Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COP...Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:A total of 120 cases of COPD patients with respiratory failure from June 2017 to December 2018 were randomly divided into two groups:60 cases in the control group and 60 cases in the observation group.The control group received spontaneous breathing trials for 2 h to select the time for non-invasive positive pressure ventilation,while the observation group received peripheral blood TREM-1(≤90.0 pg/mL)to select the time for non-invasive positive pressure ventilation.The stress hormones,clinical pulmonary infection score and vital signs of two groups after 24 h of mechanical ventilation were detected.The treatment time and the adverse reactions of the two groups were recorded.Results:There was no significant difference in rennin,adrenaline,noradrenaline and angiotensin II between two groups(P>0.05).Compared with the control group,the clinical pulmonary infection score was decreased in the observation group(P<0.05).There was no significant difference in heart rate,respiratory rate,pH,partial pressure of carbon dioxide and partial pressure of oxygen between two groups(P>0.05).There was no significant difference in intensive care monitoring time between two groups(P>0.05).Compared with the control group,the observation group had no significant difference in invasive ventilation time and total mechanical ventilation.The time of hospitalization and hospitalization had significantly decreased(P<0.05).There was no significant difference in mortality,ventilator-associated pneumonia and re-intubation between two groups(P>0.05).Conclusion:TREM-1 can be used as a switching point during invasive-noninvasive sequential ventilation for COPD patients with respiratory failure,which can shorten the time of invasive ventilation,total mechanical ventilation and hospitaliza展开更多
Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,swit...Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA.We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia(ITP)patients.Methods:This prospective,open-label,observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China.The study evaluated response rates and platelet counts at different time points after the switch,bleeding events,time to response,duration of response,and adverse events.Results:At 6 weeks after switching,response was observed in 21/49 patients(43%)who switched for inefficacy and 34/47 patients(72%)who switched for non-efficacy-related issues.In the inefficacy group,9/27 patients(33%)responded to eltrombopag,and 12/22 patients(55%)responded to rh-TPO.In the non-efficacy-related group,21/26(81%)and 13/21(62%)patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching,respectively.Response at 6 months was achieved in 24/49 patients(49%)switching for inefficacy and 37/47 patients(79%)switching for non-efficacy issues.In the inefficacy group,13/27 patients(48%)responded to eltrombopag,and 11/22 patients(50%)responded to rh-TPO.In the non-efficacy-related group,22/26 patients(85%)and 15/21 patients(71%)in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching,respectively.Both eltrombopag and rh-TPO were well tolerated.Conclusions:Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA.When the switch was motivated by other reasons,including p展开更多
Considerable efforts are currently being devoted to investigation of metal-organic, organic-organic and organic-inorganic interfaces relevant to organic electronic devices such as organic light emitting diode (OLEDs),...Considerable efforts are currently being devoted to investigation of metal-organic, organic-organic and organic-inorganic interfaces relevant to organic electronic devices such as organic light emitting diode (OLEDs), organic photovoltaic solar cells, organic field effect transistors (OFETs), organic spintronic devices and organic-based Write Once Read Many times (WORM) memory devices on both rigid and flexible substrates in laboratories around the world. The multilayer structure of these devices makes interfaces between dissimilar materials in contact and plays a prominent role in charge transport and injection efficiency which inevitably affect device performance. This paper presents results of an initial study on how switching between voltage thresholds and chemical surface treatment affects adhesion properties of a metal-organic (Au-PEDOT:PSS) contact interface in a WORM device. Contact and Tapping-mode Atomic Force Microscopy (AFM) gave surface topography, phase imaging and interface adhesion properties in addition to SEM/EDX imaging which showed that surface treatment, switching and surface roughness all appeared to be key factors in increasing interface adhesion with implications for increased device performance.展开更多
