Objective: The effects and molecular mechanisms of micheliolide on cytokine expression in myeloproliferative neoplasm cell lines were explored based on the signal transducer and activator of transcription 3 (STAT3)/nuclear factor-kappa B (NF-κB) signaling pathways. Methods: The UKE-1 and SET-2 cell lines were investigated, and micheliolide concentrations were screened using the CCK-8 assay. The UKE-1 and SET-2 cells were divided into the control and micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Each group received 1 mL of micheliolide solution at final concentrations of 2.5, 5.0, and 10.0 μmol/L, respectively, whereas the control group only received an equal volume of culture medium. The inhibition rates of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), and chemokine ligand 2 (CCL2) mRNA expression in cells from each group were detected using real-time fluorescent PCR (RT-PCR). Western blotting was used to measure STAT3 and phosphorylated STAT3 (p-STAT3) protein expression levels in cells from each group. Reversal experiments with reduced glutathione and dithiothreitol were performed using UKE-1 cells, which were divided into the control group, micheliolide, micheliolide + glutathione, micheliolide + dithiothreitol, and glutathione + dithiothreitol groups. Western blotting was used to detect the STAT3 and p-STAT3 protein expression levels in the cells of each group. UKE-1 cells were stimulated with TNF-α (5 μg/L) to replicate a pathological model of excessive cytokine secretion. Subsequently, UKE-1 cells were divided into the control, model, and three micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. RT-PCR was used to measure the indicators above. An enzyme-linked immunosorbent assay (ELISA) was used to detect the CCL2 content in the cell culture media of each group. Western blotting was performed to assess the protein expression levels of STAT3, p-STAT3, and proteins related to the NF-κB signaling pathway. Results: Compared with the control group, the proliferation inhibition rates of UKE-1 cells at 24, 48, and 72 h increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, 10.0, and 20.0 μmol/L. Similarly, the proliferation inhibition rates of SET-2 at 48 and 72 h increased in the micheliolide-treated groups at concentrations of 5.0, 10.0, and 20.0 μmol/L (P<0.05). Concentrations of 2.5, 5.0, and 10.0 μmol/L were selected for further studies to exclude the potential influence of high micheliolide concentrations on subsequent result owing to reduced cell numbers. Compared with the control group, the inhibition rates of TNF-α mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Similarly, the inhibition rates of IL-1β mRNA expression in UKE-1 and SET-2 cells also increased in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L. Additionally, the inhibition rate of CCL2 mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated group at a concentration of 10 μmol/L (P<0.05). Compared with the model group, the inhibition rates of TNF-α, IL-1β, and CCL2 mRNA expression in UKE-1 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L after stimulation with TNF-α (P<0.05). ELISA showed that compared with the control group, the CCL2 content in UKE-1 cells increased in the model group. Compared with the model group, the CCL2 content in UKE-1 cells decreased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L (P<0.05). Western blotting showed that compared with the control group, the p-STAT3 protein expression levels in UKE-1 and SET-2 cells were downregulated in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L, and the protein expression level of STAT3 in SET-2 was also downregulated (P<0.05). Compared with the control group, the p-STAT3 expression level in UKE-1 cells decreased in the micheliolide group in the reductive glutathione and dithiothreitol reversal experiments. Compared with the micheliolide group, the p-STAT3 protein expression levels in UKE-1 cells increased in the micheliolide + dithiothreitol and micheliolide + glutathione groups (P<0.05). Compared with the control group, the model group showed increased p-STAT3, p-IκKα/β, p-IκBα, and p-NF-κB p65 protein expression and decreased IκBα protein expression after stimulation with TNF-α. Compared with the model group, the micheliolide-treated groups showed decreased p-IκKα/β, p-IκBα, p-STAT3, and p-NF-κB p65 protein expression at concentrations of 2.5, 5.0, and 10.0 μmol/L, whereas the micheliolide-treated groups showed increased IκBα protein expression at concentrations of 5.0 and 10.0 μmol/L (P<0.05). Conclusion Micheliolide potently suppresses IL-1β, TNF-α, and CCL2 mRNA expression in UKE-1 and SET-2 cells, as well as CCL2 secretion by UKE-1 cells, which may be associated with STAT3 phosphorylation suppression and NF-κB signaling pathway activation.

