High-grade glioma (HGG) exhibits substantial biological heterogeneity, which complicates prognosis and treatment, and clarifying the interplay between proliferating tumor cells and tumor-associated microvasculature may improve patient outcomes. We prospectively enrolled 221 patients with HGG from four institutions and integrated diffusion-weighted and dynamic contrast-enhanced MRI within a supervoxel-based framework to delineate tumor subregions termed density-enhancement compounded voxels (DECV). Four DECV subregions (DECV1-4) with distinct imaging characteristics were identified. DECV4, characterized by low apparent diffusion coefficient and gradual enhancement, was strongly associated with tumor aggressiveness and treatment resistance. Clustering analysis further revealed two DECV phenotypes that differed significantly in progression-free and overall survival; phenotype II showed a higher DECV4 proportion and a poorer prognosis. DECV phenotypes outperformed conventional imaging markers as independent predictors of survival and were validated in an independent cohort. These DECV-based imaging phenotypes provide a robust, non-invasive biomarker for characterizing HGG heterogeneity and show potential to enhance prognostic stratification and guide personalized therapy.

Computer-aided diagnosis (CAD) technology can assist clinicians in evaluating liver lesions and intervening with treatment in time. Although CAD technology has advanced in recent years, the application scope of existing datasets remains relatively limited, typically supporting only single tasks, which has somewhat constrained the development of CAD technology. To address the above limitation, in this paper, we construct a multi-task liver dataset (LiMT) used for liver and tumor segmentation, multi-label lesion classification, and lesion detection based on arterial phase-enhanced computed tomography (CT), potentially providing an exploratory solution that is able to explore the correlation between tasks and does not need to worry about the heterogeneity between task-specific datasets during training. The dataset includes CT volumes from 150 different cases, comprising four types of liver diseases as well as normal cases. Each volume has been carefully annotated and calibrated by experienced clinicians. This public multi-task dataset may become a valuable resource for the medical imaging research community in the future. In addition, this paper not only provides relevant baseline experimental results but also reviews existing datasets and methods related to liver-related tasks.

Aβ deposition in the brain does not necessarily lead to cognitive impairment, and that blood supply may have other unexplained regulatory effects on Aβ. Therefore, there appears to be a more complex relationship between blood supply, Aβ deposition, and cognitive impairment that warrants further exploration. This cohort study collected four longitudinal follow-up datasets, including a total of 281 subjects, followed for four years. Three-dimensional time-of-flight angiography and pseudo-continuous arterial spin labeling were used to assess hippocampal vascularization pattern (VP) and hippocampal cerebral blood flow (CBF). 11 C-Pittsburgh compound B (PiB)-PET/CT-based spatial measurements were used detect hippocampal PiB uptake as a reflection of hippocampal Aβ deposition. We explored the relationships between hippocampal blood supply (VP and CBF), hippocampal PiB uptake, and the occurrence of mild cognitive impairment (MCI) using a generalized nonlinear model. We demonstrated the synergistic effect of hippocampal VP and CBF on predicting the occurrence of MCI. We conducted confirmation and quantification of the relationship between hippocampal blood supply and hippocampal PiB uptake. Additionally, the predicted value of PiB uptake based on hippocampal blood supply not only exhibited strong predictive efficacy for the occurrence of MCI (AUC = 0.831, p < 0.001), but was also validated in cerebral small vessel disease cohorts (AUC = 0.792, p < 0.001) and well validated in an independent cohort (Kappa = 0.741, p < 0.001). Overall, we reveal that hippocampal blood supply at baseline can regulate hippocampal PiB uptake, which reflects hippocampal tolerable amount of Aβ deposition and serves as an effective predictor for the occurrence of MCI, providing an important extension on the relationship between hippocampal blood supply and Aβ deposition.

