Epidemiology and nomogram of pediatric and young adulthood osteosarcoma patients with synchronous lung metastasis: A SEER analysis.

BACKGROUND: Patients with osteosarcoma and synchronous lung metastasis (SLM) have poor survival. This study aimed to explore the epidemiology data and construct a predictive nomogram to identify cases at risk of SLM occurrence among pediatric and young adulthood osteosarcoma patients. METHODS: All data were extracted from Surveillance, Epidemiology, and End Results 17 registries. The age-standardized incidence rate (ASIR) and annual percentage change was evaluated, and reported for the overall population and by age, gender, race, and primary site. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with SLM occurrence, then significant factors were used to develop the nomogram. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluated the predictive power of the nomogram. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Multivariate Cox analysis was used to determine the prognostic factors. RESULTS: A total of 278 out of 1965 patients (14.1%) presented with SLM at diagnosis. The ASIR increased significant from 0.46 to 0.66 per 1,000,000 person-years from year 2010 to 2019, with an annual percentage change of 3.5, mainly in patients with age 10-19 years, male and appendicular location. All patients were randomly assigned into train cohort and validation cohort with a spilt of 7:3. In the train cohort, higher tumor grade, bigger tumor size, positive lymph nodes and other site-specific metastases (SSM) were identified as significant risk factors associated with SLM occurrence. Then a nomogram was developed based on the four factors. The AUC and calibration curve in both train and validation cohorts demonstrated that the nomogram had moderate predictive power. The median cancer-specific survival was 25 months. Patients with age 20-39 years, male, positive lymph nodes, other SSM were adverse prognostic factors, while surgery was protective factor. CONCLUSIONS: This study performed a comprehensive analysis regarding pediatric and young adulthood osteosarcoma patients had SLM. A visual, clinically operable, and easy-to-interpret nomogram model was developed for predicting the risk of SLM, which could be used in clinic and help clinicians make better decisions.

Percutaneous Kyphoplasty Enhanced with Calcium and Zoledronic Acid for Managing Thoracolumbar Compression Fractures in Athletes with Osteoporosis and Fitness Concerns

Background: Athletes and fitness enthusiasts often encounter thoracolumbar compression fractures due to rigorous physical activities. Combining calcium (Ca) and zoledronic acid (ZOL) with percutaneous kyphoplasty (PKP) has shown promising clinical efficacy in elderly patients with osteoporotic thoracolumbar compression fractures (OTCF). However, the potential benefits of this approach in athletes and fitness enthusiasts require further investigation. Methods: We conducted a retrospective analysis of 295 athletes and fitness enthusiasts (mean age 75.91±3.74 years) with OTCF who underwent PKP. Patients were divided into three groups: PKP+Ca (n=92), receiving 1500mg/d Ca carbonate post-surgery; PKP+ZOL (n=98), receiving 5mg ZOL intravenously post-surgery; and PKP+Ca+ZOL (n=105), administered with a combination of Ca and ZOL post-surgery. A two-year follow-up was conducted, and clinical and imaging data were recorded and analyzed before and after treatment. Results: There were no significant differences in general information, lumbar bone mineral density (BMD), visual analog scale (VAS), Oswestry dysfunction index (ODI), and bone marker levels among the three groups before treatment. In the 3rd, 6th, 12th, and 24th months post-treatment, the PKP+Ca+ZOL group exhibited higher vertebral heights compared to the PKP+Ca and PKP+ZOL groups. Additionally, in the 6th, 12th, and 24th months post-treatment, the PKP+Ca+ZOL group demonstrated lower kyphosis than the PKP+Ca and PKP+ZOL groups. Furthermore, in the 12th and 24th months post-treatment, the PKP+Ca+ZOL group had higher BMD values than the PKP+ZOL and PKP+Ca groups. VAS scores in the PKP+Ca+ZOL and PKP+ZOL groups were significantly lower than those in the PKP+Ca group. ODI scores and bone marker concentrations were also lower in the PKP+Ca+ZOL group compared to the other groups. (AU)

Enabled homolog (ENAH) regulated by RNA binding protein splicing factor 3b subunit 4 (SF3B4) exacerbates the proliferation, invasion and migration of hepatocellular carcinoma cells via Notch signaling pathway.