Objective:To explore the heterogeneity in the trajectories ofperinatal depressive symptoms and identify the related factors.Methods:A longitudinal follow-up study was conducted from January 2020 to June 2021.Baseline information,marriage satisfaction and social support status were collected at enrolment.Perinatal de-pressive symptoms were measured using the Edinburgh Postnatal Depression Scale(EPDS)at five time-points from second trimester to three-months postpartum.A Latent Class Growth Model(LCGM)was used to identify sub-groups of perinatal depressive symptoms trajectories and logistic regression was applied to examine associated risk and protective factors.Results:Two latent depression trajectory subgroups were identified A majority(72.2％,n=1 023)followed a curvilinear trajectory with low baseline scores that increased over time(curvilinear group),while 27.8％(n=393)maintained high,stable scores(linear group).Older age,higher marital satisfaction,and stronger social support were associated with a lower likelihood of belonging to the linear group(OR=0.96,0.94,0.89,re-spectively),while a personal or family history of depression increased this likelihood(OR=2.50,6.51).Conclusion:Trajectories of perinatal depressive symptoms vary significantly among individuals.The risk of persis-tent high-level symptoms is lowered by older age,stronger marital satisfaction,and greater social support,and heightened by a personal or family history of depression.

Purpose To investigate the value of automated segmentation technique for quantitative study of the volume of each subregion of medial temporal lobe epilepsy(MTLE)with hippocampal sclerosis(HS).Materials and Methods A total of 37 patients with unilateral HS diagnosed by MRI or pathologically confirmed in General Hospital of Ningxia Medical University from January 2021 to May 2023 were prospectively included,including 24 cases of left-sided HS(L-HS)and 13 cases of right-sided HS(R-HS),and 42 healthy volunteers matched in gender and age during the same period were included as a control group.All subjects underwent T1-weighted equal voxel three-dimensional magnetisation-prepared rapid gradient-echo(3D T1 MP-RAGE)scanning.3D T1 MP-RAGE was post-processed by Freesurfer V7 to obtain volume data of the hippocampus and its subregions.The volume data were normalized and the volume asymmetry index was calculated.Within-group and between-group comparisons were performed for standardized volumes of the hippocampus and its subregions,and between-group comparisons were performed for volume asymmetry index values.The diagnostic efficacy of the two indices was assessed and compared using the subject operating characteristic curve and area under the curve.Results The volumes of the hippocampus and its subregions on the affected side were smaller than those on the contralateral side in both the L-HS and R-HS groups,and the volumes of the left hippocampus and its subregions were smaller than those on the right side in the control group,and the differences were statistically significant(t/Z=-15.159-8.324,all P＜0.05).The volumes of the left side of the hippocampus and its subregions in the L-HS group were smaller than those of the left hippocampus and its subregions in the R-HS group and in the control group,and the volumes of the right side of the hippocampus and its subregions in the R-HS group were smaller than those of the L-HS group and the right hippocampus and its subregions of the control group,and the differences were statistically significant(P＜0.05).The differences in the volumes of the right side of the L-HS group and the left side of the R-HS group and the corresponding side of the control group were not statistically significant(P＞0.05).The differences in the volume asymmetry index values of the L-HS group compared with those of the R-HS group and the control group,and those of the R-HS group compared with those of the control group were all statistically significant(P＜0.05).Except for the diagnostic efficacy of volume asymmetry index values of the hippocampus and subiculum in the L-HS group,which was better than that of the volume,and the difference was statistically significant(Z=2.035,1.989,both P＜0.05),the comparison of the volume and volume asymmetry index values of each volume and volume asymmetry index value of the rest of the hippocampus and subregion was not statistically significant(P＞0.05).Conclusion The automatic segmentation technique is of great value for the quantitative study of hippocampus and its subregion volume in MTLE-HS,which can provide more accurate imaging reference for clinical practice.

