Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups ( n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison. Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups( F=6.853-7.466, all P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(all P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(both P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (both P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups( F=3.826-15.440, all P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10 7, (24 133.33±1 242.04)×10 7), phosphatidylinositol (PI) ((788.78±136.11)×10 7, (953.65±131.26)×10 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10 7, (275.32±35.78)×10 7), creatine phosphate (CerP) ((239.65±18.14)×10 7, (293.82±38.28)×10 7), sphingosine (So) ((22.96±4.04)×10 7, (15.36±3.87)×10 7), diglyceride (DG) ((3.35±0.85)×10 7, (4.57±1.02)×10 7) and monoglyceride (MG) ((6.71±0.82)×10 7, (7.94±0.91)×10 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10 7, (509.22±42.09)×10 7) and acyl carnitine(AcCa) ((2.68±0.33)×10 7, (3.39±0.33)×10 7) decreased(both P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10 7, PI(83.16±91.52)×10 7, LPC(323.59±33.91)×10 7, CerP(236.39±32.02)×10 7, So(23.35±4.46)×10 7, DG(3.16±0.85)×10 7 and MG(7.03±0.26)×10 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10 7 and ACCA(2.56±0.32)×10 7 in the hippocampus of CUS+ rTMS group increased (all P<0.05). Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.

Objective To investigate the antidepressive?like effect of repetitive transcranial magnetic stimulation (rTMS) on the rats model exposing chronic unpredictable stress (CUS) and their nuclearfactor?E2?related factor2 (Nrf2) gene expression in hippocampus. Methods (1) SD rats were randomly assigned to the following 3 groups (n=8 for each group):Sham, CUS, CUS+rTMS. The Sham group received only Sham stimulation. The rats in the CUS and CUMS+ rTMS group were subjected to CUS stimulus, followed by 5Hz rTMS or Sham rTMS for 7 days. 24 h after the last stimulation, rats were given a sucrose preference test, an open filed test and a forced swim test. Finally the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus were determined by real?time PCR and western blot. (2) SD rats were randomly assigned to another 3 groups (n=8 for each group): scramble+CUS, scramble+ CUS+ rTMS and shNrf2+CUS+rTMS. Rats were injected with scramble or shNf2 lentivirus into the dentate gyrus. Two weeks later, all rats were subjected to CUS followed by rTMS or Sham rTMS stimulus for 7 days. Finally rats were given the series behavior tests, and the gene expression of hippocampal Nrf2, HO?1 and SOD?1 were then determined after being sacrificed. Results (1) In comparison with Sham, the rat in CUS group showed significant lower sucrose preference ((77.31 ± 4.69)％vs. (39.33 ± 11.85)％;F2, 21=8.32, P<0.01) and shorter centre time ((52.49±1.07) s vs. (14.70±4.27) s;F2, 21=3.84, P<0.01)) in the open filed test, but longer freezing time in the forced swim test ((24.19 ± 1.07 s vs. (38.70 ± 4.27);F2, 21=10.31, P<0.05);the expression of Nrf2, HO?1 and SOD?1 in the hippocampus was inhibited in the CUS rats. (2) Compared with CUS group, the rat in CUS+rTMS group showed significant better sucrose preference (P<0.05), longer centre time (P<0.05 in open filed test), while shorter freezing time in the forced swim test (P<0.05); the expression of Nrf2, HO?1 and SOD?1 in the hippocampus in CUS+rTMS rats was up?regulated (P<0.05);(3) Rats in shNrf2+CUS+rTMS group showed lower sucrose preference (P<0.05), shorter centre time (P<0.05) in the open filed test and longer freezing time in the forced swim test (P<0.05) and their expression of Nrf2, HO?1 and SOD?1 in the hippocampus (P<0.05) was down?regulated than rats in scramble+CUS+rTMS group. Conclusion rTMS administration may reverse depressive?like behaviors in rats under CUS paradigm and may restore the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus.

