Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model.

BACKGROUND: The choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs. METHODS: BMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation. RESULTS: The bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres. CONCLUSIONS: Our preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study.

AIMS/HYPOTHESIS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes. METHODS: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 µg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug. RESULTS: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 µg, 150 µg and 200 µg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 µg, 150 µg and 200 µg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death. CONCLUSIONS/INTERPRETATION: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

Injectable thermogel constructed from self-assembled polyurethane micelle networks for 3D cell culture and wound treatment.

Injectable hydrogels have attracted significant interest in the biomedical field due to their minimal invasiveness and accommodation of intricate scenes. Herein, we developed an injectable polyurethane-based thermogel platform by modulating the hydrophilic-hydrophobic balance of the segmented components with pendant PEG. The thermogelling behavior is achieved by a combination of the bridging from the hydrophilic PEG and the percolated network from the hydrophobic micelle core. Firstly, the thermogelation mechanism of this system was demonstrated by both DPD simulation and experimental investigation. The gelling temperature could be modulated by varying the solid content, the component of soft segments, and the length of the pendant PEG. We further applied 3D printing technology to prepare personalized hydrogel structures. This integration highlights the adaptability of our thermogel for fabricating complex and patient-specific constructs, presenting a significant advance in the field of regenerative medicine and tissue engineering. Subsequently, in vitro cell experiments demonstrated that the thermogel had good cell compatibility and could promote the proliferation and migration of L929 cells. Impressively, A549 cells could be expediently in situ parceled in the thermogel for three-dimensional cultivation and gain lifeful 3D cell spheres after 7 days. Further, in vivo experiments demonstrated that the thermogel could promote wound healing with the regeneration of capillaries and hair follicles. Ultimately, our study demonstrates the potential of hydrogels to prepare personalized hydrogel structures via 3D printing technology, offering innovative solutions for complex biomedical applications. This work not only provides a fresh perspective for the design of injectable thermogels but also offers a promising avenue to develop thermoresponsive waterborne polyurethane for various medical applications.

Polyvinyl alcohol/carboxymethyl chitosan-based hydrogels loaded with taxifolin liposomes promote diabetic wound healing by inhibiting inflammation and regulating autophagy.

With the improvement of modern living standards, the challenge of diabetic wound healing has significantly impacted the public health system. In this study, our objective was to enhance the bioactivity of taxifolin (TAX) by encapsulating it in liposomes using a thin film dispersion method. Additionally, polyvinyl alcohol/carboxymethyl chitosan-based hydrogels were prepared through repeated freeze-thawing. In vitro and in vivo experiments were conducted to investigate the properties of the hydrogel and its effectiveness in promoting wound healing in diabetic mice. The results of the experiments revealed that the encapsulation efficiency of taxifolin liposomes (TL) was 89.80 ± 4.10 %, with a drug loading capacity of 17.58 ± 2.04 %. Scanning electron microscopy analysis demonstrated that the prepared hydrogels possessed a porous structure, facilitating gas exchange and the absorption of wound exudates. Furthermore, the wound repair experiments in diabetic mice showed that the TL-loaded hydrogels (TL-Gels) could expedite wound healing by suppressing the inflammatory response and promoting the expression of autophagy-related proteins. Overall, this study highlights that TL-Gels effectively reduce wound healing time by modulating the inflammatory response and autophagy-related protein expression, thus offering promising prospects for the treatment of hard-to-heal wounds induced by diabetes.

Nanotechnology-Boosted Biomaterials for Osteoarthritis Treatment: Current Status and Future Perspectives.