Background:Antiretroviral therapy(ART)restores immune function and reduces human immunodeficiency virus(HIV)related adverse outcomes.The results of previous studies in Ethiopia were replete with inconsistent findings;...Background:Antiretroviral therapy(ART)restores immune function and reduces human immunodeficiency virus(HIV)related adverse outcomes.The results of previous studies in Ethiopia were replete with inconsistent findings;nonexistence of national representative figures and determinant factors are found as significant gap.The aim of this systematic review and meta-analysis was to assess the existing evidence on ART treatment failure and associated factors in Ethiopia.Methods:Relevant studies on ART treatment failure were retrieved from international databases:PubMed,Google Scholar,Scopus,and Science Direct systematically prior to March 14,2019.All identified studies reporting the proportion of first line treatment failure among HIV patients in Ethiopia were included.Two authors independently extracted all necessary data using a standardized data extraction format.A random-effects model was used to calculate pooled estimates and associated factors in Stata/se Version-14.The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the studies.Results:From 18 articles reviewed;the pooled proportion of first line treatment failure among ART users in Ethiopia was 15.3%(95%CI:12,18.6)with(I2=97.9%,p<0.001).The subgroup analysis by World Health Organization(WHO)treatment failure assessment criteria were carried out,accordingly the highest prevalence(11.5%)was noted on immunological and the lowest(5.8%)was observed virological treatment failure.We had found poor adherence(OR=8.6,95%CI:5.6,13.4),not disclosed(OR=2.1,95%CI:1.5,3.0),advanced WHO clinical stage III/IV(OR=2.4,95%CI:1.5,3.8),change in regimen(OR=2.5,95%CI:1.6,3.9)and being co-infected(OR=2.56,95%CI:2.2,3.0)were statistically significant factors for treatment failure.Conclusion:In this study,treatment failure among ART users in Ethiopia was significant.Adherence,co-infection,advanced WHO clinical stage,regimen change,and disclosure are determinant factors for treatment failure.Therefore,improve drug adherence,prevent co-infection,close follow 展开更多
Aim:To determine the proteins that interact with the carboxyl-terminal of theμopioid receptor(MOR-C)after chronic morphine exposure.Methods:The brain cDNA library of chronic morphine treatment rats was screened using...Aim:To determine the proteins that interact with the carboxyl-terminal of theμopioid receptor(MOR-C)after chronic morphine exposure.Methods:The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study.The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART(Switching Mechanism At 5′end of RNA Transcript)technique.Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library.RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment.Column overlay assays,immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor(NADE)or A20-binding inhibitor of nuclear factor kB(ABIN-1).Results:21 positive proteins,including 19 known proteins were screened to interact with rat MOR-C.Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment.Among these proteins,ABIN-1 and NADE were confirmed to interact with rat MOR-C by in vitro proteinprotein binding and coimmunoprecipitation in Chinese hamster ovary(CHO)cells and rat brain with or without chronic morphine treatment.Saturation binding studies showed that ABIN-1 had no effect on MOR binding.However,the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin).MOR phosphorylation,ubiquitination,and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1.The suppression of forskolinstimulated adenylylcyclase by DAMGO was also inhibited by the interaction of ABIN-1with MOR.In addition,extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1.These data suggest that ABIN-1 is a negative coregulator of MOR activation,phosphoryl展开更多
目的:本文介绍等级结构保留失效时间模型(rank preserving structural failure time models,RPSFT)和BW法(the method of Branson and Whitehead)在临床试验转组研究中的应用,并对两种方法进行比较。方法:以部分对照组受试者在试验中途...目的:本文介绍等级结构保留失效时间模型(rank preserving structural failure time models,RPSFT)和BW法(the method of Branson and Whitehead)在临床试验转组研究中的应用,并对两种方法进行比较。方法:以部分对照组受试者在试验中途转至试验组为例,采用计算机模拟试验,查看不同截尾率、转组率水平下,RPSFT法和BW法估计试验药疗效的效果。以及探讨与传统的ITT法相比,RPSFT法和BW法的检验效能和Ⅰ类错误控制情况。结果:RPSFT法和BW法估计试验药疗效的准确性高,与传统的分析方法比较,引入的偏倚小。随着转组率和截尾率增大,RPSFT法与BW法的偏倚逐渐增大,估计的试验药疗效低于真实疗效,但RPSFT法的偏倚比BW法小。两种方法估计的均方误差(MSE)十分接近。当截尾率较大(40%)时,RPSFT法的MSE比BW小。随着转组率增大,两种方法的Ⅰ类错误不断升高,普遍高于0.05。与ITT法相比,RPSFT法与BW法的检验效能受转组率的影响小,下降趋势缓慢。结论:在估计试验药疗效的临床试验中,若存在对照组受试者转组到试验组的情况,统计分析以ITT法分析为主,RPSFT法和BW法作为辅助分析方法。RPSFT法和BW法相比,当截尾率和转组率均较高时,参数估计优先考虑选择使用RPSFT法。展开更多
AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systemati...AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that 展开更多
基金This study was supported by the National Natural Science Foundation of China(Grant No.81870076)the Suzhou Medical Key Discipline Funding Project(Grant No.SZXK201821).
