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Objective:To explore the clinical characteristics of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods:The clinical data of 24 patients with anti-CASPR2 encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. According to the age of first onset, the patients were divided into early onset group (10 cases, onset age<45 years) and late onset group (14 cases, onset age≥45 years). The clinical data including clinical manifestations, auxiliary examinations, and treatment response between these 2 groups were compared.Results:Among the 24 patients, there were 13 cases with epilepsy, 13 cases with cognitive decline, 13 cases with mental disorders, 14 cases with autonomic dysfunction, 8 cases with peripheral nerve hyperexcitability, 5 cases with Morvan syndrome, 5 cases with unstable walking, and 8 cases with sleep disorders. Among the 10 cases of the early onset group, 7 cases are females, and 8 cases showed epilepsy. The incidence rate of epilepsy in the early onset group was higher than that in the late onset group (5/14, Fisher exact probability, P=0.047). Among the 14 cases of the late onset group, 6 cases are females, 9 cases showed cognitive impairment and 8 cases presented with mental disorders. There were 6 cases with abnormal brain magnetic resonance imaging (MRI). The cerebrospinal fluid protein of the late onset group [0.37 (0.29, 0.58) g/L] was higher than that in the early onset group [0.22 (0.16, 0.30) g/L; Z=-2.667, P=0.008]. The modified Rankin Scale (mRS) scores before and after treatment were 3.29±0.83 and 1.50 (0.75, 2.25), which were higher than those in the early onset group [mRS scores before and after treatment were 2.10±0.99 and 0 (0, 1.00), t=-3.188, P=0.004; Z=-2.335, P=0.020]. Conclusions:There are various symptoms in patients with anti-CASPR2 encephalitis. The early onset patients are common in women, with a higher incidence of epilepsy. The late onset patients are common in males, with prominent manifestations of cognitive impairment and mental disorders, which have a greater impact on daily living abilities. And abnormal MRI findings are common, and the cerebrospinal fluid protein is higher in late onset patients. Anti-CASPR2 antibody may cause more severe immune damage to the nervous system in elderly patients.
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Immunoadsorption can selectively remove pathogenic antibodies and has recently achieved good results in neuroimmune diseases. The type and titer of pathogenic antibodies play an important role in the clinical symptoms and severity of patients with autoimmune encephalitis. First-line immunotherapy for autoimmune encephalitis includes steroids, intravenous immunoglobulin, plasma exchange or immunoadsorption. Immunoadsorption selectively and rapidly eliminates autoantibodies and can be an effective therapeutic option as part of multimodal immunotherapy.
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Objective:To investigate the clinical characteristics of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) combined with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis. Methods:Sixty-five patients with MOGAD and 96 patients with anti-NMDAR encephalitis, admitted to our hospital from July 2018 to June 2021, were chosen in our study; 8 patients with MOGAD combined with anti-NMDAR encephalitis were selected as antibody double positive group; 21 patients with MOG antibody(+)/anti-NMDAR antibody(-) and 37 patients with anti-NMDAR antibody(+)/MOG antibody(-) were selected as controls. The differences of clinical characteristics of patients among these groups were compared.Results:(1) In these 8 patients from antibody double positive group, MOGAD and anti-NMDAR encephalitis occurred simultaneously in 6 patients, and anti-NMDAR encephalitis occurred prior to the episode of MOGAD in 2 patients. Autoimmune encephalitis was the dominant phenotype and demyelinating symptoms occurred in some patients. Both MOG antibody and anti-NMDAR antibody were detected in these 8 patients. MRI showed that lesions mostly involved in the cortex and subcortical white matter. Intravenous administration of high-dose methylprednisolone and immunoglobulin was given for patients at acute stage; two patients received mycophenolate mofetil treatment additionally during recurrence. After treatment, syndromes in these 8 patients got improvement. (2) There were no significant differences between patients from antibody double positive group and MOG antibody(+)/anti-NMDAR antibody(-) group in clinical manifestations, auxiliary examinations or treatments ( P>0.05). As compared with patients in antibody double positive group, patients in the anti-NMDAR antibody(+)/MOG antibody(-) group had significantly lower proportion of children and significantly higher modified Rankin scale (mRS) scores at the height of their illness ( P<0.05). As compared with patients in the MOG antibody(+)/anti-NMDAR antibody(-) group, patients in the anti-NMDAR antibody(+)/MOG antibody(-) group had significantly older onset age, significantly lower proportion of children, significantly higher proportion of patients with epilepsy and abnormal psychiatric behavior, significantly higher proportion of patients admitted to Intensive Care Unit, statistically higher mRS scores at the height of their illness, significantly lower proportion of patients with intracranial lesions, and significantly higher proportion of patients used immunoglobulin and plasma exchange ( P<0.05). Conclusion:MOG antibody and anti-NMDAR antibody can cause different clinical symptoms; when MOGAD patients have unusual symptoms, such as abnormal psychiatric behavior and epilepsy, or anti-NMDAR encephalitis patients develope demyelinating features, the possibility of MOGAD combined with anti-NMDAR encephalitis should be considered.
