[Multimodal Magnetic Resonance and Fluorescence Imaging of the Induced Pluripotent Stem Cell Transplantation in the Brain].

The understanding of the engrafted cell behaviors such as the survival, growth and distribution is the prerequisite to optimize cell therapy, and a multimodal imaging at both anatomical and molecular levels is designed to achieve this goal. We constructed a lentiviral vector carrying genes of ferritin heavy chain 1 (FTH1), near-infrared fluorescent protein (iRFP) and enhanced green fluorescent protein (egfp), and established the induced pluripotent stem cells (iPSCs) culture stably expressing these three reporter genes. These iPSCs showed green and near-infrared fluorescence as well as the iron uptake capacity in vitro. After transplanted the labeled iPSCs into the rat brain, the engrafted cells could be in vivo imaged using magnetic resonance imaging (MRI) and near-infrared fluorescent imaging (NIF) up to 60 days at the anatomical level. Moreover, these cells could be detected using EGFP immunostaining and Prussian blue stain at the cellular level. The developed approach provides a novel tool to study behaviors of the transplanted cells in a multi-modal way, which will be valuable for the effectiveness and safety evaluation of cell therapy.

[Preoperative serum creatinine as an independent prognostic biomarker in patients with early-stage cervical adenocarcinoma].

Objective: To investigate the effect of preoperative serum creatinine (Scr) level on the prognosis of patients with early cervical adenocarcinoma (ADC) and its predictive value. Methods: A retrospective review was performed on 199 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage ⅠA1-ⅡA1 and pathology-proven invasive ADC from January 2005 to December 2015. Patients were followed up by phone and outpatient, with a median follow-up time 77.5 (57.0, 114.0) months, 11 cases (5.5%) were missing, 19 cases (10.1%) recurred, and 17 cases (9.0%) died. Multivariate analysis was performed by Cox regression model to analyze the related factors of the prognosis of ADC patients. The optimal cut-off point was determined by the analysis of receiver operating characteristics (ROC), and the predictive value of related factors for prognosis was evaluated by the area under the curve (AUC). Results: The median age of 199 patients was 44.0 (39.0-50.0) years. Overall, 16 patients (8.0%) were stage ⅠA1; 4 patients (2.0%) were stage ⅠA2; 147 patients (74.0%) were stage ⅠB1; 13 patients (6.5%) were stage ⅠB2; 19 patients (9.5%) were stage ⅡA1. The multivariate analysis showed that FIGO stage [4.570 (1.625-12.854)] and elevated Scr [1.065 (1.006-1.128)] were correlated with DFS in patients with early ADC, as well as correlated with OS [4.412 (1.458-13.350) and 1.076 (1.012-1.144), respectively (all P<0.05)]. The optimal cut-off point of Scr level was 75.2 µmoI/L. The AUC showed that the Scr level was a predictor of DFS (AUC=0.677, 95%CI: 0.608-0.742, P=0.006) and OS (AUC=0.677, 95%CI: 0.607-0.741, P=0.012). Conclusions: The preoperative Scr level independently predicts the prognosis of early-stage ADC; patients with Scr levels>75.2 µmoL/L might require more follow-up and adjuvant treatment, as they might have a poorer prognosis.

[Analysis of clinical and endoscopic characteristics of colorectal polyps in children].

To analyze the clinical and endoscopic characteristics of colorectal polyps in children, and to explore the detection rate, age and gender distribution characteristics, endoscopic treatment effect and follow-up monitoring of colorectal polyps in children, so as to provide reference for disease management of colorectal polyps in children. The clinical and endoscopic characteristics of children with colorectal polyps in Xi 'an Children's Hospital from January 2019 to December 2019 were retrospectively analyzed. The patients were divided into 5 groups according to age (y): 0

Transcriptome analysis reveals TOR signalling-mediated plant flush shoots governing Diaphorina citri Kuwayama oviposition.

