BACKGROUND Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct.Medical care alone may result in suboptimal treatment efficacy,and endovascu...BACKGROUND Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct.Medical care alone may result in suboptimal treatment efficacy,and endovascular treatment may be accompanied by safety issues.Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies.AIM To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores.METHODS Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021.Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods.In the endovascular therapy group,there were 28 patients with minor stroke and 22 patients with large infarct cores.The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores.The National Institutes of Health Stroke Scale(NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation.The modified Rankin scale(m RS) and/or activity of daily living were assessed at hospital discharge.RESULTS There was no significant difference in NIHSS scores between the two groups before the operation(P > 0.05).NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge(all P < 0.05).The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group(P < 0.05).At hospital discharge,the m RS score was lower in the endovascular treatment group than in the drug therapy group,and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group(all P < 0.05).During a follow-up of 3 mo,17 patients(34.0%) had good prognosis(m RS ≤ 2),33 patients(66.0%) had poor prognosis(m RS > 2),and 11 patients(22.0%) died.In the medical treatment group,16 patients(m RS ≤ 2) had good prognosis(32.0%),34 patients(m RS > 2) had poor prognosis(68.0%),and 14 patients(28.0%) died.There was no significant difference in prognosis and mortality between the two groups(P > 0.05).CONCLUSION Endovascular therapy can improve NIHSS score and m RS score in patients with mild ischemic stroke and large infarct cores.It is suitable for clinical application.展开更多
BACKGROUND Low-grade fever during convalescence is an atypical symptom of coronavirus disease 2019(COVID-19).Reports of such cases are rare,and the mechanism and outcome of low-grade fever during COVID-19 convalescenc...BACKGROUND Low-grade fever during convalescence is an atypical symptom of coronavirus disease 2019(COVID-19).Reports of such cases are rare,and the mechanism and outcome of low-grade fever during COVID-19 convalescence are not completely clear.We report 3 cases with low-grade fever during COVID-19 convalescence and highlight the main clinical,radiographic,and laboratory characteristics,thereby increasing the level of expertise in the clinical management of COVID-19 during convalescence and facilitating individualized decision-making.CASE SUMMARY We describe 3 patients with COVID-19,two females aged 62 and 66 years and a male 55 years,who had low-grade fever during COVID-19 convalescence.All 3 patients had no other discomfort or comorbidities during low-grade process.Lesions on computed tomography in all 3 patients had resolved during this period.Two patients tested negative on two consecutive severe acute respiratory syndrome coronavirus 2 tests with an interval of at least 24 h between tests.Body temperature in all 3 patients returned to normal after several days without treatment,and fever recurrence was not observed.CONCLUSION Enhancing the knowledge of low-grade fever during COVID-19 convalescence may increase the expertise in the delivery of optimal healthcare services.展开更多
Summary:Renal cancer is a common genitourinary malignance,of which clear cell renal cell carcinoma(ccRCC)has high aggressiveness and leads to most cancer-related deaths.Identification of sensitive and reliable biomark...Summary:Renal cancer is a common genitourinary malignance,of which clear cell renal cell carcinoma(ccRCC)has high aggressiveness and leads to most cancer-related deaths.Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC.Here,we identified 2397 common difTerentially expressed genes(DEGs)using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas(TCGA).Then,we performed weighted gene co-expression network analysis and protein-protein interaction network analysis,17 candidate hub genes were identified.These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified.All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC.Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome.ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples,and between early stage and advanced stage ccRCC.Moreover,all the hub genes were positively associated with distant metastasis,lymph node infiltration,tumor recurrence and the expression of MKi67,suggesting these genes might promote tumor proliferation,invasion and metastasis.Furthermore,the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function.In summary,our study identified 14 potential biomarkers for predicting tumorigenesis and progression,which might contribute to early diagnosis,prognosis prediction and therapeutic intervention.展开更多
Dear Editor,Recent achievements in large-scale pre-trained models like GPT-3 and PanGu-α have demonstrated astounding performances in many downstream tasks of natural language processing (NLP),confirming AI to be use...Dear Editor,Recent achievements in large-scale pre-trained models like GPT-3 and PanGu-α have demonstrated astounding performances in many downstream tasks of natural language processing (NLP),confirming AI to be user-oriented for even industrial applications.Deep learning has been recognized as the most promising technology for pharmaceuticals,a powerful molecule pre-trained model that could economize researchers’tons of time.For the strategic application of AI capabilities to the drug discovery field,we pre-trained a model called PanGu Drug Model with 1.7 billion small molecules from ZINC20 (Irwin et al.,2020),DrugSpaceX(Yang et al.,2021),and UniChem (Chambers et al.,2013).展开更多
