Association between pain interference and motoric cognitive risk syndrome in older adults: a population-based cohort study.

OBJECTIVES: Motoric cognitive risk syndrome (MCR) is a pre-dementia condition characterized by subjective complaints in cognition and slow gait. Pain interference has previously been linked with cognitive deterioration; however, its specific relationship with MCR remains unclear. We aimed to examine how pain interference is associated with concurrent and incident MCR. METHODS: This study included older adults aged ≥ 65 years without dementia from the Health and Retirement Study. We combined participants with MCR information in 2006 and 2008 as baseline, and the participants were followed up 4 and 8 years later. The states of pain interference were divided into 3 categories: interfering pain, non-interfering pain, and no pain. Logistic regression analysis was done at baseline to examine the associations between pain interference and concurrent MCR. During the 8-year follow-up, Cox regression analysis was done to investigate the associations between pain interference and incident MCR. RESULTS: The study included 7120 older adults (74.6 ± 6.7 years; 56.8% females) at baseline. The baseline prevalence of MCR was 5.7%. Individuals with interfering pain had a significantly increased risk of MCR (OR = 1.51, 95% CI = 1.17-1.95; p = 0.001). The longitudinal analysis included 4605 participants, and there were 284 (6.2%) MCR cases on follow-up. Participants with interfering pain at baseline had a higher risk for MCR at 8 years of follow-up (HR = 2.02, 95% CI = 1.52-2.69; p < 0.001). CONCLUSIONS: Older adults with interfering pain had a higher risk for MCR versus those with non-interfering pain or without pain. Timely and adequate management of interfering pain may contribute to the prevention and treatment of MCR and its associated adverse outcomes.

Multiple reports on the causal relationship between various chronic pain and gut microbiota: a two-sample Mendelian randomization study.

Background: Previous evidence suggests a link between gut microbiota and chronic pain, but the causal relationship is not yet fully understood. Methods: We categorized gut microbiota based on phylum, class, order, family, and genus levels and gathered pain-related information from the UKB and FinnGen GWAS project. Then, we conducted MR analysis to explore the potential causal relationship between gut microbiota and chronic pain at 12 specific locations. Results: We have discovered a direct connection between genetic susceptibility in the gut microbiota (gut metabolites) and pain experienced at 12 specific locations. Notably, Serotonin (5-HT) and Glycine were found to be associated with a higher risk of pain in the extremities. On the other hand, certain microbial families and orders were found to have a protective effect against migraines. Specifically, the family Bifidobacteriaceae (IVW, FDR p = 0.013) was associated with a lower risk of migraines. Furthermore, the genus Oxalobacter (IVW, FDR p = 0.044) was found to be linked to an increased risk of low back pain. Importantly, these associations remained significant even after applying the Benjamini-Hochberg correction test. Our analysis did not find any heterogeneity in the data (p > 0.05), as confirmed by the Cochrane's Q-test. Additionally, both the MR-Egger and MR-PRESSO tests indicated no significant evidence of horizontal pleiotropy (p > 0.05). Conclusion: Our MR analysis demonstrated a causal relationship between the gut microbiota and pain, highlighting its potential significance in advancing our understanding of the underlying mechanisms and clinical implications of microbiota-mediated pain.

Identifying changes in dynamic plantar pressure associated with radiological knee osteoarthritis based on machine learning and wearable devices.

