AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD...AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric neoplasms at a single tertiary referral center. Among these, 28 patients underwent secondary ESD for a residual or locally recurrent tumor. Our analysis compared clinicopathologic factors between primary ESD and secondary ESD groups. RESULTS The en bloc resection and curative rate of resection of secondary ESD were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD was significantly longer than primary ESD(78.2 min vs 55.1 min, P = 0.004), and the adverse events rate was not significantly different but trended slightly higher in the secondary ESD group compared to the primary ESD group(10.7% vs 3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes without severe adverse events. During a mean follow-up period, no local recurrence occurred in patients who received secondary ESD. CONCLUSION Secondary ESD of residual or locally recurrent gastric tumors appears to be a feasible and curative treatment though it requires greater technical efficiency and longer procedure time.展开更多
Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brai...Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.展开更多
Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endop...Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal（1 mg/kg）, by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.展开更多
Over the last two decades multiple studies have demonstrated an increased incidence of additional malignancies in patients with intraductal papillary mucinous neoplasms(IPMNs).Additional malignancies have been identif...Over the last two decades multiple studies have demonstrated an increased incidence of additional malignancies in patients with intraductal papillary mucinous neoplasms(IPMNs).Additional malignancies have been identified in 10%-52% of patients with IPMNs.The majority of these additional cancers occur before or concurrent with the diagnosis of IPMN.The gastrointestinal tract is most commonly involved in secondary malignancies,with benign colon polyps and colon cancer commonly seen in western countries and gastric cancer commonly seen in Asian countries.Other extrapancreatic malignancies associated with IPMNs include benign and malignant esophageal neoplasms,gastrointestinal stromal tumors,carcinoid tumors,hepatobiliary cancers,breast cancers,prostate cancers,and lung cancers.There is no clear etiology for the development of secondary malignancies in patients with IPMN.Although population-based studies have shown different results from single institution studies regarding the exact incidence of additional primary cancers in IPMN patients,both have reached the same conclusion:there is a higher incidence of extrapancreatic malignancies in patients with IPMNs than in the general population.This f inding has signif icant clinical implications for both the initial evaluation and the subsequent long-term followup of patients with IPMNs.If a patient has not had recent colonoscopy,this should be performed during the evaluation of a newly diagnosed IPMN.Upper endoscopy should be performed in patients from Asian countries or for those who present with symptoms suggestive of upper gastrointestinal disease.Routine screening studies(breast and prostate) should be carried out as currently recommended for patient's age both before and after the diagnosis of IPMN.展开更多
BACKGROUND：Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE： To observe changes in white blood cells （WBC） and poly...BACKGROUND：Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE： To observe changes in white blood cells （WBC） and polymorphonuclear neutrophils （PMN） in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING： A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS： Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS： WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES： The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS： WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury （P 〈 0.01）. These measures negatively correlated to the Glasgow coma scale （r = -0.657, -0.541, respectively, P 〈 0.05）. In patients with Glasgow coma sale 〈 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 （P 〈 0.05）. Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size （P 〈 0.05）. CONCLUSION： WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale.展开更多
After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been full...After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.展开更多
Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of t...Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI.Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling pathways.Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory factors.Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.展开更多
Changes in platelet parameters are important in secondary brain injury in acute craniocerebral trauma We selected 163 patients with craniocerebral trauma who were admitted within 24 hours with nonoperative therapy. Pl...Changes in platelet parameters are important in secondary brain injury in acute craniocerebral trauma We selected 163 patients with craniocerebral trauma who were admitted within 24 hours with nonoperative therapy. Platelet parameters of 40 healthy subjects served as controls. Platelet number was decreased, while mean platelet volume and platelet distribution width values were increased, at 1 and 3 days after injury. Platelet number was lower and mean platelet volume and platelet distribution width were larger in patients with traumatic cerebral infarction and those in Glasgow Coma Scale score 〈 8 group. Platelet number was negatively correlated to volume of cerebral edema, but positively correlated to Glasgow Outcome Scale score. These data indicate that changes in platelet parameters may be utilized to indicate the state of central nervous system injury and patient prognosis .展开更多
The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to t...The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.展开更多
目的构建并验证一个模型以预测肺癌脑转移(lung cancer with brain metastases,LCBM)患者确诊后三个月内死亡的风险。方法本研究纳入监测,流行病学和最终结果(Surveillance,Epidemiology and End Results,SEER)数据库内2010年1月至2015...目的构建并验证一个模型以预测肺癌脑转移(lung cancer with brain metastases,LCBM)患者确诊后三个月内死亡的风险。方法本研究纳入监测,流行病学和最终结果(Surveillance,Epidemiology and End Results,SEER)数据库内2010年1月至2015年12月期间确诊为LCBM的患者。以是否发生早期死亡为研究终点将患者分为早期死亡组和非早期死亡组。以8∶2为比例将数据分为训练集和验证集。在训练集上采用最小绝对值收缩和筛选算子(least absolute shrinkage and selection operator,LASSO)回归法筛选预测因子,并使用多因素Logistic回归构建预测模型并创建列线图。使用受试者工作特征(receiver operating characteristic,ROC)曲线、校准曲线和临床决策曲线(decision curve analysis,DCA)分别在训练集和验证集上评估模型性能。结果共纳入5035例患者,早期死亡发生率28.3%。LASSO回归筛选出13个变量,Logistic回归最终保留了13个与LCBM患者早期死亡相关的危险因素,包括年龄、从诊断到开始治疗时间、肿瘤大小、肿瘤部位、肿瘤分化程度和组织学类型、T分期、N分期、手术、放疗、化疗、肝转移和骨转移。验证集的一致性指数(concordance index,C-index)为0.84,校准曲线和DCA显示模型具有较好的预测效能和临床净效益。结论基于多因素Logistic回归构建的LCBM患者发生早期死亡的预测模型的区分度较好,能够为临床决策提供一定的帮助。展开更多
Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Re...Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.展开更多
基金Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(NRF-2015R1C1A1A01054352)
文摘AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric neoplasms at a single tertiary referral center. Among these, 28 patients underwent secondary ESD for a residual or locally recurrent tumor. Our analysis compared clinicopathologic factors between primary ESD and secondary ESD groups. RESULTS The en bloc resection and curative rate of resection of secondary ESD were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD was significantly longer than primary ESD(78.2 min vs 55.1 min, P = 0.004), and the adverse events rate was not significantly different but trended slightly higher in the secondary ESD group compared to the primary ESD group(10.7% vs 3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes without severe adverse events. During a mean follow-up period, no local recurrence occurred in patients who received secondary ESD. CONCLUSION Secondary ESD of residual or locally recurrent gastric tumors appears to be a feasible and curative treatment though it requires greater technical efficiency and longer procedure time.
文摘Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.
文摘Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome. Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis. Therefore, endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury. In this study, a rat model of traumatic brain injury was established by lateral fluid percussion injury. Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex. Western blot assays were used to determine expression of endoplasmic reticulum stress-related proteins. Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex. Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria. Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response. Meanwhile, both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury. Furthermore, pretreatment with the endoplasmic reticulum stress inhibitor, salubrinal（1 mg/kg）, by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis. Moreover, salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury. These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.
