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Objective:To investigate the value of quantitative parameters of magnetic resonance imaging (MRI) in predicting the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for children and adolescents with mature aggressive B-cell non-Hodgkin lymphoma (NHL).Methods:It was a retrospective multicenter study.Clinical data of 44 children and adolescents diagnosed with mature aggressive B-cell NHL between January 2016 and January 2023 in Henan Cancer Hospital, Beijing Gaobo Boren Hospital, and the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed.Patients were divided into complete response (CR) group and non-CR group based on the international criteria for the diagnosis of pediatric NHL.Quantitative parameters of MRI, including T2 signal intensity, the minimal apparent diffusion coefficient (ADCmin), maximal ADC (ADCmax), and the mean ADC (ADCmean) were measured before and within 2 weeks after CAR-T infusion.The correlation between the above parameters and the achievement of CR was analyzed.The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement among observers in measuring quantitative parameters of MRI.Differences between groups were analyzed using the independent sample t-test.Factors influencing CR were identified through the binary Logistic regression analysis, and a prediction model was established.Model performance was evaluated by plotting receiver operating characteristic (ROC) curves. Results:Significant differences were observed between the CR group and non-CR group in T2 signal intensity before CAR-T infusion (267±152 vs.364±160, P=0.048), and ADCmin (0.94±0.38 vs.0.53±0.28, P<0.05), ADCmax (1.73±0.69 vs.0.84±0.43, P<0.05), ADCmean (1.28±0.48 vs.0.67±0.33, P<0.05), and T2 signal intensity within 2 weeks after CAR-T infusion (198±139 vs.345±168, P=0.004). A univariate prediction model was created by introducing the above quantitative parameters.The area under the curve (AUC), specificity, sensitivity, and accuracy of T2 signal intensity before CAR-T infusion in predicting the efficacy on children and adolescents with mature aggressive B-cell NHL were 0.800, 84.0%, 57.9%, and 72.7%, respectively.The AUC, specificity, sensitivity, and accuracy of ADCmax within 2 weeks of CAR-T infusion were 0.958, 88.0%, 78.9%, and 84.1%, respectively.The AUC, specificity, sensitivity, and accuracy of T2 signal intensity within 2 weeks of CAR-T infusion were 0.869, 84.0%, 68.4%, and 77.3%, respectively. Conclusions:Quantitative parameters of MRI, including ADC values and T2 signal intensity, are of great significance in the early prediction of CAR-T therapy efficacy on children and adolescents with mature aggressive B-cell NHL.Among these parameters, ADCmax presents the strongest predictive performance and serves as a valuable indicator for predicting a complete response with CAR-T treatment.
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BACKGROUND@#Lung cancer is the most common malignant tumor in China, lung adenocarcinoma (LUAD) is the main type of lung cancer, which is a serious threat to people's life and health. At present, there are fewer studies on the role of Dikkopf1 (DKK1) in lung adenocarcinoma. The aim of this study was to investigate the role and potential prognostic value of DKK1 in the development of lung adenocarcinoma by bioinformatics methods.@*METHODS@#Several databases, such as genotype-tissue expression (GTEx), The Cancer Genome Atlas (TCGA) and tumor-immune system interactions database (TISIDB), were used to analyze the expression, clinicopathological features, immune cell infiltration, prognosis and methylation of DKK1 in lung adenocarcinoma. Then, linked immune cell infiltration Omics database was used to analyze the co-expressed genes of DKK1 and their functional enrichment. Finally, 59 pathological samples of paraffin-embedded lung adenocarcinoma patients who underwent surgery at the Affiliated Cancer Hospital of Xinjiang Medical University between 2016 and 2017 were collected for the validation of the prognostic value of expression by immunohistochemistry (IHC) test.@*RESULTS@#The results of bioconfidence analysis showed that the expression level of DKK1 in lung adenocarcinoma tissues was higher than that in normal tissues, the expression in advanced cancers was higher than that in early stages, and the experimental validation revealed that among 59 cases of lung adenocarcinoma, there were 15 cases of negative expression (25.4%), 18 cases of weakly positive expression (30.5%), and 26 cases of strongly positive expression (44.1%). The different expression of DKK1 is related to methylation, prognosis and the activities of various immune cells. Functional enrichment shows that DKK1 may be involved in skin development and cell-substrate junction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that DKK1 is related to ABC transporters. Bioinformatics analysis and clinical case specimens showed that high DKK1 expression was associated with poorer prognosis in patients with lung adenocarcinoma.@*CONCLUSIONS@#High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.
