CVD phenotyping in oncologic disorders: cardio-miRNAs as a potential target to improve individual outcomes in revers cardio-oncology.

With the increase of aging population and prevalence of obesity, the incidence of cardiovascular disease (CVD) and cancer has also presented an increasing tendency. These two different diseases, which share some common risk factors. Relevant studies in the field of reversing Cardio-Oncology have shown that the phenotype of CVD has a significant adverse effect on tumor prognosis, which is mainly manifested by a positive correlation between CVD and malignant progression of concomitant tumors. This distal crosstalk and the link between different diseases makes us aware of the importance of diagnosis, prediction, management and personalized treatment of systemic diseases. The circulatory system bridges the interaction between CVD and cancer, which suggests that we need to fully consider the systemic and holistic characteristics of these two diseases in the process of clinical treatment. The circulating exosome-miRNAs has been intrinsically associated with CVD -related regulation, which has become one of the focuses on clinical and basic research (as biomarker). The changes in the expression profiles of cardiovascular disease-associated miRNAs (Cardio-miRNAs) may adversely affect concomitant tumors. In this article, we sorted and screened CVD and tumor-related miRNA data based on literature, then summarized their commonalities and characteristics (several important pathways), and further discussed the conclusions of Cardio-Oncology related experimental studies. We take a holistic approach to considering CVD as a risk factor for tumor malignancy, which provides an in-depth analysis of the various regulatory mechanisms or pathways involved in the dual attribute miRNAs (Cardio-/Onco-miRNAs). These mechanisms will be key to revealing the systemic effects of CVD on tumors and highlight the holistic nature of different diseases. Therefore, the Cardio-miRNAs should be given great attention from researchers in the field of CVD and tumors, which might become new targets for tumor treatment. Meanwhile, based on the principles of precision medicine (such as the predictive preventive personalized medicine, 3PM) and reverse Cardio-oncology to better improve individual outcomes, we should consider developing personalized medicine and systemic therapy for cancer from the perspective of protecting cardiovascular function.

Differentially Expressed miR-511-3p in Stroke Patients Predicts the Presence of Post-Stroke Cognitive Impairment.

INTRODUCTION: Stroke is common cerebrovascular disease in the elderly, which is characterized by neurological defects caused by cerebral vessels. Multiple studies have shown that miRNAs play important roles in stroke. In addition, a large number of evidence suggest that stroke increases the risk and severity of cognitive impairments. METHODS: miR-511-3p expression levels were detected by real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-511-3p in distinguishing stroke patients from healthy controls and to assess risk of post-stroke cognitive impairment (PSCI) in stroke patients. Pearson correlation coefficient was used to determine the relationship between miR-511-3p expression level and Montreal Cognitive Assessment Scale (MoCA) scores. RESULTS: Serum miR-511-3p expression levels were decreased in stroke patients, and the decrease was more significant in PSCI patients. ROC curve results showed that miR-511-3p had high diagnostic accuracy in distinguishing healthy controls from stroke patients. Moreover, the expression level of miR-511-3p can be used as an independent predictor for the occurrence of PSCI and is positively correlated with MoCA scores of PSCI patients. CONCLUSION: miR-511-3p may be involved in the occurrence and development of stroke. In addition, miR-511-3p may be a novel biomarker for predicting PSCI occurred in stroke patients. These results may help improve the quality of prognosis of stroke.

