Objectives: Research on effects of comorbidities disease on anticoagulation overdose in patients receiving anticoagulant therapy with vitamin K antagonists anticoagulant (VKAs) drugs at HaiPhong-VinhBao International ...Objectives: Research on effects of comorbidities disease on anticoagulation overdose in patients receiving anticoagulant therapy with vitamin K antagonists anticoagulant (VKAs) drugs at HaiPhong-VinhBao International General Hospital. Methods: Description and Prospective study. Research on 79 patients receiving anticoagulant therapy with VKAs who have an INR testing index of more than anticoagulation dose with VKAs and check INR every 4 weeks. Results: The average research age is 65.65 ± 12.17 years [33: 85], most of the elderly group. The Male group is lower than the female group (p > 0.05). Patients with hemorrhage signs account for 22.8%. The INR testing index has an average value is 5.88 ± 3.0 [3.02 - 23.95];The group of INR > 5 level is a higher risk of bleeding than the group of INR ≤ 5 levels, there is statistical difference (p Conclusion: All most patients with anticoagulation overdose are in the elderly group. The group with INR > 5 levels has a higher risk of bleeding than the group with INR ≤ 5 levels, it’s the statistical significance (p 1 but p > 0.05);Patients used VKAs drugs on the background of kidney failure or arthritis pathology are the cause of the increased risk of bleeding, it’s statistical significance (p < 0.05).展开更多
We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic ste...We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.展开更多
Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system...Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system.However,ROS under redox homeostasis regulates a wide range of life activities.Therefore,smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely.This study reports a smart antioxidant function enhancement(SAFE)strategy.On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system,thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner.Through structural modulation and ligand modification,we develop SAFE nanoparticles based on nanohybrid complexes(SAFE-complex)adapted to brain delivery of nucleic acid drugs.SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage.Moreover,SAFE-complex can stabilize storage in the form of freeze-dried powder.These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.展开更多
BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant sour...BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium.CASE SUMMARY A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However,subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient(namely, psychiatric disorders, hypertension,insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements.CONCLUSION Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.展开更多
Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes(DAGs),which are important for understanding disease initiation and developing prec...Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes(DAGs),which are important for understanding disease initiation and developing precision therapeutics.However,DAGs often contain large amounts of redundant or false positive information,leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases.In this study,a networkoriented gene entropy approach(NOGEA)is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks.In addition,we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk.Master genes may also be used to extract the underlying information of different diseases,thus revealing mechanisms of disease comorbidity.More importantly,approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network,which provides a new way for predicting drug-disease associations.Through this method,11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments.Collectively,the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence,thus providing a valuable strategy for drug efficacy screening and repositioning.NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.展开更多
Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden o...Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer＇s disease（AD）, vascular dementia（Va D）, or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January2003 to December 2012. The Charlson Comorbidity Index（CCI） was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had Va D, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients,3.4 ± 1.8 for those with Va D, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, andthe length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.展开更多
文摘Objectives: Research on effects of comorbidities disease on anticoagulation overdose in patients receiving anticoagulant therapy with vitamin K antagonists anticoagulant (VKAs) drugs at HaiPhong-VinhBao International General Hospital. Methods: Description and Prospective study. Research on 79 patients receiving anticoagulant therapy with VKAs who have an INR testing index of more than anticoagulation dose with VKAs and check INR every 4 weeks. Results: The average research age is 65.65 ± 12.17 years [33: 85], most of the elderly group. The Male group is lower than the female group (p > 0.05). Patients with hemorrhage signs account for 22.8%. The INR testing index has an average value is 5.88 ± 3.0 [3.02 - 23.95];The group of INR > 5 level is a higher risk of bleeding than the group of INR ≤ 5 levels, there is statistical difference (p Conclusion: All most patients with anticoagulation overdose are in the elderly group. The group with INR > 5 levels has a higher risk of bleeding than the group with INR ≤ 5 levels, it’s the statistical significance (p 1 but p > 0.05);Patients used VKAs drugs on the background of kidney failure or arthritis pathology are the cause of the increased risk of bleeding, it’s statistical significance (p < 0.05).
基金This work was supported by the National Key Research and Development Program of China(2017YFA0104500)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)+6 种基金the Key Program of the National Natural Science Foundation of China(81930004)Capital’s Funds for Health Improvement and Research(2018-4-4089)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-034)the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)Peking University Clinical Scientist Program(BMU2019LCKXJ003)supported by the Fundamental Research Funds for the Central Universities.
