Humans ; SARS-CoV-2 ; COVID-19

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 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.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective: To explore the association between maternal pre pregnancy and pre delivery overweight with overweight and obesity among offspring during adolescence in Guangzhou, and to provide evidence for child obesity prevention. Methods: Based on the routine physical examination of primary and secondary school students in Guangzhou, random sampling was used to 6 middle schools and questionnaire survey was conducted among 3 384 students and their parents. Students with overweight and obesity were included in the case group, and the other students were included in the control group. Propensity Score Matching (PSM) was adopted to reduce selection bias. Logistic regression model and χ 2 test were used to analyze the data before and after PSM. Results: The result of univariate analysis showed that there were statistically significant differences between overweight/obese group and the control group by gender, schooling stage (middle and high schools), picky eater, family history of obesity, family monthly income, delivery mode, high birthweight, and gestational weight gain before PSM( χ 2=42.38, 10.64, 14.47, 26.85, 10.58, 13.59 , 15.53, 20.64, P <0.05). After PSM, results showed that there were no statistically significant differences between overweight/obese group and the control group in middle and high schools, and mother delivery mode( P >0.05). Logistic regression analysis showed that the risk of overweight and obesity of maternal pre pregnancy on adolescent offspring was 1.54 times higher than control group (95% CI =1.01-2.36) before PSM, and the overweight and obesity of maternal predelivery also increased the risk of overweight and obesity of adolescent offspring( OR=2.35, 95%CI =1.67-3.31). After PSM, maternal overweight and obesity pre pregnancy ( OR=2.17, 95%CI =1.41-3.34) and maternal overweight and obesity pre delivery( OR=2.99, 95%CI =2.08-4.31) significantly increased the risk of overweight and obesity in adolescent offspring. Conclusion Maternal overweight and obesity pre pregnancy and pre delivery are associated with increased risk of overweight and obesity in adolescent offspring.

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.

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 investigate the correlations of melanin concentration hormone (MCH) in cerebrospinal fluid (CSF) and serum with sleep disorder, memory dysfunction and prognoses in patients with cerebral ischemic stroke (CIS).Methods:One hundred elderly CIS patients, admitted to Department of Neurology, He'nan Provincial People's Hospital from June 2021 to January 2022 were enrolled as CIS group, and 50 subjects collected from Physical Examination of the same hospital during the same period were enrolled as control group. MCH levels in the CSF and serum were detected by ELISA. Sleep quality was assessed by polysomnography and Pittsburgh Sleep Quality Index (PSQI). Memory function was assessed by Rivermead Behavioral Memory Test 2 nd Edition (BMT-II). Prognoses were assessed by modified Rankin Scale (mRS) 3 months after discharge. The clinical data and MCH levels of the two groups were compared; the differences in MCH levels among CIS patients with different degrees of sleep disorder, and different memory functions and prognoses were compared. Correlations of MCH level and sleep parameters with RBMT-II scores in these CIS patients were analyzed. Results:Compared with that in the control group, the proportion of patients with hypertension in CIS group was significantly higher ( P<0.05). Compared with the control group ([42.39±16.11] pg/mL), the serum MCH level in CIS group ([36.89±15.19] pg/mL) was statistically lower ( P<0.05). In CIS patients, patients with mild or severe sleep disorder had significantly decreased CSF MCH level compared with patients without sleep disorder ( P<0.05), patients with severe sleep disorder had significantly decreased CSF MCH level compared with patients with mild sleep disorder ( P<0.05); patients with severe sleep disorder had significantly decreased serum MCH level compared with patients without sleep disorder ( P<0.05); CSF MCH level was negatively correlated with PSQI scores, sleep latency and wake frequency ( P<0.05), and positively correlated with percentage of rapid eye movement ( P<0.05); serum MCH level in CIS patients was negatively correlated with PSQI scores and wake frequency ( P<0.05). In CIS patients, the CSF and serum MCH levels in patients with memory dysfunction was significantly lower compared with those with normal memory function ( P<0.05); a positive correlation was noted between RBMT-II scores and CSF MCH level ( P<0.05). In CIS patients, patients with poor prognosis had statistically lower CSF and serum MCH levels compared with those with good prognosis ( P<0.05). Conclusion:The serum MCH level in CIS patients is significantly decreased, which is closely related to the occurrence of sleep disorder and memory dysfunction after stroke; and they further affects the prognoses.

【Objective】 To investigate the impact of ceasing mutual blood donation on voluntary blood donation in Guangzhou. 【Methods】 The data of blood donation from July 2016 to December 2019 (42-month before and after the official cease of mutual blood donation) in the Blood Collection and Supply System of Guangzhou Blood Center, including whole blood donations and apheresis platelets donations, were collected for interrupted time series analysis by month. Blood donors who donated (either whole blood or platelets) during 2016 were followed up until December 31, 2019, and the re-donation rate was analyzed by Chi-square test, t test and logistic regression analysis. 【Results】 The results showed that ceasing mutual blood donation had a significantly positive effect on the increase of platelet donations, but had no significant effect on whole blood donation. In 2016, whole blood donations and platelet donations were mainly voluntary (86.4% and 60.8%, respectively). In comparison of voluntary blood donation, the overall blood deferral rate(by dual assays) of mutual blood donation was higher (P<0.01), but the difference diminished as they donated twice or more. The re-donation rate of blood donors (mutual non-remunerated, voluntary, or both) all increased after the ceasing of mutual blood donation (mutual non-remunerated, : 4.7% vs 4.0%, χ²=29.8, P<0.01; voluntary: 24.8% vs 9.9%, χ²=17295.3, P<0.01; both: 36.3% vs 28.1%, χ²=29.3, P<0.01). The re-donation rate of mutual platelet donors decreased after the ceasing of mutual blood donation, but the number of voluntary platelet donors increased. 【Conclusion】 The ceasing of mutual blood donation was in favour of voluntary blood donation in Guangzhou since various means had been previously adopted by Guangzhou Blood Center to create a long-term mechanism of voluntary blood donation. The number of voluntary blood donors has increased, and the clinical use of blood has been further guaranteed.

Objective: To determine the effect of transplanting bone marrow mononuclear cells (BMMCs) on the expression of glial fibrillary acidic protein (GFAP) and Nogo-A around the ischemic foci after focal cerebral ischemia and reperfusion, and to study any role of BMMCs in nerve function recovery. Methods: BMMCs were isolated from the bone marrow of Sprague-Dawley rats. Cerebral ischemia and reperfusion was performed using a nylon thread to occlude the right middle cerebral artery for 2h followed by 24h of reperfusion. The qualified models were selected according to the Longa scale. The 48 models selected were randomly divided into a model group and an observation group, each of 24. Each group was further divided into 7d, 14d and 21d subgroups. 100μl of BMMCs (5×10⁶ /ml) were slowly injected into the ischemic lateral striata of the observation group. The rats in the model group were similarly injected, but with buffered saline solution. The rats were evaluated using the Longa scale after 7d, 14d and 21d. The rats were then sacrificed and the brain was resected. Immunohistochemical assays quantified the expression of GFAP and Nogo-A around the ischemic foci. Results: Compared with the model group, the rats in the observation group showed less neurological deficit on the 21st day, significantly greater expression of GFAP and significantly less Nogo-A expression on days 14 and 21. Nogo-A expression on the 21st day was also significantly lower than on the 14th day in the observation group. Conclusion BMMC transplantation can promote recovery from nerve damage after focal cerebral ischemia, which is probably related to enhanced expression of GFAP and restrained expression of Nogo-A in the brain tissues surrounding ischemic lesions.