DR6 Augments Colorectal Cancer Cell Growth, Invasion, and Stemness by Activating AKT/NF-κB Pathway.

This study aims to elucidate the role and mechanisms of Death Receptor 6 (DR6), a member of the tumor necrosis factor receptor superfamily, in the malignant progression of colorectal cancer (CRC). The association of DR6 expression levels and CRC patient survival was examined using the CRC cohort data from GEPIA database. The functional role of DR6 in CRC cells was investigated by performing loss-of-function and gain-of-function experiments based on CCK-8 proliferation assay, transwell migration and invasion assay, and sphere-forming assays. Xenograft model of CRC cells in nude mouse was established to evaluate the impact of DR6 knockdown on CRC tumorigenesis. Elevated expression of DR6 was correlated with an unfavorable prognosis in CRC patients. In vitro functional assays demonstrated that silencing DR6 considerably suppressed the proliferation, migration, invasion, and stemness of CRC cells, whereas its overexpression showed an opposite effect. DR6 knockdown also attenuated tumor formation of CRC cells in the nude mice. Mechanistically, silencing DR6 reduced the phosphorylation of AKT and NF-κB in CRC cells, and the treatment with an AKT activator (SC79) abrogated the inhibitory effects of DR6 knockdown on the malignant features of CRC cells. Our data suggest that DR6 contributes to the malignant progression of CRC by activating AKT/NF-κB pathway, indicating its clinical potential as a prognostic marker and therapeutic target for CRC.

Safety and efficacy of minimally invasive McKeown esophagectomy in 1023 consecutive esophageal cancer patients: a single-center experience.

OBJECTIVE: By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center. METHODS: This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier method. RESULTS: For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%). CONCLUSIONS: This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications' morbidity, and acceptable long-term oncologic results.

CBX3 accelerates the malignant progression of glioblastoma multiforme by stabilizing EGFR expression.

CBX3, also known as HP1γ, is a major isoform of heterochromatin protein 1, whose deregulation has been reported to promote the development of human cancers. However, the molecular mechanism of CBX3 in glioblastoma multiforme (GBM) are unclear. Our study reported the identification of CBX3 as a potential therapeutic target for GBM. Briefly, we found that, CBX3 is significantly upregulated in GBM and reduces patient survival. In addition, functional assays demonstrated that CBX3 significantly promote the proliferation, invasion and tumorigenesis of GBM cells in vitro and in vivo. Mechanistically, Erlotinib, a small molecule targeting epidermal growth factor receptor (EGFR) tyrosine kinase, was used to demonstrate that CBX3 direct the malignant progression of GBM are EGFR dependent. Previous studies have shown that PARK2(Parkin) and STUB1(Carboxy Terminus of Hsp70-Interacting Protein) are EGFR-specific E3 ligases. Notably, we verified that CBX3 directly suppressed PARK2 and STUB1 at the transcriptional level through its CD domain to reduce the ubiquitination of EGFR. Moreover, the CSD domain of CBX3 interacted with PARK2 and regulated its ubiquitination to further reduce its protein level. Collectively, these results revealed an unknown mechanism underlying the pathogenesis of GBM and confirmed that CBX3 is a promising therapeutic target.

Promoting sports strength development based on the integration of physical fitness and national health / Promovendo o desenvolvimento da força esportiva com base na integração da aptidão física e da saúde nacional / Promoviendo el desarrollo de la fuerza deportiva sobre la base de una integración de la aptitud física y de la salud nacional

