[Clinical observation of spontaneous brain activity in children with congenital cortical cataract amblyopia].

Objective: To investigate the characteristics of spontaneous brain activity in children with congenital cortical cataract amblyopia. Methods: A cross-sectional study was conducted. Twenty cases of unilateral congenital cortical cataract amblyopia (unilateral amblyopia group) and 14 cases of bilateral congenital cortical cataract amblyopia (bilateral amblyopia group) were enrolled from January 2022 to December 2022 at the First Affiliated Hospital of Zhengzhou University. Seventeen age and gender matched children with normal visual acuity were recruited as the healthy control group. Resting-state functional MRI (fMRI) was performed on all participants, and the amplitude of low-frequency fluctuations (ALFF) technique was used to analyze their spontaneous brain activities. The original ALFF value of each voxel was divided by the average ALFF value of the whole brain to obtain the standardized ALFF value (referred to as ALFF value), which reflected the intensity of spontaneous brain activity in different brain regions. General demographic data were compared using one-way analysis of variance, Kruskal-Wallis test, and chi-square test. Comparison of ALFF values was conducted using one-way analysis of variance. Results: There were no significant differences in age, gender, distribution of amblyopic eye or non-dominant eye, and degree of refractive error among the three groups (all P>0.05). Compared to the healthy control group, the unilateral amblyopia group showed higher ALFF values in the right posterior lobe of the cerebellum (67 voxels, t=3.48) and left posterior lobe of the cerebellum (71 voxels, t=4.09), and lower ALFF values in the right postcentral gyrus (91 voxels, t=-3.91), right inferior parietal lobule (73 voxels, t=-4.88), right inferior frontal gyrus (78 voxels, t=-4.09), left inferior parietal lobule (556 voxels, t=-4.82), and left inferior frontal gyrus (122 voxels, t=-4.27) (all P<0.01). The bilateral amblyopia group showed higher ALFF values in the right insula (60 voxels, t=3.54), right Rolandic operculum (69 voxels, t=3.73), right posterior lobe of the cerebellum (54 voxels, t=3.43), and left posterior lobe of the cerebellum (143 voxels, t=3.69), and lower ALFF values in the left inferior frontal gyrus (99 voxels, t=-4.39), left postcentral gyrus (231 voxels, t=-4.28), and right inferior parietal lobule (54 voxels, t=-3.77) (all P<0.01). Compared to the unilateral amblyopia group, the bilateral amblyopia group showed higher ALFF values in the left middle frontal gyrus (52 voxels, t=3.15, P=0.029), left posterior lobe of the cerebellum (77 voxels, t=3.39, P=0.001), and right Rolandic operculum (53 voxels, t=3.59, P=0.007). Conclusion: Children with congenital cortical cataract amblyopia exhibit altered spontaneous brain activity in multiple brain regions, and there are differences in spontaneous brain activity changes between unilateral and bilateral amblyopia.

[Progress in treatment for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a kind of invasive malignant tumor originated from pleural tissue. The incidence of MPM is not high in the population, but the prognosis is very poor. The median survival time is only about 12 months. Pemetrexed combined with platinum is the first-line chemotherapy regimen recommended by the current guidelines. The use of bevacizumab will further prolong the survival of chemotherapy. Once resistance happened, no anti-tumor treatment has been confirmed to achieve survival benefits. Therefore, there is no recommended standard second-line MPM regimen in international and domestic guidelines, including National Comprehensive Cancer Network (NCCN) guidelines. Vinorelbine, gemcitabine and other monotherapy regimens are commonly used in clinical practice, but the median progression free survival (PFS) is only about 3 months. Immune checkpoint inhibitors (ICIS) have been proved to have a significant inhibitory effect on tumor growth in a variety of malignant tumors, and their efficacy is related to the expression of programmed death-ligand 1(PD-L1). In unresectable MPM, programmed death 1 (PD-1)/PD-L1 inhibitors have been used in a series of clinical studies in the first-line, second-line and above treatment. Some of the results have been cited and recommended by international guidelines, but the overall efficacy improvement is still limited. This review summarizes the latest clinical studies and researches in the field of MPM treatment and predicts the directions and prospect of improving the therapeutic effect in the future.

