Omeprazole and risk of osteoarthritis: insights from a mendelian randomization study in the UK Biobank.

BACKGROUND: A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. METHODS: The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. RESULTS: The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings. CONCLUSION: This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.

Multi-scale analysis provides insights into the roles of ureide permeases in wheat nitrogen use efficiency.

The ureides allantoin and allantoate serve as nitrogen (N) transport compounds in plants, and more recently, allantoin has been shown to play a role in signaling. In planta, tissue ureide levels are controlled by the activity of enzymes of the purine degradation pathway and by ureide transporters called ureide permeases (UPS). Little is known about the physiological function of UPS proteins in crop plants, and especially in monocotyledon species. Here, we identified 13 TaUPS genes in the wheat (Triticum aestivum L.) genome. Phylogenetic and genome location analyses revealed a close relationship of wheat UPSs to orthologues in other grasses and a division into TaUPS1, TaUPS2.1, and TaUPS2.2 groups, each consisting of three homeologs, with a total of four tandem duplications. Expression, localization, and biochemical analyses resolved spatio-temporal expression patterns of TaUPS genes, transporter localization at the plasma membrane, and a role for TaUPS2.1 proteins in cellular import of ureides and phloem and seed loading. In addition, positive correlations between TaUPS1 and TaUPS2.1 transcripts and ureide levels were found. Together the data support that TaUPSs function in regulating ureide pools at source and sink, along with source-to-sink transport. Moreover, comparative studies between wheat cultivars grown at low and high N strengthened a role for TaUPS1 and TaUPS2.1 transporters in efficient N use and in controlling primary metabolism. Co-expression, protein-protein interaction, and haplotype analyses further support TaUPS involvement in N partitioning, N use efficiency, and domestication. Overall, this work provides a new understanding on UPS transporters in grasses as well as insights for breeding resilient wheat varieties with improved N use efficiency.

Osteoarthritis: Role of Peroxisome Proliferator-Activated Receptors.

Osteoarthritis (OA) represents the foremost degenerative joint disease observed in a clinical context. The escalating issue of population aging significantly exacerbates the prevalence of OA, thereby imposing an immense annual economic burden on societies worldwide. The current therapeutic landscape falls short in offering reliable pharmaceutical interventions and efficient treatment methodologies to tackle this growing problem. However, the scientific community continues to dedicate significant efforts towards advancing OA treatment research. Contemporary studies have discovered that the progression of OA may be slowed through the strategic influence on peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated receptors within the nuclear hormone receptor family. The three distinctive subtypes-PPARα, PPARß/δ, and PPARγ-find expression across a broad range of cellular terminals, thus managing a multitude of intracellular metabolic operations. The activation of PPARγ and PPARα has been shown to efficaciously modulate the NF-κB signaling pathway, AP-1, and other oxidative stress-responsive signaling conduits, leading to the inhibition of inflammatory responses. Furthermore, the activation of PPARγ and PPARα may confer protection to chondrocytes by exerting control over its autophagic behavior. In summation, both PPARγ and PPARα have emerged as promising potential targets for the development of effective OA treatments.

Transcriptomic, proteomic, and physiological studies reveal key players in wheat nitrogen use efficiency under both high and low nitrogen supply.

The effective use of available nitrogen (N) to improve crop grain yields provides an important strategy to reduce environmental N pollution and promote sustainable agriculture. However, little is known about the common genetic basis of N use efficiency (NUE) at varying N availability. Two wheat (Triticum aestivum L.) cultivars were grown in the field with high, moderate, and low N supply. Cultivar Zhoumai 27 outperformed Aikang 58 independent of the N supply and showed improved growth, canopy leaf area index, flag leaf surface area, grain number, and yield, and enhanced NUE due to both higher N uptake and utilization efficiency. Further, transcriptome and proteome analyses were performed using flag leaves that provide assimilates for grain growth. The results showed that many genes or proteins that are up- or down-regulated under all N regimes are associated with N and carbon metabolism and transport. This was reinforced by cultivar differences in photosynthesis, assimilate phloem transport, and grain protein/starch yield. Overall, our study establishes that improving NUE at both high and low N supply requires distinct adjustments in leaf metabolism and assimilate partitioning. Identified key genes/proteins may individually or concurrently regulate NUE and are promising targets for maximizing crop NUE irrespective of the N supply.