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Objective:To investigate the clinical characteristics and therapeutic efficacy of spontaneous intracranial hypotension (SIH) complicated with cerebral venous thrombosis (CVT).Methods:The clinical data of 4 patients with SIH complicated with CVT admitted to our hospital from March 2014 to April 2020 were retrospectively analyzed. And the clinical data of 35 patients with SIH complicated with CVT were included for summary analysis through literature retrieval (the databases included PubMed, CNKI and Wanfang; retrieval period was from database construction to December 31, 2020).Results:These 4 patients were with onset of orthostatic headache; one was with recurred orthostatic headache after relief, and the other 3 developed persistent headache and epileptic seizure; case 1 was with superior sagittal sinus and cortical vein thrombosis, case 3 was with superior sagittal sinus thrombosis, and other 2 patients were with isolated cortical vein thrombosis. Twenty-six documented cases demonstrated headache changes: 12 patients (46.15%) developed persistent headache, 12 patients (46.15%) showed orthostatic headache persistently, and 2 patients (7.69%) had disappeared headache. The most common new symptoms were epilepsy in 17 patients (48.57%) and limb weakness in 10 patients (28.57%). Totally, these 31 patients (4 patients from our hospital+27 patients from literature retrieval) had hemorrhage after treatment; the percentage of patients having hemorrhage changes in the 17 patients accepted anticoagulant therapy was significantly increased as compared with that in 14 patients accepted other treatments (7/17 vs. 1/14, P<0.05); there were no bleeding changes in 5 patients accepted epidural blood patch and anticoagulant therapy. Conclusions:The clinical features of SIH complicated with CVT are various, and the change of headache is not a reliable marker. In the course of SIH, it is necessary to be alert to the occurrence of CVT if there are new symptoms such as epileptic attack or limb weakness. The etiological treatment of SIH is essential and the hemorrhage risk after anticoagulant therapy should be concerned in patients with SIH complicated with CVT.
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Objective:To investigate the effects of hippocampal injection of tyrosine kinase receptor binding protein B3(Ephrin-B3) agonist on spontaneous seizures and the expression of hippocampal secretory glycoprotein (Reelin) and phosphorylated adaptor protein (p-Dab1) in epileptic model rats.Methods:Seventy-eight rats were randomly divided into control group and model group according to body mass matching with 39 rats in each group.The rats in control group were fed normaly, and the rats in model group were established epilepsy model by intraperitoneal injection of lithium chloride pilocarpine. The hippocampal tissues were taken in the acute phase (7 days), quiescent phase (14 days) and chronic phase (60 days) after the successful induction of status epilepticus. The levels of Reelin protein and p-Dab1 protein in the hippocampal tissues of epileptic model rats and normal rats were detected by immunohistochemistry and Western blot.And thirteen rats were randomly selected at each time point. Another 48 rats were randomly divided into normal Fc-control group, normal EphB3-Fc group, epilepsy Fc-control group and epilepsy EphB3-Fc group, with 12 rats in each group. Rats in the first two groups were fed normally, and those in the latter two groups were established epileptic model. Seven days after modeling, all rats were injected into bilateral hippocampus with EphB3-Fc (Ephrin-B3 agonist) and FC control (control agent of Ephrin-B3 agonist) according to the grouping, once a day for 7 days. After administration, the changes of behavior and EEG were observed within two weeks. At the same time, the expression of Reelin protein and p-Dab1 protein were detected by immunohistochemistry and Western blot. SPSS 21.0 was used for statistical analysis, One-way ANOVA was used for multi group comparison, and Tukey's test was used for pairwise comparison.Results:The results of immunohistochemistry and Western blot showed that compared with the control group, the levels of Reelin and p-Dab1 protein in hippocampus of model group decreased significantly at 7, 14 and 60 days after epilepsy (all P<0.01). The results of immunohistochemistry showed that compared with epilepsy Fc-control group, the levels of p-Dab1 ((0.41±0.04), (0.58±0.06), P<0.05) in epilepsy EphB3-Fc group increased significantly.Western blot result showed that the level of p-Dab1 in epilepsy EphB3-Fc group increased compared with that of epilepsy Fc-control group (1.34±0.04), (2.26±0.10), P<0.01). Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed less average seizure duration ((39.00±1.79)s, (26.50±1.87)s; t=23.21, P<0.01), less frequencies ((2.00±0.89), (0.50±0.55); t=2.32, P<0.01) and less latent period ((6.33±1.37)day, (12.50±1.87)day; t=2.52, P<0.01) in spontaneous recurrent seizures. Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed lower average amplitude ((37.30±1.21)μV, (29.00±1.41)μV; t=25.14, P<0.01), less average seizure duration ((5.35±0.19)s, (2.35±0.19)s; t=3.13, P<0.01). Conclusion:Ephrin-B3 alleviated spontaneous recurrent seizures by upregulating Reelin and p-Dab1 in temporal lobe epilepsy rat.