Effectiveness of Rehabilitation Interventions in Individuals With Emerging Virtual Respiratory Tract Infectious Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Assessing rehabilitation effectiveness for persistent symptoms post-infection with emerging viral respiratory diseases. DATA SOURCES: Systematic review of seven databases (MEDLINE, EMBASE, Cochrane Library, PEDro, MedRxiv, CNKI, Wanfang) until 30 December 2023. REVIEW METHODS: Evaluated 101 studies (9593 participants) on respiratory function, exercise capacity, and quality of life. Methodological quality was assessed using the Cochrane Collaboration's Risk of Bias tool for randomized controlled trials (RCTs), the Newcastle-Ottawa Scale (NOS) for observational studies and non-RCTs, and the NIH Quality Assessment Tools for before-after studies. RESULTS: The most common rehabilitation program combined breathing exercises with aerobic exercise or strength training. Rehabilitation interventions significantly enhanced respiratory function, as evidenced by improvements on the Borg Scale (MD, -1.85; 95% CI, -3.00 to -0.70, low certainty), the mMRC Dyspnea Scale (MD, -0.45; 95% CI, -0.72 to -0.18, low certainty), and the Multidimensional Dyspnoea-12 Scale (MD, -4.64; 95% CI, -6.54 to -2.74, moderate certainty). Exercise capacity also improved, demonstrated by results from the Six-Minute Walk Test (MD, 38.18; 95% CI, 25.33-51.03, moderate certainty) and the Sit-to-Stand Test (MD, 3.04; 95% CI, 1.07-5.01, low certainty). CONCLUSION: Rehabilitation interventions are promising for survivors of viral respiratory diseases, yet gaps in research remain. Future investigations should focus on personalizing rehabilitation efforts, utilizing remote technology-assisted programs, improving research quality, and identifying specific subgroups for customized rehabilitation strategies to achieve the best outcomes for survivors.

HK2: a potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways.

Osteoarthritis (OA) is an age-related chronic degenerative joint disease where the main characteristics include progressive degeneration of cartilage, varying degrees of synovitis, and periarticular osteogenesis. However, the underlying factors involved in OA pathogenesis remain elusive which has resulted in poor clinical treatment effect. Recently, glucose metabolism changes provide a new perspective on the pathogenesis of OA. Under the stimulation of external environment, the metabolic pathway of chondrocytes tends to change from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Previous studies have demonstrated that glycolysis of synovial tissue is increased in OA. The hexokinase (HK) is the first rate limiting enzyme in aerobic glycolysis, participating and catalyzing the main pathway of glucose utilization. An isoform of HKs, HK2 is considered to be a key regulator of glucose metabolism, promotes the transformation of glycolysis from OXPHOS to aerobic glycolysis. Moreover, the expression level of HK2 in OA synovial tissue (FLS) was higher than that in control group, which indicated the potential therapeutic effect of HK2 in OA. However, there is no summary to help us understand the potential therapeutic role of glucose metabolism in OA. Therefore, this review focuses on the properties of HK2 and existing research concerning HK2 and OA. We also highlight the potential role and mechanism of HK2 in OA. Video abstract.

Knockdown of circHECTD1 inhibits oxygen-glucose deprivation and reperfusion induced endothelial-mesenchymal transition.

Ischemic stroke (IS) has become a cerebrovascular disease which seriously threatens the elderly people. It has been reported that circRNAs participate in multiple diseases, including IS. However, the role of circHECTD1 in IS remains largely unknown. To mimic IS in vitro, human cerebral microvascular endothelial cells (HCMECs) were treated with oxygen glucose deprivation/reperfusion (OGD/R). Meanwhile, MCAO mouse model was established to detect the expression of circHECTD1 in IS. qRT-PCR and western blot were used to test gene and protein expressions, respectively. CCK-8 assay was used to investigate the cell viability. Moreover, cell migration and tube formation were assessed by transwell and tube formation assays. In addition, RIP and luciferase assay were performed to explore the association among circHECTD1, miR-335 and NOTCH2. CircHECTD1 was significantly upregulated in IS. OGD/R significantly induced EndoMT in HCMECs, while knockdown of circHECTD1 notably reversed this phenomenon. In addition, silencing of circHECTD1 remarkably reversed OGD/R-induced promotion of HCMEC tube formation and migration. Meanwhile, circHECTD1 upregulated the level of NOTCH2 through binding with miR-335. Furthermore, miR-335 inhibited the process of EndoMT in IS via targeting NOTCH2. In summary, circHECTD1 knockdown significantly alleviated EndoMT process in HCMECs via mediation of miR-335/NOTCH2 axis. Thus, circHECTD1 might act as a potential target against IS.

