Design of 3D-printed prostheses for reconstruction of periacetabular bone tumors using topology optimization.

Background: Prostheses for the reconstruction of periacetabular bone tumors are prone to instigate stress shielding. The purpose of this study is to design 3D-printed prostheses with topology optimization (TO) for the reconstruction of periacetabular bone tumors and to add porous structures to reduce stress shielding and facilitate integration between prostheses and host bone. Methods: Utilizing patient CT data, we constructed a finite element analysis (FEA) model. Subsequent phases encompassed carrying out TO on the designated area, utilizing the solid isotropic material penalization model (SIMP), and this optimized removal area was replaced with a porous structure. Further analyses included preoperative FEA simulations to comparatively evaluate parameters, including maximum stress, stress distribution, strain energy density (SED), and the relative micromotion of prostheses before and after TO. Furthermore, FEA based on patients' postoperative CT data was conducted again to assess the potential risk of stress shielding subsequent to implantation. Ultimately, preliminary follow-up findings from two patients were documented. Results: In both prostheses, the SED before and after TO increased by 143.61% (from 0.10322 to 0.25145 mJ/mm3) and 35.050% (from 0.30964 to 0.41817 mJ/mm3) respectively, showing significant differences (p < 0.001). The peak stress in the Type II prosthesis decreased by 10.494% (from 77.227 to 69.123 MPa), while there was no significant change in peak stress for the Type I prosthesis. There were no significant changes in stress distribution or the proportion of regions with micromotion less than 28 µm before and after TO for either prosthesis. Postoperative FEA verified results showed that the stress in the pelvis and prostheses remained at relatively low levels. The results of follow-up showed that the patients had successful osseointegration and their MSTS scores at the 12th month after surgery were both 100%. Conclusion: These two types of 3D-printed porous prostheses using TO for periacetabular bone tumor reconstruction offer advantages over traditional prostheses by reducing stress shielding and promoting osseointegration, while maintaining the original stiffness of the prosthesis. Furthermore, in vivo experiments show that these prostheses meet the requirements for daily activities of patients. This study provides a valuable reference for the design of future periacetabular bone tumor reconstruction prostheses.

(E)-SIS3 suppressed osteosarcoma progression via promoting cell apoptosis, arresting cell cycle, and regulating the tumor immune microenvironment.

Osteosarcoma is a prevalent malignant bone tumor with a poor prognosis. Mothers against decapentaplegic homolog 3 (Smad3) present as a therapeutic target in antitumor treatment, whereas its functions in the osteosarcoma have not been well explored. In the current study, we aimed to investigate the effects of Smad3 in the progression of osteosarcoma. The tumor immune single-cell hub 2 website was used for graph-based visualization of Smad3 status in osteosarcoma single-cell database. Western Blot was applied to detect the expression of Smad3 protein in cell lines. Colony formation and cell counting kit-8 assays were used to evaluate cell proliferation. Transwell and wound healing assays were used to detect the migration and invasion abilities of cells. Cell apoptosis rates and cell cycle changes were explored by using flow cytometry analysis. The xenograft tumor growth model was applied to explore the effect in tumor growth after Smad3 blockage in vivo. Moreover, to confirm the potential mechanism of Smad3's effects on osteosarcoma, bioinformatics analysis was performed in TARGET-Osteosarcoma and GSE19276 databases. Our study found that the Smad3 protein is overexpressed in 143B and U2OS cells, suppressing the expression of Smad3 protein in osteosarcoma cells by Smad3 target inhibitor (E)-SIS3 or lentivirus can inhibit the proliferation, migration, invasion, promote cell apoptosis, arrest cell G1 cycle in osteosarcoma cells in vitro, and suppress tumor growth in vivo. Furthermore, the bioinformatics analysis demonstrated that high expression of Smad3 is closely associated with low immune status in TARGET-Osteosarcoma and GSE19276 databases. Our study suggested that Smad3 could contribute positively to osteosarcoma progression via the regulation of tumor immune microenvironment, and Smad3 may represent as an valuable potential therapeutic target in osteosarcoma therapy.

Six potential biomarkers in septic shock: a deep bioinformatics and prospective observational study.

