Annals of medicine
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A series of N-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound 4j exhibiting promising glioma growth inhibitory properties. Compound 4j was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. ⋯ Although exhibiting potency against glioma cells, 4j exhibited significantly less cytotoxicity against non-cancerous cells even at fourfold-fivefold the concentration. Herein we establish a novel biochemical kinase inhibitory function for N-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles and further report their anti-glioma activity in vitro for the first time. KEY MESSAGEAnti-glioma pyrano[2,3-c]pyrazole 4j inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. 4j also displayed PKBβ/AKT2 inhibitory activity. 4j is nontoxic towards non-cancerous cells.
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To evaluate the clinical characteristics and prognostic factors of hepatic systemic light chain (AL) amyloidosis. ⋯ Systemic light chain amyloidosis with hepatic involvement is associated with poor survival but rarely has specific manifestations. The significant increase of NT-proBNP and hyperbilirubinemia indicate a poor prognosis. Vigilance should be raised to the relevant clinical manifestations, early diagnosis and timely treatment can improve the prognosis. KEY MESSAGESSystemic light chain amyloidosis with hepatic involvement is associated with poor survival but rarely has specific manifestations.The significant increase of NT-proBNP and hyperbilirubinemia indicate a poor prognosis.
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Based on separate protective mechanisms related to lipid metabolism, viral cell entry and inflammation, fibrate treatment might be advantageous among patients who have been taking fibrates before SARS-CoV-2 infection and continue taking them during the infection. Based on published data on hospitalized COVID-19 patients, we recommend that the clinicians should ask their patients with metabolic syndrome who are already taking fibrates to continue fibrate treatment during the COVID-19 illness. This recommendation applies to both outpatients and hospitalized patients. ⋯ Obesity, diabetes, hypertension and dyslipidaemia, individually or clustered as a discrete phenotype, the metabolic syndrome, typically associate with a more severe course of COVID-19. Fibrate treatment seems to be most advantageous among patients who have been taken fibrates before SARS-CoV-2 infection and are continuing to take them during the infection. We recommend that the clinicians encourage their patients who are already taking fibrate to continue using the drug throughout the COVID-19 illness.
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Insulin-like growth factor binding protein-3 (IGFBP3) has been reported to be related to the risk of some cancers. Here we focussed on serum IGFBP3 as a possible biomarker of diagnosis and prognosis for oesophageal squamous carcinoma (ESCC). ⋯ We demonstrated that serum IGFBP3 was a potential biomarker of diagnosis and prognosis for ESCC. Meanwhile, the nomogram might help predict the prognosis of ESCC. Key MessageSerum IGFBP3 showed early diagnostic value in oesophageal squamous cell carcinoma with independent cohort validation. Moreover, serum IGFBP3 was identified as an independent prognostic risk factor, which was used to construct a nomogram with improved prognosis ability in oesophageal squamous cell carcinoma.
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A recent clinical practice guideline set forth recommendations for the administration of the 6 Minute Walk Test, including course set-up and using mathematical calculation to obtain the distance walked. In clinical practice and research, however, deviations from these protocols exist. ⋯ Adhering to 6 Minute Walk Test protocols, including the method of measuring the distance, is imperative to accurately interpret results and compare to existing data.Key messagesDespite recommendations for standardized administration of the 6 Minute Walk Test, deviations exist, including the method of which to obtain the total distance walked; either by use of mathematical calculation or a measuring wheel.In three different 6 minute walk test course configurations, including the American Thoracic Society's recommended protocol and the Academy of Neurologic Physical Therapy recommended protocol, the measuring wheel resulted in significantly larger distances than use of the mathematical calculation.Despite the measuring wheel able to account for the turns during the 6 Minute Walk Test, it is imperative for clinicians to utilize standardized procedures such as using mathematical calculation, in order to accurately track progress and compare to existing data, of which mathematical calculation was used to derive.