顾沅芮
中国医学科学院阜外医院 血管外科
Patients with multiple myeloma (MM) are likely to achieve poor therapeutic response when organs are involved. We produced anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells, which are in a trial for patients with relapsed/refractory MM. One enrolled patient developed severe heart failure, highly suspected as light chain cardiac amyloidosis. He exhibited increased N-terminal pro-brain natriuretic peptide with a peak of 32 299 ng/mL and heart failure with an ejection fraction of 30%. Anti-BCMA CAR-T cells were administered following lymphodepletion. The patient achieved cardiac response within 1 week with a decrease in N-terminal pro-brain natriuretic peptide by 80%, an increase in ejection fraction from 30% to 56%, and a haematological response with negative minimal residual disease at 1 month and a complete response at 1 year. To date, this patient has maintained good health without heart failure or haematological relapse. Herein, we show the efficacy of anti-BCMA CAR-T cells in patients with MM and severe heart failure.
ESC heart failure 2024
AIMS:Growing preclinical and clinical evidence has suggested the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot. Thus, the authors provided an outline of the application of UCMSCs in the treatment of diabetic foot and further summarized the roles and mechanisms of this therapy.DATA SYNTHESIS:With no time limitations, the authors searched the Web of Science, Cochrane Central Register of Controlled Trials, and PubMed (MEDLINE) databases. 14 studies were included, including 9 preclinical experiments and 5 clinical trials (3 RCTs and 2 single-arm trials).CONCLUSIONS:The UCMSCs are of great efficacy and safety, and function mainly by reducing inflammation, regulating immunity, promoting growth factors, and enhancing the functions of vascular endothelial cells, fibroblasts, and keratinocytes. As a result, ulcer healing-related biological processes ensue, which finally lead to diabetic foot ulcer healing and clinical symptom improvement. UCMSC treatment enhances diabetic foot ulcer healing and has a safety profile. They function mainly by modulating immunity, promoting growth factor secretion, and enhancing cellular functions. More well-designed preclinical and clinical studies are needed to provide the most optimal protocol, the comprehensive molecular mechanisms, as well as to further evaluate the efficiency and safety profile of UCMSC treatment in diabetic foot patients.
Journal of diabetes and its complications 2024
To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in β-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.
Laboratory investigation; a journal of technical methods and pathology 2024
OBJECTIVE:The objective of this study was to introduce our institutional experience of treatment strategies (cervical subclavian artery reconstruction, thoracotomy subclavian artery reconstruction and endovascular treatment) for proximal isolated subclavian artery aneurysms (PISAAs).METHODS:we retrospectively analyzed 15 consecutive patients with PISAAs treated by different treatment strategies (cervical reconstruction, thoracotomy reconstruction and endovascular treatment) in our institution from May 2016 to May 2022. Baseline data, surgery-related data, postoperative information and long-term follow-up were assessed.RESULTS:A total of 17 PISAAs in 15 consecutive patients were treated in our institution. The success rates of subclavian artery reconstruction in the cervical reconstruction, the thoracotomy reconstruction and the endovascular treatment were 100%, 100 and 83.33%, respectively. About the involved vertebral artery, the reconstruction rates in the cervical reconstruction, the thoracotomy reconstruction, and the endovascular treatment were 80%, 75%, and 0, respectively. The intraoperative blood loss in the thoracotomy reconstruction was significantly higher than that in the cervical reconstruction and the endovascular treatment (p<0.05). The total operation time of the thoracotomy reconstruction was significantly longer than that of the cervical reconstruction and the endovascular treatment (p<0.05). In terms of postoperative ventilator use time, total postoperative drainage fluid, total postoperative drainage time, and ICU duration, both the thoracotomy reconstruction and the cervical reconstruction were significantly more than the endovascular treatment (p<0.05). During the follow-up, one patient in the endovascular treatment underwent re-intervention 22 months after surgery due to in-stent occlusion.CONCLUSIONS:For patients with PISAAs, different treatment strategies are recommended depending on the size of the aneurysms and whether the involved vertebral arteries require reconstruction.CLINICAL IMPACT:This article is the largest study on the treatment strategies of PISAAs. By comparing the prognosis and complications of endovascular treatment with those of open surgery, it provides a certain reference basis for the choice of treatment for patients with PISAAs. For patients with aneurysms' diameter of >50 mm, the thoracotomy subclavian artery reconstruction is recommended; for patients with aneurysms' diameter of <30 mm requiring reconstruction of the involved vertebral arteries, the cervical subclavian artery reconstruction is recommended; for patients with aneurysms' diameter of <30 mm not requiring reconstruction of the involved vertebral arteries, the endovascular treatment is recommended.
Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists 2023
(1) Background: the indications for transcatheter closure of large patent ductus arteriosus (PDA) with severe pulmonary hypertension (PH) are still unclear, and scholars have not fully elucidated the factors that affect PH prognosis. (2) Methods: we retrospectively enrolled 134 consecutive patients with a PDA diameter ≥10 mm or a ratio of PDA and aortic >0.5. We collected clinical data to explore the factors affecting follow-up PH. (3) Results: 134 patients (mean age 35.04 ± 10.23 years; 98 women) successfully underwent a transcatheter closure, and all patients had a mean pulmonary artery pressure (mPAP) >50 mmHg. Five procedures were deemed to have failed because their mPAP did not decrease, and the patients experienced uncomfortable symptoms after the trial occlusion. The average occluder (pulmonary end) size was almost twice the PDA diameter (22.33 ± 4.81 mm vs. 11.69 ± 2.18 mm). Left ventricular end-diastolic dimension (LVEDD), mPAP, and left ventricular ejection fraction (LVEF) significantly reduced after the occlusion, and LVEF recovered during the follow-up period. In total, 42 of the 78 patients with total pulmonary resistance >4 Wood Units experienced clinical outcomes, and all of them had PH in the follow-up, while 10 of them had heart failure, and 4 were hospitalized again because of PH. The results of a logistic regression analysis revealed that the postoperative mPAP had an independent risk factor (odds ratio = 1.069, 95% confidence interval: 1.003 to 1.140, p = 0.040) with a receiver operating characteristic curve cut-off value of 35.5 mmHg (p < 0.001). (4) Conclusions: performing a transcatheter closure of large patent ductus arteriosus is feasible, and postoperative mPAP was a risk factor that affected the follow-up PH. Patients with a postoperative mPAP >35.5 mmHg should be considered for targeted medical therapy or should undergo right heart catheterization again after the occlusion.
Journal of clinical medicine 2023
BACKGROUND:The recommendation of the European Society for Vascular Surgery (ESVS) is that vertebral revascularization combined with ipsilateral CEA (carotid endarterectomy) should not be performed in the same operation. ESVS believes that vertebral revascularization combined with ipsilateral CEA increases perioperative death/stroke rates. In our opinion, revascularization of the first segment of vertebral artery (V1) combined with ipsilateral CEA is safe compared to vertebral V1 revascularization in the perioperative period. The purpose of this study is to prove that revascularization of V1 segment of vertebral artery combined with ipsilateral CEA is secure in the perioperative period.METHODS:We describe our experience with homochronous revascularization of V1 segment of vertebral artery with ipsilateral CEA (group B) and simple revascularization of V1 segment of vertebral artery (group A) in 48 consecutive patients during a 5-year period. O.Y. (Ouyang) incisions were used in both groups. We compare the results of the 2 procedures with aspects of mortality, stroke, morbidity, incident rates of complications, and so on.RESULTS:There was no significant difference between patients in group A and group B in terms of red blood cell reduction, postoperative ventilator using time, postoperative drainage volume, postoperative drainage days, postoperative hospitalize duration, and incident rates of postoperative complications. The postoperative complications include death, stroke, Horner syndrome, vocal paralysis, hypoglossal nerve paralysis, wound hematomas, and lymphatic leakage.CONCLUSIONS:Revascularization of vertebral artery combined with ipsilateral CEA should be divided into revascularization of V1 segment of vertebral artery combined with ipsilateral CEA and revascularization of V3 segment of vertebral artery with ipsilateral CEA. Revascularization of V1 segment of vertebral artery combined with ipsilateral CEA is safe; it can be performed for suitable patients who are fit for indications. O.Y. incisions can fully expose the target blood vessels and simplify the procedures without transecting the sternocleidomastoid muscles in operations.
Annals of vascular surgery 2023
European heart journal 2022
BACKGROUND:The most common materials of artificial blood vessels are polyethylene terephthalate and polytetrafluoroethylene. But polycarbonate polyurethane (PCU) is an ideal material for vascular prostheses because of their excellent characteristics. As far as we know, our artificial blood vessel is the first type of hybrid PCU/polyester three-layered large-diameter artificial blood vessel in the world.OBJECTIVE:The purpose of this preclinical animal experiment is to evaluate the hemocompatibility, histocompatibility, effectiveness, and safety of the three-layered large-diameter artificial blood vessel in sheep.METHODS:The artificial blood vessels took place of the initial segments of the sheep's thoracic aorta by end-to-end anastomosis.RESULTS:All of the 14 sheep are male, their average body weight (BW) was 30.57 ± 3.95 kg. All 14 artificial blood vessels successfully replaced the thoracic aortas. 5 sheep did not survive to the end of the experiment, while the remaining 9 sheep did. After the surgery, the blood biochemical and blood routine indicators fluctuate slightly within the normal range. The angiography showed that the implanted artificial blood vessels were unobstructed without obvious stenosis or expansion. 24 weeks after surgery, the lumen surfaces of the artificial blood vessels were covered by endothelia in different degrees, and the average endothelialization rate was 69.44% (range: 20% to 100%).CONCLUSIONS:This artificial blood vessel is the first to use PCU in large-diameter artificial vascular grafts. It has excellent blood compatibility, wonderful biocompatibility, high endothelialization rate, and 100% patency.
