Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.

Background::Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.Methods::The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro. A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry. Results::Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro. AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 +/CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion. Conclusions::This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

The biological effects of low-dose radiation (LDR) are still a research hotspot in the field of radiobiology. As research deepens on LDR-induced biological effects and the mechanisms, growing evidence shows that LDR produces distinct biological effects from high-dose radiation, which questions the linear non-threshold model. This article reviews LDR-induced bystander effect, hormesis, adaptive response, and hyper-radiosensitivity, as well as the mechanisms, in order to provide a reference for the transformation of basic research on LDR-related biological effects to clinical application.

N 6-methyladenosine (m 6A) is the most abundant RNA base modification in mammals, especially in eukaryotic messenger RNA (mRNA). N 6-methyladenosine modification can regulate RNA splicing, translocation, stability and ultimately affect protein synthesis. m 6A modification is catalyzed by RNA writers, reduced by erasers and also be recognized by readers. Abnormal changes ofm 6A levels are closely related to tumor occurrence and development, including proliferation, growth, invasion and metastasis. In the process of tumor radiotherapy, m 6A modification affects the efficacy of radiotherapy by affecting DNA damage, tumor stem cell generation and tumor cell radiation sensitivity. This article reviews the role of m 6A-modified epigenetic regulation in malignant tumors and the research progress of its mechanism in tumor radiotherapy, in order to provide new ideas for the development of clinical tumor molecular targeted therapies and radiosensitizers.

Objective To investigate the effect of neuropilin-1 (NRP1) on radiation-induced epithelial-mesenchymal transition (EMT) by measuring the expressions of EMT-related transcription factors in the irradiated cells with different levels of NRP 1.Methods Human lung type Ⅱ epithelial cells (A549) were transfected with NRP1 over-expression lentiviral vector and NRP1 inhibition vector to construct two cell models of NRP1high-A549 and NRP1low-A549.A NRP1 knock-down cell model was also constructed by transferring siNRP1 into normal mouse lung epithelial MLE-12 cells that was validated at both protein and mRNA levels.A single dose of 10 Gy X-ray was delivered to these cell models,then total protein and RNA were extracted at 0,12,24 and 48 h after irradiation.The expressions of EMT-related transcription factors (Twist and ZEB1) and EMT markers (β3-catenin,N-cadherin,and Vimentin) in each cell model were detected by Western blot and qPCR.Results After 10 Gy irradiation,the expressions of NRP1 mRNA and protein were significantly increased in A549 and MLE-12 cells.The expressions of the mesenchymal markers (Vimentin and N-cadherin) and the transcription factors of ZEB1 and Twist were also significantly increased (A549:t=2.917,7.361,4.852,9.278,P＜0.01;MLE-12:t=9.652,31.357,30.985,17.266,P ＜0.01).The expressions of Vimentin and N-cadherin were significantly decreased in NRP1low-A549 (t =10.077,15.707,P ＜ 0.01) and siNRP1-MLE-12 cells (t =5.745,P ＜ 0.01),but the expression of epithelial marker (β3-catenin) was significantly increased in these cells.The expressions of N-Cadherin and Vimentin were significantly elevated (t =16.055,5.560,P ＜ 0.01),while β-catenin decreased significantly in NRP1high-A549 cells.After irradiation,the transcription factor of Twist in NRP1low-A549 group was significantly decreased (t=3.987,P＜0.01),while the transcription factors of ZEB1 and Twist in the NRP1high-A549 group increased in a time-dependent manner (t =11.289,2.903,P＜0.01).After irradiation,the transcription factor of ZEB1 decreased significantly in siNRP1-MLE-12 cells (t=13.449,P＜0.01),and the protein expressions of ZEB1 and Twist in siNRP1-MLE-12 cells were lower than those of control group in a time-dependent manner.Conclusions NRP1 promotes radiation-induced EMT in human and mouse epithelial cells through up-regulation of transcription factors of ZEB1 and Twist.

BACKGROUND:In clinical application, the structure of crista lambdoidalis of L5 was unclear. It needs to expose more tissue to define L5 entry point through transverse process or superior and inferior articular process. This increased the risk of trauma and iatrogenic superior intervertebral degeneration. Therefore, it is necessary to expose L5 entry point with a minimaly invasive way. OBJECTIVE:To investigate the accuracy of L5 pedicle screw insertion with the entry point of mastoid process slope by imaging. METHODS:Mastoid process was located on the base of L5 superior articular process. A cant was formed when the highest point of L5 mastoid process backward protuberance extended inwards and downwards. The cant was defined as mastoid process slope; it was lateral to pedicle medial superior side internaly, medial to transverse process root and superior to the top of crista lambdoidalis. The slope was first easily touched and exposed in lumbar posterior surgery through paraspinal muscle space approach. Fifty patients of lumbar spine disorders were treated by L5 pedicle screws fixation through the entry point of mastoid process slope. According to preoperative radiographic and CT images, pedicle screw insertion direction of the sagittal and transverse sections was calculated. The diameter of pedicle screw was 6.5 mm. The condition of intraoperative successful rate of screws placement at one time was analyzed. The accuracy of screw placement was evaluated by postoperative radiographic and CT images. RESULTS AND CONCLUSION:With the method of the mastoid process slope, the successful rate of screw placement at one time was 96% (96/100). Totaly 100 screws were inserted into L5. According to the criterion by Gertzbein, 95 screws (95%) totaly located in pedicles and 5 screws (5%) encroached on the pedicle from medial wal. Three (3%) out of 5 inaccurately placed screws cut out less than 2 mm of the inner wal, while 2 (2%) between 2 mm and 4 mm, without neurologic deficits. The method of mastoid process slope had a high successful rate of screw placement. Combined with preoperative X-ray films and CT images could obtain a high accuracy rate of screw insertion.

In order to discriminate normal and abnormal heart sounds accurately and effectively, a new method is proposed to analyze heart sounds, namely heart sound characteristic waveform (HSCW) method. Digital stethoscope is used to collect heart sound signals. The recorded data are transmitted to a computer by USB interface for analysis based on HSCW, which is extracted from an analytical model of single degree-of-freedom (SDOF). Furthermore, a case study on the normal and abnormal cardiac sounds is demonstrated to validate the usefulness and efficiency of the proposed HSCW method. Besides, in order to test the accuracy of discriminating normal and abnormal heart sounds, 40 normal and 20 abnormal heart sounds are collected and analyzed, the accuracy performances are achieved by 92.5% and 95.0%, respectively.
Algorithms ; Heart Auscultation ; instrumentation ; methods ; Heart Sounds ; physiology ; Humans ; Phonocardiography ; methods ; Signal Processing, Computer-Assisted