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Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.
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Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC50 changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC50 of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.
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Objective To test the value of miRNA-30c(miR-30c)in early diagnosis of gastric cancer. Methods Serum miR-30c expression levels were detected by using quantitative real-time polymerase chain reaction in 80 patients with advanced gastric cancer, 35 patients with early stage gastric cancer and 35 healthy controls in the Affiliated People's Hospital of Inner Mongolia Medical University from August 2014 to August 2017. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed to test the efficacy of the miR-30c in distinguishing advanced gastric cancer, early stage gastric cancer and healthy controls. Results The expression level of serum miR-30c in advanced gastric cancer (0.45±0.11) was lower than that in early stage gastric cancer (0.54±0.15) (t = 5.2, P < 0.05). Compared with the healthy controls (0.61±0.12), miR-30c was down-expressed in the serum of early stage gastric cancer patients(t=6.7,P<0.05).Compared with the traditional tumor markers,the AUC of miR-30c was the biggest (0.92±0.03) in early stage and advanced gastric cancer groups, and the sensitivity and specificity in the diagnosis of gastric cancer were 90 % and 84 %, respectively. The AUC of miR-30c was 0.87±0.04 in early stage gastric cancer and healthy controls, and the sensitivity and specificity in the diagnosis of gastric cancer were 70 % and 86 %, respectively. Conclusion miR-30c might be used as a potential serum biomarker for the early diagnosis of gastric cancer.
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Epigenetic regulation plays an important role in breast cancer research.The epigenetic modification of histone mainly affects the occurrence and development of breast cancer by adding and removing methyl,acetyl and phosphate groups under the action of various enzymes.Because of its reversible regulatory process,it can provide advantage for the affected region to return to the normal genome state.Clinically,this can be used to develop a variety of drugs for patient diagnosis and treatment and to provide treatment targets.
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Objective:To investigate the expression of hypoxia-inducible factor-2α (HIF-2α)in non-small cell lung cancer (NSCLC)tissue,and to analyze its relationships with angiogenesis,cell proliferation and chemotherapy resistance. Methods: Total 112 cases of NSCLC and 20 cases of normal lung tissues were selected, immunohistochemical method was used to detect the expressions of HIF-2α,CD31,Ki67 and GST-π in 112 cases of cancer tissue and 20 cases of normal lung tissue,and the correlations of HIF-2α expression with microvessel density (MVD),Ki67, and GST-π were analyzed.Results:The positive expression rate of HIF-2α in NSCLC tissue was significantly higher than that in normal lung tissue (P < 0.05 ), the expression rate of HIF-2α in 112 cases of NSCLC was 47.3% (53/112).The MVD in HIF-2α protein high expression NSCLC group (31.1 ± 14.7)was higher than that in HIF-2αprotein low expression NSCLC group (24.3±15.8)(P <0.05).The cases of high expression of Ki67 in HIF-2αhigh expression group occupied 54.7% (29/53),and it was higher than that in HIF-2αlow expression group (16/59,27.1%);there was significant difference (r = 0.281,P = 0.003).The high expression of HIF-2α had no obvious correlation with the expression of GST-π (r = 0.122,P = 0.202). Conclusion:HIF-2αmay play an important role in the carcinogenesis and development of NSCLC by promoting the angiogenesis and enhancing the cell proliferation of NSCLC,but it may have no correlation with chemotherapy resistance.
