CircMTA1 promotes glioblastoma angiogenesis by encoding MTA1-134aa.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with rapid angiogenesis. How to inhibit GBM angiogenesis is a key problem to be solved. To explore the targets of inhibiting GBM angiogenesis, this study confirmed that the expression of circMTA1 (hsa_circ_0033614) was significantly upregulated in human brain microvascular endothelial cells exposed to glioma cell-conditioned medium (GECs). The expression of circMTA1 in the cytoplasm was significantly higher than that in the nucleus. Upregulated circMTA1 in GECs can promote cell proliferation, migration, and tube formation. Further exploration of the circularization mechanism of circMTA1 confirmed that KHDRBS1 protein can bind to the upstream and downstream flanking sequences of circMTA1 and promote circMTA1 biogenesis by coordinating Alu element pairing. KHDRBS1 upregulated the proliferation, migration, and tube formation of GECs by promoting the biogenesis of circMTA1. CircMTA1 can encode the protein MTA1-134aa by internal ribosome entry site sequence-mediated translation mechanism, and promote the proliferation, migration, and tube formation of GECs through the encoded MTA1-134aa. This study provides a new target for inhibiting angiogenesis in brain GBM and a new strategy for improving the therapeutic efficacy of GBM.

Dysbiosis and Staphylococcus species over representation in the exit site skin microbiota of hemodialysis patients carrying tunneled cuffed central venous catheter.

OBJECTIVES: Hemodialysis patients with end-stage renal disease (ESRD) are susceptible to infections and dysbiosis. Catheter-related infections are typically caused by opportunistic skin pathogens. This study aims to compare the skin microbiota changes around the exit site of tunneled cuffed catheters (peri-catheter group) and the contralateral site (control group). METHODS: ESRD patients on hemodialysis were recruited. The skin microbiota were collected with moist skin swabs and analyzed using high-throughput sequencing of the 16S rDNA V3-V4 region. After denoising, de-replication, and removal of chimeras, the reads were assigned to zero-radius operational taxonomic units (ZOTU). RESULTS: We found significantly reduced alpha diversity in the peri-catheter group compared to the control group, as indicated by the Shannon, Jost, and equitability indexes, but not by the Chao1 or richness indexes. Beta diversity analysis revealed significant deviation of the peri-catheter microbiota from its corresponding control group. There was an overrepresentation of Firmicutes and an underrepresentation of Actinobacteria, Proteobacteria, and Acidobacteria at the phylum level in the peri-catheter group. The most abundant ZOTU (Staphylococcus spp.) drastically increased, while Cutibacterium, a commensal bacterium, decreased in the peri-catheter group. Network analysis revealed that the skin microbiota demonstrated covariance with both local and biochemical factors. CONCLUSIONS: In conclusion, there was significant skin microbiota dysbiosis at the exit sites compared to the control sites in ESRD dialysis patients. Managing skin dysbiosis represents a promising target in the prevention of catheter-related bacterial infections.

Expression profiles and function prediction of tRNA-derived fragments in glioma.

BACKGROUND: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown. METHODS: The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3'UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively. RESULTS: tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3'UTR. CONCLUSION: tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3'UTR.

Valuing Personal Data with Privacy Consideration.

A key challenge in information privacy research is how to value personal data with privacy consideration. In this study, we propose an experimental auction approach for valuing personal data. We use the generalized second-price auction to assess the monetary values of individuals' identity, demographic, and private information. We find that individuals' economic valuation of personal data is consistent with their actual self-disclosure behaviors. The economic valuation approach also produces results that are consistent with some well-accepted observations about consumer demographics and privacy. On the other hand, individuals' stated privacy preferences and attitudes are not consistent with their economic valuation. The findings of this study suggest that the proposed approach can be an effective mechanism for measuring personal data privacy. This study also provides important insights into valuing personal information for practical uses with several implications to policy decision makers, corporate executives and managers, data analysts, as well as decision science researchers.

Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson's disease: a meta-analysis.

