Fibrinogen Deposition on Silicone Oil-Infused Silver-Releasing Urinary Catheters Compromises Antibiofilm and Anti-Encrustation Properties.

Slippery silicone-oil-infused (SOI) surfaces have recently emerged as a promising alternative to conventional anti-infection coatings for urinary catheters to combat biofilm and encrustation formation. Benefiting from the ultralow low hysteresis and slippery behavior, the liquid-like SOI coatings have been found to effectively reduce bacterial adhesion under both static and flow conditions. However, in real clinical settings, the use of catheters may also trigger local inflammation, leading to release of host-secreted proteins, such as fibrinogen (Fgn) that deposits on the catheter surfaces, creating a niche that can be exploited by uropathogens to cause infections. In this work, we report on the fabrication of a silicone oil-infused silver-releasing catheter which exhibited superior durability and robust antibacterial activity in aqueous conditions, reducing biofilm formation of two key uropathogens Escherichia coli and Proteus mirabilis by ∼99%, when compared with commercial all-silicone catheters after 7 days while remaining noncytotoxic toward L929 mouse fibroblasts. After exposure to Fgn, the oil-infused surfaces induced conformational changes in the protein which accelerated adsorption onto the surfaces. The deposited Fgn blocked the interaction of silver with the bacteria and served as a scaffold, which promoted bacterial colonization, resulting in a compromised antibiofilm activity. Fgn binding also facilitated the migration of Proteus mirabilis over the catheter surfaces and accelerated the deposition and spread of crystalline biofilm. Our findings suggest that the use of silicone oil-infused silver-releasing urinary catheters may not be a feasible strategy to combat infections and associated complications arising from severe inflammation.

Immunomodulatory effects of platelets on the severity of hand, foot, and mouth disease infected with enterovirus 71.

BACKGROUND: Enterovirus 71 (EV71) infection contributes to hand, foot, and mouth disease (HFMD) with severe neurogenic complications, leading to higher morbidity. In addition to their typical roles in coagulation, platelets could serve as essential immune regulatory cells to play a key role in the pathogenesis of this viral infection. METHODS: Platelet parameters were measured using an automatic hematology analyzer. T-helper type 1 (Th1) and Th2 cells were analyzed by flow cytometry. The levels of cytokines and key transcription factors were determined. RESULTS: The levels of platelet count and plateletcrit were positively associated with the severity of HFMD. Th1 and Th2 cells as well as their corresponding cytokines were increased in the severe group compared to the healthy volunteers. Moreover, the levels of platelets were negatively correlated with the level of interferon-γ (IFN-γ), but positively correlated with the frequency of Th1 cells. Coculture of platelets and naive CD4+ T cells showed that platelets from mild patients promote Th1 cell differentiation and IFN-γ secretion. CONCLUSIONS: Our study has shown for the first time that the distinct roles of platelets are responsible for the regulation of pathogenic CD4+ T cell differentiation and function in the pathogenesis of HFMD caused by EV71. IMPACT: Our study has shown for the first time that the distinct roles of platelets are responsible for the regulation of pathogenic CD4+ T cell differentiation and function in the pathogenesis of HFMD caused by EV71. For the first time, we have discovered the role of platelets in children's HFMD caused by EV71 infection, which may provide a better treatment for HFMD in the future. This article describes new discoveries in platelet immunity.

Safety of Cement Distribution Patterns in Metastatic Vertebral Tumors: A Retrospective Study.

BACKGROUND Kyphoplasty (KP) is a palliative treatment for patients with metastatic vertebral tumors. The distribution pattern of cement affects safety and efficacy. The distribution pattern of cement has not been previously reported for patients with metastatic vertebral tumors. MATERIAL AND METHODS From January 2013 to December 2017, patients with metastatic vertebral tumors who met our criteria were divided into cement fusion (n=91) and separation (n=97) groups. Visual analogue scale (VAS) and middle vertebral height (MVH) were evaluated preoperatively, postoperatively, and 1 year after surgery. Spinal Instability Neoplastic Score, fluoroscopy time, operation time, cement volume, cement leakage, and vertebral fractures were recorded and evaluated. RESULTS Compared with the fusion group, the separation group had significantly different (P<0.001) operation time, fluoroscopy time, and cement volume. Compared with preoperative status, VAS and MVH were significantly improved 3 days postoperatively and 1 year postoperatively in both groups (P<0.001). The difference in cement leakage between the 2 groups (P<0.05) and in the number of adjacent vertebral fractures between the 2 groups (P<0.05) were significant. CONCLUSIONS The distribution patterns of the bone cement had a good analgesic effect and preventive effect on vertebral collapse. However, the separation of bone cement may be safer.

