Impact of Geko Neuromuscular Stimulator on Preoperative Preparation in Ankle Fractures.

OBJECTIVE: To explore the impact of the Geko neuromuscular stimulator on preoperative preparation in patients with ankle fractures. STUDY DESIGN: Quasi-experiment study. Place and Duration of the Study: Department of Foot and Ankle Surgery and Department of Orthopaedics, Beijing Tongren Hospital, Capital Medical University, Beijing, China, between December 2020 and 2021. METHODOLOGY: This quasi-experiment study included patients with ankle fractures treated with Geko neuromuscular stimulator before surgical fixation. The primary outcome was limb swelling at 24, 48, and 72 hours (h) after admission, and the secondary outcomes were pain according to visual analogue scale (VAS) at 12, 24, and 48 hours after admission, preoperative waiting time, and comfort 4 and 72 h after admission. RESULTS: A total of 60 patients were included in the study; 30 in the conventional treatment group (mean age 41.16 ± 2.01 years) and 30 in the Geko group (mean age 40.22 ± 2.68 years). The limb swelling in patients was significantly different between the Geko and conventional treatment groups (p = 0.004). Besides, the swelling values at 48 (p < 0.001) and 72 (p < 0.001) hours were significantly lower than those at 24 hours. The pain in patients was significantly different between the Geko and conventional treatment groups (p = 0.007). Besides, the swelling values at 24 (p < 0.001) and 48 (p < 0.001) hours are significantly lower than those at 24 hours. Comfort was significantly higher at 4 h (69.54 ± 2.18 vs. 67.22 ± 3.14, p = 0.002) and 72 h [(88.50 (84.00 - 94.00) vs. 82.14 ± 3.08, p < 0.001)] after admission. The preoperative waiting time (3.52 ± 1.8 vs. 5.15 ± 2.1 hours, p = 0.002) was significantly shorter in the Geko group. CONCLUSION: The Geko neuromuscular stimulator is a useful option for preoperative preparation in patients with ankle fractures to reduce local swelling and pain and improve patients' comfort. KEY WORDS: Ankle fractures, Lower extremity, Neuromuscular stimulator, Peroneal nerve, Pain.

Vesicular self-assembly of copolymer-grafted nanoparticles with anisotropic shapes.

Plasmonic nanovesicles show broad applications in areas such as cancer theranostics and drug delivery, but the preparation of nanovesicles from shaped nanoparticles remains challenging. This article describes the vesicular self-assembly of shaped nanoparticles, such as gold nanocubes grafted with amphiphilic block copolymers, in selective solvents. The nanocubes assembled within the vesicular membranes exhibit two distinctive packing modes, namely square-like and hexagonal packing, depending on the relative dimensions of the copolymer ligands and nanocubes. The corresponding optical properties of the plasmonic nanovesicles can be tuned by varying the length of the grafted copolymers and the size of the nanocubes. This work provides guidance for the fabrication of functional plasmonic vesicles for applications in catalysis, nanomedicines and optical devices.

Polyprodrug Nanomedicines: An Emerging Paradigm for Cancer Therapy.

Nanomedicines have the potential to provide advanced therapeutic strategies in combating tumors. Polymer-prodrug-based nanomedicines are particularly attractive in cancer therapies owing to the maximum drug loading, prolonged blood circulation, and reduced premature leakage and side effects in comparison with conventional nanomaterials. However, the difficulty in precisely tuning the composition and drug loading of polymer-drug conjugates leads to batch-to-batch variations of the prodrugs, thus significantly restricting their clinical translation. Polyprodrug nanomedicines inherit the numerous intrinsic advantages of polymer-drug conjugates and exhibit well-controlled composition and drug loading via direct polymerization of therapeutic monomers, representing a promising nanomedicine for clinical tumor therapies. In this review, recent advances in the development of polyprodrug nanomedicines are summarized for tumor elimination. Various types of polyprodrug nanomedicines and the corresponding properties are first summarized. The unique advantages of polyprodrug nanomedicines and their key roles in various tumor therapies are further highlighted. Finally, current challenges and the perspectives on future research of polyprodrug nanomedicines are discussed.

Transformable Honeycomb-Like Nanoassemblies of Carbon Dots for Regulated Multisite Delivery and Enhanced Antitumor Chemoimmunotherapy.

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer-associated fibroblasts (CAFs) responsive honeycomb-like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs-loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.

