ABSTRACT
Background@#and PurposeHyperekplexia (HPX), a rare neurogenetic disorder, is classically characterized by neonatal hypertonia, exaggerated startle response provoked by the sudden external stimuli and followed by a shortly general stiffness. Glycine receptor alpha 1 (GLRA1) is the major pathogenic gene of the disease. We described the clinical manifestations of genetically confirmed HPX patients and made a literature review of GLRA1-related HPX to improve the early recognition and prompt the management of the disorder. @*Methods@#Extensive clinical evaluations were analyzed in 4 Chinese HPX patients from two unrelated families. Next generation sequencing was conducted in the probands. Sanger sequence and segregation analysis were applied to confirm the findings. @*Results@#All four patients including 3 males and 1 female presented with excessive startle reflex, a cautious gait and recurrent falls. Moreover, startle episodes were dramatically improved with the treatment of clonazepam in all cases. Exome sequencing revealed 2 homozygous GLRA1 mutations in the patients. The mutation c.1286T>A p.I429N has been previously reported, while c.754delC p.L252* is novel. @*Conclusions@#HPX is a treatable disease, and clonazepam is the drug of choice. By studying and reviewing the disorder, we summarized the phenotype, expanded the genotype spectrum, and discussed the possible pathogenic mechanisms to enhance the understanding and recognition of the disease. Early awareness of the disease is crucial to the prompt and proper administration, as well as the genetic counseling.
ABSTRACT
Objective To investigate the protective effect of umbilical cord mesenchymal stem cells (UCMSCs) on traumatic brain injury (TBI) in rats.Methods Thirty healthy Sprague-Dawley rats (10 rats for each group) were randomly divided into normal control group (normal),model group (injection of saline after TBI) and UCMSCs transplantation group (injection of UCMSCs after TBI).The rats in experimental groups were sacrificed on the 10th day after UCMSCs transplantation.The percentage of UCMSCs in brain tissue was detected by flow cytometry.The pathological changes of brain tissue were observed by hematoxylin-eosin (HE) staining method.The expressions of vascular endothelial growth factor (VEGF),glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) in brain tissue were measured by immunohistochemistry and immunofluorescence double staining.The neurological deficit was evaluated by neurological deficit degree.Results The percentage of CD90,CD73 and CD105 cells in the UCMSCs transplantation group was significandtly higher than that in the model group (0.4％ vs 0.1％,P＜0.05).The results of HE staining showed that the brain injury of the transplanted group was alleviated compared with the model group (P＜0.05).The VEGF of the brain tissue in injury area in the UCMSCs transplantation group was higher than that in the model group (P＜0.05).The number of GFAP and BDNF positive cells in the UCMSCs transplantation group was higher than that in the model group (P＜0.05),and the neurological deficit score was also higher than that in the model group (P＜0.05).Conclusions UCMSCs transplantation for the treatment of TBI rats can effectively reduce the vascular damage in the injury area and promote nerve recovery.
ABSTRACT
Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) expression in acute myocardium infarction (AMI) rats. Methods The human UC-MSCs were cultured to the 4th generation for experiment. Sixty male Sprague-Dawley (SD) rats were randomly divided into sham group, AMI model group and UC-MSCs group, with 20 in each group. AMI animal model was produced by ligation of anterior descending coronary artery; in the sham group, the threading vein was gone below without ligation. In UC-MSCs group 2×106 UC-MSCs were infused through the caudal vein at 24 hours after successful model production. The animals were sacrificed after 7 days; the myocardial tissue and coronary artery below the ligation line were harvested. The mRNA and protein expressions of IL-6 in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. The positive expression of VEGF in coronary artery was observed by immunohistochemisty. Results Compared with the sham group, the mRNA and protein expressions of IL-6 in myocardium in AMI model group were increased significantly (gray value: 0.732±0.131 vs. 0.321±0.080, 0.678±0.191 vs. 0.286±0.061, both P < 0.05). Compared with the AMI model group, the mRNA and protein expressions of IL-6 in myocardium in UC-MSCs group were decreased significantly (gray value: 0.300±0.104 vs. 0.732±0.131, 0.312±0.101 vs. 0.678±0.191, both P < 0.05). Observation under light microscope, the VEGF positive cells in AMI model group was increased significantly compared with the sham group (cells/HP: 21.1±2.2 vs. 7.6±1.3, P < 0.05), the VEGF positive cells in UC-MSCs group were increased significantly compared with the AMI model group (cells/HP: 41.5±3.1 vs. 21.1±2.2, P < 0.05). Conclusion Human UC-MSCs could promote angiogenesis by the improvement of VEGF in coronary artery and inhibit the inflammation by the reduction of IL-6 in rats with AMI.