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Objective:To explore a fast and accurate method to diagnose children's pneumonia according to respiratory signals, so as to avoid the cancer induction caused by traditional X-ray examination.Methods:A Mach Zehnder optical fiber sensor was used to build a respiratory signals(RSPs) detection system, and the RSPs of the monitored children were extracted according to the vibration signal generated by the children's lung rales. Preprocessing methods such as the discrete cosine transform(DCT) were used to compress and denoise the RSPs. Multi-feature extraction of RSPs was conducted through signal processing methods such as the Hilbert transform and autoregressive (AR) model spectrum estimation. A support vector machine (SVM) classification model was constructed to classify the collected RSPs.Results:The accuracy rate of the proposed RSP classification of children with or without pneumonia was 94.41%, which was higher than the previous methods.Conclusions:The children's pneumonia diagnosis system based on an optical fiber sensor has a higher detection accuracy, and is expected to be widely used in clinical practice.
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Objective@#To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study.@*Methods@#An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect.@*Results@#(1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ2=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm3, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm3, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC (F=10.833, P=0.002)as well as the left mPFC (F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory (r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers (r=-0.198, P=0.417) and the integration effect was significant (F=8.632, P=0.006).@*Conclusions@#The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.
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Objective:To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study.Methods:An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect. Results:(1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ 2=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm 3, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm 3, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC ( F=10.833, P=0.002)as well as the left mPFC ( F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory ( r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers ( r=-0.198, P=0.417) and the integration effect was significant ( F=8.632, P=0.006). Conclusions:The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.
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Objective:To explore the effect of continuous nursing on quality of life in patients after total knee replacement. Methods:100 patients with knee replacement were randomly divided into the experimental group and the control group, with 50 cases in each group. The control group received routine nursing care, while the experi-mental group received continuous nursing care on the basis of routine nursing care. Patients' quality of life ( QOL) was measured after operation, three months after operation and six months after operation. Results: A total of 96 patients participated in the study throughout the process. The QOL score of the 48 patients in the experimental group was (463. 75 ± 10. 62) points after operation, (521. 24 ± 9. 98) points three months after operation, and (530. 98 ± 12. 82) points six months after operation. The QOL score of the 48 patients in the control group was (464. 28 ± 11. 91) points after operation, (495. 01 ± 11. 22) points three months after operation, and (499. 66 ± 10. 91) points six months after operation. There was no significant difference between the two groups in QOL after operation (P>0. 05). At three months and six months after operation, the QOL of the experimental group was sig-nificantly higher than that of the control group ( P<0 . 05 ) . Conclusion: Continuous nursing after total knee re-placement can improve the quality of life of patients.
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Objective To analysis the development tendency and research focus of long-term care of chronic disease between China and abroad and guide the research and application of long-term care of chronic disease in China. Methods The PubMed database and China National Knowledge Infrastructure (CNKI) database were searched and co-word clustering analysis and multidimensional scaling analysis with Bicomb and SPSS 21.00 software were used. Results Foreign hot spots are summarized as follows:oxygen inhalation therapy; mental disorder patients; the needs and demands of long term care. And the following domestic hot spots: long term care for the aged; long term care insurance and social support. Conclusions Long-term care researches in China is still in the exploratory stage and combining with domestic and foreign research hot spots, proposal of long term care in China are summarized as follows:expand the study population of the domestic long-term care, such as the disabled and the mental disorder;enrich domestic long-term care research topics, such as long-term care model, caregivers, care quality, etc.