Osteoarthritis (OA) is a prevalent global health concern, posing a significant and increasing public health challenge worldwide. Recently, nanotechnology-boosted biomaterials have emerged as a highly promising strategy for OA therapy due to their exceptional physicochemical properties and capacity to regulate pathological processes. However, there is an urgent need for a deeper understanding of the potential therapeutic applications of these biomaterials in the clinical management of diseases, particularly in the treatment of OA. In this comprehensive review, we present an extensive discussion of the current status and future prospects concerning nanotechnology-boosted biomaterials for OA therapy. Initially, we discuss the pathophysiology of OA and the constraints associated with existing treatment modalities. Subsequently, various types of nanomaterials utilized for OA therapy, including nanoparticles, nanofibers, and nanocomposites, are thoroughly discussed and summarized, elucidating their respective advantages and challenges. Furthermore, we analyze recent preclinical and clinical studies that highlight the potential of nanotechnology-boosted biomaterials in OA therapy. Additionally, future research directions in this evolving field are highlighted. By establishing a link between the structural properties of nanotechnology-boosted biomaterials and their therapeutic functions in OA treatment, we aim to foster advances in designing sophisticated nanomaterials for OA, ultimately resulting in improved therapeutic efficacy of OA therapy through translation into clinical setting in the near future.

On Fatigue Detection for Air Traffic Controllers Based on Fuzzy Fusion of Multiple Features.

Fatigue detection for air traffic controllers is an important yet challenging problem in aviation safety research. Most of the existing methods for this problem are based on facial features. In this paper, we propose an ensemble learning model that combines both facial features and voice features and design a fatigue detection method through multifeature fusion, referred to as Facial and Voice Stacking (FV-Stacking). Specifically, for facial features, we first use OpenCV and Dlib libraries to extract mouth and eye areas and then employ a combination of M-Convolutional Neural Network (M-CNN) and E-Convolutional Neural Network (E-CNN) to determine the state of mouth and eye closure based on five features, i.e., blinking times, average blinking time, average blinking interval, Percentage of Eyelid Closure over the Pupil over Time (PERCLOS), and Frequency of Open Mouth (FOM). For voice features, we extract the Mel-Frequency Cepstral Coefficients (MFCC) features of speech. Such facial features and voice features are fused through a carefully designed stacking model for fatigue detection. Real-life experiments are conducted on 14 air traffic controllers in Southwest Air Traffic Management Bureau of Civil Aviation of China. The results show that the proposed FV-Stacking method achieves a detection accuracy of 97%, while the best accuracy achieved by a single model is 92% and the best accuracy achieved by the state-of-the-art detection methods is 88%.

Shape-Recoverable Hyaluronic Acid-Waterborne Polyurethane Hybrid Cryogel Accelerates Hemostasis and Wound Healing.

Wound dressings that promote quick hemostasis and are highly efficient in healing wounds are urgently needed to meet the increase in clinical demands worldwide. Herein, a dihydrazide-modified waterborne biodegradable polyurethane emulsion (PU-ADH) and oxidized hyaluronic acid (OHA) were autonomously cross-linked to form a hybrid hyaluronic acid-polyurethane (HA-PU) cryogel by hydrazone bonding at -20 °C. Through its specific macroporous structure (which is approximately 220 µm) constructed by aggregated PU-ADH particles and long-chain OHA, a dried cryogel can have a dramatically compressed volume (1/7 of its original volume) with stable fixation, and it can swell rapidly by absorbing water or blood to approximately 22 and 16 times its dried weight, respectively, in a few minutes. This instantaneous shape-recovering ability favors fast hemostasis in minimally invasive surgery. Moreover, this cryogel is superior to gauze, has excellent biocompatibility, and quickly coagulates blood (in approximately 2 min) by activating the endogenous coagulation system. Comparably, an injectable HA-PU hydrogel with the same components as the HA-PU cryogel was prepared at room temperature, and it exhibited good self-healing properties. An in vivo evaluation of a rat liver hemostasis model and rat skin defect model revealed that the cryogel in fast hemostasis has great potential and superior wound-healing abilities, decreases immune inflammation, and promotes the regeneration of angiogenesis and hair follicles. Consequently, this work proposes a versatile method for constructing biodegradable hybrid cryogels via autonomous cross-linking between synthesized polymer emulsions and natural polymers. The hybrid cryogels demonstrated great potential for applications as high-performance wound dressings.

Design novel three-dimensional network nanostructure for lubricant infused on titanium alloys towards long-term anti-fouling.

