Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accou...Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.展开更多
Objective:To investigate the relationship between variation of HBV preS genes and clinical consequencesof HBV infection. Methods: We selected 3 groups (3 in each) of HBV infected individuals including those of acutein...Objective:To investigate the relationship between variation of HBV preS genes and clinical consequencesof HBV infection. Methods: We selected 3 groups (3 in each) of HBV infected individuals including those of acuteinfection with complete recovery, chronic HBV carriers and chronic severe hepatitis B. The preS genes were amplified from serum samples with half nested PCR. The PCR products were cloned into M13 vectors and 10 cloneswere randomly selected for each individual and sequenced with standard methods. A total of 90 clones were sequenced and analyzed by DNA homological comparison. Results: The characteristics of the preS genes were significantly different in HBV-infected individuals with different clinical consequences.①As for acute hepatitis B, thepreS function domains were stable and no changes in epitopes for T and B cells were found. ②For chronic HBVcarriers, the function domains within preS proteins showed potentially changes with epitope drifts of T and B cellsbecause of the high variation of HBV preS genes. ③For chronic severe hepatitis B, there were special changes inthe function domains of B cells. The abnormally high immune response would cause severe liver injury in these individuals. Conclusion: This study provides experimental evidence for researches about the possible association ofvariation of preS1/S2 functional regions with clinical consequences.展开更多
We study a batch arrival MX/M/1 queue with multiple working vacation. The server serves customers at a lower rate rather than completely stopping service during the service period. Using a quasi upper triangular trans...We study a batch arrival MX/M/1 queue with multiple working vacation. The server serves customers at a lower rate rather than completely stopping service during the service period. Using a quasi upper triangular transition probability matrix of two-dimensional Markov chain and matrix analytic method, the probability generating function (PGF) of the stationary system length distribution is obtained, from which we obtain the stochastic decomposition structure of system length which indicates the relationship with that of the MX/M/1 queue without vacation. Some performance indices are derived by using the PGF of the stationary system length distribution. It is important that we obtain the Laplace Stieltjes transform (LST) of the stationary waiting time distribution. Further, we obtain the mean system length and the mean waiting time. Finally, numerical results for some special cases are presented to show the effects of system parameters.展开更多
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
文摘Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.
文摘Objective:To investigate the relationship between variation of HBV preS genes and clinical consequencesof HBV infection. Methods: We selected 3 groups (3 in each) of HBV infected individuals including those of acuteinfection with complete recovery, chronic HBV carriers and chronic severe hepatitis B. The preS genes were amplified from serum samples with half nested PCR. The PCR products were cloned into M13 vectors and 10 cloneswere randomly selected for each individual and sequenced with standard methods. A total of 90 clones were sequenced and analyzed by DNA homological comparison. Results: The characteristics of the preS genes were significantly different in HBV-infected individuals with different clinical consequences.①As for acute hepatitis B, thepreS function domains were stable and no changes in epitopes for T and B cells were found. ②For chronic HBVcarriers, the function domains within preS proteins showed potentially changes with epitope drifts of T and B cellsbecause of the high variation of HBV preS genes. ③For chronic severe hepatitis B, there were special changes inthe function domains of B cells. The abnormally high immune response would cause severe liver injury in these individuals. Conclusion: This study provides experimental evidence for researches about the possible association ofvariation of preS1/S2 functional regions with clinical consequences.
文摘We study a batch arrival MX/M/1 queue with multiple working vacation. The server serves customers at a lower rate rather than completely stopping service during the service period. Using a quasi upper triangular transition probability matrix of two-dimensional Markov chain and matrix analytic method, the probability generating function (PGF) of the stationary system length distribution is obtained, from which we obtain the stochastic decomposition structure of system length which indicates the relationship with that of the MX/M/1 queue without vacation. Some performance indices are derived by using the PGF of the stationary system length distribution. It is important that we obtain the Laplace Stieltjes transform (LST) of the stationary waiting time distribution. Further, we obtain the mean system length and the mean waiting time. Finally, numerical results for some special cases are presented to show the effects of system parameters.
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