A New Perspective on the Role of Glutamine Synthetase in Nitrogen Remobilization in Wheat (Triticum aestivum L.).

Glutamine synthetase (GS), a key enzyme in plant nitrogen metabolism, is closely related to nitrogen remobilization. However, how GS isoforms participate in nitrogen remobilization remains unclear. Here, the spatiotemporal expression of the TaGS gene family after anthesis was investigated, and the results showed that TaGS1;1 was mainly encoded by TaGS1;1-6A, while the other isozymes were mainly encoded by TaGS localized on the A and D subgenomes. TaGS1;2-4A/4D had the highest expression level, especially in rachis and peduncle. Furthermore, immunofluorescence showed TaGS1;2 was located in the phloem of rachis and peduncle. GUS (ß-glucuronidase) staining confirmed that ProTaGS1;2-4A/4D::GUS activity was mainly present in the vascular system of leaves, roots, and petal of Arabidopsis. Ureides, an important transport form of nitrogen, were mainly synthesized in flag leaves and transported to grains through the phloem of peduncle and rachis during grain filling. TaAAH, which encodes the enzyme that degrades ureides to release NH4+, had a higher expression in rachis and peduncle and was synchronized with the increase in NH4+ concentration in phloem, indicating that NH4+ in phloem is from ureide degradation. Taking the above into account, TaGS1;2, which is highly expressed in the phloem of peduncle and rachis, may participate in N remobilization by assimilating NH4+ released from ureide degradation.

Nitrogen Regulating the Expression and Localization of Four Glutamine Synthetase Isoforms in Wheat (Triticum aestivum L.).

Glutamine synthetase (GS), the key enzyme in plant nitrogen assimilation, is strictly regulated at multiple levels, but the most relevant reports focus on the mRNA level. Using specific antibodies as probes, the effects of nitrogen on the expression and localization of individual wheat GS (TaGS) isoforms were studied. In addition to TaGS2, TaGS1;1 with high affinity to substrate and TaGS1;3 with high catalytic activity were also localized in mesophyll, and may participate in cytoplasmic assimilation of ammonium (NH4+) released from photorespiration or absorbed by roots; TaGS1;2 was localized in xylem of leaves. In roots, although there were hundreds of times more TaGS1;1 than TaGS1;2 transcripts, the amount of TaGS1;1 subunit was not higher than that of TaGS1;2; NH4+ inhibited TaGS1;1 expression but stimulated TaGS1;3 expression. In root tips, nitrate stimulated TaGS1;1, TaGS1;3, and TaGS2 expression in meristem, while NH4+ promoted tissue differentiation and TaGS1;2 expression in endodermis and vascular tissue. Only TaGS1;2 was located in vascular tissue of leaves and roots, and was activated by glutamine, suggesting a role in nitrogen transport. TaGS1;3 was induced by NH4+ in root endodermis and mesophyll, suggesting a function in relieving NH4+ toxicity. Thus, TaGS isoforms play distinct roles in nitrogen assimilation for their different kinetic properties, tissue locations, and response to nitrogen regimes.

New isoforms and assembly of glutamine synthetase in the leaf of wheat (Triticum aestivum L.).