Objective:To explore the heterogeneity in the trajectories ofperinatal depressive symptoms and identify the related factors.Methods:A longitudinal follow-up study was conducted from January 2020 to June 2021.Baseline information,marriage satisfaction and social support status were collected at enrolment.Perinatal de-pressive symptoms were measured using the Edinburgh Postnatal Depression Scale(EPDS)at five time-points from second trimester to three-months postpartum.A Latent Class Growth Model(LCGM)was used to identify sub-groups of perinatal depressive symptoms trajectories and logistic regression was applied to examine associated risk and protective factors.Results:Two latent depression trajectory subgroups were identified A majority(72.2％,n=1 023)followed a curvilinear trajectory with low baseline scores that increased over time(curvilinear group),while 27.8％(n=393)maintained high,stable scores(linear group).Older age,higher marital satisfaction,and stronger social support were associated with a lower likelihood of belonging to the linear group(OR=0.96,0.94,0.89,re-spectively),while a personal or family history of depression increased this likelihood(OR=2.50,6.51).Conclusion:Trajectories of perinatal depressive symptoms vary significantly among individuals.The risk of persis-tent high-level symptoms is lowered by older age,stronger marital satisfaction,and greater social support,and heightened by a personal or family history of depression.

Purpose To investigate the value of automated segmentation technique for quantitative study of the volume of each subregion of medial temporal lobe epilepsy(MTLE)with hippocampal sclerosis(HS).Materials and Methods A total of 37 patients with unilateral HS diagnosed by MRI or pathologically confirmed in General Hospital of Ningxia Medical University from January 2021 to May 2023 were prospectively included,including 24 cases of left-sided HS(L-HS)and 13 cases of right-sided HS(R-HS),and 42 healthy volunteers matched in gender and age during the same period were included as a control group.All subjects underwent T1-weighted equal voxel three-dimensional magnetisation-prepared rapid gradient-echo(3D T1 MP-RAGE)scanning.3D T1 MP-RAGE was post-processed by Freesurfer V7 to obtain volume data of the hippocampus and its subregions.The volume data were normalized and the volume asymmetry index was calculated.Within-group and between-group comparisons were performed for standardized volumes of the hippocampus and its subregions,and between-group comparisons were performed for volume asymmetry index values.The diagnostic efficacy of the two indices was assessed and compared using the subject operating characteristic curve and area under the curve.Results The volumes of the hippocampus and its subregions on the affected side were smaller than those on the contralateral side in both the L-HS and R-HS groups,and the volumes of the left hippocampus and its subregions were smaller than those on the right side in the control group,and the differences were statistically significant(t/Z=-15.159-8.324,all P＜0.05).The volumes of the left side of the hippocampus and its subregions in the L-HS group were smaller than those of the left hippocampus and its subregions in the R-HS group and in the control group,and the volumes of the right side of the hippocampus and its subregions in the R-HS group were smaller than those of the L-HS group and the right hippocampus and its subregions of the control group,and the differences were statistically significant(P＜0.05).The differences in the volumes of the right side of the L-HS group and the left side of the R-HS group and the corresponding side of the control group were not statistically significant(P＞0.05).The differences in the volume asymmetry index values of the L-HS group compared with those of the R-HS group and the control group,and those of the R-HS group compared with those of the control group were all statistically significant(P＜0.05).Except for the diagnostic efficacy of volume asymmetry index values of the hippocampus and subiculum in the L-HS group,which was better than that of the volume,and the difference was statistically significant(Z=2.035,1.989,both P＜0.05),the comparison of the volume and volume asymmetry index values of each volume and volume asymmetry index value of the rest of the hippocampus and subregion was not statistically significant(P＞0.05).Conclusion The automatic segmentation technique is of great value for the quantitative study of hippocampus and its subregion volume in MTLE-HS,which can provide more accurate imaging reference for clinical practice.