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Objective@#The aim of this study was to investigate the effect of mitogen-activated protein kinase (MAPK) signaling pathway on apoptosis induced by chloroacetic acid in human normal bronchial epithelial 16HBE cells.@*Methods@#16HBE cells were exposed to 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 and 3.5 mmol/L chloroacetic acid for 24 h in vitro. The cytotoxicity induced by chloroacetic acid was assessed by CCK-8 and LDH assays. Cell apoptosis was detected by Annexin V-FITC and PI staining. The protein expression levels of phosphorylation of p38, ERK1/2 and JNK were determined by western blotting. 16HBE cells were pretreated with MAPK signaling pathway specific inhibitors including SB203580, U0126 and SP600125 for 1 h, and these cells were subsequently treated with 2.5 mmol/L chloroacetic acid for 24 h. The expressions of p-p38, p-ERK1/2 and p-JNK as well as the changes of cell viability and apoptosis were measured after pretreated with inhibitors for 1 h.@*Results@#The cell viability by CCK-8 and LDH methods gradually reduced in a dose-dependent manner when chloroacetic acid concentrations elevated (P<0.05) , and their correlation coefficients were -0.902 and -0.825, respectively. The detection efficiency of CCK-8 assay significantly increased compared with LDH assay (P<0.05) . The cell apoptosis rates, which were (17.2±4.0) %, (24.6± 4.2) %, (39.3 ± 5.7) % in 1.5, 2.0, 2.5 mmol/L chloroacetic acid-treated groups, were higher than that of the control group[ (5.6 ± 3.0) %] (P<0.05) . There was a time-or dose-dependent change in the protein expressions of p-p38, p-ERK1/2 and p-JNK. Compared with the control, the levels of p-p38 had 2.1 and 2.6-fold increases in 16 and 24 h treated groups (P<0.01) , while the levels of p-ERK1/2 distinctly decreased by 37% and 52% (P<0.01) . In comparison with the control group, the expressions of p-p38 had 1.9 and 2.6-fold increases in 1.5 and 2.5 mmol/L treatment groups (P<0.01) , whereas the expressions of p-ERK1/2 significantly decreased by 40% and 50% (P<0.01) . No significant change was observed in p-JNK protein expression between the chloroacetic acid-treated and control groups. In comparison with the vehicle control and the exposed group, p-p38, p-ERK1/2, p-JNK protein expressions significantly declined in the inhibitor controls and inhibitor groups. Compared with the controls, the cell survival rates had significant reductions of 28%, 18%, 36% and 26% respectively in chloroacetic acid treated group, SB203580 group, U0126 group and SP600125 group, and the apoptosis rates in the abovementioned groups were 7, 4, 8 and 7 times. Compared with chloroacetic acid-treated group, the cell viability increased by 14% in SB203580 group and decreased by 11% in U0126 group, and the cell apoptosis rates decreased by 36% in SB203580 group and increased by 18% in U0126 group (P<0.05) . But no significant changes were observed in cell viability and apoptosis between SP600125 and chloroacetic acid-treated group.@*Conclusion@#Chloroacetic acid might activate p38 MAPK signaling pathway and inhibit ERK1/2 MAPK signaling pathway. The signaling pathways of p38 and ERK1/2 MAPK are involved in 16HBE cell apoptosis induced by chloroacetic acid, but JNK is not involved in chloroacetic acid-induced 16HBE cell apoptosis.
