RESUMO
Objective:To preliminarily analyze the relationship between peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells, related cytokines and recurrence in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods:A retrospective analysis was performed on the clinical data of 72 patients with NMOSD admitted to Henan Provincial People′s Hospital between January 2019 and January 2021. According to presence or absence of recurrence within 1 year after treatment, they were divided into non-recurrence group ( n=30) and recurrence group ( n=42). The data such as gender, age and score of Extended Disability Status Scale (EDSS) at admission were collected. The levels of serum triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA) 1 and apolipoprotein B (ApoB) were detected by full-automatic biochemical analyzer. The level of total protein in cerebrospinal fluid was detected by full-automatic programmed protein analyzer. The levels of immunoglobulin (Ig) G and IgM in cerebrospinal fluid were detected by immunoturbidimetry. The counts of peripheral blood CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells were detected by flow cytometry. The levels of serum interleukin (IL)-6, IL-10 and IL-2 were detected by enzyme-linked immunosorbent assay. Results:EDSS score, neutrophils, proportions of cases with positive aquaporin 4 (AQP4) antibody and autoimmune antibody in the recurrence group were significantly higher than those in the non-recurrence group (all P<0.05). There was no statistically significant difference in serum TG, HDL-C, LDH-C, ApoB, ApoA1, total protein in cerebrospinal fluid, IgG or IgM between the non-recurrence group and the recurrence group (all P>0.05). The proportions of CD19 +B cells, CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells in the recurrence group were (1.21±0.12)%, (1.61±0.17)% and (1.39±0.25)%, significantly higher than those in the non-recurrence group [(0.85±0.07)%, (1.25±0.12)%, (0.89±0.22)%, t=15.51, 3.89, 12.06, all P<0.05]. The counts of CD19 +B cells, CD19 +CD27 +B cells and CD4 -CD8 -double-negative T cells in the recurrence group were (289.50±17.64) ×10 6/L, (4.67±0.03) ×10 6/L and (64.78±6.53) ×10 6/L, significantly higher than those in the non-recurrence group [(254.56±15.34) ×10 6/L, (3.18±0.03) ×10 6/L, (47.82±4.83) ×10 6/L, t=14.27, 4.26, 12.06, all P<0.05]. The level of serum IL-10 in the recurrence group was lower than that in the non-recurrence group [(18.56±1.97) ng/ml vs (24.72±2.52) ng/ml, t=11.64, P<0.05], while levels of IL-6 and IL-2 were significantly higher than those in the non-recurrence group [(15.12±1.54) pg/ml vs (11.47±1.23) pg/ml, (28.34±2.94) pg/ml vs (22.57±2.36) pg/ml, t=10.75, 8.89, both P<0.05]. Conclusion:The levels of peripheral blood CD19 +CD27 +B cells, CD4 -CD8 -double-negative T cells and related cytokines are abnormal in NMOSD patients, which may be related to the recurrence of NMOSD.
RESUMO
OBJECTIVE@#To explore the clinical characteristics and genetic variants in a patient with adult ceroid lipofuscinosis neuronal type 7 (ACLN7).@*METHODS@#A female patient diagnosed with ACLN7 in Henan Provincial People's Hospital in June 2021 was selected as the study subject. Clinical data, auxiliary examination and result of genetic testing were retrospectively analyzed.@*RESULTS@#The patient, a 39-year-old female, has mainly presented progressive visual loss, epilepsy, cerebellar ataxia and mild cognitive decline. Neuroimaging analysis has revealed generalized brain atrophy, prominently cerebellum. Fundus photography has revealed retinitis pigmentosa. Ultrastructural skin examination has revealed granular lipofuscin deposits in the periglandular interstitial cells. Whole exome sequencing revealed that she has harbored compound heterozygous variants of the MSFD8 gene, namely c.1444C>T (p.R482*) and c.104G>A (p.R35Q). Among these, c.1444C>T (p.R482*) was a well established pathogenic variant, while c.104G>A (p.R35Q) was a missense variant unreported previously. Sanger sequencing confirmed that the daughter, son and elder brother of the proband have respectively carried heterozygous c.1444C>T (p.R482*), c.104G>A (p.R35Q), and c.104G>A (p.R35Q) variants of the same gene. The family has therefore fit with the autosomal recessive inheritance pattern of the CLN7.@*CONCLUSION@#Compared with previously reported cases, this patient has the latest onset of the disease with a non-lethal phenotype. Her clinical features have involved multiple systems. Cerebellar atrophy and fundus photography may be indicative of the diagnosis. The c.1444C>T (p.R482*) and c.104G>A (p.R35Q) compound heterozygous variants of the MFSD8 gene probably underlay the pathogenesis in this patient.
