Objective Explore the relationship between semen quality and trace element levels in seminal plasma,as well as miR-184 levels in exosomes of male infertility patients.Methods 155 male infertility patients in our hospital from January 2022 to July 2023 were selected as the infertility group,and another 155 male patients with normal physical examination during the same period were selected as the normal group.Compare the general information,semen quality parameters,trace elements,and miR-184 levels in exosomes between two groups,and analyze the correlation between male infertility patients and the above laboratory indicators through Spearman rank correlation analysis.Results The sperm concentration,total sperm motility(PR + NP),forward motility sperm(PR),average curve velocity,average linear velocity,average path velocity,and average lateral amplitude of sperm head(ALH)in the infertile group were lower than those in the normal group(P<0.05);The levels of Zn,Mg,and Ca in the infertile group were lower than those in the normal group,while the levels of Cu,Pb,and relative expression of miR-184 were higher than those in the normal group(P<0.05);The levels of Zn and Cu elements in male infertility patients are positively and negatively correlated with sperm concentration,total sperm motility(PR+NP),and forward motility sperm(PR),respectively.The levels of Pb elements are negatively correlated with the average lateral amplitude of sperm head(ALH),and P<0.05.The relative expression level of miR-184 in male infertility patients is negatively correlated with sperm concentration,total sperm motility(PR + NP),forward motility sperm(PR),and average sperm curve velocity,with P<0.05.Conclusion The quality of semen in male infertility patients is closely related to the levels of trace elements in semen and miR-184 levels in exosomes.

Objective:To summarize the clinical and imaging features of 10 patients with genetically diagnosed neuronal intranuclear inclusion disease (NIID) to avoid clinical misdiagnosis and mismanagement of NIID.Methods:Ten patients with NIID, admitted to our hospital from January 2020 to March 2022, were chosen in our study. All patients were confirmed as having NIID by NOTCH2NLC gene assay. Their clinical data, gene detection results and skin pathological results were collected and anlyzed. Results:These patients aged from 57 to 84 years, including 8 females. The episodic symptoms as main symptoms were noted in 6 patients, including 3 patients with encephalopathy, 1 patient with TGA, 1 patient with stroke-like episode, and 1 patient with migraine-like symptoms. Chronic progressive symptoms as main symptoms were noted in 4 patients, including 3 patients with dementia and 1 patient with Parkinson's disease. There were characteristic linear hyper-intensities in diffusion weighted imaging (DWI) in the corticomedullary junction predominantly in the frontal lobes. White matter lesions appeared in T2 Flair might have been noted years before lesions appeared in DWI, with wider ranges. All had GGC repeated expansion in NOTCH2NLC gene in non-coding area, with mutation number>60. Skin biopsy was performed in 6 patients, showing the formation of intranuclear inclusion bodies in different cells; and ubiquitin and P62 were found positive in immunohistochemical staining. Conclusions:NIID patients have large clinical heterogeneity; most patients have episodic symptoms as main manifestations, often accompanied by chronic progressive symptoms; stroke attack and migraine are rare clinical phenotypes of NIID. The high signal at the cortical medullary junction in DWI is a characteristic imaging change.

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.

