Efficacy comparison of antibiotic bone cement-coated implants and external fixations for treating infected bone defects.

PURPOSE: This study aimed to investigate the clinical efficacy of antibiotic bone cement-coated implants compared with external fixations for treating infected bone defects. METHODS: We retrospectively enrolled 119 patients with infected bone defects in our hospital from January 2010 to June 2021, of which 56 were treated with antibiotic bone cement-coated implants and 63 were with external fixation. RESULTS: The pre-operative and post-operative haematological indexes were tested to assess the infection control; the post-operative CRP level in the internal fixation group was lower than that in the external fixation group. No statistical significance was found in the rate of infection recurrence, loosening and rupture of the fixation, and amputation between the two groups. Twelve patients in the external fixation group had pin tract infection. In the evaluation of the Paley score scale, bone healing aspect revealed no significant difference between the two groups, while in the limb function aspect, antibiotic cement-coated implant group showed a much better score than the external fixation group (P = 0.002). The anxiety evaluation scale result also showed lower score in the antibiotic cement implant group (P < 0.001). CONCLUSIONS: Compared with external fixation, antibiotic bone cement-coated implant had the same effect on controlling infection and was more effective in recovering limb function and mental health in the first-stage treatment of infected bone defects after debridement.

The subgenomes show asymmetric expression of alleles in hybrid lineages of Megalobrama amblycephala × Culter alburnus.

Hybridization drives rapid speciation by shaping novel genotypic and phenotypic profiles. Genomic incompatibility and transcriptome shock have been observed in hybrids, although this is rarer in animals than in plants. Using the newly sequenced genomes of the blunt snout bream (Megalobrama amblycephala [BSB]) and the topmouth culter (Culter alburnus [TC]), we focused on the sequence variation and gene expression changes in the reciprocal intergeneric hybrid lineages (F1-F3) of BSB × TC. A genome-wide transcriptional analysis identified 145-974 expressed recombinant genes in the successive generations of hybrid fish, suggesting the rapid emergence of allelic variation following hybridization. Some gradual changes of gene expression with additive and dominance effects and various cis and trans regulations were observed from F1 to F3 in the two hybrid lineages. These asymmetric patterns of gene expression represent the alternative strategies for counteracting deleterious effects of the subgenomes and improving adaptability of novel hybrids. Furthermore, we identified positive selection and additive expression patterns in transforming growth factor, beta 1b (tgfb1b), which may account for the morphological variations of the pharyngeal jaw in the two hybrid lineages. Our current findings provide insights into the evolution of vertebrate genomes immediately following hybridization.

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.

Juglone Inactivates Pseudomonas aeruginosa through Cell Membrane Damage, Biofilm Blockage, and Inhibition of Gene Expression.

Due to the strong drug resistance of Pseudomonas aeruginosa (P. aeruginosa), the inhibition effects of conventional disinfectants and antibiotics are not obvious. Juglone extracted from discarded walnut husk, as a kind of plant-derived antimicrobial agent, has the advantages of naturalness, high efficiency, and low residue, with a potential role in the inhibition of P. aeruginosa. This study elucidated the inhibitory effect of juglone on the growth of plankton and the formation of P. aeruginosa biofilm. The results showed that juglone (35 µg/mL) had an irreversible inhibitory effect on P. aeruginosa colony formation (about 107 CFU/mL). The integrity and permeability of the cell membrane were effectively destroyed, accompanied by disorder of the membrane permeability, mass leakage of the cytoplasm, and ATP consumption. Further studies manifested that juglone could induce the abnormal accumulation of ROS in cells and block the formation of the cell membrane. In addition, RT-qPCR showed that juglone could effectively block the expression of five virulence genes and two genes involved in the production of extracellular polymers, thereby reducing the toxicity and infection of P. aeruginosa and preventing the production of extracellular polymers. This study can provide support for the innovation of antibacterial technology toward P. aeruginosa in food.

