Smoking and osteoimmunology: Understanding the interplay between bone metabolism and immune homeostasis.

Smoking continues to pose a global threat to morbidity and mortality in populations. The detrimental impact of smoking on health and disease includes bone destruction and immune disruption in various diseases. Osteoimmunology, which explores the communication between bone metabolism and immune homeostasis, aims to reveal the interaction between the osteoimmune systems in disease development. Smoking impairs the differentiation of mesenchymal stem cells and osteoblasts in bone formation while promoting osteoclast differentiation in bone resorption. Furthermore, smoking stimulates the Th17 response to increase inflammatory and osteoclastogenic cytokines that promote the receptor activator of NF-κB ligand (RANKL) signaling in osteoclasts, thus exacerbating bone destruction in periodontitis and rheumatoid arthritis. The pro-inflammatory role of smoking is also evident in delayed bone fracture healing and osteoarthritis development. The osteoimmunological therapies are promising in treating periodontitis and rheumatoid arthritis, but further research is still required to block the smoking-induced aggravation in these diseases. Translational potential: This review summarizes the adverse effect of smoking on mesenchymal stem cells, osteoblasts, and osteoclasts and elucidates the smoking-induced exacerbation of periodontitis, rheumatoid arthritis, bone fracture healing, and osteoarthritis from an osteoimmune perspective. We also propose the therapeutic potential of osteoimmunological therapies for bone destruction aggravated by smoking.

Outcomes from different aspects indicate the all-inside technique may serve as an ideal option for anterior cruciate ligament reconstruction.

PURPOSE: To evaluate the postoperative outcomes of the all-inside technique in arthroscopic anterior cruciate ligament reconstruction (ACLR). METHODS: Patients who underwent ACLR using the all-inside technique between 2018 and 2021 were retrospectively assessed. All patients were followed up for at least 2 years. Functional recovery and pain relief were assessed using the International Knee Documentation Committee (IKDC) score, Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). Instrumented laxity was assessed via side-to-side difference using the Kneelax3 arthrometer. Graft maturity was estimated using the signal-to-noise quotient value based on magnetic resonance imaging (MRI). Adverse events during and after the surgery were recorded. RESULTS: A total of 78 patients were included in this study, with a mean age of 28.1 ± 7.6 years. The IKDC (p < 0.001), Lysholm (p < 0.001) and KOOS (p < 0.001 for all subgroups) scores at the final follow-up were significantly higher than those before the surgery. The VAS scores (p < 0.05) were significantly lower than those before surgery. The side-to-side difference results indicated that 50 patients had a difference of less than 3 mm, indicating a tight graft, whereas only 1 patient had a difference of >5 mm, indicating a loose graft. The median signal-to-noise quotient of the graft on MRI was 1.4 (P25, P75: 1.0, 2.0). No intraoperative adverse events were observed. Postoperative adverse events included three cases of infection, three cases of graft rerupture, two cases of cyclops lesion and one case of surgical intervention for a meniscal tear. CONCLUSION: ACLR using the all-inside technique offers promising results in patients with ACL rupture. LEVEL OF EVIDENCE: Level IV.

Global trends and research hotspots of reverse total shoulder arthroplasty: a bibliometric analysis from 1991 to 2022.

Reverse total shoulder arthroplasty (rTSA) has been demonstrated to be an effective intervention for various shoulder disorders. The number of rTSA-related studies performed has increased annually over the past three decades. The Journal of Shoulder and Elbow Surgery had the highest number of publications and citations in the rTSA-related research domain and is therefore considered to be the most influential journal in this field. The USA published the most publications and established a high degree of cooperation with many countries worldwide. The University of Florida, the Hospital for Special Surgery, and Rush University, Mayo Clinic were representative and active institutions in this field. It is anticipated that advancements in prosthesis design, specifically with regards to lateralized design concepts, expanding indications for rTSA, a trend toward younger patient populations, and the management of postoperative complications will emerge as research hotspots in the following years. The most valuable publications, influential journals, major researchers, and leading countries were analyzed. The findings of our study will help researchers gain insights into current research hotspots and frontiers and shape their research focus in the field of rTSA.

A pharmacokinetic study comparing the biosimilar HEC14028 and Dulaglutide (Trulicity®) in healthy Chinese subjects.