Self-accelerating H2O2-responsive Plasmonic Nanovesicles for Synergistic Chemo/starving therapy of Tumors.

Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H2O2-responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. Methods: Gold nanoparticles were modified with H2O2-responsive amphiphilic block copolymer PEG45-b-PABE330 by ligand exchange. The TPZ and GOx loaded GVs (TG-GVs) were prepared through the self-assembly of PEG45-b-PABE330 -grafted nanoparticles together with TPZ and GOx by solvent displacement method. Results: In response to H2O2 in tumor, the TG-GVs dissociate to release the payloads that are, otherwise, retained inside the vesicles for days without noticeable leakage. The released GOx enzymes catalyze the oxidation of glucose by oxygen in the tumor tissue to enhance the degree of hypoxia that subsequently triggers the reduction of hypoxia-activated pro-drug TPZ into highly toxic free radicals. The H2O2 generated in the GOx-catalyzed reaction also accelerate the dissociation of vesicles and hence the release rate of the cargoes in tumors. The drug-loaded GVs exhibit superior tumor inhibition efficacy in 4T1 tumor-bearing mice owing to the synergistic effect of chemo/starvation therapy, in addition to their use as contrast agents for computed tomography imaging of tumors. Conclusion: This nanoplatform may find application in managing tumors deeply trapped in viscera or other important tissues that are not compatible with external stimulus (e.g. light).

Effects of mindfulness-based cognitive therapy on breast cancer survivors with insomnia: A randomised controlled trial.

OBJECTIVE: We investigated the effects of mindfulness-based cognitive therapy on insomnia (MBCT-I) in breast cancer survivors. METHODS: In total, 136 participants were allocated randomly to a MBCT-I group or a waitlist control (WLC) group. Indicators of insomnia and mindfulness were evaluated using the Insomnia Severity Index, actigraphy and the Five Facet Mindfulness Questionnaire. Data were collected at baseline (T1), post-intervention (T2), 3-month follow-up (T3) and 6-month follow-up (T4) time points. RESULTS: Insomnia severity decreased significantly in the MBCT-I group, compared with the WLC group, at T2, T3 and T4 (all p < .001). We found that 59.6% of the MBCT-I group with moderate and severe insomnia improved to no insomnia and subclinical insomnia at T4 relative to T1, accounting for 7.9% and 55.3%, respectively. Compared with the WLC group, the MBCT-I group improved on actigraphy measures of sleep; they exhibited a pattern of decreased sleep onset latency and waking after sleep onset, as well as increased total sleep time and sleep efficiency. Mindfulness also increased more in the MBCT-I group than in the WLC group at T2, T3 and T4 (all p < .001). CONCLUSIONS: MBCT-I may be an efficacious non-pharmacologic intervention to improve sleep quality in breast cancer survivors.

Enzyme-induced in vivo assembly of gold nanoparticles for imaging-guided synergistic chemo-photothermal therapy of tumor.

This article describes a nanoplatform based on matrix metalloproteinase (MMP)-responsive gold nanoparticles (AuNPs) for tumor-targeted photoacoustic (PA) imaging-guided photothermal therapy and drug delivery. AuNPs were grafted with complementary DNA strands, tethered with doxorubicin and coated with poly(ethylene glycol) via a thermal-labile linker and a MMP-cleavable peptide, respectively. The nanoprobes remained well-isolated in healthy tissues, but formed aggregates rapidly under MMP-abundant conditions. The DNA hybridization-induced assembly of the nanoprobes led to prolonged tumor retention and strong near-infrared (NIR) absorption, which is beneficial to deep-tissue imaging and therapy. Compared with MMP-inert nanoprobes, our platform demonstrated significantly enhanced efficiency in PA imaging and photothermal conversion upon NIR irradiation. Meanwhile, doxorubicin could be released rapidly in response to the localized elevation of temperature, leading to synergistic chemo-photothermal therapy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to tumors with high specificity, safety, and universality.

Microfluidic Device Directly Fabricated on Screen-Printed Electrodes for Ultrasensitive Electrochemical Sensing of PSA.

