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The disorder of autophagy lysosomal pathway (ALP) is an important pathogenesis of neuronal damage after cerebral ischemia, and the restoration of ALP may alleviate neuronal damage after cerebral ischemia. As the main transcription factor regulating ALP, transcription factor EB (TFEB) can directly regulate autophagosome generation, autophagosome-lysosome fusion, and autophagic flux by regulating the expression of autophagic genes and lysosomal genes. Therefore, regulating TFEB can alleviate ALP dysfunction and thereby reduce cerebral ischemic damage. This article reviews the structure, biological function of TFEB and its role in regulating ALP to alleviate neuronal damage after cerebral ischemia.
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@#Abstract: Objective To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.
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CCAAT/enhancer binding protein β (C/EBPβ), a transcriptional factor of the basic-leucine zipper family, can regulate the transcription activity of downstream target genes. After acute cerebral ischemia, the activity of C/EBPβ changes, and participates in the process of cerebral ischemia injury by regulating neuronal apoptosis and inflammation. This article reviews the molecular biological characteristics of C/EBPβ and its expression changes and role in acute cerebral ischemia, providing a basis for developing new neuroprotective drugs for acute cerebral ischemia using C/EBPβ as therapeutic target.
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Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase with a kinase domain, which plays an important role in the regulation of necroptosis. After cerebral ischemia, MLKL, as the substrate protein of the receptor-interacting protein 3, undergoes oligomerization and phosphorylation, and then translocates from the cytoplasm to the plasmalemma, causing mitochondrial division and cell membrane rupture. MLKL can also mediate the inflammatory response after cerebral ischemia by inducing necroptosis and directly activating inflammasomes, thereby aggravating brain injury. Therefore, to clarify the biological characteristics of MLKL and its role and mechanism in cerebral ischemia is very important for the treatment of cerebral ischemia.
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Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm2 vs. 1.4(1.1-1.9)mm2, all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Subject(s)
Aged , Humans , Male , Middle Aged , Coronary Angiography , Inflammation , Myocardial Infarction/diagnostic imaging , Percutaneous Coronary Intervention , Plaque, Atherosclerotic/diagnostic imaging , Retrospective Studies , ST Elevation Myocardial Infarction/surgery , Stroke Volume , Thrombolytic Therapy , Ventricular Function, LeftABSTRACT
Exosomes are extracellular small molecular vesicles with lipid bilayers, which contain biologically active substances such as RNA and proteins. Exosomes can conduct material transport and information transmission between cells. After cerebral ischemia, neuron-derived exosomes affect the occurrence and development of neuroinflammation by regulating the activation of glial cells, and the activated glial cells secrete exosomes containing inflammatory factors or inflammation related microRNAs to regulate the survival or death of neurons. Studies have shown that exosomes can be used as biomarkers and therapeutic targets for inflammatory injury after cerebral ischemia. This article describes the composition and function of exosomes, as well as their role and possible mechanism in neuroinflammation after cerebral ischemia.
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p75 neurotrophin receptor (p75 NTR) is a member of the tumor necrosis factor receptor superfamily, which interacts with tropomyosin receptor kinase (Trk) receptor or binds neurotrophic factors. It mediates a variety of complex signal transduction pathways, induces synaptic growth and affects cell survival. After acute cerebral ischemia, p75 NTR binds effector factors such as pro-nerve growth factor (proNGF) and sortilin, activating downstream apoptotic signal molecules and leading to neuronal death. Therefore, elucidating the pathways and molecular mechanisms of p75 NTR that mediate neuronal apoptosis in acute cerebral ischemia is of great significance for the development of new therapeutic drugs for acute cerebral ischemia.
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Activating transcription factor 4 (ATF4) is a stress response factor containing a basic region-leucine zipper. When the body is under stress, the increased expression of ATF4 binds to cellular transcription factors, which in turn regulates the corresponding downstream target genes, thereby initiating cellular responses. After cerebral ischemia, ATF4 plays a neuroprotective role by participating in various pathophysiological processes such as regulating endoplasmic reticulum stress, oxidative stress, mitochondrial autophagy, inflammatory response, vascular regeneration, and synaptic plasticity. Therefore, ATF4 is expected to become a new target for the treatment of ischemic brain injury.
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Tricalcium phosphate (TCP) is one of the most widely used bioceramics for constructing bone tissue engineering scaffold. The three-dimensional (3D) printed TCP scaffold has precise and controllable pore structure, while with the limitation of insufficient mechanical properties. In this study, we investigated the effect of sintering temperature on the mechanical properties of 3D-printed TCP scaffolds in detail, due to the important role of the sintering process on the mechanical properties of bioceramic scaffolds. The morphology, mass and volume shrinkage, porosity, mechanical properties and degradation property of the scaffold was studied. The results showed that the scaffold sintered at 1 150℃ had the maximum volume shrinkage, the minimum porosity and optimal mechanical strength, with the compressive strength of (6.52 ± 0.84) MPa and the compressive modulus of (100.08 ± 18.6) MPa, which could meet the requirements of human cancellous bone. In addition, the 1 150℃ sintered scaffold degraded most slowly in the acidic environment compared to the scaffolds sintered at the other temperatures, demonstrating its optimal mechanical stability over long-term implantation. The scaffold can support bone mesenchymal stem cells (BMSCs) adherence and rapid proliferation and has good biocompatibility. In summary, this paper optimizes the sintering process of 3D printed TCP scaffold and improves its mechanical properties, which lays a foundation for its application as a load-bearing bone.
