Identification of four-gene signature to diagnose osteoarthritis through bioinformatics and machine learning methods.

BACKGROUND: Although osteoarthritis (OA) is one of the most prevalent joint disorders, effective biomarkers to diagnose OA are still unavailable. This study aimed to acquire some key synovial biomarkers (hub genes) and analyze their correlation with immune infiltration in OA. METHODS: Gene expression profiles and clinical characteristics of OA and healthy synovial samples were retrieved from the Gene Expression Omnibus (GEO) database. Hub genes for OA were mined based on a combination of weighted gene co-expression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF) algorithms. A diagnostic nomogram model for OA prediction was developed based on the hub genes. Receiver operating characteristic curves (ROC) were performed to confirm the abnormal expression of hub genes in the experimemtal and validation datasets. qRT-PCR using patients' samples were conducted as well. In addition, the infiltration level of 28 immune cells in the expression profile and their relationship with hub genes were analyzed using single-sample GSEA (ssGSEA). RESULTS: 4 hub genes (ZBTB16, TNFSF11, SCRG1 and KDELR3) were obtained by WGCNA, lasso, SVM-RFE, RF algorithms as potential biomarkers for OA. The immune infiltration analyses revealed that hub genes were most correlated with regulatory T cell and natural killer cell. CONCLUSION: A machine learning model to diagnose OA based on ZBTB16, TNFSF11, SCRG1 and KDELR3 using synovial tissue was constructed, providing theoretical foundation and guideline for diagnostic and treatment targets in OA.

Multiple Facial Basal Cell Carcinoma With Xeroderma Pigmentosum.

Multiple basal cell carcinomas are rare in children and adolescents. Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease characterized by photosensitivity, changes in skin pigmentation, and early onset of skin cancer. XP is extremely rare in clinical practice, with only a few cases worldwide. XP is clinically incurable. The main goal of treating this disease is to diagnose as early as possible, educate patients to strictly avoid ultraviolet radiation for life, and follow up regularly to treat skin malignant tumors in time. The authors report a 15-year-old boy with facial multiple basal cell carcinoma with XP. Its medical history, clinical features, auxiliary examination, and surgical treatment process have great reference value for the in-depth understanding of the disease. The authors will discuss how to delay the progression of the disease and treat the existing lesions in different clinical stages of the disease in combination with the existing relevant literature.

Outcomes of a novel all-inside arthroscopic anterior talofibular ligament repair for chronic ankle instability.

PURPOSE: This study aimed to introduce a novel all-inside arthroscopic anterior talofibular ligament (ATFL) repair for chronic ankle instability (CAI) with a knotless suture anchor technique-Hugging Repair, evaluate clinical outcomes, and analyze the associated risk factors. METHODS: A total of 84 patients (42 males and 42 females, mean age: 36.1 ± 11.2 years, range: 19-68 years) who underwent Hugging Repair from January 1, 2016 to December 31, 2018, were enrolled in this retrospective study. The American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), Foot and Ankle Outcome Score (FAOS), Tegner score, and Numerical Rating Scale (NRS) were evaluated pre-operatively and at final follow-up. The potential risk factors such as age, body mass index (BMI), sex, post-injury duration (time from injury to surgery), follow-up time, number of anchors, concomitant injuries [e.g., osteochondral defects (OCD), sinus tarsi syndrome (STS), anterior ankle impingement (AAI)], first-time treatment, and number of ankle sprains were also analyzed through multiple regression analysis. RESULTS: There were 68 (81%) patients followed up for a mean time of 42 (range: 35-50) months. The median AOFAS score increased from 65 (35-72) to 90 (77-100), KAFS increased from 64 (38-71) to 90 (62-100), FAOS increased from 68 (50-70) to 97 (68-100), Tegner score increased from 1 (1-3) to 4 (2-7), and NRS increased from 3.5 (2-5) to 1 (0-3). No correlation was found between the functional scores and risk factors mentioned above. In the multivariate model, age was significantly negatively associated with KAFS, FAOS, and Tegner activity scale (P = 0.013; P = 0.002; P = 0.000); female was significantly associated with poorer Tegner activity scale (P = 0.004); and the presence of concomitant injuries was significantly negatively associated with AOFAS score (P = 0.033). CONCLUSION: The novel all-inside arthroscopic ATFL repair for CAI with a knotless suture anchor technique-Hugging Repair is a safe and suitable technique that achieves satisfactory clinical outcomes and provides an effective option for the treatment of CAI. Risk factors for patients who underwent all-inside ATFL repair were older age, female sex, and concomitant injuries.

