Purpose: To determine the association between frailty and postoperative complications in elderly Chinese patients and to determine whether addition of frailty assessment improves the predictive ability of the American Society of Anesthesiologists (ASA) score, Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM), and Estimation of Physiologic Ability and Surgical Stress (E-PASS) score. Patients and methods: A prospective cohort study was conducted in a tertiary hospital. Elderly patients undergoing major thoracic or abdominal surgery were included. Frailty phenotype and ASA, POSSUM, and E-PASS scores were assessed. Demographic, preoperative, and surgical variables were extracted from medical records. Primary outcome measure was in-hospital Clavien-Dindo ≥ grade II complications. Multiple logistic regression was used to examine the association between frailty and complications. Receiver operating characteristic curves were used to explore the predictive ability of frailty. Results: Prevalence of frailty was 26.12%. Significant differences were observed between the frail and non-frail groups with respect to age, Activities of Daily Living, Charlson Comorbidity Index, respiratory function, presence of malignancy, serum albumin, prealbumin, and hemoglobin levels (P<0.05). ASA, POSSUM, and E-PASS scores were higher in the frail group. After adjusting for all covariates, frailty was significantly associated with postoperative complications in hospital [odds ratio: 16.59, 95% CI: 4.56-60.40, P<0.001]. The area under the curve (AUC) for frailty was 0.762 (95% CI: 0.703-0.814). The AUC for ASA, POSSUM, and E-PASS for prediction of complications was 0.751 (95% CI: 0.692-0.804), 0.762 (95% CI: 0.704-0.814), and 0.824 (95% CI: 0.771-0.870), respectively. Addition of frailty assessment increased the AUC to 0.858 (95% CI: 0.808-0.899), 0.842 (95% CI: 0.790-0.885), and 0.854 (95% CI: 0.803-0.896), respectively. Conclusion: Frailty is an effective predictor of postoperative complications in elderly Chinese patients undergoing major thoracic and abdominal surgery. Frailty assessment can improve the predictive ability of current surgical risk assessment tools. Frailty phenotype should be considered perioperatively. Frailty assessment could also expand the scope for nurses to evaluate patients for safety management.

Background: Oral route of administration is preferred for treating breast cancer, especially when continued disease management with good tolerability is required; however, orally administered chemotherapeutics combined with near-infrared (NIR) dyes are hindered by the low bioavailability, insufficient for the desired therapeutic efficacy. In this study, we developed a hybrid self-microemulsifying drug delivery system for co-loading curcumin-phospholipid complex and NIR dye IR780 (CUR/IR780@SMEDDS), to achieve combined phototherapeutic and chemotherapeutic effects against lung metastasis of breast cancer. Methods: CUR/IR780@SMEDDS were characterized. The efficacy against breast cancer metastasis was evaluated by photothermal and photodynamic assessment, cytotoxicity, invasion, and migration in metastatic 4T1 breast cancer cells in vitro, and in vivo oral bioavailability study in rats and pharmacodynamics studies in tumor-bearing nude mice. Results: CUR/IR780@SMEDDS improved oral bioavailability of curcumin and IR780 in rats compared with curcumin and IR780 suspensions. CUR/IR780@SMEDDS exhibited remarkable photothermal and photodynamic effects in vitro. In metastatic 4T1 breast cancer cells, CUR/IR780@SMEDDS combined with localized NIR laser irradiation induced significant cytotoxicity and inhibited invasion and migration of 4T1 cells, an outcome attributable to cumulative effects of IR780-induced hyperthermia and pharmacological effects of curcumin. In orthotopic 4T1 tumor-bearing nude mice, combination of oral administration of CUR/IR780@SMEDDS with local NIR laser irradiation inhibited tumor progression and suppressed lung metastasis.

