The role of the primary sensorimotor system in generalized epilepsy: Evidence from the cerebello-cerebral functional integration.

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high-level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello-cerebral circuit is still poorly understood. Resting-state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel-based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello-cerebral functional integration on the voxel-based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello-cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.

Different Responses to Identical Trauma Between BALB/C and C57BL/6 Mice.

BACKGROUND Different responses to identical trauma may be related to the genetic background of individuals, but the molecular mechanism is unclear. In this study we investigated the heterogeneity of trauma in mice and the potential biological explanations for the differences. MATERIAL AND METHODS Compared with other organs, the pathological response of the lung after injury is the earliest and most serious. We used C57BL/6 and BALB/C mice to explore the genetic background of different responses to trauma in the lung. We measured mortality rate, pulmonary microvascular permeability, and Cxcl15 gene expression in BALB/C and C57BL/6 mice before and after blast-wave injury. Microvascular permeability was measured using a fluorescent tracer, and Cxcl15 gene expression level and expression distribution were measured using fluorogenic probe quantitative polymerase chain reaction and northern blot. RESULTS C57BL/6 mice showed lower mortality rates and pulmonary microvascular permeability than BALB/C mice after blast-wave injury; there was no significant difference in the permeability before blast-wave injury. The Cxcl15 gene was expressed specifically in the lung tissue of mice. The level of Cxcl15 expression in BALB/C mice was higher than in C57BL/6 mice before and after injury, and the variation trend of Cxcl15 expression level after injury was significantly different between BALB/C and C57BL/6 mice. CONCLUSIONS Our results indicated that BALB/C and C57BL/6 mice had significant heterogeneity in posttraumatic response in terms of mortality and degree of lung damage. The differences in genetic factors such as Cxcl15 may have played a role in this heterogeneity.

A new model for dynamic mapping of effective connectivity in task fMRI.

Whole-brain dynamic functional connectivity is a growing area in neuroimaging research, encompassing data-driven methods for investigating how large-scale brain networks dynamically reorganize during resting states. However, this approach has been rarely applied to functional magnetic resonance imaging (fMRI) data acquired during task performance. In this study, we first combined the psychophysiological interactions (PPI) and sliding-window methods to analyze dynamic effective connectivity of fMRI data obtained from subjects performing the N-back task within the Human Connectome Project dataset. We then proposed a hypothetical model called Condition Activated Specific Trajectory (CAST) to represent a series of spatiotemporal synchronous changes in significantly activated connections across time windows, which we refer to as a trajectory. Our finding demonstrate that the CAST model outperforms other models in terms of intra-group consistency of individual spatial pattern of PPI connectivity, overall representational ability of temporal variability and hierarchy for individual task performance and cognitive traits. This dynamic view afforded by the CAST model reflects the intrinsic nature of coherent brain activities.

Clinical development of chimeric antigen receptor-T cell therapy for hematological malignancies.

ABSTRACT: Cellular therapies have revolutionized the treatment of hematological malignancies since their conception and rapid development. Chimeric antigen receptor (CAR)-T cell therapy is the most widely applied cellular therapy. Since the Food and Drug Administration approved two CD19-CAR-T products for clinical treatment of relapsed/refractory acute lymphoblastic leukemia and diffuse large B cell lymphoma in 2017, five more CAR-T cell products were subsequently approved for treating multiple myeloma or B cell malignancies. Moreover, clinical trials of CAR-T cell therapy for treating other hematological malignancies are ongoing. Both China and the United States have contributed significantly to the development of clinical trials. However, CAR-T cell therapy has many limitations such as a high relapse rate, adverse side effects, and restricted availability. Various methods are being implemented in clinical trials to address these issues, some of which have demonstrated promising breakthroughs. This review summarizes developments in CAR-T cell trials and advances in CAR-T cell therapy.

Functional and structural networks decoupling in generalized tonic-clonic seizures and its reorganization by drugs.

