A predictive model for depression in Chinese middle-aged and elderly people with physical disabilities.

BACKGROUND: Middle-aged and older adults with physical disabilities exhibit more common and severe depressive symptoms than those without physical disabilities. Such symptoms can greatly affect the physical and mental health and life expectancy of middle-aged and older persons with disabilities. METHOD: This study selected 2015 and 2018 data from the China Longitudinal Study of Health and Retirement. After analyzing the effect of age on depression, we used whether middle-aged and older adults with physical disabilities were depressed as the dependent variable and included a total of 24 predictor variables, including demographic factors, health behaviors, physical functioning and socialization, as independent variables. The data were randomly divided into training and validation sets on a 7:3 basis. LASSO regression analysis combined with binary logistic regression analysis was performed in the training set to screen the predictor variables of the model. Construct models in the training set and perform model evaluation, model visualization and internal validation. Perform external validation of the model in the validation set. RESULT: A total of 1052 middle-aged and elderly persons with physical disabilities were included in this study, and the prevalence of depression in the elderly group > middle-aged group. Restricted triple spline indicated that age had different effects on depression in the middle-aged and elderly groups. LASSO regression analysis combined with binary logistic regression screened out Gender, Location of Residential Address, Shortsightedness, Hearing, Any possible helper in the future, Alcoholic in the Past Year, Difficulty with Using the Toilet, Difficulty with Preparing Hot Meals, and Unable to work due to disability constructed the Chinese Depression Prediction Model for Middle-aged and Older People with Physical Disabilities. The nomogram shows that living in a rural area, lack of assistance, difficulties with activities of daily living, alcohol abuse, visual and hearing impairments, unemployment and being female are risk factors for depression in middle-aged and older persons with physical disabilities. The area under the ROC curve for the model, internal validation and external validation were all greater than 0.70, the mean absolute error was less than 0.02, and the recall and precision were both greater than 0.65, indicating that the model performs well in terms of discriminability, accuracy and generalisation. The DCA curve and net gain curve of the model indicate that the model has high gain in predicting depression. CONCLUSION: In this study, we showed that being female, living in rural areas, having poor vision and/or hearing, lack of assistance from others, drinking alcohol, having difficulty using the restroom and preparing food, and being unable to work due to a disability were risk factors for depression among middle-aged and older adults with physical disabilities. We developed a depression prediction model to assess the likelihood of depression in Chinese middle-aged and older adults with physical disabilities based on the above risk factors, so that early identification, intervention, and treatment can be provided to middle-aged and older adults with physical disabilities who are at high risk of developing depression.

Exploring barriers to and facilitators of the implementation of home rehabilitation care for older adults with disabilities using the Consolidated Framework for Implementation Research (CFIR).

BACKGROUND: With global aging on the rise, the number of older adults with disabilities was also increasing exponentially. There has been growing international interest in home rehabilitation care as a new method for older adults with disabilities. METHOD: The current study is a descriptive qualitative study. Guided by the Consolidated Framework for Implementation Research (CFIR), semistructured face-to-face interviews were performed to collect data. The interview data were analyzed using a qualitative content analysis method. RESULT: Sixteen nurses with different characteristics from 16 cities participated in the interviews. The findings highlighted 29 implementation determinants of home-based rehabilitation care for older adults with disabilities, including 16 barriers, and 13 facilitators. These influencing factors aligned with all four CFIR domains that were used to guide the analysis and 15 of the 26 CFIR constructs. More barriers were identified in the CFIR domain of characteristics of individuals, intervention characteristics, and the outer setting, while fewer barriers were identified in the inner setting. CONCLUSION: Nurses from the rehabilitation department reported many barriers related to the implementation of home rehabilitation care. They reported facilitators to the implementation of home rehabilitation care despite the barriers, which provided practical recommendations for directions to be explored by researchers in China and elsewhere.

Quality of clinical practice guidelines relevant to rehabilitation of knee osteoarthritis: A systematic review.

