Nomograms for Predicting Survival Outcomes in Patients with Neuroendocrine Neoplasms of the Gallbladder Undergoing Primary Tumor Resection: A Population-Based Study.

BACKGROUND: Neuroendocrine neoplasms of the gallbladder (GB-NENs) are a rare group of histologically heterogeneous tumors, and surgical resection of the primary tumor is the mainstream treatment at the moment. The current study aimed to establish and validate novel nomograms for patients with GB-NENs undergoing primary tumor resection to predict the 6-, 12-, and 18-month overall survival (OS) and cancer-specific survival (CSS). METHODS: Clinicopathological information of patients with GB-NENs undergoing primary tumor resection between 2004 and 2018 was derived from the Surveillance, Epidemiology, and End Results (SEER) database. Candidate prognostic factors were selected by Cox regression analyses, and the nomograms were constructed. Finally, concordance index (C-index), calibration plot, area under the curve from the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were utilized to assess the effective performance of the nomograms. RESULTS: A total of 221 patients with GB-NENs undergoing resection were enrolled in this retrospective study. Using the Cox regression analyses, age, pathological classification, tumor size, and SEER stage were identified as the independent prognostic factors of patients with GB-NENs undergoing resection, and nomograms were constructed. The C-indexes of OS and CSS in training dataset were 0.802 (95% CI: 0.757-0.848) and 0.846 (95% CI: 0.798-0.895), while those of internal validation dataset were 0.862 (95% CI: 0.802-0.922) and 0.879 (95% CI: 0.824-0.934), respectively. CONCLUSIONS: Taken together, the nomograms are accurate enough to predict the prognostic factors of GB-NEN patients undergoing resection, allowing for treatment decision-making and clinical monitoring for future clinical work.

Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway.

Recurrence and metastasis are important features of osteosarcoma (OS) that cause its poor prognosis. Aberrant expression of Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been reported in various kinds of cancers. However, the expression and function of Siglec-15 in OS remain unclear. In cultured OS cells (143B cells and MNNG/HOS cells) and their xenograft mouse models, we found that downregulation of Siglec-15 could inhibit the proliferation, migration and invasion of by inducing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Conversely, Siglec-15 overexpression promoted the growth, migration and invasion of OS cells in a significant manner. Then, we screened a number of differentially expressed genes (DEGs) between Siglec-15-knockdown group and control group by RNA-Seq assay. Among these DEGs, we found that dual-specificity phosphatase 1 (DUSP1/MKP1) was significantly downregulated after Siglec-15 silencing. We investigated the DUSP1 functions in influencing OS cells' biology, and found that the proliferation, migration and invasion of OS cells were promoted by overexpressing DUSP1 and crucially, the proliferation, migration and invasion of Siglec-15-knockdown OS cells were rescued by overexpressing DUSP1. Mechanically, we further showed that DUSP1-mediated inhibition of p38/MAPK and JNK/MAPK expression was attenuated when Siglec-15 expression was inhibited, suggesting that Siglec-15 promotes the malignant progression of OS cells by suppressing DUSP1-mediated suppression of the MAPK pathway. Moreover, we showed that both Siglec-15 and DUSP1 were highly expressed in human OS tissues by immunohistochemistry. High Siglec-15 expression was associated with OS lung metastasis, and high DUSP1 expression was associated with the high Enneking stage. Kaplan-Meier analysis indicated that high expression of Siglec-15 could predict poor prognosis of OS patients. Altogether, these results showed that Siglec-15 expression promoted OS development and progression by activating DUSP1 and might be a novel target in OS treatment.

The Updated Status and Future Direction of Immunotherapy Targeting B7-H1/PD-1 in Osteosarcoma.

Although the mortality rate of osteosarcoma (OS) patients has improved, there are still many unsolved problems concerning how to reduce recurrence and metastasis. In the tumor microenvironment, immune escape plays a more important role in tumor progression and development. Many costimulatory molecules of the B7 family have been reported to be involved in regulating immunological interactions between OS cells and immune cells. Among these molecules, B7-H1 and its receptor, programmed death-1 (PD-1), have been the focus of the fields of tumor immunology and have been recently applied in clinical trials of therapies for several solid tumors. These therapies, referred to as B7-H1/PD-1 checkpoint blockade therapies, are designed to block the interaction between the two molecules. Although the mechanism has been reported in some malignancies, the specific impact of B7-H1/PD-1 expression on OS has not been well defined. Here, we review the expression, function, and regulatory mechanism of the B7-H1/PD-1 axis in OS and introduce and compare the advantages and disadvantages of B7-H1/PD-1 immunotherapies in OS.

Anatomical Adaptation of Fibula and its Mechanism of Proximal Partial Fibulectomy Associated with Medial Compartment Knee Osteoarthritis.

OBJECTIVES: To reveal the anatomical adaptation of the fibula and its relations to age and settlement of the medial tibial plateau, and to explore the mechanism of proximal partial fibulectomy in treating medial compartment knee osteoarthritis (OA). METHODS: A retrospective study was performed in the Third Hospital of Hebei Medical University. Weight-bearing full-leg anteroposterior (AP) radiographs of 280 adults (560 knees) obtained from 1 January 2018 to 31 October 2018 were enrolled according to our inclusion and exclusion criteria, including 157 men and 123 women, with an average age of 50.3 ± 14.8 years (range, 19-80 years). Radiographic severity of knee OA was assessed using Kellgren and Lawrence (K-L) grading. The settlement of the medial tibial plateau was evaluated using the medial proximal tibial angle (MPTA). Curvatures of the tibia and the fibula were measured as proximal tibial curvature (PTC), distal tibial curvature (DTC), proximal fibular curvature (PFC), and distal fibular curvature (DFC). Two orthopaedic surgeons performed all the radiological measurements for 30 randomly selected patients, and repeated the measurements 1 week later. Based on the satisfactory intra-observer and inter-observer reliabilities (ICC > 0.9), each parameter was analyzed in this study. Multivariable linear regression models were used to examine relations between radiological measurements and age. RESULTS: The mean MPTA, PTC, DTC, PFC, and DFC were 85.4° ± 2.8°, 176.2° ± 1.9°, 176.8° ± 1.8°, 176.8° ± 1.9°, and 177.0° ± 2.0°, respectively. Ninety-three knees of K-L grade I were categorized as non-knee OA, and 467 knees of K-L grades II-IV were categorized as knee OA. The MPTA, PTC, and PFC of the knee OA group were significantly smaller than those of non-knee OA group (P < 0.05). The K-L grade of knee OA significantly increased with age (χ 2 = 182.169, P < 0.01). The multivariate linear regression analysis indicated that the MPTA and fibular curvatures were negatively correlated with age (the regression equation is age = 561.165-0.945 MPTA-0.937 PFC-0.959 DFC, P < 0.05), and the MPTA was negatively correlated with PFC (the regression equation is MPTA = 7.827 + 0.099 DFC, P < 0.05). CONCLUSIONS: The proximal curve of the fibula increased in patients with medial compartment knee OA, and this change was positively correlated with age and settlement of the medial tibial plateau. This anatomical adaptation of the fibula was associated with greater fibular axial load and the pulling from the peroneus longus. The proximal partial fibulectomy procedure effected a receptive foot pronation to reduce KAM and rebalance the biceps-proximal fibula-peroneus longus complex, consequently achieving medial compartment unloading.