Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia-UBE2G2-LGALS3BP axis may contribute to developing various therapeutic strategies for UM.

Subjective tinnitus refers to the subjective sound perception of patients in the absence of an external sound stimulus.Tinnitus patients are often accompanied by emotional disorders, such as depression and anxiety, which seriously affect the quality of life of patients.Therefore, understanding the mechanism underlying the occurrence of tinnitus emotional disorders can help relieve the pain of tinnitus.Tinnitus was considered a simple ear disease in the early stages, but with the progress of neuroimaging technology and the development of animal models, increasing attention has been given to the changes in the neural structure and function of tinnitus patients.As a powerful technique for in vivo investigation of neural activity in the brain, multimodal magnetic resonance has been widely used in the study of subjective tinnitus.By observing the changes of brain structure in subjective tinnitus patients, the neural mechanism of the occurrence and development of tinnitus has been explored.This article reviewed recent multimodal magnetic resonance imaging studies on the neuroimaging mechanisms of tinnitus with mood disorders, compared the differences in neural activity between subjective tinnitus patients and healthy people, and found that the limbic system, default mode network and other neural network abnormalities were closely related to the mood disorders of tinnitus.The application and development of multimodal magnetic resonance techniques in subjective tinnitus were also discussed to elucidate the neural mechanism of subjective tinnitus accompanied by mood disorders with the help of multimodal magnetic resonance techniques.

Objective:To investigate the local consistency of inferior colliculus and ventrolateral orbital cortex by resting-state functional magnetic resonance imaging (fMRI) in rats with noise induced deafness and its relationship with anxiety- and depression-like behavior.Methods:Twenty-four clean grade male four-weeks old SD rats were randomly divided into noise group and control group with 12 rats in each group.Rats in the noise group were exposed to 122 dB broadband strong noise for 2 hours to induce severe bilateral hearing loss, while rats in the control group were placed in a quiet environment. Hearing thresholds were assessed by auditory brainstem response (ABR) test. The open field test (OFT) was conducted to examine anxiety-depression related behavior, and the local consistency in the rat brain was evaluated by fMRI.SPM12 software was used to process fMRI data, and Pearson correlation analysis was conducted by SPSS 22.0 software to calculate the correlation between fMRI data and behavior.Results:The results of ABR showed that the full band hearing threshold of rats in the noise group was higher than that of rats in the control group ((85.417±6.463) dB, (20.083±8.853) dB, t=46.168, P<0.001). And compared with control group, the rats in the noise group showed obvious anxiety-depression-like behavior in the open field test, that was, low activity level.The results of OFT showed that the total distance ((39.912±5.696) m, (47.993±10.820)m, t=-2.289, P=0.032), average moving speed ((13.306±1.900)cm/s, (15.998±3.607)cm/s, t=-2.290, P=0.032) and standing times ((13.333±5.960), (23.500±7.323), t=-3.730, P=0.001) of the rats in the noise group were all lower than those in the control group. Compared with the control group, the local consistency of hypothalamus in the noise group was significantly enhanced, while the local consistency of ventrolateral orbital cortex was significantly reduced, and the abnormal neural activity was lateralized. The correlation analysis showed that the neural activity of the inferior colliculus was negatively correlated with the total distance of rats in the noise group moving in the open field( r=-0.691, P=0.013), while the neural activity of the ventrolateral orbital cortex was not significantly correlated with the anxiety-depression-like behavior in the open field. Conclusions:The neural activity of inferior colliculus is closely related to anxious-depression behavior in rats with noise-induced deafness, while the ventrolateral orbital cortex may be related with other behaviors.

Objective: To explore characteristics of dynamic and static balance of children aged 8 to 10 years, and to provide a reference for prevention of injuries caused by physical activities among obese children and the choice of facilities for physical activities. Methods: Totally 100 obese children and 100 normal children were selected as the subjects by one legged jumps from 5 primary schools in economic and technological development district of Hefei, the proportion of male and female children was 1∶1 in each group. IIM-BAL-100 balance tester was used to assess the static balance ability under double feet standing with eyes closed and right foot standing with eyes opened. The dynamic balance of double feet standing with eyes opened was measured by the Balance check dynamic balance tester. Two factor analysis of variance (ANOVA) was used to examine the effect of obesity and gender on the dynamic and the static balance. Results: In the static balance ability, when standing with both eyes closed, there was no significant difference in all static balance values between groups, genders and the interaction between the two factors( F=2.33, 0.42 ,0.76, P >0.05). When standing on one foot with eyes opened, there was significant difference in the static equilibrium index between the groups and the gender( F=2.72, 3.07, P <0.05). In terms of dynamic balance ability, all the dynamic balance indexes had statistically significant differences among the groups( F=43.67, P <0.01). Conclusion Obesity can significantly reduce the ability of single leg static balance and dynamic balance in 8-10 year old children. Sex can significantly affect the single foot static balance ability of 8-10 year old children, but it has little effect on the dynamic balance ability of 8-10 year old children.