An evidence-based tailored eHealth patient education tool for patients with knee osteoarthritis: protocol for a randomized controlled trial.

BACKGROUND: Osteoarthritis is a common and disabling condition that places heavy burden to individuals and healthcare systems. Patient education is a facilitator in the treatment decision making process, aiming to develop a treatment plan for the disease management. Electronic health (eHealth) is an alternative forum for the delivery of patient education and given the prevailing of eHealth in healthcare, introducing patient education programs using the technology has the potential to improve patient engagement, self-management and outcomes in patients with osteoarthritis. The study will evaluate the efficacy of eHealth patient education tool on patients' perception of knee osteoarthritis and treatment options, satisfaction and compliance to treatments. METHODS: This study is a prospective randomized controlled trial with a 1:1 allocation in two groups. We will recruit 216 patients diagnosed with knee osteoarthritis from the outpatient physiatry/physiotherapy clinic at West China Hospital, Sichuan University in Southwest China. Both groups will receive usual care and additionally, the intervention group will use eHealth patient education tool during the process. Measurements will be taken at baseline, post-intervention, 1 month, 3- and 6-months follow-up. Primary outcome will be patients' knowledge about disease and treatment options, measured by the validated osteoarthritis patient knowledge questionnaire. Secondary outcomes include patients' satisfaction with the consultation, the eHealth patient education tool, and their trust of the physiotherapist. DISCUSSION: The eHealth patient education tool is designed to provide participants with an innovative model of care delivery and this trial will assess the efficacy of the tool and whether this new model of patient education will have the potential to increase patient knowledge and empower self-management. Results collected from this study will further inform future research employing eHealth tool as interventions for the management of a range of other chronic conditions and help participants in communities or rural areas having the equal access to health care services. TRIAL REGISTRATION: This study was prospectively registered on the Chinese Clinical Trials Registry ( ChiCTR2100051083 ) registered 12.09.2021.

Alzheimer's disease in elderly COVID-19 patients: potential mechanisms and preventive measures.

Advanced age correlates with higher morbidity and mortality among patients affected with the novel coronavirus disease 2019 (COVID-19). Because systemic inflammation and neurological symptoms are also common in severe COVID-19 cases, there is concern that COVID-19 may lead to neurodegenerative conditions such as Alzheimer's disease (AD). In this review, we summarize possible mechanisms by which infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, may cause AD in elderly COVID-19 patients and describe preventive measures to mitigate risk. Potential mechanisms include NLRP3 inflammasome activation and IL-1ß release, renin-angiotensin system hyperactivation, innate immune activation, oxidative stress, direct viral infection, and direct cytolytic ß-cell damage. Anti-inflammatory therapies, including TNF-α inhibitors and nonsteroidal anti-inflammatory drugs, antioxidants such as the vitamin E family, nutritional intervention, physical activity, blood glucose control, and vaccination are proposed as preventive measures to minimize AD risk in COVID-19 patients. Since several risk factors for AD may converge during severe SARS-CoV-2 infection, neurologists should be alert for potential symptoms of AD and actively implement preventive measures in patients presenting with neuropsychiatric symptoms and in high-risk patients such as the elderly.

Effects of Pulsed Electromagnetic Field Therapy at Different Frequencies on Bone Mass and Microarchitecture in Osteoporotic Mice.

