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Objective:To explore the clinical characteristics of neurological syndrome associated with anti-glutamic acid decarboxylase (GAD) antibodies (Abs).Methods:Six patients with neurological syndrome associated with anti-GAD-Abs admitted to Department of Neurology, Henan Provincial People's Hospital from January 2019 to October 2022 were chosen. The clinical manifestations, imaging and laboratory results, therapeutic schedules, and follow-up prognoses of these patients were collected and summarized.Results:Three females and 3 males were included, with onset age of (54.3±17.7) years. Three patients had stiff-person syndrome (SPS), 1 had limbic encephalitis+generalized epilepsy, 1 had extralimbic encephalitis+occipital epilepsy, and 1 had cerebellar ataxia who was diagnosed with paraneoplastic syndrome associated with small cell lung cancer. Four patients had elevated level of thyroid peroxidase antibodies, and 1 patient was positive for overlapping anti-gamma aminobutyric acid B receptor antibodies and Amphiphysin antibodies. Two patients with SPS had failed lumbar puncture; 1 had slightly increased white blood cells and proteins in cerebrospinal fluid (CSF); the remaining 3 patients were basically normal. Specific oligoclonal bands in CSF were observed in 2 patients. Brain MRI showed abnormal signals in the bilateral occipital lobes in 1 patient, and no specific inflammatory lesions in other patients. All patients accepted corticosteroids and intravenous immunoglobulin/plasma exchange therapies; except for the one with paraneoplastic syndrome associated with small cell lung cancer, the remaining 5 patients had improved modified Rankin scale (mRs) scores at discharge and received long-term immunotherapy. Two patients with SPS had gradually aggravated symptoms, and mRs scores reached 5 at the last follow-up (one for 3 years and the other one for 2 years).Conclusions:The clinical manifestations of patients with neurological syndrome associated with anti-GAD-Abs include SPS, limbic encephalitis, extralimbic encephalitis, epilepsy and cerebellar ataxia; some of these patients have paraneoplastic syndromes. Immunotherapies are effective except for these patients with paraneoplastic syndromes. Some patients with SPS tend to have a chronic course and a poor prognosis.
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β-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring β-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better β-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters Km, Vmax and Kcat/Km were 0.81 mmol, 291.99 μmol/(mg·min), and 387.50 s-1 mmol-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.
Subject(s)
beta-Glucosidase , Sodium Chloride , Temperature , Glucose , Ethanol/chemistry , Ions , Hydrogen-Ion Concentration , Enzyme Stability , Substrate Specificity摘要
Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the recovery of neurological functioning and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and inflammatory factors after ischemic stroke.Methods:Sixty-four C57BL/6J mice were randomly divided into a normal control group, a model group, a sham stimulation group and an observation group, each of 16. All mice except those of the normal control group received middle cerebral artery occlusion using the suture method to model an ischemic stroke. After the modeling the observation group was given 1Hz rTMS daily for 7 consecutive days, while the sham stimulation group was given sham rTMS. After the intervention, Zea-Longa scores were used for all of the groups, and the size of the cerebral infarct was measured using triphenyltetrazolium chloride staining. The expression of NLRP3 around the cerebral infarction was detected using immunofluorescence, while that in the brain tissue was measured using Western blotting. The expression of interleukin-1β and IL-18 in the brain tissue was detected using enzyme-linked immunosorbent assays.Results:Compared with the normal control group, a significant increase was observed in the other groups′ average neurological function impairment scores. Expression of NLRP3, IL-1β and IL-18 in the model and sham stimulation groups also increased, with large cerebral infarcts in the cortex and hippocampus. Compared with the sham stimulation and model groups, there was a significant decrease in the average neurological dysfunction scores, the area of cerebral infarction in the cortex and hippocampus, as well as the expression of NLRP3, IL-1β and IL-18 in the observation group.Conclusions:Low-frequency rTMS can promote the recovery of damaged nerve function after an ischemic stroke, at least in mice. It can reduce the size of cerebral infarction, and inhibit neuronal pyroptosis, which is closely related to the down-regulation of NLRP3, IL-1β and IL-18 expression.