文摘Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:A total of 120 cases of COPD patients with respiratory failure from June 2017 to December 2018 were randomly divided into two groups:60 cases in the control group and 60 cases in the observation group.The control group received spontaneous breathing trials for 2 h to select the time for non-invasive positive pressure ventilation,while the observation group received peripheral blood TREM-1(≤90.0 pg/mL)to select the time for non-invasive positive pressure ventilation.The stress hormones,clinical pulmonary infection score and vital signs of two groups after 24 h of mechanical ventilation were detected.The treatment time and the adverse reactions of the two groups were recorded.Results:There was no significant difference in rennin,adrenaline,noradrenaline and angiotensin II between two groups(P>0.05).Compared with the control group,the clinical pulmonary infection score was decreased in the observation group(P<0.05).There was no significant difference in heart rate,respiratory rate,pH,partial pressure of carbon dioxide and partial pressure of oxygen between two groups(P>0.05).There was no significant difference in intensive care monitoring time between two groups(P>0.05).Compared with the control group,the observation group had no significant difference in invasive ventilation time and total mechanical ventilation.The time of hospitalization and hospitalization had significantly decreased(P<0.05).There was no significant difference in mortality,ventilator-associated pneumonia and re-intubation between two groups(P>0.05).Conclusion:TREM-1 can be used as a switching point during invasive-noninvasive sequential ventilation for COPD patients with respiratory failure,which can shorten the time of invasive ventilation,total mechanical ventilation and hospitaliza
基金Beijing Natural Science Foundation(No.H2018206423)National Natural Science Foundation of China(No.81970113)+1 种基金Key Program of National Natural Science Foundation of China(No.81730004)National Key Research and Development Program of China(No.2017YFA0105503)。
文摘Background:Recombinant human thrombopoietin(rh-TPO)and eltrombopag are two distinct TPO receptor agonists(TPO-RAs)with different mechanisms.During the pandemic,when immunosuppressive medications are controversial,switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA.We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia(ITP)patients.Methods:This prospective,open-label,observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People’s Hospital in China.The study evaluated response rates and platelet counts at different time points after the switch,bleeding events,time to response,duration of response,and adverse events.Results:At 6 weeks after switching,response was observed in 21/49 patients(43%)who switched for inefficacy and 34/47 patients(72%)who switched for non-efficacy-related issues.In the inefficacy group,9/27 patients(33%)responded to eltrombopag,and 12/22 patients(55%)responded to rh-TPO.In the non-efficacy-related group,21/26(81%)and 13/21(62%)patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching,respectively.Response at 6 months was achieved in 24/49 patients(49%)switching for inefficacy and 37/47 patients(79%)switching for non-efficacy issues.In the inefficacy group,13/27 patients(48%)responded to eltrombopag,and 11/22 patients(50%)responded to rh-TPO.In the non-efficacy-related group,22/26 patients(85%)and 15/21 patients(71%)in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching,respectively.Both eltrombopag and rh-TPO were well tolerated.Conclusions:Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA.When the switch was motivated by other reasons,including p
文摘Considerable efforts are currently being devoted to investigation of metal-organic, organic-organic and organic-inorganic interfaces relevant to organic electronic devices such as organic light emitting diode (OLEDs), organic photovoltaic solar cells, organic field effect transistors (OFETs), organic spintronic devices and organic-based Write Once Read Many times (WORM) memory devices on both rigid and flexible substrates in laboratories around the world. The multilayer structure of these devices makes interfaces between dissimilar materials in contact and plays a prominent role in charge transport and injection efficiency which inevitably affect device performance. This paper presents results of an initial study on how switching between voltage thresholds and chemical surface treatment affects adhesion properties of a metal-organic (Au-PEDOT:PSS) contact interface in a WORM device. Contact and Tapping-mode Atomic Force Microscopy (AFM) gave surface topography, phase imaging and interface adhesion properties in addition to SEM/EDX imaging which showed that surface treatment, switching and surface roughness all appeared to be key factors in increasing interface adhesion with implications for increased device performance.
