Higher Disability Research Articles

A network pharmacology approach to decipher the mechanism of total flavonoids from Dracocephalum Moldavica L. in the treatment of cardiovascular diseases

Aim of the studyCardiovascular disease (CVD) seriously endangers human health and is characterized by high mortality and disability. The effectiveness of Dracocephalum moldavica L. in the treatment of CVD has been proven by clinical practice. However, the mechanism by which DML can treat CVD has not been systematically determined.Materials and methodsThe active compounds in DML were screened by literature mining and pharmacokinetic analysis. Cytoscape software was used to construct the target-disease interaction network of DML in the treatment of CVD. Gene ontology and signalling pathway enrichment analyses were performed. The key target pathway network of DML compounds was constructed and verified by pharmacological experiments in vitro. A hydrogen glucose deprivation/reoxygenation model was established in H9c2 cells using hypoxia and glucose deprivation for 9 h combined with reoxygenation for 2 h. The model simulated myocardial ischaemic reperfusion injury to investigate the effects of total flavonoids of Cymbidium on cell viability, myocardial injury markers, oxidative stress levels, and reactive oxygen radical levels. Western blot analysis was used to examine NOX-4, Bcl-2/Bax, and PGC-1α protein expression.ResultsTwenty-seven active components were screened, and 59 potential drug targets for the treatment of CVD were obtained. Through the compound-target interaction network and the target-disease interaction network, the key targets and key signalling pathways, such as NOX-4, Bcl-2/Bax and PGC-1α, were obtained. TFDM significantly decreased LDH and MDA levels and the production of ROS and increased SOD activity levels in the context of OGD/R injury. Further studies indicated that NOX-4 and Bax protein levels and the p-P38 MAPK/P38 MAPK andp-Erk1/2/Erk1/2 ratios were suppressed by TFDM. The protein expression of Bcl-2 and PGC-1α was increased by TFDM.ConclusionsOur results showed that DML had multicomponent, multitarget and multichannel characteristics in the treatment of CVD. The mechanism may be associated with the following signalling pathways: 1) the NOX-4/ROS/p38 MAPK signalling pathway, which inhibits inflammation and reactive oxygen species (ROS) production, and 2) the Bcl-2/Bax and AMPK/SIRT1/PGC-1α signalling pathways, which inhibit apoptosis.

Interest in Telerehabilitation Among Patients with Mild to Severe Multiple Sclerosis: Results of the Czech Republic.

Background: Research in telerehabilitation (TR) in neurology tends to focus on patients with low to moderate disability. For neurology patients with severe mobility limitations, TR can help to enable rehabilitation for people whose mobility limitations make it difficult for them to access rehabilitation facilities. The aim of this study is to evaluate the interest of people with neurological disability caused by multiple sclerosis (MS) in TR services. Methods: This electronic survey targeted individuals with MS, specifically those with a higher level of disability. Results: A total of 355 patients with MS (155 with severe disabilities) participated in this study. There was no difference in interest in rehabilitation between people with mild-to-moderate and severe disabilities (p = 0.1258, confidence interval [CI] = 95%). However, we found a higher interest in upper limb exercises (p = 0.0006, CI = 95%) and balance training (p = 0.0000, CI = 95%) among people with higher disability. Conclusion: The results of this study may help to improve the planning and targeting of TR interventions, where a different focus of intervention is appropriate for patients with different levels of disability. This may enable TR to be maximally tailored to patient capabilities and current greatest limitations. For example, for people with severe disabilities, it is appropriate to focus on training the upper limb function to maintain self-sufficiency and implement interventions to prevent falls.

Ginsenoside Rb1 attenuates mouse cerebral ischemia/reperfusion induced neurological impairments through modulation of microglial polarization.

