ObjectiveTo investigate the effect of secreted frizzled related protein 1（SFRP1） via Wnt/β-catenin signaling pathway on calcification of vascular smooth muscle cell. MethodsPrimary human aortic vascular smooth muscle cells were transfected with SFRP1-specific small interfering RNA （siSFRP1） to knock down SFRP1 expression， transfected with lentiviral vector Lenti-Sfrp1 to overexpress SFRP1， and stimulated with 3 mmol/L sodium dihydrogen phosphate （Pi） to establish a cellular vascular calcification model. In vivo， a mouse model of acute vascular calcification was established using vitamin D₃ （VD₃） treatment. The SFRP1 inhibitor WAY-316606 was administered intraperitoneally （0.5 mg/kg daily for 7 days）. Aortic calcification was quantified by micro-computed tomography （micro-CT）. Western blot analysis was performed to detect the expression of osteogenic differentiation markers （RUNX2 and BMP2）， vascular smooth muscle cell contractile marker SM22α， and β-catenin protein in the Wnt signaling pathway. The severity of vascular calcification was evaluated through calcium content measurement and Alizarin Red staining. These approaches were employed to investigate the effect of SFRP1 on VSMC calcification. ResultsIn the primary human vascular smooth muscle cell calcification model and the acute vascular calcification model， the expression of SFRP1 protein was significantly down-regulated （0.30±0.02， P = 0.02； 0.15±0.03， P = 0.04）. The expression of RUNX2 （2.91±0.38， P ＜ 0.05） was significantly up-regulated and SM22α （0.48±0.08， P ＜ 0.05） were significantly down-regulated by small interfering RNA （siRNA）， whereas the Wnt/β-catenin signaling pathway was also significantly activated （2.01±0.11， P = 0.003）. In vivo， inhibition of SFRP1 exacerbated aortic calcification and significantly up-regulated the expression of BMP2 （3.11±0.55， P = 0.04） and β-catenin （3.97±0.44， P = 0.03）. Lentiviral overexpression of SFRP1 significantly downregulated RUNX2 （1.34±0.04， P = 0.02） and β-catenin （1.06±0.06， P = 0.04） expression， while upregulating SM22α （0.74±0.03， P= 0.03）. Quantitative alizarin red staining and calcium content assays demonstrated that SFRP1 overexpression significantly inhibited vascular smooth muscle cell calcification （1.36±0.08， P=0.000 6；1.51±0.03，P=0.002 1）. ConclusionSFRP1 attenuates vascular smooth muscle cell calcification via the Wnt/β-catenin signaling pathway.

Considering the surgical risk stratification for patients with severe calcific aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) is a reliable alternative to surgical aortic valve replacement (SAVR) (Fan et al., 2020, 2021; Lee et al., 2021). Despite the favorable clinical benefits of TAVR, stroke remains a dreaded perioperative complication (Auffret et al., 2016; Kapadia et al., 2016; Kleiman et al., 2016; Huded et al., 2019). Ischemic overt stroke, identified in 1.4% to 4.3% of patients in TAVR clinical practice, has been associated with prolonged disability and increased mortality (Auffret et al., 2016; Kapadia et al., 2016; Levi et al., 2022). The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) was reported to be about 80%, which is associated with impaired neurocognitive function and vascular dementia (Vermeer et al., 2003; Barber et al., 2008; Kahlert et al., 2010).
Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve Insufficiency ; Diffusion Magnetic Resonance Imaging ; Aortic Valve Stenosis ; Stroke

Objective:To analysis the mid-stage prognosis of transapical aortic valve implantation(TA-TAVI) using J-Valve? system for the treatment of high-risk aortic regurgitation(AR) patients.Methods:Data of 25 patients with aortic regurgitation who had underwent transapical aortic valve implantation using J-Valve? system were collected in the Second Affiliated Hospital of Medical College of ZheJiang University from September 2016 to June 2020 . Analysis and summarize their postoperative all-cause mortality, the incidence of adverse events and the improvement in cardiac function.Results:There were 25 patients, including 19 males, the age rage from 59-83 years, the average age was(72.3±27.11) years. The levels of aortic regurgitation was evaluated by transthoracic echocardiography preoperatively, showed that severe AR accounted for 88%. The New York Heart Association(NYHA) of grade 3 or above was 92%. The most common comorbidity was hypertension, accounted for 68%. Coronary heart disease and history of cardiac surgery was 5 and 3 relatively in this study. The Society of Thoracic Surgeons score before surgery was 1.511%-27.674%, the average of STS score was 4.27(2.914-6.033)%. Successful J-Valve implantation was obtained in all 25 cases, no conversion to thoracotomy. After surgery, 2 patients required permanent pacemaker implantation, 1 patient needed continuous renal replacement therapy(CRRT) due to acute kidney injury, 1 occurred moderate or above paravalvular leak. The results showed good therapeutic effects in early-stage, low incidences of adverse events. The continued improvement of cardiac function and ventricular reverse remodeling could be observed in mid-stage.Conclusion:In this study, we can summarize that high-risk patients with aortic regurgitation treated with transapical aortic valve implantation using J-Valve? system can acquire great perioperative safety and mid-stage prognosis.

