Auswahl der wissenschaftlichen Literatur zum Thema „Ding wang tai zhi“

Statement of the problem. The twentieth century marked an increased interest in polyphonic music. The geography of polyphonic works for piano expanded significantly and a creative development of many Chinese composers, writing polyphonic piano pieces, took place. Today, polyphonic pieces make up a significant part of the piano repertoire in China, but they are little studied by musicologists and performers. The objective of this study – to reveal the contribution of Chinese composers to the creation of polyphonic piano repertoire of the XX – early XXI century. Analysis of the research and publications on the theme. А large number of modern authors study polyphony from the point of physical and mathematical research methods (Igarashi, Yu. & Ito, Masashi & Ito, Akinori, 2013; Weiwei, Zhang & Zhe, Chen, & Fuliang, Yin, 2016; Li, Xiaoquan et al. others, 2018). This approach does not reveal the factual musical component of polyphonic genres. In the 20th century, musicologists explored polyphony in musical folklore (Wiant, 1936; Fan Zuyin, 2004; Li Hong, 2015) and in professional Chinese composing (Sun Wei-bo, 2006, Winzenburg, 2018). The scientific novelty. This article studies the role of Chinese composers in the development of the world polyphonic piano repertoire of the XX – early XXI century. The methodological basis for the analysis of polyphonic works was the theoretical concepts of P. Hindemith, Peng Cheng, Fang Zuin, Li Hong, Sun Wei-bo. The results of the study. The research outcomes demonstrate the evolutionary development of the genre diversity of Chinese piano polyphony as well as those composers who created magnificent musical pieces. Conclusions. Chinese composers have fully mastered the art of modern counterpoint, represented by the genres of polyphonic program pieces (He Lu Ting), invention (Xiao Shu Xian, Du Qian, Sun Yun Yin, Chen Chen Quang), polyphonic suite (Ma Gui), large polyphonic cycle ( He Shao, Chen Hua Do, Xiao Shu Xian), fugue (Li Jun Yong, Yu Su Yan, Chen Gang, Tian Lei Lei, Duan Ping Tai, Zheng Zhong, Xiao Shu Xian) and small cycle “Prelude and Fugue” (Ding Shan Te, Chen Zhi Ming, Wang Li Shan). Creatively assimilating and rethinking the experience of Western polyphonists, Chinese composers have filled their polyphonic works with national features, firmly linking them with the origins of Chinese traditional and folk music. The polyphonic way of transmitting musical material becomes the most expressive at the moments of profound creativity and musical dramatization.

Abstract Background: While primary triple-negative breast cancer (TNBC) garners significant research attention, the genomic alterations that occur in metastasis remain insufficiently understood, especially within Asian populations. Furthermore, the genomic information obtained from the primary tumor inadequately guides metastatic cancer treatment, highlighting the critical need for in-depth investigations into metastatic TNBC. Methods: We constructed the largest cohort of TNBC metastases (n = 296) among advanced TNBC patients treated at Fudan University Shanghai Cancer Center (FUSCC) between October 2018 and December 2020. Comprehensive DNA sequencing was conducted on the collected metastatic samples to analyze genomic alterations associated with treatment response. The underlying mechanisms of specific biomarkers were also explored. Results: We presented the genomic landscape of 296 TNBC metastases, encompassing mutant genes, mutation sites and copy number variations. Through multidimensional analysis, significant disparities in TNBC were observed between Western and Asian populations, primary and metastatic tumors, as well as different metastatic sites. Notably, our findings underscore the importance of sequencing TNBC metastases to guide precision therapy, which was associated with longer progression-free survival compared to physician-chosen treatments, shedding light on the pivotal clinical value of genomic studies in metastatic settings. Furthermore, efficacy analysis suggested that PKD1 mutations enriched in metastases mediated resistance to immunotherapy. These findings were further validated through three clinical trials (NCT03805399, NCT04129996, and NCT04395989). Mechanistic studies unveiled the involvement of PKD1 in TNBC immune evasion by upregulating CCL2, thereby facilitating the recruitment of M2-type tumor-associated macrophages. Conclusion: Our study emphasizes the critical significance and necessity of genomic profiling of metastases in guiding precision therapy for TNBC. Moreover, our findings reveal PKD1 as a novel and promising biomarker for immunotherapy. Citation Format: Xiu-Zhi Zhu, Yi-Fan Zhou, Yun-Yi Wang, Xiao-Hong Ding, Xi Jin, Zhi-Ming Shao, Yi-Zhou Jiang, Zhong-Hua Wang. Genomic characterization of triple-negative breast cancer metastases reveals PKD1 as a novel biomarker for immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-08.

