Unilateral biportal endoscopy vs. open decompression for lumbar epidural lipomatosis-cohort study using a prospective registry.

Objective: This study aimed to compare the outcomes of unilateral biportal endoscopy, unilateral laminectomy bilateral decompression (UBE-ULBD), and open lumbar decompression (OLD) in patients with lumbar epidural lipomatosis (LEL). Methods: This prospective observational study was conducted from March 2019 to May 2022 and encompassed 33 patients with LEL who underwent lumbar decompression. The study included 15 cases of UBE-ULBD decompression and 18 cases of open decompression, which were followed up for 1 year. The baseline characteristics, initial clinical manifestations, and surgical details [including estimated blood loss (EBL) and preoperative complications] of all patients were recorded. Radiographic evaluation included the cross-sectional area (CSA) of the thecal sac and paraspinal muscles on MRI. Clinical results were analyzed using the Short Form-36 Score (SF-36), the Numeric Pain Rating Scale (NRS) for lumbar and leg pain, creatine kinase, the Roland and Morris Disability Questionnaire (RMDQ), and the Oswestry Disability Index (ODI). Results: The dural sac CSA increased considerably at the 1-year postoperative follow-up in both groups (p < 0.001). The operative duration in the OLD group (48.2 ± 7.2 min) was shorter than that in the UBE-ULBD group (67.7 ± 6.3 min, p < 0.001). The OLD group (97.2 ± 19.8 mL) was associated with more EBL than the UBE-ULBD group (40.6 ± 13.6 mL, p < 0.001). The duration of hospitalization in the OLD group (5.4 ± 1.3 days) was significantly longer compared with the UBE-ULBD group (3.5 ± 1.2 days, p < 0.01). The SF-36, NRS, RMDQ, and ODI scores improved in both groups postoperatively (p < 0.001). Serum creatine kinase values in the UBE-ULBD group (101.7 ± 15.5) were significantly lower than those in the OLD group (330.8 ± 28.1 U/L) 1 day after surgery (p < 0.001). The degree of paraspinal muscle atrophy in the UBE-ULBD group (4.81 ± 1.94) was significantly lower than that in the OLD group (12.15 ± 6.99) at 1 year (p < 0.001). Conclusion: UBE-ULBD and OLD demonstrated comparable clinical outcomes in treating LEL. However, UBE-ULBD surgery was associated with shorter hospital stays, lower rates of incision infection, lighter paravertebral muscle injury, and lower EBL than OLD surgery. Consequently, UBE-ULBD can be recommended in patients with LEL if conservative treatment fails.

Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis.

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice. Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.

Characteristics of Talaromyces marneffei with bone destruction in Guangxi Province, China: a retrospective study.

BACKGROUND AND OBJECTIVE: This study retrospectively analyzed the clinical and imaging features of TM mycosis complicated with bone destruction with the aim to improve understanding, diagnosis, and treatment. METHODS: Data of hospitalized TM-infected patients with bone destruction from October 2012 to May 2019 were collected. The clinical and imaging features of the disease were comprehensively analyzed. RESULTS: All 35 patients were non-HIV infected, but some had underlying co-morbid illnesses. The duration of the disease was 1-36 months (median: 5 months). Fever, anemia, weight loss, and respiratory symptoms were the main clinical manifestations of the patients. There were 18 patients (51.4%) who had bone pain. Peripheral blood leukocyte count increased significantly in 27 patients (77.1%). The neutrophil count increased in 28 patients (80%). C-reactive protein (CRP) and immunoglobulin G levels increased in 93.3% (14/15) and 82.1% (23/28) patients, respectively. The imaging examination showed osteolytic lesions, which were multiple in several bony areas. CONCLUSION: Young and middle-aged patients with non-AIDS TM complicated with underlying diseases should be especially cautious in case of occurrence of bone destruction. The main clinical manifestations of patients with TM complicated with bone destruction were pulmonary symptoms and bone and joint pain, which could be accompanied by progressive consumptive diseases.