Triton X-100 improves co-production of ß-1,3-D-glucan and pullulan by Aureobasidium pullulans.

The effects of several surfactants on the biosynthesis of ß-1,3-D-glucan (ß-glucan) and pullulan by Aureobasidium pullulans CCTCC M 2012259 were investigated, and Triton X-100 was found to decrease biomass formation but increase ß-glucan and pullulan production. The addition of 5 g/L Triton X-100 to the fermentation medium and bioconversion broth significantly increased ß-glucan production by 76.6% and 69.9%, respectively, when compared to the control without surfactant addition. To reveal the physiological mechanism underlying the effect of Triton X-100 on polysaccharides production, the cell morphology and viability, membrane permeability, key enzyme activities, and intracellular levels of UDPG, NADH, and ATP were determined. The results indicated that Triton X-100 increased the activities of key enzymes involved in ß-glucan and pullulan biosynthesis, improved intracellular UDPG and energy supply, and accelerated the transportation rate of precursors across the cell membrane, all of which contributed to the enhanced production of ß-glucan and pullulan. Moreover, a two-stage culture strategy with combined processes of batch fermentation and bioconversion was applied, and co-production of ß-glucan and pullulan in the presence of 5 g/L Triton X-100 additions was further improved. The present study not only provides insights into the effect of surfactant on ß-glucan and pullulan production but also presents a feasible approach for efficient production of analogue exopolysaccharides. KEY POINTS: • Triton X-100 increased ß-glucan and pullulan production under either batch fermentation or bioconversion. • Triton X-100 increased the permeability of cell membrane and accelerated the transportation rate of precursors across cell membrane. • Activities of key enzymes involved in ß-glucan and pullulan biosynthesis were increased in the presence of Triton X-100. • Intracellular UDPG levels and energy supply were improved by Triton X-100 addition.

Polystyrene microplastic particles: In vivo and in vitro ocular surface toxicity assessment.

Microplastics (MPs) have become a global concern as a key environmental pollutant. MPs are widely found in oceans, rivers, bottled water, plastic-packaged foods, and toiletries. The ocular surface is the exposed mucosal tissue, which comes in contact with MP particles contained in toiletries, tap water, cosmetics, and air. However, the effects of MPs on ocular surface health are still unclear. In this study, the toxic effects of polystyrene MPs (PS-MPs) on the ocular surface in vivo and in vitro were explored. The results demonstrated that 50 nm or 2 µm PS-MPs, following exposure for 48 h appeared in the cytoplasm of two kinds of eye cells in vitro and caused a concentration dependent reduction in cell viability, further causing oxidative stress and cell apoptosis. In addition, after treatment for 2 or 4 weeks, 50 nm and 2 µm PS-MPs were deposited in the conjunctival sac of mice. After 2 and 4 weeks of PS-MP treatment, the number of goblet cells in the lower eyelid conjunctival sac decreased to 65% and 40% of that in the control group, respectively. Moreover, dry eye like ocular surface damage and inflammation of conjunctiva and lacrimal gland in mice were observed. In conclusion, this study revealed that PS-MPs could cause ocular surface dysfunctions in mice, thus providing a new perspective for the toxic effects of MPs on ocular surface.

Analysis of the epidemiological status, microbiology, treatment methods and financial burden of hematogenous osteomyelitis based on 259 patients in Northwest China.

Background: The incidence of hematogenous osteomyelitis is on the rise, and the prognosis is poor. There has been no large-scale epidemiological analysis of hematogenous osteomyelitis in the world, and the treatment method is still controversial. Methods: A retrospective case study method was used to collect and analyze clinical data obtained from patients with hematogenous osteomyelitis in a tertiary hospital in Northwest China from January 1, 2011, to December 31, 2020. The aim of this study was to investigate the epidemiological status, microbiological characteristics, treatment and financial burden of hematogenous osteomyelitis in Northwest China to explore the therapeutic effects of different treatment methods, elucidate the epidemiological characteristics of hematogenous osteomyelitis and to provide a basis for the choice of treatment. Results: We included 259 patients with hematogenous osteomyelitis, including 96 patients with acute hematogenous osteomyelitis and 163 patients with chronic hematogenous osteomyelitis. The cause of the disease was not obvious in most patients, the sex ratio of males to females was 1.98, and the three most common infected sites were the tibia, femur and phalanx. Regarding preoperative serum inflammatory markers, the rate of positivity for ESR was the highest at 67.58%. Among pathogenic microorganisms, Staphylococcus aureus was the most common. Regarding the financial burden, the median total cost per patient was 25,754 RMB, and medications accounted for the largest proportion of the main costs. Conclusions: The most common pathogen associated with HO infection was MSSA. Oxacillin has good PK and PD and is recommended as the first-line drug. Some blood-borne bone infections may lead to complications, such as pulmonary infection through bacteremia, which requires early detection to avoid a missed diagnosis. Regarding surgical intervention, debridement plus absorbable calcium sulfate bone cement and calcium sulfate calcium phosphate bone cement exclusion have achieved good therapeutic effects, but they are worthy of further in-depth research. Regarding the financial burden, the median total cost per patient was 25,754 RMB. The financial burden of blood-borne osteomyelitis was lower than that of traumatic osteomyelitis. Among the main costs, drugs accounted for the largest proportion.

Custom-Made Antibiotic Cement-Coated Nail for the Treatment of Infected Bone Defect.

BACKGROUND: Longbone infected bone defect remains a great challenge due to multiple surgeries, long-term treatment duration, and uncertain prognosis. Treatment principles include eradication/debridement, stabilization, and antibiotic administration. An antibiotic cement-coated nail has shown great prospects due to both local antibiotic elution and stabilization of bone defects. However, the current fabrication technique remains to be improved. METHODS: For the first time, we described a new method for custom-made cement-coated nail fabrication based on a 3D printing technique. A retrospective study of 19 consecutive patients with long bone infected bone defects from one medical center was conducted who met the inclusion and exclusion criteria from November 2016 to May 2020. The treatment involved thorough debridement, custom-made antibiotic cement-coated nail filling, and culture-specific systemic antibiotic treatment guided by a multidisciplinary team. Clinical and radiographic examinations (X-ray and CT scans) were used to evaluate bony union. Clinical and laboratory examinations were used to evaluate the infection control. The SF-36 score was used to evaluate patients' quality of life pre- and postoperatively. RESULTS: The mean follow-up was 98.8 weeks (ranging from 40 to 192). All cases achieved infection control, 3 cases achieved bone healing after one-stage operation, and 12 cases achieved bone healing after a two-stage bone graft procedure. At the last follow-up, none of the 19 patients had infection recurrence or 1 case had failure of the protective plate. The pre- and postoperative SF-36 score showed that there were statistical differences in all the 9 aspects. CONCLUSIONS: The precise custom-made antibiotic cement-coated intramedullary nail through the 3D printing technique used in this study is an effective strategy for the treatment of infected bone defects of long bone. This technique may help to increase the infection control rate and promote bone healing.

Applications and Functions of γ-Poly-Glutamic Acid and its Derivatives in Medicine.

BACKGROUND: γ-Poly-Glutamic Acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid, or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible, non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally friendly biological material. METHODS: The review concentrates on the reports revealing the functions and potential use of γ-PGA and its derivatives in medicine. RESULTS & DISCUSSION: γ-PGA is described to possess several properties that may be exploited in medicine. The biopolymer reportedly has been successfully applied not only as a metal chelator, drug carrier/ deliverer, and gene vector, but also used safely as a vaccine adjuvant, tissue engineering material, and contrast agent. CONCLUSION: γ-PGA could be potentially considered as a potential biomedical material in the field of medicine.

The Application and Functional Progress of γ-Poly-Glutamic Acid in Food: A Mini-Review.

γ-Poly-glutamic acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. As a biopolymer substance, γ-PGA possesses a few predominant features containing good water solubility, biocompatibility, degradability and non-toxicity. Based on this, γ-PGA can be used in pharmaceutical, such as drug carrier/deliverer, vaccine adjuvant, and coating material for microencapsulation, etc. Moreover, it has also been applied in a broad range of industrial fields including food, medicine, bioremediation, cosmetics, and agriculture. Especially, γ-PGA is an extremely promising food ingredient. In this mini-review, our aim is to review the function and application progress of γ-PGA in the food industry: e.g., improving taste and flavor, enhancing physical property, and promoting health.

Biodistribution and biocompatibility of glycyrrhetinic acid and galactose-modified chitosan nanoparticles as a novel targeting vehicle for hepatocellular carcinoma.

Aim: The dual-ligand glycyrrhetinic acid and galactose-modified chitosan nanoparticles were designed to further improve the targeting capability to hepatocellular carcinoma (HCC). Materials & methods: The dual-ligand glycyrrhetinic acid and galactose-modified chitosan nanoparticles were fabricated by using ionic gelation method and their characteristics have been measured. Furthermore, the biodistribution and biocompatibility of this targeting vehicle were investigated in vitro and in vivo, respectively. Results: The targeting vehicle was specifically internalized into hepatoma cells in vitro and accumulated into tumor tissue in vivo with high efficacy. Moreover, the vehicle did not induce inflammation reaction and affect morphologies and organ functions. Conclusion: The targeting accumulation in HCC tissue and great biocompatibility of the dual-ligand modified chitosan nanoparticles highlight the potential of delivering anticancer agents into HCC cells.

Alpha-helical peptide-induced vesicle rupture revealing new insight into the vesicle fusion process as monitored in situ by quartz crystal microbalance-dissipation and reflectometry.

We have used simultaneous quartz crystal microbalance-dissipation (QCM-D) monitoring and four-detector optical reflectometry to monitor in situ the structural transformation of intact vesicles to a lipid bilayer on a gold surface. The structural transformation of lipid vesicles to a bilayer was achieved by introducing a particular amphipathic, alpha-helical (AH) peptide. The combined experimental apparatus allows us to simultaneously follow the acoustic and optical property changes of the vesicle rupturing process upon interaction with AH peptides. While QCM-D and reflectometry have similar sensitivities in terms of mass and thickness resolution, there are unique advantages in operating these techniques simultaneously on the same substrate. These advantages permit us to (1) follow the complex interaction between AH peptides and intact vesicles with both acoustic and optical mass measurements, (2) calculate the amount of dynamically coupled water during the interaction between AH peptides and intact vesicles, (3) demonstrate that the unexpectedly large increase of both adsorbed mass and the film's energy dissipation is mainly caused by swelling of the vesicles during the binding interaction with AH peptides, and (4) permit us to understand the structural transformation from intact vesicles to a bilayer via the AH peptide interaction by monitoring viscoelastic properties, acoustic mass, optical mass, and thickness changes of both the binding and destabilization processes. From the deduced "hydration signature" we followed the complex transformation of lipid assemblies. On the basis of this information, a mechanism of this structural transformation is proposed that provides new insight into the process of vesicle fusion on solid substrates.

[APPLICATION OF COMPUTER-ASSISTED TECHNOLOGY IN ANALYSIS OF REVISION REASON OF UNICOMPARTMENTAL KNEE ARTHROPLASTY].