Abstract Background: Tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) remain controversial in predicting clinical outcomes of triple-negative breast cancer (TNBC), as outcomes do not always correlate with the expression of these biomarkers. Genomic and transcriptomic alterations that might contribute to the expression of these biomarkers remain incompletely uncovered. Methods: We evaluated PD-L1 immunohistochemistry (IHC) scores (SP142 and 28-8) and TILs in our TNBC multiomics dataset and two immunotherapy clinical trial cohorts. Then, we analyzed genomic and transcriptomic alterations correlated with TILs, PD-L1 expression and patient outcomes. Results: Despite TILs serving as a decent predictor for TNBC clinical outcomes, there remained exceptions. Our study revealed that several genomic alterations were correlated with unexpected events. Particularly, PD-L1 expression may cause a paradoxical relationship between TILs and prognosis in certain patients. Consequently, we classified TNBCs into four groups based on PD-L1 and TIL levels. The TIL-PD-L1+ and TIL+PD-L1- groups were not typical “hot” tumors; both were associated with worse prognoses and lower immunotherapy efficacy than TIL+PD-L1+ tumors. Copy number variation of PD-L1 and oncogenic signaling activation were correlated with PD-L1 expression in the TIL-PD-L1+ group, whereas GSK3B-induced degradation might cause undetectable PD-L1 expression in the TIL+PD-L1- group. These factors have the potential to affect the predictive function of both PD-L1 and TILs. Conclusions: Several genomic and transcriptomic alterations may cause paradoxical effects among TILs, PD-L1 expression and prognosis in TNBC. Investigating and targeting these factors will advance precision immunotherapy for TNBC patients. Keywords: Triple-negative breast cancer, PD-L1 expression, Tumor-infiltrating lymphocytes, Multiomics, Immunotherapy Citation Format: Han Wang, Xiao-Hong Ding, Cheng-Lin Liu, Yi Xiao, Ruo-Hong Shui, Yan-Ping Li, Chen Chen, Wen-Tao Yang, Zhi-Ming Shao, Yi-Zhou Jiang. Multiomics analysis reveals the landscape of PD-L1 expression in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-04.

Abstract Previous research suggests that the antineoplastic activity of sulindac is mediated by a cyclooxygenase (COX) independent mechanism involving dual inhibition of RAS and β-catenin signaling. ADT030 is a novel non-COX inhibitory sulindac-derivative designed to target RAS and phosphodiesterase 10 (PDE10) to block MAPK/AKT signaling and activate cGMP/PKG signaling to suppress oncogenic β-catenin transcription, respectively. ADT-030 potently and selectively inhibits growth and induces apoptosis of a variety of cancer cell lines and has robust antitumor activity in multiple mouse tumor models by oral administration. However, the impact of ADT-030 on the tumor microenvironment (TME) has not been examined. Here we report the antitumor activity and immunomodulatory effect of ADT-030 in preclinical models. We show that oral administration of ADT030 significantly inhibited the growth of multiple types of murine tumors in immunocompetent mice. In a metastatic breast tumor model (4T1), ADT-030 not only delayed the growth of the primary tumor but also reduced tumor metastasis, leading to improved mouse survival. Immunological analysis revealed marked reduction of MDSCs in mice, and increased T cell tumor infiltration after ADT-030 treatment. The antitumor activity of ADT030 was diminished in immunodeficient mice or immunocompetent mice depleted of CD8+ T cells, suggesting the dependence of ADT-030 on host immunity. Moreover, the combination of ADT-030 and anti-PD-1 antibody therapy led to further improved tumor growth control and mouse survival. Bulk and single-cell RNAseq is being conducted to determine the impact of ADT-030 on the cell compositions and transcriptomic changes in the TME. Altogether, our study provides insight into the mechanism of action of ADT-030 and underscores the potential of ADT-030 as a monotherapy or in combination with immunotherapies for RAS and Wnt/β-catenin driven cancers. Citation Format: Md Yeashin Gazi, Ogacheko Okoko, Xin Wang, Caitlin Brandle, Zhi-chun Ding, Amit Mitra, Veronica Ramirez-Alcantara, Xi Chen, Adam Keeton, Yulia Maxuitenko, Gary Piazza, Gang Zhou. A novel dual-acting RAS/β-catenin inhibitor activates antitumor immunity to potentiate cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 478.