BACKGROUND: Selegiline or levodopa treatment has been suggested as a therapeutic method for Parkinson's disease (PD) in many clinical trial reports. However, the combined effects of two drugs still remain controversial. The aim of this report was to evaluate the clinical efficacy and safety of selegiline plus levodopa (S + L) combination therapy in the treatment of PD compared to that of L monotherapy, to provide a reference resource for rational drug use. METHODS: Randomized controlled trials (RCTs) of S + L for PD published up to September, 2018 were searched. Mean difference (MD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Sensitivity analysis was also performed. The outcomes measured were as follows: the unified Parkinson's disease rating scale (UPDRS) scores, modified Webster score, adverse events and mortality. RESULTS: Fourteen RCTs with 2008 participants were included. Compared with L monotherapy, the pooled effects of S + L combination therapy on UPDRS score were (eleven trials; MD - 7.00, 95% CI - 8.35 to - 5.65, P < 0.00001) for total UPDRS score (nine trials; MD - 5.74, 95% CI - 7.71 to - 3.77, P < 0.00001) for motor UPDRS score (seven trials; MD - 1.61, 95% CI - 2.18 to - 1.04, P < 0.00001) for activities of daily living UPDRS score (three trials; MD - 0.38, 95% CI - 0.61 to - 0.14, P = 0.002) for mental UPDRS score. The Webster score showed significant decrease in the S + L combination therapy compared to L monotherapy (four trials; MD - 5.71, 95% CI - 7.11 to - 4.32, P < 0.00001). Compared with L monotherapy, S + L combination therapy did not increase the number of any adverse events significantly in PD patients (ten trials; OR 1.58, 95% CI 0.83-3.00, P = 0.16). CONCLUSIONS: S + L combination therapy is superior to L monotherapy for the improvement of clinical symptoms in PD patients. Moreover, the safety profile of S + L combination therapy is comparable with that of L monotherapy.

Effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys.

BACKGROUND: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys. METHODS: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment. RESULTS: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS. CONCLUSIONS: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.

Anonymizing and Sharing Medical Text Records.

Health information technology has increased accessibility of health and medical data and benefited medical research and healthcare management. However, there are rising concerns about patient privacy in sharing medical and healthcare data. A large amount of these data are in free text form. Existing techniques for privacy-preserving data sharing deal largely with structured data. Current privacy approaches for medical text data focus on detection and removal of patient identifiers from the data, which may be inadequate for protecting privacy or preserving data quality. We propose a new systematic approach to extract, cluster, and anonymize medical text records. Our approach integrates methods developed in both data privacy and health informatics fields. The key novel elements of our approach include a recursive partitioning method to cluster medical text records based on the similarity of the health and medical information and a value-enumeration method to anonymize potentially identifying information in the text data. An experimental study is conducted using real-world medical documents. The results of the experiments demonstrate the effectiveness of the proposed approach.

Anonymizing 1:M microdata with high utility.

Preserving privacy and utility during data publishing and data mining is essential for individuals, data providers and researchers. However, studies in this area typically assume that one individual has only one record in a dataset, which is unrealistic in many applications. Having multiple records for an individual leads to new privacy leakages. We call such a dataset a 1:M dataset. In this paper, we propose a novel privacy model called (k, l)-diversity that addresses disclosure risks in 1:M data publishing. Based on this model, we develop an efficient algorithm named 1:M-Generalization to preserve privacy and data utility, and compare it with alternative approaches. Extensive experiments on real-world data show that our approach outperforms the state-of-the-art technique, in terms of data utility and computational cost.

Low-dose endothelial monocyte-activating polypeptide-II increases permeability of blood-tumor barrier via a PKC-ζ/PP2A-dependent signaling mechanism.

