Objective To investigate the effect of alanyl-glutamine (Ala-Gln) on acute lung injury (ALI) in rats induced by sepsis and its mechanisms. Methods Forty healthy adult Wistar rats were randomly divided into a control group, a lipopolysaccharide (LPS)-induced shock group, an Ala-Gln treated group, and a glutamine (Gin) treated group. The control group received an intravenous infusion of 28 mL/kg lactated Ringer's solution(LR). The LPS-induced shock group received an intravenous administration of 25 mL/kg LR, and then 3 mL/kg (6 mg/kg) LPS (L-2880, Sigma, America). The AlaGin treated group received 4.5% Dipeptiven (25 mL/kg, equaling 0.75 g/kg Gin) immediately before 3 mL/kg (6 mg/kg) LPS. The Gin treated group received 3% glutamine (25 mL/kg, 0.75g/kg) immediately before 3 mL/kg (6 mg/kg) LPS. Serum (1 mL) was drawn via the femoral vein or cardiac puncture before LPS injection (T0) and 6 h after the administration of LPS (T1), respectively. All rats were killed 6 h after LPS infusion. The samples of pulmonary tissue and lung lavage fluid were collected after experiments. Tumor necrosis factor-α (TNF-α), interleukin-1β( IL-1β), and interleukin-8(IL-8) in the serum at T0 and T1 were detected by ELISA. Apoptosis in the lung epithelial cells was detected with TUNEL assays. The lung wet/dry(W/D) weight ratio and total protein in the bronchoalveolar lavage fluid (BALF) were measured. Results Six hours after the infusion of LPS (T1), the plasma concentrations of TNF-α, IL-1β, and IL-8 were much lower in the Ah-Gln treated group and the Gin treated group than those in the LPS-induced shock group (P < 0.05). Compared with the LPS-induced shock group, AlaGin and Gin significantly reduced the increase in the lung wet/dry weight ratio (P<0.05) and attenuated the morphological lung damage. Conclusion Intravenous administration of Ala-Gha can effectively protect the lung from sepsis induced injury.

Objective To explore the role and mechanism of microRNA-15b in the regulation of epithelial-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs).Methods PCR assay was used to determine the expression of microRNA-15b in the HMrSV5 induced by 138mmol/L high glucose for 24 h.MicmRNA-15b mimic or inhibitor was transfected into human peritoneal mesothelial cells (HMrSV5) to over-express or down-regulate microRNA-15b.The cells were then incubated with 138 mmol/L high glucose for 24 h,and the expressions of E-cadherin(E-Cad),Vimentin (VIM),Fibronectin(FN) and Smad7 were detected by real-time PCR and Western blotting respectively.Results microRNA-15b in the HMrSV5 ceils was over-expressed and down-regulated.Increased level of microRNA-15b was obtained in HMrSV5 cells treated with high glucose.In vitro,high glucose led to the up-regulation of vimentin as well as fibronectin and the down-regulation of E-cadherin in HMrSV5 cells (all P ＜ 0.05),which indicated EMT and fibrosis.Suppression of microRNA-15b by transfection with microRNA-15b inhibitor partially reversed the EMT and fibrosis changes (P ＜ 0.05),while over-expression of microRNA-15b by transfection with microRNA-15b mimic obviously enhanced the EMT and fibrosis changes (P ＜ 0.05).Conclusions MicroRNA-15b mediates high glucose induced EMT in human peritoneal mesothelial cells by the inhibition of Smad7 possibly.MicroRNA-15b maybe a new target for the prevention and treatment of peritoneal fibrosis during peritoneal dialysis (PD).

Objective To observe the effect of cognitive training combined with swallowing training real-time electrical stimulation on dysphagia and cognitive impairment after stroke. Methods 40 patients with dysphagia and cognitive impairment after stroke were randomly divided into observation group (n=20) and control group (n=20). The observation group accepted swallowing training (including routine vocal training and swallowing training real-time electrical stimulation) and cognitive training. The control group accepted routine vocal training and neuromuscular electrical stimulation. The cognitive function and swallowing function were accessed with Mini-Mental State Examination (MMSE) and Video Fluoroscopy Swallowing Study (VFSS) respectively before and 1 month after stroke. Results After treatment, the MMSE scores and the time for a bolus to pass the pharynx improved in both groups (P<0.05), and the observation group was superior to the control group (P<0.05). Conclusion Cognitive training combined with swallowing training real-time electrical stimulation can promote the recovery of swallowing function of patients with dysphagia and cognitive impairment after stroke.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

OBJECTIVETo explore the value of baseline serum alkaline phosphatase (ALP) for predicting 2-year fracture in patients with chronic kidney disease (CKD) on maintenance dialysis.

METHODSA total of 139 patients with CKD undergoing maintenance dialysis in our hospital were enrolled in this study. According to the median serum ALP level, the patients were divided into high ALP and low ALP groups. The demographic and clinical data of the patients including dialysis duration, serum calcium level, serum phosphorus level, and serum intact parathyroid hormone level were recorded, and their bone mineral density of the femur and the lumbar spine was measured using dual energy X-ray absorptiometry. The patients were followed up for 2 years and fracture events were recorded. The risk factors of fracture were analyzed using logistic regression analysis, and their predictive value for fracture was analyzed using receiver-operating characteristic (ROC) curve.

RESULTSThe mean baseline serum ALP level was 132.55±167.68 U/L in these patients, significantly higher than that in the normal population (=2.816, =0.006). Baseline serum ALP level was negatively correlated with the bone mineral density of the lumbar spine (=-0.203, =0.006) and the femur (=-0.196, =0.021). Fractures occurred in 21 (15.1%) of the patients during the 2-year follow-up, and the fracture rate was significantly higher in patients with high ALP levels. Logistic regression analysis identified serum ALP level as an independent risk factor of fracture (OR: 1.010, =0.001, 95%CI: 1.004-1.016). The areas under the ROC curve were 0.900 and 0.768 for serum ALP level and intact parathyroid hormone level in predicting 2-year fractures, respectively.

CONCLUSIONSSerum ALP may serve as a good indicator for predicting 2-year fractures in patients with CKD on maintenance dialysis.