Conditional knockout of the PDK-1 gene in osteoblasts affects osteoblast differentiation and bone formation.

Osteoblasts are the main functional cells of bone formation, and they are responsible for the synthesis, secretion, and mineralization of the bone matrix. Phosphatidylinositol-3-kinase/Akt is an important signaling pathway involved in the regulation of cell proliferation, death, and survival. Some studies have shown that 3-phosphoinositide-dependent protein kinase-1 (PDK-1) plays an important role in the phosphorylation of Akt. In the present study, an osteocalcin (OCN) promoter-driven Cre-LoxP system was established to specifically delete the PDK-1 gene in osteoblasts. It was found that the size and weight of PDK-1 conditional gene knockout (cKO) mice were significantly reduced. von Kossa staining and microcomputed tomography showed that the trabecular thickness, trabecular number, and bone volume were significantly decreased, whereas trabecular separation was increased, as compared with wide-type littermates, which were characterized by a decreased bone mass. A model of distal femoral defect was established, and it was found that cKO mice delayed bone defect repair. In osteoblasts derived from PDK-1 cKO mice, the alkaline phosphatase (ALP) secretion and ability of calcium mineralization were significantly decreased, and the expressions of osteoblast-related proteins, runt-related transcription factor 2, OCN, and ALP were also clearly decreased. Moreover, the phosphorylation level of Akt and downstream factor GSK3ß and their response to insulin-like growth factor-1 (IGF-1) decreased clearly. Therefore, we believe that PDK-1 plays a very important role in osteoblast differentiation and bone formation by regulating the PDK-1/Akt/GSK3ß signaling pathway.

Effects of inhibiting PDK­1 expression in bone marrow mesenchymal stem cells on osteoblast differentiation in vitro.

Osteoblasts are the main functional cells in bone formation, which are responsible for the synthesis, secretion and mineralization of bone matrix. The PI3K/AKT signaling pathway is strongly associated with the differentiation and survival of osteoblasts. The 3­phosphoinositide­dependent protein kinase­1 (PDK­1) protein is considered the master upstream lipid kinase of the PI3K/AKT cascade. The present study aimed to investigate the role of PDK­1 in the process of mouse osteoblast differentiation in vitro. In the BX­912 group, BX­912, a specific inhibitor of PDK­1, was added to osteoblast induction medium (OBM) to treat bone marrow mesenchymal stem cells (BMSCs), whereas the control group was treated with OBM alone. Homozygote PDK1flox/flox mice were designed and generated, and were used to obtain BMSCsPDK1flox/flox. Subsequently, an adenovirus containing Cre recombinase enzyme (pHBAd­cre­EGFP) was used to disrupt the PDK­1 gene in BMSCsPDK1flox/flox; this served as the pHBAd­cre­EGFP group and the efficiency of the disruption was verified. Western blot analysis demonstrated that the protein expression levels of phosphorylated (p)­PDK1 and p­AKT were gradually increased during the osteoblast differentiation process. Notably, BX­912 treatment and disruption of the PDK­1 gene with pHBAd­cre­EGFP effectively reduced the number of alkaline phosphatase (ALP)­positive cells and the optical density value of ALP activity, as well as the formation of cell mineralization. The mRNA expression levels of PDK­1 in the pHBAd­cre­EGFP group were significantly downregulated compared with those in the empty vector virus group on days 3­7. The mRNA expression levels of the osteoblast­related genes RUNX2, osteocalcin and collagen I were significantly decreased in the BX­912 and pHBAd­cre­EGFP groups on days 7 and 21 compared with those in the control and empty vector virus groups. Overall, the results indicated that BX­912 and disruption of the PDK­1 gene in vitro significantly inhibited the differentiation and maturation of osteoblasts. These experimental results provided an experimental and theoretical basis for the role of PDK­1 in osteoblasts.