Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Carboplatin-based Nanomedicine to Enhance the Anticancer Effect in SK-NEP-1 WilmsꞌTumor Cells.

Wilms tumor (WT) is the most common pediatric malignant primary renal tumor. Carboplatin (CRB), a platinum compound is widely used in the treatment of multiple cancers including ovarian, lung, head and neck, and wilm's tumor. However, lower uptake of CRB in cancer cells and toxicity concerns in healthy cells often limited its clinical outcome. The aim of this study was to investigate the antitumor effect of CRB on SK-NEP-1 wilm's cancer cells. Earlier, CRB was formulated in nanoparticulate formulations and characterized its biophysical parameters. SK-NEP-1 cell growth in vitro was assessed by MTT. Then, apoptosis potential was investigated by TUNEL, Hoechst, and colony formation assay. CRB treatment resulted in inhibition of cell proliferation of SK-NEP-1cells in a dose-dependent manner. TUNEL, Hoechst, and colony formation assay demonstrated that CRB was more effective in killing wilm's cancer cell when encapsulated in nanoparticle formulations. Overall, the present study demonstrates that CRB treatment resulted in marked inhibition of cell proliferation and cell apoptosis. These results may pave way for the effective treatment of wilm's tumor in clinical models.

[Digital skeletal age and histological evaluation for residual spine growth potential in idiopathic scoliosis].

OBJECTIVE: To ascertain the correlation between histological grades (HGs) of vertebral growth plates and Risser grades in idiopathic scoliosis (IS) patients; to identify whether digital skeletal age (DSA) is a reliable indicator for accurate evaluation of the spinal residual growth potential. METHODS: Twenty eight Chinese female patients were available for this study. Superior and inferior growth plates were obtained at each level when anterior approach surgeries were performed. Histological examinations were conducted after the specimens were processed. The patients were evaluated by DSA stages in this study. Correlations between histological grades, menarchal status, and chronological age were analyzed. RESULTS: There was a negative correlation between the following: HGs and DSA stages in 28 cases (r = -0.541, P = 0.003), and HGs and menarchal status in patients in DSA stage III (r = -0.591, P = 0.006). Statistical significance of growth activity of growth plates was found between patients in DSA-stage II and those in DSA-stage III (P = 0.014). CONCLUSIONS: DSA may be a reliable indicator for predicting the spinal residual growth potential in IS patients, but it should be correlated with menarchal status and chronological ages.

[Assessment of the residual spine growth potential in idiopathic scoliosis by risser sign and histological grading].

OBJECTIVE: To investigate the correlation between histological grade (HG) of vertebral growth plates and Risser grade in the female idiopathic scoliosis (IS) patients; and to identify whether Risser grading is a reliable indicator for accurate evaluation of the spinal residual growth potential. METHODS: Thirty-nine samples of vertebral growth plates obtained during operation from 15 females IS patients, all female, aged 15.1 (12.4 - 18.0), underwent HE staining and light microscopy to determine the values of HG. Xray photography of pelvis was conducted before operation to identify the Risser sign. The correlation of Risser grade with pubertal status was analyzed. RESULTS: All the vertebral growth plates of the IS patients with the Risser grade of 0 showed growth activity. The vertebral growth plates showed HG II activity in 6 of the 16 IS patients with the Risser grade of 4. All the vertebral growth plates showed no growth activity in the 3 IS patients with the Risser grade of 5. There was a negative correlation between the HG and Risser grade in all 39 patients (r = -0.645, P =0.000). The HG of the patients with the Risser grade of 4 was negatively correlated with the menarchal status (time between menarche and operation) (r = -0.710, P = 0.002). The residual growth potential of spinal growth plates of the patients with the Risser grades of 2 - 5 was significantly lower than of the patients with the Risser grades of 0 - 1 (P = 0.020). CONCLUSION: Risser sign may be a reliable indicator for predicting the spinal residual growth potential in IS patients, but it should be correlated with menarchal status and chronological ages.