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1.
Article En | MEDLINE | ID: mdl-38713588

OBJECTIVE: Poststroke spasticity (PSS) reduces arm function and leads to low levels of independence. This study suggested applying machine learning (ML) from routinely available data to support the clinical management of PSS. DESIGN: 172 patients with acute first-ever stroke were included in this prospective cohort study. Twenty clinical information and rehabilitation assessments were obtained to train various ML algorithms for predicting 6-month PSS defined by a modified Ashworth scale (MAS) score ≥ 1. Factors significantly relevant were also defined. RESULTS: The study results indicated that multivariate adaptive regression spline (area under the curve (AUC) value: 0.916; 95% confidence interval (CI): 0.906-0.923), adaptive boosting (AUC: 0.962; 95% CI: 0.952-0.973), random forest (RF) (AUC: 0.975; 95% CI: 0.968-0.981), support vector machine (SVM) (AUC: 0.980; 95% CI: 0.970-0.989) outperformed the traditional logistic model (AUC: 0.897; 95% CI: 0.884-0.910) (P < 0.05). Among all of the algorithms, the RF and SVM models outperformed the others (P < 0.05). FMA score, days in hospital, age, stroke location, and paretic side were the most important features. CONCLUSION: These findings suggest that ML algorithms can help augment clinical decision-making processes for the assessment of PSS occurrence, which may enhance the efficacy of management for patients with PSS in the future.

2.
Nat Cell Biol ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38671262

The mechanisms underlying the dynamic remodelling of cellular membrane phospholipids to prevent phospholipid peroxidation-induced membrane damage and evade ferroptosis, a non-apoptotic form of cell death driven by iron-dependent lipid peroxidation, remain poorly understood. Here we show that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a critical role in ferroptosis resistance by increasing membrane phospholipid saturation via the Lands cycle, thereby reducing membrane levels of polyunsaturated fatty acids, protecting cells from phospholipid peroxidation-induced membrane damage and inhibiting ferroptosis. Furthermore, the enhanced in vivo tumour-forming capability of tumour cells is closely associated with the upregulation of LPCAT1 and emergence of a ferroptosis-resistant state. Combining LPCAT1 inhibition with a ferroptosis inducer synergistically triggers ferroptosis and suppresses tumour growth. Therefore, our results unveil a plausible role for LPCAT1 in evading ferroptosis and suggest it as a promising target for clinical intervention in human cancer.

3.
Article En | MEDLINE | ID: mdl-38545792

Aims: Although there is evidence that patients with stroke who exercise regularly before stroke have a better prognosis than those who do not exercise, the detailed mechanism remains unclear. Moreover, neuronal death plays a central role in neurological dysfunction caused by ischemic stroke. Thus, we investigated whether exercise could reduce stroke-induced neuronal death and its associated mediators in the current study. Results: Ferroptosis was the most dominant form of programmed cell death in neurons. Preconditioning exercise before stroke improved the neurological function and decreased the infarct area in rats with ischemic stroke. Preconditioning exercise attenuated stroke-induced ferroptosis by reducing lipid peroxidation (LPO) production, upregulating glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and downregulating acyl-CoA synthetase long-chain family member 4 (ACSL4). High-throughput sequencing and dual luciferase reporter assays revealed that exercise-induced exosomal miR-484 inhibits Acsl4 expression. Moreover, we showed that exercise-induced exosomal miR-484 is mainly derived from skeletal muscle, and the neuroprotective effect of preconditioning exercise is suppressed by inhibiting miR-484 production in skeletal muscle. Innovation: This study suggested that neuronal ferroptosis is the most dominant form of programmed cell death in a hypoxic environment. Moreover, we showed that the ferroptosis pathway is a potential therapeutic target in ischemic stroke and that preconditioning exercise could be an effective antioxidant intervention for cerebral ischemia. Conclusion: Our work revealed that preconditioning exercise before stroke exerts neuroprotective effects against brain ischemia by skeletal muscle-derived exosomal miR-484 via inhibiting ferroptosis.

4.
Medicine (Baltimore) ; 103(10): e37446, 2024 Mar 08.
Article En | MEDLINE | ID: mdl-38457547

RATIONALE: Compound heterozygotes for deletional ß-thalassemia can be difficult to diagnose due to its diverse clinical presentations and no routine screenings. This can lead to disease progression and delay in treatment. PATIENT CONCERNS: We reported pedigree analysis and genetic research in a family with rare ß-thalassemia. DIAGNOSIS: Pedigree analysis and genetic research demonstrated that the patient was a compound heterozygote for ß-thalassemia CD17/Southeast Asian hereditary persistence of fetal hemoglobin deletion, inherited from the parents. Magnetic resonance imaging T2* examination revealed severe iron deposition in the liver. Echocardiography revealed endocardial cushion defect. INTERVENTIONS: The patient was treated with Deferasirox after receiving the final molecular genetic diagnosis. The initial once-daily dose of Deferasirox was 20 mg/kg/d. OUTCOMES: The patient discontinued the medication three months after the first visit. Two years later, the patient visited the Department of Hepatobiliary and Pancreatic Diseases. He was recommended to undergo splenectomy after surgical repair of the congenital heart disease. However, the patient refused surgical treatment because of the economic burden. LESSONS: We report that fetal hemoglobin is a sensitive indicator for screening large deletions of the ß-globin gene, which can be effectively confirmed by the multiplex ligation-dependent probe amplification assay. In non-transfusion-dependent thalassemia patients, iron status assessment should be regularly performed, and iron chelation treatment should be initiated early. This case will provide insights for the diagnosis of rare genotypes of ß-thalassemia and has important implications for genetic counseling.


beta-Thalassemia , Male , Humans , beta-Thalassemia/genetics , beta-Thalassemia/diagnosis , Fetal Hemoglobin/genetics , Pedigree , Deferasirox , Southeast Asian People , Genetic Research , China , Iron , Heterozygote
5.
Am J Speech Lang Pathol ; 33(2): 937-951, 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38266215

PURPOSE: This study was designed to examine the hypothesis that discourse task types influence language performance in Mandarin Chinese-speaking people and to reveal the discourse task-specific linguistic properties of persons with anomic aphasia compared to neurotypical controls. METHOD: Language samples from persons with aphasia (n = 31) and age- and education-matched controls (n = 31) across four discourse tasks (sequential-picture description, single-picture description, story narrative, and procedural discourse) were collected from Mandarin AphasiaBank. Task-specific distributions of parts of speech were analyzed using mosaic plots. The main effects of tasks in each group and the between-group differences within each task for several typical linguistic variables were evaluated, including the mean length of utterance, tokens, moving-average type-token ratio, words per minute, propositional density, noun-verb ratio, noun percentage, and verb percentage. RESULTS: The results revealed an impact of discourse tasks on most language variables in both groups. In the healthy controls, story narratives yielded the highest total words and lowest verb percentage. In the aphasia group, procedural discourse elicited the fewest total words and densest expressions, whereas their single-picture descriptions had the highest noun-verb ratio. For all tasks, the aphasia group performed worse than the control group in the mean length of utterance, tokens, moving-average type-token ratio, and words per minute. For noun-verb ratio, noun percentage, and verb percentage, only one task (i.e., single-picture description) showed significant between-group differences. CONCLUSION: The selection of discourse tasks should be addressed in assessments and interventions for Mandarin Chinese-speaking individuals with aphasia to obtain more accurate and feasible outcomes.


Anomia , Aphasