HomeCirculation: Cardiovascular ImagingVol. 16, No. 3Rosai-Dorfman Disease Involving the Descending Aorta Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessCase ReportPDF/EPUBRosai-Dorfman Disease Involving the Descending Aorta Luocheng Li, Zhiwei Wang, Lin Liu, Hongbing Wu, Zongli Ren and Jingping Yuan Luocheng LiLuocheng Li https://orcid.org/0000-0001-8884-5670 Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. , Zhiwei WangZhiwei Wang Correspondence to: Zhiwei Wang, MD, Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 99, Zhangzhidong Rd, Wuchang District, Wuhan, China 430060. Email E-mail Address: [email protected] https://orcid.org/0000-0001-5643-9344 Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. , Lin LiuLin Liu Department of Pathology (Lin Liu, J. Yuan), Renmin Hospital of Wuhan University, Wuhan, China. , Hongbing WuHongbing Wu Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. , Zongli RenZongli Ren Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. and Jingping YuanJingping Yuan Department of Pathology (Lin Liu, J. Yuan), Renmin Hospital of Wuhan University, Wuhan, China. Originally published8 Feb 2023https://doi.org/10.1161/CIRCIMAGING.122.014582Circulation: Cardiovascular Imaging. 2023;16Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: February 8, 2023: Ahead of Print A 41-year-old female patient presented to the emergency department in our hospital with a 1-year history of hypertension and dizziness and headache for the last 7 hours. According to her medical record, she was admitted to the Cardiology Department in our hospital for sudden onset of hypertension in October 2020, where her blood pressure was 203/101 mmHg. After administration of nifedipine (30 mg/day), allisartan isoproxil (240 mg/day), and betaloc (47.5 mg/day), her blood pressure decreased to 140/70 mmHg, and she was discharged. However, her blood pressure was badly controlled, and her antihypertension medication regimen was changed several times under the guidance of her cardiologist. The latest regimen was norvasc amlodipine (5 mg/d), telmisartan (80 mg/day), and hydrochlorothiazide (12.5 mg/day). Her past medical history was unremarkable, there was no fever, chest pain, weight loss, skin lesions, or swollen lymph nodes. On admission, her blood pressure was 201/92 mmHg. Intravenous injection of sodium nitroprusside was administered at a dose of 4 μg/kg·min with a micropump. Physical examination revealed no other positive findings. Electrocardiogram showed sinus tachycardia. X-ray was normal. Laboratory testing demonstrated her erythrocyte sedimentation rate (29 mm/hour) was slightly above the normal value. Aldosterone, renin, adrenocorticotropic hormone, cortisol, angiotensin II, IgG4 were normal, but the patient had mild anemia (99 g/L). Since the patient had no hypertension before and there was no such family history, her elevated blood pressure was suspected to be a secondary hypertension related to renal artery stenosis. Blood pressure monitoring showed that her upper limb blood pressure was 175/87 mmHg, and her lower limb blood pressure was 125/72 mmHg. She was referred for aortic computed tomography angiography, which revealed a 6-cm soft tissue mass in the descending aorta with no contrast enhancement extending from the level of the superior margin of the eighth thoracic vertebra to the inferior margin of the tenth thoracic vertebra. The mass infiltrated the descending aortic wall and nearly occluded the aortic lumen (Figure 1). The presumptive diagnosis was angioleiomyosarcoma. Because the patient was suffering from uncontrollable hypertension resulting from severe stenosis of the descending aorta, mass resection surgery was planned.Download figureDownload PowerPointFigure 1. Computed tomography scan of the aorta showing the location and extension of the mass (white arrows) before the operation. A, Coronal view of the mass. B, Sagittal view of the mass. C, Axial view at the main pulmonary artery level. D, Three-dimensional reconstruction of the descending aorta showing severe stenosis of the lumen.Following left posterolateral thoracotomy and dissection, the mass was observed to abut the esophagus. Luckily, the mass did not infiltrate the esophagus, and it was dissected surgically from the surrounding tissue. After carefully exposing the normal aorta connected to the mass, the mass was surgically resected completely, followed by a descending aorta replacement using a polytetrafluoroethylene graft (Figure 2). The excised tumor specimen was firm, with white-brown resection surfaces and relatively well-defined borders. It was sent for pathological testing, where macroscopic examination revealed a solid tumor measuring ≈ 6 cm. The mass had infiltrated through the descending aortic wall and blocked most of the aortic lumen. Histological review showed infiltration by large histiocytes, lymphocytes, and plasma cells. Immunohistochemical staining demonstrated that the histiocytes were diffusely positive for CD163 and S100, focally positive for CD68, and negative for CD1a and langerin (Figure 3). Taken together, these findings suggested a diagnosis of Rosai-Dorfman disease. The patient's postoperative aortic computed tomography angiography before discharge showed good polytetrafluoroethylene graft patency (Figure S1). At the 6-month follow-up, the aortic computed tomography angiography result was fine (Figure S2), and her blood pressure had returned to normal without any medication.Download figureDownload PowerPointFigure 2. Intraoperative images. A, Gross specimen of the tumor showing the mass almost occluding the aortic lumen (red arrow). B, The tumor is excised, and the missing part of the descending aorta is replaced with a polytetrafluoroethylene graft (white arrow).Download figureDownload PowerPointFigure 3. Pathological specimens of the tumor. A, H&E staining of the excised specimen shows infiltration by large histiocytes, lymphocytes, and plasma cells (×100). Histiocytes marked with a red circle show mononuclear inflammatory cells in the cytoplasm. B, Histiocytes show positive immunoreactivity for S-100 (red arrows). C and D, CD68 and CD163 positive immunohistochemical staining (red arrows). E and F, Immunohistochemical staining shows negative results for langerin and CD1a.Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation disease1 involving nodal and extranodal sites. According to the reports published, ≈ 43% of the RDD patients had extranodal site involvement.2 The disease mostly affects middle-aged females.3 Cardiovascular system involvement is rare, and no more than 30 patients cardiovascular RDD have been reported, Only a small number of reports retrieved from the literature have indicated that RDD involves the aorta. This patient had no nodal lesions, and the RDD was diagnosed postoperatively by pathological examination.The diagnosis of RDD is based on clinical symptoms, signs, imaging examination, and pathological findings. F-18 FDG PET/CT is valuable in both the initial evaluation and follow-up of RDD patients. The patient in this case was diagnosed postoperatively by histopathological examination, and she was referred for F-18 FDG PET/CT scanning when followed up; however, she did not undergo the examination for personal reasons. To distinguish RDD from other histiocytic disorders, histopathological examination results are needed. In typical RDD tissue samples, pathological features include histiocytic proliferation with emperipolesis and inflammatory cells infiltration, CD 68-, CD163-, and S100-positive staining, and CD1a- and langerin-negative staining.4 The findings in our case are consistent with these features.In summary, RDD involving the aorta is very rare. Preoperative diagnosis of RDD based on imaging results is challenging; thus, the pathological review of lesion specimens from is indispensable. Surgical treatment for RDD can be effective in most of the RDD patients if necessary, and the prognosis is often favorable after complete excision of the RDD mass.Article InformationSources of FundingDr Wang is supported by the National Natural Science Foundation of China (grant number 82070481).Supplemental MaterialFigures S1 and S2Disclosures None.FootnotesSupplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.122.014582For Sources of Funding and Disclosures, see page 293.Correspondence to: Zhiwei Wang, MD, Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 99, Zhangzhidong Rd, Wuchang District, Wuhan, China 430060. Email wangzhiwei@whu.edu.cnReferences1. Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, Durham BH, Braier B, Charlotte F, Donadieu J., et al. Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131:2877–2890. doi: 10.1182/blood-2018-03-839753CrossrefMedlineGoogle Scholar2. Summers MR, Pettersson G, Maalouf JF, Jaber WA. Sinus histiocytosis with massive lymphadenopathy: extra-nodal Rosai-Dorfman disease presenting as a rare aetiology of a large intracardiac mass.Eur Heart J. 2017; 38:1439–1440. doi: 10.1093/eurheartj/ehw409CrossrefMedlineGoogle Scholar3. Alruwaii ZI, Zhang Y, Larman T, Miller JA, Montgomery EA. Rosai-Dorfman disease of the digestive system - beware vasculopathy: a clinicopathologic analysis.Am J Surg Pathol. 2019; 43:1644–1652. doi: 10.1097/PAS.0000000000001343CrossrefMedlineGoogle Scholar4. Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview.J Clin Pathol. 2020; 73:697–705. doi: 10.1136/jclinpath-2020-206733CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails March 2023Vol 16, Issue 3 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.122.014582PMID: 36943911 Originally publishedFebruary 8, 2023 Keywordsaortacomputed tomography angiographyhistiocytosis, sinushypertensionsurgeryPDF download Advertisement SubjectsAngiographyCardiovascular SurgeryComputerized Tomography (CT)HypertensionVascular Disease

