Computer-aided design and 3D printing for a stable construction of segmental bone defect model in Beagles: a short term observation.

OBJECTIVE: Segmental bone defect animal studies require stable fixation which is a continuous experimental challenge. Large animal models are comparable to the human bone, but with obvious drawbacks of housing and costs. Our study aims to utilize CAD and 3D printing in the construction of a stable and reproducible segmental bone defect animal mode. METHODS: CAD-aided 3D printed surgical instruments were incorporated into the construction of the animal model through preoperative surgical emulation. 20 3D printed femurs were divided into either experimental group using 3D surgical instruments or control group. In Vitro surgical time and accuracy of fixation were analysed and compared between the two groups. A mature surgical plan using the surgical instruments was then utilized in the construction of 3 segmental bone defect Beagle models in vivo. The Beagles were postoperatively assessed through limb function and imaging at 1, 2 and 3 months postoperatively. RESULTS: In vitro experiments showed a significant reduction in surgical time from 40.6 ± 14.1 (23-68 min) to 26 ± 4.6 (19-36 min) (n = 10, p < 0.05) and the accuracy of intramedullary fixation placement increased from 71.6 ± 23.6 (33.3-100) % to 98.3 ± 5.37 (83-100) %, (n = 30, p < 0.05) with the use of CAD and 3D printed instruments. All Beagles were load-bearing within 1 week, and postoperative radiographs showed no evidence of implant failure. CONCLUSION: Incorporation of CAD and 3D printing significantly increases stability, while reducing the surgical time in the construction of the animal model, significantly affecting the success of the segmental bone defect model in Beagles.

Comprehensive Analysis of Disulfidptosis-Related LncRNAs in Molecular Classification, Immune Microenvironment Characterization and Prognosis of Gastric Cancer.

BACKGROUND: Disulfidptosis is a novel form of programmed cell death that unveils promising avenues for the exploration of tumor treatment modalities. Gastric cancer (GC) is a malignant tumor characterized by high incidence and mortality rate. However, there has been no systematic study of disulfidptosis-related long noncoding RNAs (DRLs) signature in GC patients. METHODS: The lncRNA expression profiles containing 412 GC samples were acquired from the Cancer Genome Atlas (TCGA) database. Differential expression analysis was performed alongside Pearson correlation analysis to identify DRLs. Prognostically significant DRLs were further screened using univariate COX regression analysis. Subsequently, LASSO regression and multifactorial COX regression analyses were employed to establish a risk signature composed of DRLs that exhibit independent prognostic significance. The predictive value of this risk signature was further validated in a test cohort. The ESTIMATE, CIBERSORT and ssGSEA methodologies were utilized to investigate the tumor immune microenvironment of GC populations with different DRLs profiles. Finally, the correlation between DRLs and various GC drug responses was explored. RESULTS: We established a prognostic signature comprising 12 disulfidptosis-related lncRNAs (AC110491.1, AL355574.1, RHPN1-AS1, AOAH-IT1, AP001065.3, MEF2C-AS1, AC016394.2, LINC00705, LINC01952, PART1, TNFRSF10A-AS1, LINC01537). The Kaplan-Meier survival analysis revealed that patients in the high-risk group exhibited a poor prognosis. Both univariate and multivariate COX regression models demonstrated that the DRLs signature was an independent prognostic indicator in GC patients. Furthermore, the signature exhibited accurate predictions of survival at 1-, 3- and 5- years with the area under the curve (AUC) values of 0.708, 0.689 and 0.854, respectively. In addition, we also observed significant associations between the DRLs signature and various clinical variables, distinct immune landscape and drug sensitivity profiles in GC patients. The low-risk group patients may be more likely to benefit from immunotherapy and chemotherapy. CONCLUSIONS: Our study investigated the role and potential clinical implications of DRLs in GC. The risk model constructed by DRLs demonstrated high accuracy in predicting the survival outcomes of GC and improving the treatment efficacy for GC patients.

AP4M1 as a prognostic biomarker associated with cell proliferation, migration and immune regulation in hepatocellular carcinoma.