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Chemokine CX3CL1 mainly participates in the physiological and pathological processes of nervous system by activating its receptor CX3CR1.Under physiological conditions,CX3CL1 can inhibit the activation of microglia;when cerebral ischemia and hypoxia,CX3CL1 can affect the expression of multiple downstream target genes involved in activation of adenosine receptor,inhibition of Ca 2+ influx,and promotion of blood vessel growth.It is of great significance to improve the energy metabolism disorder and to establish microcirculation around infarcts after cerebral ischemia.
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Chemokine CX3CL1 mainly participates in the physiological and pathological processes of nervous system by activating its receptor CX3CR1. Under physiological conditions, CX3CL1 can inhibit the activation of microglia; when cerebral ischemia and hypoxia, CX3CL1 can affect the expression of multiple downstream target genes involved in activation of adenosine receptor, inhibition of Ca2+ influx, and promotion of blood vessel growth. It is of great significance to improve the energy metabolism disorder and to establish microcirculation around infarcts after cerebral ischemia.
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Piwi-interacting RNA (piRNA) is a new class of small non-coding RNAs that function by specifically binding to the Piwi subfamily members of the Argonaute protein family. piRNA regulates the expression of target genes at epigenetic and post-transcriptional levels, and participates in the development and progression of cerebral ischemia by mediating pathophysiological processes such as inflammation, angiogenesis, and neuronal synaptic plasticity.
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In the central nervous system, gap junctions exist between neurons and glial cells. Among them, connexin 43 (Cx43) is one of the most abundant connexin proteins in the central nervous system,involved in the metabolic coupling of intercellular substance exchange and electrical coupling of electrical signaling. It plays an important role in regulating cell metabolism, homeostasis, and cell differentiation. After cerebral ischemia, the uncoupling of gap junctions and abnormal hemichannel activity cause a steady-state imbalance of the internal and external environment of the cells, eventually leading to brain tissue damage.Therefore, maintaining the normal function of Cx43 is essential for protecting brain tissue from neuronal damage induced by cerebral ischemia-reperfusion.
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It is unanimously accepted that stroke is a highly heterogeneous disorder.Different subtypes of ischemic stroke may have different risk factors,clinical features,and prognoses.The aim of this study was to evaluate the risk factors,clinical characteristics,and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment (TOAST) criteria.We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period.Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria.Patients were followed up till 30 and 90 days after stroke onset.It was found that large-artery atherosclerosis was the most frequent etiology of stroke (37.4％),and showed the highest male preponderance,the highest prevalence of previous transient ischemic attack,and the longest hospital stay among all subtypes.Small artery disease (36.4％) was associated with higher body mass index,higher plasma triglycerides,and lower plasma high-density lipoprotein cholesterol than cardioembolism.Cardioembolism (7.7％),which was particularly common in the elderly (i.e.,individuals aged 65 years and older),showed the highest female preponderance,the highest prevalence of atrial fibrillation,the earliest presentation to hospital after stroke onset,the most severe symptoms on admission,the maximum complications associated with an adverse outcome,and the highest rate of stroke recurrence and mortality.Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder.Studies involving risk factors,clinical features,and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.
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It is unanimously accepted that stroke is a highly heterogeneous disorder.Different subtypes of ischemic stroke may have different risk factors,clinical features,and prognoses.The aim of this study was to evaluate the risk factors,clinical characteristics,and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment (TOAST) criteria.We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period.Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria.Patients were followed up till 30 and 90 days after stroke onset.It was found that large-artery atherosclerosis was the most frequent etiology of stroke (37.4％),and showed the highest male preponderance,the highest prevalence of previous transient ischemic attack,and the longest hospital stay among all subtypes.Small artery disease (36.4％) was associated with higher body mass index,higher plasma triglycerides,and lower plasma high-density lipoprotein cholesterol than cardioembolism.Cardioembolism (7.7％),which was particularly common in the elderly (i.e.,individuals aged 65 years and older),showed the highest female preponderance,the highest prevalence of atrial fibrillation,the earliest presentation to hospital after stroke onset,the most severe symptoms on admission,the maximum complications associated with an adverse outcome,and the highest rate of stroke recurrence and mortality.Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder.Studies involving risk factors,clinical features,and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.
