Objective To investigate any neuroprotective effect of hyperbaric oxygenation (HBO) on the mitochondria of dopaminergic neurons using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.Methods Forty-eight male SPF C57BL/6 mice were randomly assigned to either a normal control group (treated with a 30 ml/kg intraperitoneal injection of physiological saline once a day),a model group ( treated with a 30 mg/kg intraperitoneal injection of MPTP once a day) or an HBO therapy group ( treated with a 30 mg/kg intraperitoneal injection of MPTP and HBO once a day).The expression of tyrosine hydroxylase (TH) protein,PINK1 protein and caspase-3 in brain tissue was measured using immunohistochemistry and Western blotting assays.Results Compared with the control group,the expression levels of TH protein and PINK1 protein were significantly lower in the neurons of the substantia nigra in the model mice.HBO therapy upregulated the expression of TH and PINK1 protein.Compared with the control group,the average level of caspase-3 protein in the neurons of the substantia nigra in the model mice was significantly higher.HBO therapy downregulates the expression of caspase-3 protein.Conclusions HBO can protect mitochondria and inhibit apoptosis of dopaminergic neurons in the substantia nigra of brains with (MPTP-induced) Parkinson's disease by upregulating the expression of PINK1 protein and TH protein,and downregulating the expression of caspase-3 protein.

Objective To explore any effect of repetitive transcranial magnetic stimulation (rTMS) on the cognitive ability of patients suffering from cognitive impairment after cerebral venous thrombosis (CVT).Methods Forty-three CVT patients with cognitive impairment were recruited and randomly assigned into an rTMS group (n =23) or a control group (n=20).Both groups received routine drug therapy and cognitive function training,while the rTMS group was additionally given rTMS.The treatment lasted 4 weeks.The Montreal cognitive assessment (MoCA),the Hamilton depression scale (HAMD),the modified auditory Barthel Index (MBI) and event-related potential P300 were used to test both groups before and after the treatment.Results After the treatment the average MoCA and MBI scores of both groups had increased significantly,while their average HAMD scores had decreased significantly compared to before the treatment.For both groups,the P300 latency had shortened significantly and the amplitude increased significantly after the treatment.The improvement in all of these indicators was significantly greater in the rTMS group than in the control group.Conclusion Supplementing drug therapy with rTMS can significantly improve the cognitive ability of CVT patients and is worth applying in clinical practice.

Objective To investigate the correlation of plasma interleukin ( IL)-17 level and IL-17 receptor (IL-17R) expression in the thymus of patients with myasthenia gravis (MG).Methods The blood samples of 63 patients (38 with glucocorticoid treatment, 25 with thymus removal) who admitted to Henan Provincial People′s Hospital between 2010 and 2014 were collected at three different stages: pre-treatment, 1 week post-treatment and 1 month post-treatment.The blood samples of 42 healthy controls were also collected.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-17 in plasma.Twenty-five thymus tissues from MG patients and another 12 thymus tissues from patients with congenital heart disease who had surgery therapy were also collected.Reverse transcription polymerase chain reaction was used to evaluate the mRNA levels of IL-17R.The possible correlation between the expression of IL-17 and IL-17R with MG was analyzed.Results Before treatment, the levels of IL-17 in the plasma were much higher in all the MG patients ( both ocular and generalized) when compared to the healthy controls ( controls (3.2 ±0.7) pg/ml, MG patients (8.5 ±1.7) pg/ml, t =2.450, P <0.01; generalized type patients (9.7 ±1.4) pg/ml, t =2.532, P <0.01).In the patients with glucocorticoid treatment, IL-17 levels began to reduce after 1 week treatment and a statistically significant difference was found when compared to the pre-treatment samples (pre-treatment (8.3 ±1.2) pg/ml, 1 week after treatment (6.3 ±0.7) pg/ml, t=2.052, P<0.05) and healthy controls (t =1.933, P<0.05).One month after the glucocorticoid treatment, the levels of IL-17 decreased to the normal level (1 month after treatment (3.9 ±0.6) pg/ml, t=2.630, P <0.01, compared to the pre-treatment; t =1.395, P >0.05, compared to the healthy controls).In the surgery therapy cases, the IL-17 levels were also reduced after the thymus removal ( pre-surgery (8.8 ±1.4) pg/ml, 1 week after surgery (5.3 ±0.7) pg/ml, t=1.950, P<0.05;1 month after surgery (3.0 ±0.4) pg/ml, t=2.683, P<0.01).In the thymus tissues of the MG patients, the mRNA levels of IL-17R were much higher than that of the controls ( relative level 2.31 folds, t =2.682, P <0.01).Meanwhile, a positive correlation was found between the plasma IL-17 levels and the relative IL-17R levels in thymus tissues ( r =0.945 4, P <0.01 ).Furthermore, IL-17 was positively correlated with quantitative myasthenia gravis scores (QMGS) either pre-treatment (r =0.798 1, P <0.01) or post-treatment (r=0.906 5, P<0.01).And IL-17R was positively correlated with QMGS pre-treatment (r=0.775 5, P<0.01).Conclusions IL-17 is increased in the plasma of MG patients (both ocular and generalized) , and is decreased upon the glucocorticoid treatment or surgery therapy, suggesting that it can be used as a parameter to determine the therapeutic effects.IL-17R is increased in the thymus tissues of MG patients, suggesting that it can potentially be used as a pathological diagnosis parameter.