Titanium alloys, recognized as a marine material with great potential, are currently facing serious biofouling problems, which greatly limits its application range. To improve the antifouling performance of titanium alloys, three unique surface of three-dimensional network, grass-like and linear nanostructures were obtained on titanium alloys via hydrothermal treatment in this work. Further, slippery liquid-infused porous surfaces (SLIPSs) were fabricated on titanium alloys via infusing PFPE lubricant into these nanostructures. Water contact angles and sliding angles of SLIPSs were measured to evaluate the effect of nanostructures on the stability of PFPE lubricant layer. Anti-fouling capability of SLIPSs were investigated by quantifying the cells of chlorella and phaeodactylum tricornutum (P. tricornutum)adhered to titanium alloys. The results shows that all the SLIPSs exhibited remarkable inhibition capacity for the settlement of chlorella and P. tricornutum. Among them, the SLIPS with three-dimensional network nanostructure displayed the longest-term anti-fouling performance, and its reduction rate of P. tricornutum and chlorella reaching 77.2 % and 84.5 % after being cultivated for 21 days, respectively, indicating that there existed a positive correlation between the stability of lubricant layer in the artificial seawater and the antifouling effect.

Evaluation Preparation of Apatinib-Loaded Polymer Nanoparticles and Its Effect in the Treatment of Advanced Ovarian Cancer.

Ovarian cancer is a common gynecological malignant tumor, second only to cervical cancer and uterine body cancer. In China, ovarian cancer has the highest mortality rate in gynecological tumors. Due to the rapid spread of cancer cells, the prognosis is relatively poor. Because the ovarian epithelial cancer is relatively insidious, there are no obvious clinical manifestations in the early stage. At present, apatinib chemotherapy is widely used, which can reduce the disease of patients by inhibiting the migration and proliferation of vascular endothelial cells. Fluorescence imaging is widely used in biomedical imaging. Organic fluorescent dyes are stable in nature and can be linked to a variety of molecules. They are often used in targeted imaging and therapeutic research. A cyanine dye is an organic molecule formed by two nitrogen-containing aromatic heterocycles connected by a polymethine bridge. Because neither MR contrast agents nor fluorescent dyes are targeted, specific biomolecules and contrast agents are often used in the research to diagnose and treat tumors. In this paper, a polymer nanoparticle loaded with apatinib was prepared and its therapeutic effect in advanced ovarian cancer was explored. The results show that nanoparticles loaded with apatinib are more effective than ordinary therapeutic drugs.

Mussel-Inspired, Injectable Polyurethane Tissue Adhesives Demonstrate In Situ Gel Formation under Mild Conditions.

Tissue adhesives are widely desired in surgical wound closure and interfacial modification of medical devices. However, poor adhesive strength, low mechanical compliance, high costs, and biotoxicity of traditional adhesives limit their biomedical applications. In this work, we fabricated a class of mussel-inspired polyurethane adhesives (MPUAs) with robust properties, including in situ gel formation under mild conditions, accommodation of intricate wounds, strong adhesion, and good biocompatibility. Dopamine-modified lysine (LDA), as a chain extender, was incorporated into linear polyurethane as a crucial adhesive unit, and biologically sourced lysine was used as a mild curing agent for in situ gel. The premixed polyurethane adhesives can be fluently injected and can fill irregular and complicated defects. After mixing for several minutes, the adhesives can strongly bond multiple substrates, such as metallic materials, organic materials, and inorganic nonmetallic materials. In particular, they can strongly cohere the fresh (wet) biological tissues with a ductile interface, and the lap shear strength (24.5 ± 2.0 kPa) of the MPUAs was six times higher than that of the commercial fibrin glue. Moreover, the bursting pressure of MPUAs on the porcine aorta was 108.2 ± 3.8 mmHg, which can satisfy most of the surgical requirements (≤20 mmHg). Given its good biocompatibility, this system would provide potential applications in clinical surgery and biological coatings of medical devices.

Synthesis and characterization of PLGA-PEG-PLGA based thermosensitive polyurethane micelles for potential drug delivery.

