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Objective: The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis. Methods: A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1-34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment. Results: Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01-0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00-0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1-34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32-2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45-0.072), with no significant difference observed in mortality rates between treatment and control groups. Conclusion: Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.

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The NRF2 pathway is a metabolic- and redox-sensitive signaling axis in which the transcription factor controls the expression of a multitude of genes that enable cells to survive environmental stressors, such as oxidative stress, mainly by inducing the expression of cytoprotective genes. Basal NRF2 levels are maintained under normal physiological conditions, but when exposed to oxidative stress, cells activate the NRF2 pathway, which is crucial for supporting cell survival. Recently, the NRF2 pathway has been found to have novel functions in metabolic regulation and interplay with other signaling pathways, offering novel insights into the treatment of various diseases. Numerous studies have shown that targeting its pathway can effectively investigate the development and progression of age-related musculoskeletal diseases, such as sarcopenia, osteoporosis, osteoarthritis, and intervertebral disc degeneration. Appropriate regulation of the NRF2 pathway flux holds promise as a means to improve musculoskeletal function, thereby providing a new avenue for drug treatment of age-related musculoskeletal diseases in clinical settings. The review summarized an overview of the relationship between NRF2 and cellular processes such as oxidative stress, apoptosis, inflammation, mitochondrial dysfunction, ferroptosis, and autophagy, and explores the potential of targeted NRF2 regulation in the treatment of age-related musculoskeletal diseases.

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Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration, subchondral sclerosis, synovitis, and osteophyte formation. OA is associated with disability and impaired quality of life, particularly among the elderly. Leptin, a 16-kD non-glycosylated protein encoded by the obese gene, is produced on a systemic and local basis in adipose tissue and the infrapatellar fat pad located in the knee. The metabolic mechanisms employed by leptin in OA development have been widely studied, with attention being paid to aging as a corroborative risk factor for OA. Hence, in this review, we have attempted to establish a potential link between leptin and OA, by focusing on aging-associated mechanisms and proposing leptin as a potential diagnostic and therapeutic target in aging-related mechanisms of OA that may provide fruitful guidance and emphasis for future research.

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BACKGROUND: The positioning error of femoral tunnel was the key factor leading to the failure of anterior cruciate ligament (ACL) reconstruction. This study aimed to propose a new femoral tunnel classification to guide revision ACL reconstruction. METHODS: Totals of 150 patients with ACL reconstruction failure from 2017 to 2023 were enrolled in this retrospective study. According to the tunnel diameter, shape, posterior wall and the positioning relationship with the Lateral Intercondylar Ridge on the three-dimensional CT imaging, we divided the femoral tunnels into four types: Type I off-target type, Type II straddled type, Type III anatomical type, and Type IV irregular type. Finally, explored the inter-observer reliability within two groups of doctors (Group A, 12 high seniorities; Group B, 12 low seniorities), and evaluated the intra-observer reliability within 6 doctors after two months. Clinical evaluation was performed using the Lysholm score, Tenger activity score, Pivot Shift and anterior knee laxity measurements. RESULTS: Among 150 cases of femoral tunnel three-dimensional CT reconstructed imaging, 144 cases were successfully included in the classification system, and 6 cases were confirmed as uncertain type. We measured the Kappa (κ) coefficient of group A was significantly higher than that of group B (κ 0.72 VS 0.68), and the κ coefficient of group A was still higher than group B (κ 0.69 VS 0.62) after further dividing Type III anatomical type into three subtypes. In addition, the κ coefficients of intra-observer reliability were all exceeded 0.73. Clinical follow-up showed that 9 patients had good knee joint motor function and stability after operation. CONCLUSION: The new femoral tunnel classification was reliable and had clinical guiding significance based on three-dimensional CT imaging. LEVEL OF EVIDENCE: Level III.

Asunto(s)

Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Fémur , Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Humanos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Femenino , Masculino , Fémur/diagnóstico por imagen , Fémur/cirugía , Estudios Retrospectivos , Adulto , Imagenología Tridimensional/métodos , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Adulto Joven , Reoperación , Reproducibilidad de los Resultados , Ligamento Cruzado Anterior/cirugía , Ligamento Cruzado Anterior/diagnóstico por imagen , Persona de Mediana Edad , Adolescente , Variaciones Dependientes del Observador , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Insuficiencia del Tratamiento

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BACKGROUND: Osteoporosis, a systemic skeletal disease, seriously affects the quality of life in postmenopausal women. As one type of cathepsin K (CatK) inhibitor, odanacatib (ODN) is a fresh medication for osteoporosis. Considering the potential of ODN, we further examined the effect and safety of ODN for postmenopausal osteoporosis (PMOP) with a meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for eligible studies from inception to December 29th, 2023. After that, we conducted a comprehensive meta-analysis following PRISMA guidelines. Risk of bias was meticulously investigated with the Cochrane Collaboration's tool. Efficacy was assessed with bone mineral density (BMD) at different sites (lumbar spine, trochanter, radius, femoral neck) and biomarkers of bone turnover (P1NP, uNTx/Cr, s-CTx, BSAP). Safety was evaluated by analyzing total, serious, other, and skin adverse events (AEs). RESULTS: Four random clinical trials (RCTs) were involved in our research. All trials were rated as having high quality and met the eligibility criteria. In the current research, ODN was found to elevate BMD at lumbar spine, femoral neck, total hip, trochanter and forearm, while it decreased the levels of serum C-telopeptides of type I collagen (s-CTx) as well as urinary N-telopeptide/creatinine ratio (uNTx/Cr). No significant differences were observed in AEs between the ODN group and the control group. CONCLUSIONS: ODN is a promising alternative for the treatment of PMOP on account of its excellent efficacy and credible safety. Unclear links between ODN and cardiovascular AEs require further research to clarify.