BACKGROUND: Knee osteoarthritis (KOA) is an irreversible degenerative disease that characterized by pain and abnormal gait. Radiography is typically used to detect KOA but has limitations. This study aimed to identify changes in plantar pressure that are associated with radiological knee osteoarthritis (ROA) and to validate them using machine learning algorithms. METHODS: This study included 92 participants with variable degrees of KOA. A modified Kellgren-Lawrence scale was used to classify participants into non-ROA and ROA groups. The total feature set included 210 dynamic plantar pressure features captured by a wearable in-shoe system as well as age, gender, height, weight, and body mass index. Filter and wrapper methods identified the optimal features, which were used to train five types of machine learning classification models for further validation: k-nearest neighbors (KNN), support vector machine (SVM), random forest (RF), AdaBoost, and eXtreme gradient boosting (XGBoost). RESULTS: Age, the standard deviation (SD) of the peak plantar pressure under the left lateral heel (f_L8PPP_std), the SD of the right second peak pressure (f_Rpeak2_std), and the SD of the variation in the anteroposterior displacement of center of pressure (COP) in the right foot (f_RYcopstd_std) were most associated with ROA. The RF model with an accuracy of 82.61% and F1 score of 0.8000 had the best generalization ability. CONCLUSION: Changes in dynamic plantar pressure are promising mechanical biomarkers that distinguish between non-ROA and ROA. Combining a wearable in-shoe system with machine learning enables dynamic monitoring of KOA, which could help guide treatment plans.

The impact of ankle-foot orthoses on mobility of dual-task walking in stroke patients? A cross-sectional two-factor factorial design clinical trial.

ABSTRACTTo assess the impact of ankle-foot orthoses (AFOs) on mobility and gait during dual-task walking in post-stroke survivors. In this cross-sectional, factorial design trial, stroke survivors performed four randomized tasks: (1) dual-task walking with AFOs, (2) single-task walking with AFOs, (3) dual-task walking without AFOs, and (4) single-task walking without AFOs. Primary outcome was the Timed Up and Go (TUG) test, with secondary outcomes including gait metrics, Tinetti scores, and auditory N-back tests. In the results, 48 subjects (38 males and 10 females; 19-65 years) completed the trial. Patients had a greater TUG score with AFOs compared with non-AFOs conditions (95% CI: 7.22-14.41, P < 0.001) in single-task and dual-task conditions. Secondary outcomes showed marked enhancement with AFOs during dual-task walking, with significant interaction effects in gait metrics, balance, and cognitive function (P < 0.05). Although not statistically significant, dual-task effects of TUG and walking speed were more pronounced during dual-task walking. In conclusion, AFOs enhance mobility and gait during both single and dual-task walking in post-stroke survivors.

BMSC-Exosomes attenuate ALP dysfunction by restoring lysosomal function via the mTOR/TFEB Axis to reduce cerebral ischemia-reperfusion injury.

BACKGROUND: The complex pathophysiological changes following cerebral ischemia-reperfusion injury (CIRI) include the accumulation of defective proteins and damaged organelles, which cause massive neuron demise. To preserve cellular homeostasis, the autophagy-lysosomal pathway (ALP) is crucial for neurons to dispose of these substances. Many studies have shown that bone mesenchymal stem cell exosomes (BMSC-Exos) can reduce CIRI. However, the specific mechanisms have not been well elucidated, a fact that limits its widespread clinical use. This study aimed to clarify whether BMSC-Exos could attenuate ALP dysfunction by restoring lysosomal function after CIRI via inhibiting mTOR and then activating TFEB nucleus translocation. METHODS: In this study, Flow cytometry, Nanoparticle tracking analysis (NTA), Transmission electron microscope (TEM), and Western blot were used to identify the BMSCs and BMSC-Exos used in this experiment as conforming to the requirements. In vivo experiments, SD rats were modeled with temporary middle cerebral artery occlusion (tMCAO), and BMSC-Exos was injected into the tail vein 2 h after modeling. Triphenyl tetrazolium chloride (TTC) staining, modified neurological severity scores (mNSS), corner turn test, and rotating rod test were used to detect neurological deficits in rats after BMSC-Exos intervention. Western blot and Immunofluorescence were used to detect ALP, transcription factor EB(TFEB) nucleus translocation, and mammalian target of rapamycin (mTOR) change at different time points after modeling and after BMSC-Exos intervention. In vitro experiments, pheochromocytoma cells (PC12) cells were subjected to oxygen-glucose deprivation and reperfusion (OGD/R) modeling to mimic CIRI, and were respectively intervened with BMSC-Exos, BMSC-Exos + MHY 1485 (the mTOR agonist), Rapamycin (the mTOR inhibitor). CCK8, Western blot, and Immunofluorescence were used to detect PC12 cell survival, TFEB nucleus translocation, and cathepsin B(CTSB) Immunofluorescence intensity. RESULTS: We found that ALP dysfunction occurred 72 h after tMCAO, and BMSC-Exos can attenuate ALP dysfunction by restoring lysosomal function. Next, we examined TFEB nucleus translocation and the expression of mTOR, a key regulator of translocation. We found that BMSC-Exos could inhibit mTOR and activate TFEB nucleus translocation. Additional in vitro tests revealed that BMSC-Exos could increase PC12 cell survival after OGD/R, activating TFEB nucleus translocation and enhancing the fluorescence intensity of CTSB, which in turn could be reversed by the mTOR agonist, MHY1485. This effect was similar to another mTOR inhibitor, Rapamycin. CONCLUSION: BMSC-Exos could attenuate ALP dysfunction by restoring lysosomal function after CIRI by inhibiting mTOR and then promoting TFEB nucleus translocation.