A pulsed electromagnetic field (PEMF) can promote osteogenesis. However, studies have shown variation in the signal characteristics in terms of waveform type, intensity, frequency, and treatment duration. Among the factors that affect electromagnetic fields, frequency plays a major role. However, few studies have investigated the effects of PEMF at different frequencies in osteoporotic mice. Therefore, our objective was to determine the effect of PEMF frequency in osteoporotic mice. Forty 3-month-old female mice were randomly divided into the following five groups: sham, OVX, and OVX followed by 1.6-mT PEMF exposure groups (8 Hz, 50 Hz, and 75 Hz, 1.6 mT). The PEMF was applied for 1 h/day, 7 days/week, for 4 weeks. After 4 weeks, the micro-computed tomography showed that PEMF with (50 and 75 Hz) ameliorated the deterioration of bone microarchitecture. Improvements in the bone histological analysis were identified for PEMF with 50 and 75 Hz groups compared with the ovariectomy (OVX) controls. Osteoclast numbers were decreased in PEMF with (50 and 75 Hz). Moreover, the real-time PCR demonstrated PEMF with (50 and 75 Hz) significantly promoted the expression of the osteoblast-related genes (ALP, OCN, Runx2), and increased the serum PINP. PEMF with (50 and 75 Hz) exerted significant inhibitory effects on the osteoclast-related mRNA expression (CTSK, NFATc1, TRAP) and bone resorption markers CTX-I and IL-1ß. Taken together, our results showed that PEMF at 50 and 75 Hz with 1.6 mT significantly ameliorate the deterioration of bone microarchitecture in OVX mice. The inhibitory effect of PEMF may be associated with IL-1ß inhibition. © 2021 Bioelectromagnetics Society.

Effect of Internet-Based Rehabilitation Programs on Improvement of Pain and Physical Function in Patients with Knee Osteoarthritis: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Osteoarthritis (OA) is a chronic, debilitating, and degenerative joint disease. However, it is difficult for patients with knee OA to access conventional rehabilitation when discharging from the hospital. Internet-based rehabilitation is one of the promising telemedicine strategies to provide a means combining monitoring, guidance, and treatment for patients with knee OA. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis for assessing the effect of internet-based rehabilitation programs on pain and physical function in patients with knee OA. METHODS: Keywords related to knee OA and internet-based rehabilitation were systematically searched in the Web of Science, MEDLINE, EMBASE, CENTRAL, Scopus, PEDro (Physiotherapy Evidence Database), CNKI, SinoMed, and WANFANG databases from January 2000 to April 2020. Only randomized controlled trials were included. The authors independently screened the literature. The main outcome measures were focused on pain and physical function. A meta-analysis was performed on the collected data. Review Manager (RevMan, version 5.3) was used for all analyses. RESULTS: The systematic review identified 6 randomized controlled trials, 4 of which were included in the meta-analysis, comprising a total of 791 patients with knee OA. The meta-analysis with the fixed-effects model showed that the internet-based rehabilitation programs could significantly alleviate the osteoarthritic pain for patients compared with conventional rehabilitation (standardized mean difference [SMD] -0.21, 95% CI -0.4 to -0.01, P=.04). No significant difference was found in the improvement of physical function in patients with knee OA compared with conventional rehabilitation within 2 to 12 months (SMD -0.08, 95% CI -0.27 to 0.12, P=.43). CONCLUSIONS: This systematic review shows that internet-based rehabilitation programs could improve the pain but not physical function for patients with knee OA. However, there was a very small number of studies that could be included in the review and meta-analysis. Thus, further studies with large sample sizes are warranted to promote the effectiveness of internet-based rehabilitation and to develop its personalized design.

Acute ischemic stroke patients with diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score ≤ 5 can benefit from endovascular treatment: a single-center experience and literature review.

PURPOSE: The recommendation strength of the guidelines for mechanical thrombectomy among patients with large pre-treatment core infarct is weak. We evaluated the safety and outcome of endovascular treatment for acute ischemic stroke with diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) ≤ 5. METHODS: Data on acute ischemic stroke patients with DWI-ASPECTS ≤ 5 who underwent endovascular treatment within 6 h, or presented an arterial spin labeling-DWI (ASL-DWI) mismatch within 12 h, at our center were retrospectively collected. We report the clinical characteristics and outcome of every patient, and review the relevant literature. RESULTS: Among the 19 patients who were enrolled, all experienced successful reperfusion, and 10 achieved a favorable outcome (modified Rankin scale (mRS) ≤ 2). Two patients presented with symptomatic intracranial hemorrhage (sICH); both of them had a poor outcome (mRS > 2). CONCLUSION: Acute ischemic stroke patients with large DWI lesions caused by large vessel occlusion can achieve a favorable clinical outcome with endovascular treatment if recanalization is performed within 6 h, or after 6 h in case of an ASL-DWI mismatch.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism, atherosclerosis and ischemic stroke.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the proprotein convertase family. It is an important regulator of cholesterol metabolism. PCSK9 can bind to low-density lipoprotein receptors (LDLRs) and induce the degradation of these receptors through the endosome/lysosome pathway, thus decreasing the LDLR levels on the cell surface of hepatocytes, resulting in increased serum low-density lipoprotein cholesterol (LDL-C) concentrations. Recent studies have found that gene polymorphisms of PCSK9 are associated with hypercholesterolemia, risk of atherosclerosis, and ischemic stroke. Furthermore, monoclonal antibodies, peptide mimetics, small molecule inhibitors and gene silencing agents that are associated with PCSK9 are some of the newer pharmaceutical therapeutic strategies and approaches for lowering serum LDL-C levels. In this review, we will discuss recent advances in PCSK9 research, which show that PCSK9 is correlated with lipid metabolism, atherosclerosis, and, in particular, ischemic stroke. We will also discuss the current state of PCSK9 therapeutics and their potential in modulating these diseases.

Higher homocysteine and fibrinogen are associated with early-onset post-stroke depression in patients with acute ischemic stroke.

Background: Post-stroke depression (PSD) is a well-established psychiatric complication following stroke. Nevertheless, the relationship between early-onset PSD and homocysteine (Hcy) or fibrinogen remains uncertain. Methods: Acute ischemic stroke (AIS) patients who met the established criteria were enrolled in this study. Early-onset PSD was diagnosed two weeks after the stroke. The severity of depressive symptoms was assessed by the Hamilton Depression Scale-17 items (HAMD-17), with patients scored ≥7 assigned to the early-onset PSD group. Spearman rank correlation analysis was employed to evaluate the associations between Hcy, fibrinogen, and HAMD scores across all patients. Logistic regression analysis was conducted to investigate the relationship between Hcy, fibrinogen, and early-onset PSD. Receiver operating characteristic curve (ROC) analysis was ASSDalso performed to detect the predictive ability of Hcy and fibrinogen for early-onset PSD. Results: Among the 380 recruited patients, a total of 106 (27.89%) patients were diagnosed with early-onset PSD. The univariate analysis suggested that patients in the PSD group had a higher admission National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale score (mRS), Hcy, and fibrinogen levels than patients in the non-PSD group (P<0.05). The logistic regression model indicated that Hcy (odds ratio [OR], 1.344; 95% confidence interval [CI] 1.209-1.494, P<0.001) and fibrinogen (OR, 1.57 6; 95% CI 1.302-1.985, P<0.001) were independently related to early-onset PSD. Area under curve (AUC) of Hcy, fibrinogen, and Hcy combined fibrinogen to predict early-onset PSD was 0.754, 0.698, and 0.803, respectively. Conclusion: This study indicates that Hcy and fibrinogen may be independent risk factors for early-onset PSD and can be used as predictive indicators for early-onset PSD.

Higher fibrinogen and neutrophil-to-lymphocyte ratio are associated with the early poor response to intravenous thrombolysis in acute ischemic stroke.

