Aims: Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM. Methods and Results: Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson’s trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all p < 0.01 vs the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all p < 0.05). Conclusion: We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.

Background:Glucose transporter 10 (GLUT10) is encoded by the SLC2A10 gene. Our recent investigations have shown that GLUT10 is not only involved in glucose metabolism but also involved in the body's immune response to cancer cells. However, the role of GLUT10 in tumor prognosis and in tumor immunity has not been reported.Methods:We knocked down SLC2A10 and performed transcriptome sequencing to analyse the biological function of GLUT10 and found that GLUT10 may be involved in immune signaling. Then, we studied the expression level of SLC2A10 in cancers by the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We also evaluated the prognostic potential of SLC2A10 in different cancers using the Kaplan‒Meier plotter database and PrognoScan online software. The correlations between SLC2A10 expression and immune infiltrates were analysed by TIMER. In addition, correlations between SLC2A10 expression and gene marker sets of immune infiltrates were analysed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). Immunofluorescence staining of cyclooxygenase-2 (COX-2) and GLUT10 in lung cancer tissue and adjacent tissue was performed to confirm our findings from the database research.Results:Knocking down SLC2A10 widely activated immune and inflammatory signaling. SLC2A10 was abnormally expressed in several tumors. The expression level of SLC2A10 was closely correlated with cancer prognosis. Low SLC2A10 expression was related to poorer prognosis and increased malignancy of lung cancer. Lung cancer patients with low expression of SLC2A10 have a much shorter median survival time than patients with high expression of SLC2A10. SLC2A10 expression is closely related to the infiltration of different types of immune cells, particularly macrophages. Both database research and lung cancer sample research revealed that GLUT10 might modulate immune cell infiltration via the COX-2 pathway.Conclusions:By transcriptome experiments, database studies, and human sample studies, we found that GLUT10 is a new immune signaling molecule involved in tumor immunity, especially in the immune cell infiltration of lung adenocarcinoma (LUAD). GLUT10 may modulate the immune cell infiltration of LUAD via the COX-2 pathway.

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

目的 探讨频发性室性早搏(PVC)对线粒体超微结构的影响.方法 14只成年比格犬随机分为对照组(CTL,n=7)和模型组(PVC-ICM,n=7).PVC-ICM组经颈外静脉植入双腔起搏器,心房电极植入右室游离壁,心室电极植入右室心尖部,起搏模式设置为VDD,形成PVC二联律起搏方式,在右室心尖部持续起搏,联律间期设置为350 ms;CTL组植入起搏器不起搏.每隔2周对犬进行心电图及超声心动图检测,通过心电图数据,确认起搏器持续工作.造模12周后关闭起搏器,注射过量戊巴比妥钠将犬处死后取材.利用透射电镜观察心室线粒体超微结构改变.结果 造模12周后,与CTL组比较,PVC-ICM组LVEF[(0.40±0.03)vs(0.62±0.03)]和FS[(0.18±0.01)vs(0.33±0.02)]明显降低,LVEDD[(36.4±1.6)mm vs(29.3±1.0)mm]和LVESD[(29.8±1.0)mm vs(19.6±0.5)m m]增厚;线粒体结构紊乱,每个视野下数量减少[(93.29±6.02)个v s(112.43±11.85)个,P<0.001],面积增大[(225.63±18.88)μm2 vs(171.37±19.64)μm2,P<0.001],体积增大[(2.42±0.18)μm2 vs(1.54±0.19)μm2,P<0.001].结论 长期频发性PVC可引起心功能障碍和线粒体超微结构改变.

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/).