Objective:To evaluate the effectiveness and prognosis of emergent transcatheter aortic valve replacement (TAVR) and to provide standardized procedural suggestion for the development of emergent TAVR in China.Methods:From January 2020 to April 2021, 12 patients who underwent emergent or salvage TAVR in the Second Affiliated Hospital Zhejiang University School of Medicine were retrospectively enrolled from the TORCH registry (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population, a prospective cohort study; NCT02803294). Baseline, periprocedural and 30-day follow up data were collected. Post-operative data were compared with pre-operative data using Paired-Samples test.Results:Patients’ median Society of Thoracic Surgeons score (STS score) was 15.432%. There was a significant decrease of mean gradient after emergent TAVR procedure (1.69 m/s vs. 4.90 m/s, P<0.01). During the 30-day follow up, there were 1 patient (8.3%) died and 2 patients received permanent pacemaker implantation. No disabling stroke, acute kidney injury, major vascular complication occurred during the first month after emergent TAVR. Among the survival patients, there was a significant releasing of heart failure symptoms to New York Heart Association function stage Ⅰ/Ⅱ in 81.8% patients at 30-day follow up. Left ventricular ejection fraction also improved significantly from (47.4±9.5)% to 58.8±8.0% ( P= 0.026). The mean gradient were (1.57±0.30) cm 2 and no patients had a moderate or severe paravalvular leakage. Besides, a significant decrease of pro-B-type natriuretic peptide (1 089.9 pg/mL vs. 12 215.5 pg/mL , P=0.001) and troponin T (0.020 ng/mL vs. 0.337 ng/mL, P=0.003) were found at 30 days after emergent TAVR. Conclusions:For patients with severe aortic stenosis and acute cardiac decompensated, emergent TAVR is a safe and effective rescue treatment.

Transcatheter aortic valve replacement (TAVR) has emerged as a viable treatment option for patients with severe aortic stenosis regardless of its surgical risk stratification (Otto et al., 2021). Aortic angulation is usually measured as the angle between the horizontal and the aortic annulus planes based on preproced‍ural multidetector computed tomography (MDCT) (Al-Lamee et al., 2011). Extremely horizontal aorta, defined as an aortic angulation greater than 70°, is an unfavorable anatomic structure that poses particular technical challenges for TAVR. Abramowitz et al. (2016) have proved that an extremely horizontal aorta increased the risk of procedural complications, such as lower device success rates, more moderate or even severe perivalvular leakage (PVL), and the need for second valve implantation. Because of the long stent frame, inflexibility, and non-steerability, it is challenging to pass the delivery system of self-expanding valves (SEVs) through an extremely horizontal aorta. As a result, patients with an extremely horizontal aorta have always been excluded from the clinical trials of TAVR, and transfemoral (TF)-TAVR with SEV is considered as an "off-label" use of TAVR (Adams et al., 2014; Kaneko et al., 2020). Herein, we present a technically difficult case, in which a patient with an extremely horizontal aorta underwent TF-TAVR with SEV by applying a unique apical-to-femoral rail strategy.
Aorta ; Humans ; Lower Extremity ; Multidetector Computed Tomography ; Transcatheter Aortic Valve Replacement