Background: Inflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear. Methods: AIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score <4 at the 24 h after thrombolysis treatment compared with that at admission. Logistic regression analysis was performed to explore the relationship of the fibrinogen level and NLR with a poor thrombolysis response. Receiver operating characteristic (ROC) analysis was used to assess the ability of the fibrinogen level and NLR to discriminate poor responders. Results: Among 700 recruited patients, 268 (38.29%) were diagnosed with a good response, and 432 (61.71%) were diagnosed with a poor response to intravenous thrombolysis. A binary logistic regression model indicated that an elevated fibrinogen level (odds ratio [OR], 1.693; 95% confidence interval [CI] 1.325-2.122, P < 0.001) and NLR (OR, 1.253; 95% CI, 1.210-2.005, P = 0.001) were independent factors for a poor response. The area under the curve (AUC) values for the fibrinogen level, NLR and fibrinogen level combined with the NLR for a poor response were 0.708, 0.605, and 0.728, respectively. Conclusions: Our research indicates that the levels of fibrinogen and NLR at admission can be used as a prognostic factor to predict early poor response to intravenous thrombolysis.

Metabolic and cardiovascular responses to continuous and intermittent plank exercises.

BACKGROUND: Plank exercise (PE) is a whole-body isometric muscle training which is beneficial for physical health. However, none of the previous studies investigated the responses within a typical isometric muscle training or PE protocol consisting of multiple sets. The application of PE was restricted for the understudied metabolic and cardiovascular responses, especially for the patients with cardiovascular diseases. This study is to alleviate the safety concerns of PE by investigating the PE-induced metabolic and cardiovascular responses. METHODS: Eleven male recreational-level college students completed a baseline cardiopulmonary exercise test, continuous PE (CPE) and intermittent PE (IPE). Ratio of maximal oxygen uptake per kilogram of body mass (%VO2max/kg), ratio of maximal heart rate (%HRmax), and respiratory exchange ratio (RER) were continuously measured during PEs and divided into seven equal timepoints. Blood pressure (BP) was measured every minute during, before, and after PEs. A mixed-model repeated measures ANOVA was used to examine the interaction effect of exercise × phase. RESULTS: The %VO2max/kg (F6,69=11.25, P < 0.001), %HRmax (F6,65=7.74, P < 0.001), RER (F6,69=11.56, P < 0.001), and BP (systolic BP, F2,26=8.42, P = 0.002; diastolic BP, F2,24=22.63, P < 0.001) increased by safe magnitudes. Compared with the corresponding period in the IPE group, the %VO2max/kg (33.5 [2.2] vs. 27.7 [1.9], P = 0.043) and %HRmax (63.2 [3.9] vs. 53.3 [2.1], P = 0.019) increased more significantly from the 40% duration of CPE. Systolic BP increased by larger magnitudes during CPE than IPE (154.2 [3.8] vs. 142.3 [4.8] mmHg, P = 0.002). RERs were over 1 during PEs without cardiovascular and metabolic variables over the anaerobic threshold. CONCLUSION: Energy was mainly supplied by anaerobic metabolism during PEs. CPE may be preferable for trainees aiming at anaerobic capacity enhancement. IPEs may be preferable to CPEs for youth patients with mild and borderline cardiovascular diseases due to their lower metabolic and cardiovascular responses.

APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is one of the most hazardous tumors in the urinary system. The regulation of oxygen consumption in renal clear cell carcinoma is a consequence of adaptive reprogramming of oxidative metabolism in tumor cells. APPL1 is a signaling adaptor involved in cell survival, oxidative stress, inflammation, and energy metabolism. However, the correlation of APPL1 with regulatory T cell (Treg) infiltration and prognostic value in KIRC remain unclear. In this study, we comprehensively predicted the potential function and prognostic value of APPL1 in KIRC. For KIRC patients, relatively low expression of APPL1 was associated with high degree of metastasis, pathological stage, and shorter overall time or poor prognosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggested that low expression of APPL1 may be adapted to the malignant progression of tumors via affecting oxygen-consuming metabolism. In addition, the expression level of APPL1 was negatively correlated with Treg cell infiltration and chemotherapy sensitivity, which indicated that APPL1 may regulate the tumor immune infiltration and chemotherapy resistance by decrease oxygen-consuming metabolic process in KIRC. Therefore, APPL1 may become one of the important prognostic factors, and it may serve as a candidate prognostic biomarker in KIRC.