Genetic liability to frailty in relation to functional outcome after ischemic stroke.

BACKGROUND: Frailty appears to be associated with unfavorable prognosis after stroke in observational studies, but the causality remains largely unknown. AIMS: The aim of this study is to investigate the potential causal effect of frailty on functional outcome at 3 months after ischemic stroke using the Mendelian randomization (MR) framework. METHODS: Genetic instruments for frailty index were identified in a genome-wide association study meta-analysis including 175,226 individuals of European descent. Corresponding genetic association estimates for functional outcome after ischemic stroke at 90 days were taken from the Genetic of Ischemic Stroke Functional Outcome (GISCOME) network of 6021 patients. We performed inverse-variance weighted MR as the main analyses, followed by several alternate methods and sensitivity analyses. RESULTS: In univariable MR, we found evidence that genetically predicted higher frailty index (odds ratio (OR) = 5.12; 95% confidence interval (CI) = 1.31-20.09; p = 0.019) was associated with worse functional outcome (modified Rankin Scale score ⩾3) after ischemic stroke. In further multivariable MR adjusting for potential confounding traits including body mass index, C-reactive protein, inflammatory bowel disease, and smoking initiation, the overall patterns between genetic liability to frailty and poor functional outcome status remained. Sensitivity analyses with complementary methods and with model unadjusted for baseline stroke severity (OR = 4.19; 95% CI = 1.26-13.90; p = 0.019) yielded broadly concordant results. CONCLUSIONS: The present MR study suggested a possible causal effect of frailty on poor functional outcome after ischemic stroke. Frailty might represent a potential target for intervention to improve recovery after ischemic stroke.

Single-Cell RNA-Seq Reveals Changes in Cell Subsets in the Cortical Microenvironment during Acute Phase of Ischemic Stroke Rats.

BACKGROUND: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. METHODS: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. RESULTS: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0-3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. CONCLUSIONS: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.

Hybrid and adaptive control of functional electrical stimulation to correct hemiplegic gait for patients after stroke.