How to fabricate scale low-cost microfluidic device for detection of biomarkers owns a great requirement. Herein, it is for the first time reported that a new microfluidic device based on bonding polydimethylsiloxane microfluidic channels onto the substrate of a screen-printed electrode with coating glass solution was fabricated for electrochemical sensing of prostate-specific antigen (PSA). Compared to traditional microfabrication processes, this method is simple, fast, low cost, and also suitable for mass production. The prepared screen-printed electrode-based microfluidic device (CASPE-MFD) was used for the detection of the PSA in human serum. The prepared CASPE-MFD had a detection limit of 0.84 pg/mL (25.8 fM) and a good linearity with PSA concentration ranging from 0.001 to 10 ng/mL, which showed a great promise platform toward the development of miniaturized, low-cost electrochemical microfluidic device for use in human health, environmental monitoring, and other applications.

Developments of nano-TiO2 incorporated hydroxyapatite/PEEK composite strut for cervical reconstruction and interbody fusion after corpectomy with anterior plate fixation.

The technique of anterior cervical corpectomy and fusion (ACCF) for strut grafting has become a widespread and actively applied for many cervical complaints including cervical degeneration of the intervertebral disks, cervical trauma, cancer, rheumatoid arthritis and multilevel cervical spondylotic diseases. To avoid the complications of the old techniques, the construct stability and long anterior screw-plate designs of the bone strut have been improved by using effective biomaterials. The nanostructured hydroxyapatite (HAp) incorporated with biocompatible polymer matrixes is an effective biomedical material and creating a functional properties applied for different tissue replacements such as dental, hips, knees, tendon and ligaments and tissue repair for maxillofacial reconstruction, stabilization of the jaw bone and spinal fusion. In the present investigation, we have successfully designed cylindrical nano titanium dioxide (n-TiO2) interbody fusion with anterior plate fixation. The n-TiO2 incorporated HAp/ Polyetheretherketone (PEEK) nanocomposite strut has a superior mechanical properties and larger contact area with high fusion rates as compared with the HAp/PEEK strut in the absence of n-TiO2 nanoparticles. It is highly able to provide appropriate strength and biological activity similar to the conventional titanium cage and also mainly it has been minimizes subsidence value. The synthesized novel material of n-TiO2 incorporated HAp/PEEK nanocomposite strut is scientifically given effective outcomes for fusion and reconstruction of the ACCF.

Glutathione-Responsive Self-Assembled Magnetic Gold Nanowreath for Enhanced Tumor Imaging and Imaging-Guided Photothermal Therapy.

Designing nanomaterials with advanced functions and physical properties to improve cancer diagnosis and treatment has been an enormous challenge. In this work, we report the synthesis of magnetic gold nanowreaths (AuNWs) by combining wet-chemical synthesis with layer-by-layer self-assembly. The presence of Au branches, small junctions, and central holes in AuNWs led to improved photothermal effect compared with Au nanoring seeds and thick Au nanoring with smooth surface. The self-assembly of exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) on the surfaces of AuNWs not only effectively quenched the T1-weighted magnetic resonance imaging (MRI) ability due to the enhanced T2 decaying effect but also provided the responsiveness to glutathione (GSH). After intravenous injection, the T1 signal of magnetic AuNWs initially in the "OFF" state can be intelligently switched on in response to the relatively high GSH concentration in tumor, and the formation of larger assemblies of ES-MIONs improved their tumor delivery compared to ES-MIONs themselves. Thus, the magnetic AuNWs showed higher MRI contrast than ES-MIONs or commercial Magnevist in T1-weighted MR imaging of tumor. Furthermore, the magnetic AuNWs have absorption in near-infrared range, leading to strong photoacoustic signal and effective photoablation of tumor. Therefore, our GSH-responsive self-assembled magnetic AuNWs could enhance T1-weighted MRI and photoacoustic imaging of tumor and be used for imaging-guided photothermal therapy.

Cooperative Assembly of Magneto-Nanovesicles with Tunable Wall Thickness and Permeability for MRI-Guided Drug Delivery.