文摘We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.
基金supported by the National Natural Science Foundation of China(Nos.32225029,22205240,52073287,22075289,and 82071552).
文摘Reactive oxygen species(ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders.The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system.However,ROS under redox homeostasis regulates a wide range of life activities.Therefore,smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely.This study reports a smart antioxidant function enhancement(SAFE)strategy.On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system,thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner.Through structural modulation and ligand modification,we develop SAFE nanoparticles based on nanohybrid complexes(SAFE-complex)adapted to brain delivery of nucleic acid drugs.SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage.Moreover,SAFE-complex can stabilize storage in the form of freeze-dried powder.These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.
文摘BACKGROUND Cumulative evidence suggests that the aberrant immune responses in acquired aplastic anemia(AA) are sustained by active chronic infections in genetically susceptible individuals. Recently, the constant source to trigger and sustain the pathophysiology has been proposed to come from the altered gut microbiota and chronic intestinal inflammation. In this case, our serendipitous finding provides convincing evidence that the persistently dysregulated autoimmunity may be generated, at least in a significant proposition of AA patients, by the altered gut microbiota and compromised intestinal epithelium.CASE SUMMARY A 30-year-old Chinese male patient with refractory severe AA experienced a 3-month-long febrile episode, and his fever was refractory to many kinds of injected broad-spectrum antibiotics. When presenting with abdominal cramps, he was prescribed oral mannitol and gentamycin to get rid of the gut infection. This treatment resulted in a quick resolution of the fever. Unanticipatedly, it also produced an excellent hematological response. He had undergone three episodes of recurrence within the one-year treatment, with each recurrence occurring 7-8 wk from the gastrointestinal inflammation eliminating preparations. However,subsequent treatments were able to produce subsequent remissions and consecutive treatments were successful in achieving durative hematological improvements, strongly indicating an etiological association between chronic gut inflammation and the development of AA. Interestingly, comorbid diseases superimposed on this patient(namely, psychiatric disorders, hypertension,insulin resistance, and renal dysfunction) were ameliorated together with the hematological improvements.CONCLUSION Chronic gut inflammation may be responsible for AA pathogenesis. The comorbidities and AA may share a common etiological association.
基金supported by the National Natural Science Foundation of China(Grant Nos.U1603285 and 81803960)the National Science and Technology Major Project of China(Grant No.2019ZX09201004-001)。
文摘Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes(DAGs),which are important for understanding disease initiation and developing precision therapeutics.However,DAGs often contain large amounts of redundant or false positive information,leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases.In this study,a networkoriented gene entropy approach(NOGEA)is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks.In addition,we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk.Master genes may also be used to extract the underlying information of different diseases,thus revealing mechanisms of disease comorbidity.More importantly,approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network,which provides a new way for predicting drug-disease associations.Through this method,11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments.Collectively,the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence,thus providing a valuable strategy for drug efficacy screening and repositioning.NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.
基金supported by a Chongqing Social Science Plan Project(2015YBSH142)
文摘Dementia is increasing dramatically and imposes a huge burden on society. To date, there is a lack of data on the health status of patients with dementia in China. In an attempt to investigate the comorbidity burden of dementia patients in China at the national level, we enrolled 2,938 patients with Alzheimer＇s disease（AD）, vascular dementia（Va D）, or other types of dementia, who were admitted to tertiary hospitals in seven regions of China from January2003 to December 2012. The Charlson Comorbidity Index（CCI） was used to evaluate the comorbidity burden of the patients with dementia. Among these patients, 53.4% had AD, 26.3% had Va D, and 20.3% had other types of dementia. The CCI was 3.0 ± 1.9 for all patients,3.4 ± 1.8 for those with Va D, and 3.0 ± 2.1 for those with AD. The CCI increased with age in all patients, andthe length of hospital stay and daily expenses rose with age and CCI. Males had a higher CCI and a longer stay than females. Moreover, patients admitted in the last 5 years of the study had a higher CCI than those admitted in the first 5 years. We found that the comorbidity burden of patients with dementia is heavy. These findings provide a better understanding of the overall health status of dementia patients, and help to increase the awareness of clinicians and policy-makers to improve medical care for patients.
