A Systematic Review on Different Treatment Methods of Bone Metastasis from Cancers

Background and objective Skeletal metastase is one of the most common complications related to advanced cancer. The aim of this study is to analyze the effectiveness and safety of radiotherapy plus intravenous bisphosphonates versus radiotherapy alone for treating bone metastasis. Methods We searched the Cochrane Library, PubMed, EMBASE, CBM, CNKI and VIP, as well as the reference lists of reports and reviews. The quality of included trials was evaluated by the Cochrane Handbook. Data were extracted and evaluated by two reviewers independently. The Cochrane Collaboration’s Rev-Man 5.0 was used for data analysis. Results Twenty-two trials involving 1 585 patients were included. Compared with radiotherapy alone, radiotherapy plus intravenous bisphosphonates was more effective in total effective rate of pain relive (RR=1.21, 95%CI: 1.13-1.30, P < 0.001), average abated time (WMD=16.00, 95%CI: 10.12-21.88, P < 0.001), and quality of life (RR=1.25, 95%CI: 1.08-1.45, P=0.003, with significant differences. Side effects have no significant differences between the two groups except fever (RR=5.61, 95%CI: 3.11-10.13, P < 0.001). Conclusion Current evidence supports more effective of radiotherapy plus intravenous bisphosphonates for bone metastases. The combine treatment is safe and effective

Betaine Inhibits Interleukin-1β Production and Release: Potential Mechanisms

Betaine is a critical nutrient for mammal health, and has been found to alleviate inflammation by lowering interleukin (IL)-1β secretion; however, the underlying mechanisms by which betaine inhibits IL-1β secretion remain to be uncovered. In this review, we summarize the current understanding about the mechanisms of betaine in IL-1β production and release. For IL-1β production, betaine affects canonical and non-canonical inflammasome-mediated processing of IL-1β through signaling pathways, such as NF-κB, NLRP3 and caspase-8/11. For IL-1β release, betaine inhibits IL-1β release through blocking the exocytosis of IL-1β-containing secretory lysosomes, reducing the shedding of IL-1β-containing plasma membrane microvesicles, suppressing the exocytosis of IL-1β-containing exosomes, and attenuating the passive efflux of IL-1β across hyperpermeable plasma membrane during pyroptotic cell death, which are associated with ERK1/2/PLA2 and caspase-8/A-SMase signaling pathways. Collectively, this review highlights the anti-inflammatory property of betaine by inhibiting the production and release of IL-1β, and indicates the potential application of betaine supplementation as an adjuvant therapy in various inflammatory diseases associating with IL-1β secretion

Case report: Acute pancreatitis in lung adenocarcinoma with small cell transformation after multiple line targeted therapy

In lung cancer, metastasis to the liver, bones, brain, and adrenal glands is more commonly observed, whereas pancreatic metastasis from lung cancer is relatively rare. We present a case of a patient with an 8-year history of lung adenocarcinoma (LUAD) who was admitted to our institution exhibiting symptoms consistent with acute pancreatitis. Subsequent histopathological examination through puncture confirmed the occurrence of pancreatic metastasis originating from small cell lung cancer (SCLC). During a multidisciplinary team discussion, we reached a consensus in diagnosing the patient with post-transformation small cell carcinoma alongside moderately severe pancreatitis, which was determined to be a consequence of pancreatic metastasis. The patient received a regimen of etoposide and cisplatin chemotherapy. This unique clinical case highlights the importance of further investigating the factors contributing to pancreatic metastasis in patients with lung cancer, as the underlying mechanisms remain unclear. Understanding these exceptional metastatic events is vital in devising effective therapeutic strategies and improving patient prognosis. Our findings emphasize the need for continued surveillance and comprehensive management of lung cancer patients, particularly those with resistant forms of the disease, to promptly identify and address the progression of metastatic events to uncommon sites such as the pancreas

Orai1 and Stim1 Mediate the Majority of Store-Operated Calcium Entry in Multiple Myeloma and Have Strong Implications for Adverse Prognosis