Assuntos
Masculino , Feminino , Humanos , Proteínas de Membrana Transportadoras/genética , Lipofuscinoses Ceroides Neuronais/diagnóstico , Estudos Retrospectivos , Atrofia , MutaçãoRESUMO
Objective: To investigate whether grain-sized moxibustion at Xinshu (BL15) and Shenshu (BL23) can alleviate cognitive decline and other pathologic features in early-stage Alzheimer disease (AD) using transgenic mice with 5 familial AD mutations (5XFAD). Methods: The genotype of transgenic mice was detected by polymerase chain reaction. A total of 40 transgenic mice (1.5 months old) were randomly and equally allocated to an AD model group (5XFAD group) or a grain-sized moxibustion group (5XFAD + GM group), with 20 wild-type (WT) mice (C57BL/6J) serving as the normal control group (WT group). Mice in the 5XFAD + GM group were treated by grain-sized moxibustion at bilateral Xinshu (BL15) and Shenshu (BL23). Mice in the WT group and 5XFAD group received no treatment but were restrained to ensure exposure to a similar experimental condition. Cognitive function and memory were assessed with the Morris water maze and Y-maze tests. The amyloid β 40 (Aβ40) and amyloid β 42 (Aβ42) levels in the brain were evaluated by enzyme-linked immunosorbent assay; amyloid plaque deposition in brain tissue sections was detected by thioflavin-S staining; the expression of glial fibrillary acidic protein (GFAP), cluster of differentiation 11b (CD11b), brain-derived neurotrophic factor (BDNF), and choline acetyltransferase (ChAT) in the hippocampus and prefrontal cortex was analyzed by immunohistochemistry. Results: In the Morris water maze test, compared with the 5XFAD group, mice in the 5XFAD + GM group had a shorter escape latency and more target area crossings and spent more time in the target quadrant (P<0.05). In the Y-maze test, compared with the 5XFAD group, the number of training times of the 5XFAD + GM group was significantly decreased (P<0.05), together with more correct responses (P<0.05). Compared with the 5XFAD group, the levels of Aβ40 and Aβ42 in the brain tissue of the 5XFAD + GM group were significantly lower (P<0.05); in the hippocampus and prefrontal cortex, the total number of amyloid β plaque deposition were significantly lower (P<0.05); the expression levels of GFAP and CD11b were significantly reduced (P<0.05); and the expression levels of ChAT and BDNF were significantly increased (P<0.05).Conclusion: Grain-sized moxibustion at Xinshu (BL15) and Shenshu (BL23) greatly improves learning and memory functions, decreases the levels of Aβ40 and Aβ42, inhibits amyloid β plaque deposition, decreases the expression of GFAP and CD11b, and increases the expression of ChAT and BDNF in AD mice to inhibit the progression of AD.