Chronic cerebral hypoperfusion-induced white matter injury (WMI) is a significant cause of vascular cognitive impairment. Emerging evidence suggests that miR-218 may be involved in the pathogenesis of WMI. However, understanding of the relationship between miR-218 and chronic hypoperfusion-induced WMI remains insufficient. Our study investigated the relationship between miR-218 and chronic hypoperfusion-induced WMI at clinical, animal, and cellular levels. We found that serum miR-218 expression was elevated in clinical WMI patients, had a certain diagnostic efficacy for WMI, and was correlated with the degree of WMI, cognitive scores, and serum inflammatory factors. In addition, we constructed a mouse model with bilateral carotid artery stenosis (BCAS) to simulate chronic hypoperfusion-induced WMI and detected an increase in miR-218 expression in the white matter of BCAS mice. Following administration of Lv-sh-miR-218 to the white matter of BCAS mice, improvements were observed in both cognitive impairment and WMI. Furthermore, Lv-sh-miR-218 also reduced M1 polarization of microglia and neuroinflammation within the white matter. Subsequently, we confirmed that SOCS3 is the specific target of miR-218 through bioinformatics analysis and luciferase reporter gene assays. Injection of LV-SOCS3 into the white matter also led to improvements in cognitive impairment and WMI in BCAS mice, along with reduced M1 polarization of microglia and neuroinflammation. Moreover, in primary cultured microglia cells, we demonstrated that after chronic hypoxia, miR-218 regulates inflammatory factors through the SOCS3/STAT3 pathway. In summary, our current results indicate a strong correlation between elevated miR-218 levels and chronic hypoperfusion-induced WMI, and downregulation of miR-218 expression can improve neuroinflammation by upregulating SOCS3, thereby ameliorating WMI and cognitive impairment.

Background:Cognitive impairment is one of the common concomitant symptoms of depression. The aims of the present study were to predict the occurrence of mild cognitive impairment (MCI) in patients with depression. Methods:In this study, 217 patients with depression were recruited. Demographic data, serum indices and ERP indices from all participants were collected in the baseline period. The participants were followed for one year, and data from 200 patients were included in final analysis. Patients with depression were divided into those with MCI group (DWM group; n=145) and those without MCI (DWOM group; n=55). Data from the DWM group and the DWOM group were used to construct a logistic regression model, and a receiver operating characteristic (ROC) curve was drawn. Another 72 patients were used to validate the accuracy of our model. Results:Compared with DWOM individuals, DWM individuals were more likely to live alone (P<0.05), had lower baseline serum levels of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 22 (FGF22) (P<0.05), and exhibited higher baseline latencies of P300, mismatch negativity (MMN), and N200 (P<0.05). Baseline serum BDNF and FGF22 levels, along with the P300 latency, were selected to construct the regression model using logistic regression. The regression equation was [Formula: see text], and the combination of the 3 indices yielded an area under the ROC curve (AUC) of 0.790 and a predictive accuracy of 0.806. Conclusion:The logistic regression model and ROC curves based on serum BDNF and FGF22 levels and the P300 latency could provide a more effective means to predict the occurrence of MCI in patients with depression.

The therapies targeting mutations of driver genes in cancer have advanced into clinical trials for a variety of tumors. In glioblastoma (GBM), epidermal growth factor receptor (EGFR) is the most commonly mutated oncogene, and targeting EGFR has been widely investigated as a promising direction. However, the results of EGFR pathway inhibitors have not been satisfactory. Limited blood-brain barrier (BBB) permeability, drug resistance, and pathway compensation mechanisms contribute to the failure of anti-EGFR therapies. This review summarizes recent research advances in EGFR-targeted therapy for GBM and provides insight into the reasons for the unsatisfactory results of EGFR-targeted therapy. By combining the results of preclinical studies with those of clinical trials, we discuss that improved drug penetration across the BBB, the use of multi-target combinations, and the development of peptidomimetic drugs under the premise of precision medicine may be promising strategies to overcome drug resistance in GBM.

This study aims to assess the effect of enlarged perivascular spaces (EPVS) in patients using the methods of scale score and 3D volume quantification and to determine whether EPVS progression is related to the occurrence of silent lacunar infarction (SLI). Three hundred sixty-seven elderly patients with EPVS were screened by MRI on the day of admission and 2 years later; 295 patients were included in the final study, among which 136 patients had EPVS with SLI (EL); and 159 patients had EPVS without SLI (EOL). Both scale score and 3D volume quantification method were used to evaluate EPVS. The 295 patients were divided into three groups based on EPVS progression state: Group 1 (no progression), Group 2 (0–50