Objective: To explore the inhibitory effect of exosomes secreted by human umbilical cord mesenchymal stem cells(HUCMSC) on apoptosis of human umbilical vein endothelial cells(HUVEC) after model group(oxygen-glucose deprivation reoxygenation), and to clarify its possible mechanism. Methods: Human umbilical cord mesenchymal stem cells were cultured. The collected cell supernatant was stored in a centrifugal tube. The exosomes secreted by human umbilical cord mesenchymal stem cells were extracted by ultracentrifugation and identified. Human umbilical vein endothelial cells were randomly divided into control group, model group and different concentrations of HUCMSC-EXO(20 μg/ml, 40 μg/ml, 60 μg/ml) treatment groups(adding HUCMSC-EXO into the model group) . The morphological changes of HUVEC cells in each group were observed by inverted phase contrast microscope, and the proliferation inhibition rate of HUVEC in each group was measured by CCK-8 reagent. Western blot was used to detect the expression of apoptosis-related proteins Caspase-3, Bax, Bcl-2 and hypoxia-associated protein hypoxia inducible factor 1α(HIF-1α). Inhibitor(HIF-1α inhibitor) + model group and HUCMSC-EXO + inhibitor + model group were added on the basis of the above experiments. Western blot analysis was performed to observe the effects of HUCMSC-EXO, inhibitor and both of them on HIF-1α and Bax expressions in HUVEC. Results: HUCMSC-EXO was successfully extracted and identified. Compared with the control group, the volume of HUVEC in the model group and the HUCMSC-EXO group with different concentrations decreased, became round, connected and evacuated, and the growth state was poor under the inverted phase contrast microscope.CCK-8 detection showed that the cell viability in the HUCMSC-EXO group was significantly higher than that in the model group, the difference was statistically significant (t=9.23, P<0.05). Western blot analysis showed that compared with the control group, the expression levels of Caspase-3 ((0.296±0.038), (0.879±0.088); t=14.92, P<0.05), Bax((0.234±0.034), (0.762±0.084); t=14.36, P<0.05) of HUVEC in the model group were up-regulated, and the expression level of Bcl-2 was down-regulated ((0.863±0.103), (0.387±0.059); t=9.85, P<0.05), with statistically significant differences. Compared with the model group, the expression levels of Caspase-3( (0.586±0.075); t=6.24, P<0.05), Bax((0.311±0.055); t=11.01, P<0.05) and Bcl-2((0.665±0.071); t=7.45, P<0.05) of HUVEC in the HUCMSC-EXO treatment group were down-regulated and the differences were statistically significant. Inhibitor intervention experiments showed that there were no significant differences between the inhibitor+ model group and HUCMSC-EXO+ inhibitor+ model group in the expression of HIF-1α protein ((0.348±0.055), (0.388±0.077); t=1.04, P>0.05)and Bax protein ((0.363±0.069), (0.370±0.064); t=0.18, P>0.05). But both of them were down-regulated compared with the model group (HIF-1α protein (0.919±0.064), Bax protein (0.902±0.071)), the differences were significant( t=13.56, t=13.03, both P<0.05). Conclusion HUCMSC-EXO has a protective effect on OGD/R model of HUVEC, and its mechanism may be related to the down-regulation of HIF-1α expression.

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.

Objective To explore the association between test results of human biological stimulation feedback instrument (EZSCAN) and blood glucose levels. Methods Data were collected from the general population who received health checkups that included examination of the autonomic nervous system function using the EZSCAN human biological stimulation feedback instrument from January to December 2017 in Shanghai Eastern Hospital. In accordance with the inclusion and exclusion criteria, 2136 cases (1122 men and 1024 women), with an average age of (50.7 ± 12.9) years, were enrolled in the final analysis. Participants were divided according to the diabetic risk scores obtained by EZSCAN into the control group (n=784 cases), low-risk group (n=801 cases), and high-risk group (n=551 cases). Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels were statistically compared between groups. Participants were divided into four groups according to FPG quartiles [Group F1 (FPG≤4.76 mmol/L, n=546 cases), Group F2 (4.76 mmol/L5.58 mmol/L, n=528 cases)] and HbA1c quartiles [Group H1 (HbA1c≤5.3％, n=630 cases), Group H2 (5.3％5.9％, n=457 cases)]. EZSCAN test results were compared between the quartile groups. Correlations between EZSCAN results and FPG levels and HbA1C levels were analyzed. Results There were statistical differences in both FPG levels and HbA1c levels between participants in the control group, low-risk group, and high-risk group [FPG: (5.10 ± 1.06) mmol/L, (5.47 ± 1.36) mmol/L, and (5.59 ± 1.32) mmol/L, respectively, F=29.47, P<0.05; HbA1C:(5.95 ± 0.99)％, (5.79 ± 0.89)％, and (5.50 ± 0.70)％, respectively, F=47.42, P<0.05]. With increases in both FPG and HbA1C quartile levels, the EZSCAN scores showed a statistically increasing tendency [Groups F1-F4:(30.1 ± 14.6), (32.9 ± 15.2), (33.8 ± 15.1), and (39.1 ± 15.6), F=32.98, P<0.05;Groups H1-H4: (29.1 ± 14.4), (31.9 ± 14.2), (37.2 ± 15.3), and (40.3 ± 15.8), F=61.36, P<0.05]. Both FPG and HbA1c levels were positively correlated with diabetic risk scores (r=0.22 and 0.32, P<0.05). Conclusion Test results using the EZSCAN human biological stimulation feedback instrument showed significantly positive correlations with blood glucose levels.

