pH-Responsive antibacterial metal-phenolic network coating on hernia meshes.

Polypropylene (PP) mesh is widely used in hernioplasty, but it is prone to contamination by pathogenic bacteria. Here, we present an infection microenvironment-responsive metal-phenolic network (MPN) coating, which is made up of Cu2+ and tannic acid (TA) (referred to as CT coating), and is fabricated on PP meshes by layer-by-layer (LbL) assembly. The CT coating provided a robust protection for the PP mesh from pathogenic bacterial infection in a pH-responsive manner due to the pH-responsive disassembly kinetics of MPN complexes. Moreover, the PP meshes with ten CT coating cycles (PP-CT(10)) exhibited excellent stability in a physiological environment, with the killing ratio against "superbug" methicillin-resistant Staphylococcus aureus (MRSA) at pH 5.5 exceeding 99% even after 28 days of PBS (pH 7.4) immersion. In addition, the PP-CT(10) exhibited excellent in vivo anti-infective ability in a rodent subcutaneous implant MRSA infection model, and the results of histological and immunohistochemical analyses demonstrated that the reduced bacterial number alleviated the inflammatory response at implant sites. This study revealed that MPN coating is a promising strategy, which could provide a self-defensive ability for various implants to combat post-surgical infections in a pH-responsive manner.

Infection Microenvironment-Responsive Coating on Titanium Surfaces for On-Demand Release of Therapeutic Gas and Antibiotic.

Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on-demand release of therapeutic gas hydrogen sulfide (H2S) and antibiotic. TiO2 nanotubes (TNT) are anodized on the Ti surface to enhance its bioactivity and serve as reservoirs for the antibiotic. An infection microenvironment-responsive macromolecular H2S donor layer is coated on top of TNT to inhibit premature leakage of antibiotic. This layer exhibits a sustained release of low-dosage H2S, which is capable of promoting the osteogenic differentiation and migration of cells. Moreover, the compactness of the macromolecular H2S donor layer could be broken by bacterial invasion, leading to rapid antibiotic release thus preventing infection. In vitro antibacterial experiments validates significant antibacterial activity of the coating against both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Crucially, this coating effectively suppresses implant-associated infection with 98.7% antibacterial efficiency in a rat femoral bone defect model, mitigates inflammation at the defect site and promotes osseointegration of the Ti orthopedic implant.

A Case of Central Venous Catheter-Related Bacteremia Caused by Enterococcus gallinarum.

A chicken farmer with cirrhosis and renal failure presented with an unusual case of catheter-related bacteremia. Testing with the VITEK® 2 Compact system, MALDI-TOF mass spectrometry, and 16S rDNA sequencing identified the pathogen as E. gallinarum. This case demonstrates the importance of maintaining a high level of contextual awareness in patients exposed to avian species to make an informed diagnosis and provide prompt treatment.

Characterization of changes in the intestinal microbiome following combination therapy with zinc preparation and conventional treatment for children with rotavirus enteritis.

Background: Rotavirus (RV) is one of the most common pathogens causing diarrhea in infants and young children worldwide. Routinely, antiviral therapy, intestinal mucosa protection, and fluid supplementation are used in clinic, however this is not efficacious in some severe cases. Zinc supplementation has previously been shown to improve resolution of symptoms from infectious diarrhea. Methods: In this study differences in response rate, duration of hyperthermia, vomiting, and diarrhea, and the persistence time of cough and lung rales in groups were compared. 16SrDNA gene sequencing technology was used to analyze and compare changes in the intestinal microflora of children with RV enteritis who received the conventional treatment with or without the zinc preparation. In addition, the correlations between the differential bacterial species and the related inflammatory factors were determined. Results: Conventional therapy combined with the zinc preparation significantly shortened the duration of hyperthermia, vomiting, and diarrhea compared with the conventional treatment alone. In addition, the time to symptom relief showed that the absorption time of cough and lung rales was significantly shorter in the combination treatment group than that in the conventional treatment group in the children with pneumonia. Further, compared with the conventional treatment, the combined treatment significantly increased the diversity and abundances of florae as compared with the conventional treatment. This combination therapy containing zinc preparation markedly increased the abundances of Faecalibacterium, Bacteroidales, Ruminoccoccoccus, and Lachnospiraceae at the genus level. The LEfSe analysis suggested that Clostridiumbolteae were most significantly altered after the combination therapy. In addition, a correlation analysis revealed significantly negative correlations between the inflammatory factors especially IL-6, TNF-a, CRP and some intestinal florae such as Bacteroides, Faecalibacterium, Blautia, Parabacteroides, Subdoligranulum, and Flavonifractor. Conclusion: Compared with the conventional therapy alone, the combined therapy with the zinc preparation significantly improves symptoms caused by RV. The combination therapy containing the zinc preparation significantly increases the diversity and abundances of some beneficial groups of bacteria. Further, The presence of these groups was further negatively correlated with relevant inflammatory factors. More importantly, this combination therapy containing the zinc preparation provides a reference for the clinical management of children with RV enteritis.

