Neutrophil extracellular traps in cancer.

Neutrophil extracellular traps (NETs), which consist of chromatin DNA studded with granule proteins, are released by neutrophils in response to both infectious and sterile inflammation. Beyond the canonical role in defense against pathogens, the extrusion of NETs also contributes to the initiation, metastasis, and therapeutic response of malignant diseases. Recently, NETs have been implicated in the development and therapeutic responses of various types of tumors. Although extensive work regarding inflammation in tumors has been reported, a comprehensive summary of how these web-like extracellular structures initiate and propagate tumor progression under the specific microenvironment is lacking. In this review, we demonstrate the initiators and related signaling pathways that trigger NETs formation in cancers. Additionally, this review will outline the current molecular mechanisms and regulatory networks of NETs during dormant cancer cells awakening, circulating tumor cells (CTCs) extravasation, and metastatic recurrence of cancer. This is followed by a perspective on the current and potential clinical potential of NETs as therapeutic targets in the treatment of both local and metastatic disease, including the improvement of the efficacy of existing therapies.

Corrigendum: Assessing the causal relationship between genetically determined inflammatory biomarkers and low back pain risk: a bidirectional two-sample Mendelian randomization study.

[This corrects the article DOI: 10.3389/fimmu.2023.1174656.].

Biodegradation mechanism of chlortetracycline by a novel fungal Aspergillus sp. LS-1.

Chlortetracycline (CTC), a widely used typical tetracycline antibiotic, has raised increasing concerns due to its potential health and environmental risks. Biodegradation is considered an effective method to reduce CTC in environment. In this study, a strain Aspergillus sp. LS-1, which can efficiently degrade CTC, was isolated from CTC-rich activated sludge. Under optimal conditions, the maximum removal efficiency of CTC could reach 95.41%. Temperature was the most significant factor affecting the degradation efficiency of LS-1. The 19 products were identified in the CTC degradation by strain LS-1, and three degradation pathways were proposed. All the degradation pathways for CTC exhibited ring-cleaving, which may accelerate the mineralization of CTC. To gain more comprehensive insights into this strain, we obtained the genome of LS-1, which had high GC content (50.1%) and completeness (99.3%). The gene annotation revealed that LS-1 contains some vital enzymes and resistance genes that may carry functional genes involved in the CTC degradation. In addition, other antibiotic resistance genes were found in the genome of LS-1, indicating that LS-1 has the potential to degrade other antibiotics. This study provides a more theoretical basis for the investigation of CTC degradation by fungi and new insights into the biodegradation of CTC.

Assessing the causal relationship between genetically determined inflammatory biomarkers and low back pain risk: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have suggested an association between inflammatory markers and low back pain (LBP), but the causal relationship between these factors remains uncertain. Methods: We conducted a bidirectional two-sample Mendelian randomization analysis (MR) study to investigate whether there is a causal relationship between inflammatory markers and low back pain. We obtained genetic data for CRP, along with its upstream inflammatory markers IL-6, IL-8, and IL-10, as well as low back pain from publicly available genome-wide association studies (GWAS). We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald Ratio, and MR-PRESSO, to test for causal relationships. Sensitivity analyses were also conducted to assess the robustness of the results. Results: Our analyses utilizing the Inverse Variance Weighted (IVW) method, the MR-Egger method, and the weighted median method indicated that IL-6 may be associated with an increased risk of LBP (Effect Size: -0.009, 95% Confidence Interval: -0.013-0.006, p = 9.16e-08); however, in the reverse direction, there was no significant causal effect of LBP on inflammatory markers. Conclusion: Our study used a Mendelian randomization approach and found that elevated IL-6 levels may reduce the risk of LBP.

Activatable Mn2+-Armed nanoagonist augments antitumor immunity in colorectal cancer: A NIR-II Photonic neoadjuvant paradigm.