OBJECTIVE: To conclude the revision reason of unicompartmental knee arthroplasty (UKA) using computer-assisted technology so as to provide reference for reducing the revision incidence and improving the level of surgical technique and rehabilitation. METHODS: The relevant literature on analyzing revision reason of UKA using computer-assisted technology in recent years was extensively reviewed. RESULTS: The revision reasons by computer-assisted technology are fracture of the medial tibial plateau, progressive osteoarthritis of reserved compartment, dislocation of mobile bearing, prosthesis loosening, polyethylene wear, and unexplained persistent pain. CONCLUSION: Computer-assisted technology can be used to analyze the revision reason of UKA and guide the best operating method and rehabilitation scheme by simulating the operative process and knee joint activities.

Bioreducible polyethylenimine-delivered siRNA targeting human telomerase reverse transcriptase inhibits HepG2 cell growth in vitro and in vivo.

One new siRNA sequence was found efficient for human telomerase reverse transcriptase (hTERT) gene silencing in vitro in five types of human cancer cells. Then, a biodegradable polyethylenimine containing multiple disulfide bonds (SS-PEI) was successfully applied as a potent non-viral carrier for intracellular delivery of the hTERT siRNA in vitro and in vivo. The SS-PEI could strongly bind siRNA to form nano-sized and positively-charged complexes, but which were readily destabilized to sufficiently release siRNA in a reducing environment. Transfection experiments showed that the complexes of SS-PEI/hTERT siRNA were able to transfect HepG2 cells in vitro, inducing reduced levels of hTERT mRNA and hTERT protein, decreased telomerase activity, cell growth inhibition and significant cell apoptosis. Besides, treatment with the complexes of SS-PEI/hTERT siRNA could inhibit HepG2 tumor growth in a xenograft mouse model. Importantly, the SS-PEI revealed relatively low cytotoxicity in vitro and at an appropriate dose had no adverse effect on liver and kidney functions in vivo. The results of this study indicate that SS-PEI/siRNA-induced hTERT gene silencing provides a promising method for human cancer gene therapy.

Coordinating IMC-PID and adaptive SMC controllers for a PEMFC.

For a Proton Exchange Membrane Fuel Cell (PEMFC) power plant with a methanol reformer, the process parameters and power output are considered simultaneously to avoid violation of the constraints and to keep the fuel cell power plant safe and effective. In this paper, a novel coordinating scheme is proposed by combining an Internal Model Control (IMC) based PID Control and adaptive Sliding Mode Control (SMC). The IMC-PID controller is designed for the reformer of the fuel flow rate according to the expected first-order dynamic properties. The adaptive SMC controller of the fuel cell current has been designed using the constant plus proportional rate reaching law. The parameters of the SMC controller are adaptively tuned according to the response of the fuel flow rate control system. When the power output controller feeds back the current references to these two controllers, the coordinating controllers system works in a system-wide way. The simulation results of the PEMFC power plant demonstrate the effectiveness of the proposed method.

Solvation effects in the quartz crystal microbalance with dissipation monitoring response to biomolecular adsorption. A phenomenological approach.

Quartz crystal microbalance with dissipation monitoring (QCM-D) has become a popular tool to investigate biomolecular adsorption phenomena at surfaces. In contrast to optical mass-sensitive techniques, which commonly detect the adsorbed nonhydrated mass, the mechanically coupled mass measured by QCM-D includes a significant amount of water. A mechanistic and quantitative picture of how the surrounding liquid couples to the deposited solutes has so far been elusive for apparently simple phenomena like the random adsorption of nanometer-sized particles on a planar surface. Using a setup that enables simultaneous measurements by reflectometry and QCM-D on the same support, we have quantified the variations in coupled water, as sensed by the QCM frequency response, as a function of coverage for the formation of monolayers of globular proteins, virus particles, and small unilamellar vesicles. We found a close-to-linear relationship between the surface coverage and the relative contribution of water to the frequency response for these adsorption scenarios. The experimental hydration curves could be reproduced quantitatively using a theoretical model that assigns a pyramid-shaped hydration coat to each adsorbed particle and that accounts for the random distribution of adsorbents on the surface. This simple model fits the experimental data well and provides insight into the parameters that affect hydration.