Objective To understand pathological TDP-43 features in the central nervous systems of patients with clinically and autopsy confirmed motor neuron disease (MND).Methods The clinical and histopathological features of 4 cases with MND confirmed by autopsy were summarized; anti-ubiquitin (Ub) and anti-TDP-43 immunohistochemical staining were carried out on tissue of brains and spinal cords from 4 cases with MND and 3 control cases without history of neurological disorders.Results These 4 cases presented with typical clinical and histologic features of MND.Ub-positive inclusions were observed in brain and spinal cord from 3 cases with the Ub-positive inclusions of skein-round-and lewy body-like structures.Strong TDP-43 pathological staining in brain and spinal cord was identified in 2 cases with MND presented as neuronal and glial cytoplasmic inclusions with various shapes.The TDP-43 positive inclusions were widely distributed in the motor cortex of brain and the anterior horn of spinal cord.TDP-43 weak staining in the spinal cord tissue was observed in 1 case with MND.No Ub-and TDP-43 positive inclusions were found in 3 control cases.Conclusion There is widespread pathological TDP-43 expression in the central nervous system of MND.TDP-43 positive inclusions in MND have relatively high specificity.It is worth further study on their formation mechanism.

BACKGROUND: Synaptic density, a key index of structure and function of brain tissues, is related to cognitive function. Synaptic loss occurs during human brain aging and in Alzheimer disease (AD), inducing the changes of synaptic density.OBJECTIVE: To observe quantitative synaptic alterations in human brain and changes of synaptic density in different parts during normal aging so as to compare them with those of AD patients.DESIGN: Sampling survey.SETTING: Senile Neurological Department of General Hospital of Chinese PLA.PARTICIPANTS: Pathological data were selected from General Hospital of Chinese PLA from June 1996 to December 2002. Inclusion criteria: had no major nervous system diseases and neuropathological changes. Brain tissues of 28 corpses in normal aging group, 23 males and 5 females aged 23-100 years with an average of (65±22.8) years, were obtained at autopsy.All corpses were divided into three groups according to their age, namely,adult group (23-55 years old, n=9), senile group (64-72 years old, n=7),and ＞75 group (76-100 years old, n=12). Cerebral hippocampal samples of other six corpses diagnosed with AD were selected from clinic. The corpses included 5 men and 1 woman aged 76-94 years with an average of (83±7.7) years.METHODS: Response intensity of synaptophysin immunochemistry remained stable after 4-8 hours of death, so brains were obtained at autopsy after 8-72 hours of death and fixed with 4% formalin for at least 6 weeks.In normal aging group, tissues were taken from left superior frontal gyrus,striatal area of left occipital lobe, left putamen (striatum section, including head of caudate nucleus), and left hippocampus (from lateral geniculate body section to medial occipitotemporal gyrus). In AD cases, tissues were taken from left hippocampus of 4 corpses and right hippocampus of other 2. All sections were stained with hematoxylin eosin (HE), toluidine blue and synaptophysin immunostaining (rabbit anti-human synaptophysin polyclonal antibody from Beijing Zhongshan Biotechnology Co., Ltd.). Morphology and distribution of positive objects in synapse immunologic reaction were observed under the light microscope. Relation between absorbance in each region and age was determined with Pearson's coefficient. Differences among groups were analyzed with nonparametric test, and the differences in hippocampal CA3 area between ＞ 75 group and AD group were analyzed with the same test.MAIN OUTCOME MEASURES:① Absorbency of synaptophysin at various sites of normal aging group and correlation with age; ② absorbance value in CA3 area between AD patients and advanced aged normal subjects (＞75 years) was compared.RESULTS:All the 34 cerebral samples entered the final analysis.①Synaptophysin-positive granules of various size were scattered through neocortex, putamen and hippocampus, neuronal somata, neuroglia, vessels and white matter. Density was particularly strong over layers Ⅱ and Ⅲ in frontal lobe, and layer ⅣV in occipital lobe. ② Synaptophysin density was negatively correlated with age, which was -0.688 in frontal lobe, -0.592 in occipital lobe, -0.458 in putamen and -0.619 in hippocampal CA2 area,respectively (P = 0.000, 0.001, 0.014, and 0.000). ③ Significant difference in synaptic density in CA3 area was found between AD patients (0.031 3±0.003 0)and normal subjects over the age of 75 (0.040 7±0.005 3) (Z=-2.997, P=0.001)in nonparametric test.CONCLUSION:① Synaptic density was found to decrease in frontal lobe, occipital lobe, CA3 area of hippocampus and putamen with age; the changes had significant correlation with age.② Synaptic density of AD patients was lower than that of normal subjects, and their cognitive hypofunction was related to synaptic loss. ③ All tissues were obtained after 8-72 hours of death and fixed over 6 weeks, which to the greatest extent reduced the effects of tissue autolysis and formalin fixation on the results.

ObjectiveTo explore the characteristics of noncompaction ventricular myocardium under ultrasonic cardiography. Methods8 patients, 1 with non-symptom and other 7 with various cardiac dysfunctions and arrhythmias, accepted ultrasonic cardiography. ResultsNumerous ventricular trabeculae and deep intertrabecular recesses, as well as left ventricular dilatations were found under ultrasonic cardiography.ConclusionNoncompaction ventricular myocardium can be diagnosed with ultrasonic cardiography reliablely.