Hybrid 1D/3D-Structured Perovskite as a Highly Selective and Stable Sensor for NO2 Detection at Room Temperature.

To exploit high-performance and stable sensing materials with a room working temperature is pivotal for portable and mobile sensor devices. However, the common sensors based on metal oxide semiconductors usually need a higher working temperature (usually above 300 °C) to achieve a good response toward gas detection. Currently, metal halide perovskites have begun to rise as a promising candidate for gas monitoring at room temperature but suffer phase instability. Herein, we construct 1D/3D PyPbI3/FA0.83Cs0.17PbI3 (denoted by PyPbI3/FACs) bilayer perovskite by post-processing spin-coating Pyrrolidinium hydroiodide (PyI) salt on top of 3D FACs film. Benefitting from the 1D PyPbI3 coating layer, the phase stability of 1D/3D PyPbI3/FACs significantly improves. Simultaneously, the gas sensor based on the 1D/3D PyPbI3/FACs bilayer perovskite presents a superior selectivity and sensitivity toward NO2 detection at room temperature, with a low detection limit of 220 ppb. Exposed to a 50 ± 3% relative humidity (RH) level environment for a consecutive six days, the 1D/3D PyPbI3/FACs perovskite-based sensor toward 10 ppm NO2 can still maintain a rapid response with a slight attenuation. Gas sensors based on hybrid 1D/3D-structured perovskite in this work may provide a new pathway for highly sensitive and stable gas sensors in room working temperature, accelerating its practical application and portable device.

Robust Self-Supported SnO2-Mn2O3@CC Electrode for Efficient Electrochemical Degradation of Cationic Blue X-GRRL Dye.

Exploration of highly efficient and robust catalyst is pivotal for electrocatalytic degradation of dye wastewater, but it still is a challenge. Here, we develop a three-dimensional self-supported SnO2-Mn2O3 hybrid nanosheets grown on carbon cloth (noted by SnO2-Mn2O3@CC) electrode via a simple hydrothermal method and annealing treatment. Benefitting from the interlaced nanosheets architecture that enlarges the surface area and the synergetic component effect that accelerates the interfacial electronic transfer, SnO2-Mn2O3@CC electrode exhibits a superior electrocatalytic degradation efficiency for cationic blue X-GRRL dye in comparison with the single metal oxide electrode containing SnO2@CC and Mn2O3@CC. The degradation efficiency of cationic blue X-GRRL on SnO2-Mn2O3@CC electrode can reach up to 97.55% within 50 min. Furthermore, self-supported architecture of nanosheets on carbon cloth framework contributes to a robust stability compared with the traditional electrode via the multiple dip/brush coating accompanied by the thermal decomposition method. SnO2-Mn2O3@CC electrode exhibits excellent recyclability, which can still retain a degradation efficiency of 94.12% after six cycles. This work may provide a new pathway for the design and exploration of highly efficient and robust electrooxidation catalysts for dye degradation.

Does radiofrequency application improve function and reduce pain in patients with insertional Achilles tendinopathy? A retrospective study with a minimum 2-year follow-up.

