p70 ribosomal protein S6 kinase (p70S6K), an important member of AGC family, is a kind of multifunctional Ser/Thr kinases, which plays an important role in mTOR signaling cascade. The p70 ribosomal protein S6 kinase is closely associated with diverse cellular processes such as protein synthesis, mRNA processing, glucose homeostasis, cell growth and apoptosis. Recent studies have highlighted the important role of S6K in cancer, which arose interests of scientific researchers for the design and discovery of anti-cancer agents. Herein, the mechanisms of S6K and available inhibitors are reviewed.

ObjectiveTo investigate the effect of glucagon-like peptide-2(GLP-2) on intestinal barrier function in the bile duct ligated rats.MethodsSeventy-two SD rats were randomly divided into three groups:GLP-2 treated group(T group),obstructive jaundice control group (C group) and sham operation group (SO group).The mRNA expression of GLP-2R was measured by semi-quantified reverse transcription polymerase chain reaction (RT-PCR)and the bcl-2 expression in the intestinal mucosa was measured by immunohistochemistry staining equipped image analyzing systems (Image proplus Version 4.5).ResultsThe mRNA expression of GLP-2 in intestinal mucosa in T group was higher than that in C group (P＜0.05) but lower than that in SO group (P＞0.05).The expression of bcl-2 in the intestinal villi of rats in C group showed more significant decrease (P＜0.05) than those in the SO and T groups especially on day 3 and 7 after operation (P＜0.05).ConclusionsGLP-2 may increase the mRNA expression of GLP-2R,stimulate the growth of intestinal mucosa,diminish the number of the apoptosis cells,and protect the intestinal barrier function in obstructive jaundice rats.

Objective To investigate the effect of glucagon-like peptide-1(GLP-1) in a dose related manner on glucose metabolism after 65% hepatectomy in rats.Methods We determined the serum glucose levels of hepatomized rats at 0,5,10,20,and 30 minutes after an intravenous glucose load(IVGTT,0.5 g/kg glucose) on the first postoperative day,and the changes of blood glucose,serum insulin and glucagon concentrations of hepatomized rats that received the volum load with normal saline or 0.3 nmol/kg GLP-1,0.45 nmol/kg GLP-1 respectively.Blood was drawn for determination of glucose(glucose oxidase),insulin,glucagon,and GLP-1(radioimmunoassay).Results The peak glucose and 30-minute glucose levels and the area under the curve(AUC 0-30) were significantly higher in the hepatomized rats compared to the control rats,which had not undergone any operation and received a same intravenous glucose load(0.5 g/kg glucose with normal saline)(P0.05).Nevertheless the peak glucose and 30-minute glucose levels and AUC 0-30 of the hepatomized rats that received with 0.45 nmol/kg GLP-1 were significantly lower compared to the rats that received the same volum load with normal saline or 0.3 nmol/kg GLP-1 respectively after liver resection.There was an increasing postoperative serum concentration of glucose,insulin,glucagon on the first day,then,the serum glucose concentration was significantly lowered after infusion of GLP-1 in rats undergoing hepatectomy(P

Clinical intemship is an important part of medical education.Medical eduezlion for foreign individuals in China has been initiated for a few years.Given the cultural and language background of foreign medical students,It is necessary to study and accumulate experience in developing an effective systern to manage their clinical intemship.We are here to present our approaches,such as teaching with both Chinese and English,arranging for Chinese students and foreign students to work together,to impmve surgical internship for foreign medical students in West China Medical School

0.05).Conclusions After hepatectomy,in rats is associated with an obvious insulin resistance,mainly due to the level of serum insulin was obviously decreased(P

Thioredoxin reductase(TrxR)is a seleniferous homodimeric flavoenzyme, which is ubiquitously expressed in all cells and plays a crucial role in the redox regulation of numerous celluar signaling pathways involved in cell survival and proliferation. TrxR maintains cellular redox equilibrium. Recent researches have illuminated that TrxR overexpressed in many tumors, is closely associated with the evolution, progression and apoptosis of tumor. TrxR contains a reactive and solvent accessible selenocysteine residue which is located on a flexible C-terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus represents an attractive binding site for inhibitors. The TrxR inhibitors as novel target-drug in cancer therapy have been extensively studied and elucidated. This article summarized the latest progress in TrxR inhibitors according to the binding capacity of TrxR and substrate.