RESUMO
Objective:To report 8 patients of sporadic Creutzfeldt-Jakob disease (sCJD) with real-time quaking-induced conversion (RT-QuIC) positive and analyze their clinical characteristics.Methods:The medical records of patients discharged from Henan Provincial People′s Hospital from January 2018 to May 2021 who were diagnosed with clinically probable sCJD and had RT-QuIC test were retrospectively analyzed. General information (gender, age, initial symptom, main clinical manifestations), accessory examination [brain magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid 14-3-3 protein, prion protein gene, antibodies related to autoimmune encephalitis and paraneoplastic syndrome] were collected. By a telephone-based follow-up survey, data about morality and total duration of course were collected. The patients were divided into two groups according to electroencephalogram, 14-3-3 protein, duration of disease and MRI results, and the differences of fluorescence peak time and fluorescence peak value in RT-QuIC results between groups were compared.Results:Among 8 patients, 7 patients had subacute onset and 1 patient had chronic onset. Main clinical manifestations included progressive cognitive decline (8/8), pyramid sign (5/8), walking instability (4/8), mental and behavior disorder (4/8), myoclonus (4/8), akinetic mutism (4/8), dizziness (3/8), limb shaking (2/8), dysarthria (2/8), visual hallucination (1/8), impaired vision (1/8). All cases had abnormal electroencephalogram and typical periodic sharp slow compound waves (PSWCs) were observed in 5 cases. Brain MRI showed high signal intensity in the cerebral cortex and/or basal ganglia on diffusion-weighted imaging in 7 cases, of which 6 cases involved bilateral basal ganglia. Cerebrospinal fluid 14-3-3 protein was positive in 2 cases, and RT-QuIC was positive in all cases. The fluorescence peak time of RT-QuIC was shorter in patients with PSWCs [(7.617±2.164) h vs (10.602±2.247) h, t=2.84, P=0.010] and high total MRI score [ (7.600±1.907) h vs (9.760±2.457) h, t=2.26, P=0.032]. Conclusions:RT-QuIC detection is a reliable method for early diagnosis of sCJD. RT-QuIC results were related to PSWCs and degree of MRI involvement.
RESUMO
Objective:To assess the value of the parotid fat fraction (FF) and T 2 relaxation time (T 2 value) in the evaluation of early parotid involvment in patients with primary Sj?gren′s syndrome (pSS) using multi-echo Dixon technique and T 2 mapping imaging. Methods:From December 2018 to December 2019, 26 early pSS patients (pSS group) and 20 healthy controls (control group), matched to age and gender, were enrolled at the First Affiliated Hospital of Zhengzhou University in this prospectively study. All subjects underwent conventional MRI, DWI, multi-echo Dixon and T 2 mapping sequences before treatment. The ADC, FF and T 2 value of bilateral parotid parenchyma in pSS group and control group were measured respectively. Paired sample t test was used to compare the differences of ADC, FF and T 2 values between left and right parotid glands for pSS group and control group, while independent sample t test was used to compare the differences of ADC, FF and T 2 values between pSS group and control group. The ROC curves were drawn to evaluate diagnostic performance of ADC, FF and T 2 values to distinguish early pSS, and the difference of diagnostic efficacy of each parameter was compared by Delong test. Binary logistic regression analysis and ROC curve were used to evaluate the diagnostic performance of the combination of the 3 parameters in early pSS. Results:There were no significant differences of ADC, FF and T 2 values between left and right parotid glands for pSS group and control group (all P>0.05). The parotid ADC values were significantly lower in pSS group than control group ( t=4.641, P=0.006), while the FF and T 2 values of pSS group were significantly higher than those of control group ( t=-2.910, -6.411, both P<0.001). The areas under the ROC curve of ADC, FF and T 2 values to distinguish early pSS were 0.666, 0.750 and 0.862, respectively. The area under ROC curve of the combination of ADC, FF and T 2 values was 0.930, with a sensitivity of 73.1% and a specificity of 97.5%. T 2 values showed a better diagnostic efficacy than ADC values ( Z=2.626, P=0.009) and FF values ( Z=2.112, P=0.035) when distinguishing pSS group from control group. The area under ROC curve of the combination of ADC, FF and T 2 values showed a better diagnostic efficacy than each parameter alone ( Z=4.869, P<0.001, Z=3.628, P<0.001, Z=2.162, P=0.031). Conclusions:Multi-echo Dixon technique and T 2 mapping can quantitatively evaluate the parotid gland fat deposition and inflammatory response in the early stage of pSS. T 2 value has great potential in evaluating early parotid gland injury of pSS, and the combination of ADC, FF and T 2 values can further improve the diagnostic efficiency.