Objective To investigate the antidepressive?like effect of repetitive transcranial magnetic stimulation (rTMS) on the rats model exposing chronic unpredictable stress (CUS) and their nuclearfactor?E2?related factor2 (Nrf2) gene expression in hippocampus. Methods (1) SD rats were randomly assigned to the following 3 groups (n=8 for each group):Sham, CUS, CUS+rTMS. The Sham group received only Sham stimulation. The rats in the CUS and CUMS+ rTMS group were subjected to CUS stimulus, followed by 5Hz rTMS or Sham rTMS for 7 days. 24 h after the last stimulation, rats were given a sucrose preference test, an open filed test and a forced swim test. Finally the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus were determined by real?time PCR and western blot. (2) SD rats were randomly assigned to another 3 groups (n=8 for each group): scramble+CUS, scramble+ CUS+ rTMS and shNrf2+CUS+rTMS. Rats were injected with scramble or shNf2 lentivirus into the dentate gyrus. Two weeks later, all rats were subjected to CUS followed by rTMS or Sham rTMS stimulus for 7 days. Finally rats were given the series behavior tests, and the gene expression of hippocampal Nrf2, HO?1 and SOD?1 were then determined after being sacrificed. Results (1) In comparison with Sham, the rat in CUS group showed significant lower sucrose preference ((77.31 ± 4.69)％vs. (39.33 ± 11.85)％;F2, 21=8.32, P<0.01) and shorter centre time ((52.49±1.07) s vs. (14.70±4.27) s;F2, 21=3.84, P<0.01)) in the open filed test, but longer freezing time in the forced swim test ((24.19 ± 1.07 s vs. (38.70 ± 4.27);F2, 21=10.31, P<0.05);the expression of Nrf2, HO?1 and SOD?1 in the hippocampus was inhibited in the CUS rats. (2) Compared with CUS group, the rat in CUS+rTMS group showed significant better sucrose preference (P<0.05), longer centre time (P<0.05 in open filed test), while shorter freezing time in the forced swim test (P<0.05); the expression of Nrf2, HO?1 and SOD?1 in the hippocampus in CUS+rTMS rats was up?regulated (P<0.05);(3) Rats in shNrf2+CUS+rTMS group showed lower sucrose preference (P<0.05), shorter centre time (P<0.05) in the open filed test and longer freezing time in the forced swim test (P<0.05) and their expression of Nrf2, HO?1 and SOD?1 in the hippocampus (P<0.05) was down?regulated than rats in scramble+CUS+rTMS group. Conclusion rTMS administration may reverse depressive?like behaviors in rats under CUS paradigm and may restore the gene expression of Nrf2, HO?1 and SOD?1 in the hippocampus.

Objective To investigate the effect of quetiapine (QUE) on the memory and doublecortin (DCX) expression in the hippocampus of C57BL/6 mice with cuprizone (CPZ)-induced schizophrenia in C57BL/ 6 mice.Methods 1％ dimethyl sulfoxide (DMSO) was used as a vehicle to dissolve QUE.Three group of mice,16 in each of three groups,were treated with vehicle (control group),0.2％ CPZ alone (CPZ group) or 0.2％ CPZ combined with 10 mg· kg-1 · d-1 QUE (QUE+CPZ group) for six weeks,respectively.Spatial working memory was evaluated by Y-type maze test 24 hours after the completion of the treatment period.The number of DCX positivenew neurons was calculated by immunofluorescence staining assay.The expression of Notch1 and Hes1 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.Results (1) Y-maze test:CPZ group achieved a much lower percentage of correct alternation than control group ((22.70±6.70) ％ vs (57.69 ±6.70)％) in Y-maze test (P＜0.05).The percentage of correct alternation in CPZ + QUE group ((54.69± 10.06) ％) was significantly increased compared with CPZ group (P＜0.01).CPZ mice exhibited significant spatial working memory impairment.(2) Immunofluorescence staining:the number of DCX-positive cells in the hippocampus of the CPZ group (6342.85± 1801.72) was significantly decreased compared with that in control group (19428.57±2507.13) (P＜0.01),and it was reversed by QUE intervention (15928.57±2049.97).(3) RT-PCR:the Notch1 and Hes1 mRNA expression in CPZ group were significant lower than that in sham and CPZ + QUE group,(Notch1 (0.97±0.29) vs (0.23±0.20),P＜0.01);Hes1 (1.00±0.41) vs (0.38±0.30),P＜0.01),and there was no significant difference between sham group and CPZ + QUE group.Conclusion QUE is helpful to relieve CPZ-induced cognitive impairment and decreases expression of DCX in hippocampal,which may be related with activation of Notch1 pathway.