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Objective To assess the association of synovial cyclic citrullinated peptide(CCP)expression with T helper 17(Th17) cells/Regulatory T cells (Treg) imbalance,the histological and clinical features of synovitis in rheumatoid arthritis (RA).Methods CCP expression in synovial specimens from 39 patients with RA and 35 controls was detected by immunohistochemistry assay(IH) using 6×His tagged anti-CCP single chain fragment V (ScFv) antibodies,which were generated by pHEN2 phagemid recombinant antibodies display system.The frequencies of Th17/Treg cells in the peripheral blood mononuclear cells (PBMCs) were determined by flow cytometry (FCM).Th17/Treg cells associated cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA).The histological scores and clinical features of synovitis were included in the study.Chi-square test and ANOVA were used for statistical analysis.Results ① The prevalences of synovial C CP expression were significantly different between RA group and the control(76.9％ and 11.4％ respectively,X2=31.9,P＜0.01).② The frequencies of Th17 cells,Th17/Treg ratio,Th17 cells associated cytokines as IL-6,IL-17a,IL-23,TNF-α,and the Treg cells associated cytokines TGF-31,the serum and synovial fluid anti-CCP antibodies in the RA patients with synovial CCP positive expression were significantly higher in RA patients with CCP positive than those with CCP negative.Disease activity score DAS28 index and histological features quantified variations of the synovial biopsy specimens (synoviocyte hyperplasia,focal aggregates of lymphocytes,and diffuse infiltrat(e)s of lymphocytes) in RA were higher in synovial CCP positive expression patients than in the negative.Conclusion Synovial CCP expression is strongly associated with the Th17/Treg imbalance and synovitis,which may play a crucial role in the pathogenesis of RA.
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Objective To explore the patterns and features of biological effects of ?-ray irradiation combined with microwave on the mouse hematopoietic system, and to provide theoretical and experimental basis for understanding the possible mechanism of the bone marrow injury caused by the combined action of microwave and ?-ray irradiation. Methods 216 healthy KM mice were randomly divided into the following four groups: normal control, microwave (S frequency range, 50mW/cm~2), ?-ray irradiation (5.5Gy), microwave combined ?-ray radiation (5.5Gy + 50mW/cm~2). They were sacrificed at 6h, 1, 3, 7, 14, 28, 90 and 180 days after radiation, respectively, then the histological and ultrastructural changes in the bone marrow and the peripheral hemogram were observed. Results Histopathological changes: the bone marrow appeared to be obviously injured either by radiation or microwave exposure, characterized by undergoing four phases, namely apoptosis-necrosis, void, regeneration and recovery phase. However, the pathological changes were more obvious and the recovery was slower in microwave combined ?-ray radiation group. Peripheral hemogram: the numbers of leucocytes, erythrocytes and platelets, and the content of hemoglobin decreased in both ?-ray irradiation group and microwave combined ?-ray radiation group, and the decrease in microwave combined radiation group was more remarkable. Ultrastructure: the bone marrow hematopoietic cells underwent obvious degeneration, apoptosis and necrosis in microwave combined ?-ray radiation group especially at 6 hours after radiation. Conclusion ?-ray combined with microwave could induce hematopoietic dysfunction and pathomorphological changes in hematopoietic organ, which were mainly caused by ?-ray, and the changes were aggravated.
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Purpose To study the anti-inflammatory,anti-allergy and immunosuppressive effect of polyglycosides of tripterygium wilfordii Hook (TⅡ). Methods Animal model of acute and subacute inflammation,adjuvant arthritis,type Ⅳ and Ⅲ allergic reaction were used.Serum haemolysin level,lymphocyte proliferation and T-cell subsets in spleen were tested. Results TⅡ 60,120 mg/kg and pre(prednisone)10 mg/kg had marked inhibitory effect on carrageenine induced swelling,tampon induced granulation and on the prevention of adjuvant arthritis.The delayed type hypersensitivity reaction(type Ⅳ) and arthus reaction (type Ⅲ) was distinctly suppressed.It had a suppressive action on serum haemolysin and lymphocyte proliferation with and without concanavatin A which was dose dependent.In the T-cell subsets:TⅡ 60 mg/kg decreased TS and TⅡ 120 mg/kg inhibited both TS and TH,preacted mainly on TH and rendered the decreased ratio of TH/TS. Conclusions TⅡ has suppressive effect on inflammation,allergic reaction and immune function.