Enabled homolog (ENAH) is an actin-binding protein that implicated in multiple malignant tumors. High ENAH expression has been verified to be associated with poor prognosis in hepatocellular carcinoma (HCC). We aimed to reveal the role of ENAH in HCC and the potential mechanism. ENAH expression in HCC tissues and the prognostic correlation were analyzed by GEPIA2 database. RT-qPCR and Western blot were used to test ENAH expression in HCC cells. Following ENAH silencing, cell proliferation was estimated by CCK-8 and colony formation assays. Transwell and wound healing assays were to assess cell invasion and migration. ENCORI database was to analyze the correlation between ENAH and splicing factor 3b subunit 4 (SF3B4) in HCC tissues, which was then verified by RIP and actinomycin D assay. Then, the expression of Notch signaling-related proteins was detected by Western blotting after ENAH knockdown. Afterward, Notch1 was overexpressed to validate whether ENAH impacted the biological events of HCC cells through mediating Notch signaling. Results revealed that ENAH expression was elevated in HCC tissues and cells and associated with poor prognosis. ENAH deficiency mitigated proliferation, invasion and migration of HCC cells. Mechanistically, ENAH was positively correlated with SF3B4 in HCC tissues. SF3B4 could bind to ENAH mRNA and stabilized ENAH. Besides, ENAH activated Notch signaling. Notch1 up-regulation reversed the influence of ENAH knockdown on biological events of HCC cells. Collectively, ENAH regulated by SF3B4 promoted the development of HCC through activating Notch signaling, which identified ENAH as a potent molecular target for HCC therapy and prognosis.

Effects and Mechanism of Berberine on the Dexamethasone-Induced Injury of Human Tendon Cells.

OBJECTIVE: To investigate the effects of berberine (Berb) on dexamethasone- (Dex-) induced injury of human tendon cells and its potential mechanism. METHODS: CCK-8 assay was used to explore the appropriate concentration of Dex-induced injury of tendon cells and the doses of Berb attenuates Dex cytotoxicity; cell wound healing assay was used to detect the effects (P < 0.05) of Berb and Dex on the migration ability of tendon cells; flow cytometry was used to measure cell apoptosis; DCF DA fluorescent probe was used to measure the ROS activity of cells. Western blotting was used to detect the expression of phenotype related factors including smooth muscle actin α (SMA-α), type I collagen (Col I), col III, apoptosis-related factors, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, and PI3K/AKT. RESULTS: CCK-8 assay showed that 1-100 µM Dex significantly inhibited the proliferation of tendon cells in a concentration-dependent manner (P < 0.05), where the inhibitory effect of 100 µM Dex was most significant (P < 0.005), and the pretreatment of 150, 200 µM Berb could reverse those inhibitions (all P < 0.05). Compared with the control group, Dex significantly inhibited cell migration (P < 0.05), while Berb pretreatment could enhance cell migration (P < 0.05). Flow cytometry and ROS assay showed that Dex could induce apoptosis and oxidative stress response of tendon cells (all P < 0.05), while Berb could reverse those responses (P < 0.05). Western blot showed that Dex could inhibit the expression of the col I and III as well as α-SMA (all P < 0.05) and enhance the expression of apoptosis-related factors including cleaved caspase-3 and cleaved caspase-9 (all P < 0.05). Besides, Dex could also inhibit the activation of the PI3K/AKT signaling pathway (all P < 0.05), thus affecting cell function, while Berb treatment significantly reversed the expression of those above proteins (all P < 0.05). CONCLUSION: Berb attenuated DEX induced reduction of proliferation and migration, oxidative stress, and apoptosis of tendon cells by activating the PI3K/AKT signaling pathway and regulated the expression of phenotype related biomarkers in tendon cells. However, further studies are still needed to clarify the protective effects of Berb in vivo.

