Objective： To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in clinical practice.This review attempted to provide a thorough comparison a...Objective： To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in clinical practice.This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib,erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.Data Sources： An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib,icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.Study Selection： The search terms or keywords included but not limited to ＆quot;lung cancer＆quot;, ＆quot;nonsmall cell lung cancer （NSCLC）＆quot;,＆quot;epidemiology＆quot;, ＆quot;EGFR＆quot;, ＆quot;TKIs＆quot;, and ＆quot;optimal selection＆quot;.Results： As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain.The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food.The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage.Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food.Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment.In marked contrast, icotinib is available only in China as the second-or third-line therapeutic approach for treating advanced lung cancer.In addition, it exhibits a similar efficacy but better safety profile than gefitinib.Conclusions： Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC.展开更多
Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much un...Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much uncertainty in clinical practice.We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention （PCI） in a long-term follow-up study.Methods：A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy （DAPT） at a single center from January 2013 to December 2013 were enrolled.Adenosine diphosphate （ADP）-induced platelet aggregation inhibition was measured by modified thromboelastography （mTEG） in 5042 patients.Propensity score matching （PSM） was applied to control differing baseline factors.Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events （MACCEs）,as well as individual events,including all-cause death,myocardial infarction,unplanned target vessel revascularization,stent thrombosis,and stroke.Results：Among the whole cohort,27.2% were prescribed PPIs.The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users （42.0 ± 30.9% vs.46.4 ± 31.4%,t =4.435,P 〈 0.001）.Concomitant PPI use was not associated with increased MACCE through 2-year follow-up （12.7% vs.12.5%,x2 =0.086,P =0.769）.Other endpoints showed no significant differences after multivariate adjustment,regardless of PSM.Conclusion：In this large cohort of real-world patients,the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.展开更多
Background： The effect of selective and non-selective cyclooxygenase （COX） inhibitors on tendon healing was variable. The purpose of the study was to evaluate the influence of non-selective COX inhibitor, ibuprofen...Background： The effect of selective and non-selective cyclooxygenase （COX） inhibitors on tendon healing was variable. The purpose of the study was to evaluate the influence of non-selective COX inhibitor, ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor, celecoxib on the tendon healing process in a rabbit model. Methods： Ninety-six New Zealand rabbits were used as rotator cuff repair models. After surgery, they were divided randomly into four groups： Ibuprofen （10 mg·kg^-1·d^-1）, celecoxib （8 mg·kg^-1·d^-1）, flurbiprofen axetil （2 mg·kg^-1·d^-1）, and control group （blank group）. All drugs were provided for 7 days. Rabbits in each group were sacrificed at 3, 6, and 12 weeks after tendon repair. Tendon biomechanical load failure tests were performed. The percentage of type I collagen on the bone tendon insertion was calculated by Pieric acid Sirius red staining and image analysis. All data were compared among the four groups at the same time point. All data in each group were also compared across the different time points. Qualitative histological evaluation of the bone tendon insertion was also performed among groups. Results： The load to failure increased significantly with time in each group. There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks （0.533 vs. 0.700, P = 0.002）, 6 weeks （0.607 vs. 0.763, P = 0.01）, and 12 weeks （0.660 vs. 0.803, P = 0.002）, and significantly lower percentage of type I collagen at 3 weeks （11.5% vs. 27.6%, P 0.001）, 6 weeks （40.5% vs. 66.3%, P = 0.005）, and 12 weeks （59.5% vs. 86.3%, P = 0.001）. Flurbiprofen axetil showed significant differences at 3 weeks （failure load： 0.600 vs. 0.700, P = 0.024; percentage of type I collagen： 15.6% vs. 27.6%, P = 0.001）, but no significant differences at 6 and 12 weeks comparing with control group, whereas the ibuprofen groups did not show any significant difference at each time point. Conclusions： Nonsteroidal anti-inflammatory drugs can delay tendon healing in the early stage after rotator cuff repair. Compared with nonselective COX inhibitors, selective COX-2 inhibitors significantly impact tendon healing.展开更多
