Association between obesity and short- and medium-term mortality in critically ill patients with atrial fibrillation: a retrospective cohort study.

BACKGROUND: There has been controversy about how obesity affects the clinical prognosis for patients with atrial fibrillation (AF), and the relationship between obesity and outcomes in critically ill patients with AF remains unclear. The purpose of this study was to explore the association between obesity and short- and medium-term mortality in critically ill patients with AF. METHODS: The Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was used to conduct a retrospective cohort analysis on 9282 critically ill patients with AF. Patients were categorized into four groups based on their body mass index (BMI) values: underweight, normal-weight, overweight, and obese. The outcomes of this study were 30-day, 90-day, and 1-year all-cause mortality. Cox proportional-hazards models and restricted cubic spline analyses were performed to investigate the association between BMI and mortality. RESULTS: For 30-day mortality, after adjustment for all confounding factors, the hazard ratio (HR) with 95% confidence interval (CI) for the underweight, overweight, and obese categories were 1.58 (1.21, 2.07), 0.82 (0.72, 0.93), and 0.79 (0.68, 0.91), respectively, compared to the normal-weight category. Using multivariable-adjusted restricted cubic spline analysis, an "L-shaped" correlation was observed between BMI and 30-day mortality. For each 1 kg/m2 increase in BMI when BMI was less than 30 kg/m2, the risk of 30-day mortality decreased by 6.4% (HR, 95% CI: 0.936 [0.918, 0.954]; P < 0.001); however, this relationship was not present when BMI was greater than or equal to 30 kg/m2. Similar results were observed for 90-day and 1-year mortality. CONCLUSIONS: There was a nonlinear relationship between BMI and all-cause mortality among critically ill patients with AF. All-cause mortality and the BMI were negatively correlated when the BMI was less than 30 kg/m2.

A composite scaffold of Wharton's jelly and chondroitin sulphate loaded with human umbilical cord mesenchymal stem cells repairs articular cartilage defects in rat knee.

To evaluate the performance of a composite scaffold of Wharton's jelly (WJ) and chondroitin sulfate (CS) and the effect of the composite scaffold loaded with human umbilical cord mesenchymal stem cells (hUCMSCs) in repairing articular cartilage defects, two experiments were carried out. The in vitro experiments involved identification of the hUCMSCs, construction of the biomimetic composite scaffolds by the physical and chemical crosslinking of WJ and CS, and testing of the biomechanical properties of both the composite scaffold and the WJ scaffold. In the in vivo experiments, composite scaffolds loaded with hUCMSCs and WJ scaffolds loaded with hUCMSCs were applied to repair articular cartilage defects in the rat knee. Moreover, their repair effects were evaluated by the unaided eye, histological observations, and the immunogenicity of scaffolds and hUCMSCs. We found that in vitro, the Young's modulus of the composite scaffold (WJ-CS) was higher than that of the WJ scaffold. In vivo, the composite scaffold loaded with hUCMSCs repaired rat cartilage defects better than did the WJ scaffold loaded with hUCMSCs. Both the scaffold and hUCMSCs showed low immunogenicity. These results demonstrate that the in vitro construction of a human-derived WJ-CS composite scaffold enhances the biomechanical properties of WJ and that the repair of knee cartilage defects in rats is better with the composite scaffold than with the single WJ scaffold if the scaffold is loaded with hUCMSCs.

Storage solution containing hydrogen improves the preservation effect of osteochondral allograft.

As an ideal antioxidant and anti-apoptotic substance, hydrogen (H2) has protective effects on many isolated organs, such as the heart, lung and kidney. In this study, we explore whether H2 improves the preservation effect of osteochondral allograft by adding it to Dulbecco's Modified Eagle Medium (DMEM) solution during the tissue culture stage. The osteochondral allograft apparatus was used to harvest 60 pieces of cylindrical allografts (l = 10 mm, d = 6 mm) cartilage in the lateral loading area of the femoral condyle from the pig knee joint in the aseptic condition, and the grafts were randomly divided into 4 groups: Control group (DMEM solution without hydrogen); H-1 group (DMEM solution with hydrogen concentration of 0.2 mmol/L); H-2 group (DMEM solution with hydrogen concentration of 0.4 mmol/L); and H-3 group (DMEM solution with hydrogen concentration of 0.8 mmol/L). The chondrocyte viability, histological changes (hematoxylin and eosin staining, Safranine O staining, and collagen type II immunohistochemistry staining) and biomechanical properties (Young's modulus) of the osteochondral allograft were investigated after 28 days' storage. The chondrocyte viability and proteoglycan and collagen type II contents in the H-3 and H-2 groups were higher than that in the Control and H-1 groups, and the H-3 group had the highest values. However, significant differences were not observed between the four groups based on Young's modulus. Hydrogen as an additive to the DMEM solution improved the preservation effect of osteochondral allograft. The preservation effect of hydrogen occurred in a concentration-dependent manner.