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β-glucosidase has important applications in food, medicine, biomass conversion and other fields. Therefore, exploring β-glucosidase with strong stability and excellent properties is a research hotspot. In this study, a GH3 family β-glucosidase gene named Iubgl3 was successfully cloned from Infirmifilum uzonense. Sequence analysis showed that the full length of Iubgl3 was 2 106 bp, encoding 702 amino acids, with a theoretical molecular weight of 77.0 kDa. The gene was cloned and expressed in E. coli and the enzymatic properties of purified IuBgl3 were studied. The results showed that the optimal pH and temperature for pNPG hydrolysis were 5.0 and 85 ℃, respectively. The enzyme has good thermal stability, and more than 85% of enzyme activity can be retained after being treated at 80 ℃ for2 h. This enzyme has good pH stability and more than 85% of its activity can be retained after being treated at pH 4.0-11.0 for 1 h. It was found that the enzyme had high hydrolysis ability to p-nitrophenyl β-d-glucoside (pNPG) and p-nitrophenyl β-d-xylopyranoside (pNPX). When pNPG was used as the substrate, the kinetic parameters Km and Vmax were 0.38 mmol and 248.55 μmol/(mg·min), respectively, and the catalytic efficiency kcat/Km was 6 149.20 s-1mmol-1. Most metal ions had no significant effect on the enzyme activity of IuBgl3. SDS completely inactivated the enzyme, while EDTA increased the enzyme activity by 30%. This study expanded the β-glucosidase gene diversity of the thermophilic archaea GH3 family and obtained a thermostable acid bifunctional enzyme with good industrial application potential.
Subject(s)
beta-Glucosidase/chemistry , Archaea/metabolism , Escherichia coli/metabolism , Hydrogen-Ion Concentration , Temperature , Glucosides , Enzyme Stability , Substrate Specificity , Kinetics摘要
Objective:To investigate the prognoses of pulmonary adenocarcinoma patients with leptomeningeal metastases (LM) and explore their influencing factors.Methods:A retrospective analysis was performed. The clinical data, imaging features and treatment plans of pulmonary adenocarcinoma patients with LM admitted to our hospital from January 2010 to June 2021 were collected. Overall survival (OS) was used as the prognostic evaluation criterion and patients were divided into good prognosis group (OS≥6 months) and poor prognosis group (OS<6 months) accordingly. Logistic regression analysis was used to evaluate the influencing factors for prognoses of pulmonary adenocarcinoma patients with LM. These patients were grouped according to different Karnofsky performance status (KPS) scores and different treatment methods, and survival curves were drawn to compare their OS.Results:A total of 173 pulmonary adenocarcinoma patients with LM were enrolled in the study, including 75 with good prognosis and 87 with poor prognosis. There were significant differences in the KPS scores, pulmonary adenocarcinoma lesion controlled status, giving third generation tyrosine kinase inhibitor (TKI) therapy or not, giving systemic chemotherapy and/or whole brain radiotherapy or not between the two groups ( P<0.05). Multivariate Logistic regression analysis showed that KPS scores and pulmonary adenocarcinoma lesion controlled status were independent influencing factors for prognoses ( OR=4.186, 95%CI: 1.583-11.070, P=0.004; OR=4.198, 95%CI: 1.499-11.760, P=0.006). Survival curves showed median OS of 8.2 months for all patients ( 95%CI: 6.5-9.8). The OS in patients with low-risk(KPS scores≥60) was significantly higher than that in patients with high-risk(KPS scores<60), that in patients accepted TKI treatment was significantly higher than that in patients not accepted TKI treatment, and that in patients accepted TKI and systemic chemotherapy was significantly higher than that in patients accepted TKI alone ( P<0.05). Conclusion:Patients with high KPS scores and controlled pulmonary adenocarcinoma can have relatively good prognosis; TKI treatment and combination therapy may prolong OS of these patients.