Background: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. Materials and methods: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 & PLUSMN; 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. Results: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. Conclusions: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and posttransplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival. & COPY; 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Angiopoietin-like protein 2 (ANGPTL2) was implicated in various cardiovascular diseases; however, its role in lipopolysaccharide (LPS)-related septic cardiomyopathy remains unclear. Herein, mice were exposed to LPS to generate septic cardiomyopathy, and adeno-associated viral vector was employed to overexpress ANGPTL2 in the myocardium. Besides, mice were treated with adenoviral vector to knock down ANGPTL2 in hearts. ANGPTL2 expressions in hearts and cardiomyocytes were upregulated by LPS challenge. ANGPTL2 overexpression aggravated, while ANGPTL2 silence ameliorated LPS-associated cardiac impairment and inflammation. Mechanically, we found that ANGPTL2 activated NLRP3 inflammasome via suppressing DUSP1 signaling, and NLRP3 knockdown abrogated the detrimental role of ANGPTL2 in aggravating LPS-induced cardiac inflammation. Furthermore, DUSP1 overexpression significantly inhibited ANGPTL2-mediated NLRP3 activation, and subsequently improved LPS-related cardiac dysfunction. In summary, ANGPTL2 exacerbated septic cardiomyopathy via activating NLRP3-mediated inflammation in a DUSP1-dependent manner, and our study uncovered a promising therapeutic target in preventing septic cardiomyopathy.