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@#Objective To explore dynamic expression of Ephrin-B3 in hippocampus of pilocarpine induced epileptic rats and the role of Ephrin-B3 in the process of epileptogenesis.Methods We first established pilocarpine induced epileptic rat model and then detected Ephrin-B3 expression at 7,14 and 60 days post status epilepticus (SE) by real time qPCR,immunohistochemistry and Western blot.Results After pilocarpine injection,rats showed facial muscles,forelimb and tail clonus and ataxic lurching,head bobbing and wet dog shakes.Real time qPCR revealed that Ephrin-B3 mRNA expression in hippocampus decreased during spontaneous seizure period.Compared with controls,epileptic rats showed decreased Ephrin-B3 expression at 7 days,reached the lowest level at 14 days and then increased slightly at 60 days post-SE (P<0.001).Ephrin-B3 protein in hippocampus also decreased at 7,14 and 60 days detected by Western blot (P<0.001).Immunohistochemistry results showed that Ephrin-B3 mainly expressed in granule cells in dentate gyrus.Analysis of immunohistochemistry revealed decreased Ephrin-B3 expression in epileptic rats compared with controls (P<0.001).Conclusion The dynamic changes of Ephrin-B3 expression in hippocampus of epileptic rats indicated that Ephrin-B3 may participate in the process of spontaneous recurrent seizures.
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Objective:To explore the changes of levels of coagulation factors at acute phase (within one week) of aneurysmal subarachnoid hemorrhage (aSAH) and their relations with deep venous thrombosis (DVT).Methods:Two hundred and two aSAH patients (aSAH group), admitted to our hospitals from March 2015 to March 2019, were selected in our study, and these patients were divided into a combined DVT subgroup and a uncombined DVT subgroup according to whether they were combined with DVT on the first and third d of onset. One hundred healthy physical examiners whose age and gender matched with those of aSAH group were selected as control group; one, 3, 5, and 7 d after onset, and one d after enrolling of subjects from the control group, thromboelastogram (TEG) was used to detect the R value of TEG (TEG-R) in all subjects. One, two, 3, 4, 5, 6 and 7 d after onset, color Doppler ultrasonography was used to determine whether aSAH patients had DVT.Results:A total of 73 patients (36.14%) were combined with DVT at acute stage of aSAH; 66 were with asymptomatic thrombosis and 7 with symptomatic thrombosis; 59 were with lower extremity intermuscular vein thrombosis and 14 were with intermuscular vein thrombosis. The incidence of DVT (68/73 [93.2%]) peaked on the 1 st-3 rd d of onset. The TEG-R of patients in aSAH group was statistically lower than that of the control group on the 1 st-3 rd d of onset ( P<0.05); the TEG-R of patients in aSAH group on the 1 st-3 rd d of onset was significantly lower than that on 5 th and 7 th d of onset ( P<0.05). The TEG-R of patients in combined DVT subgroup was significantly lower than that of the uncombined DVT subgroup ( P<0.05). Conclusions:Hyperfunction of coagulation factors at acute stage of aSAH is noted within one-3 d of onset; the incidence of DVT is the highest within 3 d of onset, mainly featured as asymptomatic intermuscular venous thrombosis. Whether or not aSAH would combine with DVT is associated with hyperfunction of coagulation factors.
