Objective To investigate the therapeutic effects and mechanisms of electroacupuncture(EA)at Fengchi points(GB20)on cerebral infarction in rats.Methods The 80 male SD rats were randomized into normal group,model group,EA group(EA at Fengchi),and EA+AS1517499 group(EA at Fengchi+intraperitoneal STAT6 phosphorylation inhibitor),with 20 rats in each group.A cerebral infarction model was established via intraluminal filament occlusion in all groups except for the normal group.After intervention,the neurological deficit scores of the rats were assessed.The cerebral infarction area was measured using 2,3,5-triphenyltetrazolium chloride(TTC)staining.Histopathological alterations in brain tissue were observed via hematoxylin-eosin(HE)staining.The rate of brain cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining.The levels of interleukin-6(IL-6),interferon-gamma(IFN-γ),interleukin-4(IL-4),and transforming growth factor-beta(TGF-β)in brain tissue were detected by enzyme-linked immunosorbent assay(ELISA).Western Blot was used to measure the protein expression of microglial markers(Iba-1,CD86,CD206)and STAT6/NF-κB pathway proteins(STAT6,p-STAT6,PPAR-γ,p-NF-κB p65).Results Compared with the normal group,the neurological deficit score,cerebral infarction area,apoptosis rate of brain cells and the levels of pro-inflammatory factors IL-6 and IFN-γ in the brain tissue of the EA group were significantly increased,and the levels of anti-inflammatory factors IL-4 and TGF-β were significantly decreased,the expression levels of M1 microglia marker CD86 and signal pathway-related protein p-NF-κB p65 were significantly increased,and the expression levels of M2 microglia marker CD206 and signal pathway-related proteins STAT6,p-STAT6 and PPAR-γ were significantly decreased,and the differences were statistically significant(P＜0.05).Compared with the model group,the neurological deficit score,cerebral infarction area,brain cell apoptosis rate and the levels of IL-6 and IFN-γ in the brain tissue of the EA group were significantly decreased,the levels of IL-4 and TGF-β were significantly increased,the expression levels of CD86 and p-NF-κB p65 were significantly decreased,and the expression levels of CD206,STAT6,p-STAT6 and PPAR-γ were significantly increased,with statistically significant differences(P＜0.05).The therapeutic effects of the above indexes in the EA group were significantly superior to those in the EA+AS1517499 group.Conclusion EA at Fengchi points mitigates cerebral infarction by shifting microglial polarization from M1 to M2 via STAT6/NF-κB pathway modulation.

OBJECTIVE：To st udy the chemical constituents of diterpenoids from Buyi medicine Isodon coetsa ，and to provide reference for the development and utilization of the medicinal resources. METHODS ：The 95％ methanol extract of Buyi medicine I. coetsa were isolated and purified with silica gel column ，Sehadex LH- 20 gel column and MCI column. The structures of the compounds were obtained by spectral analysis （mass spectrum ，hydrogen spectrum and carbon spectrum ），and then compared with active components of Miao medicine “Isodon flavidus ”. RESULTS & CONCLUSIONS ：Ten diterpenoids were obtained from I. coetsa，including rabdocoetsin B （Ⅰ），megathgrin B （Ⅱ），rabdocoetsin A （Ⅲ），enanderianin N （Ⅳ），rabdocoetsin D （Ⅴ）， megathyrin A （Ⅵ），lophanic acid （Ⅶ），rubesanolide D （Ⅷ），excisanin D （Ⅸ），excisanin K （Ⅹ）. The compounds Ⅶ，Ⅸ and Ⅹ were isolated from this specie for the first time. Compound Ⅶ（lophanic acid ）is a common active component in the Buyi medicine I. coetsa and Miao medicine “I. flavidus ”.

Mizoribine(MZR), as an orally prescribed immunosuppressive agent, has been applied in the prevention of rejection after kidney transplantation.MZR requires individual dosing due to the variation of bioavailability.However, therapeutic drug monitoring (TDM) of MZR is not well developed in China, as compared to other clinically used immunosuppressive agents.To our knowledge, this is the first TDM review of MZR.Pharmacokinetic characteristic, concentration determination methods and sample selection of MZR were summarized, also the rational therapeutic window was proposed.Furthermore, gene polymorphism and population pharmacokinetics of MZR were estimated.This review will provide reference for TDM-based individual dosing of MZR in renal transplant recipients.