This article describes the fabrication of nanosized magneto-vesicles (MVs) comprising tunable layers of densely packed superparamagnetic iron oxide nanoparticles (SPIONs) in membranes via cooperative assembly of polymer-tethered SPIONs and free poly(styrene)- b-poly(acrylic acid) (PS- b-PAA). The membrane thickness of MVs could be well controlled from 9.8 to 93.2 nm by varying the weight ratio of PS- b-PAA to SPIONs. The increase in membrane thickness was accompanied by the transition from monolayer MVs, to double-layered MVs and to multilayered MVs (MuMVs). This can be attributed to the variation in the hydrophobic/hydrophilic balance of polymer-grafted SPIONs upon the insertion and binding of PS- b-PAA onto the surface of nanoparticles. Therapeutic agents can be efficiently encapsulated in the hollow cavity of MVs and the release of payload can be tuned by varying the membrane thickness of nanovesicles. Due to the high packing density of SPIONs, the MuMVs showed the highest magnetization and transverse relaxivity rate ( r2) in magnetic resonance imaging (MRI) among these MVs and individual SPIONs. Upon intravenous injection, doxorubicin-loaded MuMVs conjugated with RGD peptides could be effectively enriched at tumor sites due to synergetic effect of magnetic and active targeting. As a result, they exhibited drastically enhanced signal in MRI, improved tumor delivery efficiency of drugs as well as enhanced antitumor efficacy, compared with groups with only magnetic or active targeting strategy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to organs/tissues that are not readily accessible by conventional delivery vehicles.

Roles of circulating endothelial progenitor cells and endothelial cells in gastric carcinoma.

The present study aimed to investigate the role of endothelial progenitor cells (EPCs) and endothelial cells (ECs) in the peripheral blood of patients with gastric cancer (GC), and to investigate vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in GC tissues. First, 6 ml peripheral blood with added anticoagulant was collected from each of the 42 patients with GC, followed by determination of the number of EPCs and ECs by flow cytometry using the surface markers cluster of differentiation (CD)34brightCD133+CD31+CD45dim and CD34dimCD133-CD31brightCD45-, respectively. VEGF expression in patients with GC was detected by the streptomycin avidin-peroxidase immunohistochemical method, and MVD was calculated using the marker CD34. EPC and EC levels were positively associated with VEGF expression level, as well as with MVD. VEGF expression was positive in 66.67% GC cases, and its level was significantly associated with tumor-node-metastasis (TNM) stage, invasion depth and lymph-node metastasis (P<0.05). VEGF expression level was also positively associated with MVD. MVD in GC was significantly larger than that in normal tissue (P<0.01), and it was significantly associated with TNM stage (P<0.05), invasion depth (P<0.01) and lymph-node metastasis (P<0.01). EPCs in the peripheral blood have an important role in GC development, and may be a promising indicator of GC diagnosis and prognosis.

Illness cognitions and the associated socio-demographic and clinical factors in Chinese women with breast cancer.

PURPOSE: Illness cognitions are important mediators between disease and psychological adjustment. Evidence related to illness cognitions among patients with breast cancer remains limited. The purpose of this study was to examine illness cognitions among Chinese women with breast cancer and associations with socio-demographic and clinical factors. METHODS: A cross-sectional study was carried out involving 313 women with breast cancer recruited from a general hospital and a social cancer support club in Beijing from October 2016 to May 2017. Data were collected using the Illness Cognition Questionnaire. RESULTS: Participants reported positive overall cognition regarding breast cancer (helplessness, 13.70 ± 4.24; acceptance, 16.86 ± 4.30; perceived benefits, 17.93 ± 3.86). A multiple regression model indicated that six factors were associated with illness cognitions: treatment phase of disease, having no children, not returning to work (positive associations with helplessness, negative associations with acceptance; age (negative associations with helplessness, positive associations with acceptance); treatment phase of disease, having no medical insurance (negative associations with perceived benefit); and disease duration (positive associations with acceptance). CONCLUSIONS: This study reports on the presence of different illness cognitions in Chinese women with breast cancer and the associated factors, and the results could help oncology medical and nursing staff identify risk factors for poor emotional adjustment to breast cancer and the patients who may benefit from interventions aimed at improving the presence of positive illness cognitions.

Suppressing Nanoparticle-Mononuclear Phagocyte System Interactions of Two-Dimensional Gold Nanorings for Improved Tumor Accumulation and Photothermal Ablation of Tumors.

The clearance of nanoparticles (NPs) by mononuclear phagocyte system (MPS) from blood leads to high liver and spleen uptake and negatively impacts their tumor delivery efficiency. Here we systematically evaluated the in vitro and in vivo nanobio interactions of a two-dimensional (2D) model, gold (Au) nanorings, which were compared with Au nanospheres and Au nanoplates of similar size. Among different shapes, Au nanorings achieved the lowest MPS uptake and highest tumor accumulation. Among different sizes, 50 nm Au nanorings showed the highest tumor delivery efficiency. In addition, we demonstrated the potential use of Au naonrings in photoacoustic imaging and photothermal therapy. Thus, engineering the shape, surface area, and size of Au nanostructures is important in controlling NP-MPS interactions and improving the tumor uptake efficiency.