The effect of blending poly (l-lactic acid) on in vivo performance of 3D-printed poly(l-lactide-co-caprolactone)/PLLA scaffolds.

Blending poly (l-lactic acid, PLLA) with poly (l-lactide-co-caprolactone, PLCL) is an effective strategy for developing new PLCL/PLLA blend based biomaterials. However, the effect of PLLA on in vivo performance of PLCL/PLLA blends is unclear yet. To address this issue, in this study, the effect of PLLA on in vivo biodegradability and biocompatibility of 3D-printed scaffolds of PLCL/PLLA blend was investigated. Three kinds of different 3D-printed PLCL/PLLA scaffolds using different blends with different mass ratios of the polymers, were prepared and implanted subcutaneously. The shrinkage and tissue responses were monitored by ultrasonography after the implantation. 2 months post-operation, the in vivo performances of the scaffolds were investigated histologically. All scaffolds showed good biocompatibility and allowed fast tissues ingrowth, however PLCL50/PLLA50 scaffold with the highest PLLA ratio induced the thickest the fibrous capsule surrounding the scaffolds and highest inflammatory scores. Furthermore, it was found that the fine porous structures of all scaffolds were well maintained, indicating the 3D-printed scaffolds were degraded through a surface erosion but not bulk erosion way. However, different scaffolds showed different shrinkage and degradation ratios, and PLCL50/PLLA50 scaffold resulted in a significant shrinkage, while PLCL90/PLLA10 scaffold showed the better structural stability. Therefore, PLLA at blending different ratio had different effects on the in vivo performance of 3D-printed PLCL/PLLA scaffolds. Particularly, PLCL/PLLA scaffolds blending with low ratio of PLLA, such as PLCL90/PLLA10 scaffold showed better application potential in tissue engineering. Our findings provide a new insight on the rational design, constrcution and application of the 3D-printed PLCL/PLLA scaffolds.

Regulation of RDN on Th1/ILC1 cell imbalance in HFMD patients caused by EV71 infection.

Enterovirus 71 (EV71) infection is more likely to cause hand, foot and mouth disease (HFMD) in children, which can lead to neurogenic complications and higher mortality. As a commonly used clinical medicine, Reduning injection (RDN) helps to shorten the symptoms of patients with HFMD and facilitate the early recovery of children. However, the regulatory mechanism of RDN on the HFMD immune system disorder caused by EV71 remains to be discussed. This study collected detailed treatment data of 56 children with HFMD who entered the affiliated Children's Hospital of Nanjing Medical University during 2019. Retrospective analysis of clinical data showed that the symptoms of the RDN treatment group were improved compared with the untreated group. To explore its mechanism, the relevant detection indicators were detected by flow cytometry, enzyme-linked immunosorbent assay and real-time quantitative PCR. It was found that the number and function of innate immune (ILCs) and adaptive immunity (Th1, Th2 and secreted cytokines) were reduced, suggesting that RDN plays a role by regulating cellular immunity. The in vitro differentiation inhibition test further confirmed that RDN affected Th1 differentiation by inhibiting the expression of transcription factors on the basis of Th1 cell differentiation in vitro.

Kyphoplasty for occult and non-occult osteoporotic vertebral fractures: a retrospective study.

OBJECTIVE: To compare the safety and efficacy of kyphoplasty in the treatment of occult and non-occult osteoporotic vertebral compression fractures (OOVF). MATERIAL AND METHODS: From 2015 to 2017, 82 OOVF and 105 non-occult osteoporotic vertebral compression fractures (N-OOVF) were evaluated with the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and vertebral height preoperatively, immediately postoperatively, and one year postoperatively. Operative time, fluoroscopy time, and cement injection volume were recorded. RESULTS: Compared with the preoperative VAS and ODI scores, the scores of both groups were significantly improved after surgery. Preoperative ODI and VAS scores of the OOVF were lower than those of the N-OOVF. The operative time, fluoroscopy time, and bone cement injection volume of the OOVF were significantly lower than those of the N-OOVF. Vertebral height of the N-OOVF improved significantly after surgery. There were differences in cement leakage and adjacent vertebral fractures between the two groups. CONCLUSION: Compared with N-OOVF, OOVF are safer with kyphoplasty, and it is necessary to diagnose OOVF in a timely manner.