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OBJECTIVE:To investigate the effects of Compound Leonurus artemisia ointment combined with Drospirenone and ethinylestradiol tablets on serum progesterone and T helper (Th) 1/Th2 cytokine after medical abortion.METHODS:A total of 228 patients underwent medical abortion selected from obstetrical outpatient of our hospital during our hospital during Mar.2013 to Jul.2015 as research object were divided into control group (109 cases) and observation group (119 cases) according to random number table.Control group was given Cefuroxime axetil tablets 0.25 g,po,bid,for consecutive 6 d for anti-infective treatment+ Drospirenone and ethinylestradiol tablets one tablet,po,qd,21 d as a treatment course,8 d later receiving second course,3 courses in total after fetal sac exclusion.Observation group was additionally given Compound L.artemisia ointment 10 g,po,bid,7 d as a treatment course,2 courses in total on the basis of control group.The levels of serum progesterone and Th1 (TNF-α,IFN-γ,IL-2)/Th2 cytokine (IL-4,IL-6,IL-10) were observed in 2 groups,and the occurrence of ADR was recorded.RESULTS:Before treatment,there was no statistical significance in serum progesterone or Th1/Th2 cytokine levels between 2 groups (P＞0.05).After treatment,serum progesterone,TNF-α,IL-2 and IL-6 levels of 2 groups were decreased significantly,and above indexes of observation group were significantly lower than those of control group.The levels of IL-4 and IL-10 in 2 groups were increased significantly,and above indexes of observation group were significantly higher than control group,with statistical significance (P＜0.05).After treatment,IFN-γ levels of 2 groups were decreased significantly,but there was no statistical significance between 2 groups (P＞0.05).No obvious ADR was found in 2 groups during treatment.CONCLUSIONS:Compound L.artemisia ointment combined with Drospirenone and ethinylestradiol tablets can regulate immune function of patients after medical abortion,and promote dynamic balance of Th1/Th2 cytokines with good safety.
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Objective To investigate the value of chromosomal microarray technique in genetic analysis of patients with embryo development arrest. Methods A total number of 273 patients with embryo development arrest were recruited for the chromosomal microarray testing.Results 41.4% of the 273 patients were chromosomal abnormalities. Among which 61(22.34%)were numerical chromosomal abnormalities,43 were structural anoma-lies,including which 15.75% were terminal deletion or duplication and microdeletion or microduplication. And 9 (3.3%)were mosaicisms.Conclusions Chromosomal microarray technique is highly accurate and specific,which can offer more genetic information than conventional karyotyping. And chromosomal microarray technique can also facilitate estimation of recurrence risk of future pregnancies for patients with embryo development arrest.
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Objective To explore the features of resting state functional magnetic resonance imaging (rs-fMRI) in the patients with mild cognitive impairment (MCI) after during the process of converting to Alzheimer's disease (AD) dementia. To study the correlation of the brain function imaging and neuropsychological scores in converted MCI subjects with the purpose of finding the potential functional biomarkers which may predict the conversion of MCI to AD dementia in short term using resting state functional MRI. Methods Twenty-seven patients with MCI and 31 age, gender and years of education matched normal controls (NC) were enrolled in this study and neuropsychological assessment and rs-fMRI data were acquired respectively at the baseline and follow-up. Functional connectivity strength (FCS) analyses were used to assess the functional differences among the groups of MCI-converters (MCI-c) , MCI-non converters (MCI-nc) and NC. Variance analyses were used to compare the group differences in age, years of education and each neuropsychological assessment. In addition, Chi-squared test was used to compare group differences in gender. Then, Kruskal-Wallis test was used to compare group differences in the interval time of twice data collection. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and neuropsychological assessment scores in MCI patients. Results (1) Significant group differences of FCS among the MCI-c, MCI-nc and NC groups were observed in bilateral angular gyri, bilateral orbitofrontal cortex, right precentral gyrus, left paracentral lobule, left precuneus, right fusiform, right middle occipital gyrus, right superior occipital gyrus, left cerebellum. (2) The MCI-c showed decreased FCS in bilateral angular gyri, right middle occipital gyrus, right superior occipital gyrus, right inferior occipital gyrus, right fusiform, left precuneus, and left paracentral lobule, as compared to MCI-nc, the cluster was 149, 114, 186, 56, 48, 33, 38 and 102 voxels, respectively;P<0.05, respectively. The correlation analysis showed that the FCS values of the right angular gyrus were negative correlated with the MMSE scores (r=-0.561, P=0.017) . Conclusions This study revealed that the comparison of rs-fMRI imaging data between MCI-c and MCI-nc at baseline is of great benefits in analysing the imaging characteristics of patients during converting from MCI to AD. The feature of FCS in rs-fMRI in right angular gyrus might serve as early indicators for the dysfunction and progression from MCI to AD.