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Compuestos de Bifenilo , Densidad Ósea , Osteoporosis Posmenopáusica , Humanos , Femenino , Osteoporosis Posmenopáusica/tratamiento farmacológico , Densidad Ósea/efectos de los fármacos , Resultado del Tratamiento , Compuestos de Bifenilo/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Biomarcadores/sangre , Catepsina K/antagonistas & inhibidores , Persona de Mediana Edad , Anciano , Remodelación Ósea/efectos de los fármacos

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BACKGROUND: Serum fibrinogen/albumin ratio (FAR) is a new inflammatory marker related to a variety of diseases, and it has been shown to be associated with stroke. This study is to investigate the relationship between serum FAR and early neurological deterioration (END) in patients with recent small subcortical infarction (RSSI). PATIENTS AND METHODS: Consecutive RSSI patients admitted to the First Affiliated Hospital of Zhengzhou University from June 2015 to June 2022 were enrolled. The National Institute of Health Stroke Scale (NIHSS) was utilized to evaluate the severity of the patients at admission and within seven days post-admission. END was defined as an increase of ≥2 points in NIHSS score from admission or ≥1 point in the motor item of the score within seven days post-admission. Multivariate logistic regression analysis was employed to identify risk factors for END. The correlation between FAR and END was investigated using restricted cubic spline (RCS) analysis. Subgroup analysis was used to assess stability across different populations. RESULTS: A total of 766 RSSI patients were included in the analysis, with 538 males (70.24%). END occurred in 115 (15.01%) patients. Multivariate logistic regression analysis revealed that FAR (OR = 1.016, 95%CI: 1.005-1.028), PAD (OR = 1.805, 95%CI: 1.161-2.807) and age (OR = 1.028, 95%CI: 1.009-1.048) were associated with END in RSSI patients. RCS analysis indicated a linear correlation between FAR and END (p for nonlinear = .128). Subgroup analysis indicated association between FAR and END in male (OR = 1.02, 95%CI: 1.00-1.03), patients aged ≤65 years (OR = 1.02, 95%CI: 1.00-1.03) and patients without smoking history (OR = 1.02, 95%CI: 1.00-1.03). CONCLUSIONS: Elevated FAR levels were associated with the occurrence of END within seven days after admission in RSSI patients, especially in men, age ≤65 years, or patients without smoking history.

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Biomarcadores , Fibrinógeno , Humanos , Masculino , Femenino , Fibrinógeno/análisis , Fibrinógeno/metabolismo , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Factores de Riesgo , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Infarto Cerebral/sangre , Índice de Severidad de la Enfermedad , Modelos Logísticos

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BACKGROUND: Knee osteoarthritis (KOA) is a widespread chronic condition. Depression frequently occurs among patients with KOA. The objective of this meta-analysis was to identify risk factors associated with comorbid depression in patients with KOA. MATERIALS AND METHODS: A comprehensive search of the PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science databases was conducted for studies related to comorbid depression in patients with KOA. We conducted statistical analyses to obtain relevant results, followed by heterogeneity tests and assessment for publication bias. RESULTS: The prevalence of comorbid depression among patients with KOA was 34% (95% CI, 28%-41%). Notable risk factors linked to comorbid depression in patients with KOA included female sex (relative risk [RR], 1.17; 95% CI, 1.11-1.23), obesity (mean difference [MD], 1.30; 95% CI, 0.88-1.71), use of analgesics (RR, 1.50; 95% CI, 1.38-1.63), comorbidities (MD, 0.20; 95% CI, 0.10-0.31), unmarried or widowed status (RR, 1.72; 95% CI, 1.56-1.91), bilateral knee pain (RR, 1.38; 95% CI, 1.11-1.71), high total Western Ontario and Mc-Master Universities Arthritis Index (WOMAC) score (MD, 14.92; 95% CI, 10.02-19.82), high WOMAC pain score (MD, 5.76; 95% CI, 2.86-8.67), low gait velocity (MD, -0.12; 95% CI, -0.16 to -0.09), and extended duration in the Timed Up and Go Test (MD, 1.56; 95% CI, 0.87-2.25). CONCLUSION: Based on the current evidence, female sex, obesity, use of analgesics, comorbidities, unmarried or widowed status, bilateral knee pain, high total WOMAC score, high WOMAC pain score, low gait velocity, and prolonged time on the Timed Up and Go Test were identified as risk factors for depression in patients with KOA. Focus should be given to these aspects when preventing depression among these patients. [Orthopedics. 2024;47(5):e225-e232.].