ABSTRACT
Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.
ABSTRACT
Objective To study the effects of umbilical cord mesenchymal stem cells (UCMSCs) on the apoptosis of human breast cancer cell line MCF-7.Methods MCF-7 cells were co-cultured with different concentrations of UCMSCs.The apoptosis of MCF-7 cells was detected by in situ apoptosis and flow cytometry.Nude mouse subcutaneous tumor model was established by inoculating MCF-7 and MSCs cells subcutaneously on the right side of the back of a mouse.The MCF-7 cells were inoculated on the left side of the mouse as control.The tumor volume was measured every week to compare the difference between the two groups.On the 17th day after inoculation,the tumor tissue was harvested and the apoptosis of tumor cells was observed by a transmission electron microscopy.Results In situ apoptosis and flow cytometry showed that the early and late apoptosis rates of MCF-7 cells increased first and then decreased with the increase of UCMSCs concentration.The differences between the control and the MCF-7+UCMSCs group were statistically significant for early (F=39.80,P＜0.001) and late apoptosis rates (F=5.68,P＜0.01).The tumor volume of MCF-7+UCMSCs group was significantly lower than that of control group in 17 days after inoculation (F=9.81,P＜0.01).The representative apoptotic cells were observed by the transmission electron microscopyin the MCF-7 +UCMSCs group.Conclusion The UCMSCs with a certain concentration can effectively promote the apoptosis of MCF-7 cells.This study provides a certain experimental basis for the clinical treatment of breast cancer.
ABSTRACT
Cell microencapsulation aims to wrap the living target cells by one or several materials with good biological compatibility and semipermeable membrane properties.Cell microencapsulation not only can achieve immune isolation and prevent the attacks by macromolecular immunes and immune cells,but also can allow the free access of metabolites,small molecule nutrients and bioactive substances to the microcapsule.With the continuous progress of interdisciplinary technologies,cell microencapsulation shows increasing application prospects of making up a variety of limitations of organ transplantation.Moreover,with the development and maturation of cell microencapsulation,it has shown a strong advantage in regenerative medicine,which will certainly promote the rapid development of artificial cells and artificial organs.In this paper,the preparation of cell microcapsules,the effects of the outer membrane of microcapsules on immunological macromolecules and cytokines,the immunogenicity of the outer membrane,and the representative applications of cell microencapsulation were summarized.
ABSTRACT
Cell microencapsulation aims to wrap the living target cells by one or several materials with good biological compatibility and semipermeable membrane properties.Cell microencapsulation not only can achieve immune isolation and prevent the attacks by macromolecular immunes and immune cells,but also can allow the free access of metabolites,small molecule nutrients and bioactive substances to the microcapsule.With the continuous progress of interdisciplinary technologies,cell microencapsulation shows increasing application prospects of making up a variety of limitations of organ transplantation.Moreover,with the development and maturation of cell microencapsulation,it has shown a strong advantage in regenerative medicine,which will certainly promote the rapid development of artificial cells and artificial organs.In this paper,the preparation of cell microcapsules,the effects of the outer membrane of microcapsules on immunological macromolecules and cytokines,the immunogenicity of the outer membrane,and the representative applications of cell microencapsulation were summarized.
ABSTRACT
Intracranial infection is a common and serious complication of acute severe traumatic brain injury, with high mortality and disability rates, which significantly affects the prognosis. In recent years, with the widespread use of antibiotics, antibiotic-resistance rates of pathogens have risen year by year, and the choice of sensitive antibiotics is less and less, sometimes even in difficulties of no drugs available. This paper reviewed the treatment process of 1 case with intracranial infection caused by multi drug-resistant Klebsiella pneumonia after severe traumatic brain injury . The aim is to summarize the clinical experience.
