Gradual stabilization and narrowing of bone tunnels following primary anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study is to dynamically assess variations in tunnel diameters following anterior cruciate ligament reconstruction (ACLR) and investigate correlations with patient-reported outcomes (PROs) and graft maturity based on signal-to-noise quotient (SNQ). METHODS: Tunnel diameter and tunnel position were measured using three-dimensional models derived from computed tomography (CT) data. Postoperative graft maturity and integration were evaluated using magnetic resonance imaging (MRI). Clinical outcomes were assessed through PROs, which included the International Knee Documentation Committee Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Scores and Lysholm scores. The correlation between tunnel enlargement extent, PROs and SNQ values, as well as correlations between confounding factors, tunnel diameter differences and SNQ were analyzed. RESULTS: A total of 73 participants underwent primary ACLR and scheduled follow-ups. At the segment of the articular aperture, the femoral tunnel was enlarged by 32.3% to 10.4 ± 1.6 mm (p < 0.05), and the tibial tunnel was widened by 17.2% to 9.6 ± 1.2 mm (p < 0.05) at the 6-month follow-up. At 1 year postoperatively, diameters at the articular aperture were not further increased on the femoral (n.s.) and tibial (n.s.) sides. In early postoperative follow-up, the femoral tunnel was anteriorly and distally shifted, coupled with posterior and lateral deviation involving the tibial side, exhibiting minimal migration at 1-year follow-up. The degree of tunnel widening was not correlated with PROs and SNQ values. Age, gender, body mass index (BMI), time from surgery to follow-up, concomitant injuries and autograft type were not correlated with tunnel diameter differences and SNQ. CONCLUSIONS: The femoral and tibial bone tunnels exhibited eccentrical widening and gradually stabilized at 1 year following ACLR. Furthermore, the enlarged bone tunnels were not correlated with unsatisfied PROs and inferior graft maturity. LEVEL OF EVIDENCE: Level IV.

Accelerated Bone Healing via Electrical Stimulation.

Piezoelectric effect produces an electrical signal when stress is applied to the bone. When the integrity of the bone is destroyed, the biopotential within the defect site is reduced and several physiological responses are initiated to facilitate healing. During the healing of the bone defect, the bioelectric potential returns to normal levels. Treatment of fractures that exceed innate regenerative capacity or exhibit delayed healing requires surgical intervention for bone reconstruction. For bone defects that cannot heal on their own, exogenous electric fields are used to assist in treatment. This paper reviews the effects of exogenous electrical stimulation on bone healing, including osteogenesis, angiogenesis, reduction in inflammation and effects on the peripheral nervous system. This paper also reviews novel electrical stimulation methods, such as small power supplies and nanogenerators, that have emerged in recent years. Finally, the challenges and future trends of using electrical stimulation therapy for accelerating bone healing are discussed.

Clinical application research of intelligent monitoring system for knee rehabilitation: a randomized controlled trial.

BACKGROUND: This study investigates the effectiveness of a self-developed intelligent monitoring system for home-based knee rehabilitation following total knee arthroplasty (TKA). METHODS: In this randomized controlled trial, 120 patients undergoing TKA were divided using random digit allocation. Preoperative and one-month postoperative assessments of knee function, quality of life, and isometric knee extension strength were conducted with the Intelligent Monitoring System. Patients received group-specific rehabilitation instructions pre-discharge and performed exercises for one month. RESULTS: Changes in isometric knee extensor strength on the affected side within one month post-surgery for the brace-monitored rehabilitation group showed a significant decrease three days after surgery compared to one day before surgery. Subsequent measurements taken at postoperative days 5, 7, 14, and 21 indicated a gradual increase in strength, although these increases did not reach statistical significance when compared with previous measurements. One month post-surgery, all groups demonstrated significant improvements in knee joint function and mobility compared to pre-surgery levels. Notably, the brace-monitored group showed statistically significant improvements in 36-Item Short-Form Health Survey (SF-36) scores over the conventional rehabilitation group. CONCLUSIONS: The Intelligent Monitoring System provides effective real-time monitoring and guidance for home-based knee rehabilitation post-TKA. It significantly enhances knee joint function, isometric knee extension strength, and quality of life shortly after surgery compared to traditional rehabilitation methods. This system offers a promising approach for improving postoperative recovery in TKA patients. TRIAL REGISTRATION: This study was approved by the Medical Ethics Committee of Xiangya Hospital, Central South University (Ethics Approval Number 202209008-2). It was registered with the China Clinical Trial Registry, a primary registry of the World Health Organization's International Clinical Trials Registry Platform (Registration Number ChiCTR2300068852).