Glutamine synthetase (GS; EC 6.3.1.2) plays a crucial role in the assimilation and re-assimilation of ammonia derived from a wide variety of metabolic processes during plant growth and development. Here, three developmentally regulated isoforms of GS holoenzyme in the leaf of wheat (Triticum aestivum L.) seedlings are described using native-PAGE with a transferase activity assay. The isoforms showed different mobilities in gels, with GSII>GSIII>GSI. The cytosolic GSI was composed of three subunits, GS1, GSr1, and GSr2, with the same molecular weight (39.2kDa), but different pI values. GSI appeared at leaf emergence and was active throughout the leaf lifespan. GSII and GSIII, both located in the chloroplast, were each composed of a single 42.1kDa subunit with different pI values. GSII was active mainly in green leaves, while GSIII showed brief but higher activity in green leaves grown under field conditions. LC-MS/MS experiments revealed that GSII and GSIII have the same amino acid sequence, but GSII has more modification sites. With a modified blue native electrophoresis (BNE) technique and in-gel catalytic activity analysis, only two GS isoforms were observed: one cytosolic and one chloroplastic. Mass calibrations on BNE gels showed that the cytosolic GS1 holoenzyme was ~490kDa and likely a dodecamer, and the chloroplastic GS2 holoenzyme was ~240kDa and likely a hexamer. Our experimental data suggest that the activity of GS isoforms in wheat is regulated by subcellular localization, assembly, and modification to achieve their roles during plant development.

A Scientometric Worldview of Artificial Intelligence in Musculoskeletal Diseases Since the 21st Century.

Purpose: Over the past 24 years, significant advancements have been made in applying artificial intelligence (AI) to musculoskeletal (MSK) diseases. However, there is a lack of analytical and descriptive investigations on the trajectory, essential research directions, current research scenario, pivotal focuses, and future perspectives. This research aims to provide a thorough update on the progress in AI for MSK diseases over the last 24 years. Methods: Data from the Web of Science database, covering January 1, 2000, to March 1, 2024, was analyzed. Using advanced analytical tools, we conducted comprehensive scientometric and visual analyses. Results: The findings highlight the predominant influence of the USA, which accounts for 28.53% of the total publications and plays a key role in shaping research in this field. Notable productivity was seen at institutions such as the University of California, San Francisco, Harvard Medical School, and Seoul National University. Valentina Pedoia is identified as the most prolific contributor. Scientific Reports had the highest number of publications in this area. The five most significant diseases are joint diseases, bone fractures, bone tumors, cartilage diseases, and spondylitis. Conclusion: This comprehensive scientometric assessment benefits both experienced researchers and newcomers, providing quick access to essential information and fostering the development of innovative concepts in this field.

Zooming in and Out of Programmed Cell Death in Osteoarthritis: A Scientometric and Visualized Analysis.

During the past decade, mounting evidence has increasingly linked programmed cell death (PCD) to the progression and development of osteoarthritis (OA). There is a significant need for a thorough scientometric analysis that recapitulates the relationship between PCD and OA. This study aimed to collect articles and reviews focusing on PCD in OA, extracting data from January 1st, 2013, to October 31st, 2023, using the Web of Science. Various tools, including VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package, were employed for scientometric and visualization analyses. Notably, China, the USA, and South Korea emerged as major contributors, collectively responsible for more than 85% of published papers and significantly influencing research in this field. Among different institutions, Shanghai Jiao Tong University, Xi'an Jiao Tong University, and Zhejiang University exhibited the highest productivity. Prolific authors included Wang Wei, Wang Jing, and Zhang Li. Osteoarthritis and Cartilage had the most publications in this area. Keywords related to PCD in OA prominently highlighted 'chondrocytes', 'inflammation', and 'oxidative stress', recognized as pivotal mechanisms contributing to PCD within OA. This study presents the first comprehensive scientometric analysis, offering a broad perspective on the knowledge framework and evolving patterns concerning PCD in relation to OA over the last decade. Such insights can aid researchers in comprehensively understanding this field and provide valuable directions for future explorations.

A bibliometric worldview of breast-conserving surgery for breast cancer from 2013 to 2023.