Purpose To evaluate the consistency and repeatability of cerebral blood flow(CBF)values measured by automatic segmentation of region of interest(ROI)and arterial spin labeling(ASL)functional image fusion in hippocampal sclerosis patients with medial temporal lobe epilepsy.Materials and Methods From January 2021 to October 2022,a total of 52 patients with medial temporal lobe epilepsy confirmed by MRI or pathology in General Hospital of Ningxia Medical University were retrospectively collected.All subjects were scanned on 3.0T MRI to obtain axial T1 weighted three-dimensional magnetization reserve gradient echo(3D-T1W1-MPGAGE)sequence and three-dimensional pseudo continuous ASL sequence.The 3D-T1W1-MPGAGE imaging were automatically segmented.Two physicians used the freeview visualization interface of freeSurfer software to fuse the ROI and ASL functional images of the hippocampal subregions and to measure the CBF values.The intra-observer and inter-observer consistency and repeatability were evaluated and analyzed.The consistency analysis and repeatability evaluation were performed via intraclass correlation coefficient(ICC),Bland-Altman diagram and Wilcoxon rank sum test.Results The ICC of CBF values measured by two physicians were all>0.750,with an average of 0.868±0.095.The ICC of left and right hippocampal subregions were as follows:subiculum(SUB):0.818/0.801,cornu ammonis(CA)1:0.920/0.907,CA2-3:0.759/0.978,CA4:0.757/0.758 and dentate gyrus(DG):0.990/0.991;The ICC delineated by the same physician's ROI were all>0.990 with an average of 0.994±0.002.The ICC of left and right hippocampal subregions were as follows:SUB:0.993/0.993,CA1:0.996/0.995,CA2-3:0.989/0.994,CA4:0.992/0.995 and DG:0.993/0.996.The Bland-Altman diagram showed the scatter distribution and consistency,and the coefficient of repeatability was obtained.The same observer had certain repeatability for the fusion measurement of automatic segmentation ROI and ASL functional images.Conclusion The CBF values measured by fusing ROI and ASL functional images of automatically segmented hippocampal subregion have higher consistency and repeatability.

Objective To explore the hippocampal(HC)microstructural changes in patients with unilateral temporal lobe epilepsy(TLE)by neurite orientation dispersion and density imaging(NODDI).Methods The NODDI indexes of the whole HC and HC subregions of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)patients,non-HS patients and healthy controls(control group)were calculated.The differences of NODDI indexes among and within the three groups were compared,and the correlation between the difference indexes and the clinical characteristics of the patients was analyzed.Results A total of 47 patients with TLE(27 cases of TLE-HS,20 cases of non-HS)and 22 cases of healthy controls were enrolled.In the TLE-HS group,the free-water isotropic vol-ume fraction(fiso)values of the HC and granular cell layer of dentate gyrus(GC-DG)subregions of the affected side were signifi-cantly higher than those of the contralateral side;the orientation dispersion index(ODI)values of the CA1 and CA4 subregions were significantly lower than those of the contralateral side;and the neurite density index(NDI)values of the HC,CA1,CA2-3,CA4 and GC-DG subregions of the affected side decreased significantly.There was no significant difference between the affected side and the contralateral side in the non-HS group.The fiso values of the HC and GC-DG subregions of the affected side in the TLE-HS group were significantly higher than those in the control group,the ODI values of the HC CA1 subregions of the affected side in the TLE-HS group were significantly lower than those in the control group and the non-HS group,the NDI values of the HC and subiculum(Sub),CA1,CA4 and GC-DG subregions of the affected side in the TLE-HS group were significantly lower than those in the con-trol group,and the NDI values of the HC and CA1,CA4 and GC-DG subregions of the affected side in the non-HS group were significantly lower than those in the control group.In the TLE-HS group,the NDI value of the HC CA4 subregion of the affected side was negatively correlated with the disease course,but there was no clear correlation between other subregion variables and disease course,onset frequency and duration of single onset.Conclusion NODDI technique has the ability to detect the microstructural changes of HC in patients with TLE,among which NDI is more likely to highlight neuronal damage and fiber reorganization in patients with TLE.