Cerebral ischemia/reperfusion causes high disability, recurrence, and mortality. Ischemic stroke is a powerful stimulus that triggers significant microglia activation. Ginsenoside Rb1 (GS-Rb1) has been demonstrated to have neuroprotective effects in the central nervous system. In this study, the effects of GS-Rb1 against cerebral ischemia/reperfusion were explored. A mouse model of middle cerebral artery occlusion (MCAO) was used to mimic the cerebral ischemia/reperfusion. Mice in MCAO + GS-Rb1 groups received 5, 10, or 20 mg/kg GS-Rb1 through intraperitoneal injection. Modified neurological severity scoring (mNSS) showed neurological function, while the open field test tested the anxiety-like behaviors. Cognitive impairment was evaluated by Morris water maze. Protein levels were evaluated by ELISA and Western blot and mRNA levels were analyzed by qRT-PCR. When compared to the MCAO mice, mice in the MCAO + GS-Rb1 group had significantly lower mNSS scores and less brain water content. GS-Rb1 alleviated both cognitive impairment and anxiety and inhibited microglial activation in the cerebral ischemia/reperfusion model. GS-Rb1 enhanced M2-type microglia polarization while inhibiting M1-type microglia polarization. In summary, we observed that GS-Rb1 had neuro-protective effects in a cerebral ischemia/reperfusion mouse model through regulating the microglia polarization.

Angiopoietin-Like Protein 2 Serves as an Independent Prognostic Biomarker and Correlates with Immune Infiltration in Osteosarcoma

Osteosarcoma mostly occurs in adolescents, with high disability and mortality rates and poor prognosis. Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein protein, which plays important roles in cellular processes and various diseases. Microarray gene expression data GSE16088 and GSE36001 were downloaded from Gene Expression Omnibus (GEO, <ext-link ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/geo">http://www.ncbi.nlm.nih.gov/geo</ext-link>). The Complex Heatmap package was used to construct heatmaps, the gglot2 R language package to plot volcanoes and differential expression data, and the “VennDiagram” R language package to plot Wayne plots. Western booting and qRT-PCR was used to detect ANGPTL2 expression in osteosarcoma tissues. proteins. In addition, the GeneMANIA database (<ext-link ext-link-type="uri" xlink:href="http://www.genemania.org">http://www.genemania.org</ext-link>) was cited to predict the ANGPTL2 interaction network. We used the single-sample gene-set enrichment analysis (ss GSEA) algorithm to quantify the immune infiltration of osteosarcoma. In the GSE16088 database there were 5005 that met the selected threshold of |log2(FC)| > 1 and P <0.05, of which 2719 were highly expressed and 2286 were lowly expressed. WB and qRT-PCR results showed that ANGPTL2 was significantly up-regulated in osteosarcoma tissues. ssGSEA showed that high ANGPTL2 expression in osteosarcoma patients had a worse prognosis. ssGSEA showed that high ANGPTL2 expression was correlated with Mast cells and Th1 cells. Collectively, ANGPTL2 can be an independent prognostic biomarker and correlated with immune infiltration in osteosarcoma.

Mechanisms and Implications of Mitochondrial Autophagy in Stroke

Stroke is an acute cerebrovascular disease that is caused by disruptions in the cerebral blood supply and leads to brain tissue damage. Its pathological mechanisms remain to be fully elucidated. Stroke has high incidence, disability, and mortality rates, thus substantially affecting life and health. Against this backdrop, intracellular mitochondria, which are central to cellular energy metabolism and crucial for cell survival, have major roles in ischemic stroke. Ischemic stroke results in brain cell oxygen and nutrient deprivation, thereby triggering oxidative stress and inflammatory reactions, impairing mitochondrial function, and disrupting energy metabolism. Mitochondrial autophagy is a protective mechanism to improve the quality and quantity of mitrochondria, and exerts neuroprotective effects. In recent years, preserving mitochondrial function after ischemic stroke has emerged as a major research topic. Increasing evidence suggests a close relationship between abnormal mitochondrial autophagy and the occurrence, progression, and pathophysiology of ischemic stroke. However, current research has not adequately explained how ischemic stroke regulates the initiation and execution of mitochondrial autophagy. Elucidating this mechanism in detail will be critical for understanding the development of stroke injury, and identifying novel and effective intervention strategies. Additionally, the optimal treatment time window must be determined to enable effective interventions in mitochondrial autophagy and minimize brain damage. To deepen understanding of mitochondrial autophagy, this review summarizes mitochondrial autophagy’s signaling pathways and its major role in ischemic stroke pathophysiology. Further exploration in this field will provide a crucial theoretical foundation for developing novel therapeutic strategies and clinical applications.