ObjectiveWe explored whether radiomics features extracted from diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) images can predict the clinical outcome of patients with acute ischaemic stroke. This study was conducted to investigate and validate a radiomics nomogram for predicting acute ischaemic stroke prognosis.MethodsA total of 257 patients with acute ischaemic stroke from three clinical centres were retrospectively assessed from February 2019 to July 2022. According to the modified Rankin scale (mRS) at 3 months, the patients were divided into a favourable outcome group (mRS of 0–2) and an unfavourable outcome group (mRS of 3−6). The high-throughput features from the regions of interest (ROIs) within the radiologist-drawn contour by AK software were extracted. We used two feature selection methods, minimum redundancy and maximum (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO), to select the features. Three radiomics models (DWI, FLAIR, and DWI-FLAIR) were established. A radiomics nomogram with patient characteristics and radiomics signature was built using a multivariate logistic regression model. The performance of the nomogram was evaluated in the test and validation sets. Ultimately, decision curve analysis was implemented to assess the clinical value of the nomogram.ResultsThe FLAIR, DWI, and DWI-FLAIR radiomics model exhibited good prediction performance, with area under the curve (AUCs) of 0.922 (95% CI: 0.876−0.968), 0.875 (95% CI: 0.815−0.935), and 0.895 (95% CI: 0.840−0.950). The radiomics nomogram with clinical characteristics including the overall cerebral small vessel disease (CSVD) burden score, hemorrhagic transformation (HT) and admission National Institutes of Health Stroke Scale score (NIHSS) score and the FLAIR Radscore presented good discriminatory potential in the training set (AUC = 0.94; 95% CI: 0.90−0.98) and test set (AUC = 0.94; 95% CI: 0.87−1), which was validated in the validation set 1 (AUC = 0.95; 95% CI: 0.88−1) and validation set 2 (AUC = 0.90; 95% CI: 0.768−1). In addition, it demonstrated good calibration, and decision curve analysis confirmed the clinical value of this nomogram.ConclusionThis non-invasive clinical-FLIAR radiomics nomogram shows good performance in predicting ischaemic stroke prognosis after thrombolysis.

目的:通过一站式头颈CTA及全脑CTP灌注成像同步研究颈动脉斑块面积占比对脑组织血流灌注情况的影响.方法:收集25例经超声确认的颈动脉斑块患者及10例正常受试者的头颈CTA及全脑CTP灌注数据,经过专业后处理软件测量及统计颈动脉斑块面积占比及全脑CTP灌注参数(包括平均血容量、平均血流量、平均达峰时间及平均通过时间),按照颈动脉斑块占比程度分组后与脑灌注参数同步进行分析.结果:颈动脉面积占比<30％,其同侧各个脑区的rCBV、rCBF、rTTP及rMTT差异均无统计学意义;颈动脉斑块占比≥30％且<50％,其同侧各个脑区rCBV差异无统计学意义,同侧内侧颞叶、纹状体及海马rCBF轻度减低,同侧岛叶、内侧颞叶、纹状体、海马rTTP及rMTT轻度延长;颈动脉斑块占比50％ ～70％,其同侧脑区rCBV差异无统计学意义,同侧岛叶、内侧颞叶、纹状体、海马及眶额区rCBF轻度减低,同侧岛叶、内侧颞叶、纹状体、海马、眶额区、前顶叶rTTP及rMTT轻度延长;颈动脉斑块占比超过70％,其同侧脑区rCBV差异无统计学意义,同侧岛叶、内侧颞叶、纹状体、海马、眶额区、前顶叶及中央前回rCBF轻度减低,同侧岛叶、内侧颞叶、纹状体、海马、眶额区、中央前回、前额叶rTTP及rMTT轻度延长.结论:颈动脉斑块面积占比导致的脑血流灌注异常区域有明显的差异,这种差异存在脑区系统及不同灌注参数上的变化特点,能够通过这些特点分析病变机制以及提供诊治方案依据.

