Annals of medicine
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Cholangiocarcinoma (CCA) is a malignant tumor originating in the bile duct and its branching epithelium. Due to its high heterogeneity, there are no specific clinical indications at the early stage, the diagnosis is often in advanced CCA. With surgical resection, the 5-year postoperative survival rate (long-term survival rate) is very poor. ⋯ However, the current targeted therapy of CCA still has many challenges, such as adverse reactions, drug resistance, and individual differences. Therefore, the researches need to further explore the targeted therapy mechanism of CCA malignancies in depth, develop more effective and safe drugs, and accurately formulate plans based on patient characteristics to further improve patient prognosis in the future. This article reviews the recent progress of targeted therapy for CCA, aiming to provide a strategy for the research and clinical work of targeted therapy for CCA.
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Postoperative neurocognitive disorders (PND) are the most common neurological disorders following surgery and anaesthesia before and within 12 months after surgery, with a high prevalence in the geriatric population. PND can severely deteriorate the quality of life of patients, especially among the elderly, mainly manifested as memory loss, attention, decline and language comprehension disorders, mostly in elderly patients, with an incidence as high as 31%. Previous studies have also raised the possibility of accelerated cognitive decline and underlying neuropathological processes associated with diseases that affect cognitive performance (e.g. ⋯ Recent research has focused on mitochondrial homeostasis. In this paper, we present a review of various studies to better understand and characterize the mechanisms of associated cognitive dysfunction. As the biochemical basis of PND becomes more clearly defined, future treatments based on mitochondrial homeostasis modulation can prove to be very promising.
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Review
From suspicion to diagnosis: exploration strategy for suspected amyotrophic lateral sclerosis.
The diagnosis of amyotrophic lateral sclerosis (ALS) is based on evidence of upper and lower motor neuron degeneration in the bulbar, cervical, thoracic, and lumbar regions in a patient with progressive motor weakness, in the absence of differential diagnosis. Despite these well-defined criteria, ALS can be difficult to diagnose, given the wide variety of clinical phenotypes. ⋯ The main challenge is to establish a diagnosis based on robust clinical and paraclinical evidence without delaying treatment initiation by increasing the number of additional tests. This approach requires a thorough knowledge of the phenotypes of ALS and its main differential diagnoses.
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AURKA is a threonine or serine kinase that needs to be activated by TPX2, Bora and other factors. AURKA is located on chromosome 20 and is amplified or overexpressed in many human cancers, such as breast cancer. AURKA regulates some basic cellular processes, and this regulation is realized via the phosphorylation of downstream substrates. ⋯ It can promote the transcription and expression of oncogenes together with other transcription factors in the nucleus, including FoxM1, C-Myc, and NF-κB. In addition, it also sustains carcinogenic signaling, such as N-Myc and Wnt signaling. This article will focus on the role of AURKA in the nucleus and its carcinogenic characteristics that are independent of its kinase activity to provide a theoretical explanation for mechanisms of resistance to kinase inhibitors and a reference for future research on targeted inhibitors.
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In the last two decades, academic medical centers in the United States have faced a new challenge, dealing with breaches of medical professionalism in their staff, house staff, and medical students. Medical education settings have largely directed their professionalism efforts toward responding reactively to negative outliers. ⋯ Professionalism programs should be vested with the authority to implement an affirmative educational program intended to nurture and promote medical professionalism in each medical student, resident, fellow, and attending and utilize methods to that end employing both virtue and care ethics.