Tissue-derived scaffolds and cells for articular cartilage tissue engineering: characteristics, applications and progress.

There are many factors to consider in the field of tissue engineering. For articular cartilage repair, this includes seed cells, scaffolds and chondrotrophic hormones. This review primarily focuses on the seed cells and scaffolds. Extracellular matrix proteins provide a natural scaffold for cell attachment, proliferation and differentiation. The structure and composition of tissue-derived scaffolds and native tissue are almost identical. As such, tissue-derived scaffolds hold great promise for biomedical applications. However, autologous tissue-derived scaffolds also have many drawbacks for transplantation, as harvesting autografts is limited to available donor sites and requires secondary surgery, therefore imparting additional damage to the body. This review summarizes and analyzes various cell sources and tissue-derived scaffolds applied in orthopedic tissue engineering.

Impaired nuclear translocation of glucocorticoid receptors: novel findings from psoriatic epidermal keratinocytes.

Psoriasis is a chronic proliferative skin disease and is usually treated with topical glucocorticoids, which act through the glucocorticoid receptor (GR), a component of the physiological systems essential for immune responses, differentiation, and homeostasis. To investigate the possible role of GR in the pathogenesis of psoriasis, normal and psoriatic lesional skin were recruited. Firstly, the immunolocalization of GR in the skin and cultured epidermal keratinocytes were determined by immunofluorescence. In normal skin and cultured human epidermal keratinocytes, intracellular GR is localized in the nuclei, while in psoriatic skin and cultured keratinocytes, GR is in the cytoplasm. Next, we investigated possible factors associated with the cytoplasmic distribution. We found that VEGF and IFN-γ led to impaired nuclear translocation of GR through p53 and microtubule-inhibitor, vincristine, and inhibited nuclear uptake of GR in normal keratinocytes. In addition to dexamethasone, interleukin (IL)-13 was also able to transfer GR into nuclei of psoriatic keratinocytes. Furthermore, discontinuation of dexamethasone induced cytoplasmic retention of GR in normal keratinocytes. In contrast, energy depletion of normal epidermal keratinocytes did not change the nuclear distribution of GR. To confirm our findings in vivo, an imiquimod-induced psoriasis-like skin mouse model was included. IL-13 ameliorated (but vincristine exacerbated) the skin lesions on the mouse. Taken together, our findings define that impaired nuclear translocation of GR is associated with VEGF, IFN-γ, p53, and microtubule. Therapeutic strategies designed to accumulate GR in the nucleus, such as IL-13, may be beneficial for the therapy of psoriasis.

Tendon extracellular-matrix-derived tissue engineering micro-tissue for Achilles tendon injury regeneration in rats.

BACKGROUND: Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles tendon in tissue engineering. METHODS: A tissue-engineered tendon micro-tissue was prepared using rat tail tendon extracellular matrix (TECM) combined with rat adipose stem cells (ADSCs) to repair Achilles tendon injuries. The TECM was prepared by repeated freezing and thawing. The in vitro characteristics of TECM and its effect on ADSCs proliferation were detected. This tissue-engineered tendon micro-tissue for Achilles tendon repair in vivo was evaluated based on general characteristics, gait analysis, ultrasound findings, histological analysis, and biomechanical testing. RESULTS: The results showed that the TECM scaffold had good biocompatibility for ADSCs. At 2 weeks post-surgery, collagen types I and III and tenomodulin expression were higher, and vascular endothelial growth factor expression was lower in the micro-tissue group than other groups. At 4 and 8 weeks post-surgery, the results of histological analysis and ultrasound findings showed that the repaired tendon tissue was smooth and lustrous, and was arranged regularly and evenly in the micro-tissue group. Gait analysis confirmed that better motor function recovery was noted in micro-tissue group than other groups. In addition, the mechanical properties of the repaired tendon tissue in micro-tissue group were better than other groups. CONCLUSION: Tissue-engineered tendon micro-tissue fabricated by TECM and ADSCs has good biocompatibility and can promote structural and functional repair of tendon in vivo. This composite biomaterial has broad application prospects in tissue engineering.

Hemoglobin-to-Red Cell Distribution Width Ratio is Associated with All-Cause Mortality in Critically Ill Patients with Traumatic Brain Injury.