ObjectiveTo explore the feasibility of using a contrast-enhanced CT image-based radiomics model to predict central cervical lymph node status in patients with thyroid nodules.MethodsPretreatment clinical and CT imaging data from 271 patients with surgically diagnosed and treated thyroid nodules were retrospectively analyzed. According to the pathological features of the thyroid nodules and central lymph nodes, the patients were divided into three groups: group 1: papillary thyroid carcinoma (PTC) metastatic lymph node group; group 2: PTC nonmetastatic lymph node group; and group 3: benign thyroid nodule reactive lymph node group. Radiomics models were constructed to compare the three groups by pairwise classification (model 1: group 1 vs group 3; model 2: group 1 vs group 2; model 3: group 2 vs group 3; and model 4: group 1 vs groups (2 + 3)). The feature parameters with good generalizability and clinical risk factors were screened. A nomogram was constructed by combining the radiomics features and clinical risk factors. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were performed to assess the diagnostic and clinical value of the nomogram.ResultsFor radiomics models 1, 2, and 3, the areas under the curve (AUCs) in the training group were 0.97, 0.96, and 0.93, respectively. The following independent clinical risk factors were identified: model 1, arterial phase CT values; model 2, sex and arterial phase CT values; model 3: none. The AUCs for the nomograms of models 1 and 2 in the training group were 0.98 and 0.97, respectively, and those in the test group were 0.95 and 0.87, respectively. The AUCs of the model 4 nomogram in the training and test groups were 0.96 and 0.94, respectively. Calibration curve analysis and DCA revealed the high clinical value of the nomograms of models 1, 2 and 4.ConclusionThe nomograms based on contrast-enhanced CT images had good predictive efficacy in classifying benign and malignant central cervical lymph nodes of thyroid nodule patients.

BACKGROUND: Stressful life events (SLEs) are an important causal factor in depression; however, the mechanism by which SLEs cause depression remains unclear. Recent studies suggested that white matter (WM) microstructures might be a potential mediator between SLEs and depression. Hence, we aimed to investigate the concrete correspondence among them using mediation effect models. METHODS: In participants (N = 194) with SLEs experience prospectively recruited from six residential communities, WM microstructures were detected with diffusion tensor imaging. The interrelationship among SLEs, WM microstructures, and depression was explored with multiple linear regression models and logistic regression models. Furthermore, the influence of WM microstructures on the association between SLEs and depression was tested with mediation effect models. RESULTS: Successfully established mediation effect models showed the specific influence of fractional anisotropy of the corpus callosum and left uncinate fasciculus on the association between SLEs and depression onset (ab path = 0.032; ab path = 0.026, respectively) and between SLEs and depressive severity (ab path = 0.052; ab path = 0.067, respectively). In addition, significant total mediation effects on the association between SLEs and depression onset (ab path = 0.031) and severity (ab path = 0.075) through fractional anisotropy of the corpus callosum and left uncinate fasciculus were noted. CONCLUSIONS: WM microstructure alterations impose a substantial mediation effect on the association between SLEs and depression, which suggest that changes in WM microstructure integrity might increase the risk of depression onset and unfavorable disease courses induced by the SLEs.

Hypoxic tumor microenvironment (TME) plays critical roles in induction of cancer stem cell-like phenotype in breast cancer and contribute to chemoresistance. However, the mechanism underlying stemness reprogramming of breast cancer cells (BCs) by hypoxic TME remains largely unknown. In the present study, we illustrated that HIF-2α, but not HIF-1α, induces stemness in BCs under hypoxia through SOD2-mtROS-PDI/GRP78-UPR ER pathway, linking mitochondrial metabolic state to endoplasmic reticulum (ER) response via mitochondrial reactive oxygen species (mtROS) level. HIF-2α activates endoplasmic reticulum unfolded protein response (UPR ER ) in drug-sensitive MCF7 and T47D cells to induce drug-resistant stem-like phenotype. Genetic depletion or pharmacological inhibition (YQ-0629) of HIF-2α abolished hypoxia-induced stem-like phenotype in vitro and in vivo. Mechanistically, HIF-2α activates transcription of superoxide dismutase 2 (SOD2) under hypoxia and thereby decreases mtROS level. With less mtROS transported to endoplasmic reticulum, the expression and activity of protein disulfide isomerase (PDI) is suppressed, allowing glucose-regulated protein 78 (GRP78) to dissociate from receptor proteins of UPR ER and bind misfolded protein to activate UPR ER , which eventually confer chemoresistance and stem-like properties to BCs. Moreover, the increase in mtROS and PDI levels caused by HIF-2α knockdown and the subsequent UPR ER inhibition could be substantially rescued by mitoTEMPOL (a mtROS scavenger), 16F16 (a PDI inhibitor), or GRP78 overexpression. Overall, we reported the critical roles of HIF-2α-SOD2-mtROS-PDI/GRP78-UPR ER axis in mediating hypoxia-induced stemness in BCs, highlighting the interaction between organelles and providing evidence for further development of targeted HIF-2α inhibitor as a promising therapeutic strategy for chemoresistant breast cancer.

Objective:To investigate the predictive values of serum fibroblast growth factor 22 (FGF22) levels and electrical P300 in depression patients occurred mild cognitive impairment (MCI).Methods:A prospective study was performed. A total of 94 depression patients without cognitive impairment admitted to our hospital from January 2020 to August 2021 were chosen. These patients were followed up for one year; Hamilton Depression Scale (HAMD)-24 items and Montreal Cognitive Assessment Scale (MoCA) were used to evaluate the neuropsychological function of the patients every 3 months; according to the occurrence of MCI, the patients were divided into depression with MCI group ( n=57), and depression without MCI group ( n=32). All patients underwent baseline P300 examination and baseline serum FGF22 levels were detected by enzyme-linked immunosorbent assay (ELISA), and the differences in clinical data, P300 examination results and serum FGF22 levels were compared between the two groups. Correlation analysis was performed to analyze the correlations of P300 latency and serum FGF22 level with MoCA scores. Multivariate Logistic regression analysis was used to screen the independent influence factors for MCI in patients with depression. The predictive value of P300 latency and serum FGF22 level in MCI in patients with depression was analyzed by receiver operating characteristic (ROC) curve. Results:As compared with the depression without MCI group, patients in the depression with MCI group had significantly lower years of education and serum FGF22 level, and significantly higher proportion of patients living alone, and statistically higher P300 latency ( P<0.05). The results of correlation analysis showed that the MoCA scores at MCI period were positively correlated with serum FGF22 level ( r=0.665, P<0.001) and negatively correlated with P300 latency ( r=-0.621, P<0.001) in patients from the depression with MCI group. Multivariate Logistic regression analysis showed that serum FGF22 level was a protective factor for MCI in patients with depression ( OR=0.805, 95%CI: 0.737-0.862, P=0.003), and P300 latency was a risk factor for MCI in patients with depression ( OR=1.136, 95%CI: 1.115-1.163, P=0.001). ROC curve analysis showed that the areas under the curve (AUC) of serum FGF22 level, P300 latency, serum FGF22 level combined with P300 latency in predicting MCI in depression patients were 0.779, 0.724, and 0.852, respectively. Conclusion:The abnormal serum FGF22 level and P300 latency are closely related to the occurrence of MCI in patients with depression, and the combination of the two can be used to predict the occurrence of MCI in patients with depression.

Objective:To investigate the regulation of Parkin-dependent mitophagy mediated by calcyclin-binding protein and Siah-1 interacting protein (CacyBP/SIP) on apoptosis and cycle of dopaminergic (DA) neurons.Methods:SH-SY5Y cells were divided into model group, control group and CacyBP/SIP group; cells in the model group were treated with 1-methyl-4-phenylpyridine (MPP +, 0.5 mmol/L) for 24 h, and cells in the control group and CacyBP/SIP group were transfected with empty lentivirus or CacyBP/SIP-sgRNA lentivirus on the basis of MMP +(0.5 mmol/L) treatment for 24 h, respectively. Western blotting was used to detect the protein expression levels of CacyBP/SIP, microtubule-associated protein l light chain 3 (LC3), lysosome-associated membrane protein 2 (LAMP2), phosphatase and tensin homolog ten induced kinase 1 (Pink1), Parkin, P53, Bcl-2, and Bax; flow cytometry was used to detect the cell apoptosis and cycle; immunofluorescent single staining was used to detect the expressions of LC3 and LAMP2; immunofluorescent double staining was used to detect the coexpressions of CacyBP/SIP and Parkin. Results:As compared with the model group and control group, the CacyBP/SIP group had significant reduction in protein expressions of CacyBP/SIP, LAMP2, Pink1, and Parkin, LC3-II/I ratio, immunofluorescent staining intensities of LC3-II and LAMP2, and Bcl-2 protein expressions ( P<0.05). As compared with the model group and control group, the CacyBP/SIP group had significantly increased Bax protein expression, significantly decreased Bcl-2/Bax ratio, significantly increased apoptosis rate, significantly increased P53 protein expression, significantly increased proportion of cells at G1 phase, and significantly decreased immunofluorescent intensity of CacyBP/SIP and Parkin co-expressions ( P<0.05). Conclusion:After knocking out CacyBP/SIP gene, the decrease of Parkin protein leads to cell cycle being arrested at G1 stage, and mediates the decrease of Parkin-dependent mitochondrial autophagy, thereby leading to increased cell apoptosis.

