MR-tomographischer Befund bei Patienten mit Kniegelenkbeschwerden in Abhängigkeit von der beruflichen und außerberuflichen Gelenkbelastung

Die Gonarthrose als multikausale chronische Erkrankung des Kniegelenks ist die weltweit häufigste Gelenkerkrankung. Ursächlich liegt ein Missverhältnis von Belastbarkeit und mechanischer Beanspruchung des Gelenkknorpels zugrunde, das zur progredienten Schädigung der kartilaginären und ossären Gelenkstrukturen sowie des umgebenden Weichteilmantels führt. Die vorliegende Arbeit untersucht detailliert den MR-tomographischen Befund am Kniegelenk in Abhängigkeit von der Kniebelastung in Beruf und Freizeit. Die Gelenkbelastung wurde individuell im strukturierten Interview mittels eines modifizierten Tegner-Scores erfasst. Es ergeben sich erstmalig Hinweise auf ein belastungskonformes Schadensbild einer durch berufliches Knien und Hocken im Sinne der neuen Berufskrankheit Gonarthrose BK 2112

The Particle Swarm Optimization Algorithm with Adaptive Chaos Perturbation

Aiming at the two characteristics of premature convergence of particle swarm optimization that the particle velocity approaches 0 and particle swarm congregate, this paper learns from the annealing function of the simulated annealing algorithm and adaptively and dynamically adjusts inertia weights according to the velocity information of particles to avoid approaching 0 untimely. This paper uses the good uniformity of Anderson chaotic mapping and performs chaos perturbation to part of particles based on the information of variance of the population’s fitness to avoid the untimely aggregation of particle swarm. The numerical simulations of five test functions are performed and the results are compared with several swarm intelligence heuristic algorithms. The results shows that the modified algorithm can keep the population diversity well in the middle stage of the iterative process and it can improve the mean best of the algorithm and the success rate of search

Colloidal quantum dots and metal halide perovskite hybridization for solar cells stability and performance enhancement

Metal halide perovskites and colloidal quantum dots (QDs) are two emerging class of photoactive materials that has been attracted considerable attention for next-generation high-performance solution-processed solar cells. In particular, the hybridization of these two materials has been recently demonstrated remarkable performance enhancement due to the complementary nature of the two constituents. In this review, we will highlight the recent progress of QDs and perovskite hybridization in solar cell applications. More specifically, the unique properties of monophase perovskite QDs will be summarised which are demonstrated by homogeneously hybridizing perovskite QDs into perovskite lattice. We also discuss the recent progress in heterogeneously hybridizing discrete colloidal QDs into perovskite layers which exhibit significant perovskite film stability enhancement as well as corresponding solar cell performance improvement. PbS QDs, other chalcogenides QDs, as well as emerging two-dimensional QDs, are further accounted through multiple methods, such as bilayer architectures, core-shell structures or blending multiple QDs into perovskite layers. In the end, an outlook perspective of this field has been proposed to point out several challenges and possible solutions

Combining PD-1 or PD-L1 inhibitors with chemotherapy is a good strategy for the treatment of extensive small cell lung cancer: A retrospective analysis of clinical studies

ObjectivesTo provide an updated systematic review and meta-analysis of published randomized controlled trials (RCTs) of the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors combined with chemotherapy versus chemotherapy alone in the treatment of extensive-stage small-cell lung cancer (ES-SCLC).MethodsPubMed, Web of Science, Embase, Clinicaltrials and the Cochrane Library were systematically searched to extract RCTs concerning the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy versus chemotherapy alone in the treatment of ES-SCLC from the time of database inception to October 31, 2022. The literature was independently selected, information was extracted and the risk of bias of the RCTs was evaluated according to the inclusion and exclusion criteria. Stata14.0 was used for the meta-analysis.ResultsSix studies involving 2,600 patients were included in the analysis. The results of the meta-analysis showed that the combination of PD-1/PD-L1 inhibitors significantly improved the OS (HR: 0.73, 95% CI: 0.66-0.80; P<0.0001), prolonged PFS (HR: 0.66,95% CI: 0.55-0.79; P<0.0001) and did not increase overall incidence of treatment-related adverse events (TRAEs) (RR: 1.03, 95% CI: 0.97-1.09; P=0.330) in ES-SCLC patients compared with chemotherapy alone. The subgroup analysis found that patients with negative PD-L1 expression (< 1%) benefited in OS, whereas patients with positive PD-L1 expression (≥1%) had no statistically significant difference in OS. There was a statistically significant difference in PFS between PD-L1-negative (< 1%) and PD-L1-positive (≥1%) patients. The addition of a PD-1 inhibitor or PD-L1 inhibitor to the chemotherapy regimen can improve OS and prolong PFS in patients with ES-SCLC.ConclusionsPD-1/PD-L1 inhibitors combination chemotherapy significantly improves PFS and OS in ES-SCLC patients without increasing the overall incidence of TRAEs

APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b

Increasing evidence suggests different, not completely understood roles of microRNA biogenesis in the development and progression of lung cancer. The overexpression of the DNA repair protein apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an important cause of poor chemotherapeutic response in lung cancer and its involvement in onco-miRNAs biogenesis has been recently described. Whether APE1 regulates miRNAs acting as prognostic biomarkers of lung cancer has not been investigated, yet. In this study, we analyzed miRNAs differential expression upon APE1 depletion in the A549 lung cancer cell line using high-throughput methods. We defined a signature of 13 miRNAs that strongly correlate with APE1 expression in human lung cancer: miR-1246, miR-4488, miR-24, miR-183, miR-660, miR-130b, miR-543, miR-200c, miR-376c, miR-218, miR-146a, miR-92b and miR-33a. Functional enrichment analysis of this signature revealed its biological relevance in cancer cell proliferation and survival. We validated DICER1 as a direct functional target of the APE1-regulated miRNA-33a-5p and miR-130b-3p. Importantly, IHC analyses of different human tumors confirmed a negative correlation existing between APE1 and Dicer1 protein levels. DICER1 downregulation represents a prognostic marker of cancer development but the mechanisms at the basis of this phenomenon are still completely unknown. Our findings, suggesting that APE1 modulates DICER1 expression via miR-33a and miR-130b, reveal new mechanistic insights on DICER1 regulation, which are of relevance in lung cancer chemoresistance and cancer invasiveness