Artificial intelligence(AI)models usually require large amounts of high-quality training data,which is in striking contrast to the situation of small and biased data faced by current drug discovery pipelines.The conce...Artificial intelligence(AI)models usually require large amounts of high-quality training data,which is in striking contrast to the situation of small and biased data faced by current drug discovery pipelines.The concept of federated learning has been proposed to utilize distributed data from different sources without leaking sensitive information of the data.This emerging decentralized machine learning paradigm is expected to dramatically improve the success rate of AI-powered drug discovery.Here,we simulated the federated learning process with different property and activity datasets from different sources,among which overlapping molecules with high or low biases exist in the recorded values.Beyond the benefit of gaining more data,we also demonstrated that federated training has a regularization effect superior to centralized training on the pooled datasets with high biases.Moreover,different network architectures for clients and aggregation algorithms for coordinators have been compared on the performance of federated learning,where personalized federated learning shows promising results.Our work demonstrates the applicability of federated learning in predicting drug-related properties and highlights its promising role in addressing the small and biased data dilemma in drug discovery.展开更多
The upper bound limit analysis(UBLA)is one of the key research directions in geotechnical engineering and is widely used in engineering practice.UBLA assumes that the slip surface with the minimum factor of safety(FSm...The upper bound limit analysis(UBLA)is one of the key research directions in geotechnical engineering and is widely used in engineering practice.UBLA assumes that the slip surface with the minimum factor of safety(FSmin)is the critical slip surface,and then applies it to slope stability analysis.However,the hypothesis of UBLA has not been systematically verified,which may be due to the fact that the traditional numerical method is difficult to simulate the large deformation.In this study,in order to systematically verify the assumption of UBLA,material point method(MPM),which is suitable to simulate the large deformation of continuous media,is used to simulate the whole process of the slope failure,including the large-scale transportation and deposition of soil mass after slope failure.And a series of comparative studies are conducted on the stability of cohesive slopes using UBLA and MPM.The proposed study indicated that the slope angle,internal friction angle and cohesion have a remarkable effect on the slip surface of the cohesive slope.Also,for stable slopes,the calculation results of the two are relatively close.However,for unstable slopes,the slider volume determined by the UBLA is much smaller than the slider volume determined by the MPM.In other words,for unstable slopes,the critical slip surface of UBLA is very different from the slip surface when the slope failure occurs,and when the UBLA is applied to the stability analysis of unstable slope,it will lead to extremely unfavorable results.展开更多
Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor microenvironment.Cell death-related signals such as ATP release from tumor cells ar...Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor microenvironment.Cell death-related signals such as ATP release from tumor cells are crucial for the activation of downstream immune responses.^(1)GOLM1,also known as GOLPH2 and GP73 as a Golgi transmembrane protein involved in the transport of protein cargo through the Golgi apparatus has been extensively studied in various cancers for its multifunctional roles in promoting cancer proliferation and metastasis through the AKT/mTOR pathway.展开更多
基金Supported by Scientific Research Fund of Hebei Health Commission 2022,No.20220591。
文摘BACKGROUND Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct.Medical care alone may result in suboptimal treatment efficacy,and endovascular treatment may be accompanied by safety issues.Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies.AIM To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores.METHODS Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021.Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods.In the endovascular therapy group,there were 28 patients with minor stroke and 22 patients with large infarct cores.The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores.The National Institutes of Health Stroke Scale(NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation.The modified Rankin scale(m RS) and/or activity of daily living were assessed at hospital discharge.RESULTS There was no significant difference in NIHSS scores between the two groups before the operation(P > 0.05).NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge(all P < 0.05).The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group(P < 0.05).At hospital discharge,the m RS score was lower in the endovascular treatment group than in the drug therapy group,and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group(all P < 0.05).During a follow-up of 3 mo,17 patients(34.0%) had good prognosis(m RS ≤ 2),33 patients(66.0%) had poor prognosis(m RS > 2),and 11 patients(22.0%) died.In the medical treatment group,16 patients(m RS ≤ 2) had good prognosis(32.0%),34 patients(m RS > 2) had poor prognosis(68.0%),and 14 patients(28.0%) died.There was no significant difference in prognosis and mortality between the two groups(P > 0.05).CONCLUSION Endovascular therapy can improve NIHSS score and m RS score in patients with mild ischemic stroke and large infarct cores.It is suitable for clinical application.