Postoperative recurrence frequently occurs in patients with colorectal cancer (CRC) due to residual microtumors and host cellular immune dysfunction, leading to major setbacks in clinical outcomes and CRC staging. As an increasingly prevalent therapeutic option for CRC patients, neoadjuvant chemoradiotherapy bears unmet challenges of limited tumor targeting and common side effects of gastrointestinal reaction and radiodermatitis. It is highly desirable to develop neoadjuvant treatment paradigms that impart both tumor-targeting accuracy and protection against recurrence of resectable CRC. Here we report a versatile photo-regulated nanoagonist of plasmonic gold blackbody (AuPB) with a polydopamine (PDA) coating carrying manganese ion (Mn2+) payloads (AuPB@PDA/Mn). When armed with second near-infrared (NIR-II) light, AuPB@PDA/Mn with broad-band localized surface plasmon resonance generates local hyperthermia and discharges Mn2+ ions, which evidently amplify the effects of immunogenic cell death in tumor cells and activate the cyclic GMP-AMP synthase/stimulator of interferon genes pathway in dendritic cells (DCs), hence potentiating the maturation of DC and the secretion of type I interferon in a synergistic way. Matured DCs undertake the task of tumor antigen presentation as the crosstalk to adaptive immunity. As such, the administration of AuPB@PDA/Mn coupled with NIR-II laser irradiation has eminently augmented the infiltration of CD8+ T cells as well as the development of memory CD8+ T cells in colorectal tumor models, substantiating enhanced immunomodulatory efficacy against primary and recurrent CRC. Our strategy highlights the potency of an integrated NIR-II photothermal and immunoregulatory modality by photo-activate delivery of Mn2+ ions, as a neoadjuvant paradigm for presurgical tumor debulking and against postoperative tumor recurrence.

Response of microbial interactions in activated sludge to chlortetracycline.

Chlortetracycline (CTC) has attracted increasing attention due to its potential environmental risks. However, its effects on bacterial communities and microbial interactions in activated sludge systems remain unclear. To verify these issues, a lab-scale sequencing batch reactor (SBR) exposed to different concentrations of CTC (0, 0.05, 0.5, 1 mg/L) was carried out for 106 days. The results showed that the removal efficiencies of COD, TN, and TP were negatively affected, and the system functions could gradually recover at low CTC concentrations (≤0.05 mg/L), but high CTC concentrations (≥0.5 mg/L) caused irreversible damage. CTC significantly altered bacterial diversity and the overall bacterial community structure, and stimulated the emergence of many taxa with antibiotic resistance. Molecular ecological network analysis showed that low concentrations of CTC increased network complexity and enhanced microbial interactions, while high concentrations of CTC had the opposite effect. Sub-networks analysis of dominant phyla (Bacteriodota, Proteobacteria, and Actionobacteriota) and dominant genera (Propioniciclava, a genus from the family Pleomorphomonadaceae and WCHB1-32) also showed the same pattern. In addition, keystone species identified by Z-P analysis had low relative abundance, but they were important in maintaining the stable performance of the system. In summary, low concentrations of CTC enhanced the complexity and stability of the activated sludge system. While high CTC concentrations destabilized the stability of the overall network and then caused effluent water quality deterioration. This study provides insights into our understanding of response in the bacteria community and their network interactions under tetracycline antibiotics in activated sludge system.

Flexible electrochemical sensors integrated with nanomaterials for in situ determination of small molecules in biological samples: A review.

Flexible biosensors have aroused research enthusiasm due to their potential for in situ quantification of chemical constituents in the human body, which perform a vital function in health monitoring and disease diagnosis. Especially, flexible electrochemical biosensors based on different advanced nanomaterials combine the merits of electrochemical analysis with unique structural/chemical properties of flexible electrode materials, and have exhibited excellent performance for in situ biomarkers detection toward different biological samples. These flexible electrochemical sensors can be integrated into implantable/wearable devices, which demonstrate great promise in invasive/noninvasive in-situ analysis. Consequently, the development of flexible electrochemical biosensors is of great significance for both scientific research and clinical application. In this review, we focus on the state-of-the-art progress in flexible electrochemical biosensors integrated with a wide spectrum of nanomaterials, which are aimed at in situ sensitive detection of small molecule metabolites in different biological specimens including live cells, tissues, body fluids (e.g., human blood, cerebrospinal fluid (CSF), and interstitial fluid (ISF)), and exudate secretion liquors (e.g., human saliva, tear, sweat, and urine). From the perspectives of flexible electrochemical biosensors toward different biological samples, we discuss their innovations in nanomaterials with diverse structures. We also introduce the research status of integrated flexible implantable and wearable electrochemical sensing devices with various types and functionalities for practical application. Furthermore, we share our opinions on the recent progress of flexible electrochemical sensors based on nanomaterials and look forward to applying flexible electrochemical sensors in medical diagnosis and healthcare.

Localized Degradation of Neutrophil Extracellular Traps by Photoregulated Enzyme Delivery for Cancer Immunotherapy and Metastasis Suppression.

Extrusion of neutrophil extracellular traps (NETs), a fundamental host innate immune defense against pathogens, has recently been linked to cancer resistance to immunotherapy and distant metastasis. These findings highlight interesting areas of cancer-elicited inflammation and potential therapeutic strategies. Disrupting existing NETs with DNase I has been proved to enhance the therapeutic efficacy of tumor immunotherapy and attenuate metastatic spread. However, systemic biodistribution of DNase I raises safety issues, potentially impairing host defense against infection. Hence, tumor-specific delivery and metastatic niche-targeted effects are attractive options for localized degradation of NETs. We have engineered a nanoplatform with a plasmonic gold blackbody (AuPB) core with broad-spectrum photo activity and a mesoporous polydopamine (mPDA) shell for efficient loading and photoregulated release of DNase I. The on-demand released DNase I triggered by the second near-infrared (NIR-II) light irradiation breaks the "NET-mediated physical barrier", thereby increasing the contact of immune cytotoxic cells with tumor cells in living mice and sensitizing immune checkpoint therapy of primary colorectal cancer (CRC). Moreover, the deposition and light-controlled cargo release from systemically delivered AuPB@mPDA carriers in liver, the most frequent site of CRC metastasis, abolished NET-mediated capture of circulating tumor cells and hence metastatic seeding. Our findings indicate that the localized, light-regulated release of DNase I by photoactive carriers in the NIR-II window represent a translational route for immune-mediated tumor regression and metastasis inhibition.

Extracellular Vesicles as Innovative Treatment Strategy for Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron degenerative disease, and it is hard to diagnose in the early stage, and treatment means are limited, and the treatment effect is unsatisfactory. Therefore, exploring a new effective treatment strategy is urgently needed for ALS patients. Extracellular vesicles (EVs) are a heterogeneous group of natural membrane vesicles containing many bioactive substances, and they play important roles in the paracrine pathway and exhibit neuroprotection effects. A growing body of evidence shows that EVs have great application potential in diagnosis, treatment, and drug delivery in ALS, and they represent an innovative treatment strategy for ALS. In this review, we will briefly introduce the biogenesis of EVs and focus on discussing the role of EVs in ALS treatment to further enrich and boost the development of EVs as an innovative treatment strategy for ALS.

One-pot synthesis of a self-reinforcing cascade bioreactor for combined photodynamic/chemodynamic/starvation therapy.

The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) have attracted a great deal of interest, but tumor hypoxia and glutathione (GSH) overproduction still limit their further applications. Herein, an intelligent reactive oxygen species (ROS) nanogenerator Ce6/GOx@ZIF-8/PDA@MnO2 (denoted as CGZPM; Ce6, GOx, ZIF-8, PDA, MnO2 are chlorin e6, glucose oxidase, zeolitic imidazolate framework-8, polydopamine and manganese dioxide respectively) with O2-generating and GSH-/glucose-depleting abilities was constructed by a facile and green one-pot method. After intake by tumor cells, the outer MnO2 was rapidly degraded by the acidic pH, and the overexpression of hydrogen peroxide (H2O2) and GSH with abundant Mn2+ and O2 produced would eventually achieve multifunctionality. The Mn2+ acted as an ideal Fenton-like agent and magnetic resonance (MR) imaging contrast agent, while the O2 promoted the PDT via hypoxia relief and facilitated the intratumoral glucose oxidation by GOx for starvation therapy (ST). Benefiting from the GOx-based glycolysis process, sufficient H2O2 was generated to improve the CDT efficacy through Mn2+-mediated Fenton-like reaction. Notably, MnO2 and PDA could decrease the tumor antioxidant activity by consuming GSH, resulting in remarkably enhanced PDT/CDT. Such a novel cascade bioreactor with tumor microenvironment (TME)-modulating capability opens new opportunities for ROS-based and combinational treatment paradigms.

Hierarchical Core-Shell Structure of 2D VS2@VC@N-Doped Carbon Sheets Decorated by Ultrafine Pd Nanoparticles: Assembled in a 3D Rosette-like Array on Carbon Fiber Microelectrode for Electrochemical Sensing.

The development of two-dimensional (2D) nanohybrid materials with heterogeneous components in nanoscale and three-dimensional (3D) well-ordered assembly in microscale has been regarded as an effective way to improve their overall performances by the synergistic coupling of the optimized structure and composition. In this work, we reported the design and synthesis of a new type of hierarchically core-shell structure of 2D VS2@VC@N-doped carbon (NC) sheets decorated by ultrafine Pd nanoparticles (PdNPs), which were vertically grown on carbon fiber (CF) and assembled into a unique 3D rosette-like array. The resultant VS2@VC@NC-PdNPs modified CF microelectrode integrated the structural and electrochemical properties of the heterogeneous hybridization of core-shell VS2@VC@NC-PdNPs sheets with a unique rosette-like array structure, and gave rise to a significant improvement in terms of electron transfer ability, electrocatalytic activity, stability, and biocompatibility. Under the optimized conditions, the VS2@VC@NC-PdNPs modified CF microelectrode demonstrated excellent electrochemical sensing performance towards biomarker hydrogen peroxide (H2O2) including a high sensitivity of 152.7 µA cm-2 mM-1, a low detection limit of 50 nM (a signal-to-noise ratio of 3:1), as well as good reproducibility and anti-interference ability, which could be used for the real-time in situ electrochemical detection of H2O2 in live cancer cells and cancer tissue. The remarkable performances of the proposed nanohybrid microelectrode will have a profound impact on the design of diverse 2D layered materials as a promising candidate for electrochemical biosensing applications.

The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females.

The relationship between females with low glucose-6-phosphate dehydrogenase activity level (LG6PD) and HBV infection is unclear. We conducted a cross sectional study of 124 406 reproductive-age Chinese females who participated in the National Free Pre-conception Check-up Projects to investigate the risk of HBV infection among females with LG6PD and its effect on liver enzyme. Based on HBV serological test results, the participants were divided into the susceptible, immunized, and HBV infected groups. The multivariable-adjusted odds ratios (ORs) for HBV infection in LG6PD participants were 1.71 (95% confidence interval (CI): 1.45-2.01) and 1.41 (95% CI: 1.23-1.62), respectively with the susceptible and immunized participants as references, compared to those without LG6PD. Participants with HBV infection only and combined with HBV infection and LG6PD had 184% and 249% significantly higher risks of elevated alanine transaminase (ALT) (susceptible participants as reference). If the immunized participants were used as reference, significant higher odds of elevated ALT occurred (3.48 (95% CI: 3.18-3.80), 4.28 (95% CI: 2.92-6.28)). Thus, reproductive-age females with LG6PD had a higher prevalence of HBV infection, and LG6PD might exacerbate ALT elevation in HBV infected females. Our findings underscore the need to explore collaborative management approaches for these two diseases among reproductive-age females for maternal and child health.

Enhancing magnetic resonance/photoluminescence imaging-guided photodynamic therapy by multiple pathways.

Mitochondria, which are a major source of adenosine triphosphate (ATP) and apoptosis regulators, are the key organelles that promote tumor cell proliferation, and their dysfunction affects tumor cell behavior. Additionally, mitochondria have been shown to play a central role in the biosynthesis of protoporphyrin IX (PpIX), which is a widely used photosensitizer that has been used for tumor detection, monitoring and photodynamic therapy. Nevertheless, photosensitizers administrated exogenously are often restricted by limited bioavailability.δ-Aminolevulinic acid (δ-ALA) is a naturally occurring delta amino acid that can be converted in situ to PpIX via the heme biosynthetic pathway in mitochondria. Because δ-ALA is the precursor for PpIX, δ-ALA-based photodynamic therapy (PDT) shows promise in treating cancer. However, the accumulation of δ-ALA within endosomal system limits the production of PpIX and eventually impedes its effectiveness. Theranostic nanoparticles (NPs) capable of endosomal escape are expected to optimize the endogenous biosynthetic yield. In this study, δ-ALA was improved with triphenylphosphoniumcation (TPP+), a high net position cation that functions in endosomal escape and as a mitochondria-targeting ligand, and was further modified with bovine serum albumin stabilized manganese dioxide (MnO2). The tumor microenvironment (TME) responsive MnO2 in this system can elevate oxygen content to relieve hypoxia. Both enhanced photosensitizer yield and elevated oxygen contributing to the final therapeutic effect. Moreover, the enhancement of magnetic resonance imaging (MRI) (r1 = 5.410 s-1mM-1) stemming from the degradation of MnO2 by the TME could serve as a guide prior to treatment for accurate location, while in situ hysteretic photoluminescence imaging derived from PpIX can be utilize as a supervisor for prognosis evaluation. This systematic design could broaden the biomedical application and highlight the considerable therapeutic promise of PDT.

Methotrexate-Loaded Extracellular Vesicles Functionalized with Therapeutic and Targeted Peptides for the Treatment of Glioblastoma Multiforme.

Despite promising in vitro evidence for effective glioblastoma treatment, most drugs are hindered from entering the central nervous system because of the presence of the blood-brain barrier (BBB). Thus, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle. Extracellular vesicles (EVs), cell-derived membrane-encapsulated structures with diameters ranging from 50 to 1000 nm, have been explored as the drug delivery system to deliver their cargo to the brain tissue. Moreover, tumor targeting and selective drug delivery has been facilitated by engineering their parent cells to secrete modified EVs. However, the method suffers from many shortcomings including poor repeatability and complex and time-consuming operations. In this context, we present an easy-to-adapt and highly versatile methodology to modify EVs with an engineered peptide capable of recognition and eradication of glioma. On the basis of molecular recognition between phospholipids on EV lipid bilayer membranes and ApoA-I mimetic peptides, we have developed methotrexate (MTX)-loaded EVs functionalized with therapeutic [Lys-Leu-Ala (KLA)] and targeted [low-density lipoprotein (LDL)] peptides. In vitro experiments demonstrated that EVs decorated with LDL or KLA-LDL could obviously ameliorate their uptake by human primary glioma cell line U87 and permeation into three-dimensional glioma spheroids in contrast to blank EVs, and consequently, the treatment outcome of the payload is improved. Both ex vivo and in vivo imaging experiments revealed that peptide LDL could obviously promote EV extravasation across the BBB and distribution in the glioma site. Furthermore, compared with the mice administrated with MTX and MTX@EVs, MTX@EVs-KLA-LDL-treated mice showed the longest median survival period. In conclusion, functionalizing with the peptide onto EV surfaces may provide a substantial advancement in the application of EVs for selective target binding as well as therapeutic effects for brain tumor treatment.

Dual nanoenzyme modified microelectrode based on carbon fiber coated with AuPd alloy nanoparticles decorated graphene quantum dots assembly for electrochemical detection in clinic cancer samples.

The development of high-efficient technologies for cancer biomarkers detection has attracted tremendous research effort for its great clinic significance. In this work, we designed a new type of flexible and robust nanohybrid microelectrode by modifying carbon fiber with dual nanoenzyme, i.e., AuPd alloy nanoparticles (AuPd-ANPs) decorated graphene quantum dots (GQDs) assembly, and explored its practical application in electrochemical sensing system for sensitive detection of cancer biomarker hydrogen peroxide (H2O2) in human breast cancer cells and tissue. For the preparation of dual nanoenzyme modified microelectrode, ionic liquid was used as the electrolyte for the effective electrodeposition of GQDs on carbon fiber substrate to form a close-packed assembly under a very negative potential, then the highly dense AuPd-ANPs were uniformly decorated on GQDs assembly by electrodeposition. In virtue of the structural merits and synergistic contribution of dual nanoenzyme in enhancing the electrocatalytic activity to H2O2, the resultant nanohybrid microelectrode exhibited good sensing performances for electrochemical detection of H2O2, including a high sensitivity of 371 µA cm-2 mM-1, a wide linear range from 1.0 µM to 18.44 mM, a low detection limit of 500 nM (a signal-to-noise ratio of 3:1), as well as good selectivity and biocompatibility, which could be used for real-time tracking H2O2 released from different types of human breast cells and in situ sensitive detection of H2O2 in clinical breast cancer tissue.

One-pot synthesis of albumin-gadolinium stabilized polypyrrole nanotheranostic agent for magnetic resonance imaging guided photothermal therapy.

Theranostic agents with perfect properties are needed urgently for the development of imaging guided photothermal therapy (PTT). In this work, Gd-integrated polypyrrole nanotheranostic agent (PPy@BSA-Gd) was successfully built through selecting bovine serum albumin (BSA) as both stabilizers for polymerization and biomimetic mineralization in "one pot". The obtained PPy@BSA-Gd possessed high stability and excellent photothermal property. Besides, relevant cellular assays indicated that PPy@BSA-Gd had fantastic cytocompatibility which could be further internalized by cancer cells. Due to their high longitudinal relaxivity value (r1 = 10.203 mM-1 s-1), PPy@BSA-Gd could serve as considerable probe for T1-weighted magnetic resonance imaging (MRI). After tail vein injection of PPy@BSA-Gd, the MR signal of tumor section exhibited a time-dependent increase, indicating effective tumor accumulation of PPy@BSA-Gd. Notably, when exposed to 808 nm laser, the tumor growth of PPy@BSA-Gd treated mice could be inhibited by photothermal ablation successfully. All the results demonstrated the well-designed PPy@BSA-Gd have the potential for tumor diagnose and photothermal therapy.

Flexible nanohybrid microelectrode based on carbon fiber wrapped by gold nanoparticles decorated nitrogen doped carbon nanotube arrays: In situ electrochemical detection in live cancer cells.

The rapidly growing demand for in situ real-time monitoring of chemical information in vitro and in vivo has attracted tremendous research efforts into the design and construction of high-performance biosensor devices. Herein, we develop a new type of flexible nanohybrid microelectrode based on carbon fiber wrapped by gold nanoparticles decorated nitrogen-doped carbon nanotube arrays, and explore its practical application in in situ electrochemical detection of cancer biomarker H2O2 secreted from live cancer cells. Our results demonstrate that carbon fiber material with microscale size and fascinating mechanical properties can be used as a robust and flexible microelectrode substrate in the electrochemical biosensor system. And the highly ordered nitrogen-doped carbon nanotube arrays that grown on carbon fiber possess high surface area-to-volume ratio and abundant active sites, which facilitate the loading of high-density and uniformly dispersed gold nanoparticles on it. Benefited from the unique microstructure and excellent electrocatalytic properties of different components in the nanohybrid fiber microelectrode, an effective electrochemical sensing platform based on it has been built up for the sensitive and selective detection of H2O2, the detection limit is calculated to be 50nM when the signal-to-noise ratio is 3:1, and the linear dynamic range is up to 4.3mM, with a high sensitivity of 142µAcm-2mM-1. These good sensing performances, coupled with its intrinsic mechanical flexibility and biocompatibility, allow for its use in in situ real-time tracking H2O2 secreted from breast cancer cell lines MCF-7 and MBA-MD-231, and evaluating the sensitivity of different cancer cells to chemotherapy or radiotherapy treatments, which hold great promise for clinic application in cancer diagnose and management.