Abstract Background: Anti-HER2 targeted therapy has achieved a series of breakthroughs. However, the current treatment strategy regarding HER2-positive breast cancer remains indiscriminate and lacks specificity, which limits the further improvement of overall treatment response and may lead to overtreatment and extra cost for some patients. Our study aims to reveal the molecular heterogeneity of HER2-positive breast cancer to guide a more precise treatment. Patients and methods: We selected HER2-positive breast cancer patients treated at Fudan University Shanghai Cancer Center between 2013 and 2014 and conducted genomic, transcriptomic, proteomic and metabolomic profiling. We then applied a non-negative matrix factorization algorithm on transcriptomic data to obtain an unsupervised classification. And we further studied the correlation between subtypes and corresponding treatment strategies in multiple cohorts of adjuvant and neoadjuvant therapy. For clinical accessibility, we developed convolutional neural network models through deep learning algorithm based on digital pathology to identify different subtypes. Additionally, we explored novel treatment strategies using the patient-derived organoids (PDOs) models. Results: We established a novel multiomics cohort of 180 HER2- breast cancer patients and classified them into four clinically significant molecular subtypes: (1) A classical HER2-enriched (HER2-CLA, N=51) subtype characterized by strong ERBB2 signaling and remarkable sensitivity to anti-HER2-targeted therapy (pathologic complete response with dual-targeted therapy: 93%). (2) an immunomodulatory (HER2-IM, N=36) subtype characterized by an immune-activated microenvironment and excellent prognosis with current treatment (no relapse in 97% of patients with a median follow-up of 86 months). Tumors of this subtype were therefore candidates for de-escalatory treatment. (3) A luminal-like (HER2-LUM, N=55) subtype distinguished by activated estrogen receptor signaling and (4) a basal/mesenchymal-like (HER2-BM, N=38) subtype enriched in activated receptor tyrosine kinase pathways. HER2-LUM and HER2- BM showed limited benefit from anti-HER2 therapy, and thus, add-on therapies might be needed. The overall area under the curve (AUC) of the convolutional neural network model based on digital pathology for identifying different subtypes is 0.77. In the exploration of novel treatment strategies, we found in the PDO model that the HER2-LUM subtype is more sensitive to a treatment regimen combining standard (chemotherapy and targeted therapy) with subsequent endocrine therapy and CDK4/6 inhibitors compared to other subtypes. Additionally, the HER2-BM subtype demonstrated greater sensitivity to treatment with a combination of EGFR inhibitors, PDGFR inhibitors or VEGFR inhibitors. Conclusion: We uncovered a high degree of molecular heterogeneity in HER2-positive breast cancer and illustrated its impact on treatment response. More precise treatment can be given according to the characteristics of different subtypes, which may achieve good efficacy and simultaneously reduce overtreatment and extra cost. The comprehensive profiling of HER2-positive breast cancers could also serve as an important resource for further exploration. Key Words: HER2-positive breast cancer cohort; molecular classification; targeted therapy; precision treatment; de-escalatory treatment. Citation Format: Yu-Wei Li, Ding Ma, Xiang-Rong Wu, Lei-Jie Dai, Shen Zhao, Yu-Zheng Xu, Xi Jin, Xiao Yi, Ying Wang, Cai-Jin Lin, Yi-Fan Zhou, Tong Fu, Wen-Tao Yang, Ming Li, Hong Lv, Yi-Zhou Jiang, Zhi-Ming Shao. Multiomics profiling and molecular classification refine precision treatment strategies for HER2-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS09-09.

Abstract Background: The emergence of anti-HER2 antibody–drug conjugates (ADCs) gave rise to the concept of HER2-low breast cancer (BC). HER2-low BC, which refers to a subgroup of HER2-negative BC with relatively higher HER2 expression (defined as 1+ or 2+ by immunohistochemistry (IHC) staining, without ERBB2 amplification), represents a rather large part of all BCs. However, the molecular nature and internal heterogeneity of HER2-low breast cancer remain obscure, and little is known about the ethnic differences of HER2-low BC. These limitations prevent us from a more precise patient selection and better drug combination strategies in the era of ADCs. To provide a comprehensive and intensive landscape of HER2-low BCs, we characterized HER2-low BCs both clinically and molecularly, which may help clinicians to achieve a more precise clinical management of these patients. Patients and methods: We established a HER2-low BC cohort (N=441) in early-stage Chinese patients and included HER2-0 (N=114) and HER2-positive (N=181) tumors as auxiliary cohorts to characterize HER2-low breast cancers both clinically and molecularly. Whole-exome sequencing, copy number variation assays, RNA sequencing and isobaric quantitative proteomics were conducted to obtain multiomics data. We compared the clinicopathological and molecular features between HER2-low tumors and other HER2 status subgroups stratified and not stratified hormone receptor (HR) status to clarify the distinctness of HER2-low BCs. And we analyzed the internal heterogeneity and ethnic difference of HER2-low BCs by characterizing a distinct subgroup of patients with unique driving mechanisms. Results: HER2-low BCs showed different molecular manifestations from HER2-0 BCs in different HR subgroups. In the HR-negative subgroup, HER2-low BCs consisted of more non-basal-like subtypes than HER2-0 tumors (40.0% vs. 9.1%, P = 0.002), which was an East Asian-specific phenomenon absent in Western cohorts. Also, HR-negative HER2-low BCs showed significant internal molecular heterogeneity, of which basal-like tumors closely mimicked HER2-0 BCs, whereas non-basal-like tumors were similar to HER2-positive BCs. These non-basal-like tumors were mostly categorized as HER2-enriched and luminal androgen receptor (LAR) subtypes. These molecularly distinct tumors might be driven by frequent mutation in PIK3CA and overexpression of FGFR4 and PTK6, which may also serve as therapeutic targets. These results have also been proved in a triple negative breast cancer cohort we reported previously. In contrast, in the HR-positive subgroup, HER2-low BCs showed no large-scale molecular difference from HER2-0 BCs or internal heterogeneity. However, HER2-low patients showed significantly better distant metastasis-free survival than HER2-0 patients (P = 0.029), which might be attributed to the lower loss/deletion levels of 17q11.12 and 17q21.31 in HER2-low breast cancers, in which genes including NF1 and BRCA1 are located. Conclusions: We reported the largest single-center multiomics HER2-low BC cohort in East Asian hitherto, and revealed its molecular nature, internal heterogeneity and ethnic difference. Compared with HR-positive diseases, HER2-low BCs in the HR-negative subgroup were more likely to be a molecularly distinct entity from HER2-0 tumors. Furthermore, HR-negative HER2-low BC also accommodates higher internal heterogeneity, which was ethnicity-specific in our East Asian cohort and may infer a different treatment response. Our work emphasized the need of a more precise stratification within HER2-low BCs and across ethnic groups, which has also been inferred by the results in the subgroup analysis of DESTINY-Breast04 trial. Citation Format: Lei-Jie Dai, Ding Ma, Yi Xiao, Xi Jin, Song-Yang Wu, Ya-Xin Zhao, Han Wang, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao. HER2-09 Multiomics Profiling Characterizes Distinct HER2-low Breast Cancer Subgroups in the East Asian Population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-09.