Asian Citrus Psyllid (ACP), Diaphorina citri, is a key vector transmitting the causative agent of Huanglongbing (HLB) disease. Population growth of ACP is evident after feeding on plant flush shoots, as they only oviposit here. However, the underlying mechanism as to why flush shoots govern oviposition is unclear. This study compares the fecundity and ovarian morphology of ACP between young flush and mature leaves. Furthermore, the transcriptome of mated females infesting Murraya paniculata was analysed. Finally, the gene of the key Target of Rapamycin (TOR) signalling pathway was silenced by RNAi. Results indicated that flush shoot feeding activated the development of the psyllids ovary and therefore induced oviposition. A total of 126 and 2794 differentially expressed genes were detected at 1 and 5 days, respectively, after pest infestation of flush shoots compared to mature leaves. Many genes are involved in protein metabolism, Mitogen-Activated Protein Kinase (MAPK) signalling pathway, hormone synthesis, and TOR signalling pathway: all thought to activate reproduction. Silencing of the positive regulator gene DcRheb in the TOR pathway resulted in lower levels of ecdysone and juvenile hormone and decreased vitellogenin synthesis, further disrupting reproductive ability. This study enhances understanding of the molecular mechanism underlying ACP's reproductive strategy.

[Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities].

To assess the positive predictive value (PPV) of extended noninvasive prenatal testing (NIPT-plus) for fetal chromosomal abnormalities. This retrospective research enrolled 511 cases of pregnant women with positive NIPT-plus results at the Obstetrics and Gynecology Hospital of Fudan University from May 2017 to January 2021. Karyotype analysis and chromosome microarray analysis (CMA) techniques was applied for verification. All cases were followed to determine their pregnancy outcome. The Chi-square test was used in PPV. 63 out of 511 refused prenatal diagnosis after counseling, 448 pregnant women with prenatal diagnosis showed that the PPVs of NIPT-plus test for fetal trisomy 21, 18 and 13 (T21, T18, T13), sex chromosome aneuploidy (SCAs) and chromosome microdeletion/microduplication syndrome (MMS) were 86.0% (92/107), 79.5% (35/44), 54.5% (12/22), 39.5% (75/190), and 41.7% (30/72), respectively. The results revealed that the PPV was higher among older pregnant women compared to young pregnant women (77.8% vs. 51.9%,P<0.01). With increasing maternal age, the PPV of NIPT-plus presented increasing trends for T21, T13, and composite PPV except for T18 or SCAs. In addition, the termination rates for confirmed SCAs fetal karyotypes 45, X; 47, XXX; 47, XXY and 47, XYY were 11/11, 3/15, 91.7% (22/24) and 1/14, respectively. NIPT-plus can safely and effectively detect fetal chromosomal abnormalities and can be extended to MMS screening, significantly reducing the proportion of interventional prenatal diagnoses, and those with positive screening still require further confirmation.

[Application of artificial intelligence-assisted diagnosis for cervical liquid-based thin-layer cytology].

Objective: To explore the application value of artificial intelligence-assisted diagnosis system for TBS report in cervical cancer screening. Methods: A total of 16 317 clinical samples and related data of cervical liquid-based thin-layer cell smears, which were obtained from July 2020 to September 2020, were collected from Southern Hospital, Guangzhou Huayin Medical Inspection Center, Shenzhen Bao'an People's Hospital(Group) and Changsha Yuan'an Biotechnology Co., Ltd. The TBS report artificial intelligence-assisted diagnosis system of cervical liquid-based thin-layer cytology jointly developed by Southern Medical University and Guangzhou F. Q. PATHOTECH Co., Ltd. based on deep learning convolution neural network was used to diagnose all clinical samples. The sensitivity,specificity and accuracy of both artificial intelligence-assisted diagnosis system and cytologists using artificial intelligence-assisted diagnosis system were analyzed based on the evaluation standard(2014 TBS). The time spent by the two methods was also compared. Results: The sensitivity of artificial intelligence-assisted diagnosis system in predicting cervical intraepithelial lesions and other lesions (including endometrial cells detected in women over 45 years old and infectious lesions) under different production methods, different cytoplasmic staining and different scanning instruments was 92.90% and 83.55% respectively, and the specificity of negative samples was 87.02%, while that of cytologists using artificial intelligence-assisted diagnosis system was 99.34%, 97.79% and 99.10%, respectively. Moreover, cytologists using artificial intelligence-assisted diagnosis system could save about 6 times of reading time than manual. Conclusions: Artificial intelligence-assisted diagnosis system for TBS report of cervical liquid-based thin-layer cytology has the advantages of high sensitivity, high specificity and strong generalization. Cytologists can significantly improve the accuracy and work efficiency of reading smears by using artificial intelligence-assisted diagnosis system.