Background: Septic shock occurs when sepsis is related to severe hypotension and leads to a remarkable high number of deaths. The early diagnosis of septic shock is essential to reduce mortality. High-quality biomarkers can be objectively measured and evaluated as indicators to accurately predict disease diagnosis. However, single-gene prediction efficiency is inadequate; therefore, we identified a risk-score model based on gene signature to elevate predictive efficiency. Methods: The gene expression profiles of GSE33118 and GSE26440 were downloaded from the Gene Expression Omnibus (GEO) database. These two datasets were merged, and the differentially expressed genes (DEGs) were identified using the limma package in R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed. Subsequently, Lasso regression and Boruta feature selection algorithm were combined to identify the hub genes of septic shock. GSE9692 was then subjected to weighted gene co-expression network analysis (WGCNA) to identify the septic shock-related gene modules. Subsequently, the genes within such modules that matched with septic shock-related DEGs were identified as the hub genes of septic shock. To further understand the function and signaling pathways of hub genes, we performed gene set variation analysis (GSVA) and then used the CIBERSORT tool to analyze the immune cell infiltration pattern of diseases. The diagnostic value of hub genes in septic shock was determined using receiver operating characteristic (ROC) analysis and verified using quantitative PCR (qPCR) and Western blotting in our hospital patients with septic shock. Results: A total of 975 DEGs in the GSE33118 and GSE26440 databases were obtained, of which 30 DEGs were remarkably upregulated. With the use of Lasso regression and Boruta feature selection algorithm, six hub genes (CD177, CLEC5A, CYSTM1, MCEMP1, MMP8, and RGL4) with expression differences in septic shock were screened as potential diagnostic markers for septic shock among the significant DEGs and were further validated in the GSE9692 dataset. WGCNA was used to identify the co-expression modules and module-trait correlation. Enrichment analysis showed significant enrichment in the reactive oxygen species pathway, hypoxia, phosphatidylinositol 3-kinases (PI3K)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling, nuclear factor-κß/tumor necrosis factor alpha (NF-κß/TNF-α), and interleukin-6 (IL-6)/Janus Kinase (JAK)/Signal Transducers and Activators of Transcription 3 (STAT3) signaling pathways. The receiver operating characteristic curve (ROC) of these signature genes was 0.938, 0.914, 0.939, 0.956, 0.932, and 0.914, respectively. In the immune cell infiltration analysis, the infiltration of M0 macrophages, activated mast cells, neutrophils, CD8 T cells, and naive B cells was more significant in the septic shock group. In addition, higher expression levels of CD177, CLEC5A, CYSTM1, MCEMP1, MMP8, and RGL4 messenger RNA (mRNA) were observed in peripheral blood mononuclear cells (PBMCs) isolated from septic shock patients than from healthy donors. Higher expression levels of CD177 and MMP8 proteins were also observed in the PBMCs isolated from septic shock patients than from control participants. Conclusions: CD177, CLEC5A, CYSTM1, MCEMP1, MMP8, and RGL4 were identified as hub genes, which were of considerable value in the early diagnosis of septic shock patients. These preliminary findings are of great significance for studying immune cell infiltration in the pathogenesis of septic shock, which should be further validated in clinical studies and basic studies.

Procyanidin B2 regulates the Sirt1/Nrf2 signaling pathway to improve random-pattern skin flap survival.

Random-pattern skin flaps have been widely used in the reconstruction of damaged tissues. Ischemia-reperfusion injury occurring in the distal regions of the flap is a common issue, which often leads to flap necrosis and restricts its clinical applications. Procyanidin B2 (PB2), a naturally occurring flavonoid in large quantities in various fruits, has been demonstrated to exhibit several significant pharmacological properties. However, the effect of PB2 on flap viability is not clearly known. Here, using Western blot analysis, immunohistochemistry, and immunofluorescence staining, we observed that PB2 significantly reduced oxidative stress and inflammation and enhanced angiogenesis. Mechanically, we provided evidence for the first time that the beneficial effects of PB2 occur through the activation of the Sirt1/Nrf2 signaling pathway. Moreover, co-administration of PB2 and EX527, a selective inhibitor of Sirt1, resulted in down-regulation of the expression of Sirt1, Nrf2, and downstream antioxidants. In summary, our study showed that PB2 might be a novel therapeutic strategy for improving the survival of random-pattern skin flaps.

