Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

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.

Proteins with specific functions and characteristics play a crucial role in biomedicine and nanotechnology. De novo protein design enables the customization of sequences to produce proteins with desired structures that do not exist in the nature. In recent years, with the rapid development of artificial intelligence (AI), deep learning-based generative models have increasingly become powerful tools, enabling the design of functional proteins with atomic-level precision. This article provides an overview of the evolution of de novo protein design, with focus on the latest algorithmic models, and then analyzes existing challenges such as low design success rates, insufficient accuracy, and dependence on experimental validation. Furthermore, this article discusses the future trends in protein design, aiming to provide insights for researchers and practitioners in this field.
Artificial Intelligence ; Proteins/chemistry* ; Algorithms ; Protein Engineering/methods* ; Deep Learning

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.

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.

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 evaluate the clinical value of intraoperative transesophageal echocardiography (TEE) in monitoring left ventricular assist device (LVAD) implantation.Methods:Between March 2019 and November 2021, 23 consecutive patients from TEDA International Cardiovascular Hospital, including 21 cases with dilated cardiomyopathy, 1 case with myocardial noncompaction and 1 case with ischemic cardiomyopathy, underwent HeartCon blood pump, a type of third generation LVAD implantation for severe heart failure. TEE was preformed in all cases before and after cardiopulmonary bypass. The dimensions of left-sided and right-sided cardiac chamber, ventricular function, de-airing, interventricular septal position, inlet cannulae position and the function of device were observed and recorded during LVAD implantation. Paired t test was used for statistical analysis of left-sided and right-sided heart parameters in pre- and post-operative measurements. Results:The left heart was dilated significantly and coexistent with right heart enlargement in some degree before LVAD implantation in total 23 cases. More than moderate mitral regurgitation (MR) in 16 cases and less than moderate MR in 7 cases were present. Mild or trace aortic regurgitation (AR) existed in 13 cases. More than moderate tricuspid regurgitation (TR) in 4 cases and less than moderate TR in 16 cases were observed. Left atrial appendage thrombosis was detected in 2 cases. After LVAD implantation, TEE revealed that the left ventricular end-diastolic diameter reduced significantly (42 mm/m 2 vs 32.8 mm/m 2, P<0.05) and left ventricular ejection fraction increased accordingly (22.2% vs 34.0%, P<0.05). There were no significant differences in right ventricular diameter and fractional area change between pre- and post-operative findings(all P>0.05). The ratio of left ventricular inner diameter to right ventricular inner diameter (2.09 vs 1.69, P<0.05) decreased in total 23 cases after LVAD implantation.Interventricular septal position became neutral position instead of pre-oprative rightward position. The severity of MR decreased in varying degrees in total 23 cases after LVAD implantation. All patients underwent tricuspid valvuloplasty with residual mild regurgitation in 8 cases. Conclusions:HeartCon blood pump can effectively unload the left ventricle with sufficient cardiac output in patients with severe congestive heart failure. TEE plays a major role in the clinical decision making during LVAD implantation, which can evaluate pre-operative cardiac abnormalities, intra-operative air embolism, inlet cannulae position, cannulas patency and cardiac function, especially blood volume status and the balance between double ventricles, which is critical for optimal functioning of the device.