OBJECTIVE: This systematic review summarized the rehabilitation recommendations for treating and managing knee osteoarthritis (OA) in practice guidelines and evaluated their applicability and quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. DATA SOURCES: PubMed, the Cochrane Library, EMBASE, CINAHL, PEDro, Guideline central, Guideline International Network and Agency for Healthcare Research and Quality (AHRQ) were used to search for relevant studies published between 1 January 2008 and 31 May 2022. METHODS: AGREE II was used to evaluate the included guidelines quality, SPSS 25.0 statistical software was used for data analysis, and the intra-group correlation coefficient value was calculated to verify the consistency between the raters. The two-way random effects model was used to calculate concordance scores, and each domain's total scores were calculated. Additionally, the median and interquartile range for domain and total scores were calculated. RESULTS: Twenty-four guidelines recommending knee OA rehabilitation were included. Inter-rater consistency evaluation ranged from 0.62 to 0.90. The domains where the guideline's overall and rehabilitation parts scored highest and lowest were scope and purpose (domain 1) and applicability (domain 5), respectively. The highly recommended rehabilitation opinions included aerobic exercise programs (21/24), weight control (16/24), self-education and management (16/24), gait/walking aids (7/24), and tai chi (6/24). However, the orthopedic insole and hot/cold therapy roles remain controversial. CONCLUSION: The clinical practice guidelines' overall quality for knee OA rehabilitation is good; however, the applicability is slightly poor. Therefore, we should improve the promoting factors and hindering factors, guideline application recommendations, tools, and resources when developing relevant guidelines.

L-Cysteine attenuates osteopontin-mediated neuroinflammation following hypoxia-ischemia insult in neonatal mice by inducing S-sulfhydration of Stat3.

We previously show that L-Cysteine administration significantly suppresses hypoxia-ischemia (HI)-induced neuroinflammation in neonatal mice through releasing H2S. In this study we conducted proteomics analysis to explore the potential biomarkers or molecular therapeutic targets associated with anti-inflammatory effect of L-Cysteine in neonatal mice following HI insult. HI brain injury was induced in postnatal day 7 (P7) neonatal mice. The pups were administered L-Cysteine (5 mg/kg) at 24, 48, and 72 h post-HI. By conducting TMT-based proteomics analysis, we confirmed that osteopontin (OPN) was the most upregulated protein in ipsilateral cortex 72 h following HI insult. Moreover, OPN was expressed in CD11b+/CD45low cells and infiltrating CD11b+/CD45high cells after HI exposure. Intracerebroventricular injection of OPN antibody blocked OPN expression, significantly attenuated brain damage, reduced pro-inflammatory cytokine levels and suppressed cerebral recruitment of CD11b+/CD45high immune cells following HI insult. L-Cysteine administration reduced OPN expression in CD11b+/CD45high immune cells, concomitant with improving the behavior in Y-maze test and suppressing cerebral recruitment of CD11b+/CD45high immune cells post-HI insult. Moreover, L-Cysteine administration suppressed the Stat3 activation by inducing S-sulfhydration of Stat3. Intracerebroventricular injection of Stat3 siRNA not only decreased OPN expression, but also reversed HI brain damage. Our data demonstrate that L-Cysteine administration effectively attenuates the OPN-mediated neuroinflammation by inducing S-sulfhydration of Stat3, which contributes to its anti-inflammatory effect following HI insult in neonatal mice. Blocking OPN expression may serve as a new target for therapeutic intervention for perinatal HI brain injury.

Altered Brain Activity and Effective Connectivity within the Nonsensory Cortex during Stimulation of a Latent Myofascial Trigger Point.

Myofascial trigger point (MTrP), an iconic characteristic of myofascial pain syndrome (MPS), can induce cerebral cortex changes including altered cortical excitability and connectivity. The corresponding characteristically reactive cortex is still ambiguous. Seventeen participants with latent MTrPs underwent functional near-infrared spectroscopy (fNIRS) to collect cerebral oxygenation hemoglobin (Δ[oxy-Hb]) signals. The Δ[oxy-Hb] signals of the left/right prefrontal cortex (L/R PFC), left/right motor cortex (L/R MC), and left/right occipital lobe (L/R OL) of the subjects were measured using functional near-infrared spectroscopy (fNIRS) in the resting state, nonmyofascial trigger point (NMTrP), state and MTrP state. The data investigated the latent MTrP-induced changes in brain activity and effective connectivity (EC) within the nonsensory cortex. The parameter wavelet amplitude (WA) was used to describe cortical activation, EC to show brain network connectivity, and main coupling direction (mCD) to exhibit the dominant connectivity direction in different frequency bands. An increasing trend of WA and a decreasing trend of EC values were observed in the PFC. The interregional mCD was primarily shifted from a unidirectional to bidirectional connection, especially from PFC to MC or OL, when responding to manual stimulation during the MTrP state compared with resting state and NMTrP state in the intervals III, IV, and V. This study demonstrates that the nonsensory cortex PFC, MC, and OL can participate in the cortical reactions induced by stimulation of a latent MTrP. Additionally, the PFC shows nonnegligible higher activation and weakened regulation than other brain regions. Thus, the PFC may be responsible for the central cortical regulation of a latent MTrP. This trial is registered with ChiCTR2100048433.