Inhibition of Cyclin D1 Expression in Human Glioblastoma Cells is Associated with Increased Temozolomide Chemosensitivity

Background/Aims: Cyclin D1 (CCND1) is frequently overexpressed in malignant gliomas. We have previously shown ectopic overexpression of CCND1 in human malignant gliomas cell lines. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blot (WB) was performed to investigate the expression of CCND1 in glioma tissues and cell lines. The biological function of CCND1 was also investigated through knockdown and overexpression of BCYRN1 in vitro. Results: Here we reported that CCND1 expression was positively associated with the pathological grade and proliferative activity of astrocytomas, as the lowest expression was found in normal brain tissue (N = 3) whereas the highest expression was in high-grade glioma tissue (N = 25). Additionally, we found that the expression level of CCND1 was associated with IC50 values in malignant glioma cell lines. Forced inhibition of CCND1 increased temozolomide efficacy in U251 and SHG-44 cells. After CCND1 overexpression, the temozolomide efficacy decreased in U251 and SHG-44 cells. Colony survival assay and apoptosis analysis confirmed that CCND1 inhibition renders cells more sensitive to temozolomide treatment and temozolomide-induced apoptosis in U251 and SHG-44 cells. Inhibition of P-gp (MDR1) by Tariquidar overcomes the effects of CCND1 overexpression on inhibiting temozolomide-induced apoptosis. Inhibition of CCND1 inhibited cell growth in vitro and in vivo significantly more effectively after temozolomide treatments than single temozolomide treatments. Finally, inhibition of CCND1 in glioma cells reduced tumor volume in a murine model. Conclusion: Taken together, these data indicate that CCND1 overexpression upregulate P-gp and induces chemoresistance in human malignant gliomas cells and that inhibition of CCND1 may be an effective means of overcoming CCND1 associated chemoresistance in human malignant glioma cells

Identification of disease-related genes and construction of a gene co-expression database in non-alcoholic fatty liver disease

Background: The mechanism of NAFLD progression remains incompletely understood. Current gene-centric analysis methods lack reproducibility in transcriptomic studies.Methods: A compendium of NAFLD tissue transcriptome datasets was analyzed. Gene co-expression modules were identified in the RNA-seq dataset GSE135251. Module genes were analyzed in the R gProfiler package for functional annotation. Module stability was assessed by sampling. Module reproducibility was analyzed by the ModulePreservation function in the WGCNA package. Analysis of variance (ANOVA) and Student’s t-test was used to identify differential modules. The receiver operating characteristic (ROC) curve was used to illustrate the classification performance of modules. Connectivity Map was used to mine potential drugs for NAFLD treatment.Results: Sixteen gene co-expression modules were identified in NAFLD. These modules were associated with multiple functions such as nucleus, translation, transcription factors, vesicle, immune response, mitochondrion, collagen, and sterol biosynthesis. These modules were stable and reproducible in the other 10 datasets. Two modules were positively associated with steatosis and fibrosis and were differentially expressed between non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver (NAFL). Three modules can efficiently separate control and NAFL. Four modules can separate NAFL and NASH. Two endoplasmic reticulum related modules were both upregulated in NAFL and NASH compared to normal control. Proportions of fibroblasts and M1 macrophages are positively correlated with fibrosis. Two hub genes Aebp1 and Fdft1 may play important roles in fibrosis and steatosis. m6A genes were strongly correlated with the expression of modules. Eight candidate drugs for NAFLD treatment were proposed. Finally, an easy-to-use NAFLD gene co-expression database was developed (available at https://nafld.shinyapps.io/shiny/).Conclusion: Two gene modules show good performance in stratifying NAFLD patients. The modules and hub genes may provide targets for disease treatment

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Purpose: To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. Results: Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010). Experimental Design: We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control. Conclusions: Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-na\uefve serum APE1 level, which correlated with its tissue level inversely associated with progressionfree survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival

Comparative study of the gasification of coal and its macerals and prediction of the synergistic effects under typical entrained-bed pulverized coal gasification Conditions

This research is focused on the gasification performance of coal and its corresponding macerals as well as on the interactions among macerals under typical gasification conditions by Aspen Plus modeling. The synergistic coefficient was employed to show the degree of interactions, while the performance indicators including specific oxygen consumption (SOC), specific coal consumption (SCC), cold gas efficiency (CGE), and effective syngas (CO + H2) content were used to evaluate the gasification process. Sensitivity analyses showed that the parent coal and its macerals exhibited different gasification behaviors at the same operating conditions, such as the SOC and SCC decreased in the order of inertinite > vitrinite > liptinite, whereas CGE changed in the order of liptinite > vitrinite > inertinite. The synergistic coefficients of SOC and SCC for the simulated coals were in the range of 0.94–0.97, whereas the synergistic coefficient of CGE was 1.05–1.13. Moreover, it was found that synergistic coefficients of gasification indicators correlated well with maceral contents. In addition, the increase in temperature was found to promote the synergistic coefficients slightly, whilst at an oxygen to coal mass ratio of 0.8 and a steam to coal mass ratio of 0.8, the highest synergistic coefficient was obtained