心肾联合移植是治疗终末期心脏病合并终末期肾病的重要手段，但心肾联合移植数量较其他多器官联合移植(如心肺移植、心肝移植)明显要少。世界首例心肾联合移植于1978年实施[1]；我国首例心肾联合移植于2000年6月开展[2]，且数量更少。2014年中国心脏移植注册中心数据显示，2001年4月至2014年6月共上报8例心肾联合移植，且院内死亡4例[3]。但国外有研究显示，终末期心脏病伴有肾功能不全者心肾联合移植比单纯心脏移植取得了更好的临床效果[4]。由此可见，心肾联合移植临床经验亟待总结。武汉大学人民医院心血管外科2017年1月至2018年6月共完成2例心肾联合移植，取得良好的临床效果，至今仍院外随访，现将临床经验总结如下。

人工心脏的发展及临床应用给终末期心脏病患者的治疗带来了希望 [1] ,也对原位心脏移植提出了更高要求。目前国际心脏移植数量不断增加,我国每年进行原位心脏移植术约400余例,临床效果与国际相当。伴随移植领域器官保护、围手术期处理以及免疫抑制剂的发展,心脏移植临床效果也得到进一步提高。2015年6月至2019年4月,武汉大学人民医院连续成功行70例单纯原位心脏移植无院内死亡,取得良好的临床效果,现总结经验如下。