Botulinum Toxin A Injection Using Esophageal Balloon Radiography Combined with CT Guidance for the Treatment of Cricopharyngeal Dysphagia.

Cricopharyngeal dysfunction, especially cricopharyngeal achalasia, is a common cause of dysphagia, while patients with brainstem stroke and medullary damage have a relatively high risk of cricopharyngeal achalasia. The aim of this article was to introduce an improved method of CT-guided method of injecting botulinum toxin A into the cricopharyngeus muscle using esophageal balloon radiography, and to assess the effect of the botulinum toxin A injection on swallowing performance. Seventeen patients with cricopharyngeal dysphagia were treated with botulinum toxin A injection using esophageal balloon radiography combined with CT guidance to the cricopharyngeal muscle. Primary outcome measures, including Functional Oral Intake Scale and Deglutition Handicap Index, were performed at baseline, 1 week, and 1 month after treatment. The Levene method was used to test the homogeneity of variance, and the Kruskal-Wallis test was used to compare the scores between the timepoints. Botulinum toxin A injection resulted in obvious improvement in 15 patients (88.2%) and no improvement in two patients (11.8%). Compared with the scores prior to treatment, the Functional Oral Intake Scale and Deglutition Handicap Index scores were significantly improved at 1 week (P < 0.001 and P = 0.008, respectively) and 1 month after the treatment (P = 0.001 and P < 0.001, respectively). Thus, CT-guided percutaneous injection of botulinum toxin A is probably a relatively safe, well-tolerated, and viable technique for the treatment of cricopharyngeal dysphagia caused by brainstem injury. Localization with a balloon radiography made the needle guidance easier to visualize.

The Occurrence Rate of Swallowing Disorders After Stroke Patients in Asia: A PRISMA-Compliant Systematic Review and Meta-Analysis.

BACKGROUND: Swallowing disorders (dysphagia) is common in stroke patients. However, the epidemiology of post-stroke dysphagia (PSD) is poorly described. We herein synthesize the data of eligible studies on occurrence rate of dysphagia in Asian populations with stroke. METHODS: We searched the electronic databases (PubMed, Embase and Web of Science) to collect the studies on the prevalence of PSD. We used the Newcastle-Ottawa Scale (NOS) to estimate the quality of studies. The pooled dysphagia occurrence rate was obtained in Asian stroke patients. RESULTS: 40 studies (including 43 observations) from 2318 initial references were selected in the synthetic analysis. The pooled occurrence rate of dysphagia in post-stroke patients was 36.3% (95% CI, 33.3%-39.3%). Meta-regression analysis showed that the "country" and "developing level" may influence the pooled occurrence rate of PSD. CONCLUSION: Dysphagia is common in Asian post-stroke patients. Our meta-analysis may raise concern about evaluating and managing dysphagia in stroke patients.

Gene therapy by lentivirus-mediated RNA interference targeting extracellular-regulated kinase alleviates neuropathic pain in vivo.