This case series study aimed to investigate patients with insertional Achilles tendinopathy (IAT) who underwent radiofrequency (RF), how much do their patient-reported outcomes scores improve and what percentage return to sport, and what patient-related factors are associated with improved scores and increased odds of return to sport, at a minimum of 2-year follow-up. Between 2012 and 2018, 41 patients were followed up. The median Victorian Institute of Sports Assessment-Achilles (VISA-A) score increased from 20 (range, 3-62) to 97 (range, 53-100), the median 11-point visual analogue scale (VAS) reduced from 8 (range, 1-10) to 0 (range, 0-3) and the median Tenger score increased from 1 (range, 0-1) to 3 (range, 2-8). Thirty-eight (92.7%) patients returned to sports with a mean time of 11 ± 4.8 months. In linear regression analysis, age was significantly associated with return-to-sports outcome (b = -0.07, 95% CI = -0.13 to -0.02, p = 0.02), while in logistic regression, symptoms duration revealed a significant impact on pain presence (OR = 1.07, 95% CI = 1.01 to 1.14, p = 0.02). In summary, RF for IAT had a 68.7 ± 14.5 VISA-A improvement at 5.4 years of follow-up regarding reliable functional restoration and pain reduction; however, the current evidence remains insufficient to support RF as an effective treatment for IAT.

Genome-Wide Identification and Characterization of KNOTTED-Like Homeobox (KNOX) Homologs in Garlic (Allium sativum L.) and Their Expression Profilings Responding to Exogenous Cytokinin and Gibberellin.

Garlic (Allium sativum L.) is an important vegetable and is cultivated and consumed worldwide for its economic and medicinal values. Garlic cloves, the major reproductive and edible organs, are derived from the axillary meristems. KNOTTED-like homeobox (KNOX) proteins, such as SHOOT MERISTEM-LESS (STM), play important roles in axillary meristem formation and development. However, the KNOX proteins in garlic are still poorly known. Here, 10 AsKNOX genes, scattered on 5 of the 8 chromosomes, were genome-wide identified and characterized based on the newly released garlic genome. The typical conserved domains of KNOX proteins were owned by all these 10 AsKNOX homologs, which were divided into two Classes (Class I and Class II) based on the phylogenetic analysis. Prediction and verification of the subcellular localizations revealed the diverse subcellular localization of these 10 AsKNOX proteins. Cis-element prediction, tissue expression analysis, and expression profilings in responding to exogenous GA3 and 6-BA showed the potential involvement of AsKNOX genes in the gibberellin and cytokinin signaling pathways. Overall, the results of this work provided a better understanding of AsKNOX genes in garlic and laid an important foundation for their further functional studies.

[Effect of qubi recipe on changes of oxygen free radical metabolism and hypoxia-inducible factor-1alpha in collagen-induced arthritis rats].

OBJECTIVE: To observe the effect of Qubi Recipe (QR) on the expression of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and hypoxia-inducible factor (HIF)-1alpha in rats with type II collagen-I induced arthritis (CIA), and to explore its therapeutic roles and mechanism. METHODS: Totally 72 male SD rats of SPF grade were recruited. Twelve were randomly selected as the blank control group. The CIA model was established in the rest 60 rats by subcutaneously injecting type II collagen of bovine emulsion from the tail root and induction of incomplete Freund's adjuvant. On day 15 after primary immunization rats were randomly divided into four groups, i.e., the CIA model group, the Tripterygium Glycosides (TG) group (at the daily dose of 9.68 mg/kg body weight), the high dose QR group (at the daily dose of 6.66 g/kg body weight), and the low dose QR group (at the daily dose of 3.33 g/kg body weight), 15 in each group. Corresponding medication was given to rats in all groups by gastrogavage once daily for 4 successive weeks. An equal volume of pure water was given to rats in the blank control group and the CIA model group by gastrogavage, once daily for 4 successive weeks. The swelling degree of the joints was measured. Rats were sacrificed after 4-week treatment. Plasma levels of SOD, MDA, and GSH-Px were measured with colorimetric method. The expression of HIF-1alpha was detected by immunohistochemistry. RESULTS: (1) Compared with the CIA model group, the swelling degree of the joints was significantly alleviated in the TG group and the high dose QR group (P < 0.01, P < 0.05), and it was obviously milder in the high dose QR group than in the TG group (P < 0.05). (2) Compared with the CIA model group, the activities of GSH-Px could be obviously elevated and activities of MDA lowered in the TG group, the high dose QR group, and the low dose QR group (P < 0.05). Plasma activities of SOD could be obviously elevated in the high dose QR group and the TG group (P < 0.05). (3) Compared with the CIA model group, the expression of HIF-1alpha obviously decreased in the TG group and the high dose QR group (P < 0.05), and it showed a decreasing tendency in the low dose QR group with no statistical difference (P > 0.05). CONCLUSIONS: QR could markedly alleviate the swelling degree of ankle joints in CIA model rats. Its therapeutic efficacy was superior to that of TG. Its mechanism might be achieved through down-regulating expression of HIF-1alpha in the joint, and regulating activities of SOD, MDA and GSH-Px in the plasma.

