Objective:To investigate the distribution of iron deposition in the substantia nigral (SN) subregions on quantitative susceptibility mapping (QSM) and the change of swallow tail sign (STS) in patients with relapsing-remitting multiple sclerosis (RRMS) of different disease stages.Methods:The clinical and imaging data of 53 patients with RRMS (case group) diagnosed at the First Hospital of Chongqing Medical University from November 2019 to December 2021 were retrospectively analyzed. The case group was divided into 0-5 years subgroup, 6-10 years subgroup, and >10 years subgroup according to the disease duration; another 37 age-and gender-matched healthy volunteers were recruited as the control group during the same period. All subjects underwent MRI and QSM reconstruction. First, the SN was divided into four subregions: rostral anterior-SN (aSNr), rostral posterior-SN (pSNr), caudal anterior-SN (aSNc), and caudal posterior-SN (pSNc) on the QSM, and the quantitative susceptibility value (QSV) of each subregion was measured, and then the STS of the SN was observed and scored on the susceptibility weighted imaging (SWI) generated by post-processing. ANOVA was used to compare the differences in the QSV of each subregion of SN among the groups, and the probability of abnormal STS was compared using the χ 2 test. Spearman′s test was used to analyze the correlation between the QSV of each subregion of SN and the STS score. Results:The differences in QSV of aSNr, pSNr, aSNc, and pSNc were statistically significant among the 0-5 years subgroup, 6-10 years subgroup,>10 years subgroup of RRMS patients and the control group ( P<0.05). The QSV of aSNr, pSNr, and aSNc in 0-5 years subgroup was higher than those in the control group ( P was 0.039, 0.008, 0.039, respectively). The QSV of aSNr, aSNc, and pSNc in the 6-10 years subgroup were higher than those in the 0-5 years subgroup ( P was <0.001, 0.020, 0.015, respectively). The QSV of the aSNc, pSNc in >10 years subgroup were lower than those in the 6-10 years subgroup ( P=0.037, 0.006). The QSV of aSNr, pSNr in >10 years subgroup were higher than those in the control group ( P was <0.001, 0.001). There were 7 cases of abnormal STS in the 0-5 years subgroup, 11 cases in the 6-10 years subgroup, 12 cases in >10 years subgroup, and 9 cases in the control subgroup, and there was a statistically significant difference in the probability of abnormal STS among the subgroups of the RRMS patients and the control subgroup (χ 2=16.20, P=0.011). Both the scores of STS in the 6-10 years subgroup and >10 years group were positively correlated with the QSV in pSNc ( r s=0.65, P=0.006; r s=0.48, P=0.045). Conclusions:In RRMS patients, SN iron deposition is concentrated on aSNr, pSNr, and aSNc in the 0-5 years subgroup and on aSNr, aSNc and pSNc in the 6-10 years subgroup. The QSVs of all SN subregions have a downward trend in >10 years subgroup compared with that in the 6-10 years subgroup. Both the QSVs of the pSNc in the 6-10 years group and >10 years group are positively related to STS scores. These help explore the potential progression pattern of SN iron deposition in RRMS patients and the cause of abnormal STS in RRMS patients.

Objective:To explore the alteration of structural network, cognitive scores in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, as well as the relationship between cognitive impairment and changes of structural networks in patients with NMDAR encephalitis.Methods:This study was a retrospective study. A total of 39 patients with anti-NMDAR encephalitis were recruited as the autoimmune encephalitis group (AE group) from the First Affiliated Hospital of Chongqing Medical University between September 2012 to December 2019, and 32 healthy volunteers with normal results of routine head MR examinations and no history of central nervous system diseases were recruited as the health control group (HC group). There were 16 males and 23 females, aged from 13 to 66 (34±15) years, with duration of disease from 11 to 110 (31±20) days in AE group, and there were 16 males and 23 females, aged from 13 to 66 (34±15) years in HC group. All subjects underwent diffusion tensor imaging (DTI) scan and cognitive function evaluation. The brain structural networks of two groups were constructed by deterministic fiber tracking techniques, and the differences of global topological properties [clustering coefficient (C p), shortest path length (L p), local efficiency (E loc), global efficiency (E glob), normalized C p (γ), normalized L p (λ), small-worldness (σ)] and local topological properties between two groups were analyzed by the graph theory approch. The correlations between characteristics of brain structural networks and cognitive function scores were further analyzed. Results:There was no significant difference in age and gender distribution between the AE group and HC group ( P>0.05). The C p [0.005(0.004, 0.007)], γ (1.76±0.13), λ (0.51±0.03) and σ value (1.57±0.13) of AE group were decreased when compared with HC group [the values were 0.007(0.004,0.017), 2.13±0.63, 0.55±0.06 and 1.73±0.36 each] ( Z=-939.00, t=-3.58, t=-4.16, t=-2.58, P<0.05). Compared with HC group, nodal efficiencies in the left middle frontal gyrus (orbital part), left and right supplementary motor areas, left olfactory cortex, left gyrus rectus, bilateral insula, left postcentral gyrus, left paracentral lobule and right heschl gyrus were changed ( P<0.05). There were five identical hub regions which contains the left middle occipital gyrus, bilateral supplementary motor areas and precuneus in both groups. However, in the AE group, three hub regions of the left middle occipital gyrus and bilateral middle temporal gyrus were reduced, and the left precentral gyrus was increased as hub region. The nodal efficiencies of the left supplementary motor areas ( r=0.393, P=0.013), right supplementary motor areas ( r=0.384, P=0.016) and left paracentral lobule ( r=0.356, P=0.026) were positively correlated with the montreal cognitive assessment scores. Conclusion:The white matter is extensively impaired in anti-NMDAR encephalitis patients and the changes of topological properties in several brain regions are correlated with cognitive decline.

