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.

Objective To investigate the status quo of fear of disease progression(FoP)in patients after pituitary neuroendocrine tumour surgery and analyse the medication effects of positive coping style on disease perception and FoP.Methods Convenient sampling method was used to select 345 patients with pituitary neuroendocrine tumours who underwent surgical operations in the neurosurgery department of a Grade IIIA hospital in Shanxi Province from January 2022 to January 2023 as the research objects.A general data questionnaire,disease perception questionnaire,medical coping style questionnaire and fear of progression questionnaire-short form(FoP-Q-SF)were used in the investigation.Pearson correlation was employed to analyse the correlations of the disease perception,active coping style and FoP among the patients.Structural equation models were used to analyse the mediating effects of positive coping styles on disease perception and FoP.Results The FoP score of patients after pituitary neuroendocrine tumour surgery was found at(35.02±4.92).FoP was positively correlated with the disease perception(r=0.672,P<0.01),and negatively with the active coping style(r=-0.679,P<0.01).Positive coping styles were positively correlated with disease perception(r=-0.610,P<0.01).Disease perception not only had a direct effect on FoP,but also had an indirect effect on FoP via active coping style,with an intermediate effect value of 0.202(P<0.001),accounting for 25.5%of total effect.Conclusion Postoperative positive coping style in patients with pituitary neuroendocrine tumour is a mediating variable between the disease perception and FoP.Medical staff should dynamically assess and early identify coping styles of patients and adopt personalised guidance programs,therefore to guide the patients to actively cope with the disease,so as to reduce the negative disease perception and alleviate the fear of disease progression of the patients.

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

ObjectiveTo observe the effect of classic prescription Ermiaosan （EMS） on the differentiation of T helper 17 （Th17） /regulatory T （Treg） cells in collagen-induced arthritis （CIA） DBA/1 mice. MethodDBA/1 mice were randomized into normal group， CIA group， EMS （5.4 g·kg^-1） group， and methotrexate （MTX，0.5 mg·kg^-1） group according to the body weight. DBA/1 mice in CIA group， EMS group， and MTX group were immunized with equal volume of bovine type Ⅱ collagen and complete Freund's adjuvant on the first day and were immunized with equal volume of bovine type Ⅱ collagen and incomplete Freund's adjuvant on the 21^st day to induce CIA. On the day of the secondary immunization， intragastric administration started and lasted 28 days （three times/week for MTX group， and once/day for other groups）. The symptoms of CIA mice such as joint redness and swelling were observed from the 22^nd day， and the arthritis was scored. After the sampling on the 49^th day， synovitis of CIA mice was observed based on hematoxylin-eosin （HE） staining. Double-labeling immunofluorescence （IF） method was used to detect the expression of Th17 cell marker IL-17 and Treg cell marker forkhead transcription factor P3 （FoxP3） in CD4⁺T cells in CIA mouse joints. The proportion of Th17 and Treg cells in the spleen and lymph nodes of mice was detected by flow cytometry. ResultCompared with the normal group， CIA group had obvious synovitis， disordered joint structure， severely damaged articular cartilage and bone， serious bone erosion （P<0.01）， high Th17/Treg value in joint tissue （P<0.01）， high proportion of Th17 cells in spleen and lymph nodes （P<0.01）， and low proportion of Treg cells （P<0.01）. Compared with CIA group， EMS group and MTX group had normal joint structure， mild bone erosion and bone destruction， complete and smooth joint surface， low Th17/Treg value （P<0.01）， low proportion of Th17 cells in spleen and lymph nodes （P<0.01）， and high proportion of Treg cells in spleen and lymph nodes （P<0.01）. ConclusionEMS regulates the balance of Th17/Treg， inhibits the expression of Th17 cells， and promotes the expression of Treg cells in CIA mice， thereby exerting therapeutic effect on RA.

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics， surgery， radiotherapy， or hormone therapy. The treatment process has limitations such as multidrug resistance， non-selective targeting of cancer cells， and drug toxicity. With the development and application of traditional Chinese medicine （TCM）， Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation， differentiation， and metastasis， and avoid drug resistance， serving as the focus of current tumor treatment research. Hedysari Radix， one of the genuine medicinal materials in Gansu province， is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation， immune regulation， anti-oxidation， prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties， Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity， scavenging free radicals， and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer， bladder cancer， gastric cancer， breast cancer， and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research， this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis， blocking cell cycle， inhibiting tumor cell proliferation， migration， and invasion， regulating micro mRNA （miRNA）， inducing cell autophagy， enhancing immune regulation， as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics， and systematically explained the anti-tumor mechanism of Hedysari Radix active components， aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

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.