Natural Essential Oils: A Promising Therapy Way for Treating Ischemic Stroke.

Stroke is an acute cerebrovascular disease with high morbidity, mortality, and disability, making it the second leading cause of death worldwide. Ischemic stroke (IS) accounts for the majority of strokes, and its pathogenesis is complex, often involving complications and sequelae. Currently, conventional clinical approaches are ineffective, with few drugs available for intravenous thrombolysis and mechanical thrombolysis limited by a short time window. With the poor efficacy of monotherapy, the search for new complementary or alternative therapies has become the focus of researchers. In traditional medicine, Chinese aromatherapy has a long history of using aromatic medicines to treat IS. Natural essential oils (EOs), as the main pharmacological substances in aromatic drugs, are composed of different ratios of active metabolites with multi-targets and multi-components, which makes EOs have a wide range of pharmacological effects. Modern studies have also shown that EOs extracts and isolated monomers are beneficial for pathologically complex CIS. Therefore, this paper summarizes the EOs and monomers obtained from EOs that can prevent and treat IS in the last 20 years, and finds that EOs exert their anti-CIS effects mainly through anti-oxidative stress, anti-inflammation, anti-apoptosis, and inhibition of excitotoxicity. The amelioration of IS complications by natural EOs and their active monomer components for the treatment of IS are further discussed.

Identification of immune-related biomarkers for intracerebral hemorrhage diagnosis based on RNA sequencing and machine learning.

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers. We collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes. In both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH. This study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.

Polyphenols for Stroke Therapy: The Role of Oxidative Stress Regulation

Stroke is associated with a high incidence and disability rate, which seriously endangers human health. Oxidative stress (OS) plays a crucial role in the underlying pathologic progression of cerebral damage...

Risk factors for intraprocedural hypoxemia in patients with acute cerebral ischemia treated with vascular intervention and its impact on prognosis: A retrospective cohort study.

Acute cerebral infarction (ACI) is one of the most common ischemic cerebrovascular diseases in neurology, with high morbidity, mortality, and disability. Early thrombolytic treatment of ACI has significant efficacy, but intraprocedural complications of hypoxemia can significantly reduce the efficacy. This study aims to analyze the risk factors for intraprocedural hypoxemia in patients with ACI, so as to take effective measures in advance to reduce the likelihood of adverse patient outcomes. We retrospectively analyzed a total of 238 patients with ACI treated with vascular interventions from May 2017 to May 2022. To assess and collate the patients' characteristics, factors associated with the development of intraprocedural hypoxemia. The independent risk factors for the development of intraprocedural hypoxemia were analyzed by binary logistic regression. A total of 238 patients were included in this study. Of these, intraprocedural hypoxemia occurred in 89 (37.4%). The results showed that old age (odds ratio [OR] = 2.666, P = 0.009), obesity (OR = 3.029, P = 0.003), smoking history (OR = 2.655, P = 0.010), preoperative oxygen saturation (SpO2) (OR = 0.001, P = 0.042), preoperative C-reactive protein (OR = 1.216, P = 0.002), and time from puncture to vascular recanalization (OR = 1.135, P = 0.000) were independent risk factors for intraprocedural hypoxemia in patients. The prognosis of the patients was assessed according to the modified Rankin scale, and the prognosis of the nonhypoxemia group was significantly better than that of the hypoxemia group. Regression analysis showed that intraprocedural hypoxemia (OR = 0.360, P = 0.001), postoperative lower extremity vein thrombosis (OR = 0.187, P = 0.018), hydrocephalus (OR = 0.069, P = 0.015), intracranial hemorrhage (OR = 0.116, P = 0.002), and reocclusion (OR = 0.217, P = 0.036) were independent risk factors for poor prognosis. Currently, intravascular hypoxemia in patients with ACI has a serious impact on prognosis. Clinical work should attach great importance to the clinical characteristics of patients, identify relevant risk factors, and aggressively take personalized therapeutic actions to improve patients' prognosis.