Introduction: Gait, as a fundamental human movement, necessitates the coordination of muscles across swing and stance phases. Functional electrical stimulation (FES) of the tibialis anterior (TA) has been widely applied to foot drop correction for patients with post-stroke during the swing phase. Although the gastrocnemius (GAS) during the stance phase is also affected, the Functional electrical stimulation of the gastrocnemius received less attention. Methods: To address this limitation, a timing- and intensity-adaptive Functional electrical stimulation control strategy was developed for both the TA and GAS. Each channel incorporates a speed-adaptive (SA) module to control stimulation timing and an iterative learning control (ILC) module to regulate the stimulation intensity. These modules rely on real-time kinematic or kinetic data during the swing or stance phase, respectively. The orthotic effects of the system were evaluated on eight patients with post-stroke foot drop. Gait kinematics and kinetics were assessed under three conditions: no stimulation (NS), Functional electrical stimulation to the ankle dorsiflexor tibialis anterior (SA-ILC DS) and FES to the tibialis anterior and the ankle plantarflexor gastrocnemius (SA-ILC DPS). Results: The ankle plantarflexion angle, the knee flexion angle, and the anterior ground reaction force (AGRF) in the SA-ILC DPS condition were significantly larger than those in the NS and SA-ILC DS conditions (p < 0.05). The maximum dorsiflexion angle during the swing phase in the SA-ILC DPS condition was similar to that in the SA-ILC DS condition, with both being significantly larger than the angle observed in the NS condition (p < 0.05). Furthermore, the angle error and force error relative to the set targets were minimized in the SA-ILC DPS condition. Discussion: The observed improvements can be ascribed to the appropriate stimulation timing and intensity provided by the SA-ILC DPS strategy. This study demonstrates that the hybrid and adaptive control strategy of functional electrical stimulation system offers a significant orthotic effect, and has considerable potential for future clinical application.

Cerebral Cortex Activation and Gait Performance between Healthy and Prefrail Older Adults during Cognitive and Walking Tasks.

Pre-frailty is a transitional stage between health and frailty. Previous studies have demonstrated that individuals with pre-frailty experience declines in cognitive and gait performances compared with healthy individuals. However, the basic neural mechanism underlying this needs to be clarified. In this cross-sectional study, twenty-one healthy older adults and fifteen with pre-frailty underwent three conditions, including a single cognitive task (SC), single walking task (SW), and dual-task (DT), while cortical hemodynamic reactions were measured using functional near-infrared spectroscopy (fNIRS). The prefrail group (PG) showed a significantly lower activation of the left dorsolateral prefrontal cortex (L-DLPFC) than the healthy group (HG) when performing SC (p < 0.05). The PG showed a significantly lower Timed Up and Go test and step speed than the HG during SW (p < 0.05). The coefficient of variation (CV) of the step length of the PG was significantly higher than that of the HG when performing DT (p < 0.05). No significant correlation in cerebral cortex activation and gait parameters in the HG when performing SW and DT was noted (p > 0.05). Participants of the PG with a higher oxygenated area in the left anterior prefrontal cortex (L-APFC) had a lower step frequency during SW (r = -0.533, p = 0.041), and so did the following indicators of the PG during DT: L-APFC and step speed (r = -0.557, p = 0.031); right anterior prefrontal cortex and step speed (r = -0.610, p = 0.016); left motor cortex and step speed (r = -0.674, p = 0.006); step frequency (r = -0.656, p = 0.008); and step length (r = -0.535, p = 0.040). The negative correlations between the cerebral cortex and gait parameters of the PG indicated a neural compensatory effect of pre-frailty. Therefore, older adults with pre-frailty promote prefrontal activation to compensate for the impaired sensorimotor systems.

Rippling Colloidal Polyelectrolyte Complex for Customized Fingerprints with High Tactile Perception.

Fingerprints possess wide applications in personal identification, tactile perception, access control, and anti-counterfeiting. However, latent fingerprints are usually left on touched surfaces, leading to the leakage of personal information. Furthermore, tactile perception greatly decreases when fingerprints are covered by gloves. Customized fingerprints are developed to solve these issues, but it is a challenge to develop fingerprints with various customized patterns using traditional techniques due to their requiring special templates, materials, or instruments. Inspired by ripples on the lake, blowing air is used to generate surface waves on a colloidal polyelectrolyte complex, leading to vertical stratification and the accumulation of particles near the top of the film layer. As water rapidly evaporates, the viscosity of these particles significantly increases and the wave is solidified, forming fingerprint patterns. These customized fingerprints integrate functions of grasping objects, personal identification without leaving latent fingerprints and tactile perception enhancement, which can be applied in information security, anti-counterfeiting, tactile sensors, and biological engineering.