Our previous study demonstrated that low-dose endothelial monocyte-activating polypeptide-II (EMAP-II) induces blood-tumor barrier (BTB) opening via the RhoA/Rho kinase/protein kinase C (PKC)-α/ß signaling pathway and that PKC-ζ is involved in this process via other mechanisms. In the present study, using an in vitro BTB model, we detected the exact signaling mechanisms by which PKC-ζ activation affects EMAP-II-induced BTB hyperpermeability. Our results showed that three types of serine/threonine (Ser/Thr) protein phosphatases (PPs), namely PP1, PP2A, and PP2B, were expressed by rat brain microvascular endothelial cells (RBMECs). There was an interaction between PKC-ζ and PP2A in RBMECs. In addition, EMAP-II induced a significant increase in both the expression and the activity of PP2A in RBMECs. Inhibition of PKC-ζ with PKC-ζ pseudosubstrate inhibitor (PKC-ζ-PI) completely blocked EMAP-II-induced PP2A activation. Conversely, inhibition of PP2A with okadaic acid (OA) had no effect on EMAP-II-induced PKC-ζ activation. Like PKC-ζ-PI, OA partially prevented EMAP-II-induced BTB hyperpermeability and occludin redistribution in RBMECs. Neither PKC-ζ-PI nor OA affected EMAP-II-induced phosphorylation of myosin light chain and redistribution of actin cytoskeleton in RBMECs. Taken together, our present study demonstrated that low-dose EMAP-II increases BTB permeability by activating the PKC-ζ/PP2A signaling pathway, which consequently leads to the disruption of TJs and impairment of endothelial barrier function.

Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin.

After demonstrating bradykinin (BK) could increase the permeability of blood-tumor barrier (BTB) via opening the tight junction (TJ), and that the possible mechanism is unclear, we demonstrated that BK could increase the expressions of eNOS and nNOS and promote ZONAB translocation into nucleus. NOS inhibitors l-NAME and 7-NI could effectively block the effect of BK on increasing BTB permeability, decreasing the expressions of claudin-5 and occludin and promoting the translocation of ZONAB. Overexpression of ZONAB could significantly enhance BK-mediating BTB permeability. Meanwhile, chromatin immunoprecipitation verified ZONAB interacted with the promoter of claudin-5 and occludin respectively. This study indicated NOS/NO/ZONAB pathway might be involved in BK's increasing the permeability of BTB.

A multicentre retrospective study of transcatheter angiographic embolization in the treatment of delayed haemorrhage after percutaneous nephrolithotomy.

OBJECTIVE: The objective is to determine the timing and indications of transcatheter angiographic embolization (TAE) for delayed haemorrhage after percutaneous nephrolithotomy (PCNL). METHODS: The medical records of 144 patients who underwent arteriography and TAE for delayed post-PCNL haemorrhage at five university hospitals between January 2005 and December 2012 were reviewed retrospectively. RESULTS: The mean time to the onset of post-PCNL haemorrhage was 10.5 days (2 - 30 days). Clinical presentation included sudden onset bleeding in 51 patients (35.4 %), intermittent bleeding in 67 patients (46. 5 %), and continuous slow bleeding in 26 patients (18.1 %). Hemodynamic instability occurred in 32 patients (22.2 %). The mean haemoglobin decrease from the first post-PCNL day to the day of TAE was 49.5 g/L (31.0 - 79.0 g/L). Renal arteriography showed pseudoaneurysms in 69 (47.9 %) patients, arteriovenous fistulas in 28 (19.4 %) patients, mixed arterial and arteriovenous lesions in 17 (11.8 %) patients, arterial lacerations in 23 (16.0 %) patients, and negative angiographic finding in seven (4.9 %) patients. TAE was successful in stopping bleeding in all 137 patients with vascular lesions. There were no major complications associated with TAE. CONCLUSIONS: TAE should be the recommended treatment for delayed post-PCNL haemorrhage in patients with hemodynamic instability and/or corrected haemoglobin decrease >30 g/L following conservative management. KEY POINTS: • Delayed haemorrhage after percutaneous nephrolithotomy occurs more than 24 hours postoperatively. • Angio-embolization is a safe and effective treatment for delayed post-PCNL haemorrhage. • Angio-embolization can treat hemodynamic instability and/or corrected haemoglobin decrease >30 g/L.

Placental transfer of dechlorane plus in mother-infant pairs in an e-waste recycling area (Wenling, China).