BACKGROUNDS: Neuropathic pain is an abnormal pain, which is related to the activation of extracellular-regulated kinase (ERK) signaling. This study was to investigate the effects of ERK knockdown via lentivirus-mediated RNA interference on allodynia in rats with chronic compression of the dorsal root ganglia (DRG) and to uncover the potential mechanisms. METHODS: The model of chronic compression of the dorsal root ganglia (CCD) was established in rats by surgery. Gene silence was induced by injecting rats with lentivirus expressing ERK short hairpin RNA (shRNA). Behavioral test was performed by calculating paw withdrawal mechanical threshold (PWMT) and thermal paw withdrawal latency (TPWL). RESULTS: We firstly generated lentivirus expressing ERK shRNA to downregulate ERK gene expression both in vitro and in vivo by using Western blot analysis and quantitative reverse transcription polymerase chain reaction. In CCD, ERK mRNA, and protein levels in DRG neurons were dramatically increased, accompanied with decreased PWMT and TPWL. Lentivirus-mediated RNA interference decreased ERK gene expression in DRG neurons and normalized the PWMT and TPWL in CCD rats, but not in rats infected with lentivirus expressing negative control shRNA. Further, calcium responses of DRG neurons to the hypotonic solution and 4α-phorbol 12,13-didecanoate were enhanced in CCD rats, which were suppressed by lentivirus-mediated ERK gene silence. Finally, the levels of transient receptor potential vanilloid 4 gene expressions in DRG neurons and L4 to L5 spinal cord isolated from CCD rats were dramatically upregulated, which were reversed by lentivirus-mediated ERK gene knockdown. CONCLUSION: Lentivirus-mediated RNA interference (RNAi) silencing targeting ERK might reverse CCD-induced neuropathic pain in rats through transient receptor potential vanilloid 4.

Intrathecal injection of bone marrow stromal cells attenuates neuropathic pain via inhibition of P2X4R in spinal cord microglia.

BACKGROUND: Neuropathic pain is one of the most debilitating of all chronic pain syndromes. Intrathecal (i.t.) bone marrow stromal cell (BMSC) injections have a favorable safety profile; however, results have been inconsistent, and complete understanding of how BMSCs affect neuropathic pain remains elusive. METHODS: We evaluated the analgesic effect of BMSCs on neuropathic pain in a chronic compression of the dorsal root ganglion (CCD) model. We analyzed the effect of BMSCs on microglia reactivity and expression of purinergic receptor P2X4 (P2X4R). Furthermore, we assessed the effect of BMSCs on the expression of transient receptor potential vanilloid 4 (TRPV4), a key molecule in the pathogenesis of neuropathic pain, in dorsal root ganglion (DRG) neurons. RESULTS: I.t. BMSC transiently but significantly ameliorated neuropathic pain behavior (37.6% reduction for 2 days). We found no evidence of BMSC infiltration into the spinal cord parenchyma or DRGs, and we also demonstrated that intrathecal injection of BMSC-lysates provides similar relief. These findings suggest that the analgesic effects of i.t. BMSC were largely due to the release of BMSC-derived factors into the intrathecal space. Mechanistically, we found that while i.t. BMSCs did not change TRPV4 expression in DRG neurons, there was a significant reduction of P2X4R expression in the spinal cord microglia. BMSC-lysate also reduced P2X4R expression in activated microglia in vitro. Coadministration of additional pharmacological interventions targeting P2X4R confirmed that modulation of P2X4R might be a key mechanism for the analgesic effects of i.t. BMSC. CONCLUSION: Altogether, our results suggest that i.t. BMSC is an effective and safe treatment of neuropathic pain and provides novel evidence that BMSC's analgesic effects are largely mediated by the release of BMSC-derived factors resulting in microglial P2X4R downregulation.

Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.

OBJECTIVE: To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. DESIGN: Prospective randomized controlled study. SETTING: Department of physical medicine and rehabilitation. PARTICIPANTS: Patients with dysphagia with medullary infarction (N=82). INTERVENTIONS: Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. MAIN OUTCOME MEASURES: Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). RESULTS: There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). CONCLUSIONS: NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infarction. A sensory approach appears to be better than a motor approach.

Full-movement neuromuscular electrical stimulation improves plantar flexor spasticity and ankle active dorsiflexion in stroke patients: a randomized controlled study.

