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 analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

OBJECTIVE To investigate the in vitro inhibitory mechanism of berberine on the proliferation of tumor stem cells and evaluate its in vivo safety. METHODS Flow cytometry was used to select tumor stem cells from mouse skin melanoma B16F10 cells； CD44， CD133， Nanog homologous box protein （NANOG） and octamer-binding transcription factor 4 （OCT4） were used as indicators to characterize tumor stem cells. Tumor stem cells were divided into control group， all-trans retinoic acid （ATRA） group， and berberine group， and the CCK-8 method was used to detect the effects of berberine on the viability of tumor stem cells； flow cytometry was adopted to detect cell apoptotic rate， the proportion of CD44+/CD133+ and the positive cell rate of sex determining region Y box protein 2 （SOX2）； the morphological changes of tumor balls were recorded after treatment with berberine； the morphology of cell pyroptosis in each group was recorded， and the release rate of lactate dehydrogenase （LDH） was detected； Western blot assay was adopted to detect the expressions of pyroptosis-related protein gasdermin E （GSDME）， GSDME- N， caspase-3 and cleaved caspase-3. Preliminary evaluation of in vivo safety of berberine was conducted by using zebrafish embryo toxicity experiments. RESULTS Compared with B16F10 cells， the proportion of CD44+/CD133+ cells in tumor stem cells and the fluorescence intensity of NANOG and OCT4 were significantly increased （P＜0.000 1）. The half-inhibitory concentration of berberine to tumor stem cells was 50.98 μmol/L. Compared with the control group， the apoptotic rate of cells in the berberine group was significantly increased， while the proportion of CD44+/CD133+ cells and the rate of SOX2 positive cells were reduced significantly （P＜0.000 1）； tumor stem cell spheroids were atrophied， with partial cell death. After treatment with berberine， tumor stem cells exhibited swelling in their outermost layer， the release rate of LDH of cells was significantly increased and the release rate of LDH increased with increasing dose； the protein expressions of GSDME-N and cleaved-caspase-3 of cells in berberine 20， 40 μmol/L groups were significantly increased， and the protein expressions of GSDME and caspase-3 were significantly reduced （except for berberine 20 μmol/L group， P＜0.05）. The embryonic development of zebrafish treated with berberine was almost unaffected， and the survival rate of embryo reached 100%， with no obvious abnormalities observed. CONCLUSIONS Berberine has good activity against the proliferation of tumor stem cells， and its mechanism of action may be related to activating GSDME and promoting cell pyroptosis； berberine has good in vivo safety.

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 analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

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.

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.

Objective: To establish the norm of the Physical Activity afterschool Questionnaire for Preschooler(P-PAQ) in urban areas of China, so as to provide a basis for graded guidance from the family perspective and to improve children s physical activity levels. Methods: From October 2020 to January 2021, 6 267 children aged 3-6 years old were recruited from 40 kindergartens in eight cities across six major administrative regions by stratified cluster sampling, and the P-PAQ initially developed by the researchers of this study were completed by the primary caregivers. The questionnaire was administered to collect data relating to the amount of physical activity undertaken by the preschoolers, and the norm was determined by quartiles. Data relating to parental concepts of sports and parental behavior were assessed by calculating mean scores in order to establish the norm. Results: Among preschoolers in urban areas, the M(P 25 ，P 75 ) of total physical activity time (min/day), moderate-to-vigorous physical activity time (min/day), outdoor time (min/day) and screen time (min/day) on school days outside kindergarten and on weekends were 84 (54,120), 22 (8,40), 12 (0,24) and 18 (6,30), and 170 (115,240), 60 (30,95), 90 (35,120) and 30 (20,60), respectively. When the score of parents sports concept and behavior (total score of 40) were≥34, 29-<34, 24-<29, <24, it was defined as four levels about above medium, medium, lower medium and lower, respectively. And for two dimensions，when the score of parental sports concept were ≥19, 17-<19, 15-<17, <15，and the score of parental behaviors were ≥16, 12-<16, 8-<12, <8, it was defined as four levels about upper medium, medium, lower medium and lower, respectively. Conclusion The norm of extracurricular activities among preschool children in Chinese cities has good representativeness and appropriate threshold values, which could provide a valuable reference for early assessment, as well as guidance in relation to out-of-school physical activity behaviors among children aged 3-6 years old.

