Assessment of cerebrovascular reserve impairment using the breath-holding index in patients with leukoaraiosis

Many studies have demonstrated that leukoaraiosis is associated with impaired cerebrovascular reserve function. However, the definitive hemodynamic changes that occur in leukoaraiosis are not clear, and there are many controversies. This study aimed to investigate hemodynamic changes in symptomatic leukoaraiosis using transcranial Doppler ultrasonography and the breath-holding test in a Chinese Han population, from northern China. A total of 203 patients who were diagnosed with ischemic stroke or clinical chronic progressive ischemic symptoms were enrolled in this study, including 97 males and 106 females, with an age range of 43-93 years. The severity of leukoaraiosis was evaluated according to the Fazekas grading scale, and patients were divided into four groups accordingly. Grade 0 was no leukoaraiosis, and grades I, II, and III were mild, moderate, and severe leukoaraiosis, respectively, with 44, 79, 44, and 36 cases in each group. Transcranial Doppler ultrasonography and the breath-holding test were performed. The mean blood flow velocity of the bilateral middle cerebral artery was measured and the breath-holding index was calculated. The breath holding index was correlated with leukoaraiosis severity and cognitive impairment. Patients with a low breath holding index presented poor performance in the Montreal Cognitive Assessment (MoCA) and executive function tests. That is, the lower the breath holding index, the lower the scores for the MoCA and the higher for the trail-making test Parts A and B. These results indicate that the breath-holding index is a useful parameter for the evaluation of cerebrovascular reserve impairment in patients with leukoaraiosis. In addition, the breath-holding index can reflect cognitive dysfunction, providing a new insight into the pathophysiology of leukoaraiosis. This study was approved by the Ethics Committee of the Fifth Peoples Hospital of Shenyang, China (approval No. 20160301) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800014421).

Functional maturation of immature β cells: A roadblock for stem cell therapy for type 1 diabetes

Type 1 diabetes mellitus(T1DM)is a chronic autoimmune disease caused by the specific destruction of pancreatic isletβcells and is characterized as the absolute insufficiency of insulin secretion.Current insulin replacement therapy supplies insulin in a non-physiological way and is associated with devastating complications.Experimental islet transplantation therapy has been proven to restore glucose homeostasis in people with severe T1DM.However,it is restricted by many factors such as severe shortage of donor sources,progressive loss of donor cells,high cost,etc.As pluripotent stem cells have the potential to give rise to all cells including isletβcells in the body,stem cell therapy for diabetes has attracted great attention in the academic community and the general public.Transplantation of isletβ-like cells differentiated from human pluripotent stem cells(hPSCs)has the potential to be an excellent alternative to islet transplantation.In stem cell therapy,obtainingβcells with complete insulin secretion in vitro is crucial.However,after much research,it has been found that theβ-like cells obtained by in vitro differentiation still have many defects,including lack of adult-type glucose stimulated insulin secretion,and multihormonal secretion,suggesting that in vitro culture does not allows for obtaining fully matureβ-like cells for transplantation.A large number of studies have found that many transcription factors play important roles in the process of transforming immature to mature human isletβcells.Furthermore,PDX1,NKX6.1,SOX9,NGN3,PAX4,etc.,are important in inducing hPSC differentiation in vitro.The absent or deficient expression of any of these key factors may lead to the islet development defect in vivo and the failure of stem cells to differentiate into genuine functionalβ-like cells in vitro.This article reviewsβcell maturation in vivo and in vitro and the vital roles of key molecules in this process,in order to explore the current problems in stem cell therapy for diabetes.