BACKGROUND: Hemoglobin-to-red cell distribution width ratio (HRR) has shown good prognostic value in various cancers. However, the relationship between HRR and outcomes in critically ill patients with traumatic brain injury (TBI) remains unclear. This study aimed to investigate the association between HRR and mortality among critically ill patients with TBI. METHODS: The Medical Information Mart for Intensive Care-IV (MIMIC-IV) database was utilized to conduct this retrospective cohort study. TBI patients were divided into four quartiles according to their HRR values. The primary outcome was 30-day mortality, whereas the secondary outcomes were 60-day and 120-day mortality. Univariable and multivariable Cox proportional risk models were performed to evaluate the hazard ratio (HR) and 95% confidence interval (CI) for the relationship between HRR and mortality. Receiver operating characteristic (ROC) curves were conducted to assess the prognostic value of HRR. RESULTS: For 30-day mortality, after adjustment for all potential covariates, the relationship remained significant with HRR treated as a continuous variable (HR, 95% CI: 0.87 [0.81, 0.92]; p < 0.001). In the fully adjusted model, the HR with 95% CI for the second, third, and fourth quartile groups were 0.67 (0.5, 0.9), 0.65 (0.46, 0.94), and 0.5 (0.32, 0.79), respectively, compared to the first quartile group. A similar relationship was also observed for 60-day mortality and 120-day mortality. HRR had a better predictive value than hemoglobin and red cell distribution width (RDW). CONCLUSIONS: A lower level of HRR is significantly associated with higher all-cause mortality among critically ill patients with TBI.

Breeding of High Daptomycin-Producing Strain by Streptomycin Resistance Superposition.

Daptomycin is a cyclolipopeptide antibiotic produced by Streptomyces roseosporus. It is widely used to treat drug-resistant bacterial infections; however, daptomycin yield in wild strains is very low. To improve the daptomycin production by the strain BNCC 342432, a modified method of ribosome engineering with superposition of streptomycin resistance was adopted in this study. The highest-yield mutant strain SR-2620 was obtained by increasing streptomycin resistance of BNCC 342432, and achieved daptomycin production of 38.5 mg/l in shake-flask fermentation, 1.79-fold higher than the parent strain and its heredity stability was stable. The morphological characteristics of the two strains were significantly different, and the 440th base G of the rpsL gene in the mutant strain was deleted, which resulted in a frameshift mutation. Our results demonstrate that gradually increasing strain resistance to streptomycin was an effective breeding method to improve daptomycin yield in S. roseosporus.

SiC/MoSi2-SiC-Si Oxidation Protective Coatings for HTR Graphite Spheres with Residual Si Optimized.

SiC/MoSi2-SiC-Si coatings for nuclear graphite spheres with different Si-Mo ratios were prepared through two-step pack cementation. XRD, SEM and EDS techniques were used to analyze the composition and microstructure of the coatings. The oxidation resistance performance of the composites at 1773 K, in static air, was investigated. The results showed that the SiC-MoSi2-Si coating could be divided into a denser inner layer and a loose outer layer, as free Si would infiltrate into the inner micropores of the coating under capillary force. When the Si/Mo ratio of the second pack cementation was 7:1, the thickness of the denser inner layer basically reached the maximum and exhibited excellent oxidation resistance ability, with a weight gain of 0.19% after 200 h oxidation. The performance improvement was analyzed as a result of the addition of SiC and C powder in the pack cementation process, effectively increasing the phase interfaces to relax the thermal stress in the coating. With different Si-Mo ratios, the content of residual Si and the formation rate of SiO2 glass layer on the coating surface were also different, thus affecting the anti-oxidation performance. The main reactions occurring at different stages of the oxidation curve were also discussed.

Diversity of the genus Sugiyamaella and description of two new species from rotting wood in China.

Species of the genus Sugiyamaella (Trichomonascaceae, Saccharomycetales), found in rotting wood in China, were investigated using morphology and the molecular phylogeny of a combined ITS and nrLSU dataset. Nine taxa were collected in China: two were new species (viz. Sugiyamaella chuxiong sp. nov. and S. yunanensis sp. nov.) and seven were known species, S. americana, S. ayubii, S. novakii, S. paludigena, S. valenteae, S. valdiviana and S. xiaguanensis. The two new species are illustrated and their morphology and phylogenetic relationships with other Sugiyamaella species are discussed. Our results indicate a potentially great diversity of Sugiyamaella spp. inhabiting rotting wood in China just waiting to be discovered.

Mrakia panshiensis sp. nov. a new member of the Cystofilobasidiales from soil in China, and description of the teleomorphic-stage of M. arctica.