OBJECTIVE: To investigate potential functional and structural large-scale network disturbances in untreated patients with generalized tonic-clonic seizures (GTCS) and the effects of antiseizure drugs. METHODS: In this study, 41 patients with GTCS, comprising 21 untreated patients and 20 patients who received antiseizure medications (ASMs), and 29 healthy controls were recruited to construct large-scale brain networks based on resting-state functional magnetic resonance imaging and diffusion tensor imaging. Structural and functional connectivity and network-level weighted correlation probability (NWCP) were further investigated to identify network features that corresponded to response to ASMs. RESULTS: Untreated patients showed more extensive enhancement of functional and structural connections than controls. Specifically, we observed abnormally enhanced connections between the default mode network (DMN) and the frontal-parietal network. In addition, treated patients showed similar functional connection strength to that of the control group. However, all patients exhibited similar structural network alterations. Moreover, the NWCP value was lower for connections within the DMN and between the DMN and other networks in the untreated patients; receiving ASMs could reverse this pattern. SIGNIFICANCE: Our study identified alterations in structural and functional connectivity in patients with GTCS. The influence of ASMs may be more noticeable within the functional network; moreover, abnormalities in both the functional and structural coupling state may be improved by ASM treatment. Therefore, the coupling state of structural and functional connectivity may be used as an indicator of the efficacy of ASMs.

Analysis of injuries and treatment of 3,401 inpatients in 2008 Wenchuan earthquake--based on Chinese Trauma Databank.

OBJECTIVE: A catastrophic earthquake struck Wenchuan region of West China on May 12, 2008 and caused more than 69 225 deaths. This study was to analyze injury characteristics and treatment of the seismic patients based on Chinese Trauma Databank, which will be helpful for improvement of future medical rescue in potential disasters. METHODS: Based on inpatients'medical records of seismic patients admitted into 11 hospitals, data were registered with Trauma Database System Version 3.0. Patients'general information, causes, clinical characteristics and treatment of injuries were studied. RESULTS: Main causes for seismic injuries were blunt strike (68.2%), crush/burying (18.7%) and slip/falling (11.5%). Slip/falling was the main cause for spinal injuries and accounted for 19.1%, which was higher than the percentage for other body part. Extremity injuries accounted for 54.8% of all injuries. Fractures accounted for 53.1%. Lower extremity fracture accounted for 70.1% of lower extremity injury and spinal fracture accounted for 85.9% of spinal injury. The proportion of spinal injuries with AIS larger than or equal to 4 was higher than that of other injured locations except for the abdomen. Debridement and suturation for single injury and multiple injury patients accounted for 64.7% and 42.9% of their operations respectively. CONCLUSIONS: Blunt strike, crush/burying and slip/falling are the main causes for seismic injuries. The most frequently injured site is extremity. The main injury type is fracture, especially for the lower extremities and the spine. Multiple injury patients were mainly treated by operation, including debridement and suturation, closed reduction and external fixation, etc.

Identification of Pathogenic Fusarium spp. Causing Maize Ear Rot and Potential Mycotoxin Production in China.

Ear rot is a serious disease that affects maize yield and grain quality worldwide. The mycotoxins are often hazardous to humans and livestock. In samples collected in China between 2009 and 2014, Fusarium verticillioides and F. graminearum species complex were the dominant fungi causing ear rot. According to the TEF-1α gene sequence, F. graminearum species complex in China included three independent species: F. graminearum, F. meridionale, and F. boothii. The key gene FUM1 responsible for the biosynthesis of fumonisin was detected in all 82 F. verticillioides isolates. Among these, 57 isolates mainly produced fumonisin B1, ranging from 2.52 to 18,416.44 µg/g for each gram of dry hyphal weight, in vitro. Three different toxigenic chemotypes were detected among 78 F. graminearum species complex: 15-ADON, NIV and 15-ADON+NIV. Sixty and 16 isolates represented the 15-ADON and NIV chemotypes, respectively; two isolates carried both 15-ADON and NIV-producing segments. All the isolates carrying NIV-specific segment were F. meridionale. The in vitro production of 15-ADON, 3-ADON, DON, and ZEN varied from 5.43 to 81,539.49; 6.04 to 19,590.61; 13.35 to 19,795.33; and 1.77 to 430.24 µg/g of dry hyphal weight, respectively. Altogether, our present data demonstrate potential main mycotoxin production of dominant pathogenic Fusarium in China.

[Comparative study on physical parameters and biological effects of blast wave on plateau and on plain].

OBJECTIVE: To compare the physical parameters and biological effects of blast wave on plateau and on plain. METHODS: Twenty-five pigs were divided into two groups: plateau group (n=15) and plain group (n=10). They were placed either 5 meters or 6 meters away from the site of explosion. Ten kilogram of TNT was detonated to produce blast injury. Physical parameters were measured with pressure transducers. The survival rate and gross morphological changes were carefully observed 28 hours later. RESULTS: There was no significant difference in propagation speed of blast wave between the two groups. Compared with plain group, the over-pressure value measured in plateau group was a slightly lower, however, the duration of positive pressure was more lengthy and impulse stronger compared with that of plain group. The survival rate was 12/15 and 8/10 respectively for plateau and plain groups 28 hours after injury. The morphological changes were mainly lung hemorrhage and edema. Intestinal subserosal hemorrhage and subendocardial hemorrhage were found in some animals. The lung injury severity in plateau group was one scale severer than that of plain group. CONCLUSION: Plateau blast wave is characterized by slightly higher impulse, longer duration, and lower over-pressure value, although the propagation speed of the wave is not different from that of plain environment. The blast injury in plateau environment is also severer, its underlying mechanisms need to be further explored.