基金Supported by Emergency Special Project on Prevention and Treatment of COVID-19 with Traditional Chinese Medicine,No.2020YBBGWL007.
文摘BACKGROUND Low-grade fever during convalescence is an atypical symptom of coronavirus disease 2019(COVID-19).Reports of such cases are rare,and the mechanism and outcome of low-grade fever during COVID-19 convalescence are not completely clear.We report 3 cases with low-grade fever during COVID-19 convalescence and highlight the main clinical,radiographic,and laboratory characteristics,thereby increasing the level of expertise in the clinical management of COVID-19 during convalescence and facilitating individualized decision-making.CASE SUMMARY We describe 3 patients with COVID-19,two females aged 62 and 66 years and a male 55 years,who had low-grade fever during COVID-19 convalescence.All 3 patients had no other discomfort or comorbidities during low-grade process.Lesions on computed tomography in all 3 patients had resolved during this period.Two patients tested negative on two consecutive severe acute respiratory syndrome coronavirus 2 tests with an interval of at least 24 h between tests.Body temperature in all 3 patients returned to normal after several days without treatment,and fever recurrence was not observed.CONCLUSION Enhancing the knowledge of low-grade fever during COVID-19 convalescence may increase the expertise in the delivery of optimal healthcare services.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81270354)Natural Science for Youth Foundation(No.81300213).
文摘Summary:Renal cancer is a common genitourinary malignance,of which clear cell renal cell carcinoma(ccRCC)has high aggressiveness and leads to most cancer-related deaths.Identification of sensitive and reliable biomarkers for predicting tumorigenesis and progression has great significance in guiding the diagnosis and treatment of ccRCC.Here,we identified 2397 common difTerentially expressed genes(DEGs)using paired normal and tumor ccRCC tissues from GSE53757 and The Cancer Genome Atlas(TCGA).Then,we performed weighted gene co-expression network analysis and protein-protein interaction network analysis,17 candidate hub genes were identified.These candidate hub genes were further validated in GSE36895 and Oncomine database and 14 real hub genes were identified.All the hub genes were up-regulated and significantly positively correlated with pathological stage and histologic grade of ccRCC.Survival analysis showed that the higher expression level of each hub gene tended to predict a worse clinical outcome.ROC analysis showed that all the hub genes can accurately distinguish between tumor and normal samples,and between early stage and advanced stage ccRCC.Moreover,all the hub genes were positively associated with distant metastasis,lymph node infiltration,tumor recurrence and the expression of MKi67,suggesting these genes might promote tumor proliferation,invasion and metastasis.Furthermore,the functional annotation demonstrated that most genes were enriched in cell-cycle related biological function.In summary,our study identified 14 potential biomarkers for predicting tumorigenesis and progression,which might contribute to early diagnosis,prognosis prediction and therapeutic intervention.
文摘Dear Editor,Recent achievements in large-scale pre-trained models like GPT-3 and PanGu-α have demonstrated astounding performances in many downstream tasks of natural language processing (NLP),confirming AI to be user-oriented for even industrial applications.Deep learning has been recognized as the most promising technology for pharmaceuticals,a powerful molecule pre-trained model that could economize researchers’tons of time.For the strategic application of AI capabilities to the drug discovery field,we pre-trained a model called PanGu Drug Model with 1.7 billion small molecules from ZINC20 (Irwin et al.,2020),DrugSpaceX(Yang et al.,2021),and UniChem (Chambers et al.,2013).