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Objective To explore the features of resting state functional magnetic resonance imaging (rs-fMRI) in the patients with mild cognitive impairment (MCI) after during the process of converting to Alzheimer's disease (AD) dementia. To study the correlation of the brain function imaging and neuropsychological scores in converted MCI subjects with the purpose of finding the potential functional biomarkers which may predict the conversion of MCI to AD dementia in short term using resting state functional MRI. Methods Twenty-seven patients with MCI and 31 age, gender and years of education matched normal controls (NC) were enrolled in this study and neuropsychological assessment and rs-fMRI data were acquired respectively at the baseline and follow-up. Functional connectivity strength (FCS) analyses were used to assess the functional differences among the groups of MCI-converters (MCI-c) , MCI-non converters (MCI-nc) and NC. Variance analyses were used to compare the group differences in age, years of education and each neuropsychological assessment. In addition, Chi-squared test was used to compare group differences in gender. Then, Kruskal-Wallis test was used to compare group differences in the interval time of twice data collection. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and neuropsychological assessment scores in MCI patients. Results (1) Significant group differences of FCS among the MCI-c, MCI-nc and NC groups were observed in bilateral angular gyri, bilateral orbitofrontal cortex, right precentral gyrus, left paracentral lobule, left precuneus, right fusiform, right middle occipital gyrus, right superior occipital gyrus, left cerebellum. (2) The MCI-c showed decreased FCS in bilateral angular gyri, right middle occipital gyrus, right superior occipital gyrus, right inferior occipital gyrus, right fusiform, left precuneus, and left paracentral lobule, as compared to MCI-nc, the cluster was 149, 114, 186, 56, 48, 33, 38 and 102 voxels, respectively;P<0.05, respectively. The correlation analysis showed that the FCS values of the right angular gyrus were negative correlated with the MMSE scores (r=-0.561, P=0.017) . Conclusions This study revealed that the comparison of rs-fMRI imaging data between MCI-c and MCI-nc at baseline is of great benefits in analysing the imaging characteristics of patients during converting from MCI to AD. The feature of FCS in rs-fMRI in right angular gyrus might serve as early indicators for the dysfunction and progression from MCI to AD.
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Objective To explore a new index for reflecting the topological information of brain functional networks in patients at high risk of Alzheimer disease using characteristics of resting-state functional connectivity strengths(FCS) in patients with amnestic mild cognitive impairment(aMCI). Methods Thirty-one aMCI patients and 42 age, gender and years of education matched normal controls were enrolled between September 2009 and April 2011 in this study. The resting-state functional MRI (rs-fMRI) data of all participants were acquired and preprocessed. Then the whole-brain functional connectivities were constructed for exploring the distribution characteristics of hub regions which had higher FCS values. Using two-sample t test to compare group differences in age, years of education and each neuropsychological assessment. In addition, using Chi-squared test to compare group differences in gender. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and behavioral scores in aMCI patients. Results The hub regions of the functional networks in the aMCI patients were mainly located in the association cortices such as the precuneuses, posterior cingulate cortices, medial prefrontal cortices, angular gyri, superior occipital gyri, fusiform gyri and lingual gyri. The distribution models in the aMCI patients were consistent with those in the normal controls. However, the FCS values of these brain regions were significantly lower in the aMCI patients than those in the normal controls. In comparison to the normal controls, the aMCI patients had significantly decreased FCS values in the bilateral fusiform gyri, lingual gyri, superior occipital gyri, left middle occipital gyrus and postcentral gyrus (the cluster was 389, 230, 187 and 107 voxels, respectively;P<0.05, respectively), and they had decreased trends of FCS values in the bilateral posterior cingulate cortices and right insulas. The correlation analysis with uncorrected conditions showed that the FCS values of the left postcentral gyri were correlatid with the clock drawing test (CDT) scores (r=0.436, P=0.026). Conclusions aMCI mainly attacks the hub regions of brain functional networks. The changes of functional connectivities in aMCI may reflect the early pathophysiologic alterations of AD.
