A 56-year male patient was implanted with a third generation magnetic levitation HeartCon left ventricular assist device (LVAD) for refractory heart failure through a left antero-lateral thoracotomy. Inflow cannula of the HeartCon blood pump was inserted via the left apex and outflow tract with the artificial blood vessel was sutured to the descending aorta. The operation process was smooth, the LVAD worked stably, and results of left ventricular assist was good. Implantation of HeartCon LVAD through the left antero-lateral thoracotomy is an alternative technique with less surgical complications, less trauma and satisfactory results.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

Purpose: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). Materials and Methods: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. Results: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. Conclusions Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Objective:To investigate and summarize the early management experience of 22 patients with end-stage heart failure(ESHF) who underwent left ventricular assist device(LVAD) implantation in an intensive care unit(ICU) in a single center.Methods:Data of 22 patients with ESHF treated with LVAD in the ICU of TEDA International Cardiovascular Hospital from September 2020 to August 2022 were retrospectively analyzed. There were 16 males and 6 females, aged from 20 to 67 years old, with a mean age of(51.0±13.3)years old. There were 21 cases with dilated cardiomyopathy, 1 case with ischemic cardiomyopathy, 6 cases with tricuspid regurgitation, 1 case with intra-aortic balloon pump for cardiogenic shock, and 5 cases with cardiac resynchronization therapy for arrhythmia. After the operation, all patients received restricted fluid therapy, a " stepwise" anticoagulation strategy, and strict blood pressure management. The postoperative complications and treatment process were reviewed, the treatment and management experience were summarized, and the prognosis of the patients was statistically analyzed.Results:All 22 patients survived within 90 days after surgery, and 21 patients(95.5%) recovered well, the pump works fine and there was no hemolysis and thrombosis of LVAD. Major complications included: 1 case of severe pneumonia(4.5%), 2 cases of pericardial tamponade(9.1%), 1 case of intracerebral hemorrhage(4.5%), 1 case of mediastinal infection(4.5%), 5 cases of positive occult blood in gastric juice(22.7%), no cases of right ventricular failure、aortic insufficiency and cerebral infarction. The duration of postoperative mechanical ventilation was 17(8.5, 51.5) h, and the ICU stay was 14(10, 27) days.Conclusion:LVAD is another effective treatment for patients with ESHF in addition to heart transplantation. Good postoperative blood pressure control, " stepwise" anticoagulation strategy and " restrictive" fluid management can reduce postoperative complications in the early phase of post-operation, which is crucial for the prognosis of patients with LVAD.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

By reporting the technical skill and the management tactics in the operation of the left ventricular assist device(LVAD) implantation, we provide our reference and experience for the colleagues in their clinical practice.

The author, as a coordinating investigator, jointly with the other ten PIs conducted a 62-case multicenter clinical trial of a domestic HeartCon implantable left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), the results of which demonstrated the safety and efficacy of the device. In the clinical practice, we have not only validated the international general knowledge, but also created some ideas and methods that are different from the international traditional practice and has been proved to be more reasonable by repeated practice. We hereby would like to share our experience and speculation, so as to provide the reference for the colleagues.

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.
Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Transformation, Neoplastic ; Down-Regulation ; Epithelial Cells/metabolism* ; Extracellular Vesicles/pathology* ; Humans ; MicroRNAs/metabolism* ; Mouth Neoplasms/pathology* ; PTEN Phosphohydrolase/metabolism* ; Tumor Suppressor Protein p53/metabolism*

Objective:To evaluate systematically the association between the c. 415>C polymorphism of NUDT15 gene and the toxicity of 6-mercaptopurine(6-MP)in children with acute lymphoblastic leukemia(ALL).Methods:The literatures in domestic and foreign databases were retrieved: PubMed, EmBase, Cochrane Library, CNKI, CBM, VIP Chinese Sci-tech Journal Database, and Wanfang Database.The language was limited to Chinese or English.A case-control study or cohort study of 6-MP treatment in pediatric ALL related to the toxicity of the NUDT15 gene c. 415>C polymorphism was included.The time of search was set from the establishment of the database to October 1st, 2020.Two researchers screened the literature independently, extracted data from the literature that met the inclusion criteria, and evaluated the quality of the included studies.The association between locus polymorphism and toxicity during 6-MP chemotherapy was analyzed by Meta analysis with Rev Man 5.3 and Stata 12.0 software.Results:Nine studies were finally included, eight of which were cohort studies and one was a case-control study, with a total of 1 068 patients.The results showed that under the five genetic models, the mutation at c. 415>C of NUDT15 gene was significantly associated with the risk of leukopenia and neutropenia( P<0.01), while hepatotoxicity was with no significant association between the occurrence risk of damage( P>0.05). Conclusion:The mutation at c. 415>C of NUDT15 gene significantly increased the incidence of leukopenia and neutropenia during 6-MP chemotherapy, while there was no significant effect on the occurrence of hepatotoxicity.

Objective:To investigate and evaluate the efficacy of HeartCon left ventricular assist device (LVAD) in the treatment of adult patients with end-stage heart failure (ESHF).Methods:A prospective and observational study was conducted. Patients with ESHF who underwent LVAD implantation in the department of cardiac surgery of Teda International Cardiovascular Hospital from September 2020 to August 2021 were selected. The left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) classification, N-terminal pro-B type natriuretic peptide (NT-proBNP), and six minute walk distance (6MWD) before operation and 90 days after operation were compared. The incidence of equipment failures and major adverse events within 90 days after operation were recorded.Results:A total of 20 patients with ESHF were included, with 15 males and 5 females. Patients' age ranged from 20 to 67 years old, with an average of (50.2±13.6) years old. The range of body weight was 49.8-106.1 kg, with an average of (67.9±15.5) kg, and the body surface area (BSA) was from 1.49 to 2.32 m 2, with an average of (17.6±0.22) m 2. The operation process of all the patients were successful. The length of hospital stay ranged from 33 to 90 days, and the average was 56.0 (42.8, 75.0) days. Complications within 90 days after operation as follows, 2 cases with pericardial tamponade (10%), 1 case with cerebral hemorrhage (5%), 1 case with mediastinum infection (5%), 3 cases with acute renal injury (AKI, 15%), 5 cases with gastrointestinal bleeding (25%). There were no mechanical failure of LVAD and hemolysis events, right ventricular failure (RVF), cerebral infarction and death occurred. Compared with preoperative, the LVEDD significantly decreased (mm: 67.50±13.98 vs. 77.40±9.73), LVEF significantly increased (%: 34.80±9.76 vs. 22.70±5.62), NT-proBNP significantly decreased (ng/L: 2 028.65±1 752.05 vs. 4 796.45±4 355.40), 6MWD significantly increased (m: 385.20±144.12 vs. 85.81±63.50) at 90 days after operation, and the differences were statistically significant (all P < 0.05). 18 cases (90%) of the 20 patients reached NYHA classification Ⅰ and 2 cases (10%) reached NYHA classification Ⅱ, which were significantly improved compared with those before surgery (all patients' NYHA classification were Ⅳ before surgery). Conclusion:HeartCon LVAD can effectively improve the life quality of patients with ESHF, which has been proved safe and effective in clinical trials, but its long-term effects and complications need further observation and study.