Tumour necrosis factor α regulates the miR-27a-3p-Sfrp1 axis in a mouse model of osteoporosis.

Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF-α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF-α treatment and miR-27a-3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF-α and decreased level of bone miR-27a-3p, and in vitro TNF-α treatment inhibited miR-27a-3p expression in BMSCs. In addition, miR-27a-3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red-S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled-related protein 1 (Sfrp1) as a downstream target of miR-27a-3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF-α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR-27a-3p on the osteogenic differentiation of BMSCs. Furthermore, the miR-27a-3p-Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a-ß-catenin signalling. In summary, this study revealed that TNF-α regulated a novel miR-27a-3p-Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.

Ultraviolet Light Responsive N-Nitroso Polymers for Antibacterial Nitric Oxide Delivery.

This study investigates the incorporation of active secondary amine moieties into the polymer backbone by co-polymerizing 2,4,6-tris(chloromethyl)-mesitylene with three diamines, namely 1,4-diaminobutane, m-phenylenediamine, and p-phenylenediamine. This process results in the stabilization of the amine moieties and the subsequently introduced nitroso groups. Charging bioactive nitric oxide (NO) into the polymers is accomplished by converting the amine moieties into N-nitroso groups. The ability of the polymers to store and release NO depends on their structures, particularly the amount of incorporated active secondary amines. With grafting photosensitive N-nitroso groups into the polymers, the derived NO@polymers exhibit photoresponsivity. NO release is completely regulated by adjusting UV light irradiation. These resulting polymeric NO donors demonstrate remarkable bactericidal and bacteriostatic activity, effectively eradicating E. coli bacteria and inhibiting their growth. The findings from this study hold promising implications for combining NO delivery with phototherapy in various medical applications.

Netrin-1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle-induced osteoclastogenesis.

BACKGROUND: Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this study was to investigate the molecular mechanism of osteoclast formation and dissolution induced by wear particles and the potential roles of Netrin-1, the ERK1/2 pathway and autophagy activation in this process. METHODS: The messenger RNA levels in cells and tissues were detected with real-time quantitative PCR. The western blotting was used to detect the expression of proteins. A CCK-8 kit was used to detect the viability of RAW 264.7 cells. Moreover, an air pouch model of bone resorption was established. Immunohistochemistry was used to detect the expression of TRAP and Netrin-1 in rat bone tissue. Cell culture supernatants were collected in the rat air pouch model of bone resorption, and the levels of RANKL and OPG were detected with enzyme-linked immunosorbent assay. The protein levels of TRAP and Netrin-1 in bone tissue were examined by immunohistochemistry. RESULTS: Titanium wear particles induced osteoclast formation and autophagy activation. Moreover, blocking autophagy suppressed the osteoclastogenesis after exposure to wear particles in vitro. The activation of the ERK1/2 pathway and the overexpression of Netrin-1 were both found to play important roles in osteoclastogenesis mediated by autophagy. Moreover, 3-MA effectively decreased the secretion of proinflammatory cytokines mediated by wear particles. CONCLUSION: Blockade of autophagy inhibits the osteoclastogenesis and inflammation induced by wear particles, thus potentially providing novel treatment strategies for abnormal osteoclastogenesis and aseptic prosthesis loosening induced by wear particles.

Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD.

BACKGROUND: Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity. OBJECTIVES: We sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16-induced COPD exacerbations and its relationship to disease severity. METHODS: Bronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests. RESULTS: RV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function. CONCLUSIONS: Experimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations.

SUMO-modified bone marrow mesenchymal stem cells promoted the repair of articular cartilage in rats.

Articular cartilage damage can lead to joint deformity, pain, and severe dysfunction. However, due to the lack of blood vessels and nerves in articular cartilage, the self-healing capacity of damaged cartilage is limited. In this study, we overexpressed small ubiquitin-like modifier (SUMO)1, SUMO2/3, and SUMO1/2/3 in bone marrow mesenchymal stem cells (BMSCs). Then, these cells were inoculated on surfaces of different hardness, and their differentiation into chondrocytes, hypoxic tolerance ability, and inflammatory response was detected. Finally, BMSCs were transplanted into the injured knee joint cavity of the rats, and the repair was evaluated. We found that BMSCs overexpressing SUMO1 were more likely to differentiate into articular cartilage along with the hardness of the surface, while BMSCs overexpressing SUMO2/3 could reduce inflammation response and improve the damaged cartilage microenvironment. In the rat model, BMSCs overexpressing SUMO1/2/3 transplanted on injured articular cartilage surface showed better survival, less inflammatory response, and improved tissue repair capability. In conclusion, BMSCs overexpressing SUMO are more tolerant to hypoxia conditions, and have stronger repair ability for damaged chondrocytes in vitro and for articular cartilage injury model in rats, and are excellent seed cells for repairing articular cartilage.

Responses of Two Coastal Algae (Skeletonema costatum and Chlorella vulgaris) to Changes in Light and Iron Levels1.

Iron (Fe) is essential for phytoplankton growth and photosynthesis, and is proposed to be an important factor regulating algal blooms under replete major nutrients in coastal environments. Here, Skeletonema costatum, a typical red-tide diatom species, and Chlorella vulgaris, a widely distributed Chlorella, were chosen to examine carbon fixation and Fe uptake by coastal algae under dark and light conditions with different Fe levels. The cellular carbon fixation and intracellular Fe uptake were measured via 14 C and 55 Fe tracer assay, respectively. Cell growth, cell size, and chlorophyll-α concentration were measured to investigate the algal physiological variation in different treatments. Our results showed that cellular Fe uptake proceeds under dark and the uptake rates were comparable to or even higher than those in the light for both algal species. Fe requirements per unit carbon fixation were also higher in the dark resulting in higher Fe: C ratios. During the experimental period, high Fe addition significantly enhanced cellular carbon fixation and Fe uptake. Compared to C. vulgaris, S. costatum was the common dominant bloom species because of its lower Fe demand but higher Fe uptake rate. This study provides some of the first measurements of Fe quotas in coastal phytoplankton cells, and implies that light and Fe concentrations may influence the phytoplankton community succession when blooms occur in coastal ecosystems.

Honokiol improved chondrogenesis and suppressed inflammation in human umbilical cord derived mesenchymal stem cells via blocking nuclear factor-κB pathway.

BACKGROUND: Cartilage degradation is the significant pathological process in osteoarthritis (OA). Inflammatory cytokines, such as interleukin-1ß (IL-1ß), activate various downstream mediators contributing to OA pathology. Recently, stem cell-based cartilage repair emerges as a potential therapeutic strategy that being widely studied, whereas, the outcome is still far from clinical application. In this study, we focused on an anti-inflammatory agent, honokiol, which is isolated from an herb, investigated the potential effects on human umbilical cord derived mesenchymal stem cells (hUC-MSCs) in IL-1ß stimulation. METHODS: Second passage hUC-MSCs were cultured for multi-differentiation. Flow cytometry, qRT-PCR, von Kossa stain, alcian blue stain and oil red O stain were used for characterization and multi-differentiation determination. Honokiol (5, 10, 25, 50 µM) and IL-1ß (10 ng/ml) were applied in hUC-MSCs during chondrogenesis. Analysis was performed by MTT, cell apoptosis evaluation, ELISA assay, qRT-PCR and western blot. RESULTS: hUC-MSC was positive for CD73, CD90 and CD105, but lack of CD34 and CD45. Remarkable osteogenesis, chondrogenesis and adipogenesis were detected in hUC-MSCs. IL-1ß enhanced cell apoptosis and necrosis and activated the expression of caspase-3, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and matrix metalloproteinase (MMP)-1, -9, 13 in hUC-MSCs. Moreover, the expression of SRY-related high-mobility group box 9 (SOX-9), aggrecan and col2α1 was suppressed. Honokiol relieved these negative impacts induced by IL-1ß and suppressed Nuclear factor-κB (NF-κB) pathway by downregulating expression of p-IKKα/ß, p-IκBα and p-p65 in dose-dependent and time-dependent manner. CONCLUSIONS: Honokiol improved cell survival and chondrogenesis of hUC-MSCs and inhibited IL-1ß-induced inflammatory response, which suggested that combination of anti-inflammation and stem cell can be a novel strategy for better cartilage repair.

A potential nitrogen sink discovered in the oxygenated Chukchi Shelf waters of the Arctic.

The western Arctic Shelf has long been considered as an important sink of nitrogen because high primary productivity of the shelf water fuels active denitrification within the sediments, which has been recognized to account for all the nitrogen (N) removal of the Pacific water inflow. However, potentially high denitrifying activity was discovered within the oxygenated Chukchi Shelf water during our summer expedition. Based on 15N-isotope pairing incubations, we estimated denitrification rates ranging from 1.8 ± 0.4 to 75.9 ± 8.7 nmol N2 L-1 h-1. We find that the spatial pattern of denitrifying activity follows well with primary productivity, which supplies plentiful fresh organic matter, and there was a strong correlation between integrated denitrification and integrated primary productivity. Considering the active hydrodynamics over the Chukchi Shelf during summer, resuspension of benthic sediment coupled with particle-associated bacteria induces an active denitrification process in the oxic water column. We further extrapolate to the whole Chukchi Shelf and estimate an N removal flux from this cold Arctic shelf water to be 12.2 Tg-N year-1, which compensates for the difference between sediment cores incubation (~ 3 Tg-N year-1) and geochemical estimation based on N deficit relative to phosphorous (~ 16 Tg-N year-1). We infer that dynamic sediment resuspension combined with high biological productivity stimulates intensive denitrification in the water column, potentially creating a nitrogen sink over the shallow Arctic shelves that have previously been unrecognized.

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats.

BACKGROUND: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor x03B3;. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. METHODS: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. RESULTS: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARx03B3; and adipocyte protein 2 were downregulated. CONCLUSION: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

Morphological characteristics of cartilage-bone transitional structures in the human knee joint and CAD design of an osteochondral scaffold.

BACKGROUND: There is a lack of understanding of the morphological characteristics of the cartilage-bone interface. Materials that are currently being used in tissue engineering do not adequately support the regeneration of bone and cartilage tissues. The present study aimed to explore the morphological characteristics of cartilage-bone transitional structures in the human knee joint and to design a biomimetic osteochondral scaffold based on morphological data. METHODS: Histology, micro-computed tomography (micro-CT), and scanning electron microscopy (SEM) were used to investigate the microstructure of the cartilage-bone transitional structures. Morphological characteristics and their distribution were obtained and summarized into a biomimetic design. A three-dimensional model of a biomimetic osteochondral scaffold was CAD designed. A prototype of the resulting subchondral bone scaffold was constructed by stereolithography using resin. RESULTS: Micro-CT revealed that subchondral bone presented a gradually changing structure from the subchondral to spongy bone tissue. The subchondral bone plate was more compact with ~20 % porosity compared with ~60 % porosity for the spongy bone. Histology and SEM showed that cartilage was stabilized on the subchondral bone plate by conjunctions, imbedding, interlocking, and binding forces generated by collagen fibers. Some scattered defects allow blood vessel invasion and nutritional supply. CONCLUSIONS: The subchondral bone plate is not an intact plate between the cartilage and bone cavity, and some scattered defects exist that allow blood vessel invasion and nutritional supply. This characteristic was used to design an osteochondral scaffold. This could be used to construct an osteochondral complex that is similar to native bones.

Section of the anterior cruciate ligament in the rabbit as animal model for osteoarthritis progression.

PURPOSE: The purpose of this study was to determine whether instability of knee is a risk factor in the progression of osteoarthritis (OA). METHODS: Twenty-four mature New Zealand White rabbits were randomly divided into four groups. The control group received 0.3 ml saline in the first, fourth and seventh days in the right knee, while the other three groups received the same dosage 4 % papain and its activator 0.03 M L-cystein. The P3w group knees were harvested at three weeks after the last papain injection, the P6w group knees received a sham surgery at three weeks and were harvested at six weeks after the last papain injection, while the P+ACLT group knees received ACL transection at three weeks and were harvested at six weeks after the last papain injection. Cartilage degradation of femoral condyles and tibial plateaus were evaluated by X-rays, macroscopy, light microscopic and transmission electron microscopy (TEM). RESULTS: According to X-rays grade scale, macroscopic grade scale, light microscopic modified Mankin scale and TEM, in the P3w knees, cartilage degeneration of femoral condyles and tibial plateaus were significantly severe compared to those of the control group (P < 0.05), but the differences were not apparent in comparison with the P6w knees (P > 0.05). However, in P+ACLT knees, cartilage degeneration of femoral condyles and tibial plateaus appeared more severe in comparison with P6w knees, and the difference was significant (P < 0.05). CONCLUSIONS: Instability of knee plays a significant role in increasing the severity of cartilage degradation in rabbit knees and should be considered as a risk factor in OA knee progression. Our data may suggest that reconstruction of knee stability may prevent or delay the progression of OA.

Predictive potential of ABCB1, ABCC3, and GSTP1 gene polymorphisms on osteosarcoma survival after chemotherapy.

Genetic polymorphisms in drug metabolism and transport genes can influence the pharmacokinetics and pharmacodynamics of chemotherapy drugs. We investigated the role of genes involved in metabolic and transport pathways in response to chemotherapy and clinical outcome of osteosarcoma patients. The association between the eight polymorphisms with response to chemotherapy and clinical outcome of patients was carried out by unconditional logistic regression analysis and Cox proportional hazard models. Of 186 patients, 98 patients showed good response to chemotherapy, 64 died, and 97 showed progression at the end of the study. Patients carrying ABCB1 rs1128503 TT genotype and T allele were more likely to have a good response to chemotherapy. ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were associated with poor response to chemotherapy. In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying ABCB1 rs1128503 TT genotype and T allele were associated with lower risk of progression-free survival (PFS) and overall survival (OS). ABCC3 rs4148416 TT genotype and T allele and GSTP1 rs1695 GG genotype and G allele were correlated with high risk of PFS and OS. The ABCB1 TT and GSTP1 GG genotypes were significantly associated with a shorter OS. In conclusion, variants of ABCB1 rs128503, ABCC3 rs4148416, and GSTP1 rs1695 are associated with response to chemotherapy and PFS and OS of osteosarcoma patients; these gene polymorphisms could help in the design of individualized therapy.

Sappanone a alleviates osteoarthritis progression by inhibiting chondrocyte ferroptosis via activating the SIRT1/Nrf2 signaling pathway.

Osteoarthritis (OA) is a common degenerative joint disease that cause pain and disability in adults. Chondrocyte ferroptosis is found to be involved in OA progression. Sappanone A has been found as an anti-inflammatory and antioxidative agent in several diseases. This study aims to investigate the effects of sappanone A on OA progression and chondrocyte ferroptosis. IL-1ß-induced chondrocytes and destabilization of the medial meniscus (DMM)-induced rats were respectively used as the OA model in vitro and in vivo. The effects of sappanone A on inflammation, extracellular matrix (ECM) metabolism, and ferroptosis were determined. Our results showed that in IL-1ß-induced chondrocytes, sappanone A suppressed the production of NO, PGE2, TNF-α, IL-6, iNOS, and COX2. Sappanone A also inhibited the expression of MMP3, MMP13, and ADAMTS5, while increasing collagen II expression. Moreover, sappanone A alleviated cytotoxicity and decreased the levels of intracellular ROS, lipid ROS, MDA, and iron, while increasing GSH levels. Additionally, sappanone A increased the protein expression of SLC7A11 and GPX4. Administration of ferroptosis activator reversed the inhibitory effects of sappanone A on IL-1ß-induced inflammation and ECM degradation. More importantly, Sappanone A activated the Nrf2 signaling by targeting SIRT1. The inhibition of sappanone A on ferroptosis was greatly eliminated due to the addition of SIRT1 inhibitor. Furthermore, intra-articular injection of sappanone A mitigated cartilage destruction and ferroptosis in DMM-induced OA rats. In conclusion, sappanone A protects against inflammation and ECM degradation in OA via decreasing chondrocyte ferroptosis by activating the SIRT1/Nrf2 signaling. These findings deepen our understanding of chondrocyte ferroptosis in OA and highlight the therapeutic potential of sappanone A for OA.

PUD@HA/PEEK Scaffold Induces Subchondral Bone Regeneration to Repair Osteochondral Defect in Rabbits.

Osteochondral defects (OCDs) pose a significant challenge in clinical practice, and recent advancements in their repair indicate that satisfying subchondral bone repair may be critical for this. Herein, a series of hydroxyapatite/poly(ether ether ketone) (HA/PEEK) scaffolds were fabricated with varying mass percentages (0, 20, 30, and 40%) to induce subchondral bone regeneration. Subsequently, an optimal scaffold with 40% HA/PEEK was selected to establish osteochondral scaffolds with poly(ether urethane) urea-Danshensu (PUD) for repairing the OCD. The material characteristics of HA/PEEK and PUD were investigated using scanning electron microscopy, tensile, swelling, and fatigue tests, and cytological experiments. The effects of serial HA/PEEK scaffolds on subchondral bone repair were then assessed by using microcomputed tomography, hard tissue slicing, and histological staining. Furthermore, the optimal 40% HA/PEEK scaffold was used to develop osteochondral scaffolds with PUD to observe the effect on the OCD repair. HA/PEEK materials exhibited an even HA distribution in PEEK. However, when composited with HA, PEEK exhibited inferior mechanical strength. 40%HA/PEEK scaffolds showed an optimum effect on in vivo subchondral bone repair. Cartilage regeneration on 40%HA/PEEK scaffolds was pronounced. After PUD was introduced onto the HA/PEEK, the PUD@40%HA/PEEK scaffold produced the expected effect on the repair of the OCD in rabbits. Therefore, achieving satisfactory subchondral bone repair can benefit surficial cartilage repair. The PUD@40%HA/PEEK scaffold could induce subchondral bone regeneration to repair the OCD in rabbits and could provide a novel approach for the repair of the OCD in clinical practice.

Is cervical disc arthroplasty superior to fusion for treatment of symptomatic cervical disc disease? A meta-analysis.

BACKGROUND: As the current standard treatment for symptomatic cervical disc disease, anterior cervical decompression and fusion may result in progressive degeneration or disease of the adjacent segments. Cervical disc arthroplasty was theoretically designed to be an ideal substitute for fusion by preserving motion at the operative level and delaying adjacent level degeneration. However, it remains unclear whether arthroplasty achieves that aim. QUESTIONS/PURPOSES: We investigated whether cervical disc arthroplasty was associated with (1) better function (neck disability index, pain assessment, SF-36 mental and physical health surveys, neurologic status) than fusion, (2) a lower incidence of reoperation and major complications, and (3) a lower risk of subsequent adjacent segment degeneration. METHODS: We conducted a comprehensive search in MEDLINE(®), EMBASE, and Cochrane Central Register of Controlled Trials and identified 503 papers. Of these, we identified 13 reports from 10 randomized controlled trials involving 2227 patients. We performed a meta-analysis of functional scores, rates of reoperation, and major complications. The strength of evidence was evaluated by using GRADE profiler software. Of the 10 trials, six trials including five prospective multicenter FDA-regulated studies were sponsored by industry. The mean follow-ups of the 10 trials ranged from 1 to 5 years. RESULTS: Compared with anterior cervical decompression and fusion, cervical disc arthroplasty had better mean neck disability indexes (95% CI, -0.25 to -0.02), neurologic status (risk ratio [RR], 1.04; 95% CI, 1.00-1.08), with a reduced incidence of reoperation related to the index surgery (RR, 0.42; 95% CI, 0.22-0.79), and major surgical complications (RR, 0.45; 95% CI, 0.27-0.75) at a mean of 1 to 3 years. However, the operation rate at adjacent levels after two procedures was similar (95% CI, 0.31-1.27). The three studies with longer mean follow-ups of 4 to 5 years also showed similar superiority of all four parameters of cervical disc arthroplasty compared with fusion. CONCLUSIONS: For treating symptomatic cervical disc disease, cervical disc arthroplasty appears to provide better function, a lower incidence of reoperation related to index surgery at 1 to 5 years, and lower major complication rates compared with fusion. However, cervical disc arthroplasty did not reduce the reoperation rate attributable to adjacent segment degeneration than fusion. Further, it is unclear whether these differences in subsequent surgery including arthroplasty revisions will persist beyond 5 years.

Direct detection and identification of periprosthetic joint infection pathogens by metagenomic next-generation sequencing.

This study assessed the application of metagenomic next-generation sequencing in pathogen detection of periprosthetic joint infections. A total of 95 cases who previously had undergone hip and knee replacement undergoing revision from January 2018 to January 2021 were included in this study. Specimens of synovial fluid and deep-tissue were collected for culture and metagenomic next-generation sequencing, and patients were retrospectively categorized as infected or aseptic using the Musculoskeletal Infection Society criteria after revision surgery. The sensitivity, specificity, positive and negative predictive values were compared. A total of 36 cases had positive culture results and 59 cases had positive metagenomic next-generation sequencing results. Culture was positive in 34 infected cases (58.6%) and 2 aseptic cases (5.4%). Metagenomic next-generation sequencing was positive in 55 infected cases (94.8%) and 4 aseptic cases (10.8%). Five cases diagnosed with infection had other potential pathogens detected by metagenomic next-generation sequencing. Among the 24 culture-negative periprosthetic joint infections, metagenomic next-generation sequencing was able to identify potential pathogens in 21 cases (87.5%). From sampling to reporting, the average time needed for culture was 5.2 (95% CI 3.1-7.3) days, while that for metagenomic next-generation sequencing was 1.3 (95% CI 0.9-1.7) days. Metagenomic next-generation sequencing is more advantageous in pathogen detection of periprosthetic joint infection after total joint replacement, especially in patients with multiple infections or negative culture results.

Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis.

BACKGROUND: Studies in cystic fibrosis (CF) generally focus on inflammation present in the airway lumen. Little is known about inflammation occurring in the airway wall, the site ultimately destroyed in end-stage disease. OBJECTIVE: To test the hypothesis that inflammatory patterns in the lumen do not reflect those in the airway wall of children with CF. METHODS: Bronchoalveolar lavage (BAL) fluid and endobronchial biopsies were obtained from 46 children with CF and 16 disease-free controls. BAL cell differential was assessed using May-Gruenwald-stained cytospins. Area profile counts of bronchial tissue immunopositive inflammatory cells were determined. RESULTS: BAL fluid from children with CF had a predominance of neutrophils compared with controls (median 810×10(3)/ml vs 1×10(3)/ml, p<0.0001). In contrast, subepithelial bronchial tissue from children with CF was characterised by a predominance of lymphocytes (median 961 vs 717 cells/mm(2), p=0.014), of which 82% were (CD3) T lymphocytes. In chest exacerbations, BAL fluid from children with CF had more inflammatory cells of all types compared with those with stable disease whereas, in biopsies, only the numbers of lymphocytes and macrophages, but not of neutrophils, were higher. A positive culture of Pseudomonas aeruginosa was associated with higher numbers of T lymphocytes in subepithelial bronchial tissue (median 1174 vs 714 cells/mm(2), p=0.029), but no changes were seen in BAL fluid. Cell counts in BAL fluid and biopsies were positively correlated with age but were unrelated to each other. CONCLUSION: The inflammatory response in the CF airway is compartmentalised. In contrast to the neutrophil-dominated inflammation present in the airway lumen, the bronchial mucosa is characterised by the recruitment and accumulation of lymphocytes.

Correlation between osteoporosis and degeneration of intervertebral discs in aging rats.

This study examined the correlation between osteoporosis and the degeneration of intervertebral discs. Sprague-Dawley rats were maintained up to 22 or 28 months. The femoral bone, tibial bone and lumbar vertebra were histologically studied and the expression of collagen type II and X in intervertebral discs was immunohistochemiscally determined. Several indices for the degeneration of intervertebral discs and osteoporosis and the correlation among them were then analyzed. Close correlations were found among the indices for the degeneration of intervertebral discs, including the relative area of the vascular bud, the ratio of the uncalcified and the calcified layers, the expression of collagen type II and X. The correlation with collagen type X was negative. There existed positive correlations among the indices for osteoporosis, including the thickness ratio of cortical bone, the relative area of bone trabecula, the density of femoral and vertebral body bones, and the maximum stress and strain on bone. Analysis on the relationship of osteoporosis and the disease on disc showed that the indices of osteoporosis were negatively correlated with the indices of the degeneration of intervertebral discs but the expression of collagen type X was positively correlated, with the density of vertebral body bones having the strongest dependence on collagen type X. The maximum stress and strain bore no correlation with the degeneration of intervertebral discs. These results suggest that osteoporosis was negatively correlated with the degeneration of intervertebral discs.

The biological uptake of dissolved iron in the changing Daya Bay, South China Sea: Effect of pH and DO.

The oceanic acidification and coastal hypoxia have potential to enhance biological uptake of dissolved iron (Fe) by phytoplankton. In this study, the Fe uptake rate (FeUR) in Daya Bay was significantly negatively correlated with pH and dissolved oxygen (DO) (r = -0.81 and -0.73, respectively, p < 0.001). In addition, binary regression (FeUR = -1.45 × pH - 0.10 × DO + 13.64) also indicated that both pH and DO played key roles in FeUR variations. As pH and DO decreased, Fe uptake by phytoplankton was promoted, and the contribution of nano-phytoplankton to Fe uptake increased significantly, while that of pico-FeUR decreased. These will result in the phytoplankton community to be miniaturized and Fe requirement of phytoplankton goes higher, thereby leading changes of phytoplankton composition and coastal ecosystem. This study helps to understand how Fe could affect the coastal ecosystem under the increasing anthropogenic influences.

Carbon and Iron Uptake by Phytoplankton in the Amundsen Sea, Antarctica.

Freshwater components in the Southern Ocean, whether sea ice meltwater or meteoric water, influence the growth of phytoplankton by affecting water stability and supplying dissolved iron (DFe). In addition, melting sea ice stimulates phytoplankton blooms by providing ice algae. In this study, sea ice meltwater and meteoric water in the Amundsen Sea (AS) were differentiated by their stable oxygen isotopic compositions (δ18O), while the phytoplankton carbon fixation rate (CFR) and iron uptake rate (FeUR) values were determined using the 14C and 55Fe tracer assays, respectively. Our results showed that FeUR exhibits a significant positive response only to sea ice meltwater, suggesting that DFe and algae provided by sea ice melting may be the main cause. In addition, the CFR had a slightly positive response to the freshwater input and a stronger correlation with the phytoplankton biomass, suggesting that the freshwater input may have enhanced the CFR through the algae released from sea ice melting. The FeUR normalized to the phytoplankton biomass was significantly positively correlated with the mixed layer depth, suggesting that water stability regulates the phytoplankton growth and the resulting Fe demand. A higher Fe demand per unit of carbon fixation during sea ice formation leads to a higher Fe/C ratio in phytoplankton. Although no significant correlations were observed between the FeUR, CFR, and meteoric water, meteoric water may have an effect on larger phytoplankton sensitive to Fe deficiencies. The results of culture experiments with DFe addition showed that the added Fe significantly enhanced the Fe uptake, carbon fixation, and Fe/C ratio of the cells, especially for micro-phytoplankton. The more pronounced response of micro-phytoplankton means that the meteoric water input may affect the efficiency of carbon export. Our study provides the first measurements of phytoplankton Fe quotas in the AS in austral late summer and early autumn, providing insights into how meteoric water and sea ice meltwater affect seasonal changes in Antarctic ecosystems.