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Objective:To explore the clinical and imaging features and prognoses of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD).Methods:Thirty-nine MOGAD patients, admitted to our hospital from January 2018 to April 2021, were chosen in our study. The clinical and imaging data and follow-up results of these patients at acute attack period (first-onset or relapse) were collected and their features were analyzed.Results:In these 39 patients with MOGAD, 20 patients (51.3%) had non-reversing course, and 19 patients (48.7%) had relapsing course. The clinical and imaging data of 55 episodes of these 39 patients were collected. In these 55 episodes, optic neuritis was noted in 27 episodes (49.1%), encephalitis was noted in 10 episodes (18.2%), brainstem encephalitis was noted in 8 episodes (14.5%), meningoencephalitis in 2 episodes (14.5%), myelitis in 3 episodes (5.5%), encephalomyelitis in 1 episode (1.8%), optic neuromyelitis in 1 episode(1.8%), optic neuritis+meningoencephalitis in 2 episodes (3.6%), and optic neuritis+encephalitis in 1 episode (1.8%). The positive rate of antinuclear antibody (ANA) was 11.1% (4/36); the cerebrospinal fluid results of 28 samples were collected from 22 patients, and CSF pleocytosis occurred in 67.9% of the samples with value of 54.89±67.70×10 6/L. Twenty-seven brain MRIs of 19 patients at the acute episode were collected; one completely normal MRI was recorded; among the remaining 26 MRIs, 6 were with one single lesion, 5 were with 2 lesions, and 15 were with 3 or more lesions; in terms of distribution, lesions involving brainstem and its adjacent structures were found in 9 MRIs, lesions involving diencephalon and deep gray matter were found in 7 MRIs, supratentorial white matter lesions were found in 13 MRIs, and cortical lesions were found in 13 MRIs. Meningeal enhancement were found in 4 contrast-enhanced brain MRIs (4/20). Long or short segmental myelitis in the spinal MRIs was noted in spinal lesions, involving cervical spinal cord, thoracic spinal cord and conus, and the "H" sign could be seen in the cross section. All patients received steroids therapy at the acute phase and the doses of steroids were tapered down gradually. Thirty-eight patients (97.4%) had good prognosis after 3 months of treatment. Conclusions:MOGAD is a disease entity widely involving the white matter, gray matter and meninges of the central nervous system with various clinical manifestations such as optic neuritis, encephalitis, brainstem encephalitis, meningoencephalitis and myelitis or a combination of the above. Immunotherapy is effective in most patients, but the recurrence rate is high, and some patients require long-term immunotherapy.
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Objective To comparatively analyze the safety and efficacy of direct mechanical thrombectomy and bridging therapy for patients with acute anterior circulation large-artery occlusive stroke.Methods A total of 116 patients with acute anterior circulation large-artery occlusive stroke,admitted to our hospitals from October 2015 to March 2018,were chosen in our study;their clinical data were analyzed retrospectively.Among them,63 patients accepted direct mechanical thrombectomy and 53 accepted bridging therapy.The preoperative baseline data and the diagnoses and treatments of the two groups were analyzed;the degrees of modified thrombolysis in cerebral infarction (mTICI),incidences of hemorrhage transformation and symptomatic intracranial hemorrhage,and modified Rankin scale (mRS) scores and mortality rate 90 d after operation were compared between the two groups.Results The preoperative Alberta stroke program early CT scale (ASPECTS) and Glasgow Coma Scale (GCS) scores of the direct mechanical thrombectomy group were significantly lower than those of the bridge therapy group (P＜0.05),and the time from onset to admission was significantly longer than that of the bridging therapy group (P＜0.05).The incidence of postoperative hemorrhage transformation in the direct mechanical thrombectomy group was significantly higher than that in the bridging therapy group (34.9％ vs.17.0％,P＜0.05),but there were no significant differences in the effective recanalization rate (69.8％ vs.79.3％),intracranial symptomatic hemorrhage rate (15.9％ vs.7.6％),favorable outcome rate (28.6％ vs.35.9％) and mortality (22.2％ vs.17.0％) between the two groups (P＞0.05).Conclusion The clinical efficacy and safety of direct mechanical thrombectomy and bridging therapy for patients with acute anterior circulation large-artery occlusive stroke are similar.