In a study on the fungal diversity in Northeast China, twelve yeast isolates were obtained from soils collected in three provinces, Helongjiang, Jilin and Liaoning. Morphological assessment and phylogenetic analyses of the nuc rDNA internal transcribed spacer (ITS) region and the D1/D2 domains of the nuc 28S rDNA (nuc 28S) gene of the 12 cultures placed them in the genus Mrakia, namely Mrakia aquatica, Mrakia arctica, Mrakia frigida, Mrakia gelida and Mrakia robertii. A total of three isolates represented a hitherto undescribed species, which is described here as M. panshiensis sp. nov. (MB 834813). The species M. panshiensis sp. nov. shares several morphological characters with M. niccombsii, M. aquatica, M. fibulata and M. hoshinonis. These species can be distinguished based on physiological traits and pairwise rDNA sequence similarities. The study also describes for the first time the formation of teliospores by previously described M. arctica.

Effects of Rolling-Sliding Mechanical Stimulation on Cartilage Preserved In Vitro.

INTRODUCTION: Mechanical stimulation is important for maintaining cartilage function. We used a loading device to exert rolling-sliding mechanical stimulation on cartilage preserved in vitro to investigate cartilage viability and the involved mechanisms. METHODS: Osteochondral grafts from pig knees were randomly classified into loading and control groups. The loading group cartilage was subjected to cycles of mechanical stimulation with specified frequency/time/pressure combinations every 3 days; Then the DMEM was refreshed, and the cartilage was preserved in vitro. The control group cartilage was preserved in DMEM throughout the process and was changed every 3 days. On days 14 and 28, the chondrocyte survival rate, histology, and Young's modulus of the cartilage were measured. Western blots were performed after 2 h of loading to evaluate the protein expression. RESULTS: The loading group showed a significantly higher chondrocyte survival rate, proteoglycan and type II collagen content, and Young's modulus than did the control group on day 14, but no statistically significant differences were found on day 28. After two hours of the loading, the phosphorylation levels of MEK and ERK1/2 increased, and the expression of caspase-3, cleaved caspase-3 and bax decreased. CONCLUSION: These results suggest that periodic rolling-sliding mechanical stimulation can increase cartilage vitality in 2 weeks; a possible mechanism is that mechanical stimulation activates the MEK/ERK signalling pathway, thus inhibiting apoptotic protein expression. This loading preservation scheme could be used by cartilage tissue banks to improve cartilage preservation in vitro and enhance the quality of cartilage repair.

Applications of stem cell-derived exosomes in tissue engineering and neurological diseases.

Exosomes are extracellular vesicles with diameters of 30-100 nm that are key for intercellular communication. Almost all types of cell, including dendritic cells, T cells, mast cells, epithelial cells, neuronal cells, adipocytes, mesenchymal stem cells, and platelets, can release exosomes. Exosomes are present in human body fluids, such as urine, amniotic fluid, malignant ascites, synovial fluid, breast milk, cerebrospinal fluid, semen, saliva, and blood. Exosomes have biological functions in immune response, antigen presentation, intercellular communication, and RNA and protein transfer. This review provides a brief overview of the origin, morphological characteristics, enrichment and identification methods, biological functions, and applications in tissue engineering and neurological diseases of exosomes.

Interleukin-17A and -17F Gene Polymorphisms in Chinese Population with Chronic Immune Thrombocytopenia.

BACKGROUND: A case-control study was conducted to evaluate the influence of interleukin (IL)-17A and -17F gene polymorphisms on the risk of primary chronic immune thrombocytopenia (ITP). METHODS: The study included 146 Chinese chronic ITP patients and 137 healthy controls. IL-17A G197A and IL-17F A7488G polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant difference in frequencies of IL-17A G197A genotypes and alleles was found between ITP patients and healthy controls, whereas frequencies of IL-17F A7488G allele A were significantly higher in ITP patients than that in healthy controls (31.85% vs. 18.98%; P<0.01). More specifically, patients with ITP had significantly higher frequencies of the IL-17F A7488G AA and AG genotypes compared with healthy controls (AA: 17.12% vs. 9.49%, P=0.02; AG: 29.46% vs. 18.98%, P=0.02). Logistic regression analysis revealed that AA and AG genotypes of IL-17F A7488G were associated with increased risk of ITP (AA: odds ratio (OR)=2.33, 95% CI 1.11-4.89; AG: OR=2.03, 95% CI 1.14-3.61). CONCLUSIONS: Our results suggest that SNPs in IL-17F A7488G but not IL-17A are associated with the development of chronic ITP in China.