Liver fibrosis is a wound-healing response that results from various chronic damages. If the causes of damage are not removed or effective treatments are not given in a timely manner, it will progress to cirrhosis, even liver cancer. Currently, there are no specific medical therapies for liver fibrosis. Adeno-associated virus (AAV)-mediated gene therapy, one of the frontiers of modern medicine, has gained more attention in many fields due to its high safety profile, low immunogenicity, long-term efficacy in mediating gene expression, and increasingly known tropism. Notably, increasing evidence suggests a promising therapeutic potential for AAV-mediated gene therapy in different liver fibrosis models, which helps to correct abnormally changed target genes in the process of fibrosis and improve liver fibrosis at the molecular level. Moreover, the addition of cell-specific promoters to the genome of recombinant AAV helps to limit gene expression in specific cells, thereby producing better therapeutic efficacy in liver fibrosis. However, animal models are considered to be powerless predictive of tissue tropism, immunogenicity, and genotoxic risks in humans. Thus, AAV-mediated gene therapy will face many challenges. This review systemically summarizes the recent advances of AAV-mediated gene therapy in liver fibrosis, especially focusing on cellular and molecular mechanisms of transferred genes, and presents prospective challenges.

Background Cell type-specific transcriptional programming results from the combinatorial interplay between the repertoire of active regulatory elements. Disease-associated variants disrupt such programming, leading to altered expression of downstream regulated genes and the onset of pathological states. However, due to the non-linear regulatory properties of non-coding elements such as enhancers, which can activate transcription at long distances and in a non-directional way, the identification of causal variants and their target genes remains challenging. Here, we provide a multi-omics analysis to identify regulatory elements associated with functional kidney disease variants, and downstream regulated genes. Results In order to understand the genetic risk of kidney diseases, we generated a comprehensive dataset of the chromatin landscape of human kidney tubule cells, including transcription-centered 3D chromatin organization, histone modifications distribution and transcriptome with HiChIP, ChIP-seq and RNA-seq. We identified genome-wide functional elements and thousands of interactions between the distal elements and target genes. The results revealed that risk variants for renal tumor and chronic kidney disease were enriched in kidney tubule cells. We further pinpointed the target genes for the variants and validated two target genes by CRISPR/Cas9 genome editing techniques in zebrafish, demonstrating that SLC34A1 and MTX1 were indispensable genes to maintain kidney function. Conclusions Our results provide a valuable multi-omics resource on the chromatin landscape of human kidney tubule cells and establish a bioinformatic pipeline in dissecting functions of kidney disease-associated variants based on cell type-specific epigenome.

Oral squamous cell carcinoma (OSCC) is an aggressive tumor whose prognosis has little improvement in the last three decades. Various immune-related genes have been suggested as significant roles in the development and progression of malignant cancers. In this study, we acquired and integrated differentially expressed genes of OSCC patients, including immune-related genes and transcription factors (TFs), from The Cancer Genome Atlas (TCGA) database. TF-mediated network was established to exploring the regulatory mechanisms of prognostic immune-related genes. A 7 immune-related genes prognostic model for OSCC was obtained, including CGB8, CTLA4, TNFRSF19, CCL26, NRG1, TPM2 and PLAU, which was further proved to be an independent prognostic indicator after adjusting for other clinical factors. The immune-related genes prognostic index was significantly negatively correlated to the infiltration abundances of B cells (P < 0.05) and CD8+ T cells (P < 0.05). The novel proposed immune-based prognostic model not only provided a promising biomarker and a way to monitor the long-term treatment of OSCC, but also gave a new insight into a potential immunotherapy strategy.