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Objective:To analyze the clinical and imaging features of patients with spontaneous intracranial hypotension (SIH) combined with vestibulocochlear nerve symptoms, and explore the mechanism of vestibulocochlear nerve damage.Methods:From January 2014 to September 2019, 72 patients with SIH were chosen in our hospital; their clinical data were retrospectively analyzed; all patients underwent brain MR imaging. Based on vestibulocochlear nerve symptoms including dizziness, vertigo, tinnitus, aural fullness, and hearing loss, these patients were divided into two groups: 27 patients with vestibulocochlear nerve symptoms and 45 patients without vestibulocochlear nerve symptoms. The clinical and brain MR imaging features were compared between the two groups. The quantitative indexes of brain MR imaging were measured including the height of the pituitary gland, distances of the suprasellar cistern and prepontine cistern, distance from optic chiasm to pituitary fossa, mamillopontine distance, pontomesencephalic angle, and angle of transverse sinus. The qualitative signs of brain MR imaging were evaluated including pachymeningeal enhancement, subdural effusion or hematoma, effaced suprasellar cistern and prepontine cistern, decreased mamillopontine distance and pontomesencephalic angle, and transverse sinus distention.Results:In 27 SIH patients with vestibulocochlear nerve symptoms, the mean CSF pressure was (37.50±27.54) mmH 2O, and 22 patients (91.7%) presented with orthostatic headache. In 45 SIH patients without vestibulocochlear nerve symptoms, the mean CSF pressure was (39.00±26.91) mmH 2O, and 39 patients (95.1%) presented with orthostatic headache. As compared with SIH patients without vestibulocochlear nerve symptoms, the patients with vestibulocochlear nerve symptoms showed significantly lower height of the pituitary gland ( P<0.05). The positive rate of effaced suprasellar cistern in SIH patients with vestibulocochlear nerve symptoms was significantly decreased as compared with those without vestibulocochlear nerve symptoms ( P<0.05); there were no significant differences in other quantitative indexes and positive rates of qualitative signs between the two groups ( P>0.05). Conclusion:The decrease of pituitary height and effaced suprasellar cistern may be closely related to the pathogenesis of vestibulocochlear nerve symptoms in SIH patients.
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Objective:To explore the incidence and dynamic change of apathy after minor stroke and its influence on the quality of life.Methods:One hundred and six patients with minor stroke(NIHSS≤3) were selected as the research group, one hundred and six cases with healthy physical examination were selected as control group.The apathy evaluation scale, clinician version(AES-C) scale was used to evaluate the degree of apathy after minor stroke, then the patients were divided into minor post-stroke apathy group(mPSA group) and non post-stroke apathy group(NPSA group). At 1, 3, 6, 9 and 12 months after onset, the follow-up visits were carried out and AES-C, modified Barthel index(MBI), modified Rankin scale(mRS) and stroke-specific quality of life scale(SS-QOL) were evaluated.The incidence of minor post-stroke apathy and its dynamic changes over time were analyzed, and the differences of related scales scores between the mPSA group and the NPSA group were compared.Results:The incidence of apathy in research group(35.1%) was higher than that of the control group(7.5%) ( P<0.05). The scores of MRS in the mPSA group at 1 month(1.06±0.86), 3 months(1.18±0.97), 6 months (1.09±0.85), 9 months(1.11±0.71), 12 months(1.11±0.72) after stroke were not significantly different from those in the NPSA group at 1 month(1.00±0.89), 3 months(0.95±0.83), 6 months (0.97±0.87), 9 months (1.00±0.80), 12 months(1.03±0.79) (all P>0.05). The scores of MBI in the mPSA group at 1 month (92.42±5.75), 3 months(91.32±5.81), 6 months (91.71±5.14), 9 months(91.67±4.78), 12 months (91.14±5.01) after stroke were not significantly different from those in the NPSA group at 1 month (91.97±5.79), 3 months(92.42±5.64), 6 months(92.29±5.67), 9 months(92.07±5.46), 12 months(92.12±5.35) (all P>0.05). The scores of SS-QOL in the mPSA group at 1 month (135.09±26.88), 3 months (132.71±24.91), 6 months (134.31±26.63), 9 months(135.89±24.86), 12 months (138.77±27.83) after stroke were lower than those in the NPSA group at 1 month (183.79±24.80), 3 months(183.77±24.18), 6 months (181.80±26.62), 9 months(179.86±28.92), 12 months (179.98±29.13) (all P<0.05). There were no significant differences in the incidence of mPSA at each time point of follow-up( P>0.05). Conclusion:The incidence of apathy after minor stroke is significantly higher than that of the control group, and it remains relatively stable in the first year and seriously affect the quality of patients' life.