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Objective To explore the clinical features,auxiliary examinations,therapies and prognoses of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods The clinical data of 11 anti-CASPR2 encephalitis patients who were admited to the People's Hospital of Zhengzhou University from March 2015 to April 2018 were retrospectively analyzed.Results The age of these 11 cases was (35.6± 19.4) years (ranged 20-74 years),and eight cases were females.There were seven cases with limbic encephalitis which included six cases of epilepsy,four cases of memory impairment,two cases of mental and behavioral abnormalities.Four cases had peripheral nerve hyperexcitability.Four cases had neuropathic pain.There were six cases with autonomic dysfunction including five cases of constipation,three cases of tachycardia,two cases of hyperhidrosis,two cases of urinary disorder.Seven cases had sleep disorder.Four cases had weight loss.Two cases showed cerebellar symptoms and two cases had hyponatremia.Magnetic resonance imaging scan of the brain showed abnormal signal in two cases,mainly involved medial temporal lobe and the hippocampus.Six cases underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) examination,and three cases showed abnormalities,including two with temporal hypermetabolism and one with cortical hypermetabolism.Chest enhanced CT and PET-CT showed thymoma in one case.All cases received immunotherapy,and after treatment their symptoms were improved.Long-term follow-up was performed in nine cases,and three cases relapsed.Conclusions The major clinical manifestations of anti-CASPR2 encephalitis were limbic encephalitis,peripheral nerve hyperexcitability,neuropathic pain,autonomic dysfunction,insomnia and so on.Immunotherapy was effective and some patients may have recurrence.
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Objective To investigate the influencing factors of cerebral infarction in elderly patients with hypertensive intracerebral hemorrhage after hematoma clearance.Methods A total of 197 elderly patients with hypertensive intracerebral hemorrhage were selected and treated with craniotomy hematoma removal and decompression of bone flap.Cerebral infarction was checked by craniocerebral CT after operation.Univariate and multivariate Logistic regression analysis was used to identify the independent risk factors for cerebral infarction.Results The incidence of cerebral infarction after hematoma clearance in hypertensive intracerebral hemorrhage was 26.90％(53/197).There was no significant difference in the incidence of cerebral infarction after hematoma clearance in hypertensive intracerebral hemorrhage on gender and age (P＞ 0.05),while the differences were statistically significant in diabetes (x2 =7.986),hypertension history (x2 =10.399),hematoma volume(x2=10.396),edema(x2=12.436),systolic blood pressure(x2 =12.128),diastolic blood pressure(x2 =13.040) and GCS score(x2 =3.940) (all P＜0.05).Logistic regression analysis showed that history of diabetes mellitus(β=1.472,0R=2.174,95％CI=1.092-2.981),history of hypertension (β =1.894,OR =2.819,95 ％ CI =1.309-3.973),volume of hematoma ＞ 35 ml (β =2.36 l,OR =3.890,95％CI=1.792-5.132),area of brain edema (＞ 65 cm3) (β=2.471,OR=4.321,95％CI=1.879-5.487),systolic pressure (＞ 150 mm Hg,1 mmHg =0.133 kPa) (β=2.073,OR=3.172,95％ CI=1.428-4.768),diastolic pressure (＞ 90 mm Hg) (β=1.715,OR=2.498,95％ CI =1.276-3.451) and GCS score ＜ 8 (β=2.592,OR=4.871,95％ CI=1.974-5.798)were independent risk factors for cerebral infarction after hematoma clearance in hypertensive intracerebral hemorrhage.Conclusion Elderly patients with cerebral infarction after hematoma clearance in hypertensive intracerebral hemorrhage is affected by diabetes mellitus,hypertension,hematoma volume,edema,systolic blood pressure,diastolic blood pressure and other factors.Early intervention on these factors may effectively reduce the incidence of cerebral infarction.