Cell division cycle associated 8 (CDCA8) is involved in the accurate regulation of cell division cycle. The expression change of CDCA8 can affect the progression of many kinds of tumors as well as the prognosis of patients. In recent years, studies have suggested that CDCA8 may play an important role in maintaining the stemness of cancer stem cells. Exploring the mechanism of CDCA8 affecting tumor is of great significance for the diagnosis and treatment of tumors.

Objective To investigate the expression of LncRNA LINC00857 in pancreatic cells and the effect of lncRNA LINC00857 down-regulation on proliferation, migration and apoptosis of pancreatic cancer PANC-1 cells and possible mechanism. Methods The lentiviral vector GV112 was constructed and infected PANC-1 cells to obtain experimental group, while the blank plasmid was transfected as a negative control group and the cells without intervention were taken as normal control group. CCK-8 assay, Transwell assay, scratch test, flow cytometry, Western blot were used to detect the effect of LINC00857 down-regulation on cell proliferation, migration, apoptosis, cell cycle and EMT-related proteins. Results LINC00857 expression in pancreatic cancer cells were significantly higher than that in normal pancreatic epithelial cells (P < 0.001). Knockdown of LINC00857 could significantly inhibit the proliferation and migration of PANC-1 cells (P < 0.0001); compared with the negative control group, the apoptosis rates of cells in the experimental groups were significantly increased (P < 0.05), the number of cells in G₀/G₁ phase increased (P < 0.01), the number of cells in S phase decreased (P < 0.05), and the cells were blocked in the G₁ phase, E-cadherin expression was significantly up-regulated (P < 0.05) and N-cadherin and Vimentin expression were significantly down-regulated (N-cadherin: P < 0.01, Vimentin: P < 0.05). Conclusion LINC00857 can promote proliferation and migration of PANC-1 cells and inhibit its apoptosis by regulating G₁/S phase transition and EMT signaling pathway.

Objective To investigate the relationship between red blood cell distribution width (RDW) and prognosis in patients with multiple myeloma (MM).Methods The population that studied consisted of 27 patients with multiple myeloma and 30 healthy controls.The RDW was calculated according to the results of blood routine examination and compared between patients and healthy controls.Then,compared the difference between the two groups of RDW.MM patients were treated with international standard staging (ISS),and the differences of RDW in different stages were analyzed.ISS staging was used to draw the receiver operating curve (receiver operating characteristic curve,ROC curve),then take RDW14.65 ％ as the best cut-off point,the MM patients were divided into low RDW group (RDW=14.65 ％) and high RDW group (RDW ＞14.65％).Overall survival (OS) condition were compared between the above two groups.The impacts of RDW on OS were analyzed by Kaplan-Meier and Log-rank test.Results The average RDW value in experimental and controlled were 15.60 ％ ± 2.35 ％ vs 12.72 ％ ±0.61 ％ separately (t=6.201,P＜0.001),with statistical differences.The average RDW value in low ISS(Ⅰ + Ⅱ stage) and high ISS (Ⅲ stage) were 13.99 ％ ± 1.08％ vs 16.55 ％±2.39％ separately (t=3.800,P=0.001).The median survival time of low RDW and high RDW group was 13 months and 8 months respectively,and the difference was statistically significant (x2=6.481,P =0.011).Conclusion RDW increased in patients with MM,the risk stratification higher prognosis is worse.

Secreted frizzled-related protein (SFRP) can inhibit the expression of Wnt signaling pathway through Frizzled protein.The silencing of SFRP gene promoter methylation is associated with the occurrence and metastasis of many cancers such as colorectal cancer,gastric cancer,liver carcinoma,lung cancer and ovarian cancer.Several studies have found that SFRP gene has latent clinical value,which is expected to become the novel target for the gene diagnosis and treatment of cancer.