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Objective:To analyze risk factors for deep vein thrombosis(DVT)in patients with severe cerebral infarction and to find early and sensitive indicators for the prediction and intervention of DVT.Methods:A total of 226 patients with severe cerebral infarction aged 62.5±12.9 years in our department from January 2017 to May 2020 were enrolled.Clinical data, biochemical examinations and color Doppler ultrasound results were collected.Risk factors for DVT were analyzed.The receiver operating characteristic curve(ROC)was used to determine the cut-off value, area under the curve, sensitivity and specificity.Results:Age, reaction(R)time of blood coagulation factors on thromboelastography(TEG)and fibrinogen degradation products(FDP)were risk factors for DVT with no adjustment of the overall effect of time on coagulation mechanisms.According to time stratified analysis, decreased R time( OR=0.58, 95% CI: 0.40-0.84)and increased FDP( OR=1.17, 95% CI: 1.02-1.33)within 3 days of onset were risk factors for DVT, and the cut-off values were 5.35 min and 0.39 mg/L, respectively; 3 and 7 days after onset, increased D-dimer was a risk factor for DVT( OR=2.73, 95% CI: 1.53-4.86; OR=2.57, 95% CI: 1.32-5.03), and the cut-off values were 0.39 mg/L and 0.76 mg/L, respectively.Excluding the effects of FDP primary and D-Dimer secondary fibrinolysis, risk factors for DVT within 3 days of onset were decreased R time on TEG and increased age, and all risk factors were not statistically significant 3 days and 7 days after onset( P<0.05). Conclusions:The key factors affecting DVT in patients with severe cerebral infarction are different at different stages.Decreased R time within 3 days of onset is a predictive indicator of DVT.FDP and D-dimer can be used to assess thrombosis, but may not be appropriate as predictive indicators.
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Objective To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.Methods The data about basic clinical features,fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs,15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology,the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected.The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed.The relevance between the diversity of intestinal microbiota and inflammatory index was explored.Results Compared with healthy controls,the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered.The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls,while their inflammation indexes,including IL-6,IL-10 and transforming growth factor (TGF)-α,in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml,t=4.197,P=0.001;(3.4±2.1) pg/ml vs (0.9±0.2)pg/ml,t=2.265,P=0.037;(21.4± 12.7) ng/ml vs (13.7±7.8) ng/ml,t=3.702,P=0.004).Compared with control group,the relative abundance of butyrivibrio,prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8％±3.5％ vs 13.0％±4.7％,t=4.941,P＜0.001;3.9％±2.2％ vs 6.9％±3.3％,t=3.282,P=0.003;5.1％±2.5％ vs 7.3％±3.0％,t=2.641,P=0.012),while the relative abundance of ackermania was increased obviously (7.0％±3.1％ vs 4.4％±2.8％,t=2.802,P=0.008);Besides,the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4％±2.4％ vs 5.5％±2.1％,t=2.784,P=0.009;7.9％±5.4％ vs 13.0％±4.7％,t=2.501,P=0.018).In the comparison between subgroups,the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1％±8.9％ vs 32.6％± 10.4％,t=2.572,P=0.016),while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4％± 1.6％ vs 1.7％± 1.4％,t=2.977,P=0.006).Moreover,there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548,P=0.003).Conclusions The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs.Moreover,there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs,which can be used as an important means of clinical auxiliary examination.
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Objective:To investigate the characteristics of magnetic resonance myelography (MRM) and its application in the treatment of spontaneous intracranial hypotension (SIH).Methods:The clinical data, MRM characteristics, and treatment of 15 patients with SIH who underwent MRM examination in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to treatment methods, nine patients were divided into conservative treatment group and six patients were divided into combined epidural blood patch treatment group. The gender, age, time interval from onset to MRM examination, cerebrospinal fluid pressure and MRM characteristics between the two groups were compared. SPSS 20.0 software was used for statistical description, and independent sample t-test was applied to compare the differences between groups. Results:All of the 15 cases reported orthostatic headache. Their cerebrospinal fluid pressure was (29.67±19.77, range 0-55) mmH 2O (1 mmH 2O=0.009 8 kPa), and onset-MRM interval was (33.07±24.22, range 7-90) days. The MRM characteristics were observed, including all 15 cases with periradicular leaks, four cases with anterior epidural fluid collections, six cases with posterior epidural fluid collections, and eight cases with high cervical (C 1-2 to C 2-3) retrospinal cerebrospinal fluid collections. There were 2 to 32 leak sites with an average of (10.20±7.87) sites. Among the 153 leak sites, 58(37.9%) sites were located at cervical vertebra, 77(50.3%) sites at thoracic vertebra, 18(11.8%) sites at lumbar vertebra, and 61(39.9%) sites at either the cervicothoracic junction (C 7-T 1 to T 1-2) or the upper thoracic region (T 2-3to T 6-7). Five patients responded well to one-time targeted autologous epidural blood patch on the basis of the location of the cerebrospinal fluid leakage. Besides, one patient improved with targeted epidural blood patch twice. There were no statistically significant differences in gender, age, onset-MRM interval, cerebrospinal fluid pressure, number and location of leak sites between the conservative treatment group and combined treatment group. Conclusions:The periradicular leaks of cerebrospinal fluid at cervical vertebra and thoracic vertebra are the most common feature of MRM in patients with SIH. MRM can identify the existence and location of cerebrospinal fluid leakage, assist in the diagnosis of SIH, and guide targeted epidural blood patch.