Objective To investigate the effects of gastrodin on neural function and the expression of myelin basic protein (MBP) and neurofilament high molecular weight (NFH) in the striatum during cerebral ischemiareperfusion in mice.Methods 36 Kunming mice were randomly divided into sham group,MCAO group and gastrodin (GAS) group.The middle cerebral artery occlusion(MCAO) was established by artery embolization.The mice in sham group were received fake surgery and saline,and the mice in MCAO and GAS group were exposed to MCAO,and received saline and GAS (100 mg/(kg · d)) injection,respectively,immediately after the operation for 7 days.On the 8th day of operation,the neurological severity scores of the mice were observed and the volume ratio of the cerebral infarction was estimated by triphenyl tetrazolium chloride (TTC) staining.Immunohistochemistry was used to detect the MBP and NF-H in the striatum.Results (1) The mice in MCAO group showed significant neurologic deficient in comparison with sham group,and the neurological severity scores of gastrodin group(3.13±0.64) were significantly higher than that(1.38±0.52) of MCAO group (P＜0.05).(2) Results of TTC staining showed that the infarction volume was obviously larger in the injured cerebral tissue in MCAO group in comparison with sham group,and the volume ratio of the cerebral infarction significantly decreased after the intervention with GAS (P＜0.05).(3) The integral optical density of MBP(272968.14±1215.23) and NF-H(12 142.73±47.16) in MCAO group decreased as compared to that((43 855.23±2434.16),(275 321.00±926.15)) in sham group and GAS group((321 531.2±2376.14),(106 135.73±598.15)) (P＜0.05).Conclusion GAS can improve neural function of mice after middle cerebral artery occlusion,and it may play an important role in protecting myelin and nerve fibers of striatum.

Objective To investigate the correlationship between depressed behaviors and interleukin-1β (IL-1β) in brain tissue in mice which are insensitive to fluoxetine,and to mimic the treatment resistant depression (TRD) in clinical condition.Methods 50 BALB/c mice were randomly divided into Control group (Control),Chronic unpredictable mild stress (CUMS) group and CUMS+fluoxetine group.Mice in Control group were raised ad libitum for 9 weeks,those in CUMS group received CUMS for 9 weeks and those in CUMS+fluoxetine group received 8 weeks' CUMS followed 1 week' s treatment with Fluoxetine(10 mg · kg-1 · d-1).At the end of the 9th week,mice in(CUMS + treatment)group were selected into antidepressant treatment-resistant mice(ATRM) as no remission and Depression Group (DM) as symptoms improved.Body mass test (BMT),open field test (OFT) and forces swim test (FST) were completed respectively in these 4 groups at the endpoint of the experiment,and the brain tissue were extracted after the tests for IL-1β Elisa test.Results (1) BMT:there was no effect of weightgain in ATRM after 1 week' s therapy with Fluoxetine.There was no difference in body-weight between ATRM ((18.56±7.56) g) and CUMS ((19.03± 8.58) g) mice,while compared with Control ((24.56±5.45) g) and DM mice ((20.12±9.17) g) ATRM and CUMS mile's body weight were significantly lower (P＜0.05).(2)OFT and FST:in OFT,there was no significant difference in of horizontal moving distance(F=0.355) either in the frequencies of entering the central zone (F=0.327) among the 4 groups;in OFT,the immobility time of ATRM ((241.50 ± ± 36.55) s) was significantly longer than that in DM ((156.00± 25.47) s) (F=13.573,P＜0.05).(3) Elisa test of IL-1β:the brain' s IL-1β serum level in ATRM ((164.90±46.70) pg/mg) was higher than those in Control ((69.68±6.56) pg/mg)),and DM ((93.09±4.65) pg/mg) (P＜0.01),while no difference with that in CUMS mice.Additionally,the depressive behaviors in ATRM showed its positive correlation with the IL-1β level in CNS (r=0.669,P=0.006).Conclusion CUMS can elicit the refractory depressive symptoms in BALB/c mice to simulate TRD' s characteristic,and the elevated level of IL-1 β within brain tissue may play an important role in the development of TRD.