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Depresión , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/epidemiología , Factores de Riesgo , Depresión/epidemiología , Comorbilidad , Prevalencia , Femenino , Obesidad/epidemiología , Obesidad/complicaciones

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BACKGROUND: Cerebral aneurysms are life-threatening cerebrovascular disorders. Currently, there are no effective treatments for preventing disease progression. Mendelian randomisation (MR) is widely used to repurify licensed drugs and identify new therapeutic targets. Therefore, this study aims to investigate effective drug targets for preventing the formation and rupture of cerebral aneurysms and analyse their potential mechanisms. METHODS: We performed a comprehensive study integrating two-sample MR analysis, colocalisation analysis and summary data-based Mendelian randomisation (SMR) to assess the causal effects of blood and brain druggable cis-expression quantitative trait loci (cis-eQTLs) on intracranial aneurysm (IA), unruptured intracranial aneurysm (UIA) and subarachnoid haemorrhage of IA rupture (SAH). Druggable genes were obtained from the study by Chris Finan et al, cis-eQTLs from the eQTLGen and PsychENCODE consortia. Results were validated using proteomic and transcriptomic data. Single-gene functional analyses probed potential mechanisms, culminating in the construction of a drug-gene regulation network. RESULTS: Through the MR analysis, we identified four potential drug targets in the blood, including prolylcarboxypeptidase (PRCP), proteasome 20S subunit alpha 4 (PSMA4), LTBP4 and GPR160 for SAH. Furthermore, two potential drug targets (PSMA4 and SLC22A4) were identified for IA and one potential drug target (KL) for UIA after accounting for multiple testing (P(inverse-variance weighted)<8.28e-6). Strong evidence of colocalisation and SMR analysis confirmed the relevance of PSMA4 and PRCP in outcomes. Elevated PRCP circulating proteins correlated with a lower SAH risk. PRCP gene expression was significantly downregulated in the disease cohort. CONCLUSIONS: This study supports that elevated PRCP gene expression in blood is causally associated with the decreased risk of IA rupture. Conversely, increased PSMA4 expression in the blood is causally related to an increased risk of IA rupture and formation.

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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.

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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).

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Artroplastia de Reemplazo de Rodilla , Calidad de Vida , Humanos , Artroplastia de Reemplazo de Rodilla/rehabilitación , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Fuerza Muscular , Resultado del Tratamiento , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentación , Terapia por Ejercicio/métodos , Terapia por Ejercicio/instrumentación , Recuperación de la Función

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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.

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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.

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Aterosclerosis , Diferenciación Celular , Colesterol , Células Espumosas , Macrófagos , Oryza , Receptor Toll-Like 4 , Animales , Aterosclerosis/tratamiento farmacológico , Ratones , Colesterol/metabolismo , Células Espumosas/efectos de los fármacos , Células Espumosas/metabolismo , Células RAW 264.7 , Diferenciación Celular/efectos de los fármacos , Humanos , Receptor Toll-Like 4/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Células THP-1 , Masculino , Dieta Alta en Grasa , Transportador 1 de Casete de Unión a ATP/metabolismo , Lipoproteínas LDL/metabolismo , Ratones Endogámicos C57BL , Péptidos/farmacología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Ratones Noqueados para ApoE , FN-kappa B/metabolismo , Apolipoproteínas E , Antiinflamatorios/farmacología

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BACKGROUND: Gut microbiota imbalance and sarcopenia are frequently observed in older adults. 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 2-sample Mendelian randomization (MR) methods with single-nucleotide polymorphisms 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 walking pace. Our study also found suggestive associations of 12 intestinal bacteria with appendicular lean mass, and of Streptococcaceae, Intestinibacter, Paraprevotella, Ruminococcaceae UCG009, and Sutterella with grip strength. Specifically, we identified 21 gut microbiota-derived metabolites that may be associated with the risk of sarcopenia. CONCLUSIONS: Utilizing a 2-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.

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Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Sarcopenia , Humanos , Sarcopenia/metabolismo , Sarcopenia/genética , Microbioma Gastrointestinal/genética , Anciano , Masculino , Factores de Riesgo , Femenino , Desequilibrio de Ligamiento

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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.

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Densidad Ósea , Remodelación Ósea , Fracturas Osteoporóticas , Complejo Vitamínico B , Humanos , Biomarcadores/sangre , Densidad Ósea/fisiología , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Remodelación Ósea/efectos de los fármacos , Suplementos Dietéticos , Ácido Fólico/uso terapéutico , Incidencia , Fracturas Osteoporóticas/prevención & control , Fracturas Osteoporóticas/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Vitamina B 12/uso terapéutico , Vitamina B 12/sangre , Vitamina B 6/uso terapéutico , Complejo Vitamínico B/uso terapéutico

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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.

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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.

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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.

RESUMEN

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.

RESUMEN

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.

RESUMEN

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.