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. METHODS: CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. RESULTS: CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/ß-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. CONCLUSIONS: CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

Downregulation of hsa_circ_0000285 serves as a prognostic biomarker for bladder cancer and is involved in cisplatin resistance.

Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state, treatment response and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis and predicting treatment response. Herein, qPCR measured the expression of hsa_circRNA_100783, hsa_circ_0000285 and hsa_circRNA_100782 in bladder cancer tissues. It was established that sa_circ_0000285, but not hsa_circRNA_100782 and hsa_circRNA_10078, are significantly reduced in bladder cancer tissues and serum compared to adjacent tissues and healthy controls. Moreover, hsa_circ_0000285 expression was lower in cisplatin-resistant bladder cancer patients than in those who were cisplatin-sensitive. Here, hsa_circ_0000285 was associated with tumor size (p<0.001), differentiation (p<0.001), lymph node metastasis (p=0.038), distant metastasis (p=0.004) and TNM stage (p=0.013). Further analysis showed that hsa_circ_0000285 would be an independent prognostic factor for bladder cancer patient outcome. In conclusion, our study indicates hsa_circ_0000285 may be a novel biomarker for bladder cancer because of its involvement in bladder cancer chemo-sensitivity.

[Construction and mechanical analysis of finite element model for bending property of controlled memory wire nickel-titanium rotary file].

OBJECTIVE: To construct a model for a controlled memory (CM) nickel-titanium (NiTi) file and another M-wire NiTi file with the same geometry by using finite element analysis. To evaluate the flexibility of a CM NiTi file by using three dimensional finite element method and to compare its mechanical responses with that M-wire NiTi. METHODS: Based on the reverse engineering, the 21 mm long, 25#/08 taper Hyflex NT NiTi file and Hyflex CM NiTi file were fixed by the cantilever bending model at a distance of 9.5 mm from the tip of the file. The mechanical tester's indenter was loaded/unloaded at a distance of 3 mm from the tip of the file. The maximum displacement was 3 mm, the load displacement curve was obtained. Subsequently, by using a micro-CT to scan (layer spacing of 8 µm) NiTi files, and ABAQUS (6.10) was introduced to construct a geometric model. Hyflex NT was considered as a shapememory alloy constitutive model, Hyflex CM was considered as a power-hardening plastic constitutive model, respectively. Comparing the load-displacement curve of cantilever bending in the three-dimensional finite element model with the load-displacement curve in the experiment. RESULTS: Two tetrahedral element models were constructed, the total number of nodes was 99 353 and the total number of cells was 63 744. When the loading displacement was 1 mm, the stress distribution of the cross section at 6.1 mm from the tip of the file was observed. The upper and lower surfaces were subjected to the maximum bending stress and entered the phase transformation yield stage. The finite element simulation could clearly show the deformation of the file. Various information such as deformation characteristics and stress distribution in the process were well fitted to the actual experimental curve. CONCLUSION: The constitutive behavior of the material has a significant effect on the mechanical behavior of NiTi file. The finite element model established for the NiTi file of the CM wire can accurately capture the characteristics of various deformation processes of the NiTi root canal file, and it has a good fit with the actual experimental curve. The finite element model can be used for study on bending properties of CM wire.

[Relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases].

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e' was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e' (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e', and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions: Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.

TIGIT expression levels on CD4+ T cells are correlated with disease severity in patients with psoriasis.