Background To evaluate the graft outcomes after orthotopic heart transplantation (HTx) with a novel bicaval anastomosis technique between recipients with and without a history of prior cardiac surgery. Methods Of 70 patients who underwent HTx with a novel four-corners traction bicaval anastomosis technique from August 2017 to November 2019, 60 recipients underwent the HTx procedure as their first cardiac surgery (group A), while 10 recipients underwent HTx after prior cardiac surgery (group B). Patients in the two groups were compared in terms of their preoperative baseline variables such as etiological categories, history of blood transfusion and panel reactive antibody (PRA), intraoperative operation time and blood infusion volume, postoperative treatment time, and complications such as acute rejection and 30-day mortality as well as survival rates. Results Preoperative variables were comparable in group A and group B except for the history of blood transfusion (0% vs. 90.0%, P<0.001, respectively); the level of PRA was 7.5%±5.8% and 9.5%±10.9% for group A and B, respectively (P=0.583), but the time of the operation was nearly 1 hour longer for group B than group A (all P<0.05). No cases of left atrial thrombosis and donor heart distortion were observed in either group. Reoperation (1.7% vs. 10.0%, P=0.267), infection (0% vs. 10.0%, P=0.142), other postoperative complications as well as the 30-day mortality (1.7% vs. 10.0%, P=0.267), and postoperative survival rates (91.5% vs. 90.0%, P=0.805) were comparable between the two groups (all P>0.05). Conclusions Four-corner traction bicaval anastomosis combined with a continuous everting suture technique may result in approximately comparable prognoses for heart recipients with a history of cardiac surgery when compared with those without a history of cardiac surgery and this technique may reduce the incidence of left atrial thrombosis and distortion. Further follow-up of the long-term outcomes will be required to validate these results.

Objectives. To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background. Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods. In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results. In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P<0.05). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (P<0.05), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (P<0.05). Conclusions. The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.

BACKGROUND: The epidemiologic and clinical characteristics of heart transplant (HTx) recipients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We studied the characteristics of HTx recipients from December 20, 2019, to February 25, 2020, in an effort to understand their risk and outcomes. METHODS: All accessible HTx recipients were included in this single-center retrospective study. We collected information on the recipients using a web-based questionnaire as well as the hospital database. RESULTS: We followed 87 HTx recipients (72.4% were men, and the average age was 51 years). A total of 79 recipients resided in Hubei, and 57 recipients had a Wuhan-related history of travel or contact. Most took precautionary measures while in contact with suspicious crowds, and 96.6% of the families and communities undertook prevention and quarantine procedures. Four upper airway infections were reported, and 3 of them tested negative for SARS-CoV-2 (the fourth recovered and was not tested). All cases were mild and successfully recovered after proper treatment. Laboratory results of 47 HTx cases within the last 2 months were extracted. Of these, 21.3% of recipients had pre-existing lymphopenia, and 87.2% of recipients had a therapeutic concentration of tacrolimus (5-12 ng/ml). Liver and kidney insufficiency was seen in 5 and 6 recipients, respectively. CONCLUSION: HTx recipients who practiced appropriate prevention measures had a low rate of infection with SARS-CoV-2 and transition to the associated disease COVID-19. These early data will require confirmation as the pandemic establishes around the world. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

Background In December 2019, Coronavirus Disease 2019(COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection appeared in Wuhan, Hubei Province, China. The disease is highly infectious. Wuhan, Hubei Province decided restrict personnel movement on January 23.We analyze relevant data to show the situation of the COVID-19 epidemic in China. Methods The data was classified according to Hubei group, non-Hubei group, Hong Kong, Macao and Taiwan group, and Chinese Mainland group, and analyze the current situation and trend of the epidemic. Results There was an explosive growth in the early stage of the epidemic. The epidemic situation began to improve in about two weeks after Wuhan was restricted,and the situation in non-Hubei was significantly better than that in Hubei. Conclusion The blockade of Wuhan was a correct decision, cut off the outflow of tinfection sources, and the epidemic situation in all places turned around after the incubation period.

We have previously demonstrated that Mettl3-silencing dendritic cells (DCs) exhibited immature properties and prolonged allograft survival in a murine heart transplantation model. Exosomes derived from donor DCs (Dex) are involved in the immune rejection of organ transplantation, and blocking Dex transfer may suppress immune rejection. Herein, this study aimed to investigate whether Mettl3 knockdown inhibits the secretion and activity of donor Dex, thereby inhibiting donor Dex–mediated immune rejection. The imDex, mDex, shCtrl-mDex, and shMettl3-mDex were obtained from the culture supernatant of DCs (immature DCs, mature DCs, shCtrl-infected mature DCs, shMettl3-infected mature DCs) derived from donor BALB/c mouse bone marrow and then co-cultured with splenic T cell lymphocyte suspension from recipient C57BL/6 mice in vitro or injected into recipient C57BL/6 mice before the cardiac transplantation. Donor shMettl3-mDex expressed lower concentration of exosomes and lower expression of Mettl3, Dex markers (ICAM-1, MHC-I, MHC-II), as well as lower ability to activate T cell immune response than shCtrl-mDex. Administration of donor shMettl3-mDex attenuated immune rejection after mouse heart transplantation and prolonged the allograft survival. In summary, Mettl3 knockdown inhibits the immune rejection of Dex in a mouse cardiac allograft model.

