Scarless Healing of Injured Vocal Folds Using an Injectable Hyaluronic Acid-Waterborne Polyurethane Hybrid Hydrogel to Tune Inflammation and Collagen Deposition.

Vocal fold (VF) scarring results from injury to the unique layered structure and is one of the main reasons for long-lasting dysphonia. A minimally invasive procedure with injectable hydrogels is a promising method for therapy. However, current surgical techniques or standard injectable fillers do not yield satisfactory outcomes. In this work, an injectable hybrid hydrogel consisting of oxide hyaluronic acid and hydrazide-modified waterborne polyurethane emulsion was injected precisely into the injury site and cross-linked in situ by a dynamic hydrazone bond. The prepared hydrogel displays excellent injectability and self-healing ability, showing favorable biocompatibility and biodegradability to facilitate endogenous newborn cell migration and growth for tissue regeneration. With the aim of evaluating the antifibrosis and regeneration capacity of the hybrid hydrogel in the VF scarring model, the morphology and vibration characteristics of VFs, inflammatory response, and healing status were collected. The hybrid hydrogel can decrease the inflammation and increase the ratio of collagen III/collagen I to heal damaged scar-free tissue. Fascinatingly, the mucosal wave oscillations of healing VF by injecting the hybrid hydrogel were vibrated like the normal VF, achieving functional restoration. This work highlights the utility of hybrid hydrogels consisting of synthetic biodegradable waterborne polyurethane emulsions and natural hyaluronic acid as promising biomaterials for scarless healing of damaged VFs.

Identification of a novel tumour microenvironment-based prognostic biomarker in skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is one of the most destructive skin malignancies and has attracted worldwide attention. However, there is a lack of prognostic biomarkers, especially tumour microenvironment (TME)-based prognostic biomarkers. Therefore, there is an urgent need to investigate the TME in SKCM, as well as to identify efficient biomarkers for the diagnosis and treatment of SKCM patients. A comprehensive analysis was performed using SKCM samples from The Cancer Genome Atlas and normal samples from Genotype-Tissue Expression. TME scores were calculated using the ESTIMATE algorithm, and differential TME scores and differentially expressed prognostic genes were successively identified. We further identified more reliable prognostic genes via least absolute shrinkage and selection operator regression analysis and constructed a prognostic prediction model to predict overall survival. Receiver operating characteristic analysis was used to evaluate the diagnostic efficacy, and Cox regression analysis was applied to explore the relationship with clinicopathological characteristics. Finally, we identified a novel prognostic biomarker and conducted a functional enrichment analysis. After considering ESTIMATEScore and tumour purity as differential TME scores, we identified 34 differentially expressed prognostic genes. Using least absolute shrinkage and selection operator regression, we identified seven potential prognostic biomarkers (SLC13A5, RBM24, IGHV3OR16-15, PRSS35, SLC7A10, IGHV1-69D and IGHV2-26). Combined with receiver operating characteristic and regression analyses, we determined PRSS35 as a novel TME-based prognostic biomarker in SKCM, and functional analysis enriched immune-related cells, functions and signalling pathways. Our study indicated that PRSS35 could act as a potential prognostic biomarker in SKCM by investigating the TME, so as to provide new ideas and insights for the clinical diagnosis and treatment of SKCM.

OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. However, due to the lack of reliable prognostic biomarkers for PTC, overtreatment has been on the rise. Therefore, our research aims to identify new and promising prognostic biomarkers and provide fresh perspectives for clinical decision making. METHODS: The RNA-seq data and clinical data of PTC samples were obtained from The Cancer Genome Atlas data portal. GSE64912 and GSE83520 datasets were downloaded through the GEOquery R package. The difference in the expression of oxoglutarate dehydrogenase like (OGDHL) between PTC and normal tissues was explored by the Wilcoxon test. Kaplan-Meier (KM) and Cox regression analyses were used to further explore the prognostic value of OGDHL. The tumor microenvironments of PTC patients were explored based on ssGSEA and Tumor Immune Estimation Resource online database. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological processes associated with OGDHL. RESULTS: The expression level of OGDHL in PTC was significantly altered compared to that in normal tissues (p < 0.05). Various biological processes associated with OGDHL were also explored through GSEA. KM analysis suggested that the low-OGDHL group had a better overall survival [OS, p = 3.49e-03, hazard ratio (HR) = 4.567]. The receiver operating characteristic curve also indicated the favorable prognostic potential of OGDHL. Moreover, OGDHL was proved to be an independent prognostic indicator in Cox analysis (p = 1.33e-02, HR = 0.152). In the analysis of the tumor microenvironment, the low-OGDHL group showed a lower immune score and stromal score, while tumor purity was higher. The expression of OGDHL was also closely correlated with the infiltration of immune cells. CONCLUSION: Our study elucidated the influence of OGDHL on the prognosis of PTC and demonstrated its potential as a novel biomarker, which would provide new insights into the prognosis monitoring and clinical decision making in PTC patients.

Experimental investigation on rockburst behavior of the rock-coal-bolt specimen under different stress conditions.

Coal and rock burst are one of the main dynamic disasters that affect coal mine production. In this paper, the burst structural model of the rock-coal-bolt (RCB) system and the burst tendency criterion are established on the background of deep thin coal seam mining. Uniaxial and triaxial mechanical tests under different stress states are carried out on RCB specimens with different angles. Combined with thermal imaging, the mechanical behavior of the inclined RCB specimen under uniaxial loading is discussed. The results show that the burst tendency of the RCB specimen increases with the angle. The stress-strain curves of some uniaxial and triaxial test specimens show two or more peaks, and the thermal imaging evolutionary process shows that the cracks of the coal and rock develop from shear to tension shear cracks. There is a further development of fracture and energy accumulation between the first and second peaks in the stress-strain curve of the specimen. Therefore, the failure degree of the second peak of the specimen may be stronger than that of the first peak. Additionally, the established stiffness coefficient and burst energy index can better describe the burst tendency of the RCB specimen under different stress states. The results show that the burst tendency of the RCB specimen under the triaxial test is much higher than that of the uniaxial test. In other words, it also explains that the essence of the burst failure of the surrounding rock in the roadway is the initial instability induced by the inside surrounding rock in the roadway. Moreover, the burst tendency is the largest when the rock and coal combination angle is 15°, and the burst damage range may also be increased by the failure of internal coal and rock mass.

[Ulna osteotomy and joint capsule release and tight for old Monteggia's fracture in children].

OBJECTIVE: To explore the experience and effect of surgical treatment in old Monteggia fracture in children. METHODS: From January 2013 to December 2017, 32 cases of old Monteggia's fracture were treated including 18 males and 14 females with an average age of(5.3±1.2) years old ranging from 2 to 9 years old. No symptoms of radial nerve injury were found. The preoperative symptoms of the patients were the pain and deformity of the elbow joint, the flexion and extension and the limited forearm rotation. The X-ray showed the union of the ulna or the "arched sign", the dislocation of the radial head or the subluxation of the head. The posterior incision of the ulna ridge was performed in the operation, and the long oblique osteotomy was performed at the most obvious point of the ulna angle deformity. Then the Boyd incision was used to expose the humeral and radial joint and the upper ulnar radial joint. The scar tissue in the joint was cleaned and the radial head was repositioned. On the premise of maintaining the stability of the elbow joint, the ulna osteotomy was treated with plate and screw internal fixation. RESULTS: All 32 cases were followed up for 12 to 24 months with an average of 14.8 months, of which 1 case had incision infection. There were no pain symptoms of elbow and wrist in 32 patients after operation, 29 patients with elbow joint flexion and extension (130±5)°/0°, forearm pronation and supination 90°/(85±5)°; 2 patients with elbow flexion and extension(119°/8°, 121°/7°), forearm pronation and supination (90°/75°, 85°/60°); 1 patient with elbow flexion and extension 90°/10°, forearm pronation and supination 80°/60°. According to Mackay criteria, the result was excellent in 29 cases, good in 2 cases, medium in 1 case. CONCLUSIONS: Ulna osteotomy, elbow posterior capsular release, anterior capsule contraction is a effective method in the treatment of old Monteggia's fracture in children.