Background: Designing a wound dressing that effectively prevents multi-drug-resistant bacterial infection and promotes angiogenesis and re-epithelialization is of great significance for wound management. Methods and results: In this study, a biocompatible composite membrane comprising biomimetic polydopamine-modified eggshell membrane nano/microfibres coated with KR-12 antimicrobial peptide and hyaluronic acid (HA) was developed in an eco-friendly manner. The physicochemical properties of the composite membrane were thoroughly characterized, and the results showed that the surface hydrophilicity and water absorption ability of the composite membrane were improved after the successive conjugation of the HA and the KR-12 peptide. Furthermore, the in vitrobiological results revealed that the composite membrane had excellent antibacterial activity against Gram-positive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, and it could prevent MRSA biofilm formation on its surface. Additionally, it promoted the proliferation of keratinocytes and human umbilical vein endothelial cells and increased the secretion of VEGF. Finally, an in vivo animal study indicated that the composite membrane could promote wound healing via accelerating angiogenesis and re-epithelialization, which were demonstrated by the enhanced expression of angiogenetic markers (CD31 and VEGF) and keratinocyte proliferation marker (PCNA), respectively. Conclusion: These results indicated that the composite membrane is a potential candidate of wound dressings.

Objective: The microbial, physico-chemical and optical corruptions threaten a variety of foods and drugs and consequently the human biological safety and its accessible resources. The humanbeing's tendency towards bio-based materials and natural plant-extracts led to an increase in the usage of antimicrobial biocomposites based on medicinal herbs. Miswak (Salvadora persica L.) extract (SPE) has been proved effective for its antimicrobial and other biological activities. Therefore, in this study, titanium dioxide (TiO2) nanoparticles (TONP) and SPE were applied to fabricate antimicrobial carboxymethyl cellulose (Na-CMC) based bio-nanocomposites which would simultaneously promote some thermo-physical and barrier properties. Methods: CMC-neat film (C1), CMC/TONP-2% (C2) and CMC/TONP-2% with 150, 300 and 450 mg/mL SPE (SPE150, SPE30 and SPE450, respectively) were fabricated. The physical and mechanical properties; elemental mapping analysis (MAP), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA-DTG); fourier transform infrared (FTIR), energy-dispersive X-ray (EDX) and UV-vis spectroscopies were done to further validate the results. Results: Addition of TONP (2%) improved the blocking of UV light at 280 nm while SPE-containing nanocomposites completely blocked it. FTIR, XRD and SEM confirmed the formation of homogeneous films and high miscibility of applied materials. TONP led to an increase in Young's modulus (YM) and stress at break (SB) while SPE decreased them and enhanced the elongation to break (EB) (flexibility) of the active nanocomposites. Compared to CMC-film, the thermo-gravimetric analysis (TGA-DTG) showed a higher thermal stability for CMC/TONP and CMC/TONP/SPE nanocomposites. The EDX spectroscopy and elemental mapping analysis (MAP) proved the existence and well-distributedness of Na, K, Cl, S, Ti, F and N elements in SPE-activated nanocomposites. The pure SPE and SPE-activated nanocomposites showed a favorable antimicrobial activity against both gram-positive (Staphylococcus aureus) and negative (Escherichia coli) bacteria. Conclusion: The CMC-TiO2-SPE nanocomposites were homogeneously produced. Combination of TiO2 nanoparticles and dose-dependent SPE led to an improvement of thermal stability, and high potential in antimicrobial and UV-barrier properties. These results can generally highlight the role of the fabricated antimicrobial bio-nanocomposites as a based for different applications especially in food/drug packaging or coating.

Background: Liver plays a vital role in the elimination of xenobiotics that can induce hepatotoxicity in living organisms.Silver nanoparticles have evolved recently as an alternative in various industries and are used for their biomedical applications.Rhizophora apiculata is a least studied mangrove-based plant that has been used in the traditional medicine of Southeast Asia for its healing properties. It is a well-known fact that the generation of free radicals has been associated with oxidative stress.  Methods: Hence, in this study we used carbon tetrachloride as a hepatotoxin to induce liver damage. The protective effects of silver nanoparticles synthesized using Rhizophora apiculata on hepatotoxin-induced liver damage in experimental mice were assessed.  Results: The results of the assessment indicate that silver nanoparticles were effective in protecting the liver from damages induced by carbon tetrachloride.  Conclusion: Among existing literature, this is the first ever approach for hepatoprotective effect of nanoparticles derived using plant extract from mangrove ecosystem.