文摘Over the last two decades multiple studies have demonstrated an increased incidence of additional malignancies in patients with intraductal papillary mucinous neoplasms(IPMNs).Additional malignancies have been identified in 10%-52% of patients with IPMNs.The majority of these additional cancers occur before or concurrent with the diagnosis of IPMN.The gastrointestinal tract is most commonly involved in secondary malignancies,with benign colon polyps and colon cancer commonly seen in western countries and gastric cancer commonly seen in Asian countries.Other extrapancreatic malignancies associated with IPMNs include benign and malignant esophageal neoplasms,gastrointestinal stromal tumors,carcinoid tumors,hepatobiliary cancers,breast cancers,prostate cancers,and lung cancers.There is no clear etiology for the development of secondary malignancies in patients with IPMN.Although population-based studies have shown different results from single institution studies regarding the exact incidence of additional primary cancers in IPMN patients,both have reached the same conclusion:there is a higher incidence of extrapancreatic malignancies in patients with IPMNs than in the general population.This f inding has signif icant clinical implications for both the initial evaluation and the subsequent long-term followup of patients with IPMNs.If a patient has not had recent colonoscopy,this should be performed during the evaluation of a newly diagnosed IPMN.Upper endoscopy should be performed in patients from Asian countries or for those who present with symptoms suggestive of upper gastrointestinal disease.Routine screening studies(breast and prostate) should be carried out as currently recommended for patient's age both before and after the diagnosis of IPMN.
文摘BACKGROUND：Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE： To observe changes in white blood cells （WBC） and polymorphonuclear neutrophils （PMN） in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING： A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS： Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS： WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES： The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS： WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury （P 〈 0.01）. These measures negatively correlated to the Glasgow coma scale （r = -0.657, -0.541, respectively, P 〈 0.05）. In patients with Glasgow coma sale 〈 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 （P 〈 0.05）. Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size （P 〈 0.05）. CONCLUSION： WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale.
基金supported by the National Natural Science Foundation of China,No. 81771327 (to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research PlatformBudget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (BYL)。
文摘After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.
基金supported by the National Natural Science Foundation of China,No. 81771327a grant for the Platform Construction of Basic Research and Clinical Translation of Nervous System Injury,China,No. PXM2020_026280_000002 (both to BYL)
文摘Proteomics is a powerful tool that can be used to elucidate the underlying mechanisms of diseases and identify new biomarkers.Therefore,it may also be helpful for understanding the detailed pathological mechanism of traumatic brain injury(TBI).In this study,we performed Tandem Mass Tag-based quantitative analysis of cortical proteome profiles in a mouse model of TBI.Our results showed that there were 302 differentially expressed proteins in TBI mice compared with normal mice 7 days after injury.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that these differentially expressed proteins were predominantly involved in inflammatory responses,including complement and coagulation cascades,as well as chemokine signaling pathways.Subsequent transcription factor analysis revealed that the inflammation-related transcription factors NF-κB1,RelA,IRF1,STAT1,and Spi1 play pivotal roles in the secondary injury that occurs after TBI,which further corroborates the functional enrichment for inflammatory factors.Our results suggest that inflammation-related proteins and inflammatory responses are promising targets for the treatment of TBI.
基金the Key Medical Construction Subject Foundation of Sichuan Province
文摘Changes in platelet parameters are important in secondary brain injury in acute craniocerebral trauma We selected 163 patients with craniocerebral trauma who were admitted within 24 hours with nonoperative therapy. Platelet parameters of 40 healthy subjects served as controls. Platelet number was decreased, while mean platelet volume and platelet distribution width values were increased, at 1 and 3 days after injury. Platelet number was lower and mean platelet volume and platelet distribution width were larger in patients with traumatic cerebral infarction and those in Glasgow Coma Scale score 〈 8 group. Platelet number was negatively correlated to volume of cerebral edema, but positively correlated to Glasgow Outcome Scale score. These data indicate that changes in platelet parameters may be utilized to indicate the state of central nervous system injury and patient prognosis .
基金funded by the National Natural Science Foundation of China,Nos.82171363(to PL),82171321(to XL),82171458(to XJ)the Youth Nova Program of Shaanxi,No.2021KJXX-19(to PL)。
文摘The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.
文摘目的构建并验证一个模型以预测肺癌脑转移(lung cancer with brain metastases,LCBM)患者确诊后三个月内死亡的风险。方法本研究纳入监测,流行病学和最终结果(Surveillance,Epidemiology and End Results,SEER)数据库内2010年1月至2015年12月期间确诊为LCBM的患者。以是否发生早期死亡为研究终点将患者分为早期死亡组和非早期死亡组。以8∶2为比例将数据分为训练集和验证集。在训练集上采用最小绝对值收缩和筛选算子(least absolute shrinkage and selection operator,LASSO)回归法筛选预测因子,并使用多因素Logistic回归构建预测模型并创建列线图。使用受试者工作特征(receiver operating characteristic,ROC)曲线、校准曲线和临床决策曲线(decision curve analysis,DCA)分别在训练集和验证集上评估模型性能。结果共纳入5035例患者,早期死亡发生率28.3%。LASSO回归筛选出13个变量,Logistic回归最终保留了13个与LCBM患者早期死亡相关的危险因素,包括年龄、从诊断到开始治疗时间、肿瘤大小、肿瘤部位、肿瘤分化程度和组织学类型、T分期、N分期、手术、放疗、化疗、肝转移和骨转移。验证集的一致性指数(concordance index,C-index)为0.84,校准曲线和DCA显示模型具有较好的预测效能和临床净效益。结论基于多因素Logistic回归构建的LCBM患者发生早期死亡的预测模型的区分度较好,能够为临床决策提供一定的帮助。
文摘目的探讨表观扩散系数(apparent diffusion coefficient,ADC)鉴别诊断肺癌脑转移瘤组织学分型的价值及其与Ki-67增殖指数之间的关系。材料与方法回顾性分析经手术病理证实的20例小细胞肺癌脑转移瘤和41例非小细胞肺癌脑转移瘤患者的资料,并测定其Ki-67增殖指数。在ADC图上测量肿瘤实性部分的最小ADC值(the minimum ADC,ADCmin)、平均ADC值(the mean ADC,ADCmean)及对侧正常脑白质ADC值,并计算相对ADCmin(relative ADCmin,rADCmin)及相对ADCmean(relative ADCmean,rADCmean)。对比分析二者ADC值的差异,绘制受试者工作特征(receiver operating characteristic,ROC)曲线评价ADC值的鉴别诊断价值,并计算ADC值与Ki-67增殖指数之间的相关性。结果小细胞肺癌脑转移瘤组的ADCmin、ADCmean、rADCmin及rADCmean值均小于非小细胞肺癌脑转移瘤组,组间差异均具有统计学意义(P<0.05)。各ADC值均能对小细胞肺癌脑转移瘤及非小细胞肺癌脑转移瘤进行有效鉴别,其中rADCmean值的鉴别诊断效能最好,曲线下面积(area under the curve,AUC)为0.950[95%置信区间(confidence interval,CI):0.907~0.994],最佳截断值为0.955,相应的敏感度和特异度分别为96.23%、83.87%,准确度为91.67%。小细胞肺癌脑转移瘤组的Ki-67增殖指数大于非小细胞肺癌脑转移瘤组,组间差异具有统计学意义(P<0.05)。61例肺癌脑转移瘤患者的ADCmin、ADCmean、rADCmin及rADCmean值均与Ki-67增殖指数呈不同程度的负相关(r=-0.506、r=-0.480、r=-0.569、r=-0.541)。结论ADC值可以对肺癌脑转移瘤的组织学分型进行鉴别诊断,并可以预测Ki-67增殖指数的表达水平。
基金supported by the National Natural Science Foundation of China,Nos.82071382(to MZ),81601306(to HS)The Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to MZ)+5 种基金Jiangsu 333 High-Level Talent Training Project(2022)(to HS)The Jiangsu Maternal and Child Health Research Key Project,No.F202013(to HS)Jiangsu Talent Youth Medical Program,No.QNRC2016245(to HS)Shanghai Key Lab of Forensic Medicine,No.KF2102(to MZ)Suzhou Science and Technology Development Project,No.SYS2020089(to MZ)The Fifth Batch of Gusu District Health Talent Training Project,No.GSWS2019060(to HS)。
文摘Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.