Our aim was to investigate the effect of avβ3 single-stranded DNA aptamer (avβ3 ssDNA) on vascular restenosis in rats after percutaneous transluminal coronary angioplasty (PTCA) via the Ras-PI3K/MAPK pathway. Sixty Sprague-Dawley rats were randomly divided into six groups: sham-operated, PTCA, PTCA+cilengitide (18 mg/kg, n = 8), and avβ3 ssDNA treatment at 50, 100, and 200 μg/kg. Hematoxylin-eosin staining was performed to evaluate the successful establishment of the PTCA model and to assess the degree of intimal hyperplasia. Immunofluorescence and in situ hybridization were carried out to observe the level of avβ3. Immunohistochemistry was used to detect the expression of E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA), angiotensin 1 (ANG1), and ANG2. The expression of osteopontin (OPN), focal adhesion kinase (FAK), Ras, mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), signal transducer and activator of transcription 1 (STAT1), and GTPase was observed by the western blot and quantitative reverse transcription polymerase chain reaction. Compared with rats subjected to PTCA only, those treated with avβ3 ssDNA showed significantly decreased vascular occlusion rate (P < .05). The protein expression of avβ3, OPN, p-FAK, ANG2, and E-cadherin was significantly increased by avβ3 ssDNA (P < .05), while the levels of ANG1, α-SMA, N-cadherin Ras, MAPK, PI3K, STAT1, and GTPase were significantly decreased (P < .05). Avβ3 ssDNA reduced the proliferation, migration, epithelial-mesenchymal transition, and vascular remodeling of vascular smooth muscle cells, and the mechanism may be related to the Ras-PI3K/MAPK pathway.

The use of doxorubicin (DOX) can result in depression of cardiac function and refractory cardiomyopathy. Currently, there are no effective approaches to prevent DOX-related cardiac complications. Asiatic acid (AA) has been reported to provide cardioprotection against several cardiovascular diseases. However, whether AA could attenuate DOX-related cardiac injury remains unclear. DOX (15 mg/kg) was injected intraperitoneally into the mice to mimic acute cardiac injury, and the mice were given AA (10 mg/kg or 30 mg/kg) for 2 weeks for protection. The data in our study found that AA-treated mice exhibited attenuated cardiac injury and improved cardiac function in response to DOX injection. AA also suppressed myocardial oxidative damage and apoptosis without affecting cardiac inflammation in DOX-treated mice. AA also provided protection in DOX-challenged cardiomyocytes, improved cell viability, and suppressed intracellular reactive oxygen species (ROS) in vitro. Detection of signaling pathways showed that AA activated protein kinase B (AKT) signaling pathway in vivo and in vitro. Furthermore, we found that AA lost its protective effects in the heart with AKT inactivation. In conclusion, our results found that AA could attenuate DOX-induced myocardial oxidative stress and apoptosis via activation of the AKT signaling pathway.

Maturation of dendritic cells (DCs) initiates adaptive immune responses and thereby provokes allograft rejection. Here, this study aimed to explore the effect of Methyltransferase-like protein 3 (METTL3) silencing on DC function and the role of METTL3-silencing donor DCs in the immune response after mouse heart transplantation. Bone marrow-derived DCs from donor BALB/c mice were infected with lentiviruses expressing METTL3-specific short hairpin RNA (LV-METTL3 shRNA) to silence METTL3. Then METTL3-silencing DCs were treated with lipopolysaccharide (LPS) for another 48 h to induce DC maturation. Recipient C57BL/6 mice were injected with phosphate-buffered saline (PBS), immature DCs, and METTL3 shRNA-DCs prior to the cardiac transplantation involving the transfer of hearts from donor BALB/c mice to recipient C57BL/6 mice. In vitro we demonstrated that METTL3-silencing DCs had lower expression of MHCII, costimulatory molecules (CD80, CD86), and DC-related cytokines (IFN-γ, IL-12) as well as lower ability to activate T-cell proliferation, which were consistent with the characteristics of tolerogenic DCs. In vivo we found that METTL3-silencing donor DCs induced immune tolerance after mouse heart transplantation and prolonged the allograft survival, which might be associated with Th1/Th2 immune deviation. In summary, METTL3-silencing DCs exhibit immature properties and prolong allograft survival.