Over the last decade, significant advancements have been made in breast-conserving surgery (BCS) for breast cancer. However, there is a lack of analytical and descriptive investigations on the trajectory, essential research directions, current research scenario, pivotal investigative focuses, and forthcoming perspectives. The objective of this research is to provide a thorough update on the progress made in BCS for breast cancer over the preceding decade. Retrieved from the Web of Science database, the data span from January 1, 2013, to November 30, 2023. Utilizing a set of advanced analytical instruments, we conducted comprehensive bibliometric and visual analyses. The findings underscore the predominant influence of the USA, representing 35.77% of the overall publications and playing a pivotal role in shaping research within this field. Notable productivity was evident at various institutions, including the Memorial Sloan Kettering Cancer Center, the University of Texas MD Anderson Cancer Center, and the University of Toronto. Annals of Surgical Oncology contributed the most publications in this field. An examination of keywords indicated a change in the concentration of research attention, transitioning from molecular subtype, ultrasonography, and intraoperative aspects to SEER, male breast cancer, and adjuvant measures. By offering a comprehensive bibliometric assessment, this study enhances our understanding of BCS for breast cancer. Consequently, this benefits both experienced researchers and newcomers alike, providing prompt access to essential information and fostering the extraction of innovative concepts within this specific field.

Unraveling differential characteristics and mechanisms of nitrogen uptake in wheat cultivars with varied nitrogen use efficiency.

Nitrogen uptake is crucial to wheat nitrogen use efficiency (NUE). The study's findings indicate that both high- and low-NUE cultivars exhibited highest nitrogen uptake efficiency (NupE) under 0.2 mM nitrogen. Under 2 mM nitrogen, their NupEs decrease significantly, while uptakes to NO3- were notably higher than that of NH4+. Strikingly, high-NUE cultivars exhibited a significantly higher NH4+ uptake rate than low NUE cultivars, resulting in a marked improvement in their ability to take up nitrogen. The NUEs of the cultivars with 5 mM nitrogen were almost half that of 2 mM nitrogen. NO3- uptake primarily occurred in the mature zone of roots, while NH4+ uptake took place in the root tip meristem and elongation zones. Notably, the NH4+ uptake in root tip meristematic zone of high-NUE cultivar was significantly higher than that of low NUE cultivar. Furthermore, the NO3- uptake of high-NUE cultivar in the root mature zone was significantly higher than that of low-NUE cultivar under 2 mM nitrogen. These findings were consistent with the significantly higher expression levels of TaAMT in root tip and of TaNRT in root mature area of high-NUE cultivar compared to low-NUE cultivar, respectively, enabling efficient absorption of NO3- and NH4+ and transport of NO3- to shoot. The high-NUE cultivars showed elevated expression of amino acid transporters further promoting nitrogen uptake, and conversion of nitrogen into ureides and amino acids further facilitated inorganic nitrogen uptake by roots. The differential findings offer valuable insights into novel variety breeding of high NUE in the future.

Targeting ferroptosis unveils a new era for traditional Chinese medicine: a scientific metrology study.

In the past 11 years, there has been a surge in studies exploring the regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, a significant gap persists in comprehensive scientometric analysis and scientific mapping research, especially in tracking the evolution, primary contributors, and emerging research focal points. This study aims to comprehensively update the advancements in targeting ferroptosis with various TCMs during the previous 11 years. The data, covering the period from 1 January 2012, to 30 November 2023, were retrieved from the Web of Science database. For in-depth scientometric and visualized analyses, a series of advanced analytical instruments were employed. The findings highlight China's predominant role, accounting for 71.99% of total publications and significantly shaping research in this domain. Noteworthy productivity was observed at various institutions, including Guangzhou University of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, and Zhejiang University. Thomas Efferth emerged as the foremost author within this field, while Frontiers in Pharmacology boasted the highest publication count. This study pinpointed hepatocellular carcinoma, chemical and drug-induced liver injury, mitochondrial diseases, acute kidney injury, and liver failure as the most critical disorders addressed in this research realm. The research offers a comprehensive bibliometric evaluation, enhancing our understanding of the present status of TCM therapy in managing ferroptosis-related diseases. Consequently, it aids both seasoned researchers and newcomers by accelerating access to vital information and fostering innovative concept extraction within this specialized field.

Unlocking the potential of exosomes: a breakthrough in the theranosis of degenerative orthopaedic diseases.

Degenerative orthopaedic diseases pose a notable worldwide public health issue attributable to the global aging population. Conventional medical approaches, encompassing physical therapy, pharmaceutical interventions, and surgical methods, face obstacles in halting or reversing the degenerative process. In recent times, exosome-based therapy has gained widespread acceptance and popularity as an effective treatment for degenerative orthopaedic diseases. This therapeutic approach holds the potential for "cell-free" tissue regeneration. Exosomes, membranous vesicles resulting from the fusion of intracellular multivesicles with the cell membrane, are released into the extracellular matrix. Addressing challenges such as the rapid elimination of natural exosomes in vivo and the limitation of drug concentration can be effectively achieved through various strategies, including engineering modification, gene overexpression modification, and biomaterial binding. This review provides a concise overview of the source, classification, and preparation methods of exosomes, followed by an in-depth analysis of their functions and potential applications. Furthermore, the review explores various strategies for utilizing exosomes in the treatment of degenerative orthopaedic diseases, encompassing engineering modification, gene overexpression, and biomaterial binding. The primary objective is to provide a fresh viewpoint on the utilization of exosomes in addressing bone degenerative conditions and to support the practical application of exosomes in the theranosis of degenerative orthopaedic diseases.

A bibliometric and visualized analysis of nanoparticles in musculoskeletal diseases (from 2013 to 2023).

As the pace of research on nanomedicine for musculoskeletal (MSK) diseases accelerates, there remains a lack of comprehensive analysis regarding the development trajectory, primary authors, and research focal points in this domain. Additionally, there's a need of detailed elucidation of potential research hotspots. The study gathered articles and reviews focusing on the utilization of nanoparticles (NPs) for MSK diseases published between 2013 and 2023, extracted from the Web of Science database. Bibliometric and visualization analyses were conducted using various tools such as VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package. China, the USA, and India emerged as the key drivers in this research domain. Among the numerous institutions involved, Shanghai Jiao Tong University, Chinese Academy of Sciences, and Sichuan University exhibited the highest productivity levels. Vallet-Regi Maria emerged as the most prolific author in this field. International Journal of Nanomedicine accounted for the largest number of publications in this area. The top five disorders of utmost significance in this field include osteosarcoma, cartilage diseases, bone fractures, bone neoplasms, and joint diseases. These findings are instrumental in providing researchers with a comprehensive understanding of this domain and offer valuable perspectives for future investigations.

Oxygen tension regulating hydrogels for vascularization and osteogenesis via sequential activation of HIF-1α and ERK1/2 signaling pathways in bone regeneration.

Angiogenesis plays a crucial role in bone regeneration. Hypoxia is a driving force of angiogenesis at the initial stage of tissue repair. The hypoxic microenvironment could activate the hypoxia-inducible factor (HIF)-1α signaling pathway in cells, thereby enhancing the proliferation, migration and pro-angiogenic functions of stem cells. However, long-term chronic hypoxia could inhibit osteogenic differentiation and even lead to apoptosis. Therefore, shutdown of the HIF-1α signaling pathway and providing oxygen at later stage probably facilitate osteogenic differentiation and bone regeneration. Herein, an oxygen tension regulating hydrogel that sequentially activate and deactivate the HIF-1α signaling pathway were prepared in this study. Its effect and mechanism on stem cell differentiation were investigated both in vitro and in vivo. We proposed a gelatin-based hydrogel capable of sequentially delivering a hypoxic inducer (copper ions) and oxygen generator (calcium peroxide). The copper ions released from the hydrogels significantly enhanced cell viability and VEGF secretion of BMSCs via upregulating HIF-1α expression and facilitating its translocation into the nucleus. Additionally, calcium peroxide promoted alkaline phosphatase activity, osteopontin secretion, and calcium deposition through the activation of ERK1/2. Both Cu2+ and calcium peroxide demonstrated osteogenic promotion individually, while their synergistic effect within the hydrogels led to a superior osteogenic effect by potentially activating the HIF-1α and ERK1/2 signaling pathways.

Frictional Wear and Thermal Fatigue Properties of Die Steel after Ultrasound-Assisted Alloying.

The surface layer of 8407 die steel was strengthened using the combination of ultrasonic surface rolling and high-energy ion implanting in the present work. The strengthened layer was then characterized via microstructure observation, composition analysis, and hardness test. After that, the frictional wear and thermal fatigue properties of high-energy ion implanting specimens and composite-reinforced specimens were compared. Results show that the pretreatment of specimens with ultrasonic surface rolling causes grain refinement in the material surface, which promotes the strengthening effect of high-energy ion implanting. The wear volume of composite-reinforced specimens at medium and high frequencies is reduced by about 20%, and the wear resistance of these specimens is significantly improved with a lower friction coefficient and wear volume at moderate and high frequencies in alternating load friction experiments. Meanwhile, the thermal fatigue crack depth of composite-reinforced specimens is reduced by about 47.5%, which effectively prevents the growth of thermal cracks in the surface, thus improving the curing ability of the implanted elements. Therefore, composite strengthening of the mold steel surface is conducive to improving the cycle life, ensuring accuracy, effectively hindering the expansion of thermal cracks, and saving the cost of production.

Global research landscape on the crosstalk between ferroptosis and musculoskeletal diseases: A bibliometric and visualized analysis.

Over the past 11 years, mounting evidence has suggested a significant association between ferroptosis and the development and progression of musculoskeletal (MSK) diseases, such as osteoporosis and osteoarthritis. However, a comprehensive bibliometric analysis summarizing the relationship between ferroptosis and MSK diseases is currently lacking. The present study collected articles and reviews on the topic of ferroptosis in MSK diseases. The data were collected from January 1st, 2012 to June 30th, 2023 by screening the Web of Science database. Various tools, including VOSviewer, CiteSpace, Pajek, the R package, and others, were used to conduct bibliometric and visualization analyses. Notably, China, the USA, and Italy emerged as primary contributors, jointly accounting for over 80 % of published documents, thereby shaping research in this domain. Among the diverse institutions, Shanghai Jiao Tong University, Soochow University, and Huazhong University of Science and Technology displayed the highest productivity levels. The most prolific authors include Sun Kai, Shang Peng, and Jing Xingzhi. Oxidative Medicine and Cellular Longevity stood out with the largest number of publications in this area. The five most significant disorders in this field are bone fractures, osteosarcoma, bone neoplasms, joint diseases, and osteoporotic fractures. This study represents an inaugural comprehensive bibliometric analysis, presenting a holistic view of the knowledge framework and developmental patterns in ferroptosis concerning MSK diseases over the previous eleven years. This information can aid researchers in acquiring a thorough grasp of this domain and offer invaluable insights for forthcoming explorations.

LncRNA XLOC_015548 affects the proliferation and differentiation of myoblasts via the MAPK signaling pathway.

In recent years, an increasing number of studies have reported that long non-coding RNAs (lncRNAs) play essential regulatory roles in myogenic differentiation. In this study, a specific LncRNA XLOC_015548 (Lnc000280) was identified. However, little research has explored its mechanism of action by constructing XLOC_015548 gene editing cell models. In this study, relevant sequences were obtained according to the RNA-seq results. Subsequently, XLOC_015548 knockdown and over-expression lentiviral vectors were constructed, and the C2C12 myoblast cell line was transfected to prepare the XLOC_015548 gene-edited myoblast model. The in vitro analysis revealed that over-expression of XLOC_015548 significantly promoted the proliferation and differentiation of myoblasts and the formation of myotubes, whereas the opposite result was obtained in the knockdown group. XLOC_015548 regulated myogenic differentiation and affected the expression of myogenic differentiation regulators such as Myod, myogenin, and MyHC. Regarding the signaling pathway, we found that XLOC_015548 correlated with the phosphorylation level of MAPK/MEK/ERK pathway proteins. And the degree of phosphorylation was positively correlated with the protein expression of myogenic differentiation regulators. In conclusion, a new gene-edited myoblast model was constructed based on the lncRNA regulator XLOC_015548. The in vitro cell experiments verified that XLOC_015548 had regulatory effects on muscle growth and myoblast differentiation. These findings provide a laboratory foundation for the clinical application of lncRNAs as regulatory factors in the treatment of disuse muscle atrophy.

Short-Term Outcomes of Enhanced Recovery after Surgery (ERAS) for Ankle Fracture Patients: A Single-Center Retrospective Cohort Study.

OBJECTIVE: Enhanced recovery after surgery (ERAS) has been successfully adopted for the improvement of medical quality and efficacy in many diseases, but the effect thereof for ankle fracture patients can vary. The aim of the present study was to explore the short-term postoperative outcomes of ERAS among ankle fracture patients. METHODS: The present study was a retrospective cohort study conducted between January 2019 and May 2019. One hundred and sixty ankle fracture participations (58 males and 102 females, aged 41.71 ± 14.51 years) were included. The participants treated with open reduction and internal fixation were divided into two groups (non-ERAS vs. ERAS) depending on whether ERAS was applied. Postoperative outcomes included American Orthopedic Foot and Ankle Society (AOFAS) score, length of stay (LOS), hospital cost, complications, and consumption of opioids. To assess the association between the groups and outcomes, generalized estimating equation (GEE) modeling and multivariable linear regression analysis were performed. RESULTS: The average follow-up periods of the participations were 24 months postoperatively. No significant differences were detected between the non-ERAS group and ERAS group with respect to the demographic of patients in terms of gender, age, Danis-Weber classification of fracture, dislocation of ankle joint, and comorbidity (P > 0.05). Significant differences in terms of a higher AOFAS score were found in the ERAS group compared with the non-ERAS group (6.73, 95% CI, 5.10-8.37, p < 0.001) at 3 months postoperatively (PO3M) and (4.73, 95% CI, 3.02-6.45, p < 0.001) at 6 months postoperatively (PO6M). However, similar AOFAS scores were found at 12 months postoperatively (PO12M) (0.28, 95% CI, -0.32 to 0.89, P > 0.05) and at 24 months postoperatively (PO24M) (0.56, 95% CI, -0.07 to 1.19, P > 0.05). Additionally, the GEE analysis and group-by-time interaction of AOFAS score revealed that the ERAS protocol could facilitate faster recovery for ankle fracture patients, with higher PO3M and PO6M (both P < 0.05). At the same time, significant differences in terms of a shorter length of stay (-3.19, 95% CI, -4.33 to -2.04, P < 0.01) and less hospital cost (-6501.81, 95% CI, -10955.21 to -2048.42, P < 0.01) were found in the ERAS group compared with the non-ERAS group. CONCLUSION: By reducing LOS and hospital cost, the ERAS protocol might improve the medical quality and efficacy. The present study can provide a realistic evaluation and comparison of the ERAS protocol among ankle fracture patients, and ultimately guide clinical decision making.

"Cross-talk" between gut microbiome dysbiosis and osteoarthritis progression: a systematic review.

Objectives: The aim of this systematic review was to summarize the available literature on gut microbiome (GMB) and osteoarthritis (OA), analyze the correlation between GMB and OA, and explore potential underlying mechanisms. Methods: A systematic search of the PubMed, Embase, Cochrane, and Web of Science with the keywords "Gut Microbiome" and "Osteoarthritis" was conducted to identify the human and animal studies exploring the association between GMB and OA. The retrieval time range was from the database inception to July 31, 2022. Studies reported the other arthritic diseases without OA, reviews, and studies focused on the microbiome in other parts of the body with OA, such as oral or skin, were excluded. The included studies were mainly reviewed for GMB composition, OA severity, inflammatory factors, and intestinal permeability. Results: There were 31 studies published met the inclusion criteria and were analyzed, including 10 human studies and 21 animal studies. Human and animal studies have reached a consistent conclusion that GMB dysbiosis could aggravate OA. In addition, several studies have found that alterations of GMB composition can increase intestinal permeability and serum levels of inflammatory factors, while regulating GMB can alleviate the changes. Owing to the susceptibility of GMB to internal and external environments, genetics, and geography, the included studies were not consistent in GMB composition analysis. Conclusion: There is a lack of high-quality studies evaluating the effects of GMB on OA. Available evidence indicated that GMB dysbiosis aggravated OA through activating the immune response and subsequent induction of inflammation. Future studies should focus on more prospective, cohort studies combined with multi-omics to further clarify the correlation.