Objective To explore the inhibitory effect ORY-1001,a lysine-specific histone demethylase 1(LSD1)inhibitor,on growth of glioblastoma(GBM)and the underlying mechanism.Methods We analyzed LSD1 expressions in GBM and normal brain tissues based on data from TCGA and HPA databases.Female BALB/c mouse models bearing xenografts derived from U87 cells or cells with lentivirus-mediated LSD1 silencing or Notch overexpression were treated with saline or 400 μg/kg ORY-1001 by gavage every 7 days,and GBM formation and survival time of the mice were recorded.The effect of ORY-1001 on GBM cell viability was assessed,and its effect on LSD1 expression was analyzed with Western blotting.The genes and pathways associated with LSD1 were analyzed using bioinformatics methods.Western blotting and qRT-PCR were used to detect Notch/HES1 pathway expression after LSD1 silencing and ORY-1001 treatment.The impact of ORY-1001 on viability of U87 cells with Notch1 silencing or overexpression was assessed,and the regulatory effects of ORY-1001 on Notch/HES1 pathway were analyzed using chromatin immunoprecipitation assay.Results A high expression of LSD1 in GBM was negatively correlated with patient survival(P<0.001).ORY-1001 and LSD1 silencing obviously reduced tumor burden and prolonged the survival time of GBM-bearing mice.ORY-1001 treatment significantly inhibited the viability and dose-dependently decreased LSD1 expression in GBM cells,and such inhibitory effect of ORY-1001 was attenuated by LSD1 silencing.The Notch pathway enriched the differential genes related to LSD1,and Notch/HES1 pathway expression was significantly down-regulated after LSD1 silencing and ORY-1001 treatment.Notch1 overexpression significantly attenuated the anti-tumor effect of ORY-1001 on GBM.Mechanistically,ORY-1001 disrupted the interaction between LSD1 and the Notch pathway target genes including Notch3,HES1 and CR2.Conclusion ORY-1001 down-regulates the Notch/HES1 pathway by inhibiting LSD1 expression to suppress the growth of GBM in mice.

Objective To explore the inhibitory effect ORY-1001,a lysine-specific histone demethylase 1(LSD1)inhibitor,on growth of glioblastoma(GBM)and the underlying mechanism.Methods We analyzed LSD1 expressions in GBM and normal brain tissues based on data from TCGA and HPA databases.Female BALB/c mouse models bearing xenografts derived from U87 cells or cells with lentivirus-mediated LSD1 silencing or Notch overexpression were treated with saline or 400 μg/kg ORY-1001 by gavage every 7 days,and GBM formation and survival time of the mice were recorded.The effect of ORY-1001 on GBM cell viability was assessed,and its effect on LSD1 expression was analyzed with Western blotting.The genes and pathways associated with LSD1 were analyzed using bioinformatics methods.Western blotting and qRT-PCR were used to detect Notch/HES1 pathway expression after LSD1 silencing and ORY-1001 treatment.The impact of ORY-1001 on viability of U87 cells with Notch1 silencing or overexpression was assessed,and the regulatory effects of ORY-1001 on Notch/HES1 pathway were analyzed using chromatin immunoprecipitation assay.Results A high expression of LSD1 in GBM was negatively correlated with patient survival(P<0.001).ORY-1001 and LSD1 silencing obviously reduced tumor burden and prolonged the survival time of GBM-bearing mice.ORY-1001 treatment significantly inhibited the viability and dose-dependently decreased LSD1 expression in GBM cells,and such inhibitory effect of ORY-1001 was attenuated by LSD1 silencing.The Notch pathway enriched the differential genes related to LSD1,and Notch/HES1 pathway expression was significantly down-regulated after LSD1 silencing and ORY-1001 treatment.Notch1 overexpression significantly attenuated the anti-tumor effect of ORY-1001 on GBM.Mechanistically,ORY-1001 disrupted the interaction between LSD1 and the Notch pathway target genes including Notch3,HES1 and CR2.Conclusion ORY-1001 down-regulates the Notch/HES1 pathway by inhibiting LSD1 expression to suppress the growth of GBM in mice.