BACKGROUND: T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells. AIM: To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis. METHODS: In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled. TIGIT expression on CD4+ T cells was evaluated by flow cytometry analysis and quantitative real-time PCR. Production of IFN-γ, IL-10 and IL-17 was measured with cytometry bead arrays, while CD4+ T cell proliferation was measured using a permeable assay. RESULTS: IGIT expression on CD4+ T cells and mRNA level were significantly lower in patients with PV compared with HCs. TIGIT expression was negatively correlated with Psoriasis Area and Severity Index. Activation of TIGIT with recombinant human CD155/Fc protein significantly inhibited psoriatic CD4+ T-cell proliferation, decreased production of IFN-γ and IL-17A, and increased IL-10. After blockade with a functional anti-human TIGIT antibody, TIGIT produced the opposite effect on IFN-γ and IL-17A, but had no significant effect on IL-10 or cell proliferation. Furthermore, the frequency of TIGIT+CD4+ T cells was significantly increased in patients with PV after 2 months of treatment with acitretin, with associated significant changes in IFN-γ, IL-10and IL-17A plasma levels. CONCLUSIONS: Downregulation of TIGIT on CD4+ T cells may contribute to the pathogenesis of psoriasis, and activation of the TIGIT signalling pathway may be a potential therapeutic target.

Long non-coding RNA PICART1 suppresses proliferation and promotes apoptosis in lung cancer cells by inhibiting JAK2/STAT3 signaling.

Lung cancer remains the most common cause of tumor-related death worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the development of various cancers, including lung cancer. This study aimed to investigate the effect and the molecular basis of lncRNA PICART1 on lung cancer. We first assessed the PICART1 expression in lung cancer in vitro and vivo by qRT-PCR. Then the expression of PICART1 in SPC-A-1 and NCI-H1975 cell lines was inhibited and overexpressed by transient transfections. Thereafter, cell viability, cell cycle, migration and apoptosis were respectively measured by MTT, Transwell and flow cytometry assay. Furthermore, qRT-PCR and western blot analysis were mainly performed to assess the expression levels of apoptosis- and migration-related proteins and JAK2/STAT3 pathway proteins. Tumor formation was measured by xenograft tumor model assay in vivo. PICART1 expression was down-regulated in human lung cancer tissues and cell lines. Knockdown of PICART1 increased cell viability of lung cancer cell lines. However, PICART1 overexpression inhibited cell cycle progression and promoted apoptosis in SPC-A-1 and NCI-H1975 cell lines. PICART1 overexpression also inhibited migration, as evidenced by up-regulation of E-cadherin, and down-regulation of Twist1, MMP2 and MMP9. Furthermore, we found PICART1 inhibition may regulate cell apoptosis and migration through activating JAK2/STAT3 pathway. In vivo experiments revealed that PICART1 knockdown significantly promoted tumor formation. This study demonstrates that PICART1 overexpression represents an anti-growth and anti-metastasis role in lung cancer cells. Additionally, PICART1 acts as a tumor suppressor may be via regulation of JAK2/STAT3 pathway.

[Surface microstructure and cyclic fatigue resistance of electro discharged machining nickel-titanium endodontic instrument].

OBJECTIVE: To compare the surface microstructures and cyclic fatigue resistance of HyFlex EDM with HyFlex CM and HyFlex NT. METHODS: Twelve 25 mm-long 25#/- HyFlex EDM and twelve 25 mm-long 25#/0.06 taper HyFlex CM or HyFlex NT were selected. The surface microstructure of the 2 instruments which were randomly selected from each group was observed by using scanning electron microscope (SEM). The remaining 10 instruments from each group were submitted to the cyclic fatigue test by using a simulated stainless steel root canal with 60° angle of curvature and curvature radius of 3.5 mm. The time till fracture was recorded, the number of cyclic fatigue (NCF) was calculated, the length of fracture fragment was evaluated, and the topographic features were analyzed by using SEM. The data were analyzed by using one-way analysis via SPSS 23.0 software. The statistical significance level was set at 0.05. RESULTS: SEM observation of the surface and microstructural characterization revealed peculiar melting appearance and evenly distributed micropores on the surface of HyFlex EDM while observations of the surface of both HyFlex CM and HyFlex NT demonstrated machining grooves and irregularities. The NCF of HyFlex EDM was 838±223, which was significantly higher than not only that of HyFlex CM (582±99), but also that of HyFlex NT (81±20) (P<0.05), and the difference between the latter two groups was significant, as well (P<0.05). The length of fractured fragments of HyFlex EDM was (7.27±0.28) mm, which was significantly longer than the HyFlex CM and HyFlex NT, with values of (6.72±0.26) mm and (6.62±0.37) mm, respectively (P<0.05). Topographic features demonstrated typical cyclic fatigue for all the three groups while the region of crack origins was more for HyFlex EDM and HyFlex CM than that of HyFlex NT. As far as the dimple area was concerned, that of HyFlex EDM was deeper and larger than that of HyFlex CM and HyFlex NT. CONCLUSION: Within the limitations of this study, electro-discharge machining leads to peculiar melting appearance with micropores instead of machining grooves and irregularities on the surface of HyFlex EDM, which may be the reason why HyFlex EDM exhibits significantly better cyclicfatigue resistance than HyFlex CM and HyFlex NT.