ABSTRACT
Objective To simulate the chemical microenvironment of traumatic brain injury (TBI) under mild hypothermia, and investigate the effect of such microenvironment on umbilical cord mesenchymal stem cells (UCMSCs) in vitro.Methods Eighteen SD rats were allocated to shamoperated group, TBI group and mild hypothermia group according to the random number table, with 6 rats per group.Rat models of TBI were made by electric cortical contusion impactor.After systemic mild hypothermia (33℃) for 4 h, brain tissue homogenate extracts were harvested.Polyacrylamide gels mimicking the elastic modulus of brain were manufactured.Human UCMSCs were isolated and cultured on the gels, added with brain tissue extracts from each group.After 24 h, the apoptosis level of UCMSCs was checked, and the medium was changed with normal one.Cell growth and morphological changes in each group were given dynamic observation.Seven days later, cell immunofluorescence was implemented, with the differentiation level of each group estimated.Results Apoptotic rate in TBI group was 73.47％,significantly higher than 10.42％ in sham-operated group (P ＜0.01).While the apoptotic rate was 28.57％ in mild hypothermia group, indicating mild hypothermia significantly reversed the apoptosis of cells in TBI group (P ＜ 0.01).Cell immunofluorescence demonstrated rate of neuronal differentiation of UCMSCs in sham-operated group, TBI group and mild hypothermia group was 16.48％, 2.59％ and 11.83％ respectively.Mild hypothermia resulted in significantly improved neuronal differentiation of UCMSCs after TBI (P ＜ 0.05).Conclusions More apoptosis and lower neuronal differentiation ability are observed in UCMSCs in the chemical microenvironment after TBI.However, mild hypothermia significantly reverses the elevation of apoptosis and restores the neuronal differentiation capacity of UCMSCs after TBI.
ABSTRACT
BACKGROUND:Currently, morphological observations of brain cavity after traumatic brain injury (TBI) via cadavers or animal specimen are difficult to obtain dynamic changes. OBJECTIVE:To explore the application effect of MRI-based three-dimensional (3D) reconstruction for evaluating the prognosis of TBI. METHODS:Five male Sprague-Dawley rats were enrol ed to establish TBI models by Electronic Cortical Contusion Injury (eCCI), and scanned by 3.0T MRI with Rat-coil to obtain the DICOM date of brain at 1 day, 1, 2 and 3 months after modeling. Brain cavities were 3-dimensional y reconstructed by Mimics16.0 software, and analyzed in the Meshmixer software. RESULTS AND CONCLUSION:(1) The outline of reconstruction model image was clear, and could be observed and measured from different sides and perspectives. (2) The cavity volume and surface area at different time points after TBI showed significant differences between each other except that at 2 and 3 months (P<0.05). (3) The results of cavity change suggested that the cavity tended to be regular after 3 months of TBI. (4) In conclusion, 3D reconstruction software Mimics combining with model analysis software Meshmixer can conveniently and quickly obtain the cavity model, and provide an intuitive way for evaluating the dynamic variations of the brain cavity after TBI.
ABSTRACT
Objective To study the effect of limited fluid resuscitation (LFR) on coagulation in patients with severe traumatic brain injury (sTBI) and investigate its clinical significance.Methods Seventy-nine patients were assigned to low volume group (≤ 2 000 ml,40 cases) and high volume group (＞ 2 000 ml,39 cases) according to the random number table.LFR was performed for all patients.Prothrombin time (PT),partial thromboplastin time (APTT),thrombin time (TT) and fibrinogen (FIB) level were measured in both groups at different time points.Mean heart rate,blood pressure,blood gas values and blood electrolytes were monitored.Meantime,NICU days,hospital length of stay and incidence of multiple organ dysfunction syndrome (MODS) were recorded.Glasgow Outcome Scale (GOS) was evaluated.Results In constrast to high volume group,PT,APTT and TI were shortened and FIB was elevated in low volume group (P ＜ 0.05).But there were no significant differences between the two groups in NICU days [(13.84 ±3.02)d vs (15.28 ±3.79)d],hospital length of stay [(36.85 ±6.73)d vs (40.01 ± 7.21) d],MODS incidence (15.0％ vs 17.9％) and mortality (27.5％ vs 38.5％) (P ＞ 0.05).The chances of good recovery in low volume group was higher than that in high volume group (22.5％ vs 7.3％) (P＜0.05).Mean heart rate,blood pressure,blood electrolytes,and blood gas values did not differ significantly between the two groups (P ＞ 0.05).Conclusion For patients with sTBI,low volume LFR can ameliorate coagulation disorders and improve prognosis,indicating a safe and effective therapy.