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Objective@#To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.@*Methods@#The data about basic clinical features, fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs, 15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected. The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed. The relevance between the diversity of intestinal microbiota and inflammatory index was explored.@*Results@#Compared with healthy controls, the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered. The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls, while their inflammation indexes, including IL-6, IL-10 and transforming growth factor (TGF)-α, in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml, t=4.197, P=0.001; (3.4±2.1) pg/ml vs (0.9±0.2) pg/ml, t=2.265, P=0.037; (21.4±12.7) ng/ml vs (13.7±7.8) ng/ml, t=3.702, P=0.004). Compared with control group, the relative abundance of butyrivibrio, prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8%±3.5% vs 13.0%±4.7%, t=4.941, P<0.001; 3.9%±2.2% vs 6.9%±3.3%, t=3.282, P=0.003; 5.1%±2.5% vs 7.3%±3.0%, t=2.641, P=0.012), while the relative abundance of ackermania was increased obviously (7.0%±3.1% vs 4.4%±2.8%, t=2.802, P=0.008); Besides, the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4%±2.4% vs 5.5%±2.1%, t=2.784, P=0.009; 7.9%±5.4% vs 13.0%±4.7%, t=2.501, P=0.018). In the comparison between subgroups, the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1%±8.9% vs 32.6%±10.4%, t=2.572, P=0.016), while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4%±1.6% vs 1.7%±1.4%, t=2.977, P=0.006). Moreover, there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548, P=0.003).@*Conclusions@#The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs. Moreover, there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs, which can be used as an important means of clinical auxiliary examination.
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To explore the clinical effect of microsurgery in the treatment of the tumor which was diagnosed with the plexiform neurofibroma (PN) of the forearm and palm. Methods From January, 2014 to June, 2017, 6 cases of the PN in the forearm and palm were removed by microsurgery such as neurovascular transplantation, separation and anastomosis under microscope, etc. There were 4 males and 2 females, with an average age of 9.2 (range, 2-18 )years. There was 1 case with PN of the median nerve, ulnar nerve and their branches in the right fore-arm and palm, 2 cases with PN of the median nerve and its branches in the right forearm and palm, 2 cases with PN of the median nerve and its branches in the left forearm and palm, and 1 case with PN of the ulnar nerve and its branches in the left forearm and palm.The postoperative function and feeling of the patients were evaluated by outpa-tient followed-up. Results The pathological results of 6 patients all showed PN, and their incisions healed primari-ly.The patients were followed-up for 6 to 36 months, with an average of 18 months. No obvious scar formation was observed in all incisions. Among them, PN of the palmar of the youngest patient recurred after the operation, and it was resected in a second operation.The remaining 5 patients had no recurrence during follow-up.The 2 point resolu-tion of each fingertip of the affected limb of the patients who had median and ulnar PN was 2-5 mm, with an average of 3.30 mm; the 2 point resolution of the thumb, indicator, middle and ring fingers of the affected limbs of the patients who had median PN was 2-5 mm, with an average of 2.95 mm; the 2 point resolution of the ring and little fingers of the affected limbs of the patients who had ulnar PN was 3-4 mm, with an average of 3.50 mm.According to the related evalu-ation criteria made by the American Orthopedic Foot and Ankle Surgery Society (AOFAS), the results of the forearm and hand functions were excellent in 5 cases, good in 1 case. Conclusion The application of microsurgical techniques in the treatment of PN in the forearm and palm can be effective separation of tumor and nerve fibers, effectively protect the branches of the median nerve and ulnar nerve and their blood circulation, prevent recurrence and reduce nerve damage after operation.
