Lipopolysaccharide modification enhances the inhibitory effect of clodronate liposomes on hepatic fibrosis by depletion of macrophages and hepatic stellate cells.

Hepatic fibrosis is a complex chronic liver disease in which both macrophages and hepatic stellate cells (HSCs) play important roles. Many studies have shown that clodronate liposomes (CLD-lipos) effectively deplete macrophages. However, no liposomes have been developed that target both HSCs and macrophages. This study aimed to evaluate the therapeutic efficacy of lipopolysaccharide-coupled clodronate liposomes (LPS-CLD-lipos) and the effects of liposomes size on hepatic fibrosis. Three rat models of hepatic fibrosis were established in vivo; diethylnitrosamine (DEN), bile duct ligation (BDL), and carbon tetrachloride (CCl4). Hematoxylin and eosin staining and serological liver function indices were used to analyze pathological liver damage. Masson's trichrome and Sirius red staining were used to evaluate the effect of liposomes on liver collagen fibers. The hydroxyproline content in liver tissues was determined. In vitro cell counting kit-8 (CCK-8) and immunofluorescence assays were used to further explore the effects of LPS modification and liposomes size on the killing of macrophages and HSCs. Both in vitro and in vivo experiments showed that 200 nm LPS-CLD-lipos significantly inhibited hepatic fibrosis and the abnormal deposition of collagen fibers in the liver and improved the related indicators of liver function. Further results showed that 200 nm LPS-CLD-lipos increased the clearance of macrophages and induced apoptosis of hepatic stellate cells, significantly. The present study demonstrated that 200 nm LPS-CLD-lipos could significantly inhibit hepatic fibrosis and improve liver function-related indices and this study may provide novel ideas and directions for hepatic fibrosis treatment.

The signature of cuproptosis-related immune genes predicts the tumor microenvironment and prognosis of prostate adenocarcinoma.

Background: Cuproptosis plays a crucial role in cancer, and different subtypes of cuproptosis have different immune profiles in prostate adenocarcinoma (PRAD). This study aimed to investigate immune genes associated with cuproptosis and develop a risk model to predict prognostic characteristics and chemotherapy/immunotherapy responses of patients with PRAD. Methods: The CIBERSORT algorithm was used to evaluate the immune and stromal scores of patients with PRAD in The Cancer Genome Atlas (TCGA) cohort. Validation of differentially expressed genes DLAT and DLD in benign and malignant tissues by immunohistochemistry, and the immune-related genes of DLAT and DLD were further screened. Univariable Cox regression were performed to select key genes. Least absolute shrinkage and selection operator (LASSO)-Cox regression analyse was used to develop a risk model based on the selected genes. The model was validated in the TCGA, Memorial Sloan-Kettering Cancer Center (MSKCC) and Gene Expression Omnibus (GEO) datasets, as well as in this study unit cohort. The genes were examined via functional enrichment analysis, and the tumor immune features, tumor mutation features and copy number variations (CNVs) of patients with different risk scores were analysed. The response of patients to multiple chemotherapeutic/targeted drugs was assessed using the pRRophetic algorithm, and immunotherapy was inferred by the Tumor Immune Dysfunction and Exclusion (TIDE) and immunophenoscore (IPS). Results: Cuproptosis-related immune risk scores (CRIRSs) were developed based on PRLR, DES and LECT2. High CRIRSs indicated poor overall survival (OS), disease-free survival (DFS) in the TCGA-PRAD, MSKCC and GEO datasets and higher T stage and Gleason scores in TCGA-PRAD. Similarly, in the sample collected by the study unit, patients with high CRIRS had higher T-stage and Gleason scores. Additionally, higher CRIRSs were negatively correlated with the abundance of activated B cells, activated CD8+ T cells and other stromal or immune cells. The expression of some immune checkpoints was negatively correlated with CRIRSs. Tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH) and copy number variation (CNV) scores were all higher in the high-CRIRS group. Multiple chemotherapeutic/targeted drugs and immunotherapy had better responsiveness in the low-CRIRS group. Conclusion: Overall, lower CRIRS indicated better response to treatment strategies and better prognostic outcomes.