Vegetables, rice, eggs and drinking water samples were collected from e-waste dismantling area of Qingyuan City, Guangdong Province. Nickel (Ni) was analyzed in each sample, and the non-carcinogenic health [the daily intake (DI) and hazard quotient (HQ)] of each sample was evaluated. In this e-waste dismantling area, the contents of Ni in rice and eggs were (0.46±0.24) and (0.16±0.13) μg/g, which were higher than those in the control area [the contents of Ni in rice and eggs were (0.17±0.03) and (0.02±0.02) μg/g, respectively] (both P values<0.05). The DI values of rice, vegetable, eggs, and drinking water were (3.61-5.86), (1.75-2.99), (0.11-0.24), and (0.08-0.12) μg·kg^-1·day^-1, respectively. The HQ values were 0.180-0.290, 0.090-0.150, 0.005-0.010, 0.005-0.006, respectively. Although the HQ values of rice, vegetable, eggs, and drinking water were all lower than 1, which was an acceptable level. However, considering the possibility of combined exposure of heavy metals, the non-carcinogenic health risks of Ni in the e-waste dismantling area should still be concerned.

Objective To investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases. Methods Spinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study , including 3 cases of multiple system strophy , 4 cases of amyotrophic lateral sclerosis , 5 cases of Alzheimer′s disease ( AD, included 2 cases of AD combined with Parkinson′s disease ) , 2 cases of progressive supranuclear palsy , 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People′s Liberation Army General Hospital.Four normal control cases were also included.Routine HE and Gallyas-Braak staining , and immunohistochemical stainings for anti-PHF tau ( AT8 ) , anti-α-synuclein , anti-TDP-43 and anti-ubiquitin were performed.Results Examination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf′s nucleus of the sacral segment , along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments.Large amount of argentophilic , ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord.Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis , 2 of which were found with Bunina bodies in neurons of the anterior horn.Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments.A few argentophilic , tau positive neurofibrillary tangles ( NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases.Examination of spinal cord in 2 cases with Parkinson′s disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment , and a few synuclein positive lewy bodies and neuritis were also observed.There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic , tau positive globous NFTs and many argentophilic , tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case.Conclusion Each common neurodegenerative diseases of the spinal cord including multiple system strophy,amyotrophic lateral sclerosis and Parkinson′s disease has its own specific histopathology and proteinopathy characteristics .

OBJECTIVETo investigate histopathology and proteinopathy in the spinal cord of patients with common neurodegenerative diseases.

METHODSSpinal cord tissues from clinically and neuropathologically confirmed neruodegnerative diseases were enrolled in this study, including 3 cases of multiple system strophy, 4 cases of amyotrophic lateral sclerosis, 5 cases of Alzheimer's disease (AD, included 2 cases of AD combined with Parkinson's disease), 2 cases of progressive supranuclear palsy, 1 case of dementia with lewy body and 1 case of corticobasal degeneration from 1955 to 2013 at Chinese People's Liberation Army General Hospital. Four normal control cases were also included. Routine HE and Gallyas-Braak staining, and immunohistochemical stainings for anti-PHF tau (AT8), anti-α-synuclein, anti-TDP-43 and anti-ubiquitin were performed.

RESULTSExamination of the spinal cord in 3 cases with multiple system strophy revealed severe neuron loss in the intermediolateral nucleus of thoracic segment and Onuf's nucleus of the sacral segment, along with moderate neuron loss in the anterior horn of the cervical segment and mild myelin pallor in the anterior funiculus and anterolateral funiculus in the cervical and thoracic segments. Large amount of argentophilic, ubiquitin and synuclein positive oligodendroglial cytoplasmic inclusions were found widely distributed in the anterior horn and the anterior funiculus and anterolateral funiculus of the full spinal cord. Severe neuron loss and several morphological changes with gliosis in the anterior horn and severe loss of myelin in the anterior funiculus and anterolateral funiculus of the full spinal cord were observed in 4 cases of amyotrophic lateral sclerosis, 2 of which were found with Bunina bodies in neurons of the anterior horn. Three amyotrophic lateral sclerosis cases had ubiquitin-positive neuronal inclusions and TDP-43 positive neuronal and glial inclusions in the anterior horn at cervical and lumbar segments. A few argentophilic, tau positive neurofibrillary tangles (NFTs) and neuropil threads in the anterior horn at cervical and lumbar segments were found in 4 AD cases. Examination of spinal cord in 2 cases with Parkinson's disease combined with AD and 1 case with dementia with lewy body revealed severe neuron loss in the intermediolateral nucleus of thoracic segment, and a few synuclein positive lewy bodies and neuritis were also observed. There was mild neuron loss in the anterior horn at cervical and lumbar segments, along with some argentophilic, tau positive globous NFTs and many argentophilic, tau positive neutrophil threads were observed in 2 progressive supranuclear palsy cases and 1 corticobasal degeneration case.

CONCLUSIONEach common neurodegenerative diseases of the spinal cord including multiple system strophy, amyotrophic lateral sclerosis and Parkinson's disease has its own specific histopathology and proteinopathy characteristics.

Alzheimer Disease ; pathology ; Amyotrophic Lateral Sclerosis ; pathology ; DNA-Binding Proteins ; metabolism ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Neurodegenerative Diseases ; pathology ; Neurofibrillary Tangles ; pathology ; Neurons ; pathology ; Parkinson Disease ; pathology ; Spinal Cord ; pathology ; Ubiquitin ; metabolism ; alpha-Synuclein ; metabolism

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.