β-asarone induces viability and angiogenesis and suppresses apoptosis of human vascular endothelial cells after ischemic stroke by upregulating vascular endothelial growth factor A.

Ischemic stroke (IS) is a disease with a high mortality and disability rate worldwide, and its incidence is increasing per year. Angiogenesis after IS improves blood supply to ischemic areas, accelerating neurological recovery. β-asarone has been reported to exhibit a significant protective effect against hypoxia injury. The ability of β-asarone to improve IS injury by inducing angiogenesis has not been distinctly clarified. The experimental rats were induced with middle cerebral artery occlusion (MCAO), and oxygen-glucose deprivation (OGD) model cells were constructed using human microvascular endothelial cell line (HMEC-1) cells. Cerebral infarction and pathological damage were first determined via triphenyl tetrazolium chloride (TTC) and hematoxylin and eosin (H&E) staining. Then, cell viability, apoptosis, and angiogenesis were assessed by utilizing cell counting kit-8 (CCK-8), flow cytometry, spheroid-based angiogenesis, and tube formation assays in OGD HMEC-1 cells. Besides, angiogenesis and other related proteins were identified with western blot. The study confirms that β-asarone, like nimodipine, can ameliorate cerebral infarction and pathological damage. β-asarone can also upregulate vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) and induce phosphorylation of p38. Besides, the study proves that β-asarone can protect against IS injury by increasing the expression of VEGFA. In vitro experiments affirmed that β-asarone can induce viability and suppress apoptosis in OGD-mediated HMEC-1 cells and promote angiogenesis of OGD HMEC-1 cells by upregulating VEGFA. This establishes the potential for β-asarone to be a latent drug for IS therapy.

Inhibition of TRAF6 alleviates secondary brain injury by reducing neuronal pyroptosis after intracerebral hemorrhage.

Secondary brain injury (SBI) is one of the main causes of high mortality and disability rates following intracerebral hemorrhage (ICH). TRAF6 plays a crucial role in the process of pyroptosis, and modulating its expression may present a novel therapeutic strategy for mitigating brain injury. This study aims to explore the mechanisms of TRAF6 in pyroptosis after ICH. C57BL/6J mice were used to establish the ICH model. Brain was collected at different time points for q-PCR and western blot to detect the level of TRAF6. After the C25-140 (the TRAF6 inhibitor) was administrated, the mice were divided into four groups. Then, the neurological deficit, brain water content, and blood-brain barrier (BBB) ​​damage were detected. Immunofluorescence and western blot were used to detect the level of pyroptosis proteins, and enzyme-linked immunosorbent assay (ELISA) and q-PCR were used to detect the levels of IL-18 and IL-1β. TRAF6 expression was upregulated after ICH and was mainly expressed in neurons. Inhibition of TRAF6 expression with C25-140 alleviated neurological deficits and reduced brain edema after ICH. In addition, inhibition of TRAF6 also reduced the expression of pyroptosis inflammasomes such as GSDMD, NLRP3, and ASC, as well as neurological damage caused by IL-18 and IL-1β after ICH. TRAF6 regulates neuronal pyroptosis in SBI after ICH. Inhibition of TRAF6 may be a potential target for alleviating inflammatory damage after ICH.

Integrative Bioinformatics Analysis Unravel the Association between Intracerebral Hemorrhage and Cellular Apoptosis through Immune Infiltration