Objective:To investigate the clinical, pathological and genetic characteristics of myopathy-type very long chain acyl-coenzyme A dehydrogenase deficiency (VLCADD).Methods:The detailed clinical data, muscle biopsy pathology and molecular results of 4 patients with genetically confirmed myopathy-type VLCADD admitted to Henan Provincial People′s Hospital and Xuanwu Hospital, Capital Medical University from June 2014 to November 2019 were retrospectively analyzed.Results:All of the 4 patients were late-onset myopathy-type VLCADD. The onset age ranged from 13 to 16 years, with a mean age of 14.5 years. The age at diagnosis ranged from 21 to 54 years, with a mean age of 42.5 years. The main clinical manifestation was repeated rhabdomyolysis, including myalgia, weakness and dark urine. Obvious somnolence was observerd in 1 patient. Muscle biopsy pathology revealed mild lipid accumulation, without vacuoles. Six ACADVL variations were detected in the 4 patients, including c.1283G>A (p.R428H), c.1532G>A (p.R511Q), c.833_835delAGA (p.K278del), c.1843C>T (p.R615 *), c.1748C>T (p.S583L) and c.1391C>T (p.T464I),among which c.1391C>T (p.T464I) was a novel variation, predicted to be likely pathogenic. Other 5 variations were reported pathogenic variations. Conclusions:Myopathy-type VLCADD is characterized by paroxysmal rhabdomyolysis and can be associated with somnolence. There is no specificity in muscle pathology. There are ACADVL variations, among which c.1391C>T is a novel variation.

Objective:To investigate the clinical and genetic features of Pompe disease, and analyze the effect of enzyme replacement therapy on it.Methods:A retrospective study was performed. The clinical data and genetic results of 14 patients with Pompe disease from 12 families, admitted to our hospital from January 2017 to June 2021, were collected. Some patients were followed up after therapies.Results:Twelve of the 14 patients were late onset, with onset age ranged from 1.5 to 37.0 years (mean 15.2 years), and the other 2 patients were infantile onset. The predominant manifestations included proximal lower limb weakness, accompanied by easy fatigue and myalgia; 8 patients presented with dyspnea, of which one had dyspnea as initial presentation. Serum creatine kinase ranged from 172 to 1397 IU/L (mean 878 IU/L). Electromyography revealed myogenic pattern in 6 patients and myotonic discharge in 4 patients. Forced vital capacity decreased in 10 patients, and scoliosis was detected in 5 patients; 13 patients had decreased acid-alpha-glucosidase (GAA) activity; muscle pathology indicated vacuolar myopathy in 8 patients. Genetic test revealed 17 variants in GAA gene, among which c.2331G>C, c.1622C>T, c.1585T>C, and c.1837T>C were 4 novel likely pathogenic variants. The c.2238G>C and c.2662G>T were found in 5 and 3 families, respectively. Muscle strength and lung function got improvement in 1 patient who received enzyme replacement therapy and had regular follow-up, while muscle strength and lung function were worsened in those who did not receive enzyme replacement therapy. Conclusions:Pompe disease is characterized by skeletal muscle weakness and pulmonary dysfunction, and may be associated with spinal deformity; creatine kinase is mildly to moderately elevated, and myotonic discharge can be detected. GAA c.2238G>C and c.2662G>T are hotspot mutations in China; the 4 novel variants enrich the GAA mutational spectrum. Enzyme replacement therapy may improve motor and pulmonary function.