OBJECTIVE: To investigate whether full-movement neuromuscular electrical stimulation, which can generate full range of movement, reduces spasticity and/or improves motor function more effectively than control, sensory threshold-neuromuscular electrical stimulation, and motor threshold-neuromuscular electrical stimulation in sub-acute stroke patients. DESIGN: A randomized, single-blind, controlled study. SETTING: Physical therapy room and functional assessment room. PARTICIPANTS: A total of 72 adult patients with sub-acute post-stroke hemiplegia and plantar flexor spasticity. METHOD: Patients received 30-minute sessions of neuromuscular electrical stimulation on the motor points of the extensor hallucis and digitorum longus twice a day, five days per week for four weeks. MEASURES: Composite Spasticity Scale, Ankle Active Dorsiflexion Score, and walking time in the Timed Up and Go Test were assessed at pretreatment, posttreatment, and at two-week follow-up. RESULTS: After four weeks of treatment, when comparing interclass pretreatment and posttreatment, only the full-movement neuromuscular electrical stimulation group had a significant reduction in the Composite Spasticity Scale (mean % reduction = 19.91(4.96)%, F = 3.878, p < 0.05) and improvement in the Ankle Active Dorsiflexion Score (mean scores = 3.29(0.91), F = 3.140, p < 0.05). Furthermore, these improvements were maintained two weeks after the treatment ended. However, there were no significant differences in the walking time after four weeks of treatment among the four groups (F = 1.861, p > 0.05). CONCLUSIONS: Full-movement neuromuscular electrical stimulation with a stimulus intensity capable of generating full movement can significantly reduce plantar flexor spasticity and improve ankle active dorsiflexion, but cannot decrease walking time in the Timed Up and Go Test in sub-acute stroke patients.

Berberine via suppression of transient receptor potential vanilloid 4 channel improves vascular stiffness in mice.

Berberine, as an alkaloid found in many Chinese herbs, improves vascular functions in patients with cardiovascular diseases. We determined the effects of berberine in hypertension and vascular ageing, and elucidated the underlying mechanisms. In isolated aortas, berberine dose-dependently elicited aortic relaxation. In cultured cells, berberine induced the relaxation of vascular smooth muscle cells (VSMCs). Overexpression of transient receptor potential vanilloid 4 (TRPV4) channel by genetic approaches abolished the berberine-induced reduction in intracellular Ca(2+) concentration in VSMCs and attenuated berberine-elicited vessel dilation in mice aortas. In deoxycorticosterone acetate (DOCA)-induced hypertensive model, treatment of mice with berberine or RN-1734, a pharmacological inhibitor of TRPV4, significantly decreased systemic blood pressure (BP) in control mice or mice infected with an adenovirus vector. However, berberine-induced effects of lowering BP were reversed by overexpressing TRPV4 in mice by infecting with adenovirus. Furthermore, long-term administration of berberine decreased mean BP and pulse BP, increased artery response to vasodilator and reduced vascular collagen content in aged mice deficient in apolipoprotein E (Apoe-KO), but not in Apoe-KO old mice with lentivirus-mediated overexpression of TRPV4 channel. In conclusion, berberine induces direct vasorelaxation to lower BP and reduces vascular stiffness in aged mice through suppression of TRPV4.

A afferent fibers are involved in the pathology of central changes in the spinal dorsal horn associated with myofascial trigger spots in rats.

A afferent fibers have been reported to participate in the development of the central sensitization induced by inflammation and injuries. Current evidence suggests that myofascial trigger points (MTrPs) induce central sensitization in the related spinal dorsal horn, and clinical studies indicate that A fibers are associated with pain behavior. Because most of these clinical studies applied behavioral indexes, objective evidence is needed. Additionally, MTrP-related neurons in dorsal root ganglia and the spinal ventral horn have been reported to be smaller than normal, and these neurons were considered to be related to A fibers. To confirm the role of A fibers in MTrP-related central changes in the spinal dorsal horn, we studied central sensitization as well as the size of neurons associated with myofascial trigger spots (MTrSs, equivalent to MTrPs in humans) in the biceps femoris muscle of rats and provided some objective morphological evidence. Cholera toxin B subunit-conjugated horseradish peroxidase was applied to label the MTrS-related neurons, and tetrodotoxin was used to block A fibers specifically. The results showed that in the spinal dorsal horn associated with MTrS, the expression of glutamate receptor (mGluR1α/mGluR5/NMDAR1) increased, while the mean size of MTrS-related neurons was smaller than normal. After blocking A fibers, these changes reversed to some extent. Therefore, we concluded that A fibers participated in the development and maintenance of the central sensitization induced by MTrPs and were related to the mean size of neurons associated with MTrPs in the spinal dorsal horn.