Vison transformer adapter-based hyperbolic embeddings for multi-lesion segmentation in diabetic retinopathy.

Diabetic Retinopathy (DR) is a major cause of blindness worldwide. Early detection and treatment are crucial to prevent vision loss, making accurate and timely diagnosis critical. Deep learning technology has shown promise in the automated diagnosis of DR, and in particular, multi-lesion segmentation tasks. In this paper, we propose a novel Transformer-based model for DR segmentation that incorporates hyperbolic embeddings and a spatial prior module. The proposed model is primarily built on a traditional Vision Transformer encoder and further enhanced by incorporating a spatial prior module for image convolution and feature continuity, followed by feature interaction processing using the spatial feature injector and extractor. Hyperbolic embeddings are used to classify feature matrices from the model at the pixel level. We evaluated the proposed model's performance on the publicly available datasets and compared it with other widely used DR segmentation models. The results show that our model outperforms these widely used DR segmentation models. The incorporation of hyperbolic embeddings and a spatial prior module into the Vision Transformer-based model significantly improves the accuracy of DR segmentation. The hyperbolic embeddings enable us to better capture the underlying geometric structure of the feature matrices, which is important for accurate segmentation. The spatial prior module improves the continuity of the features and helps to better distinguish between lesions and normal tissues. Overall, our proposed model has potential for clinical use in automated DR diagnosis, improving accuracy and speed of diagnosis. Our study shows that the integration of hyperbolic embeddings and a spatial prior module with a Vision Transformer-based model improves the performance of DR segmentation models. Future research can explore the application of our model to other medical imaging tasks, as well as further optimization and validation in real-world clinical settings.

TWEAK Signaling-Induced ID1 Expression Drives Malignant Transformation of Hepatic Progenitor Cells During Hepatocarcinogenesis.

The malignant transformation of hepatic progenitor cells (HPCs) in the inflammatory microenvironment is the root cause of hepatocarcinogenesis. However, the potential molecular mechanisms are still elusive. The HPCs subgroup is identified by single-cell RNA (scRNA) sequencing and the phenotype of HPCs is investigated in the primary HCC model. Bulk RNA sequencing (RNA-seq) and proteomic analyses are also performed on HPC-derived organoids. It is found that tumors are formed from HPCs in peritumor tissue at the 16th week in a HCC model. Furthermore, it is confirmed that the macrophage-derived TWEAK/Fn14 promoted the expression of inhibitor of differentiation-1 (ID1) in HPCs via NF-κB signaling and a high level of ID1 induced aberrant differentiation of HPCs. Mechanistically, ID1 suppressed differentiation and promoted proliferation in HPCs through the inhibition of HNF4α and Rap1GAP transcriptions. Finally, scRNA sequencing of HCC patients and investigation of clinical specimens also verified that the expression of ID1 is correlated with aberrant differentiation of HPCs into cancer stem cells, patients with high levels of ID1 in HPCs showed a poorer prognosis. This study provides important intervention targets and a theoretical basis for the clinical diagnosis and treatment of HCC.

[Experimental study on the retentive force of cobalt-chromium alloy, pure titanium and vitallium cast clasps in the simulated 3-year clinical use].