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AIM: To explore the role of purinergic signaling mediated by ATP in the Alzheimer ’ s disease (AD)-related colon motility disorder and its related molecular mechanisms .METHODS:(1)Clinical trials:AD patients in our hospital were collected and studied .Radioimmunoassay was used for the determination of plasma motilin (MTL), cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and nitric oxide (NO), and high-performance liquid chroma-tography ( HPLC) was applied to test the level of adenosine triphosphate ( ATP) .The patients were assessed by neuropsy-chology and scored accordingly .( 2 ) In animal experiments , AD mice received Morris water maze test , and the spatial learning and memory function were evaluated .The plasma levels of MTL , CCK, VIP and NO were examined by radioimmu-noassay , and the level of ATP was measured by HPLC .Choline acetyltransferase ( ChAT ) , VIP, nitric oxide synthase ( NOS) and ATP synthase were detected by immunohistochemistry .Western blot and immunohistochemistry were used to detect the expression of P2Y receptor.(3) In vitro, organ bath was applied to observe the effect of α,β-methylene ATP (α,β-MeATP), an agonist of P2Y receptor, on both spontaneous and electrically evoked contraction of colonic smooth muscle strip, and the technique of intracellular microelectrode was applied to observe the effect of α,β-MeATP on the membrane potential of colonic smooth muscle cells .RESULTS:Compared with control group , the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed.Mini-Mental State Examination (MMSE) score was decreased (P<0.05), Alzheimer’s Disease Assess-ment Scale-Cognitive Subscale (ADAS-Cog) score, Neuropsychiatric Inventory (NPI) score and Alzheimer’s Disease Co-operative Study-Activities of Daily Living Scale ( ADCS-ADL ) were all increased as compared with control group ( P <0.01).The 4~6 d escape latency of APP/PS1 AD mice was significantly prolonged (P<0.05), and the space explora-tion ability distinctly reduced (P<0.05).In AD mice, the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed .The protein expres-sion of colonic ATP synthase was significantly increased (P<0.05), but the expression of ChAT, VIP and NOS was not changed.The expression of P2Y receptor was increased (P<0.01).The results of in vitro experiment displayed that α,β-MeATP, from 20 μmol/L to 100 μmol/L, inhibited the spontaneous contraction of colonic smooth muscle strip in the nor-mal mice and AD mice ( P<0.05 or P<0.01 ) , and this inhibition was reversed by Na +channel inhibitor tetrodotoxin (TTX) (P<0.05 or P<0.01).In addition, the effect of α,β-MeATP at 100μmol/L on the AD mice was more obvious than that on the normal mice (P<0.05), and this inhibition was also antagonized by TTX (P<0.05 or P<0.01), pro-minent in AD group as compared with control group (P<0.05).In 10 Hz electrically evoked contraction of colonic smooth muscle strip,α,β-MeATP inhibited both the normal and AD mice (P<0.05 or P<0.01), while the inhibition was more obvious in the AD mice at the concentration of 40μmol/L or 100μmol/L (P<0.05 or P<0.01).CONCLUSION:AD patients and AD mice are accompanied by decreased MTL and CCK levels , and enhanced NO level , thus inducing colonic motor dysfunction along with AD .Meanwhile, ATP in plasma, purinergic neurons , and P2Y receptor expression are in-creased in the AD mice .Purinergic signaling mediated by ATP inhibits colonic smooth muscle strip contraction and further paralyzes the colonic movement function in AD .