Elevated Fibrinogen-to-Albumin Ratio Correlates with Incident Stroke in Cerebral Small Vessel Disease.

Purpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients. Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients. Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0-53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043-1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063-1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06-1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05-1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age. Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.

Is unicompartmental knee arthroplasty a better choice than total knee arthroplasty for unicompartmental osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs. total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.00001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.02), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.00001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.01) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P = 0.0002) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS: In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.

Causal Relationship between Gut Microbiota, Metabolites, and Sarcopenia: A Mendelian Randomization Study.

BACKGROUND: Gut microbiota imbalance and sarcopenia are frequently observed in the elderly population. Gut Microbiota and their metabolites are considered risk factors contributing to the heightened risk of sarcopenia, but whether these associations are causal remains unclear. METHODS: We conducted linkage disequilibrium score regression and two-sample Mendelian randomization methods with SNPs sourced from large-scale genome-wide association studies as instrumental variables to examine the causal associations linking gut microbiota with their metabolites to the sarcopenia. Following the MR analysis, subsequent sensitivity analyses were conducted to reinforce the robustness and credibility of the obtained results. RESULTS: MR analysis yielded compelling evidence demonstrating the correlation between genetically predicted gut microbiota and metabolites and the risk of sarcopenia. The abundance of Porphyromonadaceae, Rikenellaceae, Terrisporobacter, and Victivallis was found to be associated with WP. Our study also found suggestive associations of 12 intestinal bacteria with ALM, and of Streptococcaceae, Intestinibacter, Paraprevotella, Ruminococcaceae UCG009, and Sutterella with GS. Specifically, we identified 21 gut microbiota-derived metabolites that may be associated with the risk of sarcopenia. CONCLUSIONS: Utilizing a two-sample MR approach, our study elucidates the causal interplay among gut microbiota, gut microbiota-derived metabolites, and the occurrence of sarcopenia. These findings suggest that gut microbiota and metabolites may represent a potential underlying risk factor for sarcopenia, and offer the promise of novel therapeutic focal points.

B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review.

This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well-developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Rice bran active peptide (RBAP) inhibited macrophage differentiation to foam cell and atherosclerosis in mice via regulating cholesterol efflux.

BACKGROUND: Atherosclerosis is a long-lasting inflammatory condition affecting the walls of arteries, marked by the buildup of fats, plaque formation, and vascular remodeling. Recent findings highlight the significance of cholesterol removal pathways in influencing atherosclerosis, yet the connection between cholesterol removal and regulation of macrophage inflammation remains poorly understood. RBAP could serve as an anti-inflammatory agent; however, its role in atherosclerosis and the mechanism behind it are still not well understood. PURPOSE: The objective of this research is to explore how RBAP impacts cholesterol efflux, which is a considerable element in the advancement of atherosclerosis. METHODS: An atherosclerosis mouse model was established by using an ApoE KO strain mouse on a high-fat diet (HFD) to assess the effects of RBAP, conducted either orally or through injection. Additionally, in vitro experiments were conducted where the induction of THP-1 cells was conducted for the differentiation towards macrophages, and along with mouse RAW264.7 cells, were challenged with ox-LDL to evaluate the impact of RBAP. RESULTS: In this study, RBAP was found to reduce the production and downregulate TNF-α, IL-1ß, and IL-6 levels and inhibited the activation of the TLR4/MyD88/NF-κB signaling in atherosclerosis model mice, as well as in ox-LDL-challenged THP-1 cells and mouse RAW264.7 macrophages. RBAP's effectiveness also improved the enhancement of reverse cholesterol transport (RCT) and cholesterol removal to HDL and apoA1 by increasing the activity of genes related to cholesterol removal PPARγ/LXRα/ABCA1/ABCG1, both in ApoE-/- mice and in THP-1 cells and mouse RAW264.7 macrophages. Notably, RBAP exerted similar effects on atherosclerosis model mice and macrophages to those of TAK-242, an inhibitor of the TLR4 signaling. When RBAP and TAK-242 were applied simultaneously, the improvement was not enhanced compared with either RBAP or TAK-242 treatment alone. CONCLUSION: These findings suggest that RBAP, as a TLR4 inhibitor, has anti-atherosclerotic effects by improving inflammation and promoting cholesterol effection, indicating its therapeutic potential in intervening atherosclerosis.