Surgical robot-assisted tripod percutaneous reconstruction technique combined with bone cement filling technique for the treatment of acetabular metastasis.

Background: Acetabular metastasis is a type of metastatic bone cancer, and it mainly metastasizes from cancers such as lung cancer, breast cancer, and renal carcinoma. Acetabular metastasis often causes severe pain, pathological fractures, and hypercalcemia which may seriously affect the quality of life of acetabular metastasis patients. Due to the characteristics of acetabular metastasis, there is no most suitable treatment to address it. Therefore, our study aimed to investigate a novel treatment technique to relieve these symptoms. Methods: Our study explored a novel technique to reconstruct the stability of the acetabular structure. A surgical robot was used for accurate positioning and larger-bore cannulated screws were accurately inserted under the robot's guidance. Then, the lesion was curetted and bone cement was injected through a screw channel to further strengthen the structure and kill tumor cells. Results: A total of five acetabular metastasis patients received this novel treatment technique. The data relating to surgery were collected and analyzed. The results found that this novel technique can significantly reduce operation time, intraoperative bleeding, visual analogue score scores, Eastern Cooperative Oncology Group scores, and postoperative complications (e.g., infection, implant loosening, hip dislocation) after treatment. Follow-up time ranged from 3 months to 6 months, and the most recent follow-up results showed that all patients survived and no acetabular metastasis progressed in any of the patients after surgery. Conclusion: Surgical robot-assisted tripod percutaneous reconstruction combined with the bone cement filling technique may be a novel and suitable treatment in acetabular metastasis patients. Our study may provide new insights into the treatment of acetabular metastasis.

Combination of hsa_circ_0004674 and lncRNA OIP5­AS1 as a novel clinical biomarker used to predict prognosis in patients with osteosarcoma.

Osteosarcoma is a malignant tumor that predominantly occurs in children or adolescents under the age of 20 years old. Metastasis and chemotherapy resistance are two problems in the treatment of osteosarcoma, and the lack of definite biomarkers impairs the course of treatment. In recent years, non-coding RNA, as a biomarker of osteosarcoma, has become an area of research focus. The role of long non-coding RNAs (lncRNAs), such as lncRNA OIP5-AS1, and circular RNAs, such as hsa_circ_0004674, in osteosarcoma have previously been revealed, and the present study investigated their clinical significance. A total of 20 samples were collected from patients with osteosarcoma. The expression levels of lncRNA OIP5-AS1 and hsa_circ_0004674 were analyzed in tumor tissues and patient serum, and their associations with chemotherapy sensitivity, lung metastasis and prognosis were assessed. The results revealed that these two non-coding RNAs were significantly upregulated in the osteosarcoma tissues of patients compared with those in the adjacent tumor tissues. In addition, the expression levels of the two non-coding RNAs were increased in the serum of patients with osteosarcoma compared with those in patients with bone fractures (P<0.01). In patients with lung metastasis or chemotherapy resistance (tumor necrosis rate <90%), the expression levels of the two non-coding RNAs were similarly increased. By plotting the receiver operating characteristic curve, it was revealed that the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 was better than ALP or either non-coding RNA alone in predicting chemotherapy sensitivity and metastasis. Kaplan-Meier survival analysis showed that, in patients with osteosarcoma, higher expression of both non-coding RNAs was associated with worse survival time (log-rank test P=0.006). In conclusion, the combination of hsa_circ_0004674 and lncRNA OIP5-AS1 may be used as a better biomarker than traditional biomarkers, such as ALP, in a clinical setting.

Refracture after plate removal of midshaft clavicle fractures after bone union-incidence, risk factors, management and outcomes.

