 3 group [20%(8/40) vs 3.74%(4/107), χ2=10.27, P=0.003]. Conclusion:For type B aortic dissection, stent landing in Zone 2 is associated with higher rates of complications and reintervention than that in Zone 3.