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[ ABSTRACT] AIM: To explore the role of chemokine receptor CXCR 4 in the pathogenesis of protein C system (PCS) in ulcerative colitis (UC).METHODS:In vivo, the mice were divided into control group and UC group .The mac-roscopic score, microscopic score and ulcer index were assessed .The mRNA levels and activity of myeloperoxidase ( MPO) , cyclooxygenase-2 ( COX-2 ) , stromal cell-derived factor-1α( SDF-1α) and monocyte chemotactic protein 1 (MCP-1) both in colonic tissue and plasma were determined .The expression and location of CXCR4,β-arrestin, p-JNK, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) were detected.The activity of protein C (PC) and protein S ( PS) was measured in each group .In vitro, mouse colonic microvascular endothelial cells were isolated , cultured and identified.Both CXCR4-overexpressing and CXCR4-silencing colonic mucosa microvascular endothelial cells were con-structed.The effects of SDF-1αon the protein levels of EPCR , TM,β-arrestin and p-JNK, and on the activity of PC , PS and activated protein C ( APC) were observed .RESULTS:Compared with control group , UC mice showed increased gross score, histopathological score and ulcer index (P<0.05).The mRNA levels and activity of MPO, COX-2, SDF-1αand MCP-1 in colon and plasma were increased (P<0.01).The protein levels of CXCR4,β-arrestin and p-JNK were up-regu-lated, EPCR expression was down-regulated in colon, and the activity of PC and PS in plasma was decreased (P<0.05 or P<0.01).CXCR4 overexpression further aggravated SDF-1α-induced PCS inhibition in colonic mucosa microvascular en-dothelial cells, and further up-regulated the protein levels of β-arrestin and p-JNK (P<0.05).CONCLUSION:PCS is inhibited in UC.CXCR4 is involved in the regulation of PCS inhibition by mediating chemokines and acting on colonic mu -cosa microvascular endothelial cells through β-arrestin-JNK pathway .
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Objective To observe the clinical efficacy of endovascular -hypothermia in treatment of severe brain injury.Methods 40 cases of severe brain injury were given the endovascular -hypothermia treatment and the basic treatment accordingly.The time to reach target temperature and the stability to maintain target temperature were observed.The patients'ICP at different points were recorded .The cases were estimated by Glasgow Coma Scale (GCS) before and after treatment and their complications during treatment were observed .Results The time to reach target temperature was (136 ±42)min and only (6.20 ±1.68)% of the measurement time deviated from target tempera -ture.ICP was reduced as the temperature fell and maintained in normal range after re -warming process.The ICP af-ter treatment was significant difference (p <0.05).The GCS was also significant higher after treatment than before (p <0.05).The complications of the patients were fewer and can be controlled after corresponding treatments .Conclu-sion In the endovascular -hypothermia treatment, the time to reach target temperature was short and the stability to maintain target temperature was strong.The endovascular -hypothermia treatment can reduce patients 'ICP and improve their awareness.There was no serious complication during treatment .This treatment can be safe and reliable.
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Objective To study the effects of microRNA-34a-5p on erythroid differentiation of K562 cells.Methods K562 cells were transfected with the microRNA-34a-5p mimics and antisense inhibitors specifically targeting mi-croRNA-34a-5p, respectively.The effects of over-expression or knocking-down of microRNA-34a-5p were exam-ined by Quantitative RT-PCR.Flow cytometry was performed to detect specific surface marker of erythroid cells . The benzidine staining assay was used to access the differentiation of K 562 cells.Western blot was performed to de-tect miRNA targets.Results microRNA-34a-5p was down-regulated at the early stage of K562 erythroid differenti-ation.Over-expression of microRNA-34a-5p in K562 cells attenuates erythroid differentiation , in contrast, inhibi-tion of microRNA-34a-5p accelerates erythroid pheotypes in K562 cells.c-MYB was found to be the direct target of microRNA-34 a-5 p in erythroid cells .Conclusions microRNA-34 a-5 p regulates early erythroid differentiation of K562 cells via repressing c-MYB.