Treatment of 209 cases of liver injury.

OBJECTIVE: To summarize the experience of the treatment of traumatic hepatorrhexis. METHODS: The clinical data of 209 cases of liver trauma treated in the three affiliated hospitals of the Third Military Medical University from 1989 to 1999 were retrospectively analyzed. Among the 209 patients, 108 (51.7%) had Grade III or more severe liver injury. Operative treatment was performed in 186 cases and preservative treatment in 23. RESULTS: In the operated group, 169 patients were cured. The complications occurred in 18 patients and 17 of them died. In the non-operated group, the complications occurred in 22 patients and only 1 of them died. CONCLUSIONS: Severe injury and delayed treatment are two major factors leading to death from liver injuries. Surgical intervention is still the principal measure to treat traumatic hepatorrhexis. The indications for non-operative treatment should be carefully selected.

The dynamic response of heart and its injury involving chest impact.

OBJECTIVE: The dynamic response of the heart during chest impact and the characteristics of heart injuries were investigated to further understand the mechanisms of heart impact injuries. METHODS: Eleven dogs and thirty-four rabbits were subjected to front thoracic impact with different impact velocities and compression response. The accelerated movement of thoracic wall during the impact period was monitored. The pathological examination of the injured heart was done and the dynamic responses and mechanisms of injuries were analyzed with mathematics models. RESULTS: The analysis of mathematics model and experimental results showed that the injury severity of heart was well correlated with the viscous criterion. The thoracic wall was involved in bi-directional movement of compression and expansion. The injured heart showed spotty or stripy hemorrhages in the ventricle endocardium. Light microscopic examination showed interstitial bleeding and rupture of the myocardial fibers in the contusion area. The biomechanical analysis indicated that there was a large deformation caused by the stress concentration on the lateral ventricle wall. CONCLUSIONS: There is a high speed and excessive deformation of the heart during the impact period, which might be the key mechanism of heart injury. The strong impact and press coming from both sternum and vertebral column and the rapid elevation of pressure in the ventricle are the main cause of deformation.

Pathomorphological changes after liver impact injury in rabbits.

OBJECTIVE: To investigate the histopathological changes in the liver and other organs after impact injury. METHODS: The rabbits were impacted with a BIM-IV biological impacting machine at the xiphoid process. The severity of liver injury was graded and scored through gross anatomy. At the same time, the pathological changes in the liver, heart, and lung were observed by light and electron microscopes. RESULTS: Light microscopy showed that the pathological changes in the liver were: 1) loss of normal structure, hemorrhage and distortion of hepatic lobules; 2) cloudy swelling, degeneration, vacuolation and necrosis of liver cells; 3) infiltration of neutrophils. The lungs were injured and there were liver cell emboli in the small pulmonary arteries. Electron microscopy showed that the ultrastructure of the liver cells was severely damaged and the cells had significant features of necrosis. CONCLUSIONS: The major pathomorphological changes in the liver after impact injury are hemorrhage and necrosis. They may be complicated by exfoliation of liver cells to hepatic sinusoids. These cells circulate with the blood to form emboli in the pulmonary blood vessels.

[Ultrastructural features of cultured rat cortical astrocytes with stretch-induced injury].

OBJECTIVE: To investigate the changes of ultrastructural features of cultured rat cortical astrocytes after stretch-induced injury. METHODS: Rat cortical astrocytes isolated from 1- to 2-day-old rats were cultured till confluency, and then plated in tissue culture wells with flexible silastic bottom after purification. A computer-controlled device was used to produce stretch-induced injury in the astrocytes with the imposed pressure of 50, 150, and 250 kPa respectively, followed by observation of the ultrastructural changes in the astrocytes with light and electron microscopy. RESULTS: Obvious ultrastructural destruction of the astrocytes occurred when the imposed stretch pressure was 50 kPa, and scanning electron microscopy demonstrated increased intercellular space and laceration of the cell body and its processes. Transmission electron microscopy revealed mitochondria swelling 1 h after stretch-induced injury and 6 h after the injury, vacuolar degeneration of the mitochondria occurred. Increased stretch pressure caused further decrease in the amount of glial filaments and densification of astrocytes. CONCLUSIONS: Stress, even at a relatively small scale, can cause disruption of intercellular juncture and ultrastructural change of the cultured astrocyte, which may be related with extensive brain edema after traumatic brain injury.