[The value of high resolution diffusion weighted imaging in differentiating benign and malignant epithelial tumors of parotid gland].

Objective: To investigate the diagnostic value of RESOLVE DWI in the evaluation of benign and malignant epithelial tumors of parotid gland. Methods: A total of 106 patients in the First Affiliated Hospital of Zhengzhou University with epithelial tumors of parotid gland confirmed by pathology from July 2015 to October 2017 were retrospectively analyzed. All patients underwent preoperative routine MRI and RESOLVE DWI, the ADC average values were calculated, t test were used to compare the ADC values of benign and malignant epithelial tumors of parotid gland. Diagnostic performance of ADC value was compared using receiver operating characteristic (ROC)curves. Results: All lesions were solitary, including 69 benign epithelial tumors and 37 malignant epithelial tumors. The mean ADC values of pleomorphic adenoma and basal cell adenoma, adenolymphoma and malignant epithelial tumors were (1.47±0.16)×10(-3) mm(2)/s, (0.83±0.19)×10(-3) mm(2)/s and(1.14±0.14)×10(-3) mm(2)/s, the mean ADC value of adenolymphoma lower than the rest of the two groups, there were statistically significant differences among them (P<0.05). Using 0.94×10(-3) mm(2)/s≤ADC value≤1.28×10(-3)mm(2)/s as the critical value for diagnosing malignant epithelial tumors of parotid gland and comparing with pathological results, the result obtained had a sensitivity of 81.1%, specificity of 88.9%. ADC value had high correlations compared with pathological results, kappa value was 0.600. Conclusion: RESOLVE DWI can be applied in differential diagnosis between benign and malignant epithelial tumors of parotid gland.

Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.

DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.

FMNL2 destabilises COMMD10 to activate NF-κB pathway in invasion and metastasis of colorectal cancer.

BACKGROUND: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. METHODS: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay. The in vitro and in vivo function of COMMD10 in CRC was evaluated using CCK-8 proliferation assay, plate colony formation, cell cycle, apoptosis and animal models. The inhibition of NF-κB signalling by COMMD10 was detected using dual-luciferase reporter assay and western blotting. Co-IP, GST pull-down and nuclear protein extraction assay were performed to evaluate the effect on p65 by COMMD10. Real-time PCR and western blotting were performed to detect expressions of FMNL2, COMMD10 and p65 in paired tissues. RESULTS: FMNL2 targets COMMD10 for ubiquitin-mediated proteasome degradation in CRC cells. COMMD10 targets p65 NF-κB (nuclear factor-κB) subunit and reduces its nuclear translocation, thereby leading to the inactivation of NF-κB pathway and suppression of CRC invasion and metastasis. Inhibition of NF-κB signalling by COMMD10 is necessary for FMNL2-mediated CRC cell behaviours. Downregulation of COMMD10 predicts poor prognosis of CRC patients. The expressions of FMNL2, COMMD10 and p65 are highly linked in CRC tissues. CONCLUSIONS: These data demonstrate that the FMNL2/COMMD10/p65 axis acts as a critical regulator in the maintenance of metastatic phenotypes and is strongly associated with negative clinical outcomes.

[Study on age and white matter neuronal integrity in healthy volunteers based on automating fiber-tract quantification].