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Objective To explore the effect of combining mild hypothermia with intravenous thrombolytic therapy on the cognitive functioning and stress response of persons with acute cerebral infarction.Methods A total of 126 patients with acute cerebral infarction were randomly divided into a control group,a study group 1 and a study group 2,each of 42.All three groups were given intravenous thrombolytic therapy,while study group 1 also received 12 hours of mild hypothermia,and study group 2 received 24 hours.Before the treatment and 1,7,14,30 and 90 days later the National Institutes of Health stroke scale (NIHSS) was used to evaluate the subjects' nerve functions.Intracranial pressure,oxidative stress,and inflammatory cytokine levels were also measured before the treatment and 2,3 and 7 days afterward.Results The average NIHSS scores of both study groups were significantly lower than that of the control group at each time point after the treatment.Study group 2 showed significantly greater improvement than study group 1.The total effectiveness rate was 76.2％ in study group 1 and 85.7％ in study group 2,both significantly better than in the control group but without significant difference between the study groups.Both study groups' average intracranial pressures were significantly lower than the control group's average after the treatment.Moreover,3 and 7 days after the treatment,the average intracranial pressure of study group 2 was significantly lower than study group 1's average.After 1,3 and 7 days,significant differences in superoxide dismutase and malondialdehyde levels were observed between the study groups and the control group.Three days after the treatment,the average TNF-α,IL-1β and IL-6 levels of the study groups were significantly lower than the control group's average,and those of study group 2 were significantly lower than those of study group 1.The total incidence of adverse reactions was not significantly different among the 3 groups.Conclusion For patients with acute cerebral infarction,thrombolytic therapy combined with mild hypothermia for 24 hours has a definite curative effect.It can improve intracranial pressure,reduce oxidation and inflammation and improve neurological function.The patients recover well.The combined therapy is safe and worthy of clinical application.
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Objective To revise rumination on sadness scale (RSS) and evaluate the reliability and validity of the Chinese version rumination on sadness scale (RSS-C) in Chinese undergraduates.Methods A total of 1 166 undergraduates from 4 universities in Hunan province completed RSS,ruminative response scale (RRS) and Beck depression inventory-Ⅱ (BDI-Ⅱ).The test-retest was conducted in 111 participants 2 weeks later.Results Item analysis and exploratory factor analysis showed the RSS-C included 11 items,consisting of causal analysis,understanding oneself and one's sadness and uncontrollability of ruminative thinking factors.The scores of each item in the high score group were significantly higher than those in the low group(P＜0.001),and the correlation between each item and the total score was significant(r=0.594-0.719,P＜0.001).The confirmatory factor analysis indicated good fit(x2/df=3.938,GFI =0.957,NFI =0.940,CFI =0.954,TLI =0.930,IFI =0.954,RMSEA =0.070).The internal consistency for RSS-C and three factors ranged from 0.694 to 0.868,and the test-retest reliability ranged from 0.620 to 0.833.The scores on RSS-C and three factors were significantly associated with RRS(r=0.555-0.637,P＜0.01),BDI-Ⅱ (r=0.211-0.403,P＜0.01) respectively.Conclusion RSS-C has good reliability and validity and can be used as an effective instrument to assess rumination on sadness in Chinese undergraduates.