Research hotspots and frotiers of stem cells in stroke: A bibliometric analysis from 2004 to 2022.

Background: Stroke is one of the leading causes of mortality and permanent disability worldwide. However, the current stroke treatment has a limited effect. Therefore, a new treatment is urgently needed. Stem cell therapy is a cutting-edge treatment for stroke patients. This study aimed to gain better understanding of global stem cell trends in stroke via a bibliometric analysis. Methods: We used the Web of Science Core Collection to search pertinent articles about stem cells in stroke published between 2004 and 2022. Analysis was conducted using CiteSpace, VOSviewer, and the R package "bibliometrix" to identify publication outputs, countries/regions, institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords. Results: A total of 6,703 publications were included in the bibliometric analysis. The total number of citations significantly and rapidly increased between 2004 and 2022, with the most pronounced growth pattern observed in the period of 2008-2009. In terms of authoritarian countries, the USA had the most publications among the countries. As for institutions and authors, the most prolific institution was the University of South Florida, followed by Oakland University and then Shanghai Jiao Tong University, and Chopp, M. and Borlongan, Cesario V, had the most output among the authors. Regarding the journals, Cell Transplantation had the highest publication, followed by Brain Research. As for references, "Mesenchymal stem cells as trophic mediators" was the most frequently cited (2,082), and the article entitled Neuronal replacement from endogenous precursors in the adult brain after stroke had the strongest burstiness (strength = 81.35). Emerging hot words in the past decade included "adhesion molecule," "mesenchymal stromal cell," "extracellular vesicle," "pluripotent stem cells," "signaling pathway," "plasticity," and "exosomes." Conclusion: Between 2004 and 2022, the terms "neurogenesis," "angiogenesis," "mesenchymal stem cells," "extracellular vesicle," "exosomes," "inflammation," and "oxidative stress" have emerged as the hot research areas for research on stem cells in stroke. Although stem cells exert a number of positive effects, the main mechanisms for mitigating the damage caused by stroke are still unknown. Clinical challenges may include complicating factors that can affect the efficacy of stem cell therapy, which are worth a deep exploration.

Pain-Related Risk Factors Among Radiologic Stages of Knee Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether risk factors related to pain vary at different stages of knee osteoarthritis (OA). METHODS: Individuals from the Osteoarthritis Initiative with available Kellgren/Lawrence (K/L) grade and numerical rating scale (NRS) data at baseline were included in this study. Pain severity was classified into 3 categories based on NRS scores: no pain, mild pain, and moderate/severe pain. Knee OA severity was stratified into 4 categories according to the K/L system. Pain risk factors were evaluated using generalized ordinal logistic regression analysis, and a heatmap was created to compare differences in standardized regression coefficients between subgroups of patients with different knee OA severities. RESULTS: A total of 4,446 subjects were included in this study: 1,574 individuals without pain (35.4%), 1,138 individuals with mild pain (25.6%), and 1,734 individuals with moderate/severe pain (39.0%). For the entire population and subjects in the premorbid-stage subgroup, knee injury history, diabetes mellitus, depression, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and valgus malaligned knees were associated with more severe pain. Older age and stronger quadriceps muscles were associated with milder pain. As the disease progressed, the number of significant risk factors decreased. Only age and quadriceps muscle force remained significant in end-stage disease. CONCLUSION: Multiple factors are associated with pain in patients with knee OA. As the disease progresses, the number of significant risk factors gradually reduces. These findings suggest that strategies for managing pain related to knee OA should vary depending on radiographic grades.

Injectable Supramolecular Hybrid Hydrogel Delivers IL-1ß-Stimulated Exosomes to Target Neuroinflammation.

Long-term neuroinflammation is a major barrier to neurological recovery after cerebral ischemia-reperfusion injury (CIRI). Here, a thermosensitive injectable supramolecular hybrid hydrogel is developed to sustainably deliver exosomes derived from interleukin-1ß-stimulated bone marrow stromal cells (BMSCs) (ßExos) with improved exosome production and anti-inflammatory capacity for neuroinflammation inhibition and neurological recovery. The supramolecular hydrogel displays self-healing and injectable features, along with high biocompatibility and tissue-like softness. The ßExos effectively reduce the lipopolysaccharide-induced inflammatory responses in the immortalized mouse microglia (BV2) cell line, and the in situ formed hydrogel improves the exosome retention in the ischemic core area. More remarkably, in the middle cerebral artery occlusion in vivo model, glial scar formation and neuronal loss are significantly reduced by regulating neuroinflammation using the released ßExos. Therefore, the combination of interleukin-1ß-stimulated exosomes with injectable supramolecular hydrogel provides an appealing strategy for treating central nervous system diseases.

The Association Between Quadriceps Strength and Synovitis in Knee Osteoarthritis: An Exploratory Study From the Osteoarthritis Initiative.

OBJECTIVE: The aim of this study was to explore the association between quadriceps strength and synovitis in knee osteoarthritis (KOA). METHODS: This study was derived from the Osteoarthritis Initiative (OAI), which recruited adults from the OAI cohort with or at risk of KOA. Knees with complete records of isometric quadriceps strength and effusion-synovitis and Hoffa-synovitis assessments were included. Quadriceps strength was measured isometrically at baseline. Effusion-synovitis and Hoffa-synovitis were measured using the Magnetic Resonance Imaging Osteoarthritis Knee Score at baseline and at 1-year and 2-year follow-ups. Generalized estimating equations were used to analyze the associations of baseline quadriceps strength with changes in effusion-synovitis and Hoffa-synovitis in multivariable analyses. Additionally, analyses were stratified by synovitis-driven inflammatory phenotypes. RESULTS: A total of 1513 knees were included in this study. In total, 61% of the subjects were female; subjects had an average age of 61.9 (SD 8.8) years and a mean BMI of 29.4 (SD 4.7). Regarding the whole population, baseline quadriceps strength was negatively associated with baseline effusion-synovitis and follow-up changes in effusion-synovitis (odds ratio [OR] 0.77-0.86), but no significant association was observed in terms of Hoffa-synovitis. Stratified by synovitis-driven inflammatory phenotype, baseline quadriceps strength was significantly associated with follow-up changes in effusion-synovitis-but not in Hoffa-synovitis-in the population with existing effusion-synovitis (OR 0.75-0.79). CONCLUSION: Higher baseline quadriceps strength was negatively associated with changes in effusion-synovitis-but not in Hoffa-synovitis-especially in the population with existing effusion-synovitis. Our findings suggested a potential protective role of the quadriceps in effusion-synovitis.

Bibliometric and visual analysis of single-cell sequencing from 2010 to 2022.

Background: Single-cell sequencing (SCS) is a technique used to analyze the genome, transcriptome, epigenome, and other genetic data at the level of a single cell. The procedure is commonly utilized in multiple fields, including neurobiology, immunology, and microbiology, and has emerged as a key focus of life science research. However, a thorough and impartial analysis of the existing state and trends of SCS-related research is lacking. The current study aimed to map the development trends of studies on SCS during the years 2010-2022 through bibliometric software. Methods: Pertinent papers on SCS from 2010 to 2022 were obtained using the Web of Science Core Collection. Research categories, nations/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords were analyzed using VOSviewer, the R package "bibliometric", and CiteSpace. Results: The bibliometric analysis included 9,929 papers published between 2010 and 2022, and showed a consistent increase in the quantity of papers each year. The United States was the source of the highest quantity of articles and citations in this field. The majority of articles were published in the periodical Nature Communications. Butler A was the most frequently quoted author on this topic, and his article "Integrating single-cell transcriptome data across diverse conditions, technologies, and species" has received numerous citations to date. The literature and keyword analysis showed that studies involving single-cell RNA sequencing (scRNA-seq) were prominent in this discipline during the study period. Conclusion: This study utilized bibliometric techniques to visualize research in SCS-related domains, which facilitated the identification of emerging patterns and future directions in the field. Current hot topics in SCS research include COVID-19, tumor microenvironment, scRNA-seq, and neuroscience. Our results are significant for scholars seeking to identify key issues and generate new research ideas.

Rehabilitation of motor function after stroke: A bibliometric analysis of global research from 2004 to 2022.

Background and aims: The mortality rate of stroke has been increasing worldwide. Poststroke somatic dysfunctions are common. Motor function rehabilitation of patients with such somatic dysfunctions enhances the quality of life and has long been the primary practice to achieve functional recovery. In this regard, we aimed to delineate the new trends and frontiers in stroke motor function rehabilitation literature published from 2004 to 2022 using a bibliometric software. Methods: All documents related to stroke rehabilitation and published from 2004 to 2022 were retrieved from the Web of Science Core Collection. Publication output, research categories, countries/institutions, authors/cocited authors, journals/cocited journals, cocited references, and keywords were assessed using VOSviewer v.1.6.15.0 and CiteSpace version 5.8. The cocitation map was plotted according to the analysis results to intuitively observe the research hotspots. Results: Overall, 3,302 articles were retrieved from 78 countries or regions and 564 institutions. Over time, the publication outputs increased annually. In terms of national contribution, the United States published the most papers, followed by China, Japan, South Korea, and Canada. Yeungnam University had the most articles among all institutions, followed by Emory University, Fudan University, and National Taiwan University. Jang Sung Ho and Wolf S.L. were the most productive (56 published articles) and influential (cited 1,121 times) authors, respectively. "Effect of constraint-induced movement therapy on upper extremity function 3-9 months after stroke: the Extremity Constraint Induced Therapy Evaluation randomized clinical trial" was the most frequently cited reference. Analysis of keywords showed that upper limbs, Fugl-Meyer assessment, electromyography, virtual reality, telerehabilitation, exoskeleton, and brain-computer interface were the research development trends and focus areas for this topic. Conclusion: Publications regarding motor function rehabilitation following stroke are likely to continuously increase. Research on virtual reality, telemedicine, electroacupuncture, the brain-computer interface, and rehabilitation robots has attracted increasing attention, with these topics becoming the hotspots of present research and the trends of future research.

Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative.

OBJECTIVE: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). METHODS: This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45-79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. RESULTS: One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR: 0.91, 95% CI 0.84 to 0.99, P = 0.023; BMLs: OR: 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis (OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. CONCLUSIONS: Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.

SNHG5/miR-299-5p/ATF2 Axis as a Biomarker in Immune Microenvironment of Intervertebral Disc Degeneration.

Methods: The data sets of GSE56081 and GSE63492 in the Gene Expression Omnibus (GEO) database were used for screening and analysis, and the key gene markers were verified by GSE34095 and GSE126883. Finally, the infiltration of immune cells in the data were analyzed by MCPcounter analysis package. Results: In this study, a ceRNA containing 15 lncRNAs, 9 miRNAs, and 103 mRNAs was constructed. After multimodel screening and verification, key gene marker was found, namely, ATF2. The lncRNA/miRNA/mRNA axis closely related to ATF2 have also been found, namely, SNHG5/miR-299-5p/ATF2. In the analysis of immune infiltration, ATF2 was negatively correlated with T cells but positively correlated with neutrophils and endothelial cells. Conclusion: The SNHG5/miR-299-5p/ATF2 can be used as biomarker of IDD, and infiltration of immune cells plays an important role in the pathological development of IDD. In addition, as a marker of IDD, the involvement of the above-mentioned axis in the pathological development of IDD remains to be further explored.