Background： Nucleoside reverse transcriptase inhibitors （NRTIs） are the earliest and most commonly used anti-human immunodeficiency virus drugs and play an important role in high active antiretroviral therapy. Howe...Background： Nucleoside reverse transcriptase inhibitors （NRTIs） are the earliest and most commonly used anti-human immunodeficiency virus drugs and play an important role in high active antiretroviral therapy. However, NRTI drug therapy can cause peripheral neuropathic pain. In this study, we aimed to investigate the mechanisms ofrapamycin on the pain sensitization of model mice by in vivo experiments to explore the effect of mammalian target of rapamycin （mTOR） in the pathogenesis ofneuropathic pain caused by NRTIs. Methods： Male Kun Ming （KM） mice weighing 20-2 g were divided into control, 2 mg/kg rapamycin, 12 mg/kg stavudine, and CMC-Na groups. Drugs were orally administered to mice for 42 consecutive days. The von Frey filament detection and thermal pain tests were conducted on day 7, 14, 21, 28, 35, and 42 after drug administration. After the last behavioral tests, immunohistochemistry and western blotting assay were used for the measurement of mTOR and other biomarkers. Multivariate analysis of variance was used. Results： The beneficial effects ofrapamycin on neuropathic pain were attributed to a reduction in mammalian target of rapamycin sensitive complex 1 （mTORC1）-positive cells （70.80± 2.41 vs. 112.30 ± 5.66, F = 34.36, P 〈 0.01 ） and mTORC1 activity in the mouse spinal cord. Mechanistic studies revealed that Protein Kinase B （Akt）/mTOR signaling pathway blockade with rapamycin prevented the phosphorylation of mTORC1 in stavudine-intoxicated mice （0.72 ± 0.04 vs. 0.86 ± 0.03, F=4.24, P = 0.045）, as well as decreased the expression of phospho-pTOS6K （0.47 ± 0.01 vs. 0.68 ± 0.03, F=6.01, P = 0.022） and phospho-4EBP1 （0.90 ± 0.04 vs. 0.94 ± 0.06, F= 0.28, P = 0.646）. Conclusions： Taken together, these results suggest that stavudine elevates the expression and activity of mTORC1 in the spinal cord through activating the Akt/mTOR signaling pathway. The data also provide evidence that rapamycin might be useful for the treatment of peripheral neuropathic pain.展开更多
文摘Objective： To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in clinical practice.This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib,erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.Data Sources： An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib,icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.Study Selection： The search terms or keywords included but not limited to ＆quot;lung cancer＆quot;, ＆quot;nonsmall cell lung cancer （NSCLC）＆quot;,＆quot;epidemiology＆quot;, ＆quot;EGFR＆quot;, ＆quot;TKIs＆quot;, and ＆quot;optimal selection＆quot;.Results： As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain.The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food.The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage.Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food.Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment.In marked contrast, icotinib is available only in China as the second-or third-line therapeutic approach for treating advanced lung cancer.In addition, it exhibits a similar efficacy but better safety profile than gefitinib.Conclusions： Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with advanced NSCLC.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81470486）, and the National Key Research and Development Program of China during the 13^th 5-Year Plan Period （No. 2016YFC1301301）.
文摘Background：Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors （PPIs） combined with clopidogrel therapy,causing much uncertainty in clinical practice.We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention （PCI） in a long-term follow-up study.Methods：A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy （DAPT） at a single center from January 2013 to December 2013 were enrolled.Adenosine diphosphate （ADP）-induced platelet aggregation inhibition was measured by modified thromboelastography （mTEG） in 5042 patients.Propensity score matching （PSM） was applied to control differing baseline factors.Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events （MACCEs）,as well as individual events,including all-cause death,myocardial infarction,unplanned target vessel revascularization,stent thrombosis,and stroke.Results：Among the whole cohort,27.2% were prescribed PPIs.The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users （42.0 ± 30.9% vs.46.4 ± 31.4%,t =4.435,P 〈 0.001）.Concomitant PPI use was not associated with increased MACCE through 2-year follow-up （12.7% vs.12.5%,x2 =0.086,P =0.769）.Other endpoints showed no significant differences after multivariate adjustment,regardless of PSM.Conclusion：In this large cohort of real-world patients,the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.
