BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture...BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.展开更多
BACKGROUND Early identification of severe/critical coronavirus disease 2019(COVID-19)is crucial for timely treatment and intervention.Chest computed tomography(CT)score has been shown to be a significant factor in the...BACKGROUND Early identification of severe/critical coronavirus disease 2019(COVID-19)is crucial for timely treatment and intervention.Chest computed tomography(CT)score has been shown to be a significant factor in the diagnosis and treatment of pneumonia,however,there is currently a lack of effective early warning systems for severe/critical COVID-19 based on dynamic CT evolution.AIM To develop a severe/critical COVID-19 prediction model using a combination of imaging scores,clinical features,and biomarker levels.METHODS This study used an improved scoring system to extract and describe the chest CT characteristics of COVID-19 patients.The study also took into consideration the general clinical indicators such as dyspnea,oxygen saturation,alternative lengthening of telomeres(ALT),and androgen suppression treatment(AST),which are commonly associated with severe/critical COVID-19 cases.The study employed lasso regression to evaluate and rank the significance of different disease characteristics.RESULTS The results showed that blood oxygen saturation,ALT,IL-6/IL-10,combined score,ground glass opacity score,age,crazy paving mode score,qsofa,AST,and overall lung involvement score were key factors in predicting severe/critical COVID-19 cases.The study established a COVID-19 severe/critical early warning system using various machine learning algorithms,including XGBClassifier,Logistic Regression,MLPClassifier,RandomForestClassifier,and AdaBoost Classifier.The study concluded that the prediction model based on the improved CT score and machine learning algorithms is a feasible method for early detection of severe/critical COVID-19 evolution.CONCLUSION The findings of this study suggest that a prediction model based on improved CT scores and machine learning algorithms is effective in detecting the early warning signals of severe/critical COVID-19.展开更多
Glioma is the most common malignant brain tumor in central nervous system.Despite advances in the treatment of glioma such as surgery and chemoradiotherapy,most patients are easy to relapse,resulting in adverse clinic...Glioma is the most common malignant brain tumor in central nervous system.Despite advances in the treatment of glioma such as surgery and chemoradiotherapy,most patients are easy to relapse,resulting in adverse clinical outcomes.Hence,effective molecular=targeting treatment may be one of attractive strategies for glioma therapy.The dysregulated microRNAs(miRNAs),one of the candidates of therapeutic targets,are believed to play an important role in the progression of glioma.In this study,we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy.Firstly,expression profile of miRNAs in 5 normal brain tissues,5 low-grade glioma(LGG)tissues and 5 glioblastoma(GBM)tissues was detected by RNA sequencing(RNA-seq).Next,the target genes of differentially expressed miRNAs(DEmiRNAs)were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics.Finally,10 miRNAs which were significantly up-or down-regulated both in GBM and LGG were validated by real-time quantitative PCR(qRT-PCR).RNA-seq results indicated a number of DEmiRNAs in glioma.There were 64 up-regulated miRNAs and 17 down-regulated miRNAs n LGG,and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM,respectively.Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process.Selected DEmiRNAs were further confirmed by qRT-PCR.miRNA-10b-5p,miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG;while miRNA-542-3p was significantly up-regulated in LGG;miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG;miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM.The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for gl ioma.展开更多
BACKGROUND Liver injury is common and also can be fatal,particularly in severe or critical patients with coronavirus disease 2019(COVID-19).AIM To conduct an in-depth investigation into the risk factors for liver inju...BACKGROUND Liver injury is common and also can be fatal,particularly in severe or critical patients with coronavirus disease 2019(COVID-19).AIM To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk.METHODS A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9,2020 at Tongji Hospital,Wuhan,China.Data on clinical features,laboratory parameters,medications,and prognosis were collected.RESULTS COVID-19-associated liver injury more frequently occurred in patients aged≥65 years,female patients,or those with other comorbidities,decreased lymphocyte count,or elevated D-dimer or serum ferritin(P<0.05).The disease severity of COVID-19 was an independent risk factor for liver injury(severe patients:Odds ratio[OR]=2.86,95%confidence interval[CI]:1.78-4.59;critical patients:OR=13.44,95%CI:7.21-25.97).The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk(P<0.001).Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury.Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury.CONCLUSION More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients,especially patients aged≥65 years,female patients,or those with other comorbidities.Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.展开更多
BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)pat...BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.展开更多
Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a ...Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.展开更多
Cleavage of ADAMTS-18 by thrombin represents a new mechanism of platelet thrombus clearance via the release of active ~45-kDa C-terminal fragments that induces oxidative platelet fragmentation. The exact cleavage site...Cleavage of ADAMTS-18 by thrombin represents a new mechanism of platelet thrombus clearance via the release of active ~45-kDa C-terminal fragments that induces oxidative platelet fragmentation. The exact cleavage sites remain unclear, but Arg (R)775/Ser (S)776 in spacer region of ADAMTS-18 has been shown to be one of the cleavage sites of thrombin. Here, we demonstrate that R792/S793 and R823/S824 are also thrombin cleavage sites by sequence analysis, amino acid mutation and mass spectrometry assay. All these cleavage sites are thrombin-specific and insensitive to other enzymes tested (e.g. cathepsin D or trypsin). Simultaneous mutation of R775, 792, 823 to S775, 792, 823 in ADAMTS-18 completely abrogated the cleavage by thrombin and the generation of active C-terminal 45-kDa fragments. Together with previous study, a total of three thrombin-specific cleavage sites have been identified in spacer region of ADAMTS-18.展开更多
Background: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of th...Background: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gramnegative bacteria. Methods: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patienfs renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. Results: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii^ and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 土 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cniax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z =-4.157;9.6 [4.2-17.8] vs, 1.3 [0.4-4.7], Z =-4.018;both P< 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z =—3.938;11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z =—3.793;P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/ MIC values were closely associated with clinical and bacteriologic efficacies (P<0.001 in both). Conclusions: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC> 8, cannot be reached.展开更多
Background:Hospital-acquired pneumonia(HAP)is the most common hospital-acquired infection in China with substantial morbidity and mortality.But no specific risk assessment model has been well validated in patients wit...Background:Hospital-acquired pneumonia(HAP)is the most common hospital-acquired infection in China with substantial morbidity and mortality.But no specific risk assessment model has been well validated in patients with HAP.The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.Methods:This study was a single-center,retrospective study.In total,223 patients diagnosed with HAP from 2012 to 2017 were included in this study.Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index(PSI);consciousness,urea nitrogen,respiratory rate,blood pressure,and age≥65 years(CURB-65);Acute Physiology and Chronic Health Evaluation II(APACHE II);Sequential Organ Failure Assessment(SOFA);and Quick Sequential Organ Failure Assessment(qSOFA)scores.The discriminatory power was tested by constructing receiver operating characteristic(ROC)curves,and the areas under the curve(AUCs)were calculated.Results:The all-cause 30-day mortality rate was 18.4%(41/223).The PSI,CURB-65,SOFA,APACHE II,and qSOFA scores were significantly higher in non-survivors than in survivors(all P<0.001).The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores(ROC AUC:APACHE II vs.CURB-65,0.863 vs.0.744,Z=3.055,P=0.002;APACHE II vs.qSOFA,0.863 vs.0.767,Z=3.017,P=0.003;SOFA vs.CURB-65,0.856 vs.0.744,Z=2.589,P=0.010;SOFA vs.qSOFA,0.856 vs.0.767,Z=2.170,P=0.030).The cut-off values we defined for the SOFA,APACHE II,and qSOFA scores were 4,14,and 1.Conclusions:These results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments.The qSOFA score may be a simple tool that can be used to quickly identify severe infections.展开更多
Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distrib...Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of CQ.The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism.Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships.The model was also validated by clinical data from Chinese patients with COVID-19.The novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs(lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19(Day 1:750 mg BID,Days 2-5:500 mg BID,CQ phosphate),patients with moderate COVID-19(Day 1:750 mg and 500 mg,Days 2-3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations(e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.展开更多
基金supported by the China Medical BoardOpen Competition Program(20-378)Peking University Third Hospital Fund for Returned Scholars(BYSYLXHG2020004)+1 种基金JX was supported by the Peking Union Medical College Fund for Informatization of Postgraduate Courses(2021YXX001)YLZ was supported by the Sichuan University Graduate Education Reform Project(GSSCU2021046)。
文摘BACKGROUND:Shared decision-making(SDM)has broad application in emergencies.Most published studies have focused on SDM for a certain disease or expert opinions on future research gaps without revealing the full picture or detailed guidance for clinical practice.This study is to investigate the optimal application of SDM to guide life-sustaining treatment(LST)in emergencies.METHODS:This study was a prospective two-round Delphi consensus-seeking survey among multiple stakeholders at the China Consortium of Elite Teaching Hospitals for Residency Education.Participants were identified based on their expertise in medicine,law,administration,medical education,or patient advocacy.All individual items and questions in the questionnaire were scored using a 5-point Likert scale,with responses ranging from"very unimportant"(a score of 1)to"extremely important"(a score of 5).The percentages of the responses that had scores of 4-5on the 5-point Likert scale were calculated.A Kendall’s W coefficient was calculated to evaluate the consensus of experts.RESULTS:A two-level framework consisting of 4 domains and 22 items as well as a ready-touse checklist for the informed consent process for LST was established.An acceptable Kendall’s W coefficient was achieved.CONCLUSION:A consensus-based framework supporting SDM during LST in an emergency department can inform the implementation of guidelines for clinical interventions,research studies,medical education,and policy initiatives.
基金Supported by National Natural Science Foundation of China,No.81900641the Research Funding of Peking University,BMU2021MX020 and BMU2022MX008。
文摘BACKGROUND Early identification of severe/critical coronavirus disease 2019(COVID-19)is crucial for timely treatment and intervention.Chest computed tomography(CT)score has been shown to be a significant factor in the diagnosis and treatment of pneumonia,however,there is currently a lack of effective early warning systems for severe/critical COVID-19 based on dynamic CT evolution.AIM To develop a severe/critical COVID-19 prediction model using a combination of imaging scores,clinical features,and biomarker levels.METHODS This study used an improved scoring system to extract and describe the chest CT characteristics of COVID-19 patients.The study also took into consideration the general clinical indicators such as dyspnea,oxygen saturation,alternative lengthening of telomeres(ALT),and androgen suppression treatment(AST),which are commonly associated with severe/critical COVID-19 cases.The study employed lasso regression to evaluate and rank the significance of different disease characteristics.RESULTS The results showed that blood oxygen saturation,ALT,IL-6/IL-10,combined score,ground glass opacity score,age,crazy paving mode score,qsofa,AST,and overall lung involvement score were key factors in predicting severe/critical COVID-19 cases.The study established a COVID-19 severe/critical early warning system using various machine learning algorithms,including XGBClassifier,Logistic Regression,MLPClassifier,RandomForestClassifier,and AdaBoost Classifier.The study concluded that the prediction model based on the improved CT score and machine learning algorithms is a feasible method for early detection of severe/critical COVID-19 evolution.CONCLUSION The findings of this study suggest that a prediction model based on improved CT scores and machine learning algorithms is effective in detecting the early warning signals of severe/critical COVID-19.
基金supported by grants from National Natural Science Foundation of China(No.81860445,No.81960453,No.81560408,and No.81660429)Natural Science Foundation of Guangxi(No.2018GXNSFAA050058,No.2018GXNSFAA281251,No.2018GXNSFAA050151,No.2017GXNSFAA 198001,No.2018GXNSFAA281050,and No.2018GXNSFBA281187)+1 种基金Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)and Ministry of Education(No.GK2018-09,No.GKE 2019-08,and No.GKE-ZZ202006)Basic Ability Improvement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi(No.2018KY0109)。
文摘Glioma is the most common malignant brain tumor in central nervous system.Despite advances in the treatment of glioma such as surgery and chemoradiotherapy,most patients are easy to relapse,resulting in adverse clinical outcomes.Hence,effective molecular=targeting treatment may be one of attractive strategies for glioma therapy.The dysregulated microRNAs(miRNAs),one of the candidates of therapeutic targets,are believed to play an important role in the progression of glioma.In this study,we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy.Firstly,expression profile of miRNAs in 5 normal brain tissues,5 low-grade glioma(LGG)tissues and 5 glioblastoma(GBM)tissues was detected by RNA sequencing(RNA-seq).Next,the target genes of differentially expressed miRNAs(DEmiRNAs)were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics.Finally,10 miRNAs which were significantly up-or down-regulated both in GBM and LGG were validated by real-time quantitative PCR(qRT-PCR).RNA-seq results indicated a number of DEmiRNAs in glioma.There were 64 up-regulated miRNAs and 17 down-regulated miRNAs n LGG,and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM,respectively.Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process.Selected DEmiRNAs were further confirmed by qRT-PCR.miRNA-10b-5p,miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG;while miRNA-542-3p was significantly up-regulated in LGG;miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG;miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM.The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for gl ioma.
文摘BACKGROUND Liver injury is common and also can be fatal,particularly in severe or critical patients with coronavirus disease 2019(COVID-19).AIM To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk.METHODS A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9,2020 at Tongji Hospital,Wuhan,China.Data on clinical features,laboratory parameters,medications,and prognosis were collected.RESULTS COVID-19-associated liver injury more frequently occurred in patients aged≥65 years,female patients,or those with other comorbidities,decreased lymphocyte count,or elevated D-dimer or serum ferritin(P<0.05).The disease severity of COVID-19 was an independent risk factor for liver injury(severe patients:Odds ratio[OR]=2.86,95%confidence interval[CI]:1.78-4.59;critical patients:OR=13.44,95%CI:7.21-25.97).The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk(P<0.001).Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury.Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury.CONCLUSION More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients,especially patients aged≥65 years,female patients,or those with other comorbidities.Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.
文摘BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.
基金supported by grants from National Natural Science Foundation of China(No.81460382,No.81560408,No.81360371,and No.81360374)Natural Science Foundation of Guangxi(No.2016GXNSFAA380257,No.2016GXNSFBA380159,and No.2017GXNSFAA198001)+1 种基金Guangxi Key Laboratory of Biological Targeting Diagnosis and Treatment(No.GXSWBX201505)Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)and Ministry of Education(No.GJZ201603 and No.K2015-TKF03)
文摘Cancer testis antigens(CTAs)are attractive targets for tumor immunotherapy because of their tumor-specific expression.Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.In this review,we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.
文摘Cleavage of ADAMTS-18 by thrombin represents a new mechanism of platelet thrombus clearance via the release of active ~45-kDa C-terminal fragments that induces oxidative platelet fragmentation. The exact cleavage sites remain unclear, but Arg (R)775/Ser (S)776 in spacer region of ADAMTS-18 has been shown to be one of the cleavage sites of thrombin. Here, we demonstrate that R792/S793 and R823/S824 are also thrombin cleavage sites by sequence analysis, amino acid mutation and mass spectrometry assay. All these cleavage sites are thrombin-specific and insensitive to other enzymes tested (e.g. cathepsin D or trypsin). Simultaneous mutation of R775, 792, 823 to S775, 792, 823 in ADAMTS-18 completely abrogated the cleavage by thrombin and the generation of active C-terminal 45-kDa fragments. Together with previous study, a total of three thrombin-specific cleavage sites have been identified in spacer region of ADAMTS-18.
文摘Background: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gramnegative bacteria. Methods: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patienfs renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. Results: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii^ and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 土 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cniax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z =-4.157;9.6 [4.2-17.8] vs, 1.3 [0.4-4.7], Z =-4.018;both P< 0.001). The AUC/MIC and Cmax/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7-214.9] vs. 10.5 [3.8-66.1], Z =—3.938;11.4 [4.2-17.8] vs. 1.4 [0.4-5.4], Z =—3.793;P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and Cmax/ MIC values were closely associated with clinical and bacteriologic efficacies (P<0.001 in both). Conclusions: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and Cmax/MIC> 8, cannot be reached.
基金University of Michigan Health System-Peking University Health Science Center Joint Institute for Translational and Clinical Research(No.BMU2019JI006)Peking University Third Hospital(No.BYSYDL2019007)。
文摘Background:Hospital-acquired pneumonia(HAP)is the most common hospital-acquired infection in China with substantial morbidity and mortality.But no specific risk assessment model has been well validated in patients with HAP.The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.Methods:This study was a single-center,retrospective study.In total,223 patients diagnosed with HAP from 2012 to 2017 were included in this study.Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index(PSI);consciousness,urea nitrogen,respiratory rate,blood pressure,and age≥65 years(CURB-65);Acute Physiology and Chronic Health Evaluation II(APACHE II);Sequential Organ Failure Assessment(SOFA);and Quick Sequential Organ Failure Assessment(qSOFA)scores.The discriminatory power was tested by constructing receiver operating characteristic(ROC)curves,and the areas under the curve(AUCs)were calculated.Results:The all-cause 30-day mortality rate was 18.4%(41/223).The PSI,CURB-65,SOFA,APACHE II,and qSOFA scores were significantly higher in non-survivors than in survivors(all P<0.001).The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores(ROC AUC:APACHE II vs.CURB-65,0.863 vs.0.744,Z=3.055,P=0.002;APACHE II vs.qSOFA,0.863 vs.0.767,Z=3.017,P=0.003;SOFA vs.CURB-65,0.856 vs.0.744,Z=2.589,P=0.010;SOFA vs.qSOFA,0.856 vs.0.767,Z=2.170,P=0.030).The cut-off values we defined for the SOFA,APACHE II,and qSOFA scores were 4,14,and 1.Conclusions:These results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments.The qSOFA score may be a simple tool that can be used to quickly identify severe infections.
基金supported by the“13th Five-Year”National Science and Technology Major Project(grant Nos.2017ZX09101001-002-001 and 2017ZX09304012,China)Bill&Melinda Gates Foundation(OPP1204780,USA)
文摘Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of CQ.The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism.Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships.The model was also validated by clinical data from Chinese patients with COVID-19.The novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs(lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19(Day 1:750 mg BID,Days 2-5:500 mg BID,CQ phosphate),patients with moderate COVID-19(Day 1:750 mg and 500 mg,Days 2-3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations(e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