Polyurethane nanomicelle is a promising functional drug delivery system. In this work, the polyurethane (P3-PU) was synthesized from PLGA1200-PEG1450-PLGA1200 (P3, a thermosensitive and biodegradable triblock copolymer) and L-lysine ester diisocyanate (LDI). Then, reactive benzaldehyde was further imported to terminate P3-PU to obtain benzaldehyde modified polyurethane (P3-PUDA). The micelles, temperature-sensitive P3-PU nanomicelle and P3-PUDA nanomicelle, were systematically investigated, including the size, stability, temperature sensitivity, drug loading and release behavior, cytotoxic on human hepatocytes (L02), and inhibitory effect on human hepatocellular carcinoma cells (HepG2). The results show the thermosensitive behavior of the micelles can be adjusted by the terminal group. The polyurethane micelles with a uniform size between 20 nm and 30 nm showed excellent stability and good biocompatibility to L02 cells. Besides, in vitro experiments showed that Dox-loaded P3-PUDA micelles exhibited faster and higher release rate at 37 °C and better inhibitory effect on HepG2 than the Dox-loaded P3-PU micelles. Moreover, the achieved benzaldehyde modified polyurethanes also provides various possibilities to adjust further to enlarge its applications. Therefore, the polyurethane micelles will have great potential in the field of drug carriers.

Assessment of exposure to toxic metals and measures to address deficiency of essential trace elements in young children in rural Hubei, China.

Children are exposed to toxic metals via diet and environment, which results in adverse health effects. Several trace elements are important for the nutritional status of children; however, little information is available for rural regions in Asia. Our goal was to assess the body burden of lead, cadmium, and aluminum (Al) as toxic metals and calcium (Ca), zinc, copper, selenium (Se), strontium, and boron as trace elements in children. Multiple environmental samples, including soil, dust, fine particulates, drinking water, and food, were collected for each family. A survey was conducted by trained personnel to record detailed information about children attending a rural school. Twenty-four-hour urine samples were collected. The levels of toxic and essential trace elements were determined by inductively coupled plasma mass spectrometry. We found that the daily intake of toxic metals was below the recommended maximum, suggesting low health risks. More attention should be given to the ingestion of Al by the hand-to-mouth pathway. Ca deficiency was discovered to be a serious health problem for rural children, with Ca inadequacies reaching 96%. The excessive intake of Se-rich products from industry suggests an increased risk of toxicity. This study highlights the health risks to children who live in rural regions and the importance of dietary Ca supplementation in school meals.

Fly Ash-Based Zeolite-Complexed Polyethylene-Glycol on an Interdigitated Electrode Surface for High-Performance Determination of Diabetes Mellitus.

BACKGROUND: Diabetes is a complex metabolic disorder known to induce a high blood glucose level that fluctuates outside the normal range. Diabetes affects and damages the organs in the body and causes heart issues, blindness and kidney failure. Continuous monitoring is mandatory to keep the blood glucose level within a healthy range. MATERIALS AND METHODS: This research was focused on diagnosing diabetes mellitus on zeolite nanoparticle-polyethylene glycol complex-immobilized interdigitated electrode sensor (IDE) surfaces. Zeolite nanoparticles were extracted from the fly ash of a thermal power plant by alkaline extraction. The surface morphology of the synthesized nanoparticles was observed by field-emission scanning electron microscopy and transmission electron microscopy, and the presence of certain elements and the particle size were determined by energy-dispersive X-ray spectroscopy and particle size analysis, respectively. RESULTS: The crystalline PEG-zeolite nanoparticles were synthesized with a size of 40±10 nm according to high-resolution microscopy. A particle size analyzer revealed the sizes of the fly ash and PEG-zeolite particles as 60±10 µm and 50±10 nm, respectively. The IDE surface was evaluated for its ability to display antifouling properties and sense glucose levels on the abovementioned nanoparticle-modified surface. Glucose oxidase was probed on the PEG-zeolite-modified IDE surface, and glucose was detected. PEG zeolite performed well with excellent antifouling properties on the IDE sensor surface and improved the glucose detection limit to 0.03 mg/mL from 0.08 mg/mL, as determined by linear regressions [y = 5.365x - 6.803; R2 = 0.9035 (zeolite surface) and y = 5.498x + 5.914R2 = 0.9061 (PEG-zeolite surface)]. This enhancement was ~3-fold, and sensitivities were found to be 0.03 and 0.06 mg/mL glucose for the PEG-zeolite- and zeolite-modified surfaces, respectively, showing a 2-fold difference. CONCLUSION: The excellent biocompatible surface modified by PEG zeolite exhibited high performance and is useful for medical diagnosis.