Coordination of digit force variability during dominant and non-dominant sustained precision pinch.

This study examined the effects of handedness on the inter-digit coordination of force variability with and without concurrent visual feedback during sustained precision pinch. Twenty-four right-handed subjects were instructed to pinch an instrumented apparatus with their dominant and non-dominant hands, separately. During the pinch, the subjects were required to maintain a stable force output at 5 N for 1 min. Visual feedback was given for the first 30 s and removed for the second 30 s. Coefficient of variation and detrended fluctuation analysis were employed to examine the amount and structural variability of the thumb and index finger forces. Similarly, correlation coefficient and detrended cross-correlation analysis were applied to quantify the inter-digit correlation of force amount and structural variability. Results showed that, compared to the non-dominant hand, the dominant hand had higher inter-digit difference in the amount of digit force variability. Without visual feedback, the dominant hand exhibited lower digit force structural variability but higher inter-digit force structural correlation than the non-dominant hand. These results implied that the dominant hand would be more independent, less flexible and with lower dynamic degrees of freedom than the non-dominant hand in coordination of the thumb and index finger forces during sustained precision pinch. The effects of handedness on inter-digit force coordination were dependent on sensory condition, which shed light on higher-level sensorimotor mechanisms that may be responsible for the asymmetries in coordination of digit force variability.

M6A-related bioinformatics analysis indicates that LRPPRC is an immune marker for ischemic stroke.

Ischemic stroke (IS) is a common cerebrovascular disease whose pathogenesis involves a variety of immune molecules, immune channels and immune processes. 6-methyladenosine (m6A) modification regulates a variety of immune metabolic and immunopathological processes, but the role of m6A in IS is not yet understood. We downloaded the data set GSE58294 from the GEO database and screened for m6A-regulated differential expression genes. The RF algorithm was selected to screen the m6A key regulatory genes. Clinical prediction models were constructed and validated based on m6A key regulatory genes. IS patients were grouped according to the expression of m6A key regulatory genes, and immune markers of IS were identified based on immune infiltration characteristics and correlation. Finally, we performed functional enrichment, protein interaction network analysis and molecular prediction of the immune biomarkers. We identified a total of 7 differentially expressed genes in the dataset, namely METTL3, WTAP, YWHAG, TRA2A, YTHDF3, LRPPRC and HNRNPA2B1. The random forest algorithm indicated that all 7 genes were m6A key regulatory genes of IS, and the credibility of the above key regulatory genes was verified by constructing a clinical prediction model. Based on the expression of key regulatory genes, we divided IS patients into 2 groups. Based on the expression of the gene LRPPRC and the correlation of immune infiltration under different subgroups, LRPPRC was identified as an immune biomarker for IS. GO enrichment analyses indicate that LRPPRC is associated with a variety of cellular functions. Protein interaction network analysis and molecular prediction indicated that LRPPRC correlates with a variety of immune proteins, and LRPPRC may serve as a target for IS drug therapy. Our findings suggest that LRPPRC is an immune marker for IS. Further analysis based on LRPPRC could elucidate its role in the immune microenvironment of IS.

Variation in brain connectivity during motor imagery and motor execution in stroke patients based on electroencephalography.

Objective: The objective of this study was to analyze the changes in connectivity between motor imagery (MI) and motor execution (ME) in the premotor area (PMA) and primary motor cortex (MA) of the brain, aiming to explore suitable forms of treatment and potential therapeutic targets. Methods: Twenty-three inpatients with stroke were selected, and 21 right-handed healthy individuals were recruited. EEG signal during hand MI and ME (synergy and isolated movements) was recorded. Correlations between functional brain areas during MI and ME were compared. Results: PMA and MA were significantly and positively correlated during hand MI in all participants. The power spectral density (PSD) values of PMA EEG signals were greater than those of MA during MI and ME in both groups. The functional connectivity correlation was higher in the stroke group than in healthy people during MI, especially during left-handed MI. During ME, functional connectivity correlation in the brain was more enhanced during synergy movements than during isolated movements. The regions with abnormal functional connectivity were in the 18th lead of the left PMA area. Conclusion: Left-handed MI may be crucial in MI therapy, and the 18th lead may serve as a target for non-invasive neuromodulation to promote further recovery of limb function in patients with stroke. This may provide support for the EEG theory of neuromodulation therapy for hemiplegic patients.