Bone-derived PDGF-BB drives brain vascular calcification in male mice.

Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel calcifications in peripheral tissue is well studied, but microvascular calcification in the brain remains poorly understood. Here, we report that elevated platelet-derived growth factor BB (PDGF-BB) from bone preosteoclasts contributed to cerebrovascular calcification in male mice. Aged male mice had higher serum PDGF-BB levels and a higher incidence of brain calcification compared with young mice, mainly in the thalamus. Transgenic mice with preosteoclast-specific Pdgfb overexpression exhibited elevated serum PDGF-BB levels and recapitulated age-associated thalamic calcification. Conversely, mice with preosteoclast-specific Pdgfb deletion displayed diminished age-associated thalamic calcification. In an ex vivo cerebral microvascular culture system, PDGF-BB dose-dependently promoted vascular calcification. Analysis of osteogenic gene array and single-cell RNA-Seq (scRNA-Seq) revealed that PDGF-BB upregulated multiple osteogenic differentiation genes and the phosphate transporter Slc20a1 in cerebral microvessels. Mechanistically, PDGF-BB stimulated the phosphorylation of its receptor PDGFRß (p-PDGFRß) and ERK (p-ERK), leading to the activation of RUNX2. This activation, in turn, induced the transcription of osteoblast differentiation genes in PCs and upregulated Slc20a1 in astrocytes. Thus, bone-derived PDGF-BB induced brain vascular calcification by activating the p-PDGFRß/p-ERK/RUNX2 signaling cascade in cerebrovascular cells.

Dl-3-n-butylphthalide attenuates brain injury caused by cortical infarction accompanied by cranial venous drainage disturbance.

BACKGROUND: Cerebral venous disorder may have a harmful effect on ischaemic stroke; however, the underlying mechanism remains to be elucidated. Although Dl-3-n-butylphthalide is a multitarget agent for antiischaemic stroke, its neuroprotective role in brain ischaemia accompanied by brain venous disturbance remains unclear. In this study, we induced cerebral venous disturbance by the occlusion of bilateral external jugular veins (EJVs) to explore the potential mechanism of the adverse effects of cerebrovenous disorders in cerebral infarction and explore the protective effect of Dl-3-n-butylphthalide on cerebral infarction accompanied through cerebral venous disturbance. METHODS: Cerebral venous disturbance was induced in Sprague-Dawley rats through the permanent occlusion of bilateral EJVs, and cerebral ischaemic stroke was induced through the permanent occlusion of the right cortical branches of the middle cerebral artery. 2,3,5-triphenyltetrazolium chloride staining, MRI, Evans blue extravasation and behavioural test were performed to evaluate infarction volume, cerebral blood flow (CBF), blood-brain barrier (BBB) integrity and neurological function. Immunofluorescence staining and western blot analysis were performed to detect loss of neuron, endothelial cells, pericytes and tight junctions. RESULTS: Bilateral EJVs occlusion did not cause cerebral infarction; however, it increased the infarction volume compared with the simple middle cerebral artery occlusion (MCAO) group, accompanied by severe neuron loss, worse neurological function, lower CBF, increased EJVs pressure, exacerbated Evans blue extravasation and brain oedema, as well as attenuated angiogenesis. Dl-3-n-butylphthalide displayed a neuroprotective effect in rats with MCAO accompanied by EJVs occlusion by reducing neuron loss, accelerating CBF restoration, promoting angiogenesis and relieving BBB damage. CONCLUSION: Bilateral EJVs occlusion did not significantly affect normal rats but aggravated brain damage in the case of ischaemic stroke. Dl-3-n-butylphthalide treatment plays a neuroprotective role in rats with MCAO accompanied by EJVs occlusion, mainly due to the promotion of CBF restoration and BBB protection.

Effects of Internet of Things-based power cycling and neuromuscular training on pain and walking ability in elderly patients with KOA: protocol for a randomized controlled trial.