Objective: To analyze age-related change in cerebral matter tract, especially fractional anisotropy, based on automating fiber-tract quantification(AFQ). Methods: A total of 64 years old normal persons and 43 young volunteers were enrolled respectively from the Affiliated Drum Tower Hospital of Nanjing University Medical School and community from January 2015 to June 2016.All of them underwent MRI scan, which included DTI and 3D T(1)WI sequence .All cases were divided into 3 groups according to their ages, the young group 20-35 years old, the middle old group 60-75 years old, the old group 76-90 years old.AFQ was used to identify 20 major white matter tracts in brains of all subjects and make measurements at anatomically equivalent locations along their trajectories. Results: The FA change trend of each fiber was similar among three groups. The old and the middle old group had different FA value in both sides of inferior fronto-occipital fasciculus(left t=-2.73, right t=-6.12, P<0.05), thalamic radiation(left t=-4.79, right t=-19.61, P<0.05), arcuate(left t=10.53, right t=-2.72, P<0.05), callosum forceps(genu t=-2.66, splenium t=28.64, P<0.05), cingulum(left t=-4.53, right t=-2.22, P<0.05)and right corticospinal tract(t=3.10, P<0.05), among which each location of callosum forceps minor was different between the old group and the young group, and this area decreased in the middle group. The old group had different FA value in both sides of uncinate fasciculus(left t=-4.52, right t=-4.53, P<0.05), left corticospinal tract(t=-2.19, P<0.05)and right inferior longitudinal fasciculus(t=11.12, P<0.05). Compared to the young group, there was no statistical difference in the FA of both superior longitudinal fasciculus and left inferior longitudinal fasciculus in the old and the middle old group. Conclusion: AFQ has an impact on the further specific study of the age-related white matter tract.

[Feasibility and value of index of microcirculatory resistance in patients with acute myocardial infarction after primary percutaneous coronary intervention].

Objective: To evaluate the feasibility of detecting index of microcirculatory resistance (IMR) and the relationship between IMR and left ventricular (LV) systolic function after acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The patients with first AMI received primary PCI in Peking University Third Hospital were enrolled from January 2014 to March 2016. IMR were measured immediately after PCI by using pressure/temperature wire. The relationship between IMR and left ventricular ejection fraction (LVEF) assessed by echocardiography at first day and 6 months after admission was evaluated. Results: Twenty-eight patients with anterior wall AMI were enrolled, with an average age (56±13) years. The success rate of IMR detection was 100%. The mean IMR was (33±18 )mmHg·s. There was no complication related to intravenous adenosine triphosphate (ATP) (140 µg· kg(-1)· min(-1)). The IMR was negatively correlated with TIMI blood flow grade after primary PCI (r=-0.386, P=0.043), and positively correlated with female gender, CK peak value and TnT peak value (r=0.430, P=0.022; r=0.431, P=0.025; r=0.434, P=0.024). After 6 months of follow-up, no adverse cardiovascular events (including cardiac death, nonfatal myocardial infarction, malignant arrhythmia, unplanned revascularization, hospitalization for unstable angina pectoris and severe heart failure requiring hospitalization) occurred. LVEF increased significantly compared with the first day after PCI (0.54±0.08 vs 0.47±0.06, P=0.001), and IMR was negatively correlated with LVEF after 6 months (r=-0.477, P=0.014). Multivariable linear regression analysis showed that CK peak and IMR were predictors of LVEF after six months ( ß=-0.595, t=-3.814, P=0.01; ß=-0.352, t=-2.26, P=0.036). Conclusions: Immediate detection of IMR in patients with anterior wall AMI after PCI is safe and feasible. The immediate IMR after PCI reflects the extent of myocardial necrosis and myocardial perfusion, and is a predictor of LVEF at 6 months after PCI.

[Change of white matter neuronal integrity associated with spatial navigation impairment in mild cognitive impairment].