Experimental validation and comprehensive analysis of m6A methylation regulators in intervertebral disc degeneration subpopulation classification.

Intervertebral disc degeneration (IVDD) is one of the most prevalent causes of chronic low back pain. The role of m6A methylation modification in disc degeneration (IVDD) remains unclear. We investigated immune-related m6A methylation regulators as IVDD biomarkers through comprehensive analysis and experimental validation of m6A methylation regulators in disc degeneration. The training dataset was downloaded from the GEO database and analysed for differentially expressed m6A methylation regulators and immunological features, the differentially regulators were subsequently validated by a rat IVDD model and RT-qPCR. Further screening of key m6A methylation regulators based on machine learning and LASSO regression analysis. Thereafter, a predictive model based on key m6A methylation regulators was constructed for training sets, which was validated by validation set. IVDD patients were then clustered based on the expression of key m6A regulators, and the expression of key m6A regulators and immune infiltrates between clusters was investigated to determine immune markers in IVDD. Finally, we investigated the potential role of the immune marker in IVDD through enrichment analysis, protein-to-protein network analysis, and molecular prediction. By analysising of the training set, we revealed significant differences in gene expression of five methylation regulators including RBM15, YTHDC1, YTHDF3, HNRNPA2B1 and ALKBH5, while finding characteristic immune infiltration of differentially expressed genes, the result was validated by PCR. We then screen the differential m6A regulators in the training set and identified RBM15 and YTHDC1 as key m6A regulators. We then used RBM15 and YTHDC1 to construct a predictive model for IVDD and successfully validated it in the training set. Next, we clustered IVDD patients based on the expression of RBM15 and YTHDC1 and explored the immune infiltration characteristics between clusters as well as the expression of RBM15 and YTHDC1 in the clusters. YTHDC1 was finally identified as an immune biomarker for IVDD. We finally found that YTHDC1 may influence the immune microenvironment of IVDD through ABL1 and TXK. In summary, our results suggest that YTHDC1 is a potential biomarker for the development of IVDD and may provide new insights for the precise prevention and treatment of IVDD.

Electroencephalography-based biological and functional characteristics of spinal cord injury patients with neuropathic pain and numbness.

Objectives: To identify potential treatment targets for spinal cord injury (SCI)-related neuropathic pain (NP) by analysing the differences in electroencephalogram (EEG) and brain network connections among SCI patients with NP or numbness. Participants and methods: The EEG signals during rest, as well as left- and right-hand and feet motor imagination (MI), were recorded. The power spectral density (PSD) of the θ (4-8 Hz), α (8-12 Hz), and ß (13-30 Hz) bands was calculated by applying Continuous Wavelet Transform (CWT) and Modified S-transform (MST) to the data. We used 21 electrodes as network nodes and performed statistical measurements of the phase synchronisation between two brain regions using a phase-locking value, which captures nonlinear phase synchronisation. Results: The specificity of the MST algorithm was higher than that of the CWT. Widespread non-lateralised event-related synchronization was observed in both groups during the left- and right-hand MI. The PWP (patients with pain) group had lower θ and α bands PSD values in multiple channels of regions including the frontal, premotor, motor, and temporal regions compared with the PWN (patients with numbness) group (all p < 0.05), but higher ß band PSD values in multiple channels of regions including the frontal, premotor, motor, and parietal region compared with the PWN group (all p < 0.05). During left-hand and feet MI, in the lower frequency bands (θ and α bands), the brain network connections of the PWP group were significantly weaker than the PWN group except for the frontal region. Conversely, in the higher frequency bands (ß band), the brain network connections of the PWP group were significantly stronger in all regions than the PWN group. Conclusion: The differences in the power of EEG and network connectivity in the frontal, premotor, motor, and temporal regions are potential biological and functional characteristics that can be used to distinguish NP from numbness. The differences in brain network connections between the two groups suggest that the distinct mechanisms for pain and numbness.