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。

Objective:A retrospective analysis of 7 patients who died after heart transplantation in a single center, and to explore the risk factors for death after heart transplantation.Methods:From May 1, 2015 to May 1, 2019, 74 cases of orthotopic heart transplantation were performed in the Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University. By April 2020, with a follow-up time of 724 days, 65 recipients survived and 9 died. Two cases of death due to non-medical causes were excluded, and the recipients were divided into survival group (65 cases) and death group (7 cases). Preoperative, intraoperative, and postoperative parameters and corresponding donor conditions were collected for the survival group. Continuous variables that met the normal distribution were compared using the t-test, and continuous variables that were not normally distributed were analyzed using the Kruskal-Wallis test. Enumeration data were compared using Fisher′s exact test. Survival curves were plotted using the Kaplan-Meier method. Cox proportional hazards models were used to analyze risk factors for death after heart transplantation.Results:Of the 7 dead recipients, 4 died of transplant heart failure, rejection, respiratory failure and other organ failure during hospitalization, including 1 recipient of combined heart-lung transplantation and 3 recipients who died during follow-up: 2 cases with poor compliance with immunosuppressive agents, 1 case with transplant heart failure, rejection and liver failure. There were no significant differences in age at operation, body mass index, left ventricular ejection fraction, primary disease, preoperative cardiopulmonary resuscitation, vasoactive drug maintenance and ECMO transition between the surviving recipients (P>0.05). There were no significant differences in donor age, poor body weight, donor cold ischemia time, cause of brain death, donor/recipient sex and ABO blood group matching, and marginal donor ratio in the death and survival groups (P>0.05), and the proportion of donor/recipient age difference (>17 years) in the death group was higher than that in the survival group (P<0.05). The median cardiopulmonary bypass time was 201 (185, 226) and 170 (152, 197) min, the intraoperative packed red blood cell dosage was 8.0 (5.5, 9.0) and 4.0 (2.0, 6.0) U, and the platelet dosage was 4.0 (2.0, 6.0) and 2.0 (2.0, 2.0) U in the surviving recipients, and the differences were statistically significant (P<0.05). The ICU stay and postoperative ventilator use time of recipients in the death group were longer than those in the survival group, 11.1 (5.9, 17.7) and 3.8 (2.9-5.0) d, 58 (12, 172) and 8 (6, 15) h, respectively; meanwhile, the proportion of recipients who stayed in the ICU (stay >5 d) and used the ventilator for a long time (use > 24 h) in the death group was higher than that in the survival group, and the differences were statistically significant (P<0.05 for all). The 1-, 3-, and 5-year overall survival rates of the 74 recipients were 91.9%, 84.7%, and 74.1%, respectively. The factors with statistically significant differences in preoperative and intraoperative indicators and corresponding donor indicators between the two groups were included in Cox proportional hazards model analysis. The results showed that intraoperative platelet dosage was an independent risk factor for death after heart transplantation. For every U increase in intraoperative platelet use, the risk of postoperative death increased by 1.35 times (HR=2.35, 95% CI 1.28~4.32, P<0.05).Conclusions:The outcome after heart transplantation is influenced by many factors. Excessive differences in intraoperative red blood cell and platelet dosage and donor/recipient age are risk factors for death after heart transplantation.

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.

Dendritic cells (DCs) are key mediators of transplant rejection. Numerous factors have been identified that regulate transplant immunopathology by modulating the function of DCs. Among these, microRNAs (miRNAs), small non-coding RNA molecules, have received much attention. The miRNA miR-223 is very highly expressed and tightly regulated in hematopoietic cells. It plays an important role in modulating the immune response by regulating neutrophils and macrophages, and its dysregulation contributes to multiple types of immune diseases. However, the role of miR-223 in immune rejection is unclear. Here, we observed expression of miR-223 in patients and mice who had undergone heart transplantation and found that it increased in the serum of both, and also in DCs from the spleens of recipient mice, although it was unchanged in splenic T cells. We also found that miR-223 expression decreased in lipopolysaccharide-stimulated DCs. Increasing the level of miR-223 in DCs promoted polarization of DCs toward a tolerogenic phenotype, which indicates that miR-223 can attenuate activation and maturation of DCs. MiR-223 effectively induced regulatory T cells (Tregs) by inhibiting the function of antigen-presenting DCs. In addition, we identified Irak1 as a miR-223 target gene and an essential regulator of DC maturation. In mouse allogeneic heterotopic heart transplantation models, grafts survived longer and suffered less immune cell infiltration in mice with miR-223-overexpressing immature (im)DCs. In the miR-223-overexpressing imDC recipients, T cells from spleen differentiated into Tregs, and the level of IL-10 in heart grafts was markedly higher than that in the control group. In conclusion, miR-223 regulates the function of DCs via Irak1, differentiation of T cells into Tregs, and secretion of IL-10, thereby suppressing allogeneic heart graft rejection.

Background: GLUT10 is encoded by SLC2A10 gene. Recent investigations have shown that GLUT10 is not only involved in glucose metabolism, but also involved in the body's immune response to cancer cells. However, the correlations between GLUT10 expression and prognosis, immune cells infiltrating of different cancers remain unclear. Methods: We Knocked down SLC2A10 and performed transcriptome sequencing to analyze the biological function of GLUT10. The SLC2A10 expression level was analyzed by the Oncomine databases and Tumor immune Estimation Resource (TIMER) site. We evaluated the prognostic potential of SLC2A10 in different cancers using the Kaplan-Meier plotter database and the PrognoScan online software. The correlations between SLC2A10 expression and immune infiltrates were analyzed by TIMER. In addition, correlations between SLC2A10 expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA. Results: Knocking down of SLC2A10 widely activated immune and inflammatory signaling. SLC2A10 was abnormally expressed in several tumors. The expression level of SLC2A10 was closely correlated with cancer prognosis. Low SLC2A10 expression was related to poorer prognosis and increased malignancy of lung cancer. Lung cancer patients with low expression of SLC2A10 have a much shorter median survival time than patients with high expression of SLC2A10. SLC2A10 expression is closely related to different types of immune cell infiltration, particularly with macrophages. Conclusions: By using various databases and analysis software, we found that GLUT10 is involved in tumor immunity and is expected to serve as a therapeutic target in the future. Down-regulation of SLC2A10 expression predicts poor prognosis of lung cancer. GLUT10 may be a new important immune regulating molecular thus worth further focusing.