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Objective To investigate the application value ofthromboelastography (TEG) in coagulation function after aneurysmal subarachnoid hemorrhage (ASAH).Methods Thirty-two patients with ASAH with onset within 24 h and 20 healthy controls,recruited from our hospital from October 2015 to September 2016,were enrolled in this study.Traditional coagulation parameters were recorded.Parameters were analyzed by TEG.Results Traditional coagulation parameters between ASAH patients and controls were no statistically different (P＞0.05).R value of TEG in the ASAH group was obviously decreased as compared with that in the controls,with significant difference ([4.03±2.09] min vs.[6.63±1.00] min,P＜0.05).Platelet number and Angle value in ASAH group ([189.5±52.58]×109/L and 68.60 [63.63,70.78]) were significantly increased as compared with those in the control group ([233.9±68.4]×109/L and 70.55 [68.83,72.30],P＜0.05).Conclusions TEG could be used to evaluate the coagulation function at acute stage after ASAH and target the abnormal link.This targeted therapy has an important value of clinical guidance to this disease.
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BACKGROUND:The microRNAs are involved in regulation of stem cel proliferation, differentiation and aging. To study the effect of Let-7c, a member of Let-7, on the neural differentiation of bone marrow mesenchymal stem cels provides new ideas for stem cel therapy. OBJECTIVE: To investigate the role of Let-7c in the neural differentiation of bone marrow mesenchymal stem cels. METHODS: The lentiviral vectors of Let-7c-up and Let-7c-inhibition were constructed and transfected into rat bone marrow mesenchymal stem cels. Optimal multiplicity of infection was screened. The cels were divided into non-transfected group, negative control group (transfected with empty virus), transfected enhancement group (transfected with LV-rno-Let-7c-up), transfected inhibition group (transfected with LV-rno-Let-7c-5p-inhibition). Bone marrow mesenchymal stem cels were treated with fasudil as an inducer for triggering the cels to differentiate into neurons. The fluorescence expressed by transfected cels was observed under inverted fluorescence microscope. The expression of neuron-specific markers, neuron-specific enolase and microtubule-associated protein 2, were measured by immunocytochemical method. The mRNA expression of microtubule-associated protein 2 was detected by RT-PCR. The cel viability was determined by MTT method. RESULTS AND CONCLUSION:Under the inverted fluorescence microscope, the cels were successfuly transfected with LV-rno-Let-7c-up and LV-rno-Let-7c-5p-inhibition. Fasudil induced bone marrow mesenchymal stem cels to differentiate into neurons. The transfection efficiency and expression levels of neuron-specific enolase and microtubule-associated protein 2 in the transfected enhancement group were significantly higher than those in the negative control group (P < 0.05), while in the transfected inhibition group, they were lower than those in the negative control group (P < 0.05). These findings indicate that the differentiation percentage of bone marrow mesenchymal stem cels is increased by fasudil after transfection with LV-rno-Let-7c-up, and Let-7c may promote the differentiation of bone marrow mesenchymal stem cels into neurons.
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Objective To analyze the differential expressions ofmicroRNAs in patients with methylmalonic acidemia (MMA) and explore the expression rule ofmicroRNAs in MMA pathogenesis primarily to find the new biomarkers and therapeutic evaluation index of MMA represented by microRNAs.Methods Ten patients,admitted to our hospitals and diagnosed as having delayed onset vitamin B12 valid MMA from August 2011 to June 2013,were chosen as experimental group (MMA group);and their 8 healthy relatives were chosen as negative control group (NC group).Plasma microRNAs were routinely extracted and filed,and samples quality was evaluated with real-time quantitative PCR;microarray gene chip was employed to detect the expression levels ofmicroRNAs;R software of prediction analysis ofmicroarrays (PAM) was used to filter differentially expressed miRNAs.Results The results of GC/MS showed that the urine methylmalonic acid zoom ratio of MMA group was significantly higher than that of NC group.And the urine methylmalonic acid zoom ratio of MMA group had remarkable difference between before and after treatment.Real-time PCR showed the RNAs extracted from plasma samples conformed to the requirement of experiment and could be delivered to downstream chip experiment.The chip statistical analysis suggested that there were many micrornas enjoying significant differences between MMA group and NC group (P＜0.05),and differences in MMA group before and after treatment (P＜0.05).The resluts of R software of PAM indicated that mir-483 and mir-144 were strongly raised in MMA group as compared with those in NC group (P＜0.05),while mir-151,mir-30 and mir-146 were remarkably reduced in MMA group as compared with those in NC group (P＜0.05).Conclusion There are several abnormal expressions of plasma circulation microRNAs in patients with methylmalonic acidemia;the plasma circulation microRNAs might be biomarkers of methylmalonic acidemia.