Relationship between expression of vascular endothelial growth factor and cervical lymph node metastasis in papillary thyroid cancer: A meta-analysis.

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor (VEGF) and lymph node metastasis (LNM) in papillary thyroid cancer (PTC). VEGF-related articles that had been published until August 2016 were searched from the PubMed, EMBASE, and MEDLINE to identify the risk factors of LNM in PTC. RevMan 5.3 software was used for the meta-analysis. Finally, 9 articles met the inclusion criteria and were included in our meta-analysis. LNM was found to be present in 176 of 318 patients (57.8%) with high VEGF expression and in 71 of 159 patients (47.0%) with low VEGF expression. The overall OR was 2.81 (95% confidence interval, 1.49-5.29). LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression (P=0.001). Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients' country of origin and the detection methods. Our meta- analysis concluded that the VEGF protein expression is associated with LNM in PTC.

In Situ Electrochemical Sensing and Real-Time Monitoring Live Cells Based on Freestanding Nanohybrid Paper Electrode Assembled from 3D Functionalized Graphene Framework.

In this work, we develop a new type of freestanding nanohybrid paper electrode assembled from 3D ionic liquid (IL) functionalized graphene framework (GF) decorated by gold nanoflowers (AuNFs), and explore its practical application in in situ electrochemical sensing of live breast cell samples by real-time tracking biomarker H2O2 released from cells. The AuNFs modified IL functionalized GF (AuNFs/IL-GF) was synthesized via a facile and efficient dopamine-assisted one-pot self-assembly strategy. The as-obtained nanohybrid assembly exhibits a typical 3D hierarchical porous structure, where the highly active electrocatalyst AuNFs are well dispersed on IL-GF scaffold. And the graft of hydrophilic IL molecules (i.e., 1-butyl-3-methylimidazolium tetrafluoroborate, BMIMBF4) on graphene nanosheets not only avoids their agglomeration and disorder stacking during the self-assembly but also endows the integrated IL-GF monolithic material with unique hydrophilic properties, which enables it to be readily dispersed in aqueous solution and processed into freestanding paperlike material. Because of the unique structural properties and the combinational advantages of different components in the AuNFs/IL-GF composite, the resultant nanohybrid paper electrode exhibits good nonenzymatic electrochemical sensing performance toward H2O2. When used in real-time tracking H2O2 secreted from different breast cells attached to the paper electrode without or with radiotherapy treatment, the proposed electrochemical sensor based on freestanding AuNFs/IL-GF paper electrode can distinguish the normal breast cell HBL-100 from the cancer breast cells MDA-MB-231 and MCF-7 cells, and assess the radiotherapy effects to different breast cancer cells, which opens a new horizon in real-time monitoring cancer cells by electrochemical sensing platform.

Relationship between Expression of Vascular Endothelial Growth Factor and Cervical Lymph Node Metastasis in Papillary Thyroid Cancer: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor (VEGF) and lymph node metastasis (LNM) in papillary thyroid cancer (PTC).VEGF-related articles that had been published until August 2016 were searched from the PubMed,EMBASE,and MEDLINE to identify the risk factors of LNM in PTC.RevMan 5.3 software was used for the meta-analysis.Finally,9 articles met the inclusion criteria and were included in our meta-analysis.LNM was found to be present in 176 of 318 patients (57.8％) with high VEGF expression and in 71 of 159 patients (47.0％) with low VEGF expression.The overall OR was 2.81 (95％ confidence interval,1.49-5.29).LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression (P=0.001).Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients' country of origin and the detection methods.Our meta-analysis concluded that the VEGF protein expression is associated with LNM in PTC.