Background: In recent years, non-invasive imaging technologies for early cancer detection have drawn worldwide attention. In this study, an antinucleolin aptamer, AS1411, was successfully conjugated to BODIPY-labeled chitosan and studied on T47D and HEK-293 cell lines. Methods: After conjugation of the aptamer to chitosan nanoparticles and purification, its structure was confirmed using atomic force microscopy (AFM), electrophoretic light scattering (ELS) and dynamic light scattering (DLS). Results of AFM, DLS and ELS of both conjugation and chitosan were compared for confirmation of conjugation. Conjugates were mixed with BODIPY FL fluorescent dye, purified and lyophilized. The labeled conjugate was characterized using Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, ELS and DLS. In vitro cellular uptake and cytotoxic effects of BODIPY-labeled chitosan-AS1411 aptamer conjugates were evaluated using the XTT assay on T47D and HEK-293 cells and flow cytometry on T47D cells. Results: The data showed that uptake of BODIPY-labeled chitosan-AS1411 aptamer conjugate was satisfactory. Moreover, there was no statistically significant cytotoxicity of the conjugate on either cell line. Conclusion: The outcomes confirmed the potential application of this new targeted imaging agent as a novel cancer diagnostic agent for molecular imaging.

Purpose: Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment. Methods: The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin 'two in one' nanocarriers. Results: We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression. Conclusion: Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate.

Purpose: This study aimed to decorate the surface of TiO2 nanotubes (TiO2 NTs) grown on medical grade Ti-6Al-4V alloy with an antimicrobial layer of nano zinc oxide particles (nZnO) and then determine if the antimicrobial properties were maintained with a final layer of nano-hydroxyapatite (HA) on the composite. Methods: The additions of nZnO were attempted at three different annealing temperatures: 350, 450 and 550 °C. Of these temperatures, 350°C provided the most uniform and nanoporous coating and was selected for antimicrobial testing. Results: The LIVE/DEAD assay showed that ZnCl2 and nZnO alone were >90% biocidal to the attached bacteria, and nZnO as a coating on the nanotubes resulted in around 70% biocidal activity. The lactate production assay agreed with the LIVE/DEAD assay. The concentrations of lactate produced by the attached bacteria on the surface of nZnO-coated TiO2 NTs and ZnO/HA-coated TiO2 NTs were 0.13±0.03 mM and 0.37±0.1 mM, respectively, which was significantly lower than that produced by the bacteria on TiO2 NTs alone, 1.09±0.30 mM (Kruskal-Wallis, P<0.05, n=6). These biochemical measurements were correlated with electron micrographs of cell morphology and cell coverage on the coatings. Conclusion: nZnO on TiO2 NTs was a stable and antimicrobial coating, and most of the biocidal properties remained in the presence of nano-HA on the coating.

Background: Electrospun gelatin/polycaprolactone (Gt/PCL) nanofibrous scaffolds loaded with graphene are novel nanomaterials with the uniquely strong property of electrical conductivity, which have been widely investigated for their potential applications in cardiovascular tissue engineering, including in bypass tracts for atrioventricular block. Purpose: Electrospun Gt/PCL/graphene nanofibrous mats were successfully produced. Scanning electron micrography showed that the fibers with graphene were smooth and homogeneous. In vitro, to determine the biocompatibility of the scaffolds, hybrid scaffolds with different fractions of graphene were seeded with neonatal rat ventricular myocytes. In vivo, Gt/PCL scaffolds with different concentrations of graphene were implanted into rats for 4, 8 and 12 weeks. Results: CCK-8 assays and histopathological staining (including DAPI, cTNT, and CX43) indicated that cells grew and survived well on the hybrid scaffolds if the mass fraction of graphene was lower than 0.5%. After implanting into rats for 4, 8 or 12 weeks, there was no gathering of inflammatory cells around the nanomaterials according to the HE staining results. Conclusion: The results indicate that Gt/PCL nanofibrous scaffolds loaded with graphene have favorable electrical conductivity and biological properties and may be suitable scaffolds for use in the treatment of atrioventricular block. These findings alleviate safety concerns and provide novel insights into the potential applications of Gt/PCL loaded with graphene, offering a solid foundation for comprehensive in vivo studies.

Background: Attention-deficit hyperactivity disorder (ADHD) is a complex disorder in terms of etiology, clinical presentation, and treatment outcome. Pharmacological and psychological interventions are recommended as primary treatments in ADHD; however, other nonpharmacological intervention such as a dietary supplementation with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has emerged as an attractive option. Purpose: The objective of the present study was to assess whether dietary supplementation with highly concentrated ω-3 docosahexaenoic acid (DHA) triglyceride may improve symptoms in ADHD. Method: A 6-month prospective double-blind placebo-controlled randomized clinical trial was designed in 66 patients with ADHD, aged between 6 and 18 years. Participants in the experimental group received a combination of ω-3 fatty acids (DHA 1,000 mg, eicosapentaenoic acid 90 mg, and docosapentaenoic acid 150 mg). Instruments included d2-test, AULA Nesplora, EDAH scales, and abbreviated Conner's Rating Scale. Results: In the cognitive test, between-group differences were not found, but within-group differences were of a greater magnitude in the DHA group. Between-group differences in favor of the DHA arm were observed in behavioral measures, which were already detected after 3 months of treatment. Results were not changed when adjusted by ADHD medication. Conclusions: This study provides further evidence of the beneficial effect of supplementation with ω-3 DHA in the management of ADHD.

White matter lesions (WMLs) play a role in cognitive decline and dementia. Little is known about gray matter (GM) changes in WMLs. This study aimed to investigate GM changes in WML patients.

Background: Poststroke depression (PSD) is the most frequent psychological sequela after stroke. Electroacupuncture (EA) treatment is effective for PSD. The study aimed at clarifying the mechanisms of EA's antidepressant effects in a PSD rat model. Methods: We used middle cerebral artery occlusion to establish the rat model of PSD. Tests of sucrose preference and locomotor activity were performed to examine depressive-like behaviors. We measured malondialdehyde, GSH, SOD, IL6, IL1β, TNFα, and 5HT with ELISA. The hippocampal Shh-signaling pathway was assessed by Western blot. Results: EA significantly decreased sucrose preference and locomotor activities of PSD rats, reduced IL6, TNFα, increased GSH, and upregulated 5HT, and also slightly reduced IL1β and malondialdehyde, all of which were measured with ELISA. The Shh-signaling pathway assessed by Western blotting was activated by EA. Those changes were inhibited by the Shh-pathway inhibitor cyclopamine. Conclusion: EA effectively alleviated depressive-like behaviors in PSD by suppressing inflammation and oxidative stress through activation of the Shh-signaling pathway.

Background: To detect the expression of miR-124 in bladder cancer (BC) cell lines and tissue specimens and to analyze its association with the growth of the BC cells. Methods: Quantitative real-time polymerase chain reaction (qPCR) was applied to examine the expression of miR-124 in BC cell lines and tissues. The function of miR-124 in modulating cell proliferation was assessed in BC cells with miRNA-124 overexpression; the cell viability was identified by Cell Count Kit-8; flow cytometry was employed to detect the cell cycle; the expressions of E2F3, cyclin-dependent kinase 4 (CDK4), Ki-67 and vascular endothelial growth factor (VEGF) were tested by qPCR and Western blot; angiogenesis experiment was performed to analysis changes in angiogenesis rate; and bioinformatics prediction and dual luciferase reporter system were employed to identify the target of miR-124. Results: Survival curve data showed that the expression of MicroRNA-124 was positively correlated with survival. MicroRNA-124 expression was significantly decreased in BC cell lines and tissues. Bioinformatics prediction and dual luciferase reporter system verified CDK4 as a direct target of miR-124, which regulated the proliferation of BC cells by directly inhibiting CDK4. BC cells over-expressing miR-124 showed significantly inhibited cell viability, decreased angiogenesis rate, prevented cell proliferation and diminished the expression of E2F3, CDK4, Ki-67 and VEGF. All of these changes were reversed by over-expressing CDK4. Conclusion: MicroRNA-124 suppressed the proliferation of CRC cells by directly targeting CDK4, which provides a target for improving the therapeutic effect of BC.

Background: Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer morbidity and mortality worldwide. In the present study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC. Methods: The microarray datasets of GSE18842, GSE30219, GSE31210, GSE32863 and GSE40791 from Gene Expression Omnibus database were downloaded. The differential expressed genes (DEGs) between NSCLC and normal samples were identified by limma package. The construction of protein-protein interaction (PPI) network, module analysis and enrichment analysis were performed using bioinformatics tools. The expression and prognostic values of hub genes were validated by GEPIA database and real-time quantitative PCR. Based on these DEGs, the candidate small molecules for NSCLC were identified by the CMap database. Results: A total of 408 overlapping DEGs including 109 up-regulated and 296 down-regulated genes were identified; 300 nodes and 1283 interactions were obtained from the PPI network. The most significant biological process and pathway enrichment of DEGs were response to wounding and cell adhesion molecules, respectively. Six DEGs (PTTG1, TYMS, ECT2, COL1A1, SPP1 and CDCA5) which significantly up-regulated in NSCLC tissues, were selected as hub genes according to the results of module analysis. The GEPIA database further confirmed that patients with higher expression levels of these hub genes experienced a shorter overall survival. Additionally, CMap predicted the 20 most significant small molecules as potential therapeutic drugs for NSCLC. DL-thiorphan was the most promising small molecule to reverse the NSCLC gene expression. Conclusions: Based on the gene expression profiles of 696 NSCLC samples and 237 normal samples, we first revealed that PTTG1, TYMS, ECT2, COL1A1, SPP1 and CDCA5 could act as the promising novel diagnostic and therapeutic targets for NSCLC. Our work will contribute to clarifying the molecular mechanisms of NSCLC initiation and progression.

Background: Nanog has been found to be overexpressed in various cancers. However, the association between Nanog expression and prognosis or clinicopathological features is still controversial. Therefore, this meta-analysis was conducted to identify whether Nanog expression was associated with prognosis or clinicopathological characteristics in non-small cell lung cancer (NSCLC). Methods: We searched Embase, PubMed, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure database (CNKI), and the Wanfang database for articles. Pooled hazard ratios (HR), odds ratios (OR), and corresponding 95% confidence intervals (CI) were utilized to evaluate the relationship between Nanog expression and prognosis or clinicopathological characteristics in NSCLC. Results: The results showed that high expression of Nanog was significantly associated with poor overall survival (OS) (HR=1.95, 95% CI: 1.38-2.75, P=0.000). Additionally, high Nanog expression was significantly correlated with tumor differentiation (OR=3.18, 95% CI: 1.69-5.98, P=0.000) and TNM stage (OR=1.78, 95% CI: 1.28-2.47, P=0.001). However, no significant relationship was observed between Nanog expression and other clinicopathological features, including gender (OR=0.95, 95% CI: 0.69-1.33, P=0.783), age (OR=0.78, 95% CI: 0.57-1.07, P=0.119), tumor size (OR=0.87, 95% CI: 0.26-2.95, P=0.824), and lymph node metastasis (OR=1.29, 95% CI: 0.94-1.77, P=0.121). Conclusion: High Nanog expression was associated with poor prognosis in patients with NSCLC, and Nanog may serve as a prognostic predictor in NSCLC.

Background/Aims: Recently, the insulin-like growth factor mRNA-binding protein 3 (IMP3) has been reported to be involved in tumorigenesis. We aimed to study the expression and role of IMP3 in human glioblastoma. Methods: We analyzed the expression of IMP3 in 70 cases of glioma tissues, normal brain tissues and 5 kinds of cell lines using western blot. Immunohistochemistry (IHC) was used to evaluate the expression and distribution of IMP3 in glioma tissues. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of IMP3 in vitro and in vivo. The epithelial-mesenchymal transition (EMT)-related biomarkers were detected by western blot. Results: We found that the expression level of IMP3 was obviously higher in glioma tissues than that in normal brain tissues, and associated with glioma grade. In-vitro assays revealed that IMP3 overexpression significantly induced cell proliferation, migration, and invasion. Mechanically, IMP3 over-expression downregulated the expression of E-cadherin, but upregulated the expressions of N-cadherin, vimentin, snail, slug and MMP9. However, the inhibition of IMP3 impaired these oncogenic effects. In vivo assay also demonstrated that silencing of IMP3 inhibited tumor growth and improved survival of tumor-bearing xenograft nude mice. Conclusion: IMP3 can promote cell proliferation, migration and invasion by inducing EMT in glioblastoma. Thus, targeting IMP3 pathway may be a novel way to treat patients with glioblastoma.

Purpose: The prognostic role of programmed death-ligand 1 (PD-L1) in colorectal cancer remains unclear. We employed a meta-analysis to explore the prognostic value of PD-L1 and to ascertain the relationship between PD-L1 expression and clinicopathological characteristics in CRC patients. Methods: We systematically searched PubMed, Embase and the Cochrane Library until October 2018. Eligible studies about colorectal cancer that pay attention to PD-L1 expression and studies reporting survival information were included. In order to evaluate the prognostic role of PD-L1 for overall survival (OS) and recurrence-free survival (RFS)/disease-free survival (DFS), Hazard ratio (HR) with 95% confidence interval (CI) was used. Odds ratio (OR) with 95% CI was selected to appraise the correlation between PD-L1 with clinicopathological characteristics of colorectal cancer patients. Begg's funnel plot was used to assess publication bias. Results: Twelve studies involving 4344 patients published from 2013 to 2018 were included in this meta-analysis. Pooled results revealed that PD-L1 overexpression was relevant to shorter OS (HR 1.47, 95% CI =1.01-2.15, p=0.04) and shorter RFS/DFS (HR 1.47, 95% CI =1.01-2.15, p=0.04). Moreover, Patients with high expression of PD-L1 associated with inferior tumor stage (OR=0.57, 95% CI: 0.45, 0.74, p<0.0001) and Vascular invasion-negativity (OR=0.75, 95% CI: 0.6, 0.94, p=0.01). But the expression of PD-L1 is not related to age, sex, tumor location, tumor differentiation, pT stage, pN stage, MSI/MMR status. Conclusion: This meta-analysis revealed that PD-L1 can serve as a significant biomarker for negative prognosis and the adverse clinicopathological features of colorectal cancer and could facilitate the better management of individual patients.

Background: Seminoma accounts for the most part of cases of testicular germ cell tumor, which is the most common malignancy among males between ages 15 and 44 years. Understanding the molecular mechanism of tumorigenesis is important for better clinical diagnosis and treatment. Purpose: We performed bioinformatics analysis to better understand seminoma at the genetic level and to explore potential candidate genes or molecules for diagnosis, treatment, and prognosis. Methods: A gene expression profile (GSE8607), containing 40 seminoma samples and three healthy testes samples, was analyzed to identify differentially expressed genes (DEGs) associated with the occurrence of seminoma. Functional annotation was then performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Cytoscape with Search Tool for the Retrieval of Interacting Genes was used to construct a protein-protein interaction (PPI) network of the DEGs and select hub genes. Moreover, validation of expression level and Kaplan-Meier analysis for overall survival were conducted to those hub genes. Results: A total of 1,636 DEGs were identified between seminoma and healthy samples, including 701 up-regulated in seminoma that were enriched in the regulation of immune responses, defense responses, receptor activity, and signal transducer activity; 935 were down-regulated in seminoma and were associated with reproductive processes, kinase activity, and carbohydrate derivative binding. Five hub genes were selected from the PPI network according to the degree of connectivity: IL6, VEGFA, IL10, CCR5, and CXCR4. Among them, high expression levels of CCR5 and CXCR4 were associated with poor prognosis for seminoma patients. Four modules selected from the PPI network revealed that seminoma was connected with the Janus kinase-signal transducers and activators of transcription signaling pathway, chemokine signaling pathway, endocytosis, and cytokine-cytokine receptor interaction. Conclusion: These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of seminoma and have the potential to be used as diagnostic biomarkers or therapeutic targets for seminoma.

Purpose: Autophagy is a major catabolic system by which eukaryotic cells undergo self-degradation of damaged, defective, or unwanted intracellular components. An abnormal autophagic level is implicated in the pathogenesis of multiple diseases, including cancers. The aim of this study is to explore the prognostic value of autophagy in bladder cancer (BC), which is a major cause of cancer-related death globally. Patients and methods: First, 27 differentially expressed autophagy-related genes (ARGs) were identified in BC patients based on The Cancer Genome Atlas (TCGA) database. Functional enrichment analyses hinted that autophagy may act in a tumor-suppressive role in the initiation of BC. Then, the Cox proportional hazard regression model were employed to identify three key prognostic ARGs (JUN, MYC, and ITGA3), which were related with overall survival (OS) significantly in BC. The three genes represented important clinical significance and prognostic value in BC. Then a prognostic index (PI) was constructed. Results: The PI was constructed based on the three genes, and significantly stratified BC patients into high- and low-risk groups in terms of OS (HR=1.610, 95% CI=1.200-2.160, P=0.002). PI remained as an independent prognostic factor in multivariate analyses (HR=2.355, 95% CI=1.483-3.739, P<0.001). When integrated with clinical characteristics of age and stage, an autophagy-clinical prognostic index (ACPI) was finally validated, which had improved performance in predicting OS of BC patients (HR=2.669, 95% CI=1.986-3.587, P<0.001). The ACPI was confirmed in datasets of GSE13507 (HR=7.389, 95% CI=3.645-14.980, P<0.001) and GSE31684 (HR=1.665, 95% CI=0.872-3.179, P=0.122). Conclusion: This study provides a potential prognostic signature for predicting prognosis of BC patients and molecular insights of autophagy in BC.

Background: In recent years, a large number of studies have shown that differentially expressed lncRNAs are capable of promoting the occurrence and development of tumors by regulating cell proliferation and differentiation. However, the biological effects of lncRNAs in non-small cell lung cancer (NSCLC) are still needed to be further investigated. Methods: The differentially expressed lncRNAs in NSCLC tissues in the downloaded profiles from GEO database were analyzed and further verified in 100 pairs of NSCLC samples collected in our hospital. After identification of the target gene MIR210HG, the relationship between MIR210HG expression and clinical data of NSCLC patients was analyzed. Regulatory effects of MIR210HG on proliferation, migration, and invasion of NSCLC cells were detected by CCK-8, colony formation, and transwell assay, respectively. The binding condition of MIR210HG and DNA methyltransferase 1 (DNMT1) was detected by RNA binding protein immunoprecipitation. Subsequently, chromatin immunoprecipitation assay assessed the promoter binding of DNMT1 to CACNA2D2. Rescue experiments were conducted to assess whether CACNA2D2 can reverse the function of MIR210HG. Results: MIR210HG was highly expressed in NSCLC tissues not only in GSE30219 dataset but also in our collected NSCLC tissues. MIR210HG expression was correlated to tumor stage and lymph node metastasis of NSCLC patients. Besides, lower disease-free survival (DFS) and overall survival (OS) were found in NSCLC patients with high-level MIR210HG compared with those with low-level MIR210HG. Regression analysis indicated that MIR210HG was the independent risk factor for DFS and OS of NSCLC patients. In vitro experiments demonstrated that MIR210HG knockdown remarkably inhibited proliferation and migration of NSCLC cells. MIR210HG could recruit DNMT1, thereafter promoting methylation of CACNA2D2 promoter region. CACNA2D2 overexpression remarkably inhibited cell proliferation. Moreover, inhibited proliferation induced by MIR210HG knockdown was reversed by CACNA2D2 knockdown. Conclusion: MIR210HG can promote the tumorigenesis of NSCLC by inhibiting the expression of CACNA2D2. Our findings provide new therapeutic strategies for the future treatment of NSCLC.