Objective To investigate the correlation between invasion ability and cytoskeleton remodeling of hepatocarcinoma cell by atomic force microscopy (AFM) and to explore mechanical properties during genesis,development and invasion of hepatocellular carcinoma (HCC).Methods Four HCC cell lines (MHCC-97H,MHCC-97L,SMMC-7721 ,Huh-7 )with different invasive ability were studied.Mechanical parameter (Young′s modulus)was measured by AFM.The pattern of cytoskeleton remodeling of HCC cell lines with different invasive ability was detected by immunofluorescent staining. The difference of cell invasive ability was tested by cell scratch experiment in other to verify mechanical data.Kruskal-Wallis H test was used to compare the differences between groups.Results The results of AFM indicated that Young′s modulus of cytoplasma area and nucleus area decreased gradually as cell invasion ability increased (χ2 =472.78,622.43,both P <0.01).According to invasive ability from low to high,Young′s modulus of cell cytoplasm area of Huh-7,SMMC-7721 ,MHCC-97L and MHCC-97H were 1 602.43 (845 .48,3 317.25)Pa,1 055 .28 (367.48,2 280.77)Pa,1 026.78 (369.20,2 019.96)Pa and 503.12 (366.11 ,700.31)Pa,respectively.Young′s modulus of cell nucleus area of Huh-7,SMMC-7721 ,MHCC-97L and MHCC-97H were 2 823.98 (1 262.78,4 440.07 )Pa,1 313.43 (590.71 , 2 678.62)Pa,1 285 .17 (583.29,1 961 .19)Pa and 655 .57 (441 .29,943.39)Pa,respectively.The results of immunofluorescent staining showed that the stronger the cell invasive ability,the worse cytoskeletal integrity and more irregular cell microfilament distribution. In cell scratch assay, the migration rate of MHCC-97H was 46.67% in 24 h and 86.47% in 48 h,that of MHCC-97L was 45 .70%in 24 h and 82.86% in 48 h,that of SMMC-7721 was 39.41 % in 24 h and 79.85 % in 48 h and that of Huh-7 was 34.60% in 24 h and 72.09% in 48 h,which showed that the cell migration orderly in creased as the cell invasion ability increased.Conclusions It seemed that HCC with higher invasive ability had lower Young′s modulus,softer cell,stronger deformability,worse cytoskeleton integrity and more irregular cell structure,and vice versa.

OBJECTIVETo investigate whether the antioxidation and the regulation on the Extracellular Regulated Protein Kinases (ERK) signaling pathway are involved in the protective effects of blueberry on central nervous system.

METHODS30 Senescence-accelerated mice prone 8 (SAMP8) mice were divided into three groups and treated with normal diet, blueberry extracts (200 mg/kg•bw/day) and cyaniding-3-O-galactoside (Cy-3-GAL) (50 mg/kg•bw/day) from blueberry for 8 weeks. 10 SAMR1 mice were set as control group. The capacity of spatial memory was assessed by Passive avoidance task and Morris water maze. Histological analyses on hippocampus were completed. Malondialdehyde (MDA) levels, Superoxide Dismutase (SOD) activity and the expression of ERK were detected.

RESULTSBoth Cy-3-GAL and blueberry extracts were shown effective functions to relieve cellular injury, improve hippocampal neurons survival and inhibit the pyramidal cell layer damage. Cy-3-GAL and blueberry extracts also increased SOD activity and reduced MDA content in brain tissues and plasma, and increased hippocampal phosphorylated ERK (p-ERK) expression in SAMP8 mice. Further more, the passive avoidance task test showed that both the latency time and the number of errors were improved by Cy-3-GAL treatment, and the Morris Water Maze test showed significant decreases of latency were detected by Cy-3-GAL and blueberry extracts treatment on day 4.

CONCLUSIONBlueberry extracts may reverse the declines of cognitive and behavioral function in the ageing process through several pathways, including enhancing the capacity of antioxidation, altering stress signaling. Cy-3-GAL may be an important active ingredient for these biological effects.

Aging ; drug effects ; Animals ; Anthocyanins ; pharmacology ; Avoidance Learning ; Blueberry Plants ; chemistry ; Dietary Supplements ; Galactosides ; pharmacology ; Hippocampus ; drug effects ; metabolism ; Malondialdehyde ; metabolism ; Maze Learning ; Memory ; drug effects ; Mice ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation ; Plant Extracts ; pharmacology ; Superoxide Dismutase ; metabolism