[Studies on chemical constituents of Peucedanum delavayi].

OBJECTIVE: To study the chemical constituents of the radix and rhizome of Peucedanum delavayi. METHODS: The chemical constituents had been separated by manifold chromato-graphy methods, and their structures were determined by spectral analysis. RESULTS: Fifteen compounds were isolated and identified as Umbelliferone(I), Coumurayin(II), Mexoticin(III), Marmesin (IV), Ammijin(V), Delton (VI), Selinidin(VII), Anomalin(VII), Isopteryxin(IX), Ferulic acid(X), Falcarindiol(XI), Stearic acid(XII), beta-sitosterol(X III), Daucosterol(XIV) and d-Mannitol(XV). CONCLUSION: All these compounds are isolated from Peucedanum delavayi for the first time.

Analysis of the efficacy and safety of a combined gemcitabine, oxaliplatin and pegaspargase regimen for NK/T-cell lymphoma.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive neoplasm with a poor outcome. Novel L-asparaginase-based treatment regimens, such as GELOX (gemcitabine, oxaliplatin, and L-asparaginase) and P-gemox (gemcitabine, oxaliplatin, and pegaspargase), have shown promising results against stage IE/IIE ENKTL. To define the general applicability of P-gemox, in a retrospective analysis we examined the efficacy and safety of P-gemox in a cohort of 117 patients with newly diagnosed or relapsed/refractory ENKTL. Treatment included 2 to 8 cycles of P-gemox: intravenous gemcitabine (1250 mg/m2) and oxaliplatin (85 mg/m2) and intramuscular pegaspargase (2500 IU/ m2) on day 1 and repeated every 2 weeks, or intravenous gemcitabine (1000 mg/m2) on days 1 and 8 and intravenous oxaliplatin (130 mg/m2) and intramuscular pegaspargase (2500 IU/m2) on day 1 and repeated every 3 weeks. Upon completion of treatment, the overall response rate was 88.8%, and responses were similar for newly diagnosed and relapsed/refractory patients. After a median follow-up of 17 months, the 3-year overall and progression-free survival rates were 72.7% and 57.8%, respectively. Multivariate analysis showed that CR after treatment was the most significant factor affecting survival. P-gemox thus appears to be an effective and well-tolerated treatment for patients with ENKTL.

Improved performance of primary rat hepatocytes on blended natural polymers.

Alginate (Alg), chitosan (Chi), collagen (Col), gelatin (Gel), and the mixtures of every two of them were screened to determine their suitability for hepatocyte culture. The test materials were fabricated as films and then evaluated on the basis of their abilities to promote the attachment and functions of rat hepatocytes cultured on them. Cellular attachment on Col and Gel was favorable. However, cellular viability, cytoskeleton organization and function, as evaluated by albumin production, ureagenesis, and enzyme activity of cytochrome P450 as well as expression levels of hepatocyte nuclear factor 4 alpha deteriorated. Reverse cellular behavior was observed on Alg and Chi. Two blends, composed of Chi and Col or Gel, were found to be superior to other materials and sustained viability and differentiated functions of hepatocyte.

Epigenetic changes of TIMP-3, GSTP-1 and 14-3-3 sigma genes as indication of status of chronic inflammation and cancer.