RESUMO
Objective:To report the clinical and genetic features of a pedigree with familial encephalopathy with neuroserpin inclusions bodies (FENIB) and to enhance the understanding of the disease.Methods:The proband was admitted to Department of Neurology, Henan Provincial People′s Hospital in June 2020 due to cognitive impairment and epilepsy. Detailed medical history inquiry, physical examinations, and neuroimaging examination of the family were conducted. The proband completed the examination of brain magnetic resonance imaging (MRI), electroencephalogram (EEG), cerebrospinal fluid examinations. Whole exome sequencing and Sanger sequencing were used to screen the genetic variations in the proband. Sanger sequencing was performed in some family members to verify the mutation. Through literature review, the characteristics of the disease were summarized.Results:The proband was a 23-year-old young female with progressive cognitive impairment, epilepsy as the main manifestations. Brain MRI indicated moderate atrophy of bilateral cerebral cortex. Genetic sequencing revealed a heterozygous missense mutation (c.1013A>G; p.H338R) of SERPINI1 gene encoding the neuroserine protease inhibitor protein. The proband′s mother and brother had similar clinical symptoms in adolescence. Both of them passed away several years later. This mutation was a proven pathogenic mutation for FENIB. The clinical phenotype was consistent within the family. Genotype and clinical phenotype were co-segregated.Conclusion:FENIB due to SERPINI1 gene mutations should be considered in young cases of cognitive decline, epilepsy and myoclonus.
RESUMO
Objective: To investigate the quantitative analysis value of T2 mapping in the evaluation of pathological type, tumor grade and lymphovascular space invasion (LVSI) of cervical cancer. Methods: Totally 57 patients with pathologically proven cervical cancer underwent conventional MRI, DWI and T2 mapping before therapy. T2 and ADC values were obtained and compared between tumor and normal tissue (myometrium), squamous cell carcinomas and adenocarcinomas, well/moderately differentiated tumor and poorly differentiated tumor, LVSI-positive and LVSI-negative cervical cancer, respectively. ROC curve was constructed to evaluate diagnostic performances. Results: T2 and ADC values showed significant differences between cervical cancer and normal tissue (both P0.05). Compared to well/moderately differentiated tumors, poorly differentiated tumors showed decreased T2 and ADC values (both P <0.05). T2 values were significantly lower in LVSI-positive than in LVSI-negative cervical cancer (P=0.002), while ADC values were not significantly different (P=0.675). The AUC of T2 and ADC values for distinguishing tumor grade were 0.709 and 0.747, respectively. The AUC of T2 value in discriminating the presence of LVSI was 0.856. Conclusion: Quantitative T2 mapping can putatively differentiate the grade of cervical cancer. Moreover, quantitative T2 value exhibits better than ADC for discriminating the presence of LVSI.