文摘Background:Antiretroviral therapy(ART)restores immune function and reduces human immunodeficiency virus(HIV)related adverse outcomes.The results of previous studies in Ethiopia were replete with inconsistent findings;nonexistence of national representative figures and determinant factors are found as significant gap.The aim of this systematic review and meta-analysis was to assess the existing evidence on ART treatment failure and associated factors in Ethiopia.Methods:Relevant studies on ART treatment failure were retrieved from international databases:PubMed,Google Scholar,Scopus,and Science Direct systematically prior to March 14,2019.All identified studies reporting the proportion of first line treatment failure among HIV patients in Ethiopia were included.Two authors independently extracted all necessary data using a standardized data extraction format.A random-effects model was used to calculate pooled estimates and associated factors in Stata/se Version-14.The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the studies.Results:From 18 articles reviewed;the pooled proportion of first line treatment failure among ART users in Ethiopia was 15.3%(95%CI:12,18.6)with(I2=97.9%,p<0.001).The subgroup analysis by World Health Organization(WHO)treatment failure assessment criteria were carried out,accordingly the highest prevalence(11.5%)was noted on immunological and the lowest(5.8%)was observed virological treatment failure.We had found poor adherence(OR=8.6,95%CI:5.6,13.4),not disclosed(OR=2.1,95%CI:1.5,3.0),advanced WHO clinical stage III/IV(OR=2.4,95%CI:1.5,3.8),change in regimen(OR=2.5,95%CI:1.6,3.9)and being co-infected(OR=2.56,95%CI:2.2,3.0)were statistically significant factors for treatment failure.Conclusion:In this study,treatment failure among ART users in Ethiopia was significant.Adherence,co-infection,advanced WHO clinical stage,regimen change,and disclosure are determinant factors for treatment failure.Therefore,improve drug adherence,prevent co-infection,close follow
基金This work was supported by the National Natural Science Foundation of China(30901799,81473194),the Natural Science Foundation of Beijing(7092078).