Background. Intracerebral hemorrhage (ICH, IH) is a stroke syndrome characterized by high mortality and disability rates. However, the apoptotic mechanisms underlying ICH remain incompletely understood. We employed bioinformatics methods to identify key apoptotic genes associated with ICH, thereby offering potential therapeutic targets and contributing to a deeper understanding of the pathogenic mechanisms of apoptosis in ICH. Materials and Methods. We retrieved microarray data of ICH patients from the Gene Expression Omnibus database and intersected it with apoptotic genes, filtering out apoptosis‐related differentially expressed genes (ARDEGs). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted, and a logic regression‐based diagnostic model for ICH was constructed. Key genes were identified through least absolute shrinkage and selection operator regression after model validation. Subsequently, mRNA‐transcription factor (mRNA‐TF), mRNA–microRNA (mRNA–miRNA), mRNA‐RNA‐binding protein (mRNA‐RBP), and mRNA‐drug regulatory networks were established, followed by immune infiltration analysis. Results. We identified 29 ARDEGs related to ICH, primarily participating in biological processes such as the extrinsic apoptotic signaling pathway and neuroinflammatory response. The ICH model confirmed PPP1R15A, IL1R1, and TYROBP as key genes with diagnostic and therapeutic value. Thirteen immune cell types showed a correlation with ICH; notably, activated dendritic cells and CD56dim natural killer cells exhibited significant correlations, and key genes were positively correlated with all 13 immune cell types. The regulatory networks (mRNA‐TF, mRNA–miRNA, mRNA‐RBP, and mRNA‐drug) provided insights into the apoptotic gene regulation mechanisms and potential drugs in ICH. Conclusion. Through bioinformatics analysis, we identified PPP1R15A, IL1R1, and TYROBP as crucial genes in the occurrence and progression of ICH, with the potential involvement of Activated dendritic cells and CD56dim natural killer cells in these processes.

Inhibition of 15-hydroxyprostaglandin dehydrogenase protects neurons from ferroptosis in ischemic stroke.

Ischemic stroke is an acute serious cerebrovascular disease with high mortality and disability. Ferroptosis is an important regulated cell death (RCD) in ischemic stroke. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), a degrading enzyme of prostaglandin E2 (PGE2), is shown to regulate RCD such as autophagy and apoptosis. The study aimed to determine whether 15-PGDH regulates ferroptosis and ischemic stroke, and further the exact mechanism. We demonstrated that overexpression of 15-PGDH in the brain tissues or primary cultured neurons significantly aggravated cerebral injury and neural ferroptosis in ischemic stroke. While inhibition of 15-PGDH significantly protected against cerebral injury and neural ferroptosis, which benefits arise from the activation of the PGE2/PGE2 receptor 4 (EP4) axis. While the impact of 15-PGDH was abolished with glutathione peroxidase 4 (GPX4) deficiency. Then, 15-PGDH inhibitor was found to promote the activation of cAMP-response element-binding protein (CREB) and nuclear factor kappa-B (NF-κB) via the PGE2/EP4 axis, subsequently transcriptionally upregulate the expression of GPX4. In summary, our study indicates that inhibition of 15-PGDH promotes the activation PGE2/EP4 axis, subsequently transcriptionally upregulates the expression of GPX4 via CREB and NF-κB, and then protects neurons from ferroptosis and alleviates the ischemic stroke. Therefore, 15-PGDH may be a potential therapeutic target for ischemic stroke.

Migraine eye: correlation between migraine and the retina.

Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects. A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL). The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score. Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases.

CagA toxin and risk of Helicobacter pylori-infected gastric phenotype: A meta-analysis of observational studies.