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration-time curve from zero time to the estimated infinite time (AUC0-∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0-∞ geometric mean ratios were 102.9%-122.0% and 97.1%-116.9%, respectively, which were both within the range of 80.00%-125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.

The efficacy of extracorporeal shock wave therapy for knee osteoarthritis : an umbrella review.

BACKGROUND: An umbrella review was conducted to compare the effectiveness of extracorporeal shock wave therapy (ESWT) versus non-ESWT in the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: Three databases including PubMed, Embase and Web of science were searched up to September 2023. Literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Meta-analysis of outcome indicators was performed using Revman 5.4 software. RESULTS: A total of eight meta-analysis were included in this umbrella review. All meta-analysis were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and scored between 8 and 11. Compared to the sham group, the ESWT group showed better results in WOMAC (Western Ontario and McMaster Universities Arthritis Index) [mean difference (MD)=-2.94, 95% CI: -5.52, -0.37, P=0.03, I²=60%], Visual Analog Scale (VAS) (MD=-2.0, 95% CI: -2.5, -1.5, P<0.01, I²=0%), range of motion (ROM) (MD=17.55, 95% CI: 13.49, 21.61, P<0.00001, I²=0%), and Lequesne index (MD=-2.85, 95% CI: -3.64, -2.07, P<0.00001, I²=48%). CONCLUSION: Based on the results of our analysis, ESWT is now an effective therapy for improving pain and function in patients with KOA.

Accuracy and Consistency of 3-Dimensional Magnetic Resonance Imaging Is Comparable With 3-Dimensional Computed Tomography in Assessing Glenohumeral Instability: A Systematic Review.

PURPOSE: To compare the accuracy of 3-dimensional (3D) magnetic resonance imaging (MRI) with that of 3D computed tomography (CT) in evaluating glenoid bone loss (GBL). METHODS: This review aligned with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, the Cochrane Library, Embase, and Web of Science were obtained from data inception to August 28, 2023. The search term "glenoid bone loss" was extracted and analyzed via stringent inclusion and exclusion criteria. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 combined with the QUADAS-Comparative to assess the heterogeneity of included studies. RESULTS: A total of 1,589 related studies were retrieved, and 10 studies were finally included, of which a total of 143 shoulders were evaluated. The index test in QUADAS-Comparative was low risk in 9 studies. 3D MRI measurements of GBL were primarily best-fit circles (n = 9). In both clinical and cadaveric studies, the mean percentages of GBL measured by 3D MRI were 0.38% to 2.19% and 0.25% to 6.1% when compared with 3D CT and standard reference values, respectively. Intraclass correlation coefficient agreement greater than 0.9 between GBL percentages measured by 3D CT and 3D MRI. 3D MRI also could accurately measure glenoid width, glenoid height, humeral head width, and height. 3D MRI reconstruction time was similar to that of 3D CT, which was mainly 10 to 15 minutes. CONCLUSIONS: In both clinical and cadaveric studies, compared with 3D CT, 3D MRI is accurate and consistent in assessing glenohumeral bone, especially in measuring GBL, and the reconstruction time of 3D MRI is similar to 3D CT. LEVEL OF EVIDENCE: Level Ⅲ, systematic review of Level Ⅱ-Ⅲ studies.

Biochar and nano biochar: Enhancing salt resilience in plants and soil while mitigating greenhouse gas emissions: A comprehensive review.

Salinity stress poses a significant challenge to agriculture, impacting soil health, plant growth and contributing to greenhouse gas (GHG) emissions. In response to these intertwined challenges, the use of biochar and its nanoscale counterpart, nano-biochar, has gained increasing attention. This comprehensive review explores the heterogeneous role of biochar and nano-biochar in enhancing salt resilience in plants and soil while concurrently mitigating GHG emissions. The review discusses the effects of these amendments on soil physicochemical properties, improved water and nutrient uptake, reduced oxidative damage, enhanced growth and the alternation of soil microbial communities, enhance soil fertility and resilience. Furthermore, it examines their impact on plant growth, ion homeostasis, osmotic adjustment and plant stress tolerance, promoting plant development under salinity stress conditions. Emphasis is placed on the potential of biochar and nano-biochar to influence soil microbial activities, leading to altered emissions of GHG emissions, particularly nitrous oxide(N2O) and methane(CH4), contributing to climate change mitigation. The comprehensive synthesis of current research findings in this review provides insights into the multifunctional applications of biochar and nano-biochar, highlighting their potential to address salinity stress in agriculture and their role in sustainable soil and environmental management. Moreover, it identifies areas for further investigation, aiming to enhance our understanding of the intricate interplay between biochar, nano-biochar, soil, plants, and greenhouse gas emissions.

PETformer network enables ultra-low-dose total-body PET imaging without structural prior.

Objective.Positron emission tomography (PET) is essential for non-invasive imaging of metabolic processes in healthcare applications. However, the use of radiolabeled tracers exposes patients to ionizing radiation, raising concerns about carcinogenic potential, and warranting efforts to minimize doses without sacrificing diagnostic quality.Approach.In this work, we present a novel neural network architecture, PETformer, designed for denoising ultra-low-dose PET images without requiring structural priors such as computed tomography (CT) or magnetic resonance imaging. The architecture utilizes a U-net backbone, synergistically combining multi-headed transposed attention blocks with kernel-basis attention and channel attention mechanisms for both short- and long-range dependencies and enhanced feature extraction. PETformer is trained and validated on a dataset of 317 patients imaged on a total-body uEXPLORER PET/CT scanner.Main results.Quantitative evaluations using structural similarity index measure and liver signal-to-noise ratio showed PETformer's significant superiority over other established denoising algorithms across different dose-reduction factors.Significance.Its ability to identify and recover intrinsic anatomical details from background noise with dose reductions as low as 2% and its capacity in maintaining high target-to-background ratios while preserving the integrity of uptake values of small lesions enables PET-only fast and accurate disease diagnosis. Furthermore, PETformer exhibits computational efficiency with only 37 M trainable parameters, making it well-suited for commercial integration.

Safety of Early Surgery in Hip Fracture Patients Taking Clopidogrel and/or Aspirin: A Systematic Review and Meta-Analysis.

BACKGROUND: The aim of this study was to investigate the safety of early surgery in hip fracture patients who took clopidogrel and/or aspirin. METHODS: A systematic search was conducted using databases, including PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science, for studies relating to early arthroplasty or internal fixation for femoral neck fractures, intertrochanteric fractures, and subtrochanteric fractures in patients taking clopidogrel and/or aspirin. A total of 20 observational studies involving 3,077 patients were included in this meta-analysis, and analyzed in groups of early surgery versus delayed surgery, and clopidogrel and/or aspirin versus nonantiplatelet agents. RESULTS: Patients in the clopidogrel and/or aspirin group who underwent early surgery had significantly more intraoperative blood loss than those in the non-antiplatelet group (mean difference = 17.96, 95% confidence interval [CI] [4.37, 31.55], P = .01), and patients in the clopidogrel and/or aspirin group had a lower overall incidence of complications after early surgery than those in the delayed surgery group (odds ratio = 0.26, 95% CI [0.14, 0.29], P < .001) and a shorter length of hospital stay (odds ratio = 0.26, 95% CI [0.14, 0.29], P < .001). There was no significant difference in postoperative mortality and other related indicators. CONCLUSIONS: Early surgery in hip fracture patients taking clopidogrel and/or aspirin appears to be safe based on the available evidence and needs to be clarified by higher quality studies. However, the increased risk of cardiovascular events associated with discontinuation of clopidogrel or clopidogrel combined with aspirin dual antiplatelet therapy requires attention in the perioperative period.

Internal brace augmentation reconstruction versus standard anterior cruciate ligament reconstruction: a randomised controlled clinical trial study protocol.

INTRODUCTION: Anterior cruciate ligament (ACL) rupture is one of the most common knee injuries in sports, and the gold standard for treating ACL rupture is tendon graft reconstruction. Internal brace technology is being used nowadays for ligament repair; however, more relevant in vivo clinical evidence is required for using internal brace technology in ACL reconstruction (ACLR). We conducted a randomised controlled trial to investigate the clinical efficacy of internal brace technology in ACLR. METHODS AND ANALYSIS: This randomised, parallel-controlled trial included patients with ACL rupture who underwent inpatient surgery at the Department of Orthopaedics, Xiangya Hospital, Central South University. Random number table method was used to assign the participants to either the test or the control group. The test group underwent ACLR using the internal brace technique, whereas the control group underwent standard ACLR. Uniform postoperative rehabilitation protocol was used for both the groups. Patient-reported outcomes included preoperative baseline and postoperative recovery at 1, 3, 6, 12 and 24 months. The primary outcome was International Knee Documentation Committee function from baseline (ACL rupture) to 6 months postoperatively. Secondary outcomes included (1) other patient outcome reporting metrics, Lysholm knee score, Knee Injury and Osteoarthritis Outcome Score and Visual Analog Scale; (2) the use of Kneelax3 knee stabiliser to assess knee stability; (3) occurrence of adverse events, such as graft refraction or symptomatic instability, postoperative infection and contralateral injury and (4) magnetic resonance images at 12 and 24 months after ACLR. ETHICS AND DISSEMINATION: This trial was approved by the Medical Ethics Committee of the Xiangya Hospital of Central South University on 26 October 2021. Data will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200057526.

A bibliometric and visualized analysis of meniscus suture based on the WOS core collection from 2010 to 2022: A review.

Meniscus suture is an important treatment method for meniscus injury and contributes to the preservation of proprioception, restoration of knee biomechanics and alleviation of progressive osteoarthritis. However, there are few visualized analyses concerning the present studies of meniscus suture. This paper aims to evaluate the global trends, highlights and frontiers of meniscus suture. A bibliometric analysis was conducted based on the results of studies related to meniscus suture from web of science core collection. VOSviewer, GraphPad Prism, Microsoft Excel and R-bibliometrix were utilized for the bibliometric analysis of country and institution distribution, chronological distribution, source journals analysis, prolific authors and institutions analysis, keywords analysis, and reference co-citation analysis. A total of 950 publications on meniscus suture from 177 different sources were retrieved over the set time span. These publications were completed by 3177 authors from 1112 institutions in 54 countries. The United States was the most prolific country with 7960 citations and 348 publications (36.63%). Furumatsu Takayuki acted as the most prolific author (51 publications), while Robert F LaPrade with 1398 citations was the most-cited author. And more papers were published in the core journals, including American Journal of Sports Medicine, Arthroscopy-The Journal of Arthroscopic and Related Surgery, Knee Surgery Sports Traumatology Arthroscopy and Arthroscopy Techniques. Furthermore, "meniscus healing," "meniscus root tear" seem to be the emerging research hotspots. Notably, the publication trend concerning the all-inside suture technique has been rising during the past decade. The number of research publications on meniscus suture has been continuously risen since 2010. The authors, publications and institutions from the United States and East Asia were still the mainstays in this field. And the all-inside suture may become the mainstream surgical technique in the future, with meniscus healing and meniscus root tears being research highlights recently.

Research Trends of Patient-Reported Outcome Measures in Orthopedic Medical Practices: A Bibliometric and Visualized Study.

Background and Objectives: Patient-reported outcome measures (PROMs), also known as self-report measures, are critical tools for evaluating health outcomes by gathering information directly from patients without external interpretation. There has been a growing trend in the number of publications focusing on PROMs in orthopedic-related research. This study aims to identify the most valuable publications, influential journals, leading researchers, and core countries in this field using bibliometric analysis, providing researchers with an understanding of the current state and future trends of PROMs in orthopedic research. Materials and Methods: All PROMs in orthopedic-related publications from 1991 to 2022 were obtained from the WoSCC database. R software (version 4.2.2), VOSviewer (version 1.6.17), and Microsoft Excel (version 2303) were used for the bibliometric and visual analysis. Results: A total of 2273 publication records were found from 1991 to 2022. The results indicated that the United States (US) has made significant contributions to orthopedic-related PROMs. The majority of active research institutions are located in the US. J ORTHOP RES has published the most articles. J BONE JOINT SURG AM has the highest total citations. Conclusions: Our study provides a valuable reference for further exploration of the application of PROMs in orthopedics. PROMs have emerged as an increasingly popular area of research within the field of orthopedics, both in clinical practice and academic research. We conducted a bibliometric analysis in terms of journals, authors, countries, and institutions in this field. Additionally, we analyzed the potentialities and advantages of using PROMs in orthopedic research. There is an increasing trend towards using network-based or short message service (SMS)-based electronic patient-reported outcome measures (ePROMs) in orthopedic medical practices. It is anticipated that the role of PROMs in psychological and mental health research and telemedicine will continue to grow in importance.

Immulina as an Immunostimulatory Supplement: Formulation and Pharmacological Studies.

Immulina is a commercially available extract of Arthrospira platensis enriched with bacterial lipoproteins that acts as a potent Toll-like receptor 2 agonist. However, the immunostimulatory effect of Immulina is not well understood in vivo. Here, to devise an Immulina formulation suitable for in vivo oral gavage dosing, Immulina nanosuspension was prepared and freeze-dried to yield lyophilized nano-Immulina, which had an average particle size of around 300 nm and fully retained the bioactivity as a Toll-like receptor 2 agonist. Compared to the regular Immulina powder, lyophilized nano-Immulina notably accelerated the dissolution in aqueous media. Immulina nanosuspension was found to stimulate the production of proinflammatory cytokines in murine bone marrow-derived dendritic cells and macrophages. The immune response to Immulina was investigated in healthy mice by longitudinally monitoring the phagocytic activity of circulating neutrophils as a surrogate marker. Following daily oral ingestion of Immulina nanosuspension (10 mg/mouse/day), the phagocytic activity of circulating neutrophils was significantly elevated, suggesting an important mechanism for Immulina to enhance innate immunity.

The p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop mediates vasoactive intestinal peptide effects on osteoarthritis chondrocytes.

Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.

Correlation between neutrophil gelatinase phase lipocalin and cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases. The purpose of this study was to investigate whether serum NGAL levels could predict disease severity in patients with CSVD. Methods: The patients with CSVD who visited the Department of Neurology at the First Affiliated Hospital of Zhengzhou University between January 2018 and June 2022 were prospectively included. The total CSVD burden score was calculated using whole-brain magnetic resonance imaging (MRI), and the patients were divided into a mild group (total CSVD burden score < 2 points) and a severe group (total CSVD burden score ≥ 2 points). Age, sex, height, smoking and alcohol consumption history, medical history, and serological results of patients were collected to perform the univariate analysis. Multivariate logistic regression was used to analyze the risk factors that affect CSVD severity. The multiple linear regression method was used to analyze which individual CSVD markers (periventricular white matter hyperintensities, deep white matter hyperintensities, lacune, and cerebral microbleed) play a role in the association between total CSVD burden score and NGAL. Results: A total of 427 patients with CSVD (140 in the mild group and 287 in the severe group) were included in the study. A multivariate logistic regression analysis showed that the following factors were significantly associated with CSVD severity: male sex [odds ratio(OR), 1.912; 95% confidence interval (CI), 1.150-3.179], age (OR, 1.046; 95% CI, 1.022-1.070), history of cerebrovascular disease (OR, 3.050; 95% CI, 1.764-5.274), serum NGAL level (OR, 1.005; 95% CI, 1.002-1.008), and diabetes (OR, 2.593; 95% CI, 1.424-4.722). A multivariate linear regression shows that periventricular white matter hyperintensities and cerebral microbleed are associated with serum NGAL concentrations (P < 0.05). Conclusion: Serum NGAL level is closely related to CSVD severity and is a risk factor for the burden of CSVD brain damage. Serum NGAL has high specificity in reflecting the severity of CSVD.

The Diagnostic and Prognostic Value of Synovial Fluid Analysis in Joint Diseases.

Liquid biopsy is an emergent test method for the diagnosis and prognosis in the clinic. Joint fluid, also known as synovial fluid, contains a variety of bioactive constituents that can be selectively detected and further evaluated in a convenient fashion. Therefore, synovial fluid analysis functions as a specific form of liquid biopsy and plays a vital role in numerous joint diseases. In spite of the component analysis of aspirated synovial fluid beingconsidered as the gold standard for diagnosis of joint infections, biopsy of joint fluid benefits the initial diagnosis and long-term prognosis of degenerative, inflammatory, autoimmune, traumatic, congenital, and even neoplastic joint diseases. The convenience and accuracy for disease evaluation are significantly elevated as a result of the combination of synovial fluid analysis and other novel clinical technologies. In this review, we shed light on the latent role of synovial fluid in the diagnosis and prognosis of articular diseases and proposed future prospects for relevant research in this field.

Smoking, Coffee Consumption, Alcohol Intake, and Obstructive Sleep Apnea: A Mendelian Randomization Study.

BACKGROUND: Previous studies revealed that obstructive sleep apnea (OSA) and smoking, alcohol consumption, and coffee intake are closely related. This study aimed to evaluate the causal effect between these factors and OSA. METHODS: The published genome-wide association study data (GWAS) provided genetic tools. We conducted a univariable two-sample Mendelian Randomization (MR) to estimate the causal effect between smoking initiation, never smoking, alcohol consumption, coffee intake, and coffee consumption with the risk of incidence OSA. Inverse variance weighting (IVW) was used as the main method for effect evaluation, and other MR methods were used for sensitivity analysis. After adjusting for body mass index (BMI), hypertension, and diabetes respectively by multivariable MR (MVMR), we further evaluate the causal effect of these factors on OSA. RESULTS: Under univariable MR analysis, we observed that smoking initiation was associated with an increased risk of incidence OSA (OR 1.326, 95% CI 1.001-1.757, p =0.049). Never smoking was associated with decreased risk of OSA (OR 0.872, 95% CI 0.807-0.942, p <0.001). Coffee intake and coffee consumption was associated with an increased incidence of OSA (OR 1.405, 95% CI 1.065-1.854, p =0.016) and (OR 1.330, 95% CI 1.013-1.746, p =0.040). Further multivariate MR showed that the causal relationship between never smoking and OSA existed but not coffee consumption, after adjusting for diabetes and hypertension. However, the all results did not support causality after adjusting for BMI. CONCLUSION: This two-sample MR study showed that genetically predicted smoking and higher coffee intake are causally associated with an increased risk of OSA.

Surgical treatment of patellar dislocation: A network meta-analysis of randomized control trials and cohort studies.

Background: Currently, there are many surgical options for patellar dislocation. The purpose of this study is to perform a network meta-analysis of the randomized controlled trials (RCTs) and cohort studies to determine the better treatment. Method: We searched the Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, clinicaltrials.gov and who.int/trialsearch. Clinical outcomes included Kujala score, Lysholm score, International Knee Documentation Committee (IKDC) score, redislocation or recurrent instability. We conducted pairwise meta-analysis and network meta-analysis respectively using the frequentist model to compare the clinical outcomes. Results: There were 10 RCTs and 2 cohort studies with a total of 774 patients included in our study. In network meta-analysis, double-bundle medial patellofemoral ligament reconstruction (DB-MPFLR) achieved good results on functional scores. According to the surface under the cumulative ranking (SUCRA), DB-MPFLR had the highest probabilities of their protective effects on outcomes of Kujala score (SUCRA 96.5 %), IKDC score (SUCRA 100.0%) and redislocation (SUCRA 67.8%). However, DB-MPFLR (SUCRA 84.6%) comes second to SB-MPFLR (SUCRA 90.4%) in Lyshlom score. It is (SUCRA 70%) also inferior to vastus medialis plasty (VM-plasty) (SUCRA 81.9%) in preventing Recurrent instability. The results of subgroup analysis were similar. Conclusion: Our study demonstrated that MPFLR showed better functional scores than other surgical options.

Microbial mixotrophic denitrification using iron(II) as an assisted electron donor.

Mixotrophic denitrification processes have a great potential in nitrogen removal in biological wastewater treatment processes. However, so far, few studies have focused on the mixotrophic denitrification system using Fe(II) as an exclusively assisted electron donors and the underlying mechanisms in such a process remain unclear. Furthermore, the mechanisms by which microorganisms cover carbon, nitrogen, phosphorus and iron in an iron-assisted mixotrophic system remain unrevealed. In this work, we explore the feasibility of using Fe(II) as an assisted electron donor for enhancing simultaneous nitrogen and phosphorus removal via long-term reactor operation and batch tests. The results show that Fe(II) could provide electrons for efficient nitrate reduction and that biological reactions played a predominant role in these systems. In these systems Thermomonas, a strain of nitrate-reduction Fe(II)-oxidation bacterium, was enriched and accounted for a maximum abundance of 60.2%. These findings indicate a great potential of the Fe(II)-assisted mixotrophic denitrification system for practical use as an efficient simultaneous nitrogen and phosphorus removal process.

TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury.

BACKGROUND: Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. METHODS: TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. RESULTS: We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. CONCLUSION: In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.