It has been reported that breastfeeding can expose newborns to dechlorane plus (DP), but transplacental transfer of DP has not been documented. We measured DP and its dechlorinated analogs in matched maternal blood-placenta-cord blood samples from 72 residents of the e-waste recycling area of Wenling, China. DP was detected in cord sera, indicating the occurrence of prenatal DP exposure and the transfer of DP across the placenta. The concentration ratio in the cord serum and maternal serum was estimated to be 0.45 for syn-DP and 0.35 for anti-DP, indicating the placenta partially limited DP transfer with a greater extent for anti-DP. The DP concentrations in the maternal serum, placenta, and cord serum strongly correlated, indicating that DP could transfer between the tissues. The DP concentrations in the matched samples could be predicted from each other. The anti-DP/total DP concentration ratios in the placentas and cord sera were significantly different from those in the maternal sera, suggesting that DP stereoselectively bioaccumulates in human tissues. When the congener concentrations of polybrominated diphenyl ethers (PBDEs) were used as control variables, DP and total triiodothyronine concentrations were associated in the sera from mothers who had lived in Wenling for over 20 years.

Digression and Value Concatenation to Enable Privacy-Preserving Regression.

Regression techniques can be used not only for legitimate data analysis, but also to infer private information about individuals. In this paper, we demonstrate that regression trees, a popular data-analysis and data-mining technique, can be used to effectively reveal individuals' sensitive data. This problem, which we call a "regression attack," has not been addressed in the data privacy literature, and existing privacy-preserving techniques are not appropriate in coping with this problem. We propose a new approach to counter regression attacks. To protect against privacy disclosure, our approach introduces a novel measure, called digression, which assesses the sensitive value disclosure risk in the process of building a regression tree model. Specifically, we develop an algorithm that uses the measure for pruning the tree to limit disclosure of sensitive data. We also propose a dynamic value-concatenation method for anonymizing data, which better preserves data utility than a user-defined generalization scheme commonly used in existing approaches. Our approach can be used for anonymizing both numeric and categorical data. An experimental study is conducted using real-world financial, economic and healthcare data. The results of the experiments demonstrate that the proposed approach is very effective in protecting data privacy while preserving data quality for research and analysis.

Pricing and disseminating customer data with privacy awareness.

Organizations today regularly share their customer data with their partners to gain competitive advantages. They are also often requested or even required by a third party to provide customer data that are deemed sensitive. In these circumstances, organizations are obligated to protect the privacy of the individuals involved while still benefiting from sharing data or meeting the requirement for releasing data. In this study, we analyze the tradeoff between privacy and data utility from the perspective of the data owner. We develop an incentive-compatible mechanism for the data owner to price and disseminate private data. With this mechanism, a data user is motivated to reveal his true purpose of data usage and acquire the data that suits to that purpose. Existing economic studies of information privacy primarily consider the interplay between the data owner and the individuals, focusing on problems that occur in the collection of private data. This study, however, examines the privacy issue facing a data owner organization in the distribution of private data to a third party data user when the real purpose of data usage is unclear and the released data could be misused.

[Experimental study and mechanism research of 701 diedazhentonggao on acute and chronic soft tissue injury in rabbit].

OBJECTIVE: To study the effect and mechanism of 701 Diedazhentonggao on acute and chronic soft tissue injury in rabbit. METHODS: The rabbit model of acute and chronic soft tissue injury were established by heavy hammer blow method. The tissue damage scored, pain threshold value and blood rheology were detected, and histopathological and inflammatory cytokines in damaged tissue and gene chip were observed. RESULTS: 701 Diedazhentonggao significantly improved the acute soft tissue injury symptoms, increased the pain threshold, reduced the score values of local damage, improved subcutaneous ecchymosis symptoms, reduced the content of inflammatory cytokines in damaged tissue, repaired the injuried tissue, and reduced blood viscosity and the content of IL-1 and 5-HT. But the contents of IL-6 and PGE2 in acute soft tissue injury were not reduced. The gene chip study expressed the drug interfered the pathway of IL-1R and white blood cell cling. 701 Diedazhentonggao also improved the chronic soft tissue injury symptoms and the main performance on anti-inflammatory effect, and reduced the contents of IL-6, IL-1 and 5-HT, but it had little effet on reducing the contents of PGE2, Fbg, blood and histopathological examination. CONCLUSION: 701 Diedazhentonggao has ameliorative effect on acute and chronic soft tissue injury, but the effect on acute soft tissue injuries is better than on chronic soft tissue injuries, and its mechanism may be related to reducing the contents of IL-1, IL-6, 5-HT and other related inflammatory mediators.