Introdução: O número crescente de infecções causadas por fungos e o surgimento de microrganismos resistentes tem sinalizado a necessidade da busca por novos agentes antifúngicos, fomentando a pesquisa em moléculas promissoras, como os O-glicosídeos. Objetivo: Partindo dessa premissa, objetivamos a síntese e investigação da atividade antifúngica do benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo isolado e quando associado com a anfotericina B. Material e métodos: Inicialmente foi sintetizado o benzil 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo a partir da reação entre o 3,4,6-tri-O-acetil-D-glucal e álcool benzílico via catálise ácida e irradiação ultrassônica seguida por sua hidrólise em meio básico para levar ao benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo. Este foi submetido à avaliação antifúngica por meio do método da microdiluição em caldo e estudo da associação com a anfotericina B pelo método de Checkerboard. Resultados: O benzil 4,6-di-O-acetil-2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo e o benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo foram obtidos em excelentes rendimentos 91 e 94 %, respectivamente. O benzil 2,3-didesoxi-α-D-eritro-hex-2-enopiranosídeo apresentou atividade antifúngica apenas contra as cepas de Candida albicans ATCC 76615, Candida albicans ATCC 76485 e Candida guilliermondiiLM 103, e sua associação com a anfotericina B foi classificada como indiferente. Conclusão: Estes resultados possibilitam futuros estudos envolvendo esta classe de moléculas, avaliação dos possíveis mecanismos de ação e avaliar outras atividades biológicas, uma vez que esta classe molecular sustenta a expectativa de baixa toxicidade, devido ao seu padrão de biocompatibilidade. Descritores: Síntese Química; Metabolismo dos Carboidratos; Fungos; Candida. Referências Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. 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Li, W., Wang, X., Wang, X., Wang, F., Du, Z., Fu, F., Wu, W., Wang, S., Mu, Z., Chen, C., Hu, X., Ding, J., Meng, Y., Qiu, P., Fan, H. (2020). Forensic characteristics and phylogenetic analyses of one branch of Tai‐Kadai language‐speaking Hainan Hlai (Ha Hlai) via 23 autosomal STRs included in the Huaxia™ Platinum System. Molecular Genetics & Genomic Medicine, 8(10), e1462. https://doi.org/10.1002/mgg3.1462.The above article, published online on 30 August 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Suzanne Hart, and Wiley Periodicals LLC. Following publication of this article, concerns were raised by a third party regarding consent and ethical approval for the research undertaken and reported in the article. The publisher and representatives of the journal’s editorial board undertook a review of the consent documentation provided, against the research performed and reported in the article. The review uncovered inconsistencies between the consent documentation and the research reported; the documentation was not sufficiently detailed to resolve the concerns raised. As a result, the parties have made the decision to retract the article. In addition, consent documentation did not give approval for data associated with this article to be shared publicly. The associated data for this article has been withdrawn from the publication record following a concern that the data could be used to identify those who have participated in the research. The authors were informed of the retraction but did not respond.