An Enzyme-Free Signal Amplification Technique for Ultrasensitive Colorimetric Assay of Disease Biomarkers.

Enzyme-based colorimetric assays have been widely used in research laboratories and clinical diagnosis for decades. Nevertheless, as constrained by the performance of enzymes, their detection sensitivity has not been substantially improved in recent years, which inhibits many critical applications such as early detection of cancers. In this work, we demonstrate an enzyme-free signal amplification technique, based on gold vesicles encapsulated with Pd-Ir nanoparticles as peroxidase mimics, for colorimetric assay of disease biomarkers with significantly enhanced sensitivity. This technique overcomes the intrinsic limitations of enzymes, thanks to the superior catalytic efficiency of peroxidase mimics and the efficient loading and release of these mimics. Using human prostate surface antigen as a model biomarker, we demonstrated that the enzyme-free assay could reach a limit of detection at the femtogram/mL level, which is over 103-fold lower than that of conventional enzyme-based assay when the same antibodies and similar procedure were used.

Calcifying fibrous tumor of stomach: A case report.

RATIONALE: Calcifying fibrous tumor (CFT) is a rare benign soft tissue mesenchymal neoplasm. Although the gastrointestinal (GI) tract is the most common predilection site of CFT, the clinicians, even including pathologist, generally consider it as GI stromal tumor (GIST) or other submucosal tumors such as schwannoma and leiomyoma. PATIENT CONCERNS: A 55-year-old man presented with complaints of epigastric discomfort and abdominal distention for more than 1 year. DIAGNOSES: On the basis of endoscopic and computed tomography examination, preliminary diagnosis was GIST. INTERVENTIONS: Endoscopic submucosal dissection (ESD) surgery was performed to remove the gastric mass. OUTCOMES: The histopathological examination revealed a gastric CFT. LESSONS: We present a case of gastric CFT, which was misdiagnosed as GIST based on endoscopic and radiologic findings.

Anisotropic Self-Assembly of Hairy Inorganic Nanoparticles.

Current interest in functional assemblies of inorganic nanoparticles (NPs) stems from their collective properties and diverse applications ranging from nanomedicines to optically active metamaterials. Coating the surface of NPs with polymers allows for tailoring of the interactions between NPs to assemble them into hybrid nanocomposites with targeted architectures. This class of building blocks is termed "hairy" inorganic NPs (HINPs). Regiospecific attachment of polymers has been used to achieve directional interactions for HINP assembly. However, to date anisotropic surface functionalization of NPs still remains a challenge. This Account provides a review of the recent progress in the self-assembly of isotropically functionalized HINPs in both the condensed state and aqueous solution as well as the applications of assembled structures in such areas as biomedical imaging and therapy. It aims to provide fundamental mechanistic insights into the correlation between structural characteristics and self-assembly behaviors of HINPs, with an emphasis on HINPs made from NPs grafted with linear block copolymer (BCP) brushes. The key to the anisotropic self-assembly of these HINPs is the generation of directional interactions between HINPs by designing the surrounding medium (e.g., polymer matrix) or engineering the surface chemistry of the HINPs. First, HINPs can self-assemble into a variety of 1D, 2D, or 3D nanostructures with a nonisotropic local arrangement of NPs in films. Although a template is not always required, a polymer matrix (BCPs or supramolecules) can be used to assist the assembly of HINPs to form hybrid architectures. The interactions between brushes of neighboring HINPs or between HINPs and the polymer matrix can be modulated by varying the grafting density and length of one or multiple types of polymers on the surface of the NPs. Second, the rational design of deformable brushes of BCP or mixed homopolymer tethers on HINPs enables the anisotropic assembly of HINPs (in analogy to molecular self-assembly) into complex functional structures in selective solvents. It is evidenced that the directional interactions between BCP-grafted NPs arise from the redistribution and conformation change of the long, flexible polymer tethers, while the lateral phase separation of brushes on NP surfaces is responsible for the assembly of HINPs carrying binary immiscible homopolymers. For HINPs decorated with amphiphilic BCP brushes, their self-assembly can produce a variety of hybrid structures, such as vesicles with a monolayer of densely packed NPs in the membranes and with controlled sizes, shapes (e.g., spherical, hemispherical, disklike), and morphologies (e.g., patchy, Janus-like). This strategy allows fine-tuning of the NP organization and collective properties of HINP assemblies, thus facilitating their application in effective cancer imaging, therapy, and drug delivery. We expect that the design and assembly of such HINPs with isotropic functionalization is likely to open up new avenues for the fabrication of new functional nanocomposites and devices because of its simplicity, low cost, and ease of scale-up.