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This paper aims to determine the expression and clinical significance of DDX43 in lung adenocarcinoma. Expression of DDX43 gene and protein of lung adenocarcinoma tissue and para-carcinoma tissues was observed in 27 cases by RT-PCR and immunohistochemistry. These patients were diagnosed as lung adenocarcinoma in the Huaihe Hospital of Henan University from February 2015 to December 2015. The relative ratio of DDX43 mRNA expression in lung adenocarcinoma and para-carcinoma tissues was 0.87+/- 0.62 versus 0.21+/- 0.77 and the difference between the two groups was statistically significant [P<0.01]. The expression of DDX43 in normal lung tissues and lung adenocarcinoma tissues was different. The positive rate of DDX43 expression in lung adenocarcinoma tissues was significantly higher than that in normal lung tissues, and the difference was statistically significant [P<0.05]. The analysis of clinical pathological characteristics showed that the increase of protein expression was related to the stage and metastasis of lung adenocarcinoma. DDX43 is highly expressed in lung adenocarcinoma, and the expression level is related to the stage and metastasis of lung adenocarcinoma, suggesting that DDX43 is closely related to the occurrence and development of lung adenocarcinoma, and may be a molecular marker for early diagnosis of lung adenocarcinoma
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Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical antioxidative transcription factor, which participates in maintaining redox homeostasis of cells. Under the physiological state, Nrf2 is localized to the cytoplasm in an inactive state.In response to oxidative stress,the activated Nrf2 translocates to nucleus, then recognizes and binds the antioxidant response elements,and thus stimulates the transcription of antioxidant enzymes. It is essential to protect the brain tissue from oxidative damage induced by cerebral ischemia-reperfusion.
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ObjectiveTo investigate the expression change of cathepsin B (CathB) in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after cortical infarction in rats.MethodsThe adult male Sprague-Dawley rats were randomly divided into either a sham operation group or a model group.The latter was further divided into postoperative 1-, 2-, 3-, 4-, and 8-week groups.A model of cerebral cortical infarction was induced by electrocoagulation the cortical branch of middle cerebral artery.Immunohistochemical staining and immunofluorescence were used to detect the protein expression and cellular localization of CathB in the VPN at each time point.ResultsThe expression level of VPN CathB in thalamus increased gradually after cerebral cortical infarction.It reached the peak at 4 weeks, and decreased at 8 weeks, however it was still higher than the control group (all P<0.05).The release of CathB from the lysosomes into the cytoplasm were found.In addition, the expression level of CathB in the activated astrocytes was significantly increased at 3 weeks after cerebral cortical infarction.ConclusionsDuring 1-8 week after cerebral cortex infarction, CathB in the VPN of the ipsilateral thalamus maintained higher expression level, suggesting that it might play a certain role in secondary degeneration in the thalamus after cerebral cortical infarction.
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Objective To evaluate the effect of the standardized training program for resident physicians in Ruijin Hospital,and analyse the problems so as to provide reference to improve the training.Methods Questionnaire surveys were conducted among 113 resident physicians,31 teachers and 43 head nurses in Rujin Hospital by using the simple random sampling and 300.The data was analysed by Kirkpatrick's model in four layers including reaction layer,learning layer,behaviors layer and results layer.Data of reation layer was analysed by ANOVA and data of behaviors layer was compared by paired t-test.Results Reaction layer:the resident physicians' overall satisfaction score for the training is 3.45.Learning layer:all resident doctors participating in the training passed all the exams organised by the hospital.Behaviors layer:Residents made a great progress in many aspects after the standardized training program,and the difference was statistically significant (P＜0.01) according to the analysis of all questionnaires written by residents,clinical teachers and head nurses.Results layer:both the patient complaint rate and the accident rate of the 113 resident physicians was 0 while they all passed the National Medical Licensing Examination and the employment rate was 100％.Conclusions the standardized training program for resident physicians in Ruijin Hospital gets fairly good effect.Resident doctors' quality and ability in many aspects are improved and the overall satisfaction for the training is high,but in salary,benefits and sense of belonging to the hospital,the satisfaction is relatively low.
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<p><b>OBJECTIVE</b>To explore a method for combining Fluoro-Jade B (FJB) staining with immunofluorescent staining in rats with focal cortical infarction.</p><p><b>METHOD</b>Permanent distal middle cerebral artery occlusion (dMCAO) was induced in rats by electrocoagulation. The rat models were randomized into two groups, and frozen sections of the brain tissues from each group were stained with FJB followed by immunofluorescent staining or in the reverse order.</p><p><b>RESULTS</b>FJB staining followed by immunofluorescence staining clearly visualized both FJB-positive and immunofluorescence-positive cells in the frozen sections, but the staining protocol in the reverse sequence failed to clearly show the immunofluorescence-positive cells.</p><p><b>CONCLUSION</b>FJB staining prior to immunofluorescence staining does not affect the staining effect of protein immunofluorescent staining and better visualizes the positive cells.</p>