Optimal combination of MYCN differential gene and cellular senescence gene predicts adverse outcomes in patients with neuroblastoma

IntroductionNeuroblastoma (NB) is a common extracranial tumor in children and is highly heterogeneous. The factors influencing the prognosis of NB are not simple.MethodsTo investigate the effect of cell senescence on the prognosis of NB and tumor immune microenvironment, 498 samples of NB patients and 307 cellular senescence-related genes were used to construct a prediction signature.ResultsA signature based on six optimal candidate genes (TP53, IL-7, PDGFRA, S100B, DLL3, and TP63) was successfully constructed and proved to have good prognostic ability. Through verification, the signature had more advantages than the gene expression level alone in evaluating prognosis was found. Further T cell phenotype analysis displayed that exhausted phenotype PD-1 and senescence-related phenotype CD244 were highly expressed in CD8+ T cell in MYCN-amplified group with higher risk-score.ConclusionA signature constructed the six MYCN-amplified differential genes and aging-related genes can be used to predict the prognosis of NB better than using each high-risk gene individually and to evaluate immunosuppressed and aging tumor microenvironment

Position and orientation measurement technology for bolter miner body based on dual-screen visual target

Aiming at the problem that it is difficult to achieve the real-time and accurate measurement of the bolter miner’s position and orientation during the excavation process in coal mines, which leads to the difficulty in achieving directional excavation, a guidance method for bolter miner based on dual-screen visual target is proposed. Using two vertically installed light-sensitive imaging screens to form the dual-screen visual target surfaces and the indication laser emitted by the laser instrument presents light spots on the front and rear target surfaces. Combining with the visual measurement, high-precision raster calibration and other technology are applied to establish the mapping relationship of the spot centroid between 2D-3D coordinates, which is used to form the point cloud data of the coordinates. Based on the principle of grid indexing, coordinate transformation and Euler angle solving, combining with the biaxial inclinometer at the bottom of target to obtain the bolter miner body’s real-time position and orientation, the key points’ horizontal/vertical deviations relative to the roadway axis are calculated, which can provide data support for deviation correction during the excavation process. The off-target problem of the system is analyzed by constructing a mathematical model. Meanwhile, the effectiveness of the guidance method is verified by building an experimental platform. The experimental results indicate that this method can achieve a precision measurement of six-degrees-of-freedom spatial pose for the machine body. When the measurement distance is 9 m, the repeatability measurement precision of the yaw angle is better than 0.01º and the error of absolute measurement is less than 0.05º. Within the measurement range of 15−40 m, which uses the total station and mining laser to set the planning line, the measurement errors of key points’ horizontal/vertical deviations are less than 5 mm and 15 mm, respectively. The guiding system developed based on this method has also been successfully applied to the underground roadway excavation in coal mine, which fully meets the requirements of underground roadway excavation and the positioning of the machine body’s key points. The error characteristic of the guiding method is independent of the test distance. Also, all optical measurement functions involved in the method are realized inside the target, which can effectively shield the influence of the underground complex environment for the measurement function, and greatly improve the capacity of anti-dust interference in field application

Psoriasis comorbid with atherosclerosis meets in lipid metabolism

Psoriasis (PSO) is a common skin disease affecting approximately 1%–3% of the population, and the incidence rate is increasing yearly. PSO is associated with a dramatically increased risk of cardiovascular disease, the most common of which is atherosclerosis (AS). In the past, inflammation was considered to be the triggering factor of the two comorbidities, but in recent years, studies have found that lipid metabolism disorders increase the probability of atherosclerosis in patients with psoriasis. In this review, we discuss epidemiological studies, clinical treatment methods, risk factors, and lipid metabolism of psoriasis and atherosclerosis comorbidities

Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis

Background Delanzomib, a novel proteasome inhibitor, has demonstrated promising efficacy and antitumor ability in human multiple myeloma cell lines and patient‐derived cells. However, the potential therapeutic effects of delanzomib on breast cancer remain unknown. In this study, we show that delanzomib has antitumor effects and synergizes with doxorubicin (Dox) in human breast cancer cell lines. Methods Cell proliferation assay and flow cytometry were used to evaluate cell viability and apoptosis in eight human breast cancer cell lines after treatment with delanzomib or Dox. Essential molecules of the p53, MAPK, and apoptosis signaling pathways were analyzed by Western blotting. Results Delanzomib induced cell death and demonstrated synergism with Dox in all tested breast cancer cell lines. In addition, delanzomib enhanced the Dox‐induced phosphorylation of p38/JNK and the expression of transcriptional target proteins of p53, such as p21, p27, NOXA, and PUMA. Conclusion The combined regimen of the proteasome inhibitor delanzomib with Dox chemotherapy may become an effective strategy for breast cancer therapy

Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and β receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy