Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole,rivaroxaban and apixaban in rats.METHODS Male SD rats were randomly divided into voriconazole group(30 mg/kg),rivaroxaban group(2 mg/kg),apixaban group(0.5 mg/kg),Shugan jieyu capsules+voriconazole group(145 mg/kg+30 mg/kg),Shugan jieyu capsules+rivaroxaban group(145 mg/kg+2 mg/kg),Shugan jieyu capsules+apixaban group(145 mg/kg+0.5 mg/kg),with 6 rats in each group.After the rats in each group were consecutively administered solvent(0.5%sodium carboxymethyl cellulose solution)or Shugan jieyu capsules by intragastric gavage for 8 days,they were respectively given voriconazole,rivaroxaban and apixaban solution by intragastric gavage on the 8th day.Blood samples were then collected at different time points(in voriconazole group,rivaroxaban group and corresponding drug combination groups,blood was collected before administration and at 0.17,0.34,0.5,0.75,1,1.5,2,3,4,5,6,8,10 and 12 hours post-administration;in apixaban group and corresponding drug combination group,blood was collected before administration and at 0.08,0.17,0.25,0.34,0.5,0.75,1,3,5,7,10 and 12 hours post-administration).Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole,rivaroxaban and apixaban in rat plasma.The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model,and the comparisons were made between groups.RESULTS Compared with single drug group,after multiple administrations of Shugan jieyu capsules,AUC0-t,AUC0-∞ and cmax of voriconazole were significantly decreased,while CLz/F was significantly increased,and tmax was also significantly prolonged(P＜0.05).For rivaroxaban and apixaban,their tmax values were both significantly prolonged(P＜0.05).However,there were no statistically significant differences in the other pharmacokinetic parameters between the two groups(P＞0.05).CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure,increase the clearance,and delay the peak concentration of oral voriconazole.However,it does not affect the exposure levels of rivaroxaban and apixaban,but it does delay the time to reach peak concentration for both drugs.

Objective To investigate the effects of acute sleep deprivation on the behavior and synaptic protein expression of rats.Methods Seventy healthy male Wistar rats were randomly divided into seven groups,a Control group and sleep deprivation groups(24,48,72,96,120 and 144 hours).The sleep deprivation rat model was established by the modified multiplatform water environment sleep deprivation method.Spatial learning and memory were assessed by the Morris water maze.Anxiety was assessed by the open field test.The morphology and quantity of hippocampal neurons were observed by Nissl staining.Western blot and Real-time PCR were used to determine the expression of synaptophysin(SYN),post-synaptic density protein-95(PSD-95),and brain-derived neurotrophic factor(BDNF)in rats.Results Compared with the Control group,the numbers of standing and modification were significantly increased by prolongation of the sleep deprivation time(P＜0.05).The escape latency and path length were significantly increased in 120 and 144 h groups(P＜0.05),whereas the number of platform crossings and the percentage of the target quadrant time were significantly decreased(P＜0.01)and negatively correlated to the sleep deprivation time.The expression levels of BDNF,SYN,and PSD-95 were significantly decreased with the prolongation of sleep deprivation time(P＜0.01).Conclusions With the increase in sleep deprivation time,cognitive dysfunction and anxiety gradually deteriorated,which may be related to decreases in the expression of synaptic biomarkers.

Objective To prepare human SET8 monoclonal antibody and explore its effects on the proliferation,apoptosis,and cell cycle of hepatoma cells,and to evaluate its anti-tumor effect in mouse models of hepatocellular carcinoma.Methods We immunized mice with human SET8 polypeptide fragment and screened and fused B cells and myeloma cells to establish a hybridoma cell line that stably secreted SET8 monoclonal antibody.Production was expanded by intraperitoneal injection into mice and the collection and purification of ascites.We investigated the effects of SET8 monoclonal antibody on the proliferation,apoptosis,cell cycle,and apoptosis-related protein expression of hepatocellular carcinoma cells by CCK-8,flow cytometry,and Western blot,respectively.Finally,we constructed a mouse model of human hepatocellular carcinoma by cell transplantation to evaluate the inhibitory effect of SET8 monoclonal antibody on tumor growth in vivo.Results Human SET8 monoclonal antibody significantly inhibited the viability of Huh-7 and Mahlavu hepatoma cells at concentrations of 50 and 100 μg/mL,in a concentration-dependent manner(P＜0.05).Flow cytometry analysis showed that SET8 monoclonal antibody,paclitaxel,and their combination significantly increased the apoptosis rate of Mahlavu cells compared with the blank control group,with the combination group having the greatest effect(P＜0.05).SET8 monoclonal antibody also induced Mahlavu cell cycle arrest in S and G2 phases and reduced G1 phase cells.Western blot analysis showed that the monoclonal antibody increased the expression of the apoptosis-related proteins Bax and Caspase-3(P＜0.05).SET8 monoclonal antibody,alone or in combination with paclitaxel,also effectively inhibited the proliferation of hepatocellular carcinoma cells in nude mice,with the combination therapy having the most significant effect(P＜0.05).Conclusions The prepared human SET8 monoclonal antibody effectively inhibited the proliferation and promoted the apoptosis of hepatocellular carcinoma cells,and showed good anti-tumor effects in mice.

Objective To prepare human SET8 monoclonal antibody and explore its effects on the proliferation,apoptosis,and cell cycle of hepatoma cells,and to evaluate its anti-tumor effect in mouse models of hepatocellular carcinoma.Methods We immunized mice with human SET8 polypeptide fragment and screened and fused B cells and myeloma cells to establish a hybridoma cell line that stably secreted SET8 monoclonal antibody.Production was expanded by intraperitoneal injection into mice and the collection and purification of ascites.We investigated the effects of SET8 monoclonal antibody on the proliferation,apoptosis,cell cycle,and apoptosis-related protein expression of hepatocellular carcinoma cells by CCK-8,flow cytometry,and Western blot,respectively.Finally,we constructed a mouse model of human hepatocellular carcinoma by cell transplantation to evaluate the inhibitory effect of SET8 monoclonal antibody on tumor growth in vivo.Results Human SET8 monoclonal antibody significantly inhibited the viability of Huh-7 and Mahlavu hepatoma cells at concentrations of 50 and 100 μg/mL,in a concentration-dependent manner(P＜0.05).Flow cytometry analysis showed that SET8 monoclonal antibody,paclitaxel,and their combination significantly increased the apoptosis rate of Mahlavu cells compared with the blank control group,with the combination group having the greatest effect(P＜0.05).SET8 monoclonal antibody also induced Mahlavu cell cycle arrest in S and G2 phases and reduced G1 phase cells.Western blot analysis showed that the monoclonal antibody increased the expression of the apoptosis-related proteins Bax and Caspase-3(P＜0.05).SET8 monoclonal antibody,alone or in combination with paclitaxel,also effectively inhibited the proliferation of hepatocellular carcinoma cells in nude mice,with the combination therapy having the most significant effect(P＜0.05).Conclusions The prepared human SET8 monoclonal antibody effectively inhibited the proliferation and promoted the apoptosis of hepatocellular carcinoma cells,and showed good anti-tumor effects in mice.

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

OBJECTIVE：To provid e reference for hospital decision-maker to select and use repaglinide and naglinide reasonably. METHODS ：Through reviewing literautre ，guideline and instruction ，full score system was estalished for comunni- cation between pharmacists and physicians ；from the aspects of clinical necessity ，effectiveness，safety，economy，medical insu- rance attribute ，essential medicine attribute ，original research attribute ，drug packaging attribute ，drug market and enterprise attributes，the Mini health technology assessment （Mini HTA ）was carried out for repaglinide and nateglinide ，and scored on the basis of weight value. RESULTS ：Repaglinide and naglinide ’s final score were 77 and 74，respectively. For type 2 diabetes，both of them could reduce postprandial blood glucose ，and had less side effect and good safety. They were both included in the medical insurance list. Both of them were original varieties ，easy to store and had a long period of validity. Although they were expensive in the treatment of type 2 diabetes，their manufacturers had a good reputation and were widely used in the world ，which was a good choice for patients with type 2 diabetes. But they were different to certain extent ；repaglinide could be used in patients with poor renal function [eGFR ＜30 mL/min] without dose adjustment ；nateglinide should be adjusted according to eGFR for renal excretion. Repaglinide was essential medicine but nateglinide wasn ’t；repaglinide didn ’t need shading storage but nateglinide did. In addition ， a variety of liver drug enzyme inducers or inhibitors may interact with the two drugs ，and special groups should be used with. CONCLUSIONS ：Mini HTA provide reference for the selection and rational use of repaglinide and nateglinide ；patients with type 2 diabetes can select suitable drug according to their own conditions and needs. When combined with other drugs ，blood glucose should be closely monitored to prevent the occurrence of hypoglycemia.

Objective To observe the clinical effect of the method of Shugan-Yiqi-Yangyin treatment for the steroid-resistant nephrotic syndrome (SRNS). Methods A total of 80 patients with SRNS were divided into 2 groups by random number table method, 40 in each group. The control group received glucocorticoids combined with Tripterygium Glycosides;and the treatment group received Shugan-Yiqi-Yangyin on the basis of the control group, 3 month as a course. The 24 h urine protein quantitative (propagated), plasma albumin, blood lipid (total cholesterol, triglycerides), hemorrheology, blood urea nitrogen (BUN), creatinine (Cr), urinary inhibition C (Cys C) were detected before and after the treatment of two groups, and the clinical effect was compared. Results The total effective rate of the treatment group was 92.50% (37/40) and 82.50% (33/40) in the control group, and the difference was statistically significant (Z=-1.966, P<0.05). After the treatment, the 24 hPRO (1.03 ± 0.64 mg vs.2.81 ± 1.43 mg,t=3.025),Cys C(0.35 ± 0.41 mg/L vs.0.76 ± 0.51 mg/L, t=3.058) of the treatment group was significantly lower than those of the control group(P<0.05).The Alb(34.88 ± 2.17 mg vs. 31.69 ± 2.05 mg, t=2.986) of the treatment group was significantly higher than this of the control group (P<0.05), After treatment,the whole blood high shear viscosity(7.84 ± 1.42 mPa?s vs.8.94 ± 1.38 mPa?s,t=3.160),the whole blood low shear viscosity(4.55 ± 0.37 mPa?s vs.5.02 ± 0.44 mPa?s,t=3.825),plasma viscosity(1.33 ± 0.10 mPa?s vs.1.95 ± 0.26 mPa?s,t=2.981),hematocrit(0.28 ± 0.03 vs.0.34 ± 0.03,t=2.993),fibrinogen(3.96 ± 0.57 g/L vs.4.52 ± 0.47 g/L,t=4.863)of the treatment group were significantly lower than those of the control group(P<0.05).The TC(5.04 ± 1.72 mmol/L vs.6.99 ± 1.06 mmol/L,t=3.67),TG(1.4 ± 0.64 mmol/L vs.2.02 ± 0.31 mmol/L, t=3.040) of the treatment group were significantly lower than those of the control group (P<0.05). Conclusions The Shugan-Yiqi-Yangyin treatment for SRNS can obviously improve the symptoms,reduce the side effects of hormone of antagonism. The possible mechanisms are to restore kidney function, improve blood viscosity and lower blood lipid levels.

OBJECTIVE:To investigate the compatible stability of Xiao'aiping injection combined with 3 kinds of common in-jections. METHODS:Referring to package inserts,Xiao'aiping injection 40 mL was compatible with 5% Glucose injection,10%Glucose injection or 0.9% Sodium chloride injection 160 mL,respectively. At room temperature(about 25 ℃)and high tempera-ture(40 ℃),the appearance of mixtures were observed at 0,1,2,4,8,12,24,48 h;pH value and the number of insoluble particles were detected. The contents of tenacissoside A and tenacissoside Ⅰ in mixtures were determined by HPLC. RESULTS:Un-der above condition,the mixtures were brownish yellow liquid within 48 h after Xiao'aiping injection was compatible with 5%Glucose injection or 10% Glucose injection;24 h after mixed with 0.9% Sodium chloride injection,the mixture changed from brownish yellow to reddish brown,but no precipitation was found. The pH value of mixtures had no significant change(RSD<1%,n=8). The number of particles ≥25 μm was in line with the requirements of Chinese Pharmacopeia(2015 edition). For-ty-eight hours after mixing,the number of particles ≥10 μm in the mixtures exceeded the pharmacopoeia limits. Within 48 h after mixing,the relative contents of tenacissoside A and tenacissoside I in mixtures had no significant change(RSD<2%,n=8). CON-CLUSIONS:The mixture should be used up within 24 h after Xiao'aiping injection combined with 5% Glucose injection,10%Glucose injection or 0.9% Sodium chloride injection.