Protein tyrosine phosphatase 1B(PTP1B),a member of protein tyrosine phosphatases(PTPs),plays a key role in the negative regulation of insulin and leptin signalings.Recent studies showed that PTP1B had an important connection with endoplasmic reticulum(ER)stress, pancreatic beta cells proliferation and insulin secretion,and is closely related to the pathological process of type 2 diabetes mellitus(T2DM)and obesity. Therefore,PIP1B targeted inhibitors have become a research hotspot in the treatment of these metabolic disea-ses.Based on the structural features of PTP1B and its relationship with T2DM and obesity,PTP1B inhibitors were classified according to the sites of binding.Their latest research advances were reviewed in this paper,providing a reference for the development of anti-T2DM and anti-obesity drugs targeting PTP1B.

Soluble guanylate cyclase is a key signal transduction enzyme in the body, which can activate the NO-sGC-cGMP signaling pathway and inhibit the TGF-β signaling pathway. cGMP is one of the most important second messengers and also involved in a series of physiological or pathological responses including vasodilation, inhibition of platelet aggregation, inhibition of cell proliferation and so on. When TGF-β signaling pathway is inhibited, it can inhibit issue fibrosis and cell proliferation. Recent studies have shown that sGC can be activated directly to treat a variety of diseases. As a new class of potential drugs, sGC stimulators have shown many unique advantages. Herein, the mechanism and the latest research progress of sGC stimulators are reviewed, which could provide a useful information for further research of sGC stimulators.

Objective To investigate effects of pirfenidone (PFD) on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods (1) Wild-type mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg· kg-1· d-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5％ sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2) Mouse mesangial cells (SV40 MES-13 cells) were cultured as research objects.They were divided into control group,hyperosmolar group,high glucose (HG) group,and 50,100,200,400,800,1600 mg/L PFD+HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD+HG group.The mRNA expressions of α-smooth muscle actin (α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1 (TGF-β1),interleukin (IL)-1β,IL-6 and monocyte chemotactic protein-1 (MCP-1) were detected by real-time PCR.Results (1) Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ (all P ＜ 0.05).Compared with those in model group,in PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ inhibited (all P＜0.05).(2) Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD+HG groups decreased (all P ＜ 0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD+HG group (all P ＜ 0.05).Conclusions PFD can inhibit high glucose-induced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.

