严重多发伤患者创伤后早期阶段,多脏器功能衰竭是死亡的主要原因.重症监护室(intensive care unit,ICU)中创伤患者常伴有肝功能不全,约27%的严重创伤患者发生肝功能衰竭.然而创伤性肝损的发病机制复杂,主要原因有:肝脏创伤、缺血再灌注...严重多发伤患者创伤后早期阶段,多脏器功能衰竭是死亡的主要原因.重症监护室(intensive care unit,ICU)中创伤患者常伴有肝功能不全,约27%的严重创伤患者发生肝功能衰竭.然而创伤性肝损的发病机制复杂,主要原因有:肝脏创伤、缺血再灌注损伤、严重感染、危险相关分子模式等.临床上对创伤性肝损患者常采用传统的保守治疗或手术治疗,因此明确创伤性肝损的相关机制,寻找新的药物治疗靶点,规范合理地提高创伤性肝损的诊治水平至关重要.本文主要针对创伤后导致肝功能损伤的机制及主要诊疗方式作一综述.展开更多
Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associ...Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.展开更多
The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes o...The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the ＇missing self＇ and the ＇dangerous non-self＇, respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the ＇safe non-self＇ and dealing with the inevitable ＇distressed self＇, and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life＇s many stresses.展开更多
文摘严重多发伤患者创伤后早期阶段,多脏器功能衰竭是死亡的主要原因.重症监护室(intensive care unit,ICU)中创伤患者常伴有肝功能不全,约27%的严重创伤患者发生肝功能衰竭.然而创伤性肝损的发病机制复杂,主要原因有:肝脏创伤、缺血再灌注损伤、严重感染、危险相关分子模式等.临床上对创伤性肝损患者常采用传统的保守治疗或手术治疗,因此明确创伤性肝损的相关机制,寻找新的药物治疗靶点,规范合理地提高创伤性肝损的诊治水平至关重要.本文主要针对创伤后导致肝功能损伤的机制及主要诊疗方式作一综述.
基金supported by the US National Institutes of Health (R01-DE17794, R01-NS54362 and R01-NS67686)
文摘Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.
文摘The elusive task of defining the character of 76 T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and p T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, 76 T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ap T cells are particularly well equipped to respond to the ＇missing self＇ and the ＇dangerous non-self＇, respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the ＇safe non-self＇ and dealing with the inevitable ＇distressed self＇, and it is within this more complex realm 76 T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human 76 T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life＇s many stresses.