The effect of proprioception training on knee kinematics after anterior cruciate ligament reconstruction: A randomized control trial.

BACKGROUND: Proprioception is essential for the normal movement of knee joints. How proprioception training affects the postoperative knee functional recovery after anterior cruciate ligament (ACL) reconstruction remains unknown. OBJECTIVE: This study investigated the effect of proprioception training on the knee joint kinematics of patients after ACL reconstruction (ACLR). METHODS: The randomized controlled study was performed at the Department of Orthopaedics and Traumatology of Guangdong Provincial People's Hospital between December 2019 and April 2021. Forty-five patients who underwent ACLR were randomly divided into a proprioception group (n= 23) and a control group (n= 22). The patients were randomly divided into an experimental group and a control group according to whether the final digits of their ID numbers were odd or even. All patients followed a common postoperative rehabilitation program. The outcome measures included the patients Lysholm scores, hop distances, and knee kinematics during unanticipated jump-cut maneuvering measured at different follow-up times. Knee joint kinematics were described as the positional and orientational changes of the femur relative to the tibia. RESULTS: After surgery, the proprioception group did not exhibit significantly higher hop distances than the control group at the 6-month (114.8 ± 19.0 vs. 105.9 ± 20.7 cm, p= 0.137, 95% CI: -3.13 to 22.03 cm) and 1-year follow-ups (143.1 ± 19.3 vs. 133.9 ± 26.2 cm, p= 0.216, 95% CI: -5.57 to 23.87 cm). For knee joint kinematics, the members of the proprioception training group exhibited significantly reduced knee abduction (valgus) angles and external rotation and significantly increased knee flexion compared to those in the common training group. CONCLUSIONS: The results suggested that proprioceptive rehabilitation training enhances knee joint functional performance and shows altered knee joint kinematics in ACL-reconstructed populations during unanticipated jump-cut maneuvering compared with the common rehabilitation training.

Effects of Radial Extracorporeal Shock Wave Therapy on Flexor Spasticity of the Upper Limb in Post-stroke Patients: Study Protocol for a Randomized Controlled Trial.

Background: Flexor spasticity of the upper limb is common in poststroke patients and seriously affects the recovery of upper limb function. However, there are no standard management protocols for this condition. Radial extracorporeal shock wave therapy (rESWT) is widely used for various diseases, some studies reported the effects of ESWT on reducing spasticity, but the mechanism of ESWT to reduce spasticity by affecting the excitability of stretch reflex or non-neural rheological components in spastic muscles or both is not yet clear. A large randomized controlled trial with comprehensive evaluation indicators is still needed. The study is to observe the effect of rESWT on flexor spasticity of the upper limb after stroke and explore its mechanism. Methods: A prospective, randomized, double-blind controlled trial is to be performed. One hundred participants will be recruited from the Inpatient Department of Zhujiang Hospital. Eligible patients will be randomly allocated to either receive three sessions of active rESWT (group A) or sham-placebo rESWT (group B) with 3-day intervals between each session. Assessment will be performed at baseline and at 24 h after each rESWT (t1, t2, and t3). The primary assessment outcome will be the Modified Ashworth Scale, and other assessments include surface electromyography, MyotonPRO digital muscle function evaluation, and infrared thermal imaging. All data will be analyzed using intention-to-treat principles. Multiple imputation by chained equations will be used to address missing data caused by loss to follow-up and nonresponses. Per protocol, analyses will also be performed on the participants who complete other assessments. Statistical analysis will be performed using SPSS software (version 20.0) and the significance level set at p < 0.05. Discussion: This trial aims to analyze the application of rESWT for the management of spasticity after stroke via appropriate assessments. We hypothesized that after receiving active rESWT, patients would show greater improvement of upper limb muscles compared with patients within the sham-placebo group. The rESWT would be an alternative to traditional methods, and the results of this study may provide support for the further study of potential mechanisms. Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR1800016144.