结核病是由结核分枝杆菌感染引起的疾病,通过呼吸道传播,常累及肺部,也可累及全身其他部位.心肺联合移植受者因长期服用抗排斥反应药物,其免疫功能受到抑制,抗结核分枝杆菌感染的能力明显下降.心肺联合移植术后发生结核分枝杆菌感染的病例报道极少,可能与肺移植手术量有关,但单个实体器官移植术后发生结核杆菌感染的病例并不少见[1].实体器官移植受者术后发生结核病,其致死率是普通结核病患者的10倍[2].武汉大学人民医院心血管外科收治1例心肺联合移植术后下肢结核寒性脓肿形成,现报道如下.

目前,同种异体原位心脏移植是治疗终末期心脏病患者最有效的手段.2016 国际心肺移植协会(International Society of Heart and Lung Transplatation, ISHLT)注册数据显示,亚洲心脏移植数量仅占全球心脏移植数量的5. 7％,供心短缺及供心缺血时间是制约心脏移植发展的最主要瓶颈[1].供心选择标准的不断更新和完善,边缘供心的使用以及体外膜肺氧合 ( extracorporeal membrane oxygenation, ECMO)等新技术的应用,使供心数量得到一定的提高,但仍无法满足等待心脏移植患者的需求.如何更好地获取、保护有限的供心资源,对提高受者心脏移植术后近、远期疗效具有重要意义.本研究回顾性分析武汉大学人民医院心脏移植供受者临床资料,总结供心获取和保护相关经验,现报道如下.

Aim: To investigate the nature of multiple primary cancers initiated by esophageal cancer-multiple primary cancers (EC-MPC). Patients & methods: SEER data about patients'/tumor characteristics, and survival were analyzed and compared. Results & conclusion: 1727 of 29,733 registered EC patients have EC-MPC. Individuals diagnosed at 60-79 years old, earlier stage and/or moderately differentiated EC were more likely to get EC-MPC. Fewer patients in the EC-MPC group suffered from metastases. Patients in the EC-MPC group showed a longer survival rate and lower EC-specific deaths. Other factors like age, sex, race, tumor differentiation and Tumor, Node, Metastasis stage also affected survival. Radiation can improve survival. EC-MPC patients have some distinct features compared with solitary EC.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was closely involved in doxorubicin- (DOX-) induced cardiotoxicity. MicroRNA-200a (miR-200a) could target Keap1 mRNA and promote degradation of Keap1 mRNA, resulting in Nrf2 activation. However, the role of miR-200a in DOX-related cardiotoxicity remained unclear. Our study is aimed at investigating the effect of miR-200a on DOX-induced cardiotoxicity in mice. For cardiotropic expression, male mice received an injection of an adeno-associated virus 9 (AAV9) system carrying miR-200a or miR-scramble. Four weeks later, mice received a single intraperitoneal injection of DOX at 15 mg/kg. In our study, we found that miR-200a mRNA was the only microRNA that was significantly decreased in DOX-treated mice and H9c2 cells. miR-200a supplementation blocked whole-body wasting and heart atrophy caused by acute DOX injection, decreased the levels of cardiac troponin I and the N-terminal probrain natriuretic peptide, and improved cardiac and adult cardiomyocyte contractile function. Moreover, miR-200a reduced oxidative stress and cardiac apoptosis without affecting matrix metalloproteinase and inflammatory factors in mice with acute DOX injection. miR-200a also attenuated DOX-induced oxidative injury and cell loss in vitro. As expected, we found that miR-200a activated Nrf2 and Nrf2 deficiency abolished the protection provided by miR-200a supplementation in mice. miR-200a also provided cardiac benefits in a chronic model of DOX-induced cardiotoxicity. In conclusion, miR-200a protected against DOX-induced cardiotoxicity via activation of the Nrf2 signaling pathway. Our data suggest that miR-200a may represent a new cardioprotective strategy against DOX-induced cardiotoxicity.