Objective:To clarify the evidences of hippocampal injury after radiotherapy avoiding hippocampus and explore its relationships with cognition.Methods:A prospective design was adopted in this study.A total of 183 patients with nasopharyngeal carcinoma treated by intensity modulated radiation therapy (IMRT group) and 30 matched healthy control (HC group)were collected in the Affiliated Hospital of Jiangsu University and Southeast University Affiliated Zhongda Hospital from January 2017 to December 2019. All subjects were assessed by Montreal Cognitive Assessment (MoCA-B) at baseline and 6 months after radiotherapy, then the patients with nasopharyngeal carcinoma were divided into cognitive impairment group and non-cognitive impairment group. Subjects were scanned with Siemens 3.0 T MR, and T 1WI was used as analysis sequence.The individual standardized hippocampus ROIs were extracted based on Montreal Neurological Institute(MNI) brain template.All texture features were calculated using the Radiomics developed by C++and Delphi, and the intra group correlation coefficients (ICC), average direction, machine learning (random forest) and autocorrelation matrix were used for reducing the features dimension. One-way ANOVA and generalized linear models were used to compare the differences among different groups. Pearson correlations analyses were used to evaluate the relationships between important texture features and clinical data. Logistic regressions were used to calculate the abilities of texture features to predict cognitive impairment. Results:After 9 patients who lost follow-up were excluded, a total of 164 patients with nasopharyngeal carcinoma were included as IMRT group.Texture features of ROIs were extracted and dimensionally reduced successfully. Five differences features (Variance, Entropy, GlevNonU, RLNonUni and Contrast)were found among HC group, cognitive impairment group and non-cognitive impairment group, and the last three further showed significant differences within IMRT group (GlevNonU, P=0.011;RLNonUni, P<0.001;Contrast, P<0.001). Hippocampal doses were positively correlated with Variance ( r=0.448, P<0.05), and negatively correlated with Entropy ( r=-0.461, P<0.05). There was a positive correlation between MoCA-B scores with GlevNonU, RLNonUniand Contrast ( r=0.503, P<0.05; r=0.587, P<0.05; r=0.531, P<0.05). GlevNonU and Contrast were independent predictors of cognitive impairment in hippocampal avoidance of radiotherapy (OR=0.731, 95%CI 0.610-0.857; OR=0.651, 95%CI 0.496-0.853). Conclusion:Results of texture analysis could be used as micro imaging evidences of hippocampal injury in radiotherapy avoiding hippocampus, and could also effectively predict the occurrences of cognitive impairment.

Recently, circular RNAs (circRNAs) have been frequently reported to be involved in hepatocellular carcinoma (HCC) development and progression. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high-throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For instance, the expression of circPSD3, a circRNA derived from the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene, was considerably downregulated in primary hepatic stellate cells (HSCs) and liver tissues of mice with CCl4-induced HF compared to those in the vehicle group. In vivo overexpression of circPSD3 using AAV8-circPSD3 arrested the deterioration of CCl4-induced HF as indicated by reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content, liver hydroxyproline level, collagen deposition, and pro-fibrogenic gene and pro-inflammatory cytokine levels. Moreover, in vitro loss-of-function and gain-of-function analyses suggested that circPSD3 inhibited the activation and proliferation of HSCs. Mechanistically, circPSD3 served as a sponge for miR-92b-3p, subsequently promoting the expression of Smad7. In conclusion, our present findings reveal a novel mechanism by which circPSD3 alleviates hepatic fibrogenesis by targeting the miR-92b-3p/Smad7 axis, and they also indicate that circPSD3 may serve as a potential biomarker for HF.

Long non-coding RNAs (lncRNAs) have been identified as influential indicators in variety of malignancies. Among which, LncRNA RUNDC3A-AS1 is reported to upregulate in thyroid cancer. However, the expression pattern and the pathological function of lncRNA RUNDC3A-AS1 in thyroid cancer is unclear. In this study, we examined the expression levels of lncRNA RUNDC3A-AS1 in the thyroid cancer tissues and cell lines via RT-qPCR analysis. The effects of RUNDC3A-AS1 on thyroid cancer cell metastasis were detected by transwell chamber assay, scratch assay in vitro and lung metastasis model in vivo . The results indicated that RUNDC3A-AS1 was highly expressed in the thyroid cancer tissues and cell lines. Functionally, knockdown of RUNDC3A-AS1 could repress the migration and invasion of thyroid cancer cells in vitro , and inhibit thyroid cancer metastasis to lung in vivo . Mechanistically, RUNDC3A-AS1 served as an inhibitor of miR-182-5p in tumor tissues and cell lines. RUNDC3A-AS1 inhibited the expression of miR-182-5p to increase the expression level of ADAM9, thus further aggravating the malignancy of thyroid cancer. Therefore, the RUNDC3A-AS1/miR-182-5p/ADAM9 axis may be a potential therapeutic target for the treatment of thyroid cancer metastasis.