Cystine dimethyl ester cross-linked PEG-poly(urethane-urea)/nano-hydroxyapatite composited biomimetic scaffold for bone defect repair.

Polyurethane (PU) and polyurea (PUA) materials have shown significant potential for application in tissue repair. Herein, we design a glycerol ethoxylate (PEG)-based poly(urethane-urea) for bone tissue repair. The polymer precursor was prepared from the reaction of PEG and isophorone diisocyanate (IPDI). The cystine dimethyl ester was used as a cross-linker for the preparation of poly(urethane-urea) elastomers. The material was further strengthened by physical blending of nano-hydroxyapatite (nHA). The physical and biological properties of final material were evaluated by mechanical testing, scanning electron microscopy characterization, degradation tests, cell proliferation and cell differentiation assays. The obtained scaffolds showed good mechanical strength, excellent biocompatibility and osteogenic capability. All the evidences demonstrated that this type of materials has good prospects for bone tissue repair application.

Abnormalities of ILC1 in children with hand, foot and mouth disease during enterovirus 71 infection.

Children with HFMD due to EV71 infection are more likely to suffer from neurogenic complications, leading to higher morbidity and mortality. ILCs play crucial roles in the initiation of host immunity. However, the contribution of ILCs to the occurrence and development of HFMD due to EV71 infection remains to be explored. The results of our study showed that the levels of peripheral ILC1s and Th1 cells were increased in children with severe HFMD compared to healthy children, as were ILC1- and Th1-related cytokines and transcription factors. Furthermore, HFMD children with a higher frequency of circulating ILC1s exhibited a 2.9-fold greater risk of severity when HFMD was accompanied by VEM. Our study is the first to show that ILC1 abnormalities contribute to the pathogenesis of the severity of HFMD, in which ILC1s are aberrant increased and affect the cellular and humoral immunity. ILC1s could be used in the diagnosis of HFMD.

Biocompatibility of Bespoke 3D-Printed Titanium Alloy Plates for Treating Acetabular Fractures.

Treatment of acetabular fractures is challenging, not only because of its complicated anatomy but also because of the lack of fitting plates. Personalized titanium alloy plates can be fabricated by selective laser melting (SLM) but the biocompatibility of these three-dimensional printing (3D-printed) plates remains unknown. Plates were manufactured by SLM and their cytocompatibility was assessed by observing the metabolism of L929 fibroblasts incubated with culture medium extracts using a CCK-8 assay and their morphology by light microscopy. Allergenicity was tested using a guinea pig maximization test. In addition, acute systemic toxicity of the 3D-printed plates was determined by injecting extracts from the implants into the tail veins of mice. Finally, the histocompatibility of the plates was investigated by implanting them into the dorsal muscles of rabbits. The in vitro results suggested that cytocompatibility of the 3D-printed plates was similar to that of conventional plates. The in vivo data also demonstrated histocompatibility that was comparable between the two manufacturing techniques. In conclusion, both in vivo and in vitro experiments suggested favorable biocompatibility of 3D-printed titanium alloy plates, indicating that it is a promising option for treatment of acetabular fractures.

N-Acetyl cysteine (NAC)-mediated reinforcement of alpha-tricalcium phosphate/silk fibroin (α-TCP/SF) cement.

Calcium phosphate cements (CPCs) are popular bone filling materials and drug carriers. However poor mechanical properties and lack of osteoinduction restrict their clinical applications. Recent studies suggested the osteogenic properties of NAC. In our study, we incorporated NAC with α-TCP/SF. We found that the compressive strength of α-TCP/SF-NAC composites increased with increase in NAC concentration, possibly due to complex three-dimensional networks of SF induced by NAC, which was large and chemically heterogeneous and induced compact oriented growth of HA crystals. However the setting time increased slightly with the addition of NAC, due to the ruptured disulfide bonds in SF. The α-TCP/SF-NAC composites also showed decent biocompatibility in vitro. As a result, these composites hold great potential as bone filling materials for clinical applications, including minimally invasive surgeries.