Magneto-Plasmonic Janus Vesicles for Magnetic Field-Enhanced Photoacoustic and Magnetic Resonance Imaging of Tumors.

Magneto-plasmonic Janus vesicles (JVs) integrated with gold nanoparticles (AuNPs) and magnetic NPs (MNPs) were prepared asymmetrically in the membrane for in vivo cancer imaging. The hybrid JVs were produced by coassembling a mixture of hydrophobic MNPs, free amphiphilic block copolymers (BCPs), and AuNPs tethered with amphiphilic BCPs. Depending on the size and content of NPs, the JVs acquired spherical or hemispherical shapes. Among them, hemispherical JVs containing 50 nm AuNPs and 15 nm MNPs showed a strong absorption in the near-infrared (NIR) window and enhanced the transverse relaxation (T2 ) contrast effect, as a result of the ordering and dense packing of AuNPs and MNPs in the membrane. The magneto-plasmonic JVs were used as drug delivery vehicles, from which the release of a payload can be triggered by NIR light and the release rate can be modulated by a magnetic field. Moreover, the JVs were applied as imaging agents for in vivo bimodal photoacoustic (PA) and magnetic resonance (MR) imaging of tumors by intravenous injection. With an external magnetic field, the accumulation of the JVs in tumors was significantly increased, leading to a signal enhancement of approximately 2-3 times in the PA and MR imaging, compared with control groups without a magnetic field.

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis.

CONTEXT: Diabetic patients have a higher risk of colorectal cancer (CRC). The role of metformin in CRC incidence among type 2 diabetes mellitus (T2DM) remains controversial. OBJECTIVE: A meta-analysis was performed to evaluate the role of metformin treatment in the occurrence of CRC among T2DM patients. METHODS: Search was performed throughout PubMed, Embase, Springer databases up to November 2014. The search terms were (biguanides or metformin) and (bowel or colon or rectal or colorectal) and (cancer or neoplasm or neoplasia). Relative risk (RR) and 95% confidence interval (CI) was pooled using random-effects model or fixed-effect model basing on heterogeneity, which was calculated basing on Q statistics and χ2 test. In addition, subgroup analyses were performed according to region, study design and control treatment. Finally, publication bias was evaluated using Egger's regression test and trim and fill analysis. RESULTS: A total of 11 studies, including eight cohort studies and three case-control studies, were enrolled in the meta-analysis. Obvious heterogeneity was noted, and a 25% lower CRC incidence was found among diabetic patients treated with metformin (pooled RR=0.75, 95% CI: 0.66-0.86), using the random-effects model. Subgroup analyses showed that CRC incidence significantly reduced among T2DM in different regions, non-metformin treatment and cohort studies. Evidence supported significant publication for studies investigating from Egger's regression test. Conversely, no missing data were found using trim and fill analysis. CONCLUSION: In conclusion, the meta-analysis suggests metformin may reduce CRC incidence among diabetics, which is useful medical information for clinicians.

DNA-inorganic hybrid nanovaccine for cancer immunotherapy.

Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation. Here we present DNA-inorganic hybrid nanovaccines (hNVs) for efficient uptake into APCs, prolonged tumor retention, and potent immunostimulation and cancer immunotherapy. hNVs were self-assembled from concatemer CpG analogs and magnesium pyrophosphate (Mg2PPi). Mg2PPi renders hNVs resistant to nuclease degradation and thermal denaturation, both of which are demanding characteristics for effective vaccination and the storage and transportation of vaccines. Fluorophore-labeled hNVs were tracked to be efficiently internalized into the endolysosomes of APCs, where Mg2PPi was dissolved in an acidic environment and thus CpG analogs were exposed to hNVs. Internalized hNVs in APCs led to (1) elevated secretion of proinflammatory factors, and (2) elevated expression of co-stimulatory factors. Compared with molecular CpG, hNVs dramatically prolonged the tissue retention of CpG analogs and reduced splenomegaly, a common side effect of CpG. In a melanoma mouse model, two injections of hNVs significantly inhibited the tumor growth and outperformed the molecular CpG. These results suggest hNVs are promising for cancer immunotherapy.