Objective: To analyze the correlation between white matter integrity and spatial navigation impairment in patients with mild cognitive impairment (MCI). Methods: A total of 27 MCI subjects and 24 healthy controls were enrolled from the Affiliated Drum Tower Hospital of Nanjing University Medical School from May 2015 to February 2016, who underwent 3.0 T MRI scan and 2D-computer version spatial navigation test.DTI preprocessing and tract-based spatial statistics (TBSS) were performed by PANDA.Two sample t-test and partial correlation coefficients were performed to investigate the correlation of white matter impairments and spatial navigation decline. Results: Relative to controls, MCI showed worse egocentric navigation (t=-2.202, P<0.05). Decreased FA in superior longitudinal fasciculus (left t=2.95, right t=2.95, P<0.05), inferior longitudinal fasciculus and inferior fronto-occipital fasciculus (left t=2.66, right t=2.96, P<0.05), corpus callosum (t=2.09, P<0.05), cingulum (left t=2.76, right t=2.41, P<0.05), fornix (t=4.83, P<0.05), and corticospinal tract (left t=2.33, right t=2.26, P<0.05), were found in the MCI subjects.The decreased FA value of superior longitudinal fasciculus (left r=-0.354, right r=-0.347, P<0.05), inferior longitudinal fasciculus (left r=-0.338, right r=-0.336, P<0.05), cingulum (left r=-0.395, right r=-0.370, P<0.05), right corticospinal tract (r=-0.362, P<0.05) and fornix (r=-0.369, P<0.05) were correlated with increased ego average total error.Allo average total error were negative correlated with FA value of superior longitudinal fasciculus (left r=-0.329, right r=-0.350, P<0.05), inferior longitudinal fasciculus (left r=-0.349, right r=-0.378, P<0.05), splenium of corpus callosum (r=-0.364, P<0.05) and cingulum (left r=-0.340, right r=-0.406, P<0.05). Conclusion: This study implicated the potential white matter structural basis of spatial navigation impairment and will have an impact on the further study of the neurobiological mechanisms of human spatial navigation ability.

[Influence of occupational stress and 5-hydroxytryptamine 2A receptor gene polymorphisms on depression in workers in a thermal power plant].

Objective: To investigate the association of occupational stress and 5-hydroxytryptamine 2A (5-HT2A) receptor gene polymorphisms with depression. Methods: In November 2010, cluster sampling was used to select 589 workers in a thermal power plant as study subjects. Questionnaires were used to investigate demographic features and occupational stressors. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of T102C and A-1438G in 5-HT2A receptor gene in 589 workers. Results: High-level daily hassles (OR=3.013, 95%CI 1.642~5.530) , more negative emotion (OR=4.808, 95% CI 2.662~8.681) , more body needs (OR=1.890, 95% CI 1.034~3.453) , and severe role conflict (OR=1.815, 95% CI 1.002~3.288) were risk factors for depression, while high rewards (OR=0.424, 95% CI 0.226~0.796) was the protective factor against depression (all P<0.05). There were no significant differences in T102C genotype and allele distributions between the groups with and without depression (P>0.05) ; there was a significant difference in A-1438G genotype distribution between the groups with and without depression (χ2= 9.573, P<0.05) , while there was no significant difference in A-1438G allele distribution between these groups (P>0.05). The risk of depression in the workers with high-level daily hassles who carried TC genotype (OR= 4.473, 95% CI 1.161~17.238) or CC genotype (OR=5.176, 95% CI 1.367~19.593) of T102C was 4.473 and 5.176 times that in those with low-level daily hassles who carried TT genotype, and the risk of depression in the workers with more negative emotions who carried TC genotype (OR=5.667, 95%CI 1.204~26.673) or CC genotype (OR=8.114, 95% CI 1.747~37.677) of T102C was 5.667 and 8.114 times that in those with less negative emotion who carried TT genotype. The risk of depression in the workers with high-level daily hassles who carried AG genotype (OR=4.505, 95% CI 2.215~9.162) or GG genotype (OR=6.484, 95% CI 2.562~ 16.414) of A-1438G was 4.505 and 6.484 times that in those with low-level daily hassles who carried AA genotype, and the risk of depression in the workers with more negative emotion who carried AG genotype (OR= 4.877, 95%CI 2.326~10.223) or GG genotype (OR=9.090, 95%CI 3.491~23.673) of A-1438G was 4.877 and 9.090 times that in those with less negative emotion who carried AA genotype. The risk of depression in the workers with higher rewards who carried AG genotype (OR=0.152, 95%CI 0.074~0.310) or GG genotype (OR= 0.384, 95% CI 0.153~0.964) of A-1438G was 0.152 and 0.384 times that in those with lower rewards who carried AA genotype. Conclusion: Occupational stress is associated with the development of depression and interacts with 5-HT2A receptor gene polymorphisms.