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Objective To explore the influence of high fat diet on learning and memory,as well as the alteration of the number of neurons and morphology of dendritic spines in rat hippocampi.Methods 24 male adult SD rats were randomly assigned to high fat diet group or control group.The rats were fed with high-fat diet or standaM laboratory rodent chow diet for 12 weeks.Learning and memory were tested by Morris water maze and object recognition tests, and mood and motor ability were tested by open field tests.Golgi staining detected dendritic spine density of hippocampal neurons, and Nissl staining was used to observe the number of hippocampal neurons and pathological changes.Results High-fat diet induced rat spatial learning deficits, which was demonstrated by the prolonged escape latency ((38.50±9.70) s, (20.08±7.35) s, (19.96± 10.56) s, (22.75± 12.51) s, (14.56±4.82) s) compared with the control ((33.61±12.41) s, (14.25±7.89) s, (15.06±7.59) s, (5.53±2.81) s, (4.7± 1.58) s).The spatial memory deficits demonstrated that the latency reaching platform ((30.46± 21.43) s) was prolonged compared with control ((5.18± 1.33)s).The working memory was impaired, which was demonstrated by the prolonged escape latency compared with control group (P＜ 0.05).Discrimination index lowered than control group ((0.67±0.12) vs (0.81±0.08)), and the difference was significant (P=0.038), but no anxiety behaviors were observed(P=0.461).The neuron number of hippocampal neurons and dendritic spine density were significantly lowered than those in the control group((209.73±24.29) vs (262.2±18.94), (17.9±2.84) vs (21.93±2.56) ,respectively) (P＜0.05).Conclusion Intake of high-fat diet can impair learning and memory in rats, as well as decrease the number of neurons and the density of dendritic spines in the hippocampus.
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Objective To identify research fronts of synthetic biology by mapping knowledge domains .Methods The research articles were clustered by co-cited analysis and bibliographic coupling while research domains of synthetic biology were mapped using software VOSviewer .Results There were seven research clusters by co-cited analysis and 32 clusters by bibliographic coupling .The articles published in the last two years have changed the structure of research domains .Con-clusion Bibliographic coupling is better at recognizing research fronts .Synthetic bioengineering , RNA expression , biology bone, biology library,and biology parts are research fronts of synthetic biology .
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Objective To investigate the relationship between hyperhomocysteinaemia and unstable angina pectoris (UAP). Methods Selected 159 patients with senile hypertension combined with angina pectoris from April 2013 to April 2014, 78 cases of hyperhomocysteinaemia patients as observation group, 81 cases of simple hypertension patients as control group. All of the patients were performed coronary angiography examination, using the Gensini score method calculated the integral of the coronary lesions (CAS). Detected the level of the serum homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP), fasting blood glucose (FBG) and blood lipid levels. Results The gender, age, the levels of FBG and lipid in two groups had no significant differences ( P>0.05). The incidence of UAP,CAS and hs-CRP in observation group were 44.9%(35/78), (44.34±10.67) scores,(4.31±1.01)μg/L, in control group were14.8%(12/81), (30.24±8.76) scores, (2.13±0.95)μg/L. The incidence of UAP, CAS and hs-CRP in observation group were significantly higher than those in control group ( P<0.05). The levels of serum Hcy,TC,TG,LDL-C, hs-CRP, HDL-C in UAP patients of observation group and control group were (23.21 ± 7.35) and (8.86 ±2.43) μmol/L, (6.54 ±0.75) and (6.67 ±0.82) mmol/L, (1.84 ±0.95) and (1.62 ±0.83) mmol/L, (4.65±0.78) and (4.42±0.72)mmol/L,(5.15±1.24) and(3.21±1.15) mg/L, (1.02±0.32) and(1.01±0.35) mmol/L. The levels of serum Hcy,TC,TG,LDL-C, hs-CRP, HDL-C in SAP patients of observation group and control group were (12.54±4.37) and (6.52±1.36)μmol/L, (4.23±0.54) and (4.43±0.57) mmol/L, (1.45 ±0.76) and (1.25 ±0.68) mmol/L, (2.67 ±0.45) and (2.43 ±0.43) mmol/L, (3.02 ±1.13) and (1.52±0.98) mg/L, (1.24±0.36) and (1.26±0.34) mmol/L.There were significant differences (P<0.05). Multi-factor Logistic regression analysis showed that the senile H-type hypertension was independent risk factor of UAP (OR=4.324, 95%CI 2.463-6.874, P=0.001). Conclusions The levels of serum Hcy is closely related to the stability of the coronary artery atheromatous plaque and lesion severity of coronary artery. The senile H-type hypertension is independent risk factor of UAP.