Background/Aims: Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite the development and application of novel agents, MM still undergoes an aggressive and incurable course in the vast majority of patients. Ca2+ is one of the critical regulators of cell migration. Ca2+ influx is essential for the migration of various types of cells including tumor cells. However, the role of store-operated calcium entry (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been reported in MM cell survival. Methods: We evaluated the expression of Stim1 and Orai1 (two key regulators of SOC) in MM tissues and cell lines by immunohistochemical assay, quantitative real-time PCR assay and western blot. MM cell lines were pretreated with pharmacological blockers and siRNAs, and then MM cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the expression of Stim1 (or Orai1) level and outcome in MM were assessed by using Progress Free Survival (PFS). Results: Stim1 and Orai1 were both abundantly expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated with the clinical outcome of MM. Conclusion: The Stim1/Orai1-mediated signaling participates in the pathogenesis of MM, which represents an attractive target for future therapeutic intervention

In utero Exposure to Atrazine Disrupts Rat Fetal Testis Development

Atrazine (ATR) is a commonly used agricultural herbicide and a potential endocrine disruptor that may cause testicular dysgenesis. The objective of the present study was to investigate the effects of atrazine on fetal testis development after in utero exposure. Female Sprague-Dawley rats were gavaged daily with vehicle (corn oil, control) or atrazine (25, 50, and 100 mg/kg body weight/day) from gestational day 12 to 21. Atrazine dose-dependently decreased serum testosterone levels of male pups, with a significant difference from the control recorded at a dose of 100 mg/kg. In addition, atrazine significantly increased fetal Leydig cell aggregation at a dose of 100 mg/kg. Atrazine increased fetal Leydig cell number but not Sertoli cell number. However, atrazine down-regulated Scarb1 and Cyp17a1 in the fetal Leydig cell per se and Hsd17b3 and Dhh in the Sertoli cell per se. These results demonstrated that in utero exposure to atrazine disrupted rat fetal testis development

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

A Preliminary Study on the Resolution of Electro-Thermal Multi-Physics Coupling Problem Using Physics-Informed Neural Network (PINN)

The problem of electro-thermal coupling is widely present in the integrated circuit (IC). The accuracy and efficiency of traditional solution methods, such as the finite element method (FEM), are tightly related to the quality and density of mesh construction. Recently, PINN (physics-informed neural network) was proposed as a method for solving differential equations. This method is mesh free and generalizes the process of solving PDEs regardless of the equations’ structure. Therefore, an experiment is conducted to explore the feasibility of PINN in solving electro-thermal coupling problems, which include the electrokinetic field and steady-state thermal field. We utilize two neural networks in the form of sequential training to approximate the electric field and the thermal field, respectively. The experimental results show that PINN provides good accuracy in solving electro-thermal coupling problems

A Preliminary Study on the Resolution of Electro-Thermal Multi-Physics Coupling Problem Using Physics-Informed Neural Network (PINN)

The problem of electro-thermal coupling is widely present in the integrated circuit (IC). The accuracy and efficiency of traditional solution methods, such as the finite element method (FEM), are tightly related to the quality and density of mesh construction. Recently, PINN (physics-informed neural network) was proposed as a method for solving differential equations. This method is mesh free and generalizes the process of solving PDEs regardless of the equations&rsquo; structure. Therefore, an experiment is conducted to explore the feasibility of PINN in solving electro-thermal coupling problems, which include the electrokinetic field and steady-state thermal field. We utilize two neural networks in the form of sequential training to approximate the electric field and the thermal field, respectively. The experimental results show that PINN provides good accuracy in solving electro-thermal coupling problems

Pathological Mechanistic Studies of Osimertinib Resistance in Non-Small-Cell Lung Cancer Cells Using an Integrative Metabolomics-Proteomics Analysis

Background. Osimertinib is the first-line therapeutic option for the T790M-mutant non-small-cell lung cancer and the acquired resistance obstructs its application. It is an urgent challenge to identify the potential mechanisms of osimertinib resistance for uncovering some novel therapeutic approaches. Methods. In the current study, the cell metabolomics based on ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry and the qualitative and tandem mass tags quantitative proteomics were performed. Results. 54 differential metabolites and 195 differentially expressed proteins were, respectively, identified. The amino acids metabolisms were significantly altered. HIF-1 signaling pathway modulating P-glycoproteins expression, PI3K-Akt pathway regulating survivin expression, and oxidative phosphorylation were upregulated, while arginine and proline metabolism regulating NO production and glycolysis/gluconeogenesis were downregulated during osimertinib resistance. Conclusion. The regulation of HIF-1 and PI3K-Akt signaling pathway, energy supply process, and amino acids metabolism are the promising therapeutic tactics for osimertinib resistance