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Objective To evaluate the reliability and validity of the Chinese-version of the scale for the assessment of illness behavior(SAIB) in Chinese medical college students. Methods In view of the professional and cultural basis of the translation of SAIB,723 medical students were asked to complete the SAIB and the Illness Attitude Scale. After two weeks,75 students were followed to complete the SAIB. Re-sults After the analysis of the scale project analysis and the exploratory factor analysis,23 entries were re-tained and five common factors were extracted( verification of diagnosis,expression of symptoms,medication/treatment,consequences of illness,somatic symptom scanning),and accounted for 56.14％ of the total vari-ance.The confirmatory factor analysis identified a five factors model(SRMR=0.057,χ2/df=1.80,SRMR=0.06,RMSEA=0.05,GFI=0.912,CFI=0.93,TLI=0.91,IFI=0.93,PGFI=0.72,AGFI=0.89).The correla-tion validity between SAIB scale total score and treatment experience and symptoms affected in IAS scale were -0.31,-0.36 (P<0.01).Reliability coefficients of the five dimensions and total score ranged from 0.61 to 0.88,and the test-retest reliability was 0.78. Conclusion The Chinese version of the scale for the assess-ment of illness behavior is a reliable and valid instrument in Chinese.
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Objective To explore the reliability and validity of the preliminary revision of the Philadelphia Mindfulness Scale (PHLMS) in Chinese undergraduates.Methods Considering the differences in the cultural and linguistic,the PHLMS was translated and used to conduct a questionnaire survey among 1 221 undergraduates.All participants were also surveyed with five facets mindfulness questionnaire (FFMQ),the white bear suppression inventory (WBSI) and acceptance and action questionnaire-2rd edition (AAQ-Ⅱ) as conduct reliability and validity test.Results The exploratory factor analysis showed that PHLMS could extract two factors,and the cumulative variance contribution rate was 40.355％.The confirmatory factor analysis indicated good fit (x2/df=2.781,CFI =0.945,NFI =0.884,IFI =0.922,TLI =0.906,CFI =0.922,RMSEA =0.053).The internal consistency reliability of the awareness subscales was 0.785,and the internal consistency reliability of the acceptance subscales was 0.772.The correlation coefficients among the PHLMS and FFMQ was significant(r=0.398,P＜0.01).The acceptance subscales were significantly negatively correlated with WBSI and AAQ-Ⅱ(r=-0.458,-0.288,P＜0.01).Conclusion The validity and reliability of the Chinese version of PHLMS meet the measurement criterion.
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Objective To explore the relationship between asymmetrically hypointense veins (AHVs) on susceptibility-weighted imaging (SWI) and collateral circulation.Methods We retrospectively enrolled acute ischemic stroke patients with severe stenosis or occlusion of M1 segment of the middle cerebral artery ± intracranial internal carotid artery.All the patients underwent diffusion-weighted imaging (DWI),SWI,and computed tomography angiography (CTA) of intracranial and cervical arteries within 72 hours from symptom onset.We explored the association of the level of AHVs with the degree of the regional leptomeningeal score (rLMC) on baseline CTA and other clinical and image data.The factors that might influence the prognosis of stroke were also analyzed.Results Fifteen patients with mild AHVs and 15 with extensive AHVs were enrolled in our study.The level of AHVs was positively correlated with CTA rLMC (r =0.481,P =0.007) and the degree of collateral circulation (r =0.402,P =0.028).Patients with extensive AHVs had better collateral status,smaller DWI infarction lesion ((11.62 ± 9.07) ml vs (95.77 ± 91.12) ml,t =3.559,P =0.001),and lower NIHSS scores on admission (6.47 ± 4.34 vs 12.33 ± 7.60,t =2.595,P =0.015)and at discharge (4.80 ± 4.69 vs 9.60 ± 7.03,t =2.200,P =0.036).The high degree of rLMC,small DWI lesion,young age and lower NIHSS scores,but not extensive AHVs were related with favorable outcome at 3 months after stroke.Conclusion Extensive AHVs can reflect good collateral circulation to some extent,but cannot be equivalent to or replace the collateral status.