Objective:To observe the preventive effects of infliximab in autoimmune hepatitis (AIH) and to explore its mechanism.Methods:The mice AIH model was established by injecting concanavalin A (Con-A) into the caudal vein. Forty mice were divided into prevention group and control group, with 20 mice in each group. The mice of prevention group were injected intravenously with infliximab (20 mg/kg) one hour before Con-A injection and the mice of control group were administrated with 200 μL phosphate buffered saline (PBS). Serum was collected 3, 8, 12 and 24 h after Con-A/PBS injection. The serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was detected by colorimetry. The level of cytokine interleukin (IL)-6, IL-1β, interferon gamma (IFN-γ), IL-4, IL-17A, IL-10 and chemokine C-X-C motif ligand 10 (CXCL10) was measured by enzyme-linked immunosorbent assay (ELISA). Liver samples were taken 12 h after Con-A/PBS injection for hematoxylin-eosin staining. Liver infiltrated lymphocytes were assessed by flow cytometry. The expression of T-box transcription factor 21 ( TBX21), GATA binding protein 3 ( GATA3), RAR related orphan receptor C ( RORC) and CXCL10 at mRNA level was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of CXCL10 in liver was detected by Western blotting. Paired t test and one-way analysis of variance were used for statistic analysis. Results:At 8, 12, and 24 h after Con-A injection, the serum ALT level, AST level, IL-1β and IFN-γ of prevention group were all lower than those of control group ((545.8±190.3) U/L vs. (865.8±237.7) U/L, (947.6±267.9) U/L vs. (1 448.0±403.5) U/L, (508.6±131.1) U/L vs. (976.6±207.6) U/L; (620.7±132.0) U/L vs. (952.9±106.8) U/L, (801.6±212.0) U/L vs. (1 424.8±236.0) U/L, (632.1±117.8) U/L vs. (1 008.3±187.5) U/L; (31.38±10.12) ng/L vs. (48.12±11.53) ng/L, (39.34±11.40) ng/L vs. (60.00±14.17) ng/L, (29.49±8.22) ng/L vs. (46.89±5.50) ng/L; and (432.93±66.82) ng/L vs. (674.66±97.88) ng/L, (655.09±169.17) ng/L vs. (937.90±166.36) ng/L, (263.40±54.97) ng/L vs. (410.74±86.64) ng/L), and the differences were statistically significant ( t = 2.350, 2.308, 4.263, 4.374, 4.860, 3.806, 2.440, 2.541, 3.939, 4.560, 2.660 and 3.210; all P<0.05). The serum IL-6 levels 3, 8, 12 and 24 h after Con-A injection of prevention group were all lower than those of control group ((1 075.79±303.77) ng/L vs. (1 914.48±317.80) ng/L, (1 945.97±271.85) ng/L vs. (2 100.80±378.42) ng/L, (1 578.60±504.54) ng/L vs. (2 525.40±406.55) ng/L, (1 020.64±280.03) ng/L vs. (1 582.00±311.96) ng/L), and the differences were statistically significant ( t=4.266, 2.903, 3.267 and 2.994; all P < 0.05). At 3 h after Con-A injection, serum CXCL10 level and CXCL10 mRNA expression in liver tissues of prevention group were both lower than those of control group ((1 755.8±148.1) ng/L vs. (2 102.0±334.0) ng/L and 7.20±3.00 vs. 27.60±1.90), and the differences were statistically significant ( t=2.356 and 2.623, both P<0.05). At 3 and 8 h after Con-A injection, T- bet expression at mRNA level in liver tissues of prevention group was lower than that of control group (6.94±2.29 vs. 15.20±3.48 and 9.38±3.48 vs. 18.17±4.48), and the differences were both statistically significant ( t = 4.427 and 3.673, both P<0.05). However, 3, 8, 12 and 24 h after Con-A injection, there were no statistically significant differences in serum IL-4, IL-17A, IL-10, or GATA3 or RORC expression at mRNA level between prevention group and control group (all P > 0.05). Conclusions:Infliximab has certain preventive effects in mice AIH model, which may be achieved by antagonizing TNF-α and decreasing the expression of CXCL10 in liver, reducing the infiltration of T-helper 1 cells and CD8 + T cells into liver, and by reducing T lymphocyte activation induced by inflammatory cytokines thus alleviating the damage of T lymphocytes to hepatocytes.

OBJECTIVE：To know about the research status of health utility value obtained by mapping method in pharmacoeconomic evaluation ，and to provide reference for bibliometric study in pharmacoeconomic evaluation . METHODS ： Using“Mapping method ”“Health utility value ”“Cost-utility”“Utility point system ”as Chinese and English keywords ，retrieved from CNKI ，Wanfang database ，PubMed，Medline，Ebsco，Ovid and Wiley database ，empirical journal documents published from the inception to Dec. 31st，2018 about using mapping method to obtain health utility value were collected. The bibliometrics was used to statistically analyze basic information of included literature ，the construction and test of the model ，the type of the best model and so on. RESULTS ：The 124 included documents were all published in English journal. In the construction and testing of the mapping model ，the most frequently used econometric methods ，performance evaluation indicators and model testing methods were ordinary least squares （OLS），mean absolute error （MAE）and residual normality test ，application frequency of which were 97 times（31.60％），89 times（24.93％）and 62 times（21.09％）. There are 117 articles that define the best mapping model ，of which 101 articles（86.32％）have the best direct mapping effect. Most of the non-utility measurement scales adopted specific scales （92 articles，77.97％），and a few literatures adopted the universal scale （26 articles，22.03％）. The most utility measurement scales were 3-level European 5-dimensional health scale （79 articles，66.95％）. CONCLUSIONS ：The domestic empirical researches that use the mapping method to obtain health utility values need to be developed yet. A series of mapping models successfully developed by foreign scholars not only provide the feasibility of using non-utility measurement scales for cost-utility analysis ，but also provide more ideas for China to choose the corresponding econometric methods ，evaluation indicators and mapping methods in the empirical research of the mapping method in the future.