文摘Aim:To determine the proteins that interact with the carboxyl-terminal of theμopioid receptor(MOR-C)after chronic morphine exposure.Methods:The brain cDNA library of chronic morphine treatment rats was screened using rat MOR-C to investigate the regulator of opioids dependence in the present study.The brain cDNA library from chronic morphine-dependent rats was constructed using the SMART(Switching Mechanism At 5′end of RNA Transcript)technique.Bacterial two-hybrid system was used to screening the rat MOR-C interacting proteins from the cDNA library.RT-qPCR and immunoblotting were used to determine the variation of MOR-C interacting proteins in rat brain after chronic morphine treatment.Column overlay assays,immunocytochemistry and coimmunoprecipitation were used to demonstrate the interaction of MOR-C and p75NTR-associated cell death executor(NADE)or A20-binding inhibitor of nuclear factor kB(ABIN-1).Results:21 positive proteins,including 19 known proteins were screened to interact with rat MOR-C.Expression of several of these proteins was altered in specific rat brain regions after chronic morphine treatment.Among these proteins,ABIN-1 and NADE were confirmed to interact with rat MOR-C by in vitro proteinprotein binding and coimmunoprecipitation in Chinese hamster ovary(CHO)cells and rat brain with or without chronic morphine treatment.Saturation binding studies showed that ABIN-1 had no effect on MOR binding.However,the interaction of ABIN-1 and MOR inhibited the activation of G proteins induced by DAMGO([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin).MOR phosphorylation,ubiquitination,and internalization induced by DAMGO were decreased in Chinese hamster ovary cells that coexpressed MOR and ABIN-1.The suppression of forskolinstimulated adenylylcyclase by DAMGO was also inhibited by the interaction of ABIN-1with MOR.In addition,extracellular signal-regulated kinase activation was also negatively regulated by overexpression of ABIN-1.These data suggest that ABIN-1 is a negative coregulator of MOR activation,phosphoryl
文摘目的:本文介绍等级结构保留失效时间模型(rank preserving structural failure time models,RPSFT)和BW法(the method of Branson and Whitehead)在临床试验转组研究中的应用,并对两种方法进行比较。方法:以部分对照组受试者在试验中途转至试验组为例,采用计算机模拟试验,查看不同截尾率、转组率水平下,RPSFT法和BW法估计试验药疗效的效果。以及探讨与传统的ITT法相比,RPSFT法和BW法的检验效能和Ⅰ类错误控制情况。结果:RPSFT法和BW法估计试验药疗效的准确性高,与传统的分析方法比较,引入的偏倚小。随着转组率和截尾率增大,RPSFT法与BW法的偏倚逐渐增大,估计的试验药疗效低于真实疗效,但RPSFT法的偏倚比BW法小。两种方法估计的均方误差(MSE)十分接近。当截尾率较大(40%)时,RPSFT法的MSE比BW小。随着转组率增大,两种方法的Ⅰ类错误不断升高,普遍高于0.05。与ITT法相比,RPSFT法与BW法的检验效能受转组率的影响小,下降趋势缓慢。结论:在估计试验药疗效的临床试验中,若存在对照组受试者转组到试验组的情况,统计分析以ITT法分析为主,RPSFT法和BW法作为辅助分析方法。RPSFT法和BW法相比,当截尾率和转组率均较高时,参数估计优先考虑选择使用RPSFT法。
文摘AIM: To review evidence supporting pharmacological treatments for treatment-resistant depression(TRD) and to discuss them according to personal clinical experience.METHODS: Original studies, clinical trials, systematic reviews, and meta-analyses addressing pharmacological treatment for TRD in adult patients published from 1990 to 2013 were identified by data base queries(Pub Med, Google Scholar e Quertle Searches) using terms: "treatment resistant depression", "treatment refractory depression", "partial response depression", "non responder depression", "optimization strategy", "switching strategy", "combination strategy", "augmentation strategy", selective serotonin reuptake inhibitors antidepressants(SSRI), tricyclic antidepressants(TCA), serotonin norepinephrine reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione, monoamine oxidase inhibitor antidepressant(MAOI), lithium, thyroid hormones, second generation antipsychotics(SGA), dopamine agonists, lamotrigine, psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S-adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents. Other citations of interest were further identified from references reported in the accessed articles. Selected publications were grouped by treatment strategy:(1) switching from an ineffective antidepressant(AD) to a new AD from a similar or different class;(2) combining the current AD regimen with a second AD from a different class; and(3) augmenting the current AD regimen with a second agent not thought to be an antidepressant itself.RESULTS: Switching from a TCA to another TCA provides only a modest advantage(response rate 9%-27%), while switching from a SSRI to another SSRI is more advantageous(response rate up to 75%). Evidence supports the usefulness of switching from SSRI to venlafaxine(5 positive trials out 6), TCA(2 positive trials out 3), and MAOI(2 positive trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three reviews demonstrated that
