Inhibition of Escherichia coli nitroreductase by the constituents in Syzygium aromaticum / 中国天然药物

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds, hydroxylamines or aromatic amines, most of which are carcinogenic and mutagenic agents. Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon, so as to prevent colon diseases. In this study, the inhibitory effects of 55 herbal medicines against Escherichia coli(E. coli) nitroreductase (EcNfsA) were examined. Compared with other herbal extracts, Syzygium aromaticum extract showed superior inhibitory potency toward EcNfsA mediated nitrofurazone reduction. Then, the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted. Compared with other tested natural compounds, ellagic acid, corilagin, betulinic acid, oleanic acid, ursolic acid, urolithin M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA, with IC50 values ranging from 0.67 to 28.98 mol·L-1. Furthermore, the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA (Ki < 2 μmol·L -1) in a competitively inhibitory manner, which created strong interactions with the catalytic triad of EcNfsA. In summary, our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum, where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacterial nitroreductase.

Safety and Efficacy of Dexamethasone Intravitreal Implant in Secondary Macular Edema Patients: A Meta-analysis / 中国药学杂志

OBJECTIVE: To systematically review the safety and efficacy of dexamethasone intravitreal implant (DEX) in secondary macular edema (ME) patients. METHODS: Multiple databases were searched electronically for randomized controlled trials (RCTs) of DEX in secondary ME patients up to April 2019. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Meta-analysis was performed using Rev Man 5.3 software. RESULTS: A total of nine randomized controlled trials involving 1 530 patients were included. There were 737 patients in the experimental group and 793 patients in the control group. DEX was retrieved. Anti-vascular endothelial growth factor (anti-VEGF) or sham injection were used to treat the patients in the control group. The efficacy analysis results showed that the improvement rate of best corrected visual acuity (BCVA) in DEX group was significant higher than the control group in retinal vein occlusion (RVO) patients [MD=-10.59, 95%CI: -13.96--7.23,P=0.01]. The CST/CRT decrease in DEX was significant lower than control group in diabetic macular edema(DME) patients [MD=-63.60, 95%CI: -114.83--12.37,P=0.01], but higher than the control group in RVO [MD=-114.89, 95%CI: -48.68--181.09,P=0.00]. The safty analysis results showed that the incidence of serious adverse events (SAEs) in DEX was significant higher than control group [9.36% (28/299) : 5.23%(19/363), RR=1.94, 95%CI: 1.05-3.59, P=0.04]in RVO. The cataractin DEX was significant higher in RVO [4.87%(22/452) : 0.97% (5/513), RR=5.06, 95%CI: 1.96-13.06, P=0.00] than the control group. CONCLUSION: DEX has better efficacy than anti-VEGF in DME patients. DEX is similar in efficacy but inferior in safety to anti-VEGF in patients with ME secondary to RVO.

Meta-Analysis of the Efficacy and Safety of Uninterrupted NOACs in Patients Undergoing Atrial Fibrillation Catheter Ablation / 中国药学杂志

OBJECTIVE: To systematically assess the efficacy and safety of uninterrupted novel oral anticoagulation (NOAC) in patients undergoing atrial fibrillation catheter ablation. METHODS: Databases including multiple databases were searched electronically for randomized controlled trial (RCT) of NOAC in patients undergoing atrial fibrillation catheter ablation up to October, 2018. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Meta-analysis was performed using Rev Man 5.3 software. RESULTS: A total of 5 RCTs involving 1 843 patients were included. Experimental group including apixaban, rivaroxaban and dabigatran; control group using warfarin. Efficacy outcome including stroke and transient ischemic attack (TIA); safety outcome was major bleeding. RESULTS were as followsthere was no significant difference between experimental group and control group in efficacy outcome; the safety of the experimental group was significantly superior to that of the control group. CONCLUSION: Compared with warfarin, uninterrupted NOACs during percutaneous atrial fibrillation catheter ablation could reduce the risk of major bleeding and would not increase the incident of stroke and TIA.

Using RCT Data to Evaluate the Association of DPP-4 Inhibitors on Pancreatitis and/or Pancreatic Cancer Risk in T2DM: A Systematic Review and Meta-analysis / 中国药学杂志

OBJECTIVE: To review systematically the association of dipeptidyl peptidase-4 inhibitors on pancreatitis and/or pancreatic cancer risk in type-2 diabetes mellitus. METHODS: Databases including The Cochrane Library, PubMed, Embase, Clinical Trials. gov, CNKI, WanFang Data and CBM, were searched electronically for randomized controlled trials (RCTs) of DPP-4 inhibitors in pancreatitis and pancreatic cancer risk in T2DM patients up to June 2017. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Metaanalysis was performed using Rev Man 5.3 software. RESULTS: A total of 39 RCTs involving 65 189 patients were included. The results of Meta-analysis showed that there were no significant differences between the DPP-4 inhibitors group and the control group in the pancreatitis and/or pancreatic cancer adverse events (RR = 0.92, 95%CI 0.69 to 1.23, P = 0.59), pancreatitis (RR = 1.05, 95% CI 0.76 to 1.4, P = 0.79) and pancreatic cancer (RR = 0.62, 95%CI (0.35, 1.08), P = 0.09). Subgroup analyses showed there were no significant differences of acute pancreatitis events between DPP-4 inhibitors group and the control group (RR = 1.42, 95%CI 0.82 to 2.47, P = 0.21). CONCLUSION: The present Meta-analysis of RCTs data does not suggest that DPP-4 inhibitors are associated with pancreatitis and/or pancreatic cancer. Long-term clinical studies are required to further prove this conclusion.

Risk Evaluation of Abnormal Liver Function Associated with LMWH in 76 PTE Patients of Our Hospital / 中国药学杂志

OBJECTIVE: To explore the clinical regularities and risk factor of abnormal liver function associated with LMWH in pulmonary thromboembolism patients. METHODS: Clinical date of pulmonary thromboembolism patients in use of LMWH was collected and analyzed from January 2008 to December 2016. RESULTS: 97 cases were enrolled. Of them, there were 76 cases were assessed as probable or possible. Single factor analysis showed the the levels of Scr (P=0.000), ALT (P=0.000), AST (P=0.000), γ-GGT (P=0.000), ALP (P=0.023), co-infection (P=0.024) and Ccr (P=0.026) had statistically significant difference. Multivariate analysis indicated that co-infection (OR=1.982, P=0.022) and high level of Scr (OR=1.045, P=0.000) were the independent risk factors of abnormal liver function associated with LMWH in PTE. CONCLUSION: The incidence of abnormal liver function due to LMWH in PTE patients is high. With high level of Scr and/or co-infection patients are high-risk persons of abnormal liver function. It is necessary to dynamically evaluate the liver function during hospitalization. Symptomatic treatment can be significant if the liver function become abnormal.