ABSTRACT
Objective To study the effect of mild hypothermia combined with edaravone on the expressions of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cerebrospinal fluid(CSF)of patients with severe traumatic brain injury(sTBI)and on their prognoses. Methods A prospective randomizd controled trial was conducted. Seventy-seven patients in the Center for Neurology and Neurosurgery of Affiliated Hospital of Logistics University of Chinese People's Armed Police Forces were randomly assigned into control group(38 cases)and treatment group(39 cases)according to random number table. All the patients were treated with routine treatments such as dehydration of intracranial pressure(ICP),neural nutrition,anti-infection,mechanical ventilation and maintenance of water and electrolyte balance in control group,while in treatment group,the patients received mild hypothermia combined with edaravone on the basis of routine treatment within 24 hours after injury. The contents of TNF-αand IL-6 in CSF were measured by radio-immunoassay(RIA)at different time points in both groups. In the meantime,the ICP was also measured. The prognosis was evaluated after 6 months of injury according to Glasgow outcome scale(GOS). Results Compared to control group,in the treatment group,the expression levels of TNF-αand IL-6 in CSF had no significant difference(both P>0.05)on the 1st day after injury,but they were significantly increased on the 3rd day after injury,began to decline on the 7th day,and reached to the valley value on the 14th day after injury,the degree of descent in treatment group being more significant than that in control group〔TNF-α(μg/L):2.43±0.39 vs. 3.12±0.47,IL-6(ng/L):83.53±11.48 vs. 101.69±13.64,both P0.05),but it was gradually increased on the 1st day after injury in both groups,it reached the peak value on the 3rd day after injury,and began to decline on the 7th day after injury,the degree of descent being more significant in treatment group〔mmHg(1 mmHg=0.133 kPa):14.88±3.73 vs. 21.76±4.78,P<0.01〕. The favorable prognosis rate was significantly higher〔35.9%(14/39)vs. 21.1%(8/38),P<0.05〕,and the mortality was obviously lower in treatment group than those of control group〔28.2%(11)vs. 42.1%(16),P<0.05〕. Conclusion In patients with sTBI,mild hypothermia combined with edaravone can protect brain tissue through alleviating high ICP and decreasing the expression levels of TNF-αand IL-6 in CSF, resulting in promoting the recovery of nerve functions and improving prognosis.
ABSTRACT
Objective To investigate the effect of mild hypothermia on proliferation and differentiation of neural stem cells (NGCs) in hippocampal subgranular zone after traumatic brain injury (TBI) and the underlying mechanism.Methods SD rats were divided into sham-injured group (only left dura mater exposed),hypothermia group (sham injury + mild hypothermia therapy for 72 hours),TBI group (unilateral fluid percussion was used to generate severe TBI),and TBI + hypothermia group (TBI + mild hypothermia therapy for 72 hours) according to the random number table,with 8 rats per group.Hippocampal homogenates or brain tissues were harvested after BrdU (100 mg/kg) was intraperitoneally administered to rats once a day for 7 days postTBI.Expressions of BrdU and double cortin in hippocampal subgranular zone were respectively detected by immunohistochemical or immunofiuorescence staining.Level of Sirt1 (silence information regulatory proteins,Sirt1) in hippocampus was detected by Western blot.Results BrdU-and double cortin-positive cells in rat hippocampal subgranular zone greatly increased at 7 days after TBI in comparison with sham-injured group (P ＜ 0.01).Moreover,BrdU and double cortin in rat hippocampal subgranular zone in TBI + hypothermia group was significantly higherthan that in TBI group [(257.4 ± 34.3) vs (196.4 ± 23.8) ; (346.4 ± 42.2) vs (245.7 ± 33.2),P ＜0.01].Moreover,mild hypothermia reversed TBI-induced over-expression of Sirt1 [(0.62 ± 0.075) vs(1.18 ± 0.11),P ＜ 0.01].Conclusion Mild hypothermia therapy can promote proliferation andneuronal differentiation of NSCs in hippocampal subgranular zone after TBI and the possible mechanismmay relate to the inhibition of over-expression of Sia1.
ABSTRACT
Objectives To observe the frequencies of mutations at glycophorin A(GPA)of erythro-cytes in patients with high arsenic coal poisoning(HACP)in comparison with normal controls.Methods The peripheral erythrocytes were isolated and immunolabelled,and were detected by flow cytometry in40patients and18normal adults.Results The mutation frequencies(MF)were(21.23?13.97)?10 -6 for type NN,(33.13?25.72)?10 -6 for type NO,(110.90?63.58)?10 -6 for type MM,and(20.35?21.26)?10 -6 for type MO of erythrocytes in patients with HACP,which were significantly higher than those in normal controls.The mutation frequencies were(31.50?16.13)?10 -6 for type NN,(54.50?38.13)?10 -6 for type NO,(159.33?66.22)?10 -6 for type MM,and(45.16?12.69)?10 -6 for type MO of erythrocytes in tumor group of HACP patients,which were significantly higher than those of non-tumor group of the patients.Conclusions Arsenic poisoning may induce the mutation at the glycophorin-A locus of erythrocytes,sug-gesting that arsenic may be one of potential mutagens.GPA-MF may serve as a parameter for the detection of patients with HACP.