Microstructure and Tensile Properties of AZ61 Alloy Sheets Processed by High-Ratio Extrusion with Subsequent Direct Aging Treatment.

A high extrusion ratio of 166:1 was applied to commercial AZ61 alloy in one step with an extrusion speed of 2.1 m·min-1. The effects of DA (direct aging) treatment on the microstructure and tensile properties of extruded alloy were investigated. The extruded alloy exhibits fine DRXed grains and the average grain size is ~11 µm. After DA treatment at 170 °C, the tensile strength and 0.2% offset yield strength is enhanced from 314 to 336 MPa and from 169 to 191 MPa respectively, sacrificing elongation from 26.5% to 23.3%. The grain size and texture distribution of extruded AZ61 scarcely evolve during the post aging treatment. However, the enhanced strength in peak-aged alloy is mainly caused by the high-density elliptical Mg17Al12 precipitates distributing uniformly along the grain boundaries or within the grains, by precipitation and dispersion hardening. Furthermore, the nano-sized precipitates effectively inhibit grains from coarsening by triggering pinning effects along the grain boundaries at elevated temperature. As a result, the peak-aged alloy exhibits a better superplasticity of 306.5% compared with that of 231.8% of extruded sample. This work provides a practical one-step method for mass-producing Mg alloy sheets with excellent tensile strength and ductility compared with those fabricated by conventional extrusion methods.

Isolation and determination of four potential antimicrobial components from Pseudomonas aeruginosa extracts.

Background:Pseudomonas aeruginosa can cause disease and also can be isolated from the skin of healthy people. Additionally, it exhibits certain antimicrobial effects against other microorganisms.Methods: We collected 60 strains of P. aeruginosa and screened their antimicrobial effects against Staphylococcus aureus (ATCC 25923) using the filter paper-disk method, the cross-streaking method and the co-culture method and then evaluated the antimicrobial activity of the chloroform-isolated S. aureus extracts against methicillin-resistant S. aureus (MRSA, Gram-positive cocci), vancomycin intermediate-resistant S. aureus (VISA, Gram-positive cocci), Corynebacterium spp. (CS, Gram-positive bacilli), Acinetobacter baumannii (AB, Gram-negative bacilli), Moraxella catarrhalis (MC, Gram-negative diplococcus), Candida albicans (CA, fungi), Candida tropicalis (CT, fungi), Candida glabrata (CG, fungi) and Candida parapsilosis (CP, fungi). Results: The PA06 and PA46 strains have strong antimicrobial effects. High-performance liquid chromatography (HPLC) analysis revealed that the major components of PA06 and PA46 that exhibit antimicrobial activity are functionally similar to phenazine-1-carboxylic acid (PCA) and pyocyanin. Preparative HPLC was performed to separate and isolate the 4 major potential antimicrobial components: PA06ER10, PA06ER16, PA06ER23 and PA06ER31. Further, the molecular masses of PA06ER10 (260.1), PA06ER16 (274.1), PA06ER23 (286.1) and PA06ER31 (318.2) were determined by electrospray ionization (ESI) mass spectrometry. Conclusion:P. aeruginosa can produce small molecules with potential antimicrobial activities against MRSA, VISA, CS, MC, CA, CT, CG and CP but not against AB.

GM-CSF alters dendritic cells in autoimmune diseases.