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Objective To analyze the clinical and electrophysiological features in a family with spinal muscular atrophy (SMA), and assess the probable causative gene mutations for the family. Methods To identify the nosogenesis of the proband with weakness and atrophy in the double lower proximal limbs, clinical data of his 12 family members were collected, and the proband and his mother were selected for clinical examinations, including laboratory tests, electromyogram (EMG), F-wave, H-reflex, X-ray of the spine and double lower limbs, brain and spinal cord magnetic resonance imaging, etc. Moreover, human whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics (ACMG) and the Association for Molecular Pathology (AMP). Subsequently, the strong pathogenic mutation was validated by Sanger sequencing. Results Familial investigation showed seven of 12 family members presented with weakness in the double lower proximal limbs. Among them, three had the main manifestation of atrophy in the double lower proximal limbs, one had high arched foot as the main presentation, and the others had weakness in the double lower proximal limbs. EMG studies showed the abnormal results in the anterior horn of the spinal cord. The strong pathogenic mutation in DYNC1H1 gene (exon8, c.2327C＞T, p.P776L) was identified from the proband according to ACMG and AMP guidelines. Sanger sequencing revealed six patients had this variant and it was passed mainly from his maternal grandmother. Conclusions A pathogenic mutation of the DYNC1H1 p.P776L in six Chinese pedigrees which cosegregated with SMA was identified. There existed individual differences in clinical presentations. This finding may have important implications for the study of SMA in Chinese patients.
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Objective To analyze the clinical, imaging characteristics and NOTCH3 mutations of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) in Henan, China.Methods CADASIL patients diagnosed by gene or biopsy in People′s Hospital of Zhengzhou University between 2012-2016 were recruited.Clinical and imaging features of these patients were analyzed retrospectively.The distribution of NOTCH3 gene mutations hotspots was described in Henan region at the same time.Results There were 37 patients from 19 families who were diagnosed as CADASIL by genetic testing or biopsy, 27 of whom had symptoms of CADASIL.Two families were confirmed by pathological examination and 17 by genetic testing.Of these 17 families, 13 mutations were found.Mutations in exon 11 were found in eight families, in exon 4 were detected in four families, and in exon 13 were found in two families.Mutation in exons 3, 8 and 20 was detected in one family respectively.Most patients presented with stroke and several presented with cognitive decline.Twelve patients had been attacked by risk factors.Magnetic resonance imaging (MRI) was performed on 22 patients.White-matter lesions were distributed in brain stem, basal ganglia, subcortical, temporal pole, external capsule.There were 19 patients with white-matter lesions in temporal pole and seven in capsula externa, showed as a high signal in T2WI.Conclusions CADASIL patients can be associated with risk factors.T2WI hyperintensities in the anterior temporal lobe were more common than that in the capsular external.Exon 11 and exon 4 were the hotspots for the NOTCH3 mutation in Henan patients.