Recent Advances in Bioelectronics for Localized Drug Delivery.

The last decade has witnessed remarkable advancements in bioelectronics, ushering in a new era of wearable and implantable devices for drug delivery. By utilizing miniaturized system design and/or flexible materials, bioelectronics illustrates ideal integration with target organs and tissues, making them ideal platforms for localized drug delivery. Furthermore, the development of electrically assisted drug delivery systems has enhanced the efficiency and safety of therapeutic administration, particularly for the macromolecules that encounter additional challenges in penetrating biological barriers. In this review, a concise overview of recent progress in bioelectronic devices for in vivo localized drug delivery, with highlights on the latest trends in device design, working principles, and their corresponding functionalities, is provided. The reported systems based on their targeted delivery locations as wearable systems, ingestible systems, and implantable systems are categorized. Each category is introduced in detail by highlighting the special requirements for devices and the corresponding solutions. The remaining challenges in this field and future directions are also discussed.

MiR-33a Overexpression Exacerbates Diabetic Nephropathy Through Sirt6-dependent Notch Signaling.

INTRODUCTION: Diabetic nephropathy (DN) belongs to the major cause of end-stage kidney disease. We probed the functions of a microRNA miR-33a in inducing podocytes injury during childhood  DN (CDN). METHODS: Kidney samples were collected from 20 children with DN. Matrix deposition and glomerular basement membranes thickness were examined by periodic acid-Schiff staining. Immunofluorescence staining was performed to assess kidney function-related proteins. MicroRNA (MiR)-33a mimic together with miR-33a inhibitor was transfected into podocytes for determining the roles of miR-33a. Glomerular podocyte apoptosis was determined by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining along with flow cytometry. RESULTS: Down-regulation of Nephrin and Podocin and increased podocyte apoptosis rate were observed in the glomerulus of CDN as well as podocytes treated with high glucose. MiR-33a was up regulated in the glomeruli and glucose-treated podocytes. Injury in podocytes was aggravated with miR-33a elevation but alleviated with miR-33a inhibition. Moreover, the expression of Sirtuin 6 (Sirt6) was decreased while the levels of notch receptor 1 (Notch1) and notch receptor 4 (Notch4) were elevated in the glomerulus and glucose-treated podocytes. Decreased level of Sirt6 upon glucose treatment was abrogated by miR-33a inhibition, and the podocytes injury induced by glucose exposure was relieved by Sirt6 via Notch signaling. CONCLUSION: These findings indicated that miR-33a promoted podocyte injury via targeting Sirt6-dependent Notch signaling in CDN, which might provide a novel sight for CDN treatment. DOI: 10.52547/ijkd.7904.

Predictive Modeling for Functional Outcomes After All-Inside Arthroscopic Anterior Talofibular Ligament Repair of Chronic Ankle Instability.

BACKGROUND: Arthroscopic anterior talofibular ligament repair (AATFLR) is a surgical strategy to treat chronic ankle instability (CAI) patients. This study identified risk factors that influenced the functional outcomes of AATFLR for CAI and developed prognostic nomogram for predicting functional outcomes in future AATFLR cases. METHODS: Patients undergoing AATFLR from January 2016 to June 2022 with at least 10 months of follow-up were included in the study. The Karlsson Ankle Functional Score (KAFS) was evaluated preoperatively and at last follow-up visit. A total of 15 potential predictors including age, sex, body mass index, side affected, time from injury to surgery, sports-related injury, osteophyte, loose bodies, distal tibiofibular syndesmosis, ATFL avulsion fracture, Outerbridge classification of osteochondral lesions, postoperative immobilization method, ambulation time, walking time, and follow-up time, were recorded. We first used univariate binary logistic regression analysis to select the potential significant prognostic features, which were then subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for final feature selection. A nomogram based on the regression model was developed to estimate the functional outcomes of patients. Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. RESULTS: Overall, 200 ankles fit inclusion criteria. Of these 200, a total of 185 (92.5%) ankles were eligible and divided into development (n = 121) and validation (n = 64) cohorts. Four predictors were ultimately included in the prognostic nomogram model: age, sex, sports-related injury, and postoperative immobilization method. CONCLUSION: We found in our cohort that the significant predictors of poorer functional outcomes of AATFLR were postoperative immobilization with lower-leg cast, female sex, non-sports-related ankle sprain, and increasing age. Prognostic nomograms were created.

Balance Error Scoring System in the assessment of chronic ankle stability: A systematic review and meta-analysis.

OBJECTIVE: Chronic ankle instability (CAI) is a common musculoskeletal injury associated with static balance deficits. The Balance Error Scoring System (BESS) is commonly used to assess static balance in individuals with CAI. However, the sensitivity of BESS in detecting balance deficits in CAI is unknown. This study compared BESS performance between people with CAI and controls and investigated which stances most effectively identified balance deficits in individuals with CAI. LITERATURE SURVEY: Seven electronic databases (Web of Science, CINAHL, Embase, PubMed, Scopus, SPORTDiscus, and Cochrane Library) were searched from July 13, 2023, to September 10, 2023, using the ankle instability and balance related terms as keywords to search original studies and perform a systematic review. METHODS: Studies that compared BESS scores between individuals with CAI and healthy controls were systematically identified. Extracted data included study characteristics, participant demographics, and assessment details. The risk of bias was assessed using the Newcastle-Ottawa Scale. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes to compare groups for the BESS components used to assess CAI. RESULTS: Six studies met the eligibility criteria. The double-leg foam stance yielded an SMD of -0.02 (95% CI: -0.32 to 0.29), with an I2 value of 3.5%. Significant differences between groups were noted in the single foam (SMD = 0.89; 95% CI: 0.33-1.45; I2 = 78.3%) and single firm (SMD = 0.62; 95% CI: 0.14-1.10; I2 = 72.1%) performances, although both demonstrated high heterogeneity. Conversely, the tandem foam (SMD = 0.77; 95% CI: 0.51-1.02; I2 = 0.0%) and tandem firm (SMD = 0.38; 95% CI: 0.11-0.68; I2 = 23.8%) performances showed small to moderate between-group differences with considerably lower heterogeneity. CONCLUSION: This review indicates that tandem stances on foam and firm surfaces in the BESS are reliable indicators of static balance deficits in individuals with CAI.

Capsular Repair Versus No Repair After Hip Arthroscopy in Patients Without Dysplasia or Generalized Ligamentous Laxity: A Systematic Review and Meta-analysis.

Background: Many recent studies have shown that patients who undergo capsular repair after hip arthroscopy achieve superior clinical outcomes compared with those who do not. However, patients with dysplasia or generalized ligamentous laxity (GLL) were not excluded from most of these studies, which may have affected the outcomes. Purpose: To determine whether capsular repair influences the outcomes of hip arthroscopy for patients without dysplasia or GLL. Study Design: Systematic review; Level of evidence, 1. Methods: Under the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, randomized controlled trials comparing the outcomes of capsulotomy with versus without repair were included, but studies that included patients with dysplasia or GLL were excluded. The study outcomes were patient-reported outcome measures (PROMs) at 6 months and 2 years postoperatively-including the modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sport-Specific Subscale (HOS-SSS)- and were compared between the repair and no-repair groups. A narrative analysis and meta-analysis were performed to integrate and compare the results of the 2 groups. In the meta-analysis of the outcome measures, studies with significant differences in the preoperative scores between the repair and no-repair groups were excluded because previous studies have shown that these can affect the outcomes. Results: A total of 761 studies were initially identified, of which 3 were included. Of the 322 included patients, 136 underwent capsular repair, and 186 underwent capsulotomy with no repair. The meta-analysis showed that capsular repair was associated with significantly higher postoperative PROMs: the mHHS at 2 years (P = .03), the HOS-ADL at 6 months (P = .02) and 2 years (P < .0001), and the HOS-SSS at 6 months (P = .02) and 2 years (P = .001). Conclusion: Capsular repair after hip arthroscopy was associated with superior clinical outcomes when compared with no capsular repair in patients without dysplasia or GLL.

Causal Relationships of Ligamentous Injuries in the Knee on Corticospinal Tract Structure: A Mendelian Randomization Analysis.

BACKGROUND: The association between ligamentous knee injuries and corticospinal tract (CST) structure has attracted attention; however, any causal relationship remains uncertain. We performed Mendelian randomization (MR) analysis to identify the causal effects of ligamentous knee injuries on the CST. HYPOTHESIS: Ligamentous knee injuries impair CST microstructure (ie, by reducing fractional anisotropy [FA] and increasing mean diffusivity [MD]). STUDY DESIGN: MR analysis. LEVEL OF EVIDENCE: Level 2. METHODS: MR uses genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Summary data for ligamentous injuries in knee and CST structure were obtained from genome-wide association study datasets. Significant and independent (5 × 10-6; r2 < 0.001; 10,000 kb) single-nucleotide polymorphisms were extracted for MR analysis. Three methods for MR analysis were used (hypothesis-driven 1-tailed inverse variance weighted, MR-Egger, and weighted median), and sensitivity analyses were conducted to test reliability and stability. RESULTS: Results from 3 MR methods consistently demonstrated that ligamentous knee injuries increased MD of the right CST (ß, 0.063; 90% CI, 0.003-0.123; P = 0.04), and weak statistical significance suggested increased MD of the left CST (ß, 0.060; 90% CI, -0.002 to -0.121; P = 0.05). However, no significant causal relationships were observed in CST FA, and no significant pleiotropy or heterogeneity was observed. Sensitivity analysis utilizing 2-tailed tests had no significant associations between ligamentous knee injuries and changes in CST structure. CONCLUSION: There is statistically weak genetic evidence that corticospinal pathway abnormalities may evolve after ligamentous knee injuries, which manifests as abnormally organized neurites. CLINICAL RELEVANCE: Ligamentous knee injuries require attention not only to damage to the structure of the knee joint itself but also to the process of maladaptive neuroplasticity that leads to structural and functional changes of the CST; novel interventions that target the corticospinal pathway may provide subsequent treatment of ligamentous knee injuries.

Combined Amniotic Membrane and Self-Powered Electrical Stimulator Bioelectronic Dress Promotes Wound Healing.

Human amniotic membranes (hAMs) are widely used as wound management biomaterials, especially as grafts for corneal reconstruction due to the structure of the extracellular matrix and excellent biological properties. However, their fragile nature and rapid degradation rate hinder widespread clinical use. In this work, we engineered a novel self-powered electronic dress (E-dress), combining the beneficial properties of an amniotic membrane and a flexible electrical electrode to enhance wound healing. The E-dress displayed a sustained discharge capacity, leading to increased epidermal growth factor (EGF) release from amniotic mesenchymal interstitial stem cells. Live/dead staining, CCK-8, and scratch-wound-closure assays were performed in vitro. Compared with amniotic membrane treatment alone, the E-dress promoted cell proliferation and migration of mouse fibroblast cells and lower cytotoxicity. In a mouse full-skin defect model, the E-dress achieved significantly accelerated wound closure. Histological analysis revealed that E-dress treatment promoted epithelialization and neovascularization in mouse skin. The E-dress exhibited a desirable flexibility that aligned with tissue organization and displayed maximum bioactivity within a short period to overcome rapid degradation, implying great potential for clinical applications.

Postural Control Deficits During Static Single-leg Stance in Chronic Ankle Instability: A Systematic Review and Meta-Analysis.

CONTEXT: Postural control deficits arising from injured ankles are central to chronic ankle instability (CAI) and its persistent symptoms. This is usually measured by recording the center of pressure (CoP) trajectory during static single-leg stance using a stable force plate. However, existing studies have produced conflicting results on whether this mode of measurement adequately reveals the postural deficits in CAI. OBJECTIVE: To determine whether postural control during static single-leg stance is impaired in CAI patients when compared with uninjured healthy controls. DATA SOURCES: Literature databases, PubMed, Embase, Web of Science, Cochrane Library, Scopus, CINAHL, and SPORTDiscus, were searched from inception to April 1, 2022, using ankle-, injury-, and posture-related terms. STUDY SELECTION: Two authors independently performed the step-by-step screening of article titles, abstracts, and full texts to select peer-reviewed studies investigating CoP trajectory during static single-leg stance using a stable force plate in CAI patients and healthy controls. A total of 13,637 studies were reviewed, and 38 studies (0.003%) met the selection criteria. STUDY DESIGN: Meta-analyses of descriptive epidemiological study. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: CoP parameters, sway directions, visual condition, and numerical data (means and standard deviations) were extracted. RESULTS: The injured ankles of CAI patients had higher standard deviations of sway amplitude in both anterior-posterior and medial-lateral directions (standardized mean difference [SMD] = 0.36 and 0.31, respectively) under conditions of open eyes than controls. Higher mean sway velocity in anterior-posterior, medial-lateral, and total directions (SMD = 0.41, 0.37, and 0.45, respectively) with closed eyes was also found. CONCLUSION: CAI patients had deficits of postural control during static single-leg stance, and these deficits were identified by the CoP trajectory. Further methodological explorations of CoP parameters and corresponding test conditions are required to enhance the sensitivity and reliability of postural deficit assessments in CAI using force plates.

In Vivo Characterization of Cerebellar Peduncles in Chronic Ankle Instability: A Single and Multishell Diffusion-Weighted Imaging Study.

BACKGROUND: Ankle sprain causes proprioceptor injuries and prolonged joint deafferentation, which might lead to maladaptive neuroplasticity in patients with chronic ankle instability (CAI), especially in the cerebellum. Previous studies have indicated the impairment of superior cerebellar peduncle (SCP), but the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) have not been fully analyzed. HYPOTHESIS: The cerebellar peduncles of participants with CAI would have altered fractional anisotropy (FA) and orientation dispersion index (ODI) in comparison with healthy controls without ankle injury history. In addition, FA and ODI would be correlated with the duration or severity of the sensorimotor deficits in CAI. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: A group of 27 participants with CAI and 26 healthy controls underwent diffusion-weighted imaging scanning, with the cerebellar peduncles as the regions of interest. The measures obtained by single-shell diffusion tensor imaging and the multishell neurite orientation dispersion and density imaging were used. Correlation analyses were performed to examine the potential relationship between the FA/ODI and both the normalized Y-balance scores and the durations of ankle instability. RESULTS: The ipsilateral ICP of the injured ankle in participants with CAI showed significantly lower FA (Cohen d 95% CI, -1.33 to -0.21; P = 0.04) and marginally significant higher ODI (Cohen d 95% CI, 0.10 to 1.20, P = 0.08) when compared with the same measures in the control group, with the ODI being positively correlated with the duration of ankle instability (r = 0.42, P = 0.03). CONCLUSION: The ICP in participants with CAI exhibited impaired integrity and a trend of abnormally organized neurites in comparison with a healthy control group. CLINICAL RELEVANCE: The impairments of ICP might be an ongoing part of the pathological process of CAI, having the potential to become a target for the diagnostic evaluation of this clinical entity.

Insufficient recovery of proprioception in chronic ankle instability after surgical restabilization: A systematic review.

Surgical repair or reconstruction of the lateral ligaments for patients with chronic ankle instability (CAI) could, logically, restore the proprioception of ankle through retensing receptors. To validate this hypothesis, seven databases were systematically searched, and thirteen studies comprising a total of 347 patients with CAI were included. Although five studies reported improved proprioceptive outcomes after surgeries, the other five studies with between-limb/group comparisons reported residual deficits at final follow-up, which does not consistently support proprioceptive recovery after existing surgical restabilization for CAI. More controlled studies are needed to provide evidence-based protocols to improve proprioceptive recovery after ankle restabilization for CAI.