基金This study was supported by the grants from the National Natural Science Foundation，from the Training Program of Beijing Senior Medical Technical Personnel
文摘Background： The effect of selective and non-selective cyclooxygenase （COX） inhibitors on tendon healing was variable. The purpose of the study was to evaluate the influence of non-selective COX inhibitor, ibuprofen and flurbiprofen axetil and selective COX-2 inhibitor, celecoxib on the tendon healing process in a rabbit model. Methods： Ninety-six New Zealand rabbits were used as rotator cuff repair models. After surgery, they were divided randomly into four groups： Ibuprofen （10 mg·kg^-1·d^-1）, celecoxib （8 mg·kg^-1·d^-1）, flurbiprofen axetil （2 mg·kg^-1·d^-1）, and control group （blank group）. All drugs were provided for 7 days. Rabbits in each group were sacrificed at 3, 6, and 12 weeks after tendon repair. Tendon biomechanical load failure tests were performed. The percentage of type I collagen on the bone tendon insertion was calculated by Pieric acid Sirius red staining and image analysis. All data were compared among the four groups at the same time point. All data in each group were also compared across the different time points. Qualitative histological evaluation of the bone tendon insertion was also performed among groups. Results： The load to failure increased significantly with time in each group. There were significantly lower failure loads in the celecoxib group than in the control group at 3 weeks （0.533 vs. 0.700, P = 0.002）, 6 weeks （0.607 vs. 0.763, P = 0.01）, and 12 weeks （0.660 vs. 0.803, P = 0.002）, and significantly lower percentage of type I collagen at 3 weeks （11.5% vs. 27.6%, P 0.001）, 6 weeks （40.5% vs. 66.3%, P = 0.005）, and 12 weeks （59.5% vs. 86.3%, P = 0.001）. Flurbiprofen axetil showed significant differences at 3 weeks （failure load： 0.600 vs. 0.700, P = 0.024; percentage of type I collagen： 15.6% vs. 27.6%, P = 0.001）, but no significant differences at 6 and 12 weeks comparing with control group, whereas the ibuprofen groups did not show any significant difference at each time point. Conclusions： Nonsteroidal anti-inflammatory drugs can delay tendon healing in the early stage after rotator cuff repair. Compared with nonselective COX inhibitors, selective COX-2 inhibitors significantly impact tendon healing.
文摘Background： Nucleoside reverse transcriptase inhibitors （NRTIs） are the earliest and most commonly used anti-human immunodeficiency virus drugs and play an important role in high active antiretroviral therapy. However, NRTI drug therapy can cause peripheral neuropathic pain. In this study, we aimed to investigate the mechanisms ofrapamycin on the pain sensitization of model mice by in vivo experiments to explore the effect of mammalian target of rapamycin （mTOR） in the pathogenesis ofneuropathic pain caused by NRTIs. Methods： Male Kun Ming （KM） mice weighing 20-2 g were divided into control, 2 mg/kg rapamycin, 12 mg/kg stavudine, and CMC-Na groups. Drugs were orally administered to mice for 42 consecutive days. The von Frey filament detection and thermal pain tests were conducted on day 7, 14, 21, 28, 35, and 42 after drug administration. After the last behavioral tests, immunohistochemistry and western blotting assay were used for the measurement of mTOR and other biomarkers. Multivariate analysis of variance was used. Results： The beneficial effects ofrapamycin on neuropathic pain were attributed to a reduction in mammalian target of rapamycin sensitive complex 1 （mTORC1）-positive cells （70.80± 2.41 vs. 112.30 ± 5.66, F = 34.36, P 〈 0.01 ） and mTORC1 activity in the mouse spinal cord. Mechanistic studies revealed that Protein Kinase B （Akt）/mTOR signaling pathway blockade with rapamycin prevented the phosphorylation of mTORC1 in stavudine-intoxicated mice （0.72 ± 0.04 vs. 0.86 ± 0.03, F=4.24, P = 0.045）, as well as decreased the expression of phospho-pTOS6K （0.47 ± 0.01 vs. 0.68 ± 0.03, F=6.01, P = 0.022） and phospho-4EBP1 （0.90 ± 0.04 vs. 0.94 ± 0.06, F= 0.28, P = 0.646）. Conclusions： Taken together, these results suggest that stavudine elevates the expression and activity of mTORC1 in the spinal cord through activating the Akt/mTOR signaling pathway. The data also provide evidence that rapamycin might be useful for the treatment of peripheral neuropathic pain.
