A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma.

Osteosarcoma is generally considered a cold tumor and is characterized by epigenetic alterations. Although tumor cells are surrounded by many immune cells such as macrophages, T cells may be suppressed, be inactivated, or not be presented due to various mechanisms, which usually results in poor prognosis and insensitivity to immunotherapy. Immunotherapy is considered a promising anti-cancer therapy in osteosarcoma but requires more research, but osteosarcoma does not currently respond well to this therapy. The cancer immunity cycle (CIC) is essential for anti-tumor immunity, and is epigenetically regulated. Therefore, it is possible to modulate the immune microenvironment of osteosarcoma by targeting epigenetic factors. In this study, we explored the correlation between epigenetic modulation and CIC in osteosarcoma through bioinformatic methods. Based on the RNA data from TARGET and GSE21257 cohorts, we identified epigenetic related subtypes by NMF clustering and constructed a clinical prognostic model by the LASSO algorithm. ESTIMATE, Cibersort, and xCell algorithms were applied to analyze the tumor microenvironment. Based on eight epigenetic biomarkers (SFMBT2, SP140, CBX5, HMGN2, SMARCA4, PSIP1, ACTR6, and CHD2), two subtypes were identified, and they are mainly distinguished by immune response and cell cycle regulation. After excluding ACTR6 by LASSO regression, the prognostic model was established and it exhibited good predictive efficacy. The risk score showed a strong correlation with the tumor microenvironment, drug sensitivity and many immune checkpoints. In summary, our study sheds a new light on the CIC-related epigenetic modulation mechanism of osteosarcoma and helps search for potential drugs for osteosarcoma treatment.

Knockdown of long noncoding RNA HOTAIR inhibits osteoarthritis chondrocyte injury by miR-107/CXCL12 axis.

BACKGROUND: Osteoarthritis (OA) is a joint disease characterized via destruction of cartilage. Chondrocyte damage is associated with cartilage destruction during OA. Long noncoding RNAs (lncRNAs) are implicated in the regulation of chondrocyte damage in OA progression. This study aims to investigate the role and underlying mechanism of lncRNA homeobox antisense intergenic RNA (HOTAIR) in OA chondrocyte injury. METHODS: Twenty-three OA patients and healthy controls without OA were recruited. Chondrocytes were isolated from OA cartilage tissues. HOTAIR, microRNA-107 (miR-107) and C-X-C motif chemokine ligand 12 (CXCL12) levels were measured by quantitative real-time polymerase chain reaction and western blot. Cell proliferation, apoptosis and extracellular matrix (ECM) degradation were measured using cell counting kit-8, flow cytometry and western blot. The target interaction was explored by bioinformatics, luciferase reporter and RNA immunoprecipitation assays. RESULTS: HOTAIR expression was enhanced, and miR-107 level was reduced in OA cartilage samples. HOTAIR overexpression inhibited cell proliferation, but induced cell apoptosis and ECM degradation in chondrocytes. HOTAIR knockdown caused an opposite effect. MiR-107 was sponged and inhibited via HOTAIR, and knockdown of miR-107 mitigated the effect of HOTAIR silence on chondrocyte injury. CXCL12 was targeted by miR-107. CXCL12 overexpression attenuated the roles of miR-107 overexpression or HOTAIR knockdown in the proliferation, apoptosis and ECM degradation. CXCL12 expression was decreased by HOTAIR silence, and restored by knockdown of miR-107. CONCLUSION: HOTAIR knockdown promoted chondrocyte proliferation, but inhibited cell apoptosis and ECM degradation in OA chondrocytes by regulating the miR-107/CXCL12 axis.

A Novel Fast Mobile-Window Small Incision Technique for Hip Arthroplasty in the Elderly and Comparison with Conventional Incision.

BACKGROUND We deeloped a novel technique - fast mobile-window small incision (FMWSI) - a modification of minimally invasive surgery for total hip arthroplasty, which we believe is particularly suited to elderly patients with hip fractures. The present article aimed to introduce this technique and compare the clinical effects between the FMWSI technique and conventional incision (CI) for hip arthroplasty in elderly patients. MATERIAL AND METHODS This study included 240 consecutive patients who underwent hip arthroplasty. Half received total hip arthroplasty and half received hemi hip arthroplasty. The 120 patients in each group were further divided into FMWSI and CI groups. The following parameters were compared between the FMWSI and CI groups: length of incision, operation time, bleeding volume, drainage volume, postoperative ambulation time, and Harris score. RESULTS Compared with the CI group, the FMWSI group had a significantly shorter incision length, operation time, and postoperative ambulation time, as well as lower bleeding and drainage volumes, irrespective of whether the treatment was total or hemi hip arthroplasty (P<0.05). However, no significant difference was found in the Harris score between the FMWSI and CI groups (P>0.05). CONCLUSIONS The novel FMWSI technique introduced in this study is a useful method for hip arthroplasty, especially for elderly patients with poor constitutions or tolerance to surgery.

Treatment of metastatic spinal tumors by percutaneous vertebroplasty versus percutaneous vertebroplasty combined with interstitial implantation of 125I seeds.

BACKGROUND: As the most frequent bone metastasis, spinal metastases cause severe pain and damage to vertebral bodies such as spinal osteolytic destruction and compression fractures. To avoid the trauma and complications of open surgery, a minimally invasive procedure, percutaneous vertebroplasty (PVP), has recently been developed to treat metastatic spinal tumors. PURPOSE: To analyze the treatment outcomes of metastatic spinal tumors by percutaneous vertebroplasty (PVP) alone or PVP combined with interstitial implantation of 125I seeds. MATERIAL AND METHODS: 80 patients with metastatic spinal tumors were randomized to receive PVP alone (40 cases) or PVP combined with 125I seed implantation (40 cases). Digital subtraction angiography (DSA)-guided vertebroplasty was performed under local anesthesia, and acrylic bone cement was injected into the vertebra through a bone trocar to the center of the lesion, with or without simultaneous interstitial implantation of 125I seeds. RESULTS: At 6-month follow-up, PVP combined with 125I seed implantation resulted in zero cases with complete relief (CR), 36 with partial relief (PR), four with no changes (NC), and zero with progression of disease (PD), while PVP alone without seed implantation resulted in 0 CR, 31 PR, 7 NC, and 2 PD. While the combined-treatment group and the single-PVP group showed overall clinical benefit rates without significant difference (100% and 95.0%, respectively), their visual analogue pain scales (VAS; 2.26+/-1.05 and 5.41+/-0.94, respectively) and Karnofsky performance scores (KPS; 92.5+/-7.1 and 87.7+/-7.3, respectively) were significantly different after treatment (P = 0.028 and P = 0.009, respectively). Patients in both groups had 1-year follow-up, and the mean time to tumor progression (TTP) was 9.0 and 8.9 months, respectively (not significant). CONCLUSION: PVP is a minimally invasive procedure with small wounds and minor complications. It is effective in the alleviation of pain in metastatic spinal tumor patients, and its clinical outcomes can be enhanced by the combination of interstitial implantation of 125I seeds.