Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. ⋯ Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.
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MicroRNAs have been reported to play an important role in tumor development and progression by targeting oncogenes and tumor suppressors. miR-23a has been described as significantly upregulated in multiple cancers and involved in tumorigenesis. The aim of this study was to evaluate the potential roles of miR-23a in pancreatic ductal adenocarcinoma (PDAC). We found that miR-23a level was significantly increased in tissues of PDAC compared with that in the control by real-time PCR. ⋯ Moreover, restoration of FOXP2 impaired the pro-proliferation and proinvasion effects of miR-23a, indicating FOXP2 is a direct mediator of miR-23a functions. In conclusion, our findings suggest a novel miR-23a/FOXP2 link contributing to PDAC development and invasion. It may be a potential diagnostic and therapeutic target for PDAC.
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Clear health benefits are associated with intensive glucose control in type 1 diabetes mellitus (T1DM). However, maintaining near-normal glycemia remains an elusive goal for many patients, in large part owing to the risk of severe hypoglycemia. In fact, recurrent episodes of hypoglycemia lead to 'hypoglycemia-associated autonomic failure' (HAAF), characterized by defective counter-regulatory responses to hypoglycemia. ⋯ In this review, we present an overview of the literature focused on pharmacological approaches that may prevent the development of HAAF. The purported underlying mechanisms of HAAF include: 1) central mechanisms (opioid receptors, ATP-sensitive K+(KATP) channels, adrenergic receptors, serotonin selective receptor inhibitors, γ-aminobuyric acid receptors, N-methyl D-aspartate receptors); 2) hormones (cortisol, estrogen, dehydroepiandrosterone (DHEA) or DHEA sulfate, glucagon-like peptide-1) and 3) nutrients (fructose, free fatty acids, ketones), all of which have been studied vis-à-vis their ability to impact the development of HAAF. A careful review of the current literature reveals many promising therapeutic approaches to treat or reduce this important limitation to optimal glycemic control.
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This study aimed to investigate the associations among dementia, psychotropic medications and the risk of overall injuries. In this nationwide matched cohort study, a total of 144 008 enrolled patients ≥age of 50, with 36 002 study subjects who suffered from dementia and 108 006 controls matched for sex and age, from the Inpatient Dataset, for the period 2000-2010 in Taiwan were selected from the National Health Insurance Research Database, according to International Classification of Diseases, 9th Revision, Clinical Modification. When adjusting for the confounding factors, a Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 10 years of follow-up. ⋯ Psychotropic medications in the subjects with dementia were associated with the risk of injury (adjusted HR=0.217, 95% CI: 0.206 to 0.228, P<0.001). Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, were associated with the risk of injury in the study subjects after being adjusted for all comorbidities and medications (adjusted HR=0.712(95% CI=0.512 to 0.925, P<0.01)). In conclusion, patients who suffered dementia had a higher risk of developing injury, and the cognitive enhancers were associated with the decreased risk of injury.
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Observational Study
Biological tapering and sonographic flare in rheumatoid arthritis.
This study aimed to evaluate the risk of ultrasound-detected synovitis after antitumor necrosis factor (TNF) tapering in patients with rheumatoid arthritis. We recruited patients with rheumatoid arthritis who accepted TNF tapering. Gray-scale synovitis and power Doppler score in bilateral wrists at the dorsal radiolunate joint were evaluated. ⋯ The dose of biological tapering was the major determinant of ultrasound synovitis. Patients with moderate tapering had a higher risk of synovitis than those with mild tapering. We recommend not tapering by more than 25% to reduce subclinical inflammation and future joint damage.