BACKGROUND: Osteoarthritis (OA) is a common and highly disabling disease that imposes a heavy burden on individuals and society. Although physical therapy is recommended as an important method to relieve OA symptoms, patients cannot continue treatment after returning home. Research on Internet telerehabilitation for knee osteoarthritis (KOA) can reduce pain and improve patient quality of life, and Internet of Things (IoT)-based telerehabilitation is a new form of delivering rehabilitation. This study will evaluate the effect of telerehabilitation via IoT, as a medium to deliver exercises, on pain and walking in patients with KOA. METHODS: This study is a single-blind randomized controlled trial. We will recruit 42 middle-aged and elderly patients with KOA aged ≥ 50 years and randomly divided into power cycling group, neuromuscular exercise group, and control group, and intervention will last for 12 weeks. Outcome measures will be taken at baseline and 4 weeks, 8 weeks, and 12 weeks post-intervention. The pre- and posttreatment differences in knee pain and physical function between participants undergoing power cycling and neuromuscular training and those in the control group will be determined by each scale. The effectiveness will be assessed by the Western Ontario and McMaster Universities Osteoarthritis Index Score (WOMAC) and an 11-point numerical pain rating scale. Walking function and quality of life will be assessed by the timed up and go and walk test, 6-min walk test, and quality of life health status questionnaires. DISCUSSION: The findings from this trial will establish the feasibility and effectiveness of IoT-based power cycling and neuromuscular training on elderly patients with KOA in the community. As a result, this trial may help provide experimental evidence for finding a better exercise method suitable for elderly patients with KOA in the community. TRAIL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2200058924. Prospectively registered on 6 May 2022.

Inverted U-shaped Relationship Between Mean Platelet Volume/Platelet Count Ratio and Post-thrombolytic Early Neurological Deterioration in Patients with Mild and Moderate Stroke.

OBJECTIVE: The objective of this study is to investigate the relationship between mean platelet volume (MPV)/platelet count (PC) ratio and post-thrombolytic early neurological deterioration (END) in patients with mild and moderate stroke. METHODS: Mild and moderate stroke patients treated with intravenous thrombolysis (IVT) at the Affiliated Changsha Central Hospital of the University of South China between January 2016 and March 2022 were prospectively and consecutively enrolled. END was defined as an increase in the total National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or an increase in the motor items of ≥1 point within 24 hours after IVT treatment. Logistic regression and restricted cubic spline models were used to estimate the relationship between the MPV/PC ratio and postthrombolytic END. RESULTS: Among the 406 patients recruited, 64 (15.8%) patients developed END. Patients in the first quintile of MPV/PC ratio (adjusted OR = 0.27, 95% CI = 0.11-0.66, p = 0.004) and the fifth quintile (adjusted OR = 0.26, 95% CI = 0.10-0.69, p = 0.007) had a significantly lower risk of END compared with those in the third quintile. Restricted cubic spline analysis revealed an inverted U-shaped relationship between the MPV/PC ratio and END (p for nonlinearity = 0.016). MPV/PC ratio cut-off value associated with the highest END risk was 51.0. An MPV/PC ratio ≤ 51.0 was shown to be positively associated with END (adjusted OR = 1.07, 95% CI = 1.02-1.14, p = 0.012), while an MPV/PC ratio >51.0 was negatively associated with END (adjusted OR = 0.94, 95% CI = 0.88-1.00, p = 0.040). A significant interaction existed between the MPV/PC ratio and age in the low MPV/PC ratio group (p = 0.012). MPV/PC ratio was positively associated with END only in patients ≥ 60 years, whereas this association was insignificant in patients < 60 years. CONCLUSION: An inverted U-shaped relationship between the MPV/PC ratio on admission and postthrombolytic END was identified in patients with mild and moderate stroke, with a threshold MPV/PC ratio of 51.0. The MPV/PC ratio closer to the threshold was associated with a higher risk of post-thrombolytic END.