BACKGROUND: AP4M1 is a protein-coding gene that plays a crucial role in transporter activity, recognition, and hereditary-associated diseases, but it's largely unknown in cancers. METHODS: The expression level of AP4M1 in cancers was investigated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the correlation between AP4M1 and hepatocellular carcinoma (HCC) clinicopathological parameters were analyzed. Univariate and multifactorial COX regression analyses were performed to clarify the prognostic value of AP4M1 in HCC. The correlation between AP4M1 and immune cell infiltration was analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA). Besides, we verified the biological function of AP4M1 by applying Cell Counting Kit-8 (CCK8), colony formation, and transwell assays. RESULTS: The expression of AP4M1 was significantly elevated in HCC and was correlated with patients' pathological grades, AFP, and BMI. Kaplan-Meier survival curves indicated that patients with AP4M1 overexpression had worse overall survival. Univariate and multivariate COX regression analyses showed that AP4M1 was an independent risk factor affecting the prognosis of HCC. In addition, we observed that AP4M1 positively correlated with most immune checkpoint suppressor genes in HCC. Moreover, in vitro experiments further confirmed that AP4M1 could promote the proliferation and invasion of HCC. CONCLUSIONS: AP4M1 is highly expressed and associated with poor prognosis in HCC. AP4M1 is closely related to cancer-immune regulation and could be a novel target for HCC, and guiding new strategies for the diagnosis and treatment of HCC patients.

Effects of radiation therapy on tumor microenvironment: an updated review.

ABSTRACT: Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.

AhR Promotes the Development of Non-small cell lung cancer by Inducing SLC7A11-dependent Antioxidant Function.

Objective: Aryl hydrocarbon receptor (AhR) is a transcription factor. It is reported that AhR is associated with non-small cell lung cancer (NSCLC), but the mechanisms underlying this relationship remain unclear. Therefore, we investigated the role of AhR in NSCLC to elucidate the underlying mechanisms. Methods: We collected clinical lung cancer samples and constructed AhR overexpression and knockdown cell lines to investigate the tumorigenicity of AhR in vivo and in vitro. Furthermore, we performed a ferroptosis induction experiment and chromatin immunoprecipitation experiment. Results: AhR was highly expressed in NSCLC tissue. AhR knockdown cells showed ferroptosis related phenomenon. Furthermore, Chromatin immunoprecipitation confirmed the correlation between AhR and solute carrier family 7 member 11 (SLC7A11) and ferroptosis induction experiment confirmed that AhR affects ferroptosis via SLC7A11. Specifically, AhR regulates ferroptosis-related SLC7A11, which affects ferroptosis and promotes NSCLC progression. Conclusions: AhR promoted NSCLC development and positively correlated with SLC7A11, affecting its actions. AhR bound to the promoter region of SLC7A11 promotes NSCLC by activating SLC7A11 expression, improving the oxidative sensitivity of cells, and inhibiting ferroptosis. Thus, AhR affects ferroptosis in NSCLC by regulating SLC7A11, providing foundational evidence for novel ferroptosis-related treatments.

[Measurement of cortical bone thickness of zygomatic alveolar ridge in adolescents by Cone-beam CT and its correlation with cervical vertebral bone age].

PURPOSE: To measure the cortical bone thickness of zygomatic alveolar ridge in adolescents and explore the correlation between cortical bone thickness and cervical vertebral bone age. METHODS: Cone-beam CT data of 80 adolescents were collected, including 20 adolescents with cervical vertebral bone ages of Cvs3, Cvs4, Cvs5 and Cvs6, respectively. CBCT images were reconstructed with the maxillary occlusal plane as the reference plane. Cortical bone thickness of different slices in the left maxillary zygomatic alveolar ridge area was measured in the direction parallel to and 60° from the reference plane, and the measured data were statistically analyzed by SPSS 21.0 software package. RESULTS: When the measurement direction was parallel to the reference plane and at 60°, the cortical bone thickness in the zygomatic alveolar ridge area of Cvs3-Cvs6 adolescents was (0.90±0.09) -(1.72±0.21) mm and (1.35±0.44)-(3.98±1.48) mm, respectively. There was significant difference in cortical bone thickness between Cvs4 and Cvs5 group(P＜0.05). Spearman correlation analysis showed a strong positive correlation(P＜0.01) between cortical bone thickness of zygomatic alveolar ridge and cervical vertebral bone age in adolescents. CONCLUSIONS: The cortical bone thickness of zygomatic alveolar ridge in adolescents increases with the increase of cervical vertebral bone age, and the cortical bone thickness may increase significantly during Cvs4-Cvs5. In terms of cortical bone thickness, all slices of zygomatic alveolar ridge of CVS3-CVS6 adolescents are suitable for implanting miniscrews, and the anterior slices should be selected for implantation as far as possible for Cvs3 and Cvs4 adolescents.

Comprehensive analysis of the expression profile and clinical implications of regulator of chromosome condensation 2 in pan-cancers.

The Regulator of Chromosome Condensation 2 (RCC2) is an important gene that regulates mitosis and cytoplasmic division in the cell cycle. Although there have been reported in several individual tumors, an integrative analysis of RCC2 and its clinical significance across diverse cancer types is poorly elucidated. In this study, we performed integrative bioinformatics analyses to profile the expression landscape and assess the prognostic value of RCC2 in pan-cancers. Correlations between RCC2 expression and tumor-infiltrating immune cells, tumor mutation burden (TMB), microsatellite instability (MSI), chemokine and their receptors were analyzed using TCGA, ESTIMATE algorithm, and TISIDB database. We also explored the potential molecular functions of RCC2 through functional enrichment analysis and protein interaction networks. We discovered that RCC2 was highly expressed in various tumor tissues and was closely associated with cancer prognosis. Different RCC2-associated immune infiltration patterns were exhibited in different tumor-infiltrating immune cells. In addition, the RCC2 had a potential role in regulating the tumor immune microenvironment and the formation of cancer-associated fibroblasts (CAFs). Meanwhile, RCC2 showed a significant correlation with TMB, MSI, chemokines and their receptors in different tumor types. The role of RCC2 as a clinical therapeutic target was further revealed from the perspective of the immune microenvironment. In conclusion, RCC2 is closely associated with tumorigenesis and cancer-immune infiltration, and could be a promising prognostic and therapeutic biomarker in diverse cancers.

Feasibility of Computer-Aided Design in Limb Lengthening Surgery: Surgical Simulation and Guide Plates.

OBJECTIVE: To evaluate the feasibility and utility of computer-aided design (CAD) in surgical treatment of leg length discrepancy (LLD) using monorail external fixators. METHODS: In the present case series, we retrospectively analyzed seven patients diagnosed with LLD who were surgically treated using a monorail external fixator between June 2018 and August 2020. A personalized surgical emulation of each patient was designed using CAD based on preoperative CT scans to measure limb parameters. Through reverse engineering, a surgical guide plate was then designed to assist with correcting the limb deformity. Patient general information and clinical history, leg length, mechanical lateral distal femoral angle (mLDFA), anatomical anterior distal tibial angle (aADTA), and surgical parameters were recorded during the perioperative period. Three months after external fixator removal, distraction-consolidation time (DCT), healing index (HI), and lower extremity function score (LEFS) were calculated, and statistically analyzed by paired T-test. RESULTS: The mean limb lengthening achieved was 6.41 ± 2.54 (range, 3.30-10.54) cm with either varus or valgus correction. The mean operative duration was 151 ± 41.87 (84-217) minutes and mean blood loss was 53.58 ± 22.51(25-87) ml. The mean distraction-consolidation time was 3.67 ± 1.13 (range, 2.5-6.0) months and mean external fixator duration was 11 ± 2.45 (range, 8-14) months. The mean healing index (HI) was 18.11 ± 3.58 (range, 12.8-22.7) days/cm. Mean LEFS scores improved postoperatively from 32.17 ± 8.57 (range, 24-45) to 61.17 ± 6.68 (range, 50-67) with a significant difference (T = -14.26,P < 0.001). CONCLUSIONS: Simultaneous length and angular correction can be achieved by incorporating CAD into the surgical treatment of patients with LLD, without compromising postoperative lower limb function. CAD demonstrates utility in the surgical treatment of LLD by improving the functionality of monorail external fixators.

Close evolutionary relationship between rice black-streaked dwarf virus and southern rice black-streaked dwarf virus based on analysis of their bicistronic RNAs.

BACKGROUND: Rice black-streaked dwarf virus (RBSDV) and Southern rice black-streaked dwarf virus (SRBSDV) seriously interfered in the production of rice and maize in China. These two viruses are members of the genus Fijivirus in the family Reoviridae and can cause similar dwarf symptoms in rice. Although some studies have reported the phylogenetic analysis on RBSDV or SRBSDV, the evolutionary relationship between these viruses is scarce. METHODS: In this study, we analyzed the evolutionary relationships between RBSDV and SRBSDV based on the data from the analysis of codon usage, RNA recombination and phylogenetic relationship, selection pressure and genetic characteristics of the bicistronic RNAs (S5, S7 and S9). RESULTS: RBSDV and SRBSDV showed similar patterns of codon preference: open reading frames (ORFs) in S7 and S5 had with higher and lower codon usage bias, respectively. Some isolates from RBSDV and SRBSDV formed a clade in the phylogenetic tree of S7 and S9. In addition, some recombination events in S9 occurred between RBSDV and SRBSDV. CONCLUSIONS: Our results suggest close evolutionary relationships between RBSDV and SRBSDV. Selection pressure, gene flow, and neutrality tests also supported the evolutionary relationships.