PURPOSE: To investigate the changes of retentive force of cobalt-chromium alloy, pure titanium and vitallium cast clasps in the simulated 3-year clinical use. METHODS: Fifteen metal abutment crowns made of No.QT800-2 nodular cast iron were used in the test. Five clasps from each of the following alloys: cobalt-chromium alloy, pure titanium and vitallium were fabricated. The undercut depth was 0.25 mm. A masticatory simulator was used to cycle the clasp on and off the metal abutment crown 5000 times, simulating 3-year clinical use. Retentive force was measured 11 times during this process. SPSS13.0 software package was used to analyze the results. Casting defects were observed using X-ray non destructive testing (X-ray NDT) before cyclic test. Surface characteristics were qualitatively evaluated using scanning electron microscope (SEM) before and after cyclic test. RESULTS: The results indicated that there were significant differences (P=0.000) in the retentive force of the 3 groups before and after the cyclic test. The highest retentive force was recorded in the vitallium clasps, and the lowest retentive force was measured in the pure titanium clasps. The results of X-ray NDT depicted the typical casting defect seen at the end of the connector. SEM examination revealed that no evidence of pores and cracks in the inner surfaces of the 3 groups was found before cyclic test. Wear was evident in the inner surfaces of the 3 groups but none of the clasps exhibited any evidence of cracks after cyclic test through SEM examination. CONCLUSIONS: In this in vitro test, vitallium clasps show the best retentive force in the 3 groups before and after 5000 cycles at 0.25 mm undercut depth. Cobalt-chromium alloy and vitallium clasps can maintain ideal retentive force at 0.25mm undercut depth in the long-term use. Wear may be one of the reasons for the loss of retentive force of clasps in the cyclic test.

[Rehabilitation by hollow obturator prosthesis immediately after total maxillectomy for malignant tumor].

OBJECTIVE: The feasibility and clinical effects of hollow obturator prosthesis for the repair of maxillofacial defect immediately after maxillectomy for cancer were assessed. METHODS: Thirteen patients with T3-4aN0M0 maxillary neoplasm were treated by the prostheses immediately after maxillectomy. According to the 3D-CT reconstruction of nasal sinus, the 3D stereoscopic prototype was constructed before the surgery. Simulating surgery with Surgicare 5.0 software and then the prosthesis 3D stereoscopic model was shaped. The prosthesis was made quickly and precisely with methacrylate resins according to the model and the print mold before surgery, with supplementary tooth at the bottom of prosthesis. In the surgery, the prosthesis was installed instantly after maxillectomy. The patients were followed up at 1, 3 and 6 month after the surgery, respectively. The facial features and the pronunciation clarity were examined and the questionnaires were carried out in the patients, with comparation by paired t-test. The hollow obturator prosthesis would be replaced by permanent prosthesis made of methacrylate resins at 6 month after the surgery. RESULTS: The hollow obturator prostheses were installed accurately and maxillofacial defects were repaired immediately after maxillectomy in the 13 patients. Postoperative follow-up showed there were significant differences in eyeball sagging (t = 4.67, P < 0.05), mid-facial region collapse (t = 5.67, P < 0.05), and pronunciation clarity (t = 16.38, P < 0.05) between patients with and without prostheses. Questionnaires showed that all the patients were satisfied with the retention of prostheses, the improvement of appearance, the improvement of the symptom of water choking and speech definition. Six months after the surgery, the hollow obturator prostheses were replaced smoothly by permanent prostheses in 11 of the 13 patients. CONCLUSION: The precise and instant repair of maxillofacial defect by prosthesis after maxillectomy can improve survival quality of patient.

[The reconstruction of geometric models of dentition defects based on 3-dimensional industrial computed tomography image].

PURPOSE: A technique on data capture of plaster models for building 3-dimensional geometric models of dentition defects was presented for the purpose of further computer-aided design and manufacture (CAD/CAM)of removable partial denture. METHODS: A plaster model with dentition defects was scanned with low energy X-ray industrial computed tomography (ICT) for ICT image. The data after image processing and vectorization were transferred to a customized reverse engineering software system, and a CAD model of dentition defects was reconstructed. Then a 3-dimensional digital model of removable partial denture framework was created with CAD/CAM software system. Import/export of the data was in STL format. RESULTS: Dense and uniform data points without blind areas were acquired and the structure of the reconstructed CAD model of dentition defects was clean and smooth. CAD model of framework was then obtained. CONCLUSIONS: The method presented is practical for 3-dimensional data capture, and it helps build reliable 3-dimensional geometric models with better spatial resolution and higher precision than conventional technique with medical CT.