[Pathomorphological changes in abdominal viscerae in dogs subjected to underwater blast wave injury].

OBJECTIVE: To explore the pathomorphological changes in abdominal viscerae injuries produced by underwater blast waves. METHODS: Sixty-one adult mongrel dogs were used in this study. Underwater explosions in different intensity were produced by detonating 200 g, 500 g and 1,000 g TNT, respectively. The physical parameters of blast wave were measured by PCB dynamic pressure transducers specially designed for underwater explosion. The pathomorphological changes in abdominal viscerae were observed at 6 hours after injury. RESULTS: The physical features of underwater blast wave were characterized by high peak pressure, short positive action duration, and higher intensity of impulse. The pathomorphological observation revealed high incidence of injuries of gastrointestinal tract (62.30 percent), manifesting mainly various degrees of subserosal and submucous bleeding in gastrointestinal tract. Rupture of seromuscular layer, subserosal hematoma, and even, perforations of gastrointestinal tract occurred in some animals. Injuries of the liver, spleen, pancreas and other parenchymatous organs injuries, such as subcapsular bleeding, hematoma, and ruptures, appeared with low incidence. No obvious injuries were found in the gallbladder or urinary bladder and other fluid containing organs. CONCLUSION: Underwater blast wave can induce injuries to many abdominal viscerae. Gastrointestinal tract injuries, occurring in high incidence are usually severe, and they should be given early treatment in underwater blast injuries.

[Intoxication induced by unsymmetrical dimethylhydrazine: characteristics and mechanism of its acute and chronic injuries].

OBJECTIVE: To investigate the characteristics and mechanism of the acute and chronic injuries induced by unsymmetrical dimethylhydrazine (UDMH). METHODS: A total of 128 male rats were randomly divided into four groups: UDMH intoxication acute response group and chronic response group, and corresponding control groups. UDMH was administrated through inhalation at the concentration of 8x10(-4)g/m(3) for 15 minutes. Animals of each group were sacrificed at 3, 6, 12, 24, 48 and 72 hours respectively after the intoxication. Pathologic changes and blood gas were examined. Chronic injuries and pathologic changes were also observed 1 year after the intoxication. RESULTS: Major pathological changes in the intoxication group were cerebral edema, degeneration and necrosis of neuron, enlargement and hemorrhage of capillary. Damages of different degree were found in liver, kidney, lung, heart, spleen, stomach, intestine, thymus, blood, bone marrow. Pallium ischemia was also found in the intoxicated rats 1 year after the intoxication, including ischemia damage of neuron in cerebral cortex, hemorrhage and focal liquefaction of thalamus and medulla conducting bind, dissociation, rupture, not uniform circuitry in conducting fibers. CONCLUSION: Our study reveals the basic pathological induced by intoxication of UDMH. The most severe stage of the injury appears 2-6 hours after intoxication. Long term investigation reveals pallium ischemia, thalamus hemorrhage and liquefaction in the medulla oblongata 1 year after the intoxication with UDMH. All the changes are significant.

[Characteristics of acute and chronic intoxication induced by rocket propellant nitrogen tetroxide].

OBJECTIVE: To investigate the characteristics of acute and chronic injuries of the nitrogen tetroxide, a kind of propellant of rocket. METHOD: 128 male rats were divided randomly into 4 groups: acute control group (56), acute nitrogen tetroxide intoxication group (56), long-term response group (8). The animals were killed sequentially at 3, 6, 12, 24, 48 and 72 h. Nitrogen tetroxide was administrated through inhalation at the concentration of 81 mg/m3 for 15 min. Chronic injuries and pathologic changes were also observed one year after the intoxication. RESULT: Pulmonary edema was the main pathological changes after intoxication, complicated with partial haemorrhage. Data acquired from long-term observations showed 75% pulmonary fibrosis and one case of adenocarcinoma of lung. CONCLUSION: The first 2 to 6 h after intoxication is the most severe stage of the injury. During the long-term observation, we find that intoxication with nitrogen tetroxide can induce pulmonary fibrosis and adenocarcinoma.

[Effects of stimulation of intact vagus nerve on systemic inflammatory response in rats].