ABSTRACT Objective: Sports play a crucial role in China's national sportsmanship. Therefore, it is necessary to further promote China's development as a sports powerhouse. People's health needs to be raised to the pinnacle of the national fitness strategy, and the government should seriously implement people's health work. Methods: the construction of the "Powerful Country for Sports" and "Healthy China" provides a more precise direction for the development of national fitness and opens a broader path for the development of national health. The dream of a powerful country in sports has a long history, and different times have different definitions. Results: building a sports power is a strategic project for the development of modern socialist capability with Chinese characteristics. Accelerating the construction of a sports power is related to national prosperity and rejuvenation, and is closely related to the happiness of the people. Conclusions: the barrier preventing the sustainable development of national sports break and create a new driving force for the development of a sports power only by solving the problem of displacement in building a sports power and promoting the deep integration of national fitness and health. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Objetivo: O esporte desempenha um papel crucial no espírito esportivo nacional da China. Portanto, é necessário promover ainda mais o desenvolvimento da China como uma potência esportiva. A saúde das pessoas precisa ser elevada ao auge da estratégia nacional de aptidão física, e o governo deveria implementar seriamente o trabalho de saúde das pessoas. Métodos: a construção do "País poderoso para o esporte" e da "China saudável" fornece uma direção mais precisa para o desenvolvimento da aptidão física nacional e abre um caminho mais amplo para o desenvolvimento da saúde nacional. O sonho de um país poderoso no esporte tem uma longa história, e tempos diferentes têm definições diferentes. Resultados: a construção de uma potência esportiva é um projeto estratégico para o desenvolvimento de uma capacidade socialista moderna com características chinesas. Acelerar a construção de uma potência esportiva está relacionado com a prosperidade e o rejuvenescimento nacional, e está intimamente relacionado com a felicidade do povo. Conclusões: somente resolvendo o problema do deslocamento na construção de uma potência esportiva e promovendo a integração profunda da condição física e da saúde nacional se poderá quebrar a barreira que impede o desenvolvimento sustentável do esporte nacional e criar uma nova força motriz para o desenvolvimento de uma potência esportiva. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

Resumen Objetivo: Los deportes desempeñan un papel crucial en el espíritu deportivo nacional de China. Por lo tanto, es necesario seguir promoviendo el desarrollo de China como potencia deportiva. Es necesario elevar la salud del pueblo a la cúspide de la estrategia nacional de aptitud física, y el gobierno debe implementar seriamente el trabajo de salud de las personas. Métodos: la construcción del "País poderoso en deportes" y de la "China saludable" proporciona una dirección más precisa para el desarrollo de la aptitud física nacional y abre un camino más amplio para el desarrollo de la salud nacional. El sueño de un país poderoso en el deporte tiene una larga historia, y diferentes épocas tienen diferentes definiciones. Resultados: la construcción de una potencia deportiva es un proyecto estratégico para el desarrollo de la capacidad socialista moderna con características chinas. Acelerar la construcción de una potencia deportiva está relacionado con la prosperidad y el rejuvenecimiento nacionales, y está estrechamente relacionado con la felicidad del pueblo. Conclusiones: sólo resolviendo el problema del desplazamiento en la construcción de una potencia deportiva y promoviendo la integración profunda de la aptitud y la salud nacionales se puede romper la barrera que impide el desarrollo sostenible del deporte nacional y crear una nueva fuerza motriz para el desarrollo de una potencia deportiva. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Clinical analysis of the predictive value of recurrent laryngeal nerve lymph nodes status for supraclavicular lymph node metastasis in esophageal squamous cell carcinoma / 中国胸心血管外科临床杂志

@#Objective    To investigate the predictive value of recurrent laryngeal nerve lymph nodes (RLN) status for supraclavicular lymph node (SLN) metastasis in esophageal squamous cell carcinoma. Methods    We retrospectively analyzed the clinical data of 83 patients with esophageal squamous cell carcinoma who underwent McKeown three-field lymphadenectomy from January 2017 to April 2018 in our hospital, including 53 males and 30 females with an average age of 64.07±7.05 years. Results    The SLN metastasis rate of the patients was 24.1%. The rate in the thoracic and abdominal metastases positive (N1-3) group and negative (N0) group was 37.8% and 13.0%, respectively, with a statistical difference (P<0.05). The rate of SLN metastasis was significantly different between the RLN metastasis positive (RLN+) and negative (RLN–) groups (39.1% vs. 18.3%, P<0.05). One side of RLN metastasis could lead to SLN metastasis on the opposite side. No correlation between the SLN metastasis and age, gender, location, differentiation degree, maximum tumor diameter, T-staging or histologic type was observed (P>0.05). Multivariate analysis showed that lymph node metastasis in chest or abdomen was an independent predictor of SLN metastasis. Conclusion    RLN+ is not the independent predictor for SLN metastasis. SLN should be dissected in N1-3 patients with esophageal squamous cell carcinoma without considering tumor location and T-staging. Bilateral SLN dissection should be recommended even if RLN metastasis is only unilateral.