目的;分析内皮祖细胞(EPCs)来源的外泌体(EXOs)对血管内皮细胞缺氧性损伤的影响.方法:体外培养EPCs,提取培养基中的EXOs并通过透射电镜和Western blot检测膜性标志物进行鉴定.将体外培养人脐静脉内皮细胞(HUVECs)分为3组:(1)正常对照组,常规培养的HUVECs;(2)缺氧组,将HUVECs于低氧环境中培养8h;(3)缺氧+EPCs-EXOs组,HUVECs于缺氧处理前加入EPCs来源的EXOs(EPCs-EXOs)处理,再在低氧环境中培养8h.于0h、24h和48h采用CCK-8增殖检测试剂盒、划痕实验及流式细胞术检测各组细胞的增殖、迁移和凋亡情况.结果:EPCs-EXOs在电镜下呈椭圆形或杯状膜性囊泡,直径约40-110nm,其膜性标志蛋白CD63、CD81呈阳性表达.与正常对照组比较,缺氧组细胞增殖和迁移能力下降,细胞凋亡率增加(P<0.05).与缺氧组比较,缺氧+EPCs-EXOs组细胞增殖和迁移能力得到一定程度的恢复(P<0.01),与正常对照组相比无明显差异(P>0.05),同时其细胞凋亡率较缺氧组下降(P<0.01),但仍高于正常对照组(P<0.05).结论:EPCs-EXOs可改善缺氧内皮细胞的增殖和迁移能力,减少内皮细胞凋亡,减轻血管内皮细胞的缺氧性损伤.

Aortic dissection (AD) diseases are characterized by degeneration of the aortic media. Oxidative stress plays a crucial role in the development of AD. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1) deficiency reduces the incidence of aortic dissection induced by angiotensin II, but its mechanism remains to be further elucidated. The expression of Fibulin-5 is decreased in patients with AD, but its upstream mechanism is still unclear. This study was to clarify the relationship between NOX1 and Fibulin-5 in the AD. Results showed that the expressions of NOX1 and Fibulin-5 were increased and decreased in the AD, respectively. Next, by employing gain- and loss-of-function approaches in vitro, NOX1 negatively regulated Fibulin-5 in the vascular smooth muscle cells. Moreover, the blunted activity of NOX1 with VAS2870 could upregulate the expression of Fibulin-5. These findings indicate NOX1 is a negative modulator of Fibulin-5 in the AD.

Objective:To study the expression of fibulin-2(FBLN2) in aortic samples from acute type A aortic dissection patients and the function of FBLN2 regulated TGF-beta/Smad signaling in VSMCs apoptosis.Methods:Immunohistochemical staining and Western Blot methods were used for detecting the expression of FBLN2 in aortic samples from acute type A aortic dissection patients.In vitro cultured mouse aortic smooth muscle cells were treated with recombinant mouse FBLN2 and the expression of TGF-β1,Smad2/3,and phosphorylated Smad2/3 were examined by Western Blot.A83-01 was also added to VSMCs and the apoptosis of VSMCs was evaluated by flow cytometry.Results:The expression of FBLN2 was markedly elevated in the media of aortic wall samples from acute type A aortic dissection patients (P＜0.01).Recombinant mouse FBLN2 upregulated the expression of TGF-β1 and pSmad2/3 in cultured VSMCs and repressed the apoptosis of VSMCs in vitro(P＜0.01).When TGF-β/Smad signaling pathway was blocked by A83-01,the apoptosis inhibition of cultured VSMCs by recombinant mouse FBLN2 was neutralized (P＜0.05).Conclusion:The expression of FBLN2 elevates significantly in aortic wall samples from acute type A aortic dissection patients.FBLN2 inhibits VSMCs apoptosis in vitro via TGF-β/Smad signaling pathway and may involve in the development of acute type A aortic dissection.