Deciphering the Atomic-Scale Structural Origin for Photoluminescence Quenching in Tin-Lead Alloyed Perovskite Nanocrystals.

The development of tin-lead alloyed halide perovskite nanocrystals (PNCs) is highly desirable for creating ultrastable, eco-friendly optoelectronic applications. However, the current incorporation of tin into the lead matrix results in severe photoluminescence (PL) quenching. To date, the precise atomic-scale structural origins of this quenching are still unknown, representing a significant barrier to fully realizing the potential of these materials. Here, we uncover the distinctive defect-related microstructures responsible for PL quenching using atomic-resolution scanning transmission electron microscopy and theoretical calculations. Our findings reveal an increase in point defects and Ruddlesden-Popper (RP) planar faults with increasing tin content. Notably, the point defects include a spectrum of vacancies and previously overlooked antisite defects with bromide vacancies and cation antisite defects emerging as the primary contributors to deep-level defects. Furthermore, the RP planar faults exhibit not only the typical rock-salt stacking pattern found in pure Pb-based PNCs but also previously undocumented microstructures rich in bromide vacancies and deep-level cation antisite defects. Direct strain imaging uncovers severe lattice distortion and significant inhomogeneous strain distributions caused by point defect aggregation, potentially breaking the local force balance and driving RP planar fault formation via lattice slippage. Our work illuminates the nature and evolution of defects in tin-lead alloyed halide perovskite nanocrystals and their profound impact on PL quenching, providing insights that support future material strategies in the development of less toxic tin-lead alloyed perovskite nanocrystals.

Obesity induces osteoimmunology imbalance: Molecular mechanisms and clinical implications.

The notion that obesity can be a protective factor for bone health is a topic of ongoing debate. Increased body weight may have a positive impact on bone health due to its mechanical effects and the production of estrogen by adipose tissue. However, recent studies have found a higher risk of bone fracture and delayed bone healing in elderly obese patients, which may be attributed to the heightened risk of bone immune regulation disruption associated with obesity. The balanced functions of bone cells such as osteoclasts, osteoblasts, and osteocytes, would be subverted by aberrant and prolonged immune responses under obese conditions. This review aims to explore the intricate relationship between obesity and bone health from the perspective of osteoimmunology, elucidate the impact of disturbances in bone immune regulation on the functioning of bone cells, including osteoclasts, osteoblasts, and osteocytes, highlighting the deleterious effects of obesity on various diseases development such as rheumatoid arthritis (RA), osteoarthritis (AS), bone fracture, periodontitis. On the one hand, weight loss may achieve significant therapeutic effects on the aforementioned diseases. On the other hand, for patients who have difficulty in losing weight, the osteoimmunological therapies could potentially serve as a viable approach in halting the progression of these disease. Additional research in the field of osteoimmunology is necessary to ascertain the optimal equilibrium between body weight and bone health.

Core decompression combined with bone marrow mononuclear cells in the treatment of femoral head necrosis: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of bone marrow mononuclear cells combined with core decompression in the treatment of femoral head necrosis is controversial. The purpose of this study was to conduct a meta-analysis and systematic review of the evaluation of bone marrow mononuclear cells combined with core decompression in the treatment of femoral head necrosis, and to compare the therapeutic effect of this method with that of core decompression alone, so as to provide a basis for subsequent research and clinical treatment. METHODS: We conducted detailed searches across four databases in Embase, PubMed, Web of Science, and the Cochrane Library (up to October 2023), including eight studies with a total of 370 participants and 491 hip cases. This meta-analysis followed the Preferred Reporting Project (PRISMA) guidelines. Review Manager 5.4 was used to summarize and analyze the outcome indicators and the quality and reliability of the MAs were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). RESULTS: Eight studies were included inclusion criteria. The results of meta-analysis showed that the therapeutic effect of CD combined with BMMC on VAS was better than that of CD alone (MD =-5.32, 95%CI: -9.90, -0.74, P=0.02, I²=98%), and there was no statistically significant difference between CD combined with BMMC and CD alone in the treatment of HHS (MD =2.73, 95%CI: -2.63,8.09, P=0.32, I²=82%). We conducted sensitivity analysis, the results showed that CD joint BMMC treatment effect on the HHS is superior to the single CD (MD = 5.57, 95% CI: 1.94, 9.20, P = 0.003, I squared = 0%), both no significant differences in VAS (MD = 0.47, 95% CI: -1.74, 0.79, P=0.46, I²=83%). CONCLUSION: In this study, we found that core decompression combined with bone marrow monocyte therapy improved femoral head necrosis better than core decompression alone.

Efficacy and safety of zoledronic acid in the treatment of osteoporosis: A meta-analysis of randomized controlled trials.

Purpose: Zoledronic acid can inhibit the activity of osteoclasts, and thus, may slow or inhibit bone loss. The purpose of this study was to systematically evaluate the efficacy and safety of zoledronic acid in the treatment of osteoporosis. Methods: Four databases, PubMed, Embase, Cochrane Library, and Web of Science, were systematically searched up to December 26, 2022. The primary outcomes included bone mineral density (BMD), carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal prope-ptide (P1NP), adverse events, and fracture. Secondary outcomes included serum sclerostin level, Visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI). Results: A total of 22 randomized controlled trials were included in this meta-analysis. Meta-analysis results showed that zoledronic acid was effective in increasing BMD of the lumbar spine, femoral neck, trochanter and serum sclerostin level; and reduced CTX, BSAP, P1NP, VAS score, and ODI in patients with osteoporosis. Regarding safety, zoledronic acid could reduce the incidence of fractures but had relatively more adverse events. Conclusion: Zoledronic acid can significantly improve BMD of the lumbar spine, femoral neck and trochanter, and effectively reduce incidence of fracture in patients with osteoporosis, thereby significantly improving patients' quality of life. However, the incidence of adverse events was higher than that of patients treated with placebo.

Extracorporeal shock wave therapy with imaging examination for early osteonecrosis of the femoral head: a systematic review.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) is a traditional non-invasive therapy to treat osteonecrosis of the femur head (ONFH). This systematic review aims to investigate whether ESWT can improve the clinical function of ONFH and whether differences in improvement can be observed in radiographic outcomes. MATERIALS AND METHODS: Two authors independently searched PubMed, Embase, Cochrane Library, and Web of Science for English articles until October 21, 2023. After screening and reading the literature, the two authors independently used corresponding scales to evaluate the quality of the included articles and extracted data. The key data extracted included the Harris Hip Score (HHS), Visual Analog Scale (VAS), changes in lesion size, the change in the Association Research Circulation Osseous (ARCO) stage, and bone marrow edema stage. RESULTS: Nine articles included 468 males and 248 females. The average age was 43.29 years and the mean follow-up time was 15.19 months. After receiving ESWT, five studies involving 146 hips showed a higher HHS (MD=-33.38; 95%CI, -46.31, -20.45), and the difference was statistically significant (P<0.00001). The average VAS before treatment was above 5, but it dropped to 1.2 after ESWT (MD=4.64; 95%CI, 3.63, 5.64), and the difference was statistically significant (P<0.00001). Three studies found no significant differences in the areas of femoral head necrosis before and after treatment with ESWT(MD=9.66; 95%CI, -0.36, 19.67; P=0.06; I2=84%). Two articles showed that the use of ESWT had no significant effect on the change in the ARCO stage (MD=1.11; 95%CI, 0.76, 1.62; P=0.60; I2=0%). Three studies indicated that using ESWT could improve the bone marrow edema symptom in the early stage of ONFH (MD=4.35; 95%CI, 1.32, 14.37; P=0.02; I2=62%). CONCLUSION: Based on the current evidence, ESWT shows promise as a therapy to enhance hip function and alleviate pain in the early stage of ONFH. With the advancement of more precise imaging techniques, ESWT can potentially reduce the area affected by ONFH. However, such reduction was not found to be statistically significant at the imaging level. Additionally, ESWT could improve symptoms of bone marrow edema in the early stage. However, no significant change in ARCO grade was observed with ESWT treatment.

Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family.

Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.

Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications.

SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets.

Sarcopenia is an aging-related skeletal disease characterized by decreased muscle mass, strength, and physical function, severely affecting the quality of life (QoL) of the elderly population. Sirtuin 1 (SIRT1), as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, has been reported to participate in various aging-related signaling pathways and exert protective effect on many human diseases. SIRT1 functioned as an important role in the occurrence and progression of sarcopenia through regulating key pathways related to protein homeostasis, apoptosis, mitochondrial dysfunction, insulin resistance and autophagy in skeletal muscle, including SIRT1/Forkhead Box O (FoxO), AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor κB (NF-κB), SIRT1/p53, AMPK/SIRT1/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and SIRT1/live kinase B1 (LKB1)/AMPK pathways. However, the specific mechanisms of these processes have not been fully illuminated. Currently, several SIRT1-mediated interventions on sarcopenia have been preliminarily developed, such as SIRT1 activator polyphenolic compounds, exercising and calorie restriction. In this review, we summarized the predominant mechanisms of SIRT1 involved in sarcopenia and therapeutic modalities targeting the SIRT1 signaling pathways for the prevention and prognosis of sarcopenia.

Identifying novel proteins for migraine by integrating proteomes from blood and CSF with genome-wide association data.

BACKGROUND: Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co-localization analysis methods. METHODS: We utilized cis-protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co-localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins. RESULTS: We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955-0.981, p = 1.27 × 10-6) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024-1.065, p = 1.08 × 10-5) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946-0.982, p = 8.74 × 10-5) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies. CONCLUSIONS: We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms.

Acute anterior cruciate ligament rupture: can repair become an alternative to reconstruction: a meta-analysis of randomized controlled trials and cohort studies.

PURPOSE: To perform a meta-analysis to compare clinical outcomes of anterior cruciate ligament (ACL) repair and ACL reconstruction for acute ACL rupture. METHOD: We searched Pubmed, Embase, the Cochrane Library, and Web of Science databases to seek relevant studies. Clinical outcomes included failure rate, hardware removal rate, anteroposterior (AP) knee laxity, and patient-reported outcomes. In addition, subgroup analysis was carried out according to repair techniques, rupture locations, and study designs. Funnel plots were used to detect publication bias. All statistical analysis was performed using STATA (version 14.2, StataCorp). RESULTS: A total of 10 articles were included in this study, comprising 5 randomized controlled trials (RCTs) and 5 cohort studies, involving a total of 549 patients. We found no statistical differences between the ACL repair and ACL reconstruction in the following outcomes: failure rate, AP knee laxity, International Knee Documentation Committee (IKDC) score, Lysholm score, Knee Injury and Osteoarthritis Outcome (KOOS) Score, and Tegner score. However, the ACL repair group had a higher hardware removal rate. Except for AP knee laxity results on different repair techniques, there was no statistical difference in other subgroup analyses. CONCLUSION: Compared with ACL reconstruction, ACL repair shows similar results in clinical outcomes, and it is promising to be an effective alternative treatment for acute ACL rupture. Larger samples and higher-quality studies are needed to support our results and further explore the advantages of ACL repair in other aspects. LEVEL OF EVIDENCE: Level III.