PLAG1 Promotes High Glucose-Induced Angiogenesis and Migration of Retinal Endothelial Cells by Regulating the Wnt/ß-Catenin Signalling Pathway.

Proliferation and migration of retinal endothelial cells (RECs) contribute to the development of diabetic retinopathy. PLAG1 (pleomorphic adenoma gene 1) functions as a zinc-finger transcription factor to participate in the development of lipoblastomas or pleomorphic adenomas of the salivary glands through regulation of cell proliferation and migration. The role of PLAG1 in diabetic retinopathy was investigated in this study. Firstly, RECs were induced under high glucose conditions, which caused reduction in viability and induction of apoptosis in the RECs. Indeed, PLAG1 was elevated in high glucosetreated RECs. Functional assays showed that silence of PLAG1 increased viability and suppressed apoptosis in high glucose-induced RECs, accompanied with up-regulation of Bcl-2 and down-regulation of Bax and cleaved caspase-3. Moreover, migration of RECs was promoted by high glucose conditions, while repressed by knockdown of PLAG1. High glucose also triggered angiogenesis of RECs through up-regulation of vascular endothelial growth factor (VEGF). However, interference of PLAG1 reduced VEGF expression to retard the angiogenesis. Silence of PLAG1 also attenuated high glucose-induced up-regulation of Wnt3a, ß-catenin and c-Myc in RECs. Moreover, silence of PLAG1 ameliorated histopathological changes in the retina of STZ-induced diabetic rats through down-regulation of ß-catenin. In conclusion, knockdown of PLAG1 suppressed high glucose-induced angiogenesis and migration of RECs, and attenuated diabetic retinopathy by inactivation of Wnt/ ß-catenin signalling.

miR-326 inhibits the progression of papillary thyroid carcinoma by targeting MAPK1 and ERBB4.

Papillary thyroid carcinoma (PTC) is the prevalent histotype of thyroid cancer, with increasing incidence worldwide. MicroRNAs (miRNAs) could play an important role in the development and progression of human cancers. Interestingly, miR-326 was validated as one of the downregulated miRNAs in PTC. Therefore, it is necessary to research the function of miR-326 involved in the progression of PTC. In the current study, we detected the downregulation of miR-326 in PTC tissues and cell lines. The miR-326 overexpression or knockdown was conducted in TPC-1 or HTh83 PTC cells. miR-326 mimics decreased the proliferation, clone formation ability and caused G1-phase accumulation. In addition, the reduction of migration and invasion abilities was induced by miR-326 mimics. Western blot analysis showed that the cells with miR-326 mimics exhibited the inhibition of vimentin and N-cadherin, as well as enhancement of E-cadherin. Importantly, miR-326 could directly target mitogen activated protein kinase 1 (MAPK1) and epidermal growth factor receptor 4 (ERBB4). MAPK1 or ERBB4 overexpression rescued the effects of miR-326 on proliferation, migration, and invasion in PTC cells. Notably, miR-326 reduced tumorigenesis in vivo, including the decrease of tumor volume and weight, suppression of Ki-67, N-cadherin, MAPK1 and ERBB4. In all, these results might provide a new therapeutic target for the diagnosis of PTC.

Supraglottic jet oxygenation and ventilation enhances oxygenation during upper gastrointestinal endoscopy in patients sedated with propofol: a randomized multicentre clinical trial.

BACKGROUND: Hypoventilation is the main reason for hypoxia during upper gastrointestinal endoscopy procedures with sedation. The key to preventing hypoxia is to maintain normal ventilation during the procedure. We introduced supraglottic jet oxygenation and ventilation (SJOV) through a new Wei nasal jet tube (WNJ) to reduce the incidence of hypoxia in patients sedated with propofol during upper gastrointestinal endoscopy procedures. METHODS: In a multicentre, prospective randomized single-blinded study, 1781 outpatients undergoing routine upper gastrointestinal endoscopy who were sedated with propofol by an anaesthetist were randomized into the following three groups: the supplementary oxygen via nasal cannula group [nasal cannula oxygen: O 2 (2 litres min -1 ) was administered via a nasal cannula]; the supplementary oxygen via WNJ group [WNJ oxygen: O 2 (2 litres min -1 ) was administered through a WNJ]; and the SJOV via WNJ group (WNJ SJOV: SJOV was administered via WNJ) at three centres from March 2015 to July 2016. The primary outcome of interest was the incidence of hypoxia (peripheral oxygen saturation of 75-89%). Other adverse events were also recorded. RESULTS: Supraglottic jet oxygenation and ventilation decreased the incidence of hypoxia from 9 to 3% ( P <0.0001). No severe hypoxia occurred in the WNJ SJOV group, one instance occurred in the WNJ oxygen group, and two instances were observed in the nasal cannula oxygen supply control group. Supraglottic jet oxygenation and ventilation-related minor adverse events increased significantly within 1 min after the procedure but decreased 30 min later. CONCLUSIONS: The use of SJOV during upper gastrointestinal endoscopy for patients who are sedated with propofol reduces the incidence of hypoxia, with minor and tolerable adverse events. Supraglottic jet oxygenation and ventilation has a favourable risk-to-benefit ratio and may improve patient safety. CLINICAL TRIAL REGISTRATION: NCT02436018.

Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.

Disruption of intracellular Ca2+ homeostasis plays an important role as an upstream pathology in Alzheimer's disease (AD), and correction of Ca2+ dysregulation has been increasingly proposed as a target of future effective disease-modified drugs for treating AD. Calcium dysregulation is also an upstream pathology for the COVID-19 virus SARS-CoV-2 infection and replication, leading to host cell damage. Clinically available drugs that can inhibit the disturbed intracellular Ca2+ homeostasis have been repurposed to treat COVID-19 patients. This narrative review aims at exploring the underlying mechanism by which lithium, a first line drug for the treatment of bipolar disorder, inhibits Ca2+ dysregulation and associated downstream pathology in both AD and COVID-19. It is suggested that lithium can be repurposed to treat AD patients, especially those afflicted with COVID-19.

Supraglottic jet oxygenation and ventilation during colonoscopy under monitored anesthesia care: a controlled randomized clinical trial.

OBJECTIVE: Supraglottic jet oxygenation and ventilation may provide active pulse oxygenation and ventilation in patients with respiratory suppression. This randomized controlled clinical study was designed to determine the efficacy and safety of supraglottic jet oxygenation/ventilation during monitored anesthesia care (MAC) by intravenous (IV) infusion of propofol in patients undergoing colonoscopy. PATIENTS AND METHODS: Forty-nine adult patients receiving colonoscopy were randomly divided into two groups: the control group with passive oxygen supply from regular nasal cannula (N = 24) and the supraglottic jet oxygenation/ventilation (SJV) group with active pulse oxygen supply and ventilation using a manual jet ventilator (N = 25). MAC was induced and maintained by intravenous injection of propofol. HR, ECG, BP, SaO2 were continuously monitored during and 1 hour after the procedure. RESULTS: Demographic characteristics were similar in height, weight, age and BMI (Body Mass Index) between the two groups. Compared to the control group, the SJV group had similar averaged lowest SaO2, but highest SaO2 in SJV group were significantly lower during operation (p = 0.01). The proportion of maximum chest rise movement were increased significantly in SJV group (p = 0.03) compared with control group. Demographic characteristics were similar in the times needed to use facial mask ventilation, percentage of time to maintain SaO2 above 96%, average PetCO2 during the procedure, or complications between the two groups. CONCLUSIONS: SJV can provide adequate oxygenation/ventilation during monitored anesthesia care and convenient monitoring for patients' breath, without complications.

Hemodynamic effects of high frequency jet ventilation during acute hypovolemia.

The hemodynamic effects of high frequency jet ventilation (HFJV) at three different rates (60, 100, 200/min) and at rate 200/min combined with jet sighs 12/min (HFJV-200 + 12S) during two degrees of hemorrhagic hypovolemia were investigated in dogs. Also, the results were compared with those of intermittent positive pressure ventilation (IPPV). Two degrees of hypovolemia were produced by bleeding dogs until mean arterial pressure was 25% or 50% lower than basic value respectively. At both periods of hypovolemia, HFJV at rate 60 or 100 were found to have better hemodynamic effects than IPPV due to their lower airway pressures. However, HFJV at rate 200 or HFJV-200 + 12S did not demonstrate the same superiority because of their higher airway pressure, the latter even represented a tendency of worse hemodynamic effect than IPPV. The best cardiovascular effect was seen during HFJV at rate 100. Our study indicated that the hemodynamic effect of HFJV better than that of IPPV during acute hypovolemia can be seen only when proper ventilatory settings are chosen. Jet sighs at 12/min added to usual HFJV are not beneficial to circulatory function. It is recommended that HFJV at a rate below 200/min without jet sighs be used in patients who need respiratory support during acute hypovolemia or shock.

Clinical studies on high frequency two-way jet ventilation.

A new mode of jet ventilation, high frequency two-way jet ventilation (HFTJV) was devised and introduced to increase carbon dioxide elimination during jet ventilation. Its ventilatory efficiency and features were investigated and compared with those of high frequency jet ventilation (HFJV) in 10 patients with normal cardiopulmonary function. Random sample selection and randomized cross-over trial were used for comparison between HFTJV and HFJV at the same ventilatory settings of driving pressure 1 kg/cm2 (14.22 Psi), respiratory rate 100/min and I/E ratio 1:2. Peak inspiratory pressure (PIP), end-expiratory pressure (EEP) and main variables of air blood gas analysis (PaO2, PaCO2, pH) were measured and recorded during the use of HFJV and HFTJV. PIP and EEP were significantly lower than with HFTJV than with HFJV. EEP of HFTJV showed a slightly negative pressure (-0.17 +/- 0.03 kPa). PaCO2 with HFTJV was significantly lower than that with HFJV, but PaO2 and pH with HFTJV were significantly higher than those with HFJV. HFTJV was shown to have a ventilatory feature of decreasing airway pressure and simultaneously increasing carbon dioxide elimination, as compared with HFJV. Whether this ventilatory feature of HFTJV can be utilized for various respiratory support in patients with abnormal cardiopulmonary function needs to be further studied.