Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds

Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.     

结直肠癌与自然杀伤细胞的相关性探讨北大核心

目的:研究结直肠癌及其配对的癌旁组织的自然杀伤(nature killer,NK)细胞数量及分布情况。方法:结直肠癌及其配对的癌旁组织各40例,以SP免疫组化法检测NK细胞。结果:结直肠癌及其配对的癌旁组织中均未检测到NK细胞的浸润。结论:结直肠癌及其配对的癌旁组织中缺乏NK细胞浸润可能与肿瘤微环境、生理微环境、未知的NK细胞亚型相关,结直肠癌患者可能不适用NK细胞进行免疫治疗。     

Histological interpretation of temporal artery biopsies

Temporal artery biopsy is recommended for diagnosis of suspected giant cell arteritis, a systemic vasculitis of older adults. There is currently no formal consensus for histological interpretation of the biopsies. Typical histological findings include a transmural lymphocytic infiltrate with a population of macrophages resulting in destruction of the internal elastic lamina. However, it is a patchy process and multiple tissue levels must be examined. It is important to be aware of various subtle features that may lead to a diagnosis of arteritis, and immunohistochemistry can be helpful in some cases. Some biopsies show unusual features that could raise a differential diagnosis of alternative vasculitides. When there is no evidence of arteritis in a specimen, there are often non-specific features seen in the context of age-related changes. All of these histological patterns require close clinicopathological correlation to ensure correct interpretation.     

Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

新型驱动基因融合阳性非小细胞肺癌脑转移的研究进展北大核心

肺癌是我国最常见且死亡率最高的恶性肿瘤之一,随着表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)及活性氧1(ROS1)等驱动基因及其相应分子靶向药物的出现,晚期非小细胞肺癌的治疗和预后发生了革命性变化。此外,一些少见新型驱动基因融合,包括神经调节蛋白1(NRG1)、神经营养酪氨酸受体激酶(NTRK)和转染重排因子(RET),正逐渐发展成为全身性治疗选择。然而,这些罕见新型融合驱动基因在NSCLC脑转移中的作用机制,以及优化控制和预防脑转移的意义人们所知甚少。因此,本文就近几年罕见驱动基因融合在NSCLC脑转移中的研究进行综述。     

经颅磁刺激的多尺度建模仿真研究

经颅磁刺激是一种无创无痛的电磁刺激手段，被广泛应用于神经调控，在临床上对多种精神疾病和神经类疾病有明显的治疗效果。本文从电磁场建模仿真，细胞跨膜电位建模仿真，以及神经元响应建模仿真3个方面对经颅磁刺激多尺度建模仿真研究进行了详细的综述，并提出现阶段存在的问题以及对未来的展望。经颅磁刺激的多尺度建模仿真对磁刺激仪的设计开发具有指导意义，对磁刺激的导航系统提供重要的理论基础，有助于我们更好的理解电磁刺激的神经调控机制。     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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Functional outcomes after submandibular gland-sparing neck dissection in patients with oral squamous cell carcinoma

The feasibility of submandibular gland (SMG) preservation during neck dissection has been described. The aim of this study was to analyse the functional outcomes in patients undergoing SMG preservation during neck dissection for cT1–2N0 oral squamous cell carcinoma. Consecutive patients were divided into two groups based on the management of the SMG, and underwent a saliva flow test before surgery, 7 days after surgery, and at 3, 6, 9, and 12 months after surgery. All enrolled patients completed the fourth version of the University of Washington Quality of Life (UWQOL) questionnaire at 12 months after surgery. In patients who underwent SMG preservation during neck dissection, the flow rate at 7 days after surgery was significantly lower than that preoperative; however, it gradually returned to baseline at 9 months after surgery. The saliva flow rate at 9 months after surgery was similar to that at 12 months after surgery. Further, patients with SMG preservation had higher scores for the activity, swallowing, chewing, and saliva domains than patients without SMG preservation. The results of the study suggest that saliva secretion ability can be preserved following SMG-sparing neck dissection, and that SMG preservation improves postoperative quality of life.