INTRODUCTION: There is a great debate on the routine use of open reduction and internal fixation (ORIF) for midshaft clavicle fractures, and one concern is the adverse events after ORIF, such as implant removal after bone union. In this retrospective study, we assessed the incidence, risk factors, management and outcomes of refracture after plate removal of midshaft clavicle fractures after bone union. MATERIALS AND METHODS: Three hundred fifty-two patients diagnosed with acute midshaft clavicle fractures who had complete medical records from primary fractures to refracture were recruited. Details of imaging materials and clinical characteristics were carefully reviewed and analysed. RESULTS: The incidence rate of refracture was 6.5% (23/352), and the average interval from implant removal to refracture was 25.6 days. Multivariate analysis showed that the risk factors were Robinson type-2B2 and fair/poor reduction. Females were 2.4 times more likely to have refracture, although it was not significant in multivariate analysis (p = 0.134). Postmenopausal females with a short interval (≤ 12 months) from primary surgery to implant removal had a significant risk for refracture. Tobacco use and alcohol use during bone healing were potential risk factors for male patients, although they were not significant in multivariate analysis. Ten patients received reoperation with or without bone graft, and they had a higher rate of bone union than 13 patients who refused reoperation. CONCLUSION: The incidence of refracture following implant removal after bone union is underestimated, and severe comminute fractures and unsatisfactory reduction during primary surgery are risk factors. Implant removal for postmenopausal female patients is not recommended due to a high rate of refracture.

Analysis of preoperative sleep quality and related influencing factors in cancer patients.

PURPOSE: The sleep disturbance in cancer patients is more prevalent, and it significantly affects these patients' recovery after the operation. However, the clinical characteristics regarding sleep quality are scarce. This study aimed to evaluate the quality of preoperative sleep quality and its risk factors in different cancer patients requiring elective surgery. PATIENTS AND METHODS: Cancer patients who were scheduled for elective surgery were selected. The demographic data, basic preoperative diseases, and factors related to the preoperative hospital environment were also recorded. Self-made questionnaires (such as gender, age, and personal history), and the Anxiety Self-Assessment Scale were used to assess the patient's underlying condition. The modified Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the preoperative sleep status. RESULTS: A total of 297 patients completed the investigation. The incidence of preoperative sleep disturbance in cancer patients was 47.8%. Multiple logistic regression showed that patients with PSQI ≥ 7 were associated with females (odds ratios [95% confidence intervals]): 1.815 [1.031-3.193], p = 0.039), and the ward space was confined (3.127 [1.016-9.625], p = 0.047), which increased the possibility of sleep disturbance in cancer patients. Meanwhile, increased anxiety levels (1.323 [1.261-1.439], p < 0.001) significantly increased the likelihood of sleep disorders in cancer patients. CONCLUSION: 47.8% of sleep disturbance in cancer patients before surgery. Female patients, preoperative anxiety, and confined ward environment were independent risk factors of subjective sleep disturbance.

LncRNA ODRUL regulates progression of osteosarcoma by regulating IL-6 via sponging miR-6874-3p.

Accumulating evidence has shown that many long non-coding RNAs (lncRNA) participate in the tumorigenesis, including osteosarcoma (OS). Of them, lncRNA ODRUL was previously reported to act as a possible oncogene in OS doxorubicin resistance. However, the underlying molecular mechanism of ODRUL involved in the progression of OS still remains to be thoroughly investigated. In the current study, we reported another mechanism by which ODRUL regulates OS progression. QRT-PCR and WB were conducted to detect ODRUL, miR-6874-3p and IL-6 expression in OS tissues and cells. The Kaplan-Meier was used to assess the relevance between the expression level of miR-6874-3p and the overall survival of OS patients. Wound healing assays and Transwell assays were used to evaluate the invasion and migration of OS cells. Furthermore, the binding sites of ODRUL and IL-6 to miR-6874-3p were predicted by bioinformatics and verified by dual-luciferase reporter gene assays. ODRUL and IL-6 were highly expressed in OS cells and tissues, while miR-6874-3p was expressed at low levels. The overall survival of high miR-6874-3p expression of OS patients was longer than that of low miR-6874-3p expression of OS patients. MiR-6874-3p overexpression markedly inhibited the progression of OS cells. Both ODRUL and IL-6 could bind to miR-6874-3p at the predicted binding sites which were authenticated by dual-luciferase reporter gene assay. MiR-6874-3p could inhibit OS cell proliferation and metastasis and ODRUL could reverse the suppression induced by miR-6874-3p in vivo. In conclusion, ODRUL could effectively sponge miR-6874-3p to upregulate the expression of IL-6 in OS progression.