Objective:To investigate the efficacy and safety of black tomato concentrated sauce in the treatment of benign prostatic hyperplasia(BPH) with lower urinary tract symptoms(LUTS).Methods:An open, randomized and controlled trial was conducted, and 150 BPH patients with LUTS were randomly assigned to three groups: experimental group(60 cases), placebo group (45 cases) and positive control group(45 cases) in the Department of Urology, Lanzhou University Second Hospital from December 2018 to September 2020.Inclusion criteria: age≥50 years old; first diagnosis of BPH, or interrupted medical treatment of BPH for more than 1 month; maximum urinary flow rate (Q max) <15ml/s; prostate volume (PV)≥20ml; IPSS≥8, QOL≥2. Exclusion criteria: lower urinary tract obstruction not caused by BPH, post-void residual urine volume(PVR) >250 ml; history of acute urinary retention in the last 3 months; prostate nodules and suspected prostate cancer were revealed by digital rectal examination and transrectal B-ultrasoundor; prostate-specific antigen (PSA)≥10 ng/ml; neurogenic bladder, perivous history of bladder, prostate, or urethra operations; suffering from serious heart, lung, liver, kidney and other diseases. The patients in the experimental group were orally treated with black tomato concentrated sauce(30 g/once, 3 times/day). The patients in the placebo group were orally administrated with placebo. In the positive control group, the patients with PV≤30ml were orally treated with tamsulosin(0.2mg/once, 1 time/day), the patients with PV>30ml were orally administrated with tamsulosin and finasteride(5 mg/once, 1 time/day). All enrolled patients were treated for 3 months. At the end of third month, the IPSS, QOL, PV, PVR, Q max, average urinary flow rate(Q ave), total PSA(tPSA), free PSA (fPSA), testosterone(TST) and the incidence of adverse reaction were assessed. Results:128 of 150 cases, including 52 cases in experimental group, 36 cases in placebo group and 40 cases in positive control group, completed the study, the rest was excluded due to not take medication regularly and fail to follow-up. There were no significant differences in baseline parameters among experimental group, placebo group and positive control group ( P>0.05) in age[(63.21±8.61) vs.(62.36±6.32) vs. (63.94±7.78)years old], body mass index[(23.74±3.17) vs. (23.94±3.09) vs. (24.26±2.91)kg/m 2], IPSS[(17.5±6.6) vs. (15.4±5.8) vs. (17.9±6.8)], QOL[4.0(3.0, 4.0) vs. 4.0(3.0, 4.5) vs. 4.0(3.0, 5.0)], Q max [(8.60±3.04) vs. (9.13±2.92) vs. (9.58±3.26) ml/s], Q ave[(4.39±1.69) vs. (4.66±1.76) vs. (4.88±1.60)ml/s], PV [32.00(25.55, 45.40)vs. 30.00(24.45, 38.35)vs. 34.80(27.65, 56.65)ml], PVR[23.50(8.25, 45.75) vs.5.50(0, 47.75) vs. 29.00(0, 84.00)ml], tPSA [1.53(0.89, 3.00) vs. 1.23(0.69, 1.98) vs. 2.23(0.90, 4.15)ng/ml], fPSA [0.37(0.28, 0.76) vs. 0.37(0.22, 0.52) vs. 0.54(0.30, 0.97) ng/ml] and TST[(443.64±156.32) vs. (493.97±176.16) vs. (450.89±135.08)ng/dl]. After 3 months of treatment, the IPSS in experimental group was(9.9±5.7), QOL score 2.0(2.0, 3.0), Q max(11.78±5.24)ml/s, Q ave(5.86±3.00)ml/s, tPSA 1.64(0.96, 3.32)ng/ml and TST (475.91±177.33)ng/dl, which were significantly different compared with pre-treatment( P<0.05). In positive control group, IPSS was (9.0±6.2), QOL 2.0(2.0, 3.0), Q max(11.73±4.50)ml/s, Q ave(6.11±2.53)ml/s, tPSA 1.57(0.80, 3.09)ng/ml, fPSA 0.37(0.24, 0.63)ng/ml and TST (526.11±126.88)ng/dl, which were statistically different compared with pre-treatment( P<0.01). However, there were no significant differences in all the above indexes in placebo control group compared with the baseline( P>0.05). The numerical changes of IPSS, QOL, Q maxand Q ave between experimental group and placebo group had statistically significant differences ( P<0.05). The changes of IPSS, QOL, Q max, Q ave, PV, tPSA, fPSA and TST between positive control group and placebo group had significant differences ( P<0.05). The changes of PV, tPSA and fPSA between positive control group and experimental group had statistically significant differences ( P<0.05). The incidence of adverse reactions was 5.77% (3/52, including 1 headache and 2 stomach discomfort) in experimental group, 5.56% (2/36, including 1 headache and 1 stomach discomfort) in placebo group, and 10.00%(4/40, including 1 dizzy, 1 nasal obstruction and 2 erectile dysfunction) in positive control group. And there was no statistical difference in the incidence of adverse reactions among three groups ( P>0.05). Conclusions:Black tomato concentrated sauce shows an excellent effect on patients with LUTS/BPH, and improves the quality of life with few adverse events.