Objective To explore the value of automatic segmentation technique combined with neurite dispersion and density imaging(NODDI)for displaying volume and microstructure changes of hippocampal subregion in patients with hippocampal sclerosis medial temporal lobe epilepsy(mTLE-HS).Methods MRI data of 33 patients with left mTLE-HS(mTLE-HS group)and 35 healthy adults(control group)were retrospectively analyzed.The hippocampal subregions were automatically segmented using FreeSurfer software,the volume of cornu Ammonis(CA)1,CA2-3,CA4,granulose cell-dentate gyrus(GC-DG)and subiculum were measured,then the NODDI parameters of each subregion were obtained through post-processing.The intra-and inter-groups hippocampal subregion volumes and NODDI parameters were compared,and the correlations of parameters being significantly different with the onset age and disease courses were analyzed.Results The volume of hippocampal subregions in mTLE-HS group were all lower than those in control group(all P＜0.05).In mTLE-HS group,the neurite density index(NDI)of left CA1 and CA4 subregions were both lower,while the free-water isotropic volume fraction(fiso)of the left CA1 subregion was higher than those of the right side(all P＜0.05).The orientation dispersion index(ODI)of left CA1,CA2-3 and CA4 subregions,as well as NDI of left CA1,CA4 and GC-DG subregions in mTLE-HS group were all lower than those in control group(all P＜0.05),while fiso of left CA1,GC-DG and subiculum subregions in mTLE-HS group were all higher than those in control group(all P＜0.05).The volume of left hippocampal subregions in patients with mTLE-HS were all moderately positively correlated with the onset age(r=0.540-0.667,all P＜0.001)but weakly negatively correlated with disease courses(r=-0.492--0.386,all P＜0.05).NDI of left CA4 and GC-DG subregions in patients with mTLE-HS were both weakly negatively correlated with disease courses(r=-0.418,-0.388,both P＜0.05).Conclusion Automatic segmentation technique combined with NODDI could be used to display the volume and microstructure changes of mTLE-HS.NDI might be a biomarker of mTLE-HS being sensitive to progressive neuronal damage.

Human myelination begins in the fifth month of fetal development and continues after birth.Myelin development plays a key role in establishing and maintaining information conduction,coordination and communication within the brain,so prenatal quantitative assessment of myelin development is important.In recent years,many MRI techniques for myelin imaging have been developed and implemented,and quantitative MRI assessment of fetal myelin development has received increasing attention.In this review,we discuss the known structural and functional changes in the development of the myelin sheath of the fetal central nervous system,and review the research progress and future expectations of quantitative fetal MRI imaging.

Purpose To investigate the changes of cerebral cortex thickness in adult temporal lobe epilepsy(TLE)assessed by Freesurfer automatic segmentation technique.Materials and Methods Eighty-four TLE confirmed by clinical manifestations and electroencephalography from January 2021 to September 2023 in General Hospital of Ningxia Medical University were retrospectively collected,including 32 patients with MRI nonlesional TLE,30 patients with left hippocampal sclerosis,and 22 patients with right hippocampal sclerosis.Fifty volunteers were recruited as the control group.All the ascending axial T1WI three-dimensional magnetization pre-gradient echo scans were performed.Freesurfer software was used to segment the cerebral cortex of T1W images,the cortical thickness values of different types of TLE patients were analyzed and compared.Results Compared with the control group,the cortical thickness of 14 regions in MRI-negative TLE group decreased,mainly located in bilateral frontal lobe and right parietal lobe,and the difference was statistically significant(P＜0.05);cortical thickness decreased in 34 regions in the left hippocampal sclerosis group,mainly located in the bilateral frontal,temporal and parietal lobes,the difference was statistically significant(P＜0.05);the cortical thickness of 27 regions in the right hippocampal sclerosis group decreased,mainly located in the bilateral frontal,parietal lobe and right temporal lobe,and the difference was statistically significant(P＜0.05).Conclusion The automatic segmentation technique can evaluate the thickness changes of different cortical regions in the brain of patients with different types of TLE,which is helpful to further understand the development of TLE and provide value for better treatment or preoperative evaluation.