The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,w...The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.展开更多
Peridynamics (PD), a recently developed theory of solid mechanics, which employs a non-local model of force interaction and makes use of integral formulation rather than the spatial partial differential equations used...Peridynamics (PD), a recently developed theory of solid mechanics, which employs a non-local model of force interaction and makes use of integral formulation rather than the spatial partial differential equations used in the classical continuum mechanics theory, has shown effectiveness and promise in solving discontinuous problems at both macro and micro scales. In this paper, the peridynamics theory is used to analyze damage and progressive failure of concrete structures. A non-local peridynamic model for a rectangular concrete plate is developed, and a central pairwise force function is introduced to describe the interior interactions between particles within some definite distance. Damage initiation, evolution and crack propagation in the concrete model subject to in-plane uni-axial tension, in-plane uni-axial compression and out-of-plane impact load are investigated respectively. The numerical results show that discontinuities appear and grow spontaneously as part of the solution to the peridynamic equations of motion, and no special failure criteria or re-meshing techniques are required, which proves the potential of peridynamic modeling as a promising technique for analyzing the progressive failure of concrete materials and structures.展开更多
Background： Jejunal feeding tube allows the nutrition of critical care patients more easy and safe. However, its placement remains a challenge. This study aimed to introduce a jejunal feeding tube through an ultrasou...Background： Jejunal feeding tube allows the nutrition of critical care patients more easy and safe. However, its placement remains a challenge. This study aimed to introduce a jejunal feeding tube through an ultrasound-guided antral progressive water injection method and subsequently to examine its efficacy. Methods： Between April 2016 and April 2017, 54 patients hospitalized in the Department of Critical Care Medicine, Peking Union Medical College Hospital, China who needed nutritional support through a jejunal feeding tube were recruited for this study. Patients who applied ultrasound-guided antral progressive water injection method were classified into the experimental group. Patients who applied conventional method were registered as control group. Results： No significant differences were found in age, body mass index, and Acute Physiology and Chronic Health Evaluation score, but a significant difference in operation time was found between the experimental group and the control group. Of the 24 individuals in the control group, 17 displayed clear catheter sound shadows once the tube entered the esophagus. In comparison, of the 30 individuals in the experimental group, all harbored catheter sound shadows through the esophageal gas injection method. Subsequent observation revealed that in the control group （via ultrasonographic observation）, 15 individuals underwent successthl antral tube entry, for a success rate of 63%. In the experimental group （via antral progressive water injection）, 27 individuals underwent successful antral tube entry, for a success rate of 90%. There was a significant difference between the success rates of the two groups （x2 = 5.834, P= 0.022）. Conclusion： The antral progressive water injection method for the placement of a jejunal feeding tube is more effective than the traditional ultrasonic placement method.展开更多
Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
基金supported by an intramural research programme,NHGRI,National Institutes of Health(NIH)the National Science Foundation for Excellent Young Scholars of China(grant no.813220170)+1 种基金the Innovation Team of Sichuan Province(2015TD0011)the China Scholarship Council
文摘The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.
基金supported by the National Basic Research Program of China ("973" Project) (Grant No. 2007CB714104)the National Natural Science Foundation of China (Grant No. 10972072)+1 种基金the Fundamental Research Funds for the Central Universities (Grant No. 2009B14914)the Special Fund of State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering at Hohai University (Grant Nos. 2009587012, 2009585912)
文摘Peridynamics (PD), a recently developed theory of solid mechanics, which employs a non-local model of force interaction and makes use of integral formulation rather than the spatial partial differential equations used in the classical continuum mechanics theory, has shown effectiveness and promise in solving discontinuous problems at both macro and micro scales. In this paper, the peridynamics theory is used to analyze damage and progressive failure of concrete structures. A non-local peridynamic model for a rectangular concrete plate is developed, and a central pairwise force function is introduced to describe the interior interactions between particles within some definite distance. Damage initiation, evolution and crack propagation in the concrete model subject to in-plane uni-axial tension, in-plane uni-axial compression and out-of-plane impact load are investigated respectively. The numerical results show that discontinuities appear and grow spontaneously as part of the solution to the peridynamic equations of motion, and no special failure criteria or re-meshing techniques are required, which proves the potential of peridynamic modeling as a promising technique for analyzing the progressive failure of concrete materials and structures.
文摘Background： Jejunal feeding tube allows the nutrition of critical care patients more easy and safe. However, its placement remains a challenge. This study aimed to introduce a jejunal feeding tube through an ultrasound-guided antral progressive water injection method and subsequently to examine its efficacy. Methods： Between April 2016 and April 2017, 54 patients hospitalized in the Department of Critical Care Medicine, Peking Union Medical College Hospital, China who needed nutritional support through a jejunal feeding tube were recruited for this study. Patients who applied ultrasound-guided antral progressive water injection method were classified into the experimental group. Patients who applied conventional method were registered as control group. Results： No significant differences were found in age, body mass index, and Acute Physiology and Chronic Health Evaluation score, but a significant difference in operation time was found between the experimental group and the control group. Of the 24 individuals in the control group, 17 displayed clear catheter sound shadows once the tube entered the esophagus. In comparison, of the 30 individuals in the experimental group, all harbored catheter sound shadows through the esophageal gas injection method. Subsequent observation revealed that in the control group （via ultrasonographic observation）, 15 individuals underwent successthl antral tube entry, for a success rate of 63%. In the experimental group （via antral progressive water injection）, 27 individuals underwent successful antral tube entry, for a success rate of 90%. There was a significant difference between the success rates of the two groups （x2 = 5.834, P= 0.022）. Conclusion： The antral progressive water injection method for the placement of a jejunal feeding tube is more effective than the traditional ultrasonic placement method.
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