BACKGROUND:The advantages of prosthesis eversion method in patients diagnosed with Stanford type A acute aortic dissection (AAD) undergoing ascending aorta replacement (AAR) is unknown. This research is designed to explore it. METHODS:We retrospectively analyzed the data of a total of 283 patients diagnosed with type A aortic dissection that underwent surgery in Renmin Hospital of Wuhan University from March, 2006 to April, 2020. Eighty-eight patients underwent surgical repair with traditional continuous suture technique, and 195 patients received prosthesis eversion. Baseline data, intra-operative data and early-stage clinical results were collected and statistically analyzed. RESULTS:Baseline data were similar except for age, incidence of hyperlipidemia and taking ACEI/ARB drugs (P<0.05). Cardiopulmonary bypass time, cross-clamp time, circulation arrest time, hemostasis time and total operation time in the traditional method group were far longer than in the prothesis eversion group (P<0.01). The operative mortality was similar (P>0.01). Post-operatively, there was no statistically significant difference in the mean ventilation time, mortality, incidence of re-exploration, tracheostomy, paraplegia, long-term coma and stroke between the two groups (P>0.05). Patients in the traditional method group had a longer duration stay in ICU and hospital than patients in the prosthesis eversion group (P<0.05). Patients in the traditional method group received more red blood cells (RBC) (P<0.01), plasma (P<0.05), fibrinogen (P<0.01) and albumin (P<0.05) transfusions, and CoSeal™ surgical sealant (P<0.05) than patients in the prosthesis eversion group. CONCLUSIONS:Our experience and statistical analysis showed prosthesis eversion method to have some advantage in reducing blood loss and improving clinical results compared with repair with continuous suture. This technique is both simple to learn and perform.

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.

Objective:To retrospectively analyze the experience of our center in the use of marginal donor heart, and to explore the principle of use and risk control of marginal donor heart.Methods:A total of 31 patients with end-stage heart disease underwent orthotopic heart transplantation in our center from January 2018 to December 2018, including 28 cases of pure heart transplantation, 2 cases of combined heart-lung transplantation, and 1 case of combined heart-kidney transplantation. 26 of the 31 cases were marginal donor hearts. These patients were all anastomosed by a double lumen method.Results:The rates of postoperative use of ECMO, IABP and acute rejection were zero in this study. The time of cardiopulmonary bypass in the marginal donor group was significantly longer compared with the conventional donor group( P<0.05), but there was no significant difference between the two groups in terms of hospitalization time, mechanical ventilation time, ICU stay time, abnormal rate of ECG, LVEF and blood biochemical indexes(all P>0.05). The postoperative follow-up rate was 100% in the two groups. One case of combined heart-lung transplantation in the marginal donor group died of multiple organ failure in the first month after surgery. During the postoperative follow-up period, the incidence of moderate to severe tricuspid regurgitation and the incidence of recurrent heart failure were zero in the two groups. There was no significant difference in the incidence of arrhythmia, LVEF, infection and blood biochemical parameters. Conclusion:The application of marginal donor heart has no significant effect on the short-term survival rate and recovery of patients after heart transplantation, but the long-term effect needs further follow-up.

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.

目的 探讨心脏移植术后患者出现精神障碍的原因并分析护理对策.方法 回顾性分析55例接受心脏移植手术患者的临床资料,采用焦虑自评量表(SAS)对术后患者进行评估,分析患者术后出现精神障碍的原因,总结相关护理对策.结果 55例患者中1例术后出现幻觉、被害妄想及攻击行为,1例术后神志未清醒,两例均无法完成SAS评估;其余53例患者SAS评分为(47.3±16.7)分.19例患者表现出不同程度的紧张、焦虑或抑郁等,其中轻度焦虑9例,中度焦虑4例,重度焦虑6例.心脏移植术后患者精神障碍发生率为36.36％(20/55).结论 接受心脏移植手术的患者术后精神障碍发生率较高,护理人员应及时评估患者的临床表现,给予针对性的护理干预,以促进患者生理及心理的康复.

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.

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.

BACKGROUND:Retrograde type A aortic dissection (RTAD) is a fatal aortic disease secondary to descending aortic dissection, and might be misdiagnosed due to its atypical symptoms lead to catastrophic outcomes.CASE PRESENTATION:We herein reported a case of a 40-year old Chinese non-comorbid man who received conservative treatment for acute type B aortic dissection and progressed to RTAD in a painless manner in a week. After open surgical aortic repair with stented elephant truck technique, the patient survived without obvious complication and cured with a satisfactory outcome in a half-year follow-up.CONCLUSION:This case indicates that RTAD may present without typical symptoms, early diagnosis and open surgical procedure are imperative for treating RTAD.