Prevalence of hepatitis B virus and hepatitis C virus in patients with human immunodeficiency virus infection in Central China.

Co-infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has an adverse effect on liver disease progression. This study investigated the prevalence of HBV and/or HCV co-infection in HIV-infected patients in Central China. A total of 978 HIV-infected patients from Hunan Province were enrolled. HBV serum markers, anti-hepatitis-C-virus antibody (anti-HCV), HBV DNA, and HBV genotypes were analyzed. The prevalence of hepatitis B surface antigen (HBsAg) and anti-HCV in HIV-infected patients was 19.4 % and 62.4 %, respectively. The prevalence of anti-HCV in HIV-positive intravenous drug users was 93.6 %. Among HBsAg-positive patients, 88.1 % were found to have at least one HBV serum marker. The rates of HIV mono-infection, HBV/HIV dual infection, HCV/HIV dual infection, and HBV/HCV/HIV triple infection were 30.4 %, 7.2 %, 50.2 %, and 12.2 %, respectively. Antibody to HBsAg (Anti-HBs) was more common in anti-HCV-positive than anti-HCV-negative patients (53.3 % vs 40.2 %, P = 0.000), but isolated hepatitis B core antibody (anti-HBc) was more common in anti-HCV-negative than anti-HCV-positive patients (24.2 % vs 12.3 %, P = 0.000). Hepatitis B e antigen (HBeAg) and sexual transmission were independent risk factors for active HBV replication. Intravenous drug use and male sex were independent risk factors, but old age and presence of HBeAg were independent protective factors for anti-HCV. Co-infection of HBV and/or HCV with HIV infection is common in central China. HCV status is associated with anti-HBs and isolated anti-HBc in co-infected patients.

Deep Learning for Predicting Distant Metastasis in Patients with Nasopharyngeal Carcinoma Based on Pre-Radiotherapy Magnetic Resonance Imaging.

IMPORTANCE: Accurate pre-treatment prediction of distant metastasis in patients with Nasopharyngeal Carcinoma (NPC) enables the implementation of appropriate treatment strategies for high-risk individuals. PURPOSE: To develop and assess a Convolutional Neural Network (CNN) model using pre-therapy Magnetic Resonance (MR) imaging to predict distant metastasis in NPC patients. METHODS: We retrospectively reviewed data of 441 pathologically diagnosed NPC patients who underwent complete radiotherapy and chemotherapy at Renmin Hospital of Wuhan University (Hubei, China) between February 2012 and March 2018. Using Adobe Photoshop, an experienced radiologist segmented MR images with rectangular regions of interest. To develop an accurate model according to the primary tumour, Cervical Metastatic Lymph Node (CMLN), the largest area of invasion of the primary tumour, and image segmentation methods, we constructed intratumoural and intra-peritumoural datasets that were used for training and test of the transfer learning models. Each model's precision was assessed according to its receiver operating characteristic curve and accuracy. Generated high-risk-related Grad-Cams demonstrated how the model captured the image features and further verified its reliability. RESULTS: Among the four models, all intra-peritumoural datasets performed better than the corresponding intratumoural datasets, with the CMLN intra-peritumoural dataset exhibiting the best performance (average area under the curves (AUCs) = 0.88). There was no significant difference between average AUCs of the Max and NPC tumour datasets. AUCs of the eight datasets for the four models were higher than those of the Tumour-Node-Metastasis staging system (AUC=0.67). In most datasets, the xception model had higher AUCs than other models. The efficientnet-b0 and xception models efficiently extracted high-risk features. CONCLUSION: The CNN model predicted distant metastasis in NPC patients with high accuracy. Compared to the primary tumour, the CMLN better predicted distant metastasis. In addition to intratumoural data, peritumoural information can facilitate the prediction of distant metastasis. With a larger sample size, datasets of the largest areas of tumour invasion may achieve meaningful accuracy. Among the models, xception had the best overall performance.

Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3ß signaling pathway.

BACKGROUND: Diabetic encephalopathy is manifested by cognitive dysfunction. Salidroside, a nature compound isolated from Rhodiola rosea L, has the effects of anti-inflammatory and antioxidant, hypoglycemic and lipid-lowering, improving insulin resistance, inhibiting cell apoptosis, and protecting neurons. However, the mechanism by which salidroside alleviates neuronal degeneration and improves learning and memory impairment in diabetic mice remains unclear. OBJECTIVE: To investigate the effects and mechanisms of salidroside on hippocampal neurons in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into 4 groups to receive either sham (control group (CON)), diabetes mellitus (diabetes group (DM)), diabetes mellitus + salidroside (salidroside group (DM + SAL)), and diabetes mellitus + salidroside + phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (diabetes mellitus + salidroside + LY294002 group (DM + SAL + LY294002)). After 12 weeks of diabetes onset, the cognitive behaviors were tested using Morris water maze. The number of hippocampal neurons was detected by Nissl staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, GSK-3ß, p-GSK-3ß, cleaved caspase-3, caspase-3, Bax, Bcl-2, MAP2, and SYN in the hippocampus were detected by Western blot. Moreover, the expression of MAP2 and SYN in the hippocampus was further confirmed by immunofluorescence staining. RESULTS: Salidroside increased the time of diabetic mice in the platform quadrant and reduced the escape latency of diabetic mice. Salidroside also increased the expression of p-PI3K, p-Akt, p-GSK-3ß, MAP2, SYN, Bcl-2, while suppressed the expression of cleaved caspase-3, caspase3, and Bax in the DM + SAL group compared with the DM group (P < 0.05). The Nissl staining showed that the number of hippocampus neurons in the DM + SAL group was increased with the intact, compact, and regular arrangement, compared with the DM groups (P < 0.05). Interestingly, the protective effects of salidroside on diabetic cognitive dysfunction, hippocampal morphological alterations, and protein expressions were abolished by inhibition of PI3K with LY294002. CONCLUSIONS: Salidroside exerts neuroprotective properties in diabetic cognitive dysfunction partly via activating the PI3K/Akt/GSK-3ß signaling pathway.

Cyclophilin A (CyPA) induces chemotaxis independent of its peptidylprolyl cis-trans isomerase activity: direct binding between CyPA and the ectodomain of CD147.

Cyclophilin A (CyPA) is a ubiquitously distributed peptidylprolyl cis-trans isomerase (PPIase) that possesses diverse biological functions. Extracellular CyPA is a potent chemokine, which can directly induce leukocyte chemotaxis and contribute to the pathogenesis of inflammation-mediated diseases. Although it has been identified that the chemotaxis activity of CyPA is mediated through its cell surface signaling receptor CD147, the role of CyPA PPIase activity in this process is disputable, and the underlying molecular mechanism is still poorly understood. In this study, we present the first evidence that CyPA induces leukocyte chemotaxis through a direct binding with the ectodomain of CD147 (CD147(ECT)), independent of its PPIase activity. Although NMR study indicates that the CD147(ECT) binding site on CyPA overlaps with the PPIase active site, the PPIase inactive mutant CyPA(R55A) exhibits similar CD147(ECT) binding ability and chemotaxis activity to those of CyPA(WT). Furthermore, we have identified three key residues of CyPA involved in CD147(ECT) binding and found that mutations H70A, T107A, and R69A result in similar levels of reduction in CD147(ECT) binding ability and chemotaxis activity for CyPA, without affecting the PPIase activity. Our findings indicate that there exists a novel mechanism for CyPA to regulate cellular signaling processes, shedding new light on its applications in drug development and providing a new targeting site for drug design.