RESUMO
Objective To investigate the clinical manifestations,imaging features,molecular genetic characteristics and possible pathogenic mechanisms of hereditary cerebral small vessel disease (CSVD) caused by heterozygous mutation of HtrA serine protease-1 (HTRA1) gene.Methods The clinical data of a Chinese Han family with CSVD carrying a heterozygous mutation of HTRA 1 gene,which came from the Department of Neurology,Henan Provincial People's Hospital in March 2018,were analyzed retrospectively.The clinical and radiographic features were summarized.Several high-throughput whole exon high-throughput sequencing was used to capture the mutation sites and the Sanger sequencing was used to validate the results.The family diagram was drawn and the 3D model construction and mutation function prediction were performed using silico tools.The relevant literature was reviewed and the pathogenesis was explored.Results The pedigree map showed that the family had an autosomal dominant inheritance pattern.Three generations of the family were investigated,and three family members in the same generation suffered from the disease.The first symptom of the proband was diplopia at the age of 39,accompanied by recurrent stroke,cognitive impairment and mood disorders,without alopecia.Head magnetic resonance imaging revealed bilateral diffuse,symmetric lesions,multiple lacunar infarcts,perivascular space,and microbleeds.The elder sister of the proband developed symptoms of left limb weakness at the age of 46,whose other clinical and imaging features were similar to those of the proband.The proband's mother died at the age of 59 due to repeated strokes.Whole exon sequencing indicated heterozygous missense mutation at c.821G＞A locus of HTRA1 gene in the proband and her 4th elder sibling,which was a new pathogenic mutation after consulting several mutation sites of databases.Function prediction suggested pathogenicity.Conclusions The heterozygous mutation of c.821G＞A in HTRA1 gene may lead to autosomal dominant CVSD.This genetic type should be given clinical attention.
RESUMO
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.
RESUMO
Objective To investigate the value of ADC and T2WI in differentiating of skull base chordoma and invasive pituitary adenomas(IPA).Methods 15 patients with skull base chordoma and 19 patients with IPA which involve paranasal sinus were reviewed retrospectively.All diagnosis were demonstrated by pathology.Quantitative analysis of minimum ADC, normal ADC and rT2WI values were performed.Differences in minimum ADC, normal ADC and rT2WI values between skull base chordoma and IPA were evaluated using the independent samples t test and receiver operating curves(ROC).Results Statistical analysis revealed a significant difference among normal ADC, minimum ADC and rT2WI values (P<0.01),and the area under the ROC curves decreased in turn.Conclusion Both ADC values and rT2WI SI are effective parameter for differentiating diagnosis of skull base chordoma and IPA.
RESUMO
Objective To observe the value of diffusion-weighted imaging (DWI)and ADC value in the differential diagnosis of benign and malignant lesions of the tongue.Methods 75 patients with lingual lesions,including 32 benign lesions and 43 malignant tumors,underwent conventional MRI,contrast-enhanced MRI and DWI with b values of 0 and 1 000 s/mm2 before therapy.ADC maps were reconstructed,and the ADC values of the lingual lesions were calculated.Diagnostic performance of ADC was compared using receiver operating characteristic curves (ROC).Results The mean ADC values of benign lesions and malignant tumors were (1.84±0.47)×10 -3 mm2/s and (1.12±0.21)×10 -3 mm2/s,respectively.Malignant tumors had lower ADCs than benign lesions (t=-8.038,P <0.000).The areas under the ROC curves of ADC diagnosing benign and malignant lesions of the tongue was 0.957±0.022.The optimal cutoff values of ADC for differentiating benign and malignant lesions of the tongue was 1.30 × 10 -3 mm2/s with sensitivity of 90.7%,specificity of 93.8% and accuracy of 92%.And ADC had a high consistency compared with pathological results (Kappa values were 0.813).Conclusion Different features between benign and malignant lesions of the tongue are able to be identified with DWI,which can be applied as a complementary tool in the detection of benign and malignant lesions of the tongue.
RESUMO
Objective To make a accurate, simple method for determination which is suitable for application in basic level units to test nitrate nitrogen in drinking water. Methods Based on the principle that catalyzed by the Cu2+, NO3- is reduced by hydrazine sulfate into NO2-, then it reacts on sulfanilamide in hydrochloric acid to produce a diazo compound, the latter reacts on NEDD to produce a rose dye. Results The maximum wave-length of the was 555 nm, the molar absorption coefficient was 6.5?106L/(mol?cm), RSD were 0.55%-2.07%, the rates of recovery were 91.3%-109.6%. Beer's law was obeyed in the range of 40-320 ?g/L(1-8 ?g /25 ml). Conclusion This method is simple, rapid, accurate and suitable for application in basic level units to determine nitrate nitrogen in drinking water.