Helicobacter pylori (H. pylori) is frequently associated with non-cardia type gastric cancer, and it is designated as a group I carcinogen. This study aimed to systematically review and meta-analyze the evidence on the prevalence of CagA status in people with gastric disorders in the Indo-Pacific region, and to examine the association of CagA positive in the risk of gastric disorders. This study focused on the Indo-Pacific region owing to the high disability adjusted life-years related to these disorders, the accessibility of efficient treatments for this common bacterial infection, and the varying standard of care for these disorders, particularly among the elderly population in the region. Relevant studies were identified in the health-related electronic databases including PubMed, Ovid, Medline, Ovid Embase, Index Medicus, and Google Scholar that were published in English between 1 January 2000, and 18 November 2023. For pooled prevalence, meta-analysis of proportional studies was done, after Freeman-Tukey double arcsine transformation of data. A random-effect model was used to compute the pooled odds ratio (OR) and 95% confidence interval (CI) to investigate the relationship between CagA positivity and gastric disorders. Twenty-four studies from eight Indo-Pacific countries (Bhutan, India, Indonesia, Malaysia, Myanmar, Singapore, Thailand, Vietnam) were included. Overall pooled prevalence of CagA positivity in H. pylori-infected gastric disorders was 83% (95%CI = 73-91%). Following stratification, the pooled prevalence of CagA positivity was 78% (95%CI = 67-90%) in H. pylori-infected gastritis, 86% (95%CI = 73-96%) in peptic ulcer disease, and 83% (95%CI = 51-100%) in gastric cancer. Geographic locations encountered variations in CagA prevalence. There was a greater risk of developing gastric cancer in those with CagA positivity compared with gastritis (OR = 2.53,95%CI = 1.15-5.55). Findings suggest that the distribution of CagA in H. pylori-infected gastric disorders varies among different type of gastric disorders in the study countries, and CagA may play a role in the development of gastric cancer. It is important to provide a high standard of care for the management of gastric diseases, particularly in a region where the prevalence of these disorders is high. Better strategies for effective treatment for high-risk groups are required for health programs to revisit this often-neglected infectious disease.

Dual-network DNA-silk fibroin hydrogels with controllable surface rigidity for regulating chondrogenic differentiation.

Osteoarthritis (OA) is a common joint disease known for cartilage degeneration, leading to a substantial burden on individuals and society due to its high disability rate. However, current clinical treatments for cartilage defects remain unsatisfactory due to the unclear mechanisms underlying cartilage regeneration. Tissue engineering hydrogels have emerged as an attractive approach in cartilage repair. Recent research studies have indicated that stem cells can sense the mechanical strength of hydrogels, thereby regulating their differentiation fate. In this study, we present the groundbreaking construction of dual-network DNA-silk fibroin (SF) hydrogels with controllable surface rigidity. The supramolecular networks, formed through DNA base-pairing, induce the development of β-sheet structures by constraining and aggregating SF molecules. Subsequently, SF was cross-linked via horseradish peroxidase (HRP)-mediated enzyme reactions to form the second network. Experimental results demonstrated a positive correlation between the surface rigidity of dual-network DNA-SF hydrogels and the DNA content. Interestingly, it was observed that dual-network DNA-SF hydrogels with moderate surface rigidity exhibited the highest effectiveness in facilitating the migration of bone marrow mesenchymal stem cells (BMSCs) and their chondrogenic differentiation. Transcriptome sequencing further confirmed that dual-network DNA-SF hydrogels primarily enhanced chondrogenic differentiation of BMSCs by upregulating the Wnt and TGF-β signaling pathways while accelerating collagen II synthesis. Furthermore, in vivo studies revealed that dual-network DNA-SF hydrogels with moderate surface rigidity significantly accelerated cartilage regeneration. In summary, the dual-network DNA-SF hydrogels represent a promising and novel therapeutic strategy for cartilage regeneration.

Together We Can Be #GreaterThanStroke

Stroke remains a disease that currently causes the highest disability among all diseases with thepotential to induce disability. Approximately 10 percent of stroke cases occur in patients under 45years of age, a period considered productive. Instant and drastic lifestyle changes constitute one of therisk factors for stroke. This is a concern for all of us because it not only holds the potential to lead tofinancial losses for patients and their families but also for th e country.Efforts to restore independence and facilitate a return to work are crucial aspects of evidence-basedrehabilitation management for post-stroke patients. The tagline commemorating International StrokeDay 2023, “Together We Can Be #GreaterThanStroke,”

Correlations between the Michigan Retinal Degeneration Questionnaire and visual function parameters in patients with retinitis pigmentosa.

To validate the use of best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD; the difference between BCVA and LLVA), mean macular sensitivity and fixation stability as parameters of vision-related quality of life based on the novel Michigan Retinal Degeneration Questionnaire (MRDQ) in retinitis pigmentosa (RP) patients. In this prospective cross sectional study, 30 patients with RP (47% female) were included with a median age of 41.0 years (interquartile range: 24.1-58.3 years). BCVA, LLVA and LLD were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Mesopic microperimetry was performed to measure mean macular sensitivity and fixation stability. Patients completed a Dutch translation of the MRDQ which results in an experienced disability (Θ-)score of seven domains. Spearman's rank correlation was used. BCVA correlated significantly to the MRDQ domain of central vision (r = 0.657; p < 0.001) and colour vision (r = 0.524; p = 0.003). Lower LLVA significantly correlated to higher experienced disability in the MRDQ domains for central vision (=0.550; p = 0.002) and contrast sensitivity (r = 0.502; p = 0.005). LLD was significantly correlated to the MRDQ domains of scotopic function (r = -0.484; p = 0.007) and mesopic peripheral function (r = -0.533; p = 0.002). Lower mean macular sensitivity was significantly associated with high experienced disability in all domains except for photosensitivity. The majority of the MRDQ domains is strongly associated with visual function parameters. These findings show that visual function measurements, especially LLVA, LLD and mean macular sensitivity on microperimetry, reflect vision-related quality of life and can be used as relevant outcome measures in clinical trials for RP.

Current Study on Brain Computer Interface with Virtual Reality in Upper Limb Rehabilitation

Cerebral stroke has been a great issue in the world due to its high mortality rate and disability rate. Rehabilitation for stroke patients has been a hot research field. However, conventional therapies for disabled patients depend mainly on medication and rehabilitation therapist, which is a painful and time-consuming process. Besides, the rehabilitation process requires volitional movement, which is a challenge for severe stroke patients. Therefore, researchers came up with an approach to combine brain-computer interface (BCI) with traditional therapies. Through brain-computer interface technology, researchers collect brain signals to strengthen the motor pathway. Virtual reality (VR) is also a new technique that can be utilized in rehabilitation. This paper studied research from several teams. A research team came up with a hybrid VR-BCI system and designed a classification model based on neural network. Another research team introduced an experiment on a VR- BCI combined platform called REINVENT. The team assessed the feasibility and effect of the platform by analyzing data collected during the study. In addition, A VR game was developed for mild patients. Current studies on VR-BCI combined system have proved its feasibility. However, more clinical data and further research are also needed to assess its effect on rehabilitation.

Characteristics of recurrence risk perception and coping strategies in patients with neuromyelitis optica spectrum disorder: A qualitative study

BackgroundAlthough neuromyelitis optica spectrum disorder (NMOSD) has high recurrence and disability rates, cases of relapses can be recognized, and timely intervention can be provided if the risk of relapse is properly perceived. However, there have been no studies to explore patients’ perceptions of recurrence risk and coping strategies. This study aimed to explore the characteristics of relapse risk perception and coping strategies of patients with NMOSD. MethodsWe adopted the phenomenological method of qualitative research. Face-to-face, semi-structured in-depth interviews were conducted with 15 patients with NMOSD. The interview data were then analyzed using the Colaizzi seven-step analysis. ResultsThe analysis revealed five major themes. The first theme was the 'perception of possibility of relapse', which included subjectively underestimating the likelihood of relapse and shifted from underestimation to overestimation; the second theme was 'relapse warning signs perception'; the third theme was 'perception of relapse triggers', which included understanding relapse triggers, potential misconceptions about relapse triggers, and no identifiable cause of recurrence; the fourth theme was 'perception of the relapse consequences', encompassing severe impairment of body structure and function, prominent psychological problems, limited family roles and social functions, and heavy financial burden; and the final theme was 'relapse risk coping strategies', which included actively yearning for and seeking information support, recurrence risk prevention/management, limitations of coping strategies. ConclusionsThis study's findings revealed that newly diagnosed patients as well as those who relapsed subjectively underestimated the likelihood of relapse before they had experienced multiple (two or more) relapses. In contrast, patients who had experienced multiple relapses had transitioned from initial underestimation to subsequent overestimation. Additionally, patients’ compliance with medication was identified as a relapse-risk behaviors that was very manageable. The occurrence of relapse is associated with significant and extensive adverse effects on patients. Consequently, patients are eager to communicate with their healthcare providers regarding treatment planning and relapse management.