OBJECTIVE: To observe the effects of stimulation of intact vagus nerve (IVNS) on systemic inflammatory response in rats. METHODS: The model of systemic inflammatory response was reproduced by lipopolysaccharide (LPS). One hundred Sprague Dawley rats were randomly divided into A group (with intravenous injection of LPS), B group (with stimulation of efferent nerve trunk of vagus nerve after intravenous injection of lipopolysaccharide and vagotomy), C group (with stimulation of intact vagus nerve after intravenous injection of LPS), D group (with vagus nerve stimulation after injection of equivalent isotonic saline), E group (with intravenous injection of equivalent isotonic saline), with 20 rats in each group. Five rats of each group were used to determine mean aortic pressure (MAP) before injection and l0 min, 0.5 h, 1 h, 2 h, 4 h and 6 h after injection. The serum levels of tumor necrosis factor (TNF) alpha and interleukin (IL) 10 were determined with enzyme linked immunosorbent assay before injection and 2, 4 and 6 hour after injection. RESULTS: The level of MAP rose in A, B, C groups at 10 min after injection, especially in A group (134.40 +/- 7.3 mm Hg, l mm Hg = 0.033 kPa, P < 0.05), but it dropped in above groups at 30 min after injection. The level of MAP in A group was obviously lower than that in B, C groups during 10 min -6 h after injection. The serum level of TNF-alpha in A group was significantly higher than that in B, C groups at 2, 4, 6 hours after injection (P < 0.05). Compared with that in C group, the serum level of IL-10 in A, B groups lowered markedly at 4, 6 hours after injection (P < 0.05). CONCLUSION: IVNS can stabilize hemodynamics and exert have anti-inflammatory effects at early stage of systemic inflammatory response.

[Histological evaluation of poly (dextrogyr-levogyr) lactide acid-triiodothyronine in sciatic nerve defect of rat].

OBJECTIVE: To make a histological evaluation of poly (dextrogyr-levogyr)lactide acid-triiodothyronine (PDLLA-T3) in sciatic nerve defect of rat. METHODS: Ninety SD rats were evenly divided into 3 groups (autograft group A, PDLLA-T3 group B and PDLLA group C). Group D was control group. The left sciatic nerves were cut off by operation and 1 cm-nerve-defect was set up. The specimens were collected 2 weeks, 1 month and 2 months after the operation respectively, simultaneously the right sciatic nerves were collected as normal control group D. HE staining, electron microscope, S-100 immunohistochemistry, and Bielschowsky staining were done in all the specimens, the quantity and quality of the regenerated nerves were observed, and all the results were processed by image analyzer. RESULTS: Two weeks after the operation,histological observation indicated that the materials in groups B and C were not completely degraded. Transmission electron microscopic observation showed that the myelin sheath was not thick and it was about 0.5 microm in thickness. There was no significant difference among the 3 groups. One month after the operation, histological observation indicated that in group A the regenerated nerves passed through the scaffold and in the new nerves there were regenerated blood vessels. The materials in groups B and C were not completely degraded. S-100 immunohistochemical observation and Bielschowsky staining showed that in group B PDLLA-T3 repaired the defect successfully and the regenerated nerve myelin sheath was 1.81+/-0.19 microm in thickness. The effect in group B was better than that of groups A and C (P> 0.05). Two months after the operation, the materials in groups B and C were completely degraded. The quantity of the regenerated nerves in group B confirmed by S-100 immunohistochemical observation and Bielschowslcy staining was more than that in group C(P<0.05) and close to that in group A. The regenerated nerve myelin sheath in group B was 2.15+/-0.27 microm in the thickness and was thicker than that in group C (P<0.05), but thinner than that in groups A and D (P<0.05). CONCLUSION: PDLLA-T3 can repair the defect of rat sciatic nerve with satisfactory quantity and quality of regenerated nerves.

[Role of thyroid hormone in peripheral nerve regeneration].

OBJECTIVE: To review the role of thyroid hormone in the peripheral nerve regeneration. METHODS: The recent literatures of experimental study and clinical application on the role of thyroid hormone in nerve regeneration were reviewed. The researches on expression, isoform and changes of thyroid hormones in rat sciatic nerve in normal or injury were summarized. The effect of thyroid hormone on local rat sciatic nerve was studied, too. RESULTS: Nuclear thyroid hormone receptors expressed in numerous nuclei of sciatic nerve during a limited period of development extending from the third week of embryonic life to the end of the second postnatal week and after injury of adult sciatic nerve. A single and local administration of thyroid hormone at the level of the transected sciatic nerve produced a lasting effect on peripheral nerve regeneration. CONCLUSION: The beneficial effects of thyroid hormones upon injured peripheral nerve may have considerable therapeutic potential.