Objectives: Chordoma is a rare bone malignancy that affects the spine and skull base. Treatment dilemma leads to a high rate of local relapse and distant metastases. Molecular targeted therapy (MTT) is an option for advanced chordoma, but its therapeutic efficacy and safety have not been investigated systematically. Therefore, a systematic review was conducted on studies reporting MTT regimens for chordoma. Methods: Clinical trials, case series and case reports on chordoma MTT were identified using MEDLINE, Cochrane library and EMBASE, and systematically reviewed. Data on clinical outcomes, such as median overall survival, progression-free survival, response rate and adverse events (AEs) were extracted and analyzed. Results: Thirty-three eligible studies were selected for the systematic review, which indicated that imatinib and erlotinib were the most frequently used molecular targeted inhibitors (MTIs) for chordoma. For PDGFR-positive and/or EGFR-positive chordoma, clinical benefits were achieved with acceptable AEs. Monotherapy is preferred as the first-line of treatment, and combined drug therapy as the second-line treatment. In addition, the brachyury vaccine has shown promising results. Conclusions: The selection of MTIs for patients with advanced or relapsed chordoma should be based on gene mutation screening and immunohistochemistry (IHC). Monotherapy of TKIs is recommended as the first-line management, and combination therapy (two TKIs or TKI plus mTOR inhibitor) may be the choice for drug-resistant chordoma. Brachyury vaccine is a promising therapeutic strategy and requires more clinical trials to evaluate its safety and efficacy.

Soft tissue sarcoma (STS) is one of the most challenging tumors for medical oncologists, with a high rate of recurrence after initial resection. In this study, a recurrent STS-specific competitive endogenous RNA (ceRNA) network including seven recurrence and overall survival (OS)-associated genes (LPP-AS2, MUC1, GAB2, hsa-let-7i-5p, hsa-let-7f-5p, hsa-miR-101-3p and hsa-miR-1226-3p) was established based on the gene expression profiling of 259 primary sarcomas and 3 local recurrence samples from the TCGA database. The algorithm "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)" was applied to estimate the fraction of immune cells in sarcomas. Based on 5 recurrence and OS-associated immune cells (NK cells activated, dendritic cells resting, mast cells resting, mast cells activated and macrophages M1), we constructed a recurrent STS-specific immune cells network. Both nomograms were identified to have good reliabilities (Area Under Curve (AUC) of 5-year survival is 0.724 and 0.773, respectively). Then the co-expression analysis was performed to identify the potential regulation network among recurrent STS-specific immune cells and ceRNAs. Hsa-miR-1226-3p and MUC1 were significantly correlated and dendritic cells resting was related to hsa-miR-1226-3p. Additionally, the expression of MUC1 and dendritic cell marker CD11c were also verified by immunohistochemistry (IHC) assay and multidimensional databases. In conclusion, this study illustrated the potential mechanism of hsa-miR-1226-3p regulating MUC1 and dendritic cells resting might play an important role in STS recurrence. These findings might provide potential prognostic biomarkers and therapeutic targets for recurrent STS.

Background: Chordoma is a rare mesenchymal malignancy, with a high recurrence rate and unclear tumorigenic mechanism. Genetic alterations, epigenetic regulators, and chromatin spatial organization play crucial roles in the initiation and progression of chordoma. In the current study, we aim to uncover the novel therapeutical targets for chordoma via using integrated multi-omics analysis. Methods: The RNA-sequencing (RNA-seq), assay for transposable accessible chromatin by high-throughput sequencing (ATAC-seq), and Hi-C were performed between chordoma and human nucleus pulposus (HNP), along with imageological examination and clinical information. The expressions of identified targets were validated by clinical samples and their functions were further evaluated by cell and animal experiments via gene knockdown and inhibitors. Results: The integrated multi-omics analysis revealed the important roles of bone microenvironment in chordoma tumorigenesis. By comparing the hierarchical structures, CA2 (carbonic anhydrase II) and THNSL2 (threonine synthase-like 2) were identified in the switched compartments, cell-specific boundaries, and loops. Additionally, CA2 was highly expressed in chordoma but barely found in HNP. The cell growth and migration of chordoma cells were dramatically suppressed via inhibition of CA2 either with genetic deletion or pharmaceutical treatment with Dorzolamide HCl. Furthermore, Dorzolamide HCl also regulated the bone microenvironment by blocking the osteoclast differentiation of bone marrow monocytes. Conclusion: This study uncovers the roles of bone microenvironment in the chordoma tumorigenesis and identifies CA2 as a novel therapeutic target for chordoma. Besides, our findings suggest Dorzolamide HCl as a promising therapeutic option for chordoma.

Tumor-induced osteomalacia (TIO) is a rare disorder, which is commonly found in craniofacial locations and in the extremities. To the best of our knowledge, only 16 cases have been described in the spine, and this is the first report to describe a case of patient with TIO in the thoracic spine combined with a mesenchymal hamartoma which had confused the therapeutic strategies to date. We report the case of a 60-year-old patient with hypophosphatemia and presented with limb weakness. Treating with phosphate did not correct the hypophosphatemia and an 111In pentetreotide scintigraphy (octreotide scan) revealed an increased uptake at the right forearm. The tumor was resected totally, and the histopathology revealed a mesenchymal hamartoma, but we noticed that hypophosphatemia was not corrected after the tumor resection. Then a whole-body magnetic resonance imaging (WB-MRI) was performed and the results revealed tumorous tissues at the right T1 vertebral pedicle. The tumor was removed with an en bloc method, and the pathology showed phosphaturic mesenchymal tumor. Follow-up at 1 year after surgery revealed no recurrence, and the serum phosphorus level of the patient was normal. Tumor-induced osteomalacia is exceedingly rare with only 16 cases in spine published in the literature. It is difficult to find and leads to years of suffering debilitating complications. In this regard, the WB-MRI is a better method to locate the real tumor. Treating with phosphate can only relieve symptoms, and a complete surgical removal remains the gold standard treatment.

Objective: Cancer 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.Methods: Randomized 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.Results: Fifteen 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.Conclusion: This meta-analysis identifies MRgFUS as a reliable therapeutic option to relieve cancer pain for patients with metastatic bone tumors with controllable related complications.

Medical students' perceptions of the medical school learning environment (MSLE) have an important impact on their professional development, and physical and mental health. Few studies reported potential factors that influenced medical students' perceptions of MSLE. Thus, the main goal of this study was to identify influencing factors for medical students' perception levels of MSLE. The perception levels of MSLE were assessed by the Johns Hopkins Learning Environment Scale. The univariate and multivariate logistic regression analyses were performed to identify significant predictors for the perceptions of MSLE. The nomograms were established to predict medical students' perception levels of MSLE. In the multivariate logistic regression model, gender, university category, grade, mother education level, learning environment of schools, interests in medicine, and Kolb learning experience were significantly associated with medical students' perceptions of MSLE. Correspondently, the nomograms were built based on significant variables identified by the univariate logistic regression analysis. The validation of the nomograms showed that the model had promising predictive accuracy, discrimination, and accordance (area under the curve (AUC) = 0.751). This study identified influencing factors of medical students' perceptions of MSLE. It is essential to implement corresponding interventions to improve medical students' perceptions.