MiRNA-26a promotes angiogenesis in a rat model of cerebral infarction via PI3K/AKT and MAPK/ERK pathway.

OBJECTIVE: To investigate the specific role of microRNA-26 (miRNA-26a) in a rat model of cerebral ischemic stroke and the underlying mechanism. MATERIALS AND METHODS: A rat model of middle cerebral artery occlusion (MCAO) was established to induce permanent cerebral infarction. Neuro-behavior was observed and scored after model establishment. The expression of miRNA-26a in brain tissue and brain microvascular endothelial cells (BMECs) of rats after cerebral ischemic stroke was detected by quantitative polymerase chain reaction (qPCR). The formation of the endothelial lumen was detected by Matrigel assay after BMECs were transfected with miR-26a mimics or inhibitors. Besides, cell proliferation after miRNA-26a transfection was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The protein levels related to PI3K/AKT and MAPK/ERK signaling pathway were detected by Western blot. RESULTS: miRNA-26a expression was elevated after cerebral infarction injury. Further investigation showed that miRNA-26a mimics could promote endothelial lumen formation and cell proliferation in BMECs, while miRNA-26a inhibitor inhibited the capacity of lumen formation and cell proliferation. Notably, we found that miRNA-26a might up-regulate the expression of HIF-1a via activating the AKT and ERK1/2 pathway, thus mediating the transcriptional activity of VEGF and promoting lumen formation and cell proliferation in BMECs. CONCLUSIONS: MiRNA-26a promotes angiogenesis in a rat model of cerebral ischemic via PI3K/AKT and MAPK/ERK pathway.

LncRNA MEG3 participates in neuronal cell injury induced by subarachnoid hemorrhage via inhibiting the Pi3k/Akt pathway.

OBJECTIVE: To explore the effect of LncRNA MEG3 in the subarachnoid hemorrhage (SAH) and its underlying mechanism. PATIENTS AND METHODS: The expressions of lncRNA MEG3 in SAH patients and animal model were detected by quantitative real-time PCR (qRT-PCR). After LncRNA MEG3 was overexpressed in neurons by lentivirus, viability and apoptosis abilities were detected by cell counting kit-8 (CCK-8) assay, flow cytometry, and TUNEL assay, respectively. The apoptosis-related genes and Pi3k/Akt pathway-related proteins were further detected by a Western blot. RESULTS: The expressions of lncRNA MEG3 in SAH patients were remarkably higher than normal controls, which were positively correlated with SAH severity. After lncRNA MEG3 overexpression, neuronal cell activity was decreased and cell apoptosis was increased. Moreover, the expressions of Bax, p53, and cleaved Caspase-3 were increased, whereas the expression of Bcl-2 and Pi3k/Akt pathway-related proteins were decreased after lncRNA MEG3 overexpression. CONCLUSIONS: LncRNA MEG3 is up-regulated in SAH, which may promote SAH-induced neuronal cell injury via inhibition of the Pi3k/Akt pathway.

MiR-519d reduces the 5-fluorouracil resistance in colorectal cancer cells by down-regulating the expression of CCND1.

OBJECTIVE: To investigate the effects of miR-519d on the 5-fluorouracil resistance in colorectal cancer cells and to explore the mechanism. MATERIALS AND METHODS: Colorectal cancer cells HCT116 and SW480 were transfected with miR519d-mimic or siCCND1 by transient transfection. The sensitivity of cells to 5-Fu was assayed by MTT assay. Dual luciferase assay was used to examine the effect of CCND1 on the sensitivity of cells to 5-Fu mediated by miR-519d. RESULTS: MiR-519d was overexpressed in colorectal cancer cells after transient transfection with miR-519d mimics. Overexpression of miR-519d increased the sensitivity of colorectal cancer cells to 5-Fu. MiR-519d negatively regulated the expression of CCND1 via directly bound to CCND1 3`UTR. si-CCND1 could downregulate the CCND1 expression in colorectal cancer HCT116 and SW480 cells. si-CCND1 increased the sensitivity of colorectal cancer cells to 5-Fu. CONCLUSIONS: miR-519d inhibits the expression of CCND1 and then plays a role in alleviating 5-Fu resistance in colorectal cancer cells.