AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other t...AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.展开更多
Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral f...Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.展开更多
Mdm2 and Mdm4 are negative regulators of the tumour suppressor p53; hence, this relationship is the focus of many cancerrelated studies. A multitude of experiments across various developmental stages have been conduct...Mdm2 and Mdm4 are negative regulators of the tumour suppressor p53; hence, this relationship is the focus of many cancerrelated studies. A multitude of experiments across various developmental stages have been conducted to explore the tissuespecific roles of these proteins in the mouse. When Mdm2 or Mdm4 are deleted in the germiine or specific tissues, they display different phenotypic defects, some of which lead to embryonic lethaLity. Mdm2 loss is often more deleterious than toss of its homotogue Mdm4. ALL tissues experience activation of p53 target genes upon toss of Mdm2 or Mdm4; however, the degree to which the p53 pathway is perturbed is highly tissue-specific and does not correlate to the severity of the morphological pheno- types. Therefore, a need for further understanding of how these proteins regulate p53 activity is warranted, as therapeutic targeting of the p53 pathway is rapidly evoLving and gaining attention in the field of cancer research. In this review, we discuss the tissue-specificity of Mdm proteins in regulating p53 and expose the need for investigation at the celt-specific level.展开更多
随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿...随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿刺活检已经逐渐取代手术活检,多数患者在手术切除时已经有了明确诊断.为了更精准测量肿瘤的位置,客观地评判手术范围,准确地评估肿瘤分期和治疗反应,乳腺标本的大体取材受到临床与病理的共同重视,取材方法也在逐渐改进[1-5].准确的大体检查往往依赖于病理医师、放射医师及外科医师的合作.我们旨在介绍乳腺癌手术切除标本和前哨淋巴结的大体取材方法,其主要内容来自于美国MD安德森癌症中心(MD Anderson Cancer Center,MDACC) 行之有效的多年实践.展开更多
We investigate and compare the performance of four optical transport schemes for distributing Local Multipoint Distribution Service (LMDS) signals using an optical fiber backbone.
Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment....Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment.Using phage display techniques,we previously identified a potent peptide activator of P53,termed PMI(TSFAEYWNLLSP),with binding affinities for both MDM2 and MDMX in the low nanomolar concentration range.Here we report an ultrahigh affinity,dual-specificity peptide antagonist of MDM2 and MDMX obtained through systematic mutational analysis and additivitybased molecular design.Functional assays of over 100 peptide analogs of PMI using surface plasmon resonance and fluorescence polarization techniques yielded a dodecameric peptide termed PMI-M3(LTFLEYWAQLMQ)that bound to MDM2 and MDMX with K_(d)values in the low picomolar concentration range as verified by isothermal titration calorimetry.Co-crystal structures of MDM2 and of MDMX in complex with PMI-M3 were solved at 1.65 and 3.0 A resolution,respectively.Similar to PMI,PMI-M3 occupied the P53-binding pocket of MDM2/MDMX,which was dominated energetically by intermolecular interactions involving Phe3,Tyr6,Trp7,and Leu 10.Notable differences in binding between PMI-M3 and PMI were observed at other positions such as Leu4 and Met11 with MDM2,and Leu1 and Met11 with MDMX,collectively contributing to a significantly enhanced binding affinity of PMI-M3 for both proteins.By adding lysine residues to both ends of PMI and PMI-M3 to improve their cellular uptake,we obtained modified peptides termed PMI-2K(KTSFAEYWNLLSPK)and M3-2K(KLTFLEYWAQLMQK).Compared with PMI-2K,M3-2K exhibited significantly improved antitumor activities in vitro and in vivo in a P53-dependent manner.This super-strong peptide inhibitor of the P53-MDM2/MDMX interactions may become,in its own right,a powerful lead compound for anticancer drug development,and can aid molecular design of other classes of P53 activators as well for anticancer therapy.展开更多
2021年7月17—22日河南省发生了一次历史罕见的持续性强降水,造成了巨大的经济损失。目前极端降水预报仍是次季节气候预测研究的热点和难点。区域气候模式有着比全球模式更精细的空间分辨率和更为完善的物理过程参数化方案,为进一步提...2021年7月17—22日河南省发生了一次历史罕见的持续性强降水,造成了巨大的经济损失。目前极端降水预报仍是次季节气候预测研究的热点和难点。区域气候模式有着比全球模式更精细的空间分辨率和更为完善的物理过程参数化方案,为进一步提高中国次季节降水预报能力提供了新途径。使用区域气候模式CWRF(regional Climate-Weather Research and Forecasting model)对中国气象局全球气候模式次季节预测系统CMA_CPSv3(China Meteorological Administration Climate Prediction System version 3)的预报结果进行中国区域动力降尺度,分析了CWRF和CMA_CPSv3模式对河南省2021年7月17—22日持续性强降水的预测效果。结果表明,区域模式和全球模式预报的降水空间分布和量级存在明显差异。尽管两个模式都低估了此次强降水过程的降水量,但总体上CWRF模式预报的降水量更大且更好地捕捉到了降水的空间分布。CWRF模式自6月26和29日起报的降水预报明显好于同一起报日CMA_CPSv3模式的预报结果。与CMA_CPSv3预报相比,CWRF显著地改善了东亚低空风场和低空急流的预报。CWRF对低空急流和水汽通量输送方向的改善尤为明显,预报的水汽在山脉的迎风坡辐合,为降水提供了有利的水汽条件。同时CWRF更好地预报了郑州上空的垂直上升运动,这些改善都有利于CWRF模式对降水有更高的预报技巧。展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.展开更多
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
文摘AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.