Objective To investigate the effect of quetiapine on the behavior and expression of pERK1/2 in chronic unpredictable stress(CUS) model rats.Methods 32 adult male Sprague Dawley rats were randomly divided into four groups (n =8 for each group):control group,CUS group,CUS + QUE (5 mg/kg,L) group and CUS + QUE(10 mg/kg,M)group.The rats in control group were left undisturbed in their home cage for 28 days and the other groups were exposed to 28 consecutive days of CUS,then the rats in control group and CUS group were treated with 1％ DMSO in saline (5 ml/kg,intraperitoneal injection),the rats in CUS + QUE (L)group and CUS + QUE(M) group respectively treated with quetiapine (5 mg/kg)or quetiapine(10 mg/kg) for consecutive 7 days.The weight data of each group were recorded,and the behavioral changes in these rats were analyzed by open field test and forced swimming test;and the expression of pERK1/2 was measured by Western blot.Results (1)Compared with control group,quetiapine (10 mg/kg) ameliorated the inhibition of body weight gain that induced by chronic unpredictable stress (P ＜ 0.05),but quetiapine (5 mg/kg) did not have this effect.(2)Open field and Forced swimming test showed significant difference (P ＜ 0.05) of horizontal motion distance (F =17.846),the number of central region entering(F=4.720) and the immobility time(F=26.090) in each group.And these tests showed that horizontal motion distance and the number of central region entering in CUS group ((6696.30 ±1061.19)mm,(19.63 ±9.15)times) were significantly lower than that of control group ((10824.61 ± 1399.37) mm,(37.75 ± 13.02) times) and CUS + QUE (M) group ((9637.51 ± 1630.16) mm,(32.38 ± 6.23)),while the immobility time (110.73 ± 15.98)s were significantly higher than that of control group((66.13 ± 5.18)s)and CUS + QUE (M) group((73.40 ± 11.99) s,P ＜ 0.05).But there was no significant difference between that of CUS group and CUS + QUE(L) group(P＞0.05).(3)The expression of pERK1/2 in CUS group showed significant decrease when compared with control group or CUS + QUE (M) group,but showed no significant difference with CUS + QUE(L) group(F=6.641,P＜ 0.01).Conclusion Quetiapine can ameliorate depressive-like behaviors induced by chronic unpredictable stress,and this effect may be carried out by up-regulation the expression of pERK1/2 in the hippocampus.

Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the depressive like behaviors and expression of brain derived neurotrophic factor (BDNF),IL-1β and NF-κB of hippocampal in chronic unpredictable mild stress (CUMS) rats.Methods Thirty-two adult male rats were randomly divided into four groups (n =8):Control group,Control + rTMS group,CUMS group and CUMS + rTMS group.The sucrose preference test,forced swim test and open field test were used to evaluate depressive like behaviors for each groups.In addition,the expression of BDNF,NF-κB and IL-1 β in hippocampal were detected by western blot and ELISA after behavioral test,respectively.Results 1.The effects of rTMS on depressive like behaviors of CUMS rats:in the sucrose preference test,the sucrose preference rate of CUMS rats (0.67 ± 0.06) was significantly lower than Control group (0.91 ± 0.04),which was higher in the CUMS + rTMS group (0.83 ±0.08).In the forced swim test,the immobility time of CUMS group ((26.88 ± 11.33) s) was longer than Control group ((15.22 ± 6.75) s) and CUMS + rTMS group ((18.41 ± 6.95) s).In the open field test,both the total distance travelled and number of central area entry times of CUMS group((849.165 ± 769.01) cm,(7.42 ± 5.68))were significantly shorter ((6224.81 ± 1403.2) cm) and smaller (22.86 ± 3.72) than Control group,and those of the CUMS + rTMS were longer ((4105.57 ± 1516.92)cm) and larger (21.25 ± 3.45).All the behavioral results were statistically significant (P＜ 0.05).And of all the aforementioned behavioral parameters,there were no significant differences between Control group and Control + rTMS group(P＞0.05).2.The effects of rTMS on the hippocampal expressions of BDNF,NF-κB and IL-1β in CUMS rats:compared with Control group,the hippocampal expression of BDNF in CUMS rats was significantly decreased,while the expressions of NF-κB and IL-1β in the hippocampus were significantly increased (P＜ 0.05).Compared with CUMS group,the hippocampa expression of BD-NF in the CUMS + rTMS group was increased,and the expressions of NF-κB and IL-1β in the hippocampus was significantly decreased (P ＜ 0.05).The expressions of BDNF,NF-κB and IL-1β had no differences between Control group and Control + rTMS group.Conclusion rTMS increased the expression of BDNF,reduced the production of NF-κB and IL-1β,and alleviated depressive like behaviors in CUMS rats.