Autoimmune diseases arise from an inappropriate immune response against self components, including macromolecules, cells, tissues, organs etc. They are often triggered or accompanied by inflammation, during which the levels of granulocyte macrophage colony-stimulating factor (GM-CSF) are elevated. GM-CSF is an inflammatory cytokine that has profound impact on the differentiation of immune system cells of myeloid lineage, especially dendritic cells (DCs) that play critical roles in immune initiation and tolerance, and is involved in the pathogenesis of autoimmune diseases. Although GM-CSF was discovered decades ago, recent studies with some new findings have shed an interesting light on the old hematopoietic growth factor. In the inflammatory autoimmune diseases, GM-CSF redirects the normal developmental pathway of DCs, conditions their antigen presentation capacities and endows them with unique cytokine signatures to affect autoimmune responses. Here we review the latest advances in the field, with the aim of demonstrating the effects of GM-CSF on DCs and their influences on autoimmune diseases. The summarized knowledge will help to design DC-based strategies for the treatment of autoimmune diseases.

MicroRNA-21 with therapeutic potential in autoimmune diseases.

INTRODUCTION: Small, non-coding, microRNAs (miRNAs) have emerged as key mediators of post-transcriptional gene silencing in both pathogenic and pathological aspects of disorders. Recently, miR-21 was identified to regulate a variety of immune cells. Functional analysis indicated that miR-21 played a crucial role in a plethora of biological functions and diseases including development, cancer and inflammation, especially correlated with the pathogenesis of autoimmune diseases. AREAS COVERED: This review provides a comprehensive view on the association of miR-21 and autoimmune disorders, such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, systemic sclerosis and psoriasis. Especially the mechanisms of miR-21 perform in these diseases, and the mechanisms that regulate miR-21. EXPERT OPINION: Though the exact roles of miR-21 in autoimmune diseases have not been fully elucidated, targeting miR-21 may serve as a promising therapy strategy.

[Effects of low-dose aspirin on primary prevention of cardiovascular events: a systematic review].

OBJECTIVE: To evaluate the effect and safety of low-dose aspirin for primary prevention of cardiovascular events. METHODS: We searched for randomized controlled trials (RCT) in the following electronic databases: MEDLINE, EMbase, the Cochrane Library (Issue 3, 2008), CBM, CNKI. Quality assessment and data extraction were conducted by two reviewers independently. All data were analyzed using Review Manager 4.2. RESULTS: Six studies (TPT, HOT, PPP, WHS, POPADAD, J-PAD) involving a total of 72,466 participants met the inclusion criteria. Meta-analysis results showed that: (1) Compared with placebo, the incidences of total cardiovascular events (RR = 0.85, 95% CI: 0.80-0.92), stroke (RR = 0.87, 95% CI: 0.77-0.98), nonfatal stroke (RR = 0.81, 95% CI: 0.70-0.95) and transient ischemic attack (RR = 0.76, 95% CI: 0.64-0.90) were significantly lower in low-dose aspirin group than those in placebo control group (all P < 0.05). (2) Nonfatal myocardial infarction (RR = 0.89, 95% CI: 0.77-1.02), death from cardiovascular causes (RR = 0.98, 95% CI: 0.86-1.13) and death from any cause (RR = 0.95, 95% CI: 0.88-1.02) were similar between the 2 groups (all P > 0.05). (3) The risk of coronary heart disease was reduced in low-dose aspirin group in the elderly (RR = 0.81, 95% CI: 0.70-0.94, P < 0.05). (4) The risk of bleeding was higher in low aspirin group compared to placebo group (RR = 1.15, 95% CI: 1.12-1.18, P < 0.01). CONCLUSIONS: Low-dose aspirin use could reduce the incidences of total cardiovascular events, stroke, nonfatal stroke and transient ischemic attack but increase the risk of bleeding, the incidence of nonfatal myocardial infarction, death from cardiovascular causes and death from any cause was not affected by low-dose aspirin use. Low-dose aspirin use was also significantly reduced the risk of coronary heart disease in the elderly.