Vertebrobasilar dolichoectasia(VBD ) can increase the risk of stroke. Significant expansion, elongation and tortuosity of the vertebrobasilar arteries are the main morphology manifestations of VBD. However, there is no consensus on the quantitative imaging assessment of VBD. Many studies showed that some quantitative parameters, such as basilar artery length and bending length, basilar angulation, vertebral tortuosity index can be used for the quantitative imaging assessment of VBD.

Objective:To evaluate the performance of three antibody kits for novel coronavirus (SARS-CoV-2) and to investigate the feasibility and advantages of them in clinical application.Methods:A total of 104 patients who were admitted to Guangzhou Eighth People′s Hospital with COVID-19 from January to February 2020 were selected as research group. Fifty-one healthy subjects were selected during the same period as negative control group. Serum antibodies (IgM/IgG) against SARS-CoV-2 were detected using two kinds of colloidal gold kits (A and B kits) and one chemiluminescence kit (C kit). The positive rates of SARS-CoV-2 nucleic acid in different samples from patients with COVID-19 were retrospectively analyzed.Results:The clinical sensitivity of A kit to detect SARS-CoV-2-specific IgM and IgG was 77.88% (81/104) and 65.38% (68/104), respectively, and the clinical specificity was 70.59% (36/51) and 100.00% (51/51). However, the false positive rate in IgM detection was as high as 29.41% (15/51). The sensitivity of B kit to test total antibodies to SARS-CoV-2 was 63.46% (66/104), and the clinical specificity was 94.12% (48/51). The clinical sensitivity of C kit to detect SARS-CoV-2-specific IgM and IgG were respectively 31.73% (33/104) and 64.42% (67/104), and the clinical specificity were both 98.04% (50/51). There was a moderate correlation between the detection results of two colloidal gold kits and the chemiluminescence kit with the Kappa values of 0.462 and 0.587 ( Z=6.157, P<0.01; Z=7.345, P<0.01). C kit had the highest positive detection rate for IgG, and would be more reliable to be used for IgG detection in COVID-19 patients 14 d after onset. The total positive detection rate of nucleic acid in all types of samples was 63.46% (66/104). The highest positive detection rate was in throat swabs or sputum samples, followed by those in blood samples and anal swabs. No viral nucleic acid was detected in urine samples for the time being. Conclusions:SARS-CoV-2-specific antibodies could be detected in the early or late stage of COVID-19. The method of antibody detection has the advantages of shorter detection time, simple operation and high biological safety, indicating that it could be used as a supplementary or auxiliary detection for the diagnosis of suspected COVID-19 cases with negative nucleic acid test results. The chemiluminescence kit has good sensitivity and specificity, and is well recommended for clinical laboratories.

Objective: To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy. Methods: Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband. Results: The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c. 341G>A (p.G114D) mutation in exon 2 of the INF2 gene. Conclusion The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c. 341G>A mutation of the INF2 gene.

Objective: To analyze the clinical data of a family with early-onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family. Methods: The clinical data of a proband who was clinically diagnosed as early-onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, 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. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3. Results: The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta-amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy. Conclusions The study identified the pathogenic mutation of the beta-amyloid precursor protein gene p.V717I in six patients of a family with early-onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early-onset Alzheimer′s disease in Chinese population.

OBJECTIVE: To explore phenotypic and mutational characteristics of a pedigree affected with autosomal dominant Charcot-Marie-Tooth disease (CMT) and nephropathy. METHODS: Clinical data of the proband and his family members was collected. Electrophysiology, renal biopsy and next-generation sequencing were carried out for the proband. RESULTS: The proband presented with distal lower limb weakness and proteinuria in childhood. His mother and brother had similar symptoms. Electrophysiological test of the proband revealed demyelination and axonal changes in both motor and sensory nerves. Renal biopsy suggested focal segmental glomerulosclerosis. Genetic testing revealed a heterozygous c.341G>A (p.G114D) mutation in exon 2 of the INF2 gene. CONCLUSION The phenotypic feature of the pedigree is autosomal dominant intermediate CMT and focal segmental glomerulosclerosis, which may be attributed to the c.341G>A mutation of the INF2 gene.
Charcot-Marie-Tooth Disease ; complications ; genetics ; Child ; Female ; Glomerulosclerosis, Focal Segmental ; complications ; genetics ; Heterozygote ; Humans ; Male ; Microfilament Proteins ; genetics ; Mutation ; Pedigree