Objective:To compare the left ventricular (LV) reverse remodeling after transcatheter aortic valve replacement (TAVR) between patients with bicuspid aortic valve (BAV) stenosis and tricuspid aortic valve (TAV) stenosis.Methods:The data of patients who underwent TAVR procedure from March 2013 to December 2018 in the Second Affiliated Hospital of Zhejiang University were retrospectively reviewed. The patients were divided into BAV group and TAV group according to cardiac computed tomography. Echocardiographic parameters, including aortic valve peak velocity (Vmax), mean gradient (PGmean), effective orifice area(EOA), interventricular septum diastolic thickness (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), left ventricular end diastolic diameter( LVEDd), LV mass index (LVMI), ΔLVMI%, left ventricular ejection fraction( LVEF) of the two groups at baseline, 1 week, 1 month and 1 year post TAVR procedure were obtained and compared.Results:①Compared with preoperative measurements, both groups showed decreases in Vmax, PGmean and increase in EOA at 1 week, 1 month, 1 year follow-ups(all P<0.05). No significant differences were found in Vmax, PGmean, EOA, moderate/sever perivalvular leakage(PVL), moderate/sever prosthetic-patient mismatch(PPM) between BAV group and TAV group at 1 year. ②Both groups showed decreases in IVSd, LVPWd, LVEDd at 1 month, 1 year post TAVR compared with those before the procedure (all P<0.05), as well as increases in LVEF at 1 week, 1 month, 1 year (all P<0.05). Downward trends of LVMI were detected in both groups within 1 year follow-up( P<0.05). ③Compared to TAV group, BAV group showed smaller baseline LVMI( P<0.05), while there were no significant differences in ΔLVMI% post TAVR for all follow-up times of the two groups(all P>0.05). Repeated measures analysis of variance also showed no significant differences in downward trend of LVMI between the two groups after TAVR within 1 year( P>0.05). Conclusions:Left ventricular reverse remodeling can be detected in both BAV and TAV patients after TAVR, which starts from 1 week and can be lasted for 1 year post procedure. Patients with bicuspid morphology might experience similar reverse LV remodeling post TAVR versus patients with tricuspid morphology.

Objective:To explore the value of transesophageal echocardiography(TEE) guidance for transcatheter DragonFly? system edge-to-edge tricuspid regurgitation (TR) repair.Methods:Five cases who were chosen in the Second Affiliated Hospital, Zhejiang University School of Medicine from December 2020 to January 2021 with surgical high-risk and severe functional TR underwent transcatheter DragonFly edge-to-edge repair with the guidance of TEE. Preoperative TEE was used to evaluate the tricuspid valve anatomy and the origin and etiology of regurgitation in detail; intra-procedure guidance of TEE was performed during the DragonFly system for tricuspid valve edge-to-edge repair intervention and after release of the DragonFly clip, the effect of surgery was assessed immediately and compared with pre-procedure TEE.Results:A total of 10 DragonFly clips were implanted in 5 patients (3 in each of patients, 2 in 1 patient, and 1 in each of patients). One of the 3 clips in 1 patient fell off unilaterally from the septal valve after release, and the other 9 clips were well positioned and fixed. Immediately post-operation assessment by TEE depicted the TR in 3 patients declined to mild and 2 to moderate. The vena contracta area by using three-dimensional color blood flow quantitative assessment was reduced[(0.93±0.26)cm 2 vs (0.20±0.11)cm 2]. No complications such as serious tricuspid valve injury, pericardial tamponade, thromboembolism occurred in the 5 patients. Conclusions:TEE plays an important role in guiding and monitoring transcatheter DragonFly system edge-to-edge TR repair during the entire procedure.

Objective:To explore the evaluation of transesophageal echocardiography(TEE) in patients with massive regurgitation of posterior mitral valve prolapse undergoing transapical off-pump NeoChord repair.Methods:Eight patients from April to July 2019 in the Second Affilliated Hospital of Zhejiang Univerity with massive regurgitation of posterior mitral valve prolapse underwent NeoChord repair mitral valve morphology, prolapse position and regurgitation degree were evaluated before NeoChord implantation by TEE. Under TEE guidance, the puncture site was identificated, the position and length of artificial chordae were adjusted during implantation. NeoChord′s function and positon after implantation were observed. The complications were monitored during the operation.Results:Mitral valve repair by NeoChord system was successfully performed with implantation of 2 to 4 artificial chordaes in eight patients respectively. Intraoperative TEE and pre-discharge transthoracic echocardiography(TTE) showed moderate MR in two patients, mild to moderate MR in one patient, mild MR in the remaining five patients. Reexaminations with TTE at 1 month after operation showed moderate MR in six patients, and mild to moderate MR in two patients. And no postoperative complications were noted.Conclusions:NeoChord system is a safe, effective and feasible treatment method for patient with mitral valve prolapse, TEE plays an important role during NeoChord implantation.

Due to the particularity of oncology,which is not included in undergraduate coume,most of the physicians gain the oncology knowledge in a fragmented way.The process of diagnosis and treatment of cancer needs to be concluded and systematization.According to characteristics of standardized training in the Department of Oncology,combined with the characteristics of internal medicine and oncology,we should increase the training of strengthening concept of multidisciplinary team cooperation for students,clinical thinking of cancer subjects,the training of transitional medical ideas and humanistic care knowledge with tumor characteristic,on the basis of strengthening skill training on Oncology.We should also encourage the general physicians of non cancer majors to participate in the standardized training of cancer specialties and explore more teaching methods and forms,as well as the positive significance of cross professional training.