[Analysis of rehabilitation effects of cochlear implantation in elderly patients with prelingual deafness].

Objective:The auditory and speech rehabilitation effects were assessed by the Categories of Auditory Performance（CAP） and the speech intelligibility rating scale（SIR） after cochlear implantation（CI） in prelingually elderly patients by telephone follow-up or face-to-face conversation. Methods:The clinical data of the prelingually deaf patients who underwent unilateral CI in the Department of Otorhinolaryngology and Head and Neck Surgery, Shanxi People's Hospital, from December 2016 to December 2021 were collected. Thirty-eight patients were divided into Group A（SIR 1, 17 cases）, Group B（SIR 2, 10 cases） and Group C（SIR 3, 11 cases） according to the preoperative SIR Score. Nineteen patients with post-lingual hearing impairment were selected as the control group（Group D, 19 cases）. The effects of hearing and speech rehabilitation were evaluated using CAP and SIR Scores before surgery, 6 months after startup, and 1 year after startup. Results:There were no significant differences in CAP scores among the three groups of patients with prelingually deaf patients at 6 months and 1 year after startup（P>0.05）, but there were significant differences between group A and group D at 6 months and 1 year after startup（P<0.05）; the SIR Score of group A had statistical difference before surgery and 6 months after startup（P<0.05）, group B had statistical difference before surgery and 1 year after startup（P<0.05）, and group C and D had no statistical difference before surgery and 6 months and 1 year after startup, respectively（P>0.05）. Conclusion:For the prelingually deaf elderly patients, hearing will develop rapidly 6 months after startup, and the effect of postoperative auditory rehabilitation was positively correlated with the preoperative speech ability. In the aspect of speech, the prelingually dear elderly patients who have poor preoperative speech ability could benefit more from CI early after surgery. CI is not contraindicated in prelingually deaf elderly patients, even those with poor preoperative speech function.

The effects of free Cys residues on the structure, activity, and tetrameric stability of mammalian uricase.

Mammalian uricases contain four conserved cysteine (Cys) residues, but little is known about their structures and functions. In this study, we first confirmed that all four Cys residues are free and not involved in disulfide bond formation, using canine uricase as a model protein. Cys residues had a greater effect on stability than on activity based on single Cys-to-Ser (serine) substitutions. Circular dichroism (CD) and homology modeling indicated that C188S reduces ß-sheet contents and inter- and intra-subunit hydrophobic interaction, potentially impairing the core tetrameric ß-barrel structure of the tunneling-fold protein, and ultimately decreased the tetrameric stability. Additionally, the inactivation of C188S during the stability tests may be a complex process involving depolymerization followed by irregular aggregation. Double mutations or thiol blockage of Cys188 and Cys195 significantly disrupted the formation and stability of tetrameric uricase, which may be mediated by the free thiols in Cys residues. The present results demonstrated that the free Cys residues are essential for tetrameric formation and stability in mammalian uricase. This implies that free cysteine residues, although not involved in disulfide bonding, may play important structural roles in certain proteins, underscoring the significance of the hydrophobic characteristics of the free thiols in Cys residues. KEY POINTS: • Four Cys residues are not involved in disulfide bonding in mammalian uricase. • The hydrophobicity of free thiols is critical for tetrameric stability in uricase. • Free Cys residues can serve structural roles without involving in disulfide bonds.

Nonreleasing AgNP Colloids Composite Hydrogel with Potent Hemostatic, Photodynamic Bactericidal and Wound Healing-Promoting Properties.

