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Summary Bone defects caused by trauma and surgery are common clinical problems encountered by orthopedic surgeons. Thus, a hard-textured, natural-like biomaterial that enables encapsulated cells to obtain the much-needed biophysical stimulation and produce functional bone tissue is needed. Incorporating nanomaterials into cell-laden hydrogels is a straightforward tactic for producing tissue engineering structures that integrate perfectly with the body and for tailoring the material characteristics of hydrogels without hindering nutrient exchange with the surroundings. In this review, recent developments in inorganic nanocomposite hydrogels for bone tissue engineering that are of vital importance but have not yet been comprehensively reviewed are summarized.

ObjectiveCancer pain, the most common skeleton-related event of bone metastases, significantly disturbs patients’ life. MRI-guided focused ultrasound (MRgFUS) is a therapeutic option to relieve pain; however, its efficacy and safety have not been fully explored. Therefore, we aim to conduct a meta-analysis on studies reporting MRgFUS for patients with bone metastases.MethodsRandomized controlled trials (RCT) and non-RCTs on MRgFUS treatment for patients with bone metastases were collected using PubMed, MEDLINE In-Process (US National Library of Medicine), National Institutes of Health (US National Library of Medicine), Embase (Elsevier), Web of Science, CINAHL, and the Cochrane Library between August 2007 and September 2019. Data on quantitative pain assessment before/after MRgFUS, response rate, and complication were extracted and analyzed.ResultsFifteen eligible studies with 362 patients were selected in this meta-analysis. The average pain score was 6.74 (95% CI: 6.30–7.18) at baseline, 4.15 (95% CI: 3.31–4.99) at 0–1 week, 3.09 (95% CI: 2.46–3.72) at 1–5 weeks, and 2.28 (95% CI: 1.37–3.19) at 5–14 weeks. Compared with baseline, the pain improvement at 0–1 week was 2.54 (95% CI: 1.92–3.16, p < 0.01), at 1–5 weeks was 3.56 (95% CI: 3.11–4.02, p < 0.01), and at 5–14 weeks was 4.22 (95% CI: 3.68–4.76, p < 0.01). Change from baseline in OMEDD at 2 weeks after treatment was −15.11 (95% CI: −34.73, 4.50), at 1 month after treatment was −10.87 (95% CI: −26.32, 4.58), and at 3 months after treatment was −5.53 (95% CI: −20.44, 9.38). The overall CR rate was 0.36 (95% CI: 0.24–0.48), PR rate was 0.47 (95% CI: 0.36–0.58), and NR rate was 0.23 (95% CI: 0.13–0.34). Among 14 studies including 352 patients, 93 (26.4%) patients with minor complications and 5 (1.42%) patients with major complications were recorded.ConclusionThis meta-analysis identifies MRgFUS as a reliable therapeutic option to relieve cancer pain for patients with metastatic bone tumors with controllable related complications.

Background The most common and deadly subtype of renal carcinoma is kidney renal clear cell carcinoma (KIRC), which accounts for approximately 75% of renal carcinoma. However, the main cause of death in KIRC patients is tumor metastasis. There are no obvious clinical features in the early stage of kidney cancer, and 25–30% of patients have already metastasized when they are first diagnosed. Moreover, KIRC patients whose local tumors have been removed by nephrectomy are still at high risk of metastasis and recurrence and are not sensitive to chemotherapy and radiotherapy, leading to poor prognosis. Therefore, early diagnosis and treatment of this disease are very important. Methods KIRC-related patient datasets were downloaded from the GEO database and TCGA database. DEG screening and GO, KEGG and GSEA enrichment analysis was firstly conducted and then the LASSO and support vector machine (SVM) RFE algorithms were adopted to identify KIRC-associated key genes in training sets and validate them in the test set. The clinical prognostic analysis including the association between the expression of key genes and the overall survival, stage, grade across KIRC, the immune infiltration difference between normal samples and cancer samples, the correlation between the key genes and immune cells, immunomodulator, immune subtypes of KIRC were investigated in this research. Results We finally screened out 4 key genes, including ACPP, ANGPTL4, SCNN1G, SLC22A7. The expression of key genes show difference among normal samples and tumor samples, SCNN1G and SLC22A7 could be predictor of prognosis of patients. The expression of key genes was related with the abundance of tumor infiltration immune cells and the gene expression of immune checkpoint. Conclusion This study screened the 4 key genes, which contributed to early diagnosis, prognosis assessment and immune target treatment of patients with KIRC.

BackgroundThe interleukin-17 (IL-17) family contains six homologous genes, IL-17A to IL-17F. Growing evidence indicates that dysregulated IL-17 family members act as major pathogenic factors in the early and late stages of cancer development and progression. However, the prevalence and predictive value of IL-17 for immune checkpoint inhibitor (ICI) therapeutic effectiveness in multiple tumor types remain largely unknown, and the associations between its expression levels and immunotherapy-associated signatures also need to be explored.MethodsThe pan-cancer dataset in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (http://xena.ucsc.edu/). The immunotherapeutic cohorts included IMvigor210, which were obtained from the Gene Expression Omnibus database and included in a previously published study. Other datasets, namely, the GEO dataset and PRECOG, GEO, and METABRIC databases, were also included. In 33 TCGA tumor types, a pan-cancer analysis was carried out including their expression map, clinical risk assessment, and immune subtype analysis, along with their association with the stemness indices, tumor microenvironment (TME) in pan-cancer, immune infiltration analysis, ICI-related immune indicators, and drug sensitivity. RT-PCR was also carried out to verify the gene expression levels among MCF-10A and MCF-7 cell lines.ResultsThe expression of the IL-17 family is different between tumor and normal tissue in most cancers, and consistency has been observed between gene activity and gene expression. RT-PCR results show that the expression differences in the IL-17 family of human cell (MCF-10A and MCF-7) are consistent with the bioinformatics differential expression analysis. Moreover, the expression of the IL-17 family can be a sign of patients’ survival prognosis in some tumors and varies in different immune subtypes. Moreover, the expression of the IL-17 family presents a robust correlation with immune cell infiltration, ICI-related immune indicators, and drug sensitivity. High expression of the IL-17 family is significantly related to immune-relevant pathways, and the low expression of IL-17B means a better immunotherapeutic response in BLCA.ConclusionCollectively, IL-17 family members may act as biomarkers in predicting the prognosis of the tumor and the therapeutic effects of ICIs, which provides new guidance for cancer treatment.

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Internal implants are widely used in most orthopedic surgeries, of which titanium and its alloys are most widely used owing to the excellent corrosiveness resistance, low elastic modulus and good biocompatibility. However, implant failure still occurs for that titanium and its alloys themselves do not own antibacterial and osteogenic properties. In this work, we successfully fabricated berberine-loaded graphene oxide (GO) on the surface of biomedical titanium and systematically investigated its capabilities of antibacteria and osteogenesis. In vitro results showed that berberine had low antibacterial activity, but GO loaded with berberine on titanium (Ber&GO@Ti) exhibited superior antibacterial activity against Staphylococcus aureus (S. aureus) with the synergistic effect of GO and berberine. Meanwhile, Ber&GO@Ti performed satisfactory cytocompatibility and was capable of promoting osteogenic differentiation of MC3T3-E1 cells. In the vivo experiment, Ber&GO@Ti showed excellent antibacterial properties and inflammatory cells e.g., neutrophils had seldom been found. No visceral toxicity had been found. This multifunctional coating showed great potential in orthopedic implants.