Clinical Features Post Anterior Cruciate Ligament Reconstruction Associated with Structural Alterations in Corticospinal Tract.

CONTEXT: Structural evidence for corticospinal tract (CST) abnormality between patients with ACLR and healthy controls, and the relationships between CST structure and clinical features of the patients (e.g., objective sensorimotor outcomes, postoperative duration) are lacking. OBJECTIVES: To investigate whether the structural features of CST 1) differ between patients with ACLR and healthy controls, and 2) were associated with clinical features in patients following ACLR. DESIGN: Cross-sectional study. SETTING: Sports medicine laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-six patients who had undergone ACLR and twenty-six healthy controls were enrolled in this cross-sectional investigation. MAIN OUTCOME MEASURE(S): Using the CST as the region of interest, we performed diffusion tensor imaging to measure the microstructure of white matter tracts. Between-group comparisons and correlation analyses with clinical features in patients with ACLR were performed. RESULTS: The patients with ACLR showed significant, moderate lower fractional anisotropy (FA, Cohen's d = -0.666, 95% CIs -1.221 to -0.104), lower axial diffusivity (AD, Cohen's d = -0.526, 95% CIs -1.077 to 0.030), and higher radial diffusivity (RD, Cohen's d = 0.514, 95% CIs -0.042 to 1.064) when compared to that of healthy controls, with the RD values being significantly correlated with the postoperative duration (r = 0.623, p < 0.001) after controlling the age, sex, and BMI in patients with ACLR. CONCLUSIONS: This study revealed that patients with ACLR have impaired integrity (lower FA values and higher RD values) in the CST contralateral to the ACLR injured limb in comparison with healthy controls. Decreased integrity (higher RD) of the CST in patients was significantly associated with longer postoperative duration, which hinted that impaired structural integrity of the CST may be a maladaptive process of neuroplasticity in ACLR.

Association between Neural Plasticity and Pain-Related Fear in Chronic Ankle Instability: A Structural Neuroimaging Study.

CONTEXT: Pain-related movement fear is a contributing factor to residual pain and functional deficits in chronic ankle instability (CAI), but its underlying neural mechanisms remain unclear. OBJECTIVES: We aimed to (1) delineate whether participants with CAI exhibit discernible differences in specific emotion and pain-related brain regions, compared to a healthy control (HC) cohort and (2) explore potential neural mechanisms underlying pain and fear in participants with CAI, with an emphasis on investigating possible associations with pain-related neural plasticity. DESIGN: Cross-sectional study. SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: 28 participants with CAI (17males and 11 females; age: 31.28±6.31 years) and 28 HCs (16 males and 12 females; age: 30.18±7.59 years). MAIN OUTCOME MEASURE(S): We analyzed T1 structural imaging data from participants and assessed their fear of movement and pain intensity using the Tampa Scale for Kinesiophobia (TSK) and the Visual Analog Scale (VAS) for pain, respectively. We compared the mean gray matter (GM) density of pain-related area between the two groups and their correlations with the TSK and VAS scores. RESULTS: In comparison with the HC group, participants with CAI showed a significant decrease in the mean GM density in the prefrontal cortex (Cohen's d = -0.808) and periaqueductal gray (Cohen's d = -0.934). In participants with CAI, the mean GM density of the prefrontal cortex (PFC) was negatively correlated with the TSK scores (r = -0.531). During intense exercise, the mean GM density of the periaqueductal gray (PAG) was negatively correlated with the VAS scores (r = -0.484). Additionally, TSK scores were positively correlated with VAS scores (r = 0.455). CONCLUSIONS: Our exploratory findings suggest that, in participants with CAI, the atrophy of the PFC and PAG may be associated with pain-related fear. Future clinical diagnosis and treatment for CAI should consider the impact of psychological barriers on functional recovery.