Objective To analyze the imaging features of congenital spinal deformity (CSD) associated with split cord malformation (SCM) and other intraspinal abnormalities, and to investigate the relationship to neurological symptoms. Methods 105 cases CSD with SCM were retrospectively studied. Analysis the imaging features of SCM (including type of SCM, location of SCM, location and apical vertebrae, symmetry of divided cord) and other intraspinal abnormalities. To investigate the relationship of the factors and neurological symptoms using Chi?square test of one factor and multiple factors logistic regression analysis. Re?sults 28 cases (26.7%) were formation failure, 33 cases (31.4%) were segmentation failure, and 44 cases (41.9%) were combina?tion of 2 disorders. 41 cases had neurological symptoms, 64 cases were asymptomatic. The distribution of SCM combined with spi?nal deformities:thoracic (11 cases), thoracolumbar (18 cases) and lumbar (20 cases) in type I SCM, thoracic (31 cases), thoracolum?bar (20 cases) and lumbar (5 cases) in type II, none was in cervical. The location of SCM upper than apical vertebrae 29 cases, on apical vertebrae 25 cases, lower than apical vertebrae 51 cases. Spinal cord was splitted symmetric 27 cases and asymmetric 78 cases. 66 cases combined with other intraspinal abnormalities, lower conus 42 cases, syringomyelia 38 cases, meningocele 10 cas?es and sakrale zyste 5 cases. Associated with intraspinal abnormalities, the rate of neural symptoms was different. According to Chi?square test of one factor and multiple factors logistic regression analysis, lumbar SCM, spinal cord asymmetric and lower conus were related with neurological symptoms. Conclusion The predilection spinal deformity of type I is combination, type II SCM is segmentation failure. When SCM patients associated with other intraspinal abnormalities, the incidence of neurologic symptoms is increased. The lumbar SCM, hemicords asymmetry and lower lying conus have significant relationship with neurologic symptoms.

Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN-deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.
Animals ; Ascorbic Acid ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line ; Cellular Senescence ; drug effects ; DNA Damage ; DNA Repair ; drug effects ; DNA Replication ; drug effects ; Disease Models, Animal ; Heterochromatin ; metabolism ; pathology ; Humans ; Mesenchymal Stem Cells ; metabolism ; pathology ; Mice ; Nuclear Lamina ; metabolism ; pathology ; Reactive Oxygen Species ; metabolism ; Telomere Homeostasis ; drug effects ; Werner Syndrome ; drug therapy ; genetics ; metabolism

Objective To explore the social support and characteristics of ecological executive function in adult patients with epilepsy,and their correlation.Methods Evaluate the social support and ecological executive function in 65 cases of adult epilepsy patients and 60 normal ones of the same gender,age group and educational level using the Social Support Rating Scale (SSRS) and the Behavior Rating Inventory of Executive Function-adult version (BRIEF-A).The date were statistically analyzed with independent sample t test,Pearson correlation analysis and multiple stepwise regression analysis.Results The scores of adult epilepsy patients in global executive composite,subjective support,objective support and support utilization of SSRS(respectively,37.01±6.74,19.51 ± ±4.77,7.18±2.73,7.45± 1.75) were lower than those of the control group(respectively,40.89±8.54,23.52±2.85,11.02±2.43,9.55±2.88).The scores of adult epilepsy patients in global executive composite (GEC),behavioral regulation index(BRI) and metacognition index(MI) of BRIEF(respectively,55.12± 10.49,53.74± 10.35,56.60± 10.99) were significantly higher than those of the control group (respectively,48.10± 6.3,47.18± 5.84,48.16± 6.23) (P＜0.01).SSRS scores,subjective support,objective support and support utilization were obviously negative to BRIEF scores,behavioral regulation index (BRI) and metacognition index (MI) (P＜ 0.01).Seizure type and SSRS scores were closely related to BRIEF (P＜0.01).Conclusion The epilepsy patients show a lack of social support and ecological executive function dysfunction.The lack of social support is significantly related with ecological executive dysfunction.