基金supported by the Shanghai Municipal Science and Technology Major Projectthe National Natural Science Foundation of China(81773634)+1 种基金the National Science and Technology Major Project of the Ministry of Science and Technology of China(2018ZX09711002)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12050201 and XDA12020368)。
文摘Artificial intelligence(AI)models usually require large amounts of high-quality training data,which is in striking contrast to the situation of small and biased data faced by current drug discovery pipelines.The concept of federated learning has been proposed to utilize distributed data from different sources without leaking sensitive information of the data.This emerging decentralized machine learning paradigm is expected to dramatically improve the success rate of AI-powered drug discovery.Here,we simulated the federated learning process with different property and activity datasets from different sources,among which overlapping molecules with high or low biases exist in the recorded values.Beyond the benefit of gaining more data,we also demonstrated that federated training has a regularization effect superior to centralized training on the pooled datasets with high biases.Moreover,different network architectures for clients and aggregation algorithms for coordinators have been compared on the performance of federated learning,where personalized federated learning shows promising results.Our work demonstrates the applicability of federated learning in predicting drug-related properties and highlights its promising role in addressing the small and biased data dilemma in drug discovery.
基金financially supported by the National Natural Science Foundation of China(No.51878668)the Guizhou Provincial Department of Transportation Foundation(Nos.2017-123-033,2018-123-040)+1 种基金the Innovation-Driven Project of Central South University(No.2016CX012)the Science and Technology Project Plan for Key Projects of Jiangxi Transportation Department(No.2019C0011)
文摘The upper bound limit analysis(UBLA)is one of the key research directions in geotechnical engineering and is widely used in engineering practice.UBLA assumes that the slip surface with the minimum factor of safety(FSmin)is the critical slip surface,and then applies it to slope stability analysis.However,the hypothesis of UBLA has not been systematically verified,which may be due to the fact that the traditional numerical method is difficult to simulate the large deformation.In this study,in order to systematically verify the assumption of UBLA,material point method(MPM),which is suitable to simulate the large deformation of continuous media,is used to simulate the whole process of the slope failure,including the large-scale transportation and deposition of soil mass after slope failure.And a series of comparative studies are conducted on the stability of cohesive slopes using UBLA and MPM.The proposed study indicated that the slope angle,internal friction angle and cohesion have a remarkable effect on the slip surface of the cohesive slope.Also,for stable slopes,the calculation results of the two are relatively close.However,for unstable slopes,the slider volume determined by the UBLA is much smaller than the slider volume determined by the MPM.In other words,for unstable slopes,the critical slip surface of UBLA is very different from the slip surface when the slope failure occurs,and when the UBLA is applied to the stability analysis of unstable slope,it will lead to extremely unfavorable results.
基金supported by the CAMS Initiative for Innovative Medicine(No.2016-I2M-1-005,2019-I2M-1-003)National Science and Technology Major Project for“Significant New Drugs Innovation and Development”(2015ZX09102023)+5 种基金National Natural Science Foundation of China(NSFC 91542201,81590765,82073181,81802870,81702987,81871286)Natural Science Foundation of Jiangsu Province Grant(BK20170407,BK20151253,BK20161246)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(3332018131,2020-PT310-006)L.L.is supported by the Chinese Postdoctoral Science Foundation(2019M650564)the Innovation and Entrepreneurial Doctor grant(2020-2022)M.S.is supported by the Key Project of Jiangsu Provincial Health Commission(No.K2019021).
文摘Dear Editor,Immune-mediated tumor elimination depends on the production of cytokines and the recruitment of immune cells in the tumor microenvironment.Cell death-related signals such as ATP release from tumor cells are crucial for the activation of downstream immune responses.^(1)GOLM1,also known as GOLPH2 and GP73 as a Golgi transmembrane protein involved in the transport of protein cargo through the Golgi apparatus has been extensively studied in various cancers for its multifunctional roles in promoting cancer proliferation and metastasis through the AKT/mTOR pathway.