基金the support from the National Science Foundation of China(Grants Nos.61401117 and 61201017)the Fundamental Research Funds for the Central Universities(Grants Nos.HIT.IBRSEM.201303 and HIT.IBRSEM.B.201401).
文摘Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.
文摘Mdm2 and Mdm4 are negative regulators of the tumour suppressor p53; hence, this relationship is the focus of many cancerrelated studies. A multitude of experiments across various developmental stages have been conducted to explore the tissuespecific roles of these proteins in the mouse. When Mdm2 or Mdm4 are deleted in the germiine or specific tissues, they display different phenotypic defects, some of which lead to embryonic lethaLity. Mdm2 loss is often more deleterious than toss of its homotogue Mdm4. ALL tissues experience activation of p53 target genes upon toss of Mdm2 or Mdm4; however, the degree to which the p53 pathway is perturbed is highly tissue-specific and does not correlate to the severity of the morphological pheno- types. Therefore, a need for further understanding of how these proteins regulate p53 activity is warranted, as therapeutic targeting of the p53 pathway is rapidly evoLving and gaining attention in the field of cancer research. In this review, we discuss the tissue-specificity of Mdm proteins in regulating p53 and expose the need for investigation at the celt-specific level.
文摘随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿刺活检已经逐渐取代手术活检,多数患者在手术切除时已经有了明确诊断.为了更精准测量肿瘤的位置,客观地评判手术范围,准确地评估肿瘤分期和治疗反应,乳腺标本的大体取材受到临床与病理的共同重视,取材方法也在逐渐改进[1-5].准确的大体检查往往依赖于病理医师、放射医师及外科医师的合作.我们旨在介绍乳腺癌手术切除标本和前哨淋巴结的大体取材方法,其主要内容来自于美国MD安德森癌症中心(MD Anderson Cancer Center,MDACC) 行之有效的多年实践.
文摘We investigate and compare the performance of four optical transport schemes for distributing Local Multipoint Distribution Service (LMDS) signals using an optical fiber backbone.
基金supported by grants from the National Natural Science Foundation of China,No.21807112(to Xiang Li),No.82030062(to Wuyuan Lu),Nos.91849129 and 22077078(to Honggang Hu)Shanghai Rising-Star Program(to Xiang Li,China)+1 种基金supported by the U.S.Department of Energy,Office of Science,Office of Basic Energy Sciences under Contract No.DE-AC02-76SF00515supported by the DOE Office of Biological and Environmental Research,and by the National Institutes of Health,National Institute of General Medical Sciences
文摘Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment.Using phage display techniques,we previously identified a potent peptide activator of P53,termed PMI(TSFAEYWNLLSP),with binding affinities for both MDM2 and MDMX in the low nanomolar concentration range.Here we report an ultrahigh affinity,dual-specificity peptide antagonist of MDM2 and MDMX obtained through systematic mutational analysis and additivitybased molecular design.Functional assays of over 100 peptide analogs of PMI using surface plasmon resonance and fluorescence polarization techniques yielded a dodecameric peptide termed PMI-M3(LTFLEYWAQLMQ)that bound to MDM2 and MDMX with K_(d)values in the low picomolar concentration range as verified by isothermal titration calorimetry.Co-crystal structures of MDM2 and of MDMX in complex with PMI-M3 were solved at 1.65 and 3.0 A resolution,respectively.Similar to PMI,PMI-M3 occupied the P53-binding pocket of MDM2/MDMX,which was dominated energetically by intermolecular interactions involving Phe3,Tyr6,Trp7,and Leu 10.Notable differences in binding between PMI-M3 and PMI were observed at other positions such as Leu4 and Met11 with MDM2,and Leu1 and Met11 with MDMX,collectively contributing to a significantly enhanced binding affinity of PMI-M3 for both proteins.By adding lysine residues to both ends of PMI and PMI-M3 to improve their cellular uptake,we obtained modified peptides termed PMI-2K(KTSFAEYWNLLSPK)and M3-2K(KLTFLEYWAQLMQK).Compared with PMI-2K,M3-2K exhibited significantly improved antitumor activities in vitro and in vivo in a P53-dependent manner.This super-strong peptide inhibitor of the P53-MDM2/MDMX interactions may become,in its own right,a powerful lead compound for anticancer drug development,and can aid molecular design of other classes of P53 activators as well for anticancer therapy.
文摘2021年7月17—22日河南省发生了一次历史罕见的持续性强降水,造成了巨大的经济损失。目前极端降水预报仍是次季节气候预测研究的热点和难点。区域气候模式有着比全球模式更精细的空间分辨率和更为完善的物理过程参数化方案,为进一步提高中国次季节降水预报能力提供了新途径。使用区域气候模式CWRF(regional Climate-Weather Research and Forecasting model)对中国气象局全球气候模式次季节预测系统CMA_CPSv3(China Meteorological Administration Climate Prediction System version 3)的预报结果进行中国区域动力降尺度,分析了CWRF和CMA_CPSv3模式对河南省2021年7月17—22日持续性强降水的预测效果。结果表明,区域模式和全球模式预报的降水空间分布和量级存在明显差异。尽管两个模式都低估了此次强降水过程的降水量,但总体上CWRF模式预报的降水量更大且更好地捕捉到了降水的空间分布。CWRF模式自6月26和29日起报的降水预报明显好于同一起报日CMA_CPSv3模式的预报结果。与CMA_CPSv3预报相比,CWRF显著地改善了东亚低空风场和低空急流的预报。CWRF对低空急流和水汽通量输送方向的改善尤为明显,预报的水汽在山脉的迎风坡辐合,为降水提供了有利的水汽条件。同时CWRF更好地预报了郑州上空的垂直上升运动,这些改善都有利于CWRF模式对降水有更高的预报技巧。
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
基金Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