[Effect of hydrogen sulfide on H2O2-stimulated primary neonatal rat cardiomyocytes].

OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on H2O2-stimulated primary neonatal rat cardiomyocytes and related mechanism. METHODS: Primary neonatal rat cardiomyocytes were treated with various concentrations of H2O2 (10, 100, 1000 µmol/L) for 24 h to establish the oxidative stress-induced cell injury model after 3 days' conventional culture. In addition, different concentrations of NaHS (1, 10, 100 µmol/L) were added to cardiomyocytes in the absence and presence of 100 µmol/L H2O2 for 24 h. The viability of cardiomyocytes was measured by MTT assay. The SOD vitality was measured by xanthine oxidase method and MDA content was determined by thiobarbituric acid colorimetric method. LDH activity was measured by chemical colorimetric method. The percentage of apoptotic cells was assessed by flow cytometry (FCM). The mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 (Rh123) staining and photofluorography. The level of reactive oxygen species (ROS) in cardiomyocytes was measured by DCFH-DA staining and photofluorography. RESULTS: Cell viability and SOD vitality were significantly reduced while MDA content and LDH activity were significantly increased with increasing H2O2 concentrations. These effects could be partly reduced by cotreatment with H2O2 in a concentration-dependent manner (all P < 0.05). Compared with control group, the DCF fluorescence intensity significantly increased in the 100 µmol/L H2O2 group (P = 0.003), which could be attenuated by NaHS in a dose-dependent manner. Compared with control group, the MMP significantly decreased in the 100 µmol/L H2O2 group (P = 0.000), which could be partly reversed by cotreatment with NaHS in a dose-dependent manner. Moreover, H2O2 treatment also significantly reduced 100 µmol/L H2O2 induced apoptosis in a dose-dependent manner. CONCLUSION: H2S protects primary neonatal rat cardiomyocytes against H2O2-induced oxidative stress injury through inhibition of H2O2 induced overproduction of ROS, dissipation of MMP and apoptosis.

[Effects of simvastatin on homocysteine-induced endothelial dysfunction and inflammatory response].

OBJECTIVE: To investigate the effects of simvastatin (SIM) on homocysteine (HCY)-induced endothelial dysfunction and inflammatory response. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from the umbilical cords from healthy lying-in women and cultured and added with HCY of the concentrations of 0.1, 0.25, 0.5, and 1 mmol/L respectively, or HCY 0.25 mmol/L + SIM of the concentrations of 1, 10 and 20 micromol/L respectively for 1 hour. ELISA was used to detect the cell viability with MTT method. Western blotting was used to examine the protein expression of the cell inflammatory factors, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, macrophage chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1, ELISA was used to detect the contents of the cell inflammatory factors. RESULTS: HCY of different doses inhibited the viability of HUVECs dose-dependently (all P < 0. 01). The survival rates of the HCY-induced HUVECs pretreatment by SIM of the concentrations of 1, 10 and 20 micromol/L for 1 hour were 1.72 +/- 0.03 times, 2.54 +/- 0.09 times, and 3.14 +/- 0.11 times respectively that of the control group (all P < 0. 01). HCY of different concentration of 0.25 mmol/L increased the protein expression of TNF-alpha, IL-6, MCP-1, and ICAM-1 significantly; however, the expression levels of TNF-alpha, IL-6, MCP-1, and ICAM-1 of the 0.25 mmol/L HCY-treated HUVECs that were pretreated by SIM of the concentration of 10 micromol/L for 1 hour were, 0.23 +/- 0.05, 0.14 +/- 0.03, 0.13 +/- 0.04, and 0.21 +/- 0.07 respectively, not significantly different from those at the time of 0 hour (all P > 0.05). CONCLUSION: Simvastatin inhibits the homocysteine-induced endothelial impairment and inflammatory response.