Objective To evaluate the in vitro antimicrobial activity of tigecycline in combination with imipenem against multi-drug resistant and pan-drug resistant Acinetobacter baumannii isolates,so as to discuss the feasibility of drug combination and provide the basis for chnical rational use of antimicrobial agents.Methods Sixteen multi-drug resistant and pan-drug resistant Acinetobacter baumannii isolates were collected between January and April in 2015 from all kinds of infected specimens of Nanjing Drun Tower Hospital.The protocol was designed by checkerboard method,and the minimum inhibitory concentration (MIC) of antibiotics was determined by microdilution broth method,and the fractional inhibitory concentration (FIC) index was calculated according to MIC results.Results The average value of MIC (MICG),MIC50,MIC90 of tigecycline and imipenem single were 1.73,1,4 μg·mL-1and 31.00,32,64 μg·mL-1.When tigecycline was combined with imipenem,MICG,MIC50,MIC90 of tigecycline and imipenem were 0.24,0.25,0.50 μg·mL-1 and 8.16,8.00,16.00 μg·mL-1,respectively.Compared with the drug single use groups,MIC was significandy decreased in the drug combination group.In 6 strains (37.50％),synergy effect (FIC≤0.5) was observed,and in 10 strains (62.50％),additive effect (0.5 ＜ FIC ≤ 1) was found.No negative and independent effects were shown.Conclusion Both additive and synergistic action is observed when tigecyclineis combined with imipenem against multi-drug resistant and pan-drug resistant Acinetobacter baumannii isolates.No negative and independent effects are shown.This combination use against multi-drug resistant and pan-drug resistant Acinetobacter baumannii may be an effective therapy for clinical treatment.

AIM:To investigate the effect of Shenci capsule combined with cisplatin ( DDP) in reversing DDP resistance by PI3K/AKT/mTOR signaling pathway in nude mice bearing A 549/DDP tumor.METHODS:The patient-de-rived lung adenocarcinoma A 549/DDP cell xenograft model was established .The tumor-bearing nude mice were randomly divided into control group , Shenci capsule group , DDP group and Shenci capsule combined with DDP group .The mice in control group was treated with normal saline , while the mice in other groups were treated with different drugs for 21 d.After treatment, the mice were killed and lung cancer tissues were collected .Flow cytometry was used to analyze the cell cycle and apoptosis.FQ-PCR was used to determined the mRNA levels of PTEN , P-glycoprotein, PI3K, AKT and mTOR in A549/DDP lung tumor .RESULTS:Compared with control group , the cell proliferation in all the drug treatment groups was inhibited .Compared with other drug treatment groups , Shenci capsule combined with DDP blocked the cell cycle of A 549/DDP cells at G2/M phase, promoted the apoptosis rate , increased the mRNA expression of PTEN and inhibited the mRNA expression of P-glycoprotein, PI3K, AKT and mTOR.CONCLUSION:Shenci capsule increases the sensitivity of A 549/DDP resistant cells in nude mice to DDP by blocking PI 3K/AKT/mTOR signaling pathway , increasing the expression of PTEN or inhibiting P-glycoprotein-mediated resistance pathway .

Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.

OBJECTIVE:To provide reference for rational use of antidepressive drugs. METHODS:In retrospective study,the utilization of antidepressive drugs in 31 hospitals of Nanjing area during 2013-2015 was analyzed statistically in respects of consump-tion sum,DDDs,DDC,B/A,etc. RESULTS:There were a total of 20 kinds of antidepressive drugs in 31 hospitals of Nanjing ar-ea,and total consumption sum increased year by year,increasing from 76 085 200 yuan in 2013 to 100 812 500 yuan in 2015,in-creased by 17.43% compared to 2014 and by 12.83% compared to 2015. The top 4 drugs in the list of consumption sum and DDDs were paroxetine,escitalopram,sertraline and venlafaxine. The sum of their consumption sum accounted for more than 60% of total consumption sum. The consumption sum of plant antidepressive drugs increased rapidly. B/A and DDC of antidepressive drugs kept sta-ble each year compared to last year,among which DDC of doxepin,clomipramine and amitriptyline was less than 2 yuan,B/A val-ues of sertraline,fluvoxamine,flupentixol and melitracen,doxepin,clomipramine and amitriptyline were all more than 1.00. CON-CLUSIONS:Of antidepressive drugs in 31 hospitals of Nanjing area during 2013-2015,selective serotonin reuptake inhibitors and se-lective serotonin-norepinephrine reuptake inhibitors took up dominant place,and plant antidepressive drugs is promising in the future.

Drug for cholestasis therapy is extremely limited.Ur-sodeoxycholic acid is currently the only FDA approved drug to treat primary biliary cirrhosis,whereas its efficacy is limited to early stage of the disease.Therefore,developing novel drugs re-presents a major goal for both pharmaceutical industry and aca-demic researchers.Targeting nuclear receptors in cholestasis is an intriguing approach since these receptors are critically in-volved in the regulation of bile acid homeostasis.This review summarizes the roles of individual nuclear receptors in cholestasis and evaluates their potential clinical application.