Reactive oxygen species (ROS) produced by noble metallic nanoparticles under visible light is an effective way to combat drug-resistant bacteria colonized on the wound. However, the photocatalytic efficiency of noble metallic nanoparticles is limited by its self-aggregation in water media. Moreover, the fast release of noble metallic ions from nanoparticles might engender cellular toxicity and hazardous environmental issues. Herein, we chose AgNPs, the most common plasmonic noble metallic nanoparticles, as an example, modifying the surface of AgNPs with oleic acid and n-butylamine and imbedded them into calcium alginate (CA) hydrogel that holds tissue adhesion, rapid hemostatic, sunlight-sensitive antibacterial and anti-inflammatory abilities, and thus effectively promotes the healing of wounds. Unlike conventional AgNP-based materials, the constrain of colloids and hydrogel networks hinders the leach of Ag+. Nonetheless, the CA/Ag hydrogels exhibit on-demand photodynamic antibacterial efficacy due to the generation of ROS under visible light. In addition, the CA/Ag hydrogel can effectively stop the hemorrhage in a mouse liver bleeding model due to their skin-adaptive flexibility and tissue adhesiveness. The potent sunlight-responsive antibacterial activity of the CA/Ag hydrogel can effectively kill multidrug-resistant bacteria both in vitro (>99.999%) and in vivo (>99.9%), while the diminished Ag+ release guarantees its biocompatibility. The CA/Ag hydrogel significantly promotes the wound healing process by the downregulation of proinflammatory cytokines (TNF-α and IL-6) in a rodent full-thickness cutaneous wound model. Overall, the proposed multifunctional CA/Ag nanocomposite hydrogel has excellent prospects as an advanced wound dressing.

Efficacy of Chinese medicine in the adjuvant treatment of Hashimoto's thyroiditis with hypothyroidism: a systematic review and meta-analysis.

The quality of the studies was assessed using the Cochrane risk bias assessment tool and the results were analyzed using Review Manager 5.3 software. The evidence was also evaluated for its strength using GRADE. A total of 18 randomized controlled trials were included in the study, involving 1247 patients. The primary outcomes of this study included overall efficacy, effectiveness in treating specific symptoms, and the Traditional Chinese Medicine symptom score. The secondary outcomes included the levels of FT3, FT4, and TSH, the size of the thyroid gland, and any adverse events. The results of the meta-analysis showed that CHM combined with WM has a better curative effect and a more effective reduction in clinical symptoms than WM alone: comprehensive efficacy [OR = 4.83; 95% CI (3.45, 6.76)], syndrome efficacy [OR = 5.95; 95% CI (3.94, 8.99)], TCM symptom score SMD = -1.49; 95% CI (-1.86, -1.11)], FT3 [SMD = 0.59; 95% CI (0.48, 0.71)], FT4 [SMD = 0.59; 95% CI (0.48, 0.71)], TSH SMD = -0.97; 95% CI (-1.35, -0.58)], and thyroid volume SMD = -0.25; 95% CI (-0.34, 0.15)]. The incidence of adverse events between the groups was not significantly different [OR = 1.00; 95% CI (0.14, 7.27)]. Because of the effectiveness of CHM, we support using CHM to improve clinical efficacy in the treatment of HTH. The results of our research suggest that the use of Chinese Herbal Medicine (CHM) in combination with Western Medicine (WM) may result in improved clinical efficacy in the treatment of hypothyroidism (HTH) compared to using WM alone.

Metal-Phenolic Networks Assembled on TiO2 Nanospikes for Antimicrobial Peptide Deposition and Osteoconductivity Enhancement in Orthopedic Applications.

The lack of antimicrobial and osteoconductive activities of titanium (Ti) for orthopedic implants has led to problems such as infection and structural looseness, which bring physical and psychological sufferings to patients as well as economic burden on the healthcare system. To endow Ti implants with anti-infective function and bioactivity, in this study, we successfully constructed TiO2 nanospike (TNS) structure on the surface of Ti followed by assembling metal-polyphenol networks (MPNs) and depositing antimicrobial peptides (AMPs). The TNSs' structure can disrupt the bacteria by physical puncture, and it was also proved to have excellent photothermal conversion performance upon near-infrared light irradiation. Furthermore, with the assistance of contact-active chemo bactericidal efficacy of AMPs, TNS-MPN-AMP nanocoating achieved physical/photothermal/chemo triple-synergistic therapy against pathogenic bacteria. The anti-infective efficiency of this multimodal treatment was obviously improved, with an antibacterial ratio of >99.99% in vitro and 95.03% in vivo. Moreover, the spike-like nanostructure of TNSs and the bioactive groups from MPNs and AMPs not only demonstrated desirable biocompatibility but also promoted the surface hydroxyapatite formation in simulated body fluid for further osseointegration enhancement. Altogether, this multifaceted TNS-MPN-AMP nanocoating endowed Ti implants with enhanced antibacterial activity, excellent cytocompatibility, and desirable osteoconductive ability.

Preparation of Conotoxin-Encapsulated Chitosan Nanoparticles and Evaluation of Their Skin Permeability.

µ-Conotoxin CnIIIC (conotoxin, CTX)-loaded chitosan nanoparticles (CTX-NPs) were prepared using the ionic cross-linking method. The CTX-NPs were spherical and well with a polydispersity index of 0.292 ± 0.039, drug loading efficiency of 25.9 ± 1.2%, and encapsulation efficiency of 95.6 ± 1.3%. In vitro release studies showed that the release behavior of CTX-NPs in a pH 5.0 acetate buffer followed zero-order kinetics. In vitro transdermal experiments using Franz diffusion cells mounted with mouse abdominal skin demonstrated that the cumulative intradermal deposition amount of CTX per unit area in 8 h (D8) and permeability coefficient (Pf) of CTX loaded on CTX-NPs were 2.30- and 7.71-times that of the CTX solution. In vivo transdermal experiments in mice showed that the amount of CTX deposited in the skin after 8 h of CTX saline administration was significantly lower than that of CTX deposited in the skin after administration of CTX-NPs. In vitro fluorescence labeling transdermal studies through Franz diffusion cells mounted with mouse abdominal skin indicated that CTX-NPs aggregated at hair follicles. Skin irritation tests in mice indicated that the irritation due to CTX-NPs was negligible. The cytotoxicity experiment showed that the viability of Balb/c 3T3 cells with CTX-NPs containing 230 µg/mL (0.08 µM) CTX was greater than 75%. CTX-NPs increase intradermal deposition of CTX by accumulating in hair follicles, which has positive implications for transdermal penetration of CTX.

Molecular mechanism of Sishen pills in the treatment of diarrheal diabetic enteropathy based on network pharmacology.

This study aimed to explore the effectiveness and safety of Sishen pills for the treatment of diarrheal diabetic enteropathy (DDE). The Traditional Chinese Medicine (TCM) Systems Pharmacology and BATMAN-TCM databases were used to determine the chemical composition of Sishen pills and thus predict information on protein targets. We searched for potential targets of DDE in the GeneCards, DrugBank, Therapeutic Target (TTD), and DisGeNET databases. Using the intersection of the drug and disease targets, protein-protein interaction (PPI) networks and molecular interaction modules were constructed, and key targets were screened. The intersecting gene targets were imported into the Metascape database to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The core targets and active ingredients were then docked at the molecular level. Sishen pills contain 70 active ingredients, 463 targets, and 566 disease targets. A module analysis of the targets revealed that the module was mainly related to adrenergic receptor activity, the adenosine phosphate kinase signaling pathway, and the G protein-coupled receptor signaling pathway. The GO and KEGG pathway enrichment results indicated that the protein genes regulated by Sishen pills were mainly enriched in the response to lipopolysaccharides, the AMPK signaling pathway, the JAK-STAT signaling pathway, and other signaling pathways. The molecular docking results showed that the core active compounds exhibited good binding activity with the predicted targets. Sishen pills can regulate the immune function of the body through anti-inflammatory and antibacterial effects for the treatment of DDE.

An Electroluminodynamic Flexible Device for Highly Efficient Eradication of Drug-Resistant Bacteria.

Photodynamic therapy (PDT) has attracted wide attention in antibacterial applications due to its advantages of spatial-temporal selectivity, noninvasiveness, and low incidence to develop drug resistance. To make it more convenient, universal, and manipulatable for clinical application, a conceptually antibacterial strategy, namely "electroluminodynamic therapy" (ELDT), is presented by nanoassembly of an electroluminescent (EL) material and a photosensitizer, which is capable of generating reactive oxygen species (ROS) in situ under an electric field, i.e., the fluorescence emitted by the EL molecules excites the photosensitizer to generate singlet oxygen (1 O2 ), for the oxidative damage of pathogens. Based on the scheme of ELDT, a flexible therapeutic device is fabricated through a hydrogel loading with ELDT nanoagents, followed by integration with a flexible battery, satisfying the requirements of being light and wearable for wound dressings. The ELDT-based flexible device presents potent ROS-induced killing efficacies against drug-resistant bacteria (>99.9%), so as to effectively inhibit the superficial infection and promote the wound healing. This research reveals a proof-of-concept ELDT strategy as a prospective alternative to PDT, which avoids the utilization of a physical light source, and achieves convenient and effective killing of drug-resistant bacteria through a hydrogel-based flexible therapeutic device.

Simultaneous Efficient Decontamination of Bacteria and Heavy Metals via Capacitive Deionization Using Polydopamine/Polyhexamethylene Guanidine Co-deposited Activated Carbon Electrodes.

The contamination of pathogenic micro-organisms and heavy metals in drinking water sources poses a serious threat to human health, which raises the demand for efficient water treatments. Herein, multi-functional capacitive deionization (CDI) electrodes were developed for the simultaneous decontamination of bacteria and heavy metal contaminants. Polyhexamethylene guanidine (PHMG), an antibacterial polymer, was deposited on the surface of the activated carbon (AC) electrode with the assistance of mussel-inspired polydopamine (PDA) chemistry. The main characterization results proved successful co-deposition of PDA and PHMG on the AC electrode, forming a hydrophilic coating layer in one step. Electrochemical analyses indicated that the AC-PDA/PHMG electrodes presented satisfactory capacitive behaviors, with outstanding salt adsorption capacity and cycling stability. The modified electrodes also exhibit excellent disinfection performance and heavy metal adsorption performance. The bacterial elimination rate of co-deposited electrodes grew along with the increase in the PHMG content. Particularly, AC-PDA/PHMG2 electrodes successfully removed and deactivated 99.11% Escherichia coli and 98.67% Pseudomonas aeruginosa (104 CFU mL-1) in water within 60 min. Furthermore, three flow cells made by AC-PDA/PHMG2 electrodes connected in series achieved efficient removal of salt, heavy metals such as lead and cadmium, and bacteria simultaneously, which indicated that the adsorption performance is significantly improved compared with pristine AC electrodes. These results denote the enormous potential of this one-step prepared multi-functional electrodes for facile and effective water purification using CDI technology.

Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections.

Due to the emerging bacterial resistance and the protection of tenacious biofilms, it is hard for the single antibacterial modality to achieve satisfactory therapeutic effects nowadays. In recent years, photothermal therapy (PTT)-derived multimodal synergistic treatments have received wide attention and exhibited cooperatively enhanced bactericidal activity. PTT features spatiotemporally controllable generation of hyperthermia that could eradicate bacteria without inducing resistance. The synergy of it with other treatments, such as chemotherapy, photo-dynamic/catalytic therapy (PDT/PCT), immunotherapy, and sonodynamic therapy (SDT), could lower the introduced laser density in PTT and avoid undesired overheating injury of normal tissues. Simultaneously, by heat-induced improvement of the bacterial membrane permeability, PTT is conducive for accelerated intracellular permeation of chemotherapeutic drugs as well as reactive oxygen species (ROS) generated by photosensitizers/sonosensitizers, and could promote infiltration of immune cells. Thereby, it could solve the currently existing sterilization deficiencies of other combined therapeutic modes, for example, bacterial resistance for chemotherapy, low drug permeability for PDT/PCT/SDT, adverse immunoreactions for immunotherapy, etc. Admittedly, PTT-derived synergistic treatments are becoming essential in fighting bacterial infection, especially those caused by antibiotic-resistant strains. This review firstly presents the classical and newly reported photothermal agents (PTAs) in brief. Profoundly, through the introduction of delicately designed nanocomposite platforms, we systematically discuss the versatile photothermal-derived multimodal synergistic therapy with the purpose of sterilization application. At the end, challenges to PTT-derived combinational therapy are presented and promising synergistic bactericidal prospects are anticipated.

Titanium dioxide nanotubes as drug carriers for infection control and osteogenesis of bone implants.

Titanium implants have been widely used as one of the most effective treatments of bone defects. However, the lack of osteogenesis and bacteria-resistant activities result in high infection and loosening rates of titanium implants. Anodic oxidation could easily construct titanium dioxide nanotubes (TNTs) array on the surface of titanium, and the rough surface of TNTs is beneficial to the growth of osteoblast-related cells on the surface. And TNTs could be excellent drug carriers because of their single-entry tubular hollow structure. In this review, we aim at detailing the application of TNTs as drug carriers in the field of bone implants. Starting from the topography of TNTs, we illustrated the biological activity of the TNTs surface, the drugs for loading in TNTs, and the controlled and responsive release strategies of drug-loaded TNTs, respectively. At the end of this review, the shortcomings of TNTs as the drug carrier in the field of bone implants are discussed, and the development direction of this research field is also prospected.

Determination of PEGylation homogeneity of polyethylene glycol-modified canine uricase.

Polyethylene glycol-modified canine uricase (PEG-UHC) was prepared by modifying the ε-amino group of lysine residues on the canine uricase (UHC) protein to near-saturation with 5 kDa monomethoxyl-polyethylene glycol succinimide (mPEG-SPA-5k). In order to accurately determine the PEGylation uniformity of PEG-UHC, CZE, 3-8% gradient gel SDS-PAGE, and imaging CIEF (iCIEF) analyses were compared. CZE could not effectively separate PEG-UHC proteins with different degrees of modification, 3-8% gradient gel SDS-PAGE could separate PEG-UHC into seven gel bands; however, most of the gel bands were smeared or blurred, and the separation of PEG-UHC samples by iCIEF was significantly better than that by 3-8% gradient gel SDS-PAGE. Under denatured conditions, iCIEF separated 12 pI peaks, and could also accurately quantify the relative monomer PEG-UHC content. More than 85% of the total monomeric PEG-UHC was conjugated with 7-12 PEG molecules; of this 85%, approximately 40% was conjugated with 9-10 PEG molecules. These results demonstrated that iCIEF exhibits good potential for determining the PEGylation homogeneity of PEGylated protein drugs.

A multifunctional shape-adaptive and biodegradable hydrogel with hemorrhage control and broad-spectrum antimicrobial activity for wound healing.

Hemorrhage is the leading cause of preventable death of injured military and civilian patients, and subsequent infection risks endanger their lives or impede the healing of their wounds. Here, we report an injectable biodegradable hydrogel with hemostatic, antimicrobial, and healing-promoting properties. The hydrogel was prepared by dynamic cross-linking of a natural polysaccharide (dextran) with antimicrobial peptide ε-poly-l-lysine (EPL) and encapsulating base fibroblast growth factor (bFGF). The amino groups of EPL were allowed to react with the aldehyde of oxidized dextran (OD) through the Schiff-base reaction for the generation of hydrogels that have fast self-healing and injectable characteristics and adapt to the shapes of wounds. The prepared OD/EPL hydrogels promoted blood clotting in vitro and stopped bleeding in a rat liver injury model within 6 min through their platelet-aggregating ability and sealing effect. These hydrogels exhibited inherent antimicrobial effects without the use of antibiotics and effectively killed a broad spectrum of pathogenic microbes, including Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli, and Pseudomonas aeruginosa and fungus Candida albicans in vitro. Moreover, these OD/EPL hydrogels were compatible with mammalian cells in vitro and in vivo and biodegradable in the mouse body. The loaded bFGF can be released sustainably, and it can promote angiogenesis, endothelial cell migration, and consequently accelerate the healing of wounds. The OD/EPL hydrogel inhibited MRSA infection in a rat full-thickness skin wound model and promoted healing. This kind of multifunctional hydrogel is a promising wound dressing for the emergency treatment of acute deep or penetrating injuries.

Pharmacokinetics of Polyethylene Glycol-Modified Canine Uricase Following Single and Multiple Intravenous Injections in Cynomolgus Monkeys.

BACKGROUND AND OBJECTIVE: Polyethylene glycol-modified canine uricase (PEG-UHC) prepared with a lower-molecular-weight (5 kDa) PEG is used to treat gout. This study investigated the comparative pharmacokinetics of single and multiple doses of PEG-UHC administered intravenously and a single dose of uricase (UHC) administered intravenously in cynomolgus monkeys. METHODS: A noncompartmental model was used to fit the plasma drug concentration-time curve and calculate the pharmacokinetic parameters of PEG-UHC, which were compared with those obtained for UHC at the equivalent dose (2 mg/kg). To study the pharmacokinetics after multiple dose administration, cynomolgus monkeys were administered five intravenous injections of PEG-UHC (0.5 mg/kg), with one injection performed every 15 days. RESULTS: The area under the curve (AUC) and the maximum plasma concentration (Cmax) of PEG-UHC were positively correlated with dose, whereas plasma half-life (t1/2) and clearance (CL) did not change significantly with increasing dose, suggesting that these pharmacokinetic characteristics are linear. Intravenous PEG-UHC exhibited an average t1/2 that was 125.79 times longer and an AUC0-t that was 64.45 times larger than the corresponding values for UHC at the same dose (2 mg/kg), while the CL of PEG-UHC was 1/72.73 times the CL of intravenous UHC. The plasma drug concentration reached a steady state after five injections, and the t1/2 values following the first and last drug administration did not differ significantly. CONCLUSION: Our data show that PEG-UHC is markedly superior to UHC in terms of duration of action, and that the pharmacokinetics of PEG-UHC in cynomolgus monkeys are linear. Sequential administration of PEG-UHC did not accelerate drug clearance. Our findings provide the basis for future clinical studies of PEG-UHC.

Mussel-Inspired, Surface-Attachable Initiator for Grafting of Antimicrobial and Antifouling Hydrogels.

In this work, a novel biomimetic surface-attachable initiator is successfully synthesized by the conjugation of 3,4-dihydroxyphenylacetic acid and thermal 2,2'-azobis(2-methylpropionamide) dihydrochloride (V-50). The synthesized initiator (DOPV) can adhere to various material surfaces in a mussel-inspired way and initiate the surface grafting polymerization. Hydrogel coatings are facilely prepared by the thermal-initiated radical copolymerization of antimicrobial polyhexamethylene guanidine and antifouling polyethylene glycol oligomers. The developed hydrogel coatings not only show antimicrobial activity toward gram-negative and gram-positive bacteria but also demonstrate protein resistance, antibiofilm efficacy, hemocompatibility, and low cytotoxicity in vitro. Most importantly, the hydrogel coatings reveal excellent antimicrobial efficacy with a log reduction above 5 in a rodent subcutaneous infection model. These results demonstrate the potential fabrication of bio-functional coatings for biomedical devices or implants through an inexpensive, facile, and environmentally friendly mussel-inspired technique.

[Clinical evaluation of the consistency between two diagnostic criteria for diabetic peripheral neuropathy].

OBJECTIVE: To evaluate the consistency between the clinical diagnostic criteria and the ascertained diagnostic criteria for diabetic peripheral neuropathy (DPN) in the Preventive and Treatment Guidelines of Diabetes in China (2013) and explore an economic, convenient, and accurate approach to DPN diagnosis. METHODS: The patients with type 2 diabetes admitted in our department from April to June, 2014 were examined for nerve conduction velocity, 10 g nylon silk, vibration threshold value, sense of temperature and pain, and ankle reflex. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and Kappa value were calculated to assess the diagnostic power of the two diagnostic criteria. RESULTS: Of the 151 patients enrolled, 106 (70.2%) had a diagnosis of DPN consistent with the ascertained diagnostic criteria, as compared to 86 (56.95%) who were diagnosed according to the clinical diagnostic criteria; the latter patients accounted for 81.13% of former cases. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and Kappa value of the clinical diagnostic criteria were 80.19%, 97.78%, 98.84%, 67.69%, 77.97%, and 0.69, respectively, which were highly consistent with those of the ascertained diagnostic criteria; the sensitivity to compression showed a poor consistency between the two diagnostic criteria. In the 5 screening tests, the combined test of temperature sensation, vibration perception, and ankle reflex showed the highest AUC value among their different combinations. CONCLUSION: The clinical diagnostic criteria for DPN show good consistency with the ascertained diagnostic criteria, and for patients with clinical symptoms or with only one positive sign, combination of the two diagnostic criteria can achieve the maximum diagnostic power.