Journal of biomaterials applications 2022
Vascular smooth muscle cells (VSMCs) contribute to plaque stability. VSMCs are also a major source of CTH (cystathionine gamma-lyase)-hydrogen sulfide (H2S), a protective gasotransmitter in atherosclerosis. However, the role of VSMC endogenous CTH-H2S in pathogenesis of plaque stability and the mechanism are unknown. In human carotid plaques, CTH expression in ACTA2+ cells was dramatically downregulated in lesion areas in comparison to non-lesion areas. Intraplaque CTH expression was positively correlated with collagen content, whereas there was a negative correlation with CD68+ and necrotic core area, resulting in a rigorous correlation with vulnerability index (r = -0.9033). Deletion of Cth in VSMCs exacerbated plaque vulnerability, and were associated with VSMC autophagy decline, all of which were rescued by H2S donor. In ox-LDL treated VSMCs, cth deletion reduced collagen and heightened apoptosis association with autophagy reduction, and vice versa. For the mechanism, CTH-H2S mediated VSMC autophagosome formation, autolysosome formation and lysosome function, in part by activation of TFEB, a master regulator for autophagy. Interference with TFEB blocked CTH-H2S effects on VSMCs collagen and apoptosis. Next, we demonstrated that CTH-H2S sulfhydrated TFEB at Cys212 site, facilitating its nuclear translocation, and then promoting transcription of its target genes such as ATG9A, LAPTM5 or LDLRAP1. Conclusively, CTH-H2S increases VSMC autophagy by sulfhydration and activation of TFEB, promotes collagen secretion and inhibits apoptosis, thereby attenuating atherogenesis and plaque vulnerability. CTH-H2S may act as a warning biomarker for vulnerable plaque.Abbreviations ATG9A: autophagy related 9A; CTH: cystathionine gamma-lyase; CQ: chloroquine; HASMCs: human aortic smooth muscle cells; H2S: hydrogen sulfide; LAMP1: lysosomal associated membrane protein 1; LAPTM5: lysosomal protein transmembrane 5; NaHS: sodium hydrosulfide hydrate; ox-LDL: oxidized-low density lipoprotein; PPG: DL- propagylglycine; TFEB: transcription factor EB; 3-MA: 3-methyladenine; VSMCs: vascular smooth muscle cells.
Autophagy 2022
Background:Transcatheter closure of inferior sinus venosus defect (ISVD) is still contraindication. To explore whether transcatheter closure with patent ductus arteriosus (PDA) occluders is possible for ISVD.Methods:From June 2014 to March 2021, 12 patients were recruited diagnosed as <25 mm ISVD. The three-dimensional printing (3DP) heart model was produced based on multi-slice computed tomography (MSCT) scans. Preoperative closure simulation was planned on the personalized 3D model for each patient. Follow-up including electrocardiography (ECG), transthoracic echocardiography (TTE), and X-ray was traced.Results:3DP models of 12 patients were successfully printed. Twelve patients had been diagnosed with <25 mm ISVD and 4 of them had another secundum atrial septal defect (ASD). All patients were produced interventional therapy successfully. PDA occluder was implanted to closed ISVD, and ASD was closed using ASD occluder simultaneously. The average diameter of ISVD measured by TTE was (12.67±3.80), and the average diameter of sagittal axes and longitudinal axes measured by the 3D-printed model was (17.08±3.20) and (18.42±4.62) mm, respectively. The average size of PDA (diameter of pulmonary artery side) was (28.17±3.35) mm. Compared with the preoperative, the X-ray cardiothoracic ratio (0.51±0.04 vs. 0.47±0.06, P=0.007) and the right ventricle anterior-posterior diameter (31.17±5.65 vs. 24.58±3.75 mm, P<0.001) of postoperative was significantly decreased. During the average (47.75±27.52) months follow-up, it has achieved satisfying results, and there were no severe adverse events such as device transposition, death, and pericardial tamponade occurred.Conclusions:Assisting by 3D heart model, transcatheter closure of ISVD with PDA occluder had an excellent outcome. This method provides a new considerable treatment strategy for ISVD.
Journal of thoracic disease 2022