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Objective To explore the predictive value of susceptibility vessel sign (SVS) in clinical outcomes of patients with acute anterior circulation ischemic stroke. Methods The clinical and imaging data of patients with acute anterior circulation ischemic stroke, admitted to our hospital from January 2013 to April 2015, were prospectively collected. All of them underwent diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and magnetic resonance angiography (MRA) within 72 h of symptom onset. According to the results of the examination, the presence, location and length of SVS, DWI lesion volumes, degrees of vascular stenosis, perfusion status of distal blood flow and vascular stenosis sites were assessed and recorded. The prognoses of the patients were evaluated by modified Rankin scale (mRS) 3 months after stroke. The univariate analysis and multivariate Logistic regression analyses were used to explore the independent risk factors for poor prognosis. Results One hundred and sixteen patients were enrolled in this study. There were 43 patients in the SVS(+) group and 73 patients in the SVS(-) group. As compared with patients from the SVS(-) group, patients from SVS(+) group had higher systolic pressure, lower thrombolysis in cerebral infarction scale (TICI) scores, larger infarction volume, higher NIHSS scores on admission and lower percentage of favorable outcome, with statistically significant differences (P<0.05). Of the 116 patients, 40 had poor outcome while 76 achieved favorable prognosis;as compared with the patients with favorable outcome, those with poor outcome had higher percentage of the elderly, higher percentages of atrial fibrillation and SVS, lower TICI scores, larger infarction volumes, and higher NIHSS scores on admission, with statistically significant differences (P<0.05). Multivariate Logistic regression analysis revealed that NIHSS on admission (OR=1.278, 95％CI:1.145-1.426, P=0.000), age (OR=1.085, 95％CI: 1.036-1.136, P=0.001), and presence of SVS (OR=3.390, 95％CI: 1.122-10.240, P=0.030) were independent parameters to predict poor prognosis. For patients with SVS(+) status, 18 patients achieved favorable outcome, while 25 had poor outcome;patients with poor outcome had larger infarction volumes on DWI, higher NIHSS scores on admission, higher rate of SVS located at the proximal M1 and longer SVS, with statistically significant differences (P<0.05). On multivariate Logistic regression analysis, NIHSS score on admission was an independent predictor of poor outcome (OR=1.341, 95％CI: 1.123-1.602, P=0.001). Conclusion The presence of SVS is an independent predictor for poor clinical outcome in patients with acute anterior circulation ischemic stroke.
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Objective To investigate the NOTCH3 gene mutation and clinical features in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) families.Methods The clinical features of 4 CADASIL probands in Henan,China were analyzed retrospectively,and the incidences of other members in their families were investigated.The NOTCH3 gene mutations in the 3rd,4th,llth,and 18th exons were detected and the results were analyzed in the patients and some family members.Results Gene sequencing showed that 6 patients in 4 families and 1 mutant carrier had NOTCH3 gene R607C mutation in exon llth,they all met the clinical features of CADASIL.Three patients accompanied with vascular risk factors.The clinical stroke patients had unilateral limb weakness.All 5 patients with complete head MRIdata had thalamic infarction.Conclusions In the 4 CADASIL families of R607C mutation,the clinical features of 6 patients with CADASIL were similar,but there were individual differences in different family members.Imaging examination has important role in the diagnosis of CADASIL.The vascular risk factors,such as hyperte.
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Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.
Subject(s)
Humans , Adjuvants, Immunologic , Pharmacology , Administration, Intranasal , Administration, Oral , Antigens , Drug Delivery Systems , Proteins , Vaccination摘要
Objective To study the relationship between the selection of tube tension in digitalchest radiograph and image quality.Methods When tube current was fixed at 4 mAs, the choice of X-ray tube voltage changed from 60 to 120 kV.CDRAD2.0 contrast details phantom and normal human chest were exposed by X-ray system with 7 kinds of tube voltage (the difference between tube voltage was 10 kV) ,and the X-ray incidental dose of phantom surface was measured.Five radiologists with 3 years working experience evaluated the image quality on monitor and calculated the image quality factor (IQF) and image reading score.Statistics analysis was then performed by using ANOVA test and t test.According to the results, the optimum tube voltage range was determined.Results (1) The incidental dose of phantom surface increased with the higher tube voltage.(2)When the tube voltage was changed from 60 kV to 120 kV, the IQF value observed in CDRAD2.0 phantom image on monitor was 75.0±10.4,57.1±6.4,52.7±2.5,47.9±4.5, 46.0±3.8,46.0±2.8,45.2±3.5 ,there was significant statistical differences between groups(F=19.10, P<0.01).(3)The integrated score of the chest image quality in the tube voltage 90 kV and 120 kV were 12.4±0.9 and 13.0±0.7, respectively, and there was no statistical difference between two groups(t= 1.500,P>0.05).Conclusions (1)With the increase of tube tension,the display capacity of display device gradually strengthened.When the tube tension exceeded 90 kV, the increase of image quality on monitor was not evident.(2) With proper radiation dose, the value of tube tension in digital X-ray chest photograph was about 90 kV.