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Chendong Wang,1,* Bin Leng,1,* Ran You,1,* Zeyu Yu,1 Ya Lu,1 Lingfeng Diao,1 Hao Jiang,1 Yuan Cheng,2 Guowen Yin,1 Qingyu Xu1 1Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Cheng, Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 34 Changfu Street, Nanjing, Jiangsu, 210007, People’s Republic of China, Email chengyuan@csco.ac.cn Qingyu Xu, Department of Interventional Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, No. 42 Baiziting, Nanjing, Jiangsu, 210009, People’s Republic of China, Email xqy1984king@njmu.edu.cnPurpose: The response to transarterial chemoembolization (TACE) varies among individuals with hepatocellular carcinoma (HCC). This study aimed to identify a biomarker for predicting TACE response in HCC patients and to investigate its correlations with the tumor microenvironment and pre-TACE radiomics features.Patients and Methods: GSE104580 data were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene analysis and machine learning algorithms were used to identify genes for constructing the TACE failure signature (TFS). TFS scores were then calculated for HCC patients in The Cancer Genome Atlas (TCGA) cohort. After obtaining images from The Cancer Imaging Archive (TCIA), tumor labeling and radiomics feature extraction, the Rad-score model was generated. Correlation analysis was performed between the TFS score and the Rad-score. CIBERSORT, ssGSEA and TME analysis were performed to explore differences in the immune landscape among distinct risk groups. The immunotherapy response was compared between different groups.Results: ADH1C, CXCL11, EMCN, SPARCL1 and LIN28B were selected and incorporated into the TFS, which demonstrated satisfactory performance in predicting TACE response. Patients in the high TFS score group had poorer overall survival (OS) than those in the low TFS score group. The Rad-score model was constructed using six radiomics features, and the Rad-score was significantly correlated with hub gene expression and the TFS score. The high-TFS group was also characterized by an immunosuppressive tumor microenvironment and exhibited unfavorable responses to immunotherapy with PD-1 and CTLA-4 checkpoint inhibitors.Conclusion: This study established a transcriptomic biomarker for predicting the efficacy of TACE that correlates with radiomics features on pretreatment imaging, tumor immune microenvironment characteristics, and the efficacy of immunotherapy and targeted therapy in HCC patients.Keywords: hepatocellular carcinoma, transarterial chemoembolization, transcriptomic, radiomics, tumor microenvironment

Juanyong Zhao, Haiyang Liu, Ming Xia, Qian Chen, Lili Wan, Bin Leng, Chengyuan Tang, Guochun Chen, Yu Liu, Lei Zhang, Hong Liu Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Hong Liu; Lei Zhang, Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-13973116951 ; +86-18673174522, Email liuhong618@csu.edu.cn; zhanglei_xp@163.comPurpose: Accumulating clinical evidence showed that Tripterygium hypoglaucum (Lév.) Hutch (THH) is effective against IgA nephropathy (IgAN), but the mechanism is still unclear. This study is to evaluate the renal protective effect and molecular mechanism of THH against IgAN via network pharmacology, molecular docking strategy and experimental validation.Methods: Several databases were used for obtaining the active ingredients of THH, the corresponding targets, as well as the IgAN-related genes. The critical active ingredients, functional pathways, and potential for the combination of the hub genes and their corresponding active components were determined through bioinformatics analysis and molecular docking. The IgAN mouse model was treated with celastrol (1 mg/kg/d) for 21 days, and the aggregated IgA1-induced human mesangial cell (HMC) was treated with various concentrations of celastrol (25, 50 or 75 nM) for 48 h. The immunohistochemistry and Western blot techniques were applied to evaluate the protein expression of the predicted target. The cell counting kit 8 (CCK8) was used to detect HMC proliferation.Results: A total of 17 active ingredients from THH were screened, covering 165 IgAN-related targets. The PPI network identified ten hub targets, including PTEN. The binding affinity between the celastrol and PTEN was the highest (− 8.69 kJ/mol). The immunohistochemistry showed that celastrol promoted the expression of PTEN in the glomerulus of IgAN mice. Furthermore, the Western blot techniques showed that celastrol significantly elevated the expression of PTEN and inhibited PCNA and Cyclin D1 in vitro and in vivo. The CCK8 assay determined that celastrol decreased HMC proliferation in a concentration-dependent manner.Conclusion: This study suggests that activating PTEN by celastrol may play a pivotal role in THH alleviating IgAN renal injury.Keywords: IgA nephropathy, Tripterygium hypoglaucum (Lév.) Hutch, network pharmacology, molecular docking, celastrol, PTEN

The effectiveness of second-line therapy following initial first-line treatment for oligoprogression hepatocellular carcinoma (HCC) remain dismal. This study aims to evaluate whether the addition of radiotherapy to oligoprogressive lesions in combination with continuous first-line therapy can improve clinical outcomes in patients with oligoprogressive HCC compared with second-line therapy combined with radiotherapy or alone. A retrospective cohort of 84 patients exhibiting oligoprogression subsequent to initial HCC treatment were enrolled between October 2018 and April 2023. After propensity match based on age, sex, BCLC stage, Child-Pugh grade and ECOG grade, these patients underwent either radiotherapy for oligoprogression lesions combined with continuous first-line therapy (n = 31, 37%), radiotherapy for oligoprogression lesions along with second-line therapy (n = 27, 32%), or second-line therapy alone (n = 26, 31%). Our primary endpoint was progression-free survival (PFS) and second endpoint was overall survival (OS). When comparing oligoprogression lesion radiotherapy plus continuous first-line therapy to second-line therapy alone, the PFS was 7.45 months versus 3.2 months (95% CI 0.11-0.42, HR 0.22, p<0.0001). Similarly, when comparing oligoprogression lesion radiotherapy plus second-line therapy to second-line therapy alone, the PFS was 5 months versus 3.2 months (95% CI 0.24-0.76, HR 0.43, p = 0.0028). When comparing oligoprogression lesion radiotherapy plus first-line therapy to oligoprogression lesion radiotherapy plus second-line therapy, PFS was 7.45 months compared to 5 months (95% CI 0.89-2.58, HR 1.51, p = 0.13). The OS has not been reached. In comparison, the combination of radiotherapy with continuous first-line therapy has greater potential to benefit HCC patients than the combination of radiotherapy with switched second-line therapy or second-line therapy alone. The study suggests that incorporating radiotherapy into the management of oligoprogression in HCC without switching to second-line treatment and optimizing the role of first-line treatment may have potential clinical utility, providing insights for optimizing treatment strategies in this patient population. [ABSTRACT FROM AUTHOR]

Inefficient and ineffective management of technical product changes during ramp-up phases of new model ranges in series production endanger the defined time-to-market and, concurrently, a company's expected earnings. One of the research projects at the Bremen Institute of Industrial Technology and Applied Work Science at the University of Bremen deals with this topic, and, accompanied by industry, significant weaknesses with regard to the organizational aspects have been identified. Today's product change management processes are based on DIN 199/4, a German standard publicized by the German Institute for Standardization in 1981, which focuses on a documentation scheme for bills of materials as well as engineering drawings. Unfortunately, the management of a physical product change process is not described. The project, however, shows the organizational deficits in this area of research. This article points out the main weaknesses of today's product change management and proposes a new approach for a product change classification scheme as well as an approach for a new organization scheme for product change management teams in order to reduce product change implementation lead times. [ABSTRACT FROM AUTHOR]