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Objective:To evaluate the influence of bone marrow stem cells ( BMSCs ) in the serological indicators of hepatolenticular degeneration combined liver fibrosis.Methods:60 cases were randomly divided into 3 groups: penicillamine group, BMSCs group and BMSCs+penicillamine group.BMSCs(2 ml)were injected into vein with normal saline(100 ml) every 10 days ( 3 times for a period of treatment).Liver tissue pathology biopsy was inspected and TBIL, ALT, ALB, CHE, PDGF-BB, TGF-β1, IL-6 and TNF-αwere detected at 0,4 ,8 and 12 weeks.Results: The level of serological indicators about liver functions were reduced in every group, while the changes in BMSCs+penicillamine group were especially obvious ( P<0.05 ).Conclusion: Penicillamine combined with BMSCs was effective in the improvement of liver functions of hepatolenticular degeneration combined liver fibrosis.
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Objective To investigate the changes of learning and memory function ,vascular endothelial growth factor (VEGF) and heme oxygenase‐1(HO‐1) expression in cerebral cortex and hippocampus of chronic ischemic vascular dementia rats . Methods Thirty‐six healthy SD rats were divided into the control group ,sham operation group and model group ,12 cases in each group .The chronic ischemic vascular dementia rat model was established by the permanent bilateral carotid artery occlusion The sham operation group received the same treatment to the model group except without bilateral carotid artery occlusion .The learning and memory abilities were tested by the Morris water maze experiment and climbing rope strength experiment at 1 ,4 ,8 ,12 weeks respectively .The expressions of VEGF and HO‐1 in rat cerebral cortex and hippocampus was determined by immunohistochemical SP technique .Results The escape latency time at 8 ,12 weeks in the model group was longer than that in the sham operation group and control group ,and the number of crossing the platform was less than that in the sham operation group and control group ,the differences were statistically significant (P0 .05) .The positive expression of HO‐1 and VEGF protein contents in the control group and sham operation group was less than that in the model group with sta‐tistical difference(P<0 .05) .Conclusion Chronic cerebral hypoperfusion has a permanent damage to the learning and memory abil‐ities in rats ,while has no influence on the motor function .VEGF and HO‐1 may play a protective role in chronic cerebral ischemia .
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BACKGROUND:There is no clear understanding about the effect of let-7f and interleukin-6 (IL-6) on the proliferation of bone marrow mesenchymal stem cels and their relationship. OBJECTIVE: To explore the effects of expression levels of let-7f and IL-6 on the proliferation of bone marrow mesenchymal stem cels and their relationship. METHODS:(1) LV-rno-let-7f-up and LV-rno-let-7f-down were constructed and transfected into bone marrow mesenchymal stem cels of Sprague-Dawley rats, respectively. Then, there were four groups in the study: transfection upregulation group transfected with LV-rno-let-7f-up), transfection inhibition group (transfected with LV-rno-let-7f-down), negative control group (transfected with FU-RNAi-NC-LV), and untransfected group. The expression level of let-7f in each group was detected by qRT-PCR. The proliferation ability of cels and expression levels of IL-6 when let-7f expression was at different levels were detected by MTT, flow cytometry and ELISA. The expression of Cyclin D1 at mRNA and protein levels was detected by qRT-PCR and western blot, respectively. (2) To predict the potential target gene of let-7f, the wild-type/mutant IL-6 3’UTR reporter gene vectors were constructed, and cotransfected with let-7f/let-7f inhibitor respectively into the 293T cels to measure the luciferase. RESULTS AND CONCLUSION: Compared with the negative control group, the proliferative and cloning capacities of cels in the transfection upregulation group were higher; the number of cels was significantly decreased at G1 stage and increased at S stage, and the apoptotic cels were reduced in number (P 0.05). Luciferase activity of cels transfected with wide-type IL-6 3’UTR and let-7f was significantly reduced (P < 0.05). These findings indicate that up-regulation of let-7f can promote the proliferative and cloning capacities of bone marrow mesenchymal stem cels and reduce cel apoptosis, but downrelation of let-7f exhibits an inhibitory effect. Overexpression of IL-6 can suppress the proliferation of bone marrow mesenchymal stem cels, which is considered to be a target gene of let-7f, and let-7f may suppress the expression of IL-6 to promote the cel proliferation.