A clinical model to predict the progression of knee osteoarthritis: data from Dryad.

BACKGROUND: Knee osteoarthritis (KOA) is a multifactorial, slow-progressing, non-inflammatory degenerative disease primarily affecting synovial joints. It is usually induced by advanced age and/or trauma and eventually leads to irreversible destruction of articular cartilage and other tissues of the joint. Current research on KOA progression has limited clinical application significance. In this study, we constructed a prediction model for KOA progression based on multiple clinically relevant factors to provide clinicians with an effective tool to intervene in KOA progression. METHOD: This study utilized the data set from the Dryad database which included patients with Kellgren-Lawrence (KL) grades 2 and 3. The KL grades was determined as the dependent variable, while 15 potential predictors were identified as independent variables. Patients were randomized into training set and validation set. The training set underwent LASSO analysis, model creation, visualization, decision curve analysis and internal validation using R language. The validation set is externally validated and F1-score, precision, and recall are computed. RESULT: A total of 101 patients with KL2 and 94 patients with KL3 were selected. We randomly split the data set into a training set and a validation set by 8:2. We filtered "BMI", "TC", "Hypertension treatment", and "JBS3 (%)" to build the prediction model for progression of KOA. Nomogram used to visualize the model in R language. Area under ROC curve was 0.896 (95% CI 0.847-0.945), indicating high discrimination. Mean absolute error (MAE) of calibration curve = 0.041, showing high calibration. MAE of internal validation error was 0.043, indicating high model calibration. Decision curve analysis showed high net benefit. External validation of the metabolic syndrome column-line graph prediction model was performed by the validation set. The area under the ROC curve was 0.876 (95% CI 0.767-0.984), indicating that the model had a high degree of discrimination. Meanwhile, the calibration curve Mean absolute error was 0.113, indicating that the model had a high degree of calibration. The F1 score is 0.690, the precision is 0.667, and the recall is 0.714. The above metrics represent a good performance of the model. CONCLUSION: We found that KOA progression was associated with four variable predictors and constructed a predictive model for KOA progression based on the predictors. The clinician can intervene based on the nomogram of our prediction model. KEY INFORMATION: This study is a clinical predictive model of KOA progression. KOA progression prediction model has good credibility and clinical value in the prevention of KOA progression.

Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment.

Background: Asthma was a chronic inflammatory illness driven by complicated genetic regulation and environmental exposure. The complex pathophysiology of asthma has not been fully understood. Ferroptosis was involved in inflammation and infection. However, the effect of ferroptosis on asthma was still unclear. The study was designed to identify ferroptosis-related genes in asthma, providing potential therapeutic targets. Methods: We conducted a comprehensive analysis combined with WGCNA, PPI, GO, KEGG, and CIBERSORT methods to identify ferroptosis-related genes that were associated with asthma and regulated the immune microenvironment in GSE147878 from the GEO. The results of this study were validated in GSE143303 and GSE27066, and the hub genes related to ferroptosis were further verified by immunofluorescence and RT-qPCR in the OVA asthma model. Results: 60 asthmatics and 13 healthy controls were extracted for WGCNA. We found that genes in the black module (r = -0.47, p < 0.05) and magenta module (r = 0.51, p < 0.05) were associated with asthma. CAMKK2 and CISD1 were discovered to be ferroptosis-related hub genes in the black and magenta module, separately. We found that CAMKK2 and CISD1 were mainly involved in the CAMKK-AMPK signaling cascade, the adipocytokine signaling pathway, the metal cluster binding, iron-sulfur cluster binding, and 2 iron, 2 sulfur cluster binding in the enrichment analysis, which was strongly correlated with the development of ferroptosis. We found more infiltration of M2 macrophages and less Tregs infiltration in the asthma group compared to healthy controls. In addition, the expression levels of CISD1 and Tregs were negatively correlated. Through validation, we found that CAMKK2 and CISD1 expression were upregulated in the asthma group compared to the control group and would inhibit the occurrence of ferroptosis. Conclusion: CAMKK2 and CISD1 might inhibit ferroptosis and specifically regulate asthma. Moreover, CISD1 might be tied to the immunological microenvironment. Our results could be useful to provide potential immunotherapy targets and prognostic markers for asthma.