OBJECTIVES: This study aimed to compare the epigenetic changes via hypermethylation status of TIMP-3, GSTP-1 and 14-3-3σ genes, between healthy subjects and patients with reversible chronic inflammatory disease, and between healthy subjects and patients with irreversible malignant disease, to highlight the genetic changes that occur in the progression from an inflammatory condition to irreversible genetic changes commonly observed in cancer patients. METHODS: DNA was extracted from the blood of 680 healthy subjects, and tissues and blood of 110 patients with chronic inflammation disease of the gums, as well as neoplastic tissues of 108 breast cancer patients. Methylation-specific polymerase chain reaction (PCR) for TIMP-3, GSTP-1 and 14-3-3σ was performed, and hypermethylation status was analyzed and compared between the 3 groups. RESULTS: The hypermethylation frequencies of TIMP-3 and GSTP-1 of reversible chronic inflammatory gum disease and the control group were similar, but both were significantly lower than those for malignant disease patients (p<0.0001). The methylation frequency of 14-3-3σ in chronic inflammatory gum disease was higher than in the cancer and control groups (p<0.0001). The methylation of CpG islands in TIMP-3 and GSTP-1 in chronic inflammation patients occurred as frequently as in the control group, but less frequently than in breast cancer patients. However, the epigenetic silencing of 14-3-3σ occurred more frequently in the chronic inflammation group than in cancer patients and healthy controls. CONCLUSIONS: The epigenetic silencing of 14-3-3σ might be essential for chronic inflammatory gum disease. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to cancer.

Aqueous synthesis of porous platinum nanotubes at room temperature and their intrinsic peroxidase-like activity.

Platinum nanotubes (PtNTs) exhibiting high porosity were constructed by sacrificing the exterior of tellurium nanowires (TeNWs) and disintegrating the inner part spontaneously in aqueous solution at room temperature, in which the Kirkendall effect may play an important role. The present PtNTs exhibited intrinsic peroxidase-like activity in the presence of H2O2.

[Clinical application of self-made drainage tube with balloon for iatrogenic colonic perforation].

OBJECTIVE: To investigate the clinical efficacy of colonic bypass drainage by self-made drainage tube with balloon for iatrogenic colonic perforation. METHODS: A retrospective analysis of 8 patients with iatrogenic colonic perforations from January 2009 to March 2011 was performed. Self-made drainage tubes with balloon were placed in the bowel lumen endoscopically after perforations were closed with endoclips or endoloops under endoscope. The inflatable balloon at the front-end of the tube was fixed at the mouth side of colonic perforation to achieve continuous drainage of stool and intestinal juice. RESULTS: Endoscopic bypass continuous drainage by using self-made drainage tube with balloon was successfully carried out in all the 8 patients. All the perforations healed and no surgical intervention required. Bypass drainage continued for 3-10 days(mean 7.6 days). One patient received colonoscopy 3 days after the procedure, and displacement of the drainage tube was noticed requiring endoscopic adjustment. All the drainage tubes were removed uneventfully, and no ulceration or perforation occurred at balloon fixed site after removal. After follow up ranging from 12 to 36 months, no chronic fistula, adhesive obstruction, or abdominal infection occurred. CONCLUSION: Colonic bypass drainage by self-made drainage tube with balloon for iatrogenic colonic perforation is simple, feasible, safe and reliable.

Zn-Al-NO(3)-layered double hydroxides with intercalated diclofenac for ocular delivery.

This study was aimed to evaluate the potential use of a drug delivery system, drug-layered double hydroxide (LDH) nanocomposites for ocular delivery. Diclofenac was successfully intercalated into Zn-Al-NO(3)-LDH by coprecipitation method. The nanocomposites were characterized by particle size, elemental chemical analysis, thermogravimetric analysis, etc. A tilt bilayer of diclofenac molecules formed in the interlayer with the gallery height of 1.868 nm. In vivo precorneal retention studies were conducted with diclofenac sodium (DS) saline, diclofenac-LDH nanocomposite dispersion, 2% polyvinylpyrrolidone (PVP) K30-diclofenac-LDH nanohybrid dispersion and 10% PVP K30-diclofenac-LDH nanohybrid dispersion, separately. Compared with DS saline, all the dispersions have extended the detectable time of DS from 3h to 6h; C(max) and AUC(0-t) of diclofenac-LDH nanocomposite dispersion showed 3.1-fold and 4.0-fold increase, respectively; C(max) and AUC(0-t) of 2% PVP K30-LDH nanohybrid dispersion were about 5.3-fold and 6.0-fold enhancement, respectively. Results of the Draize test showed that no eye irritation was demonstrated in rabbits after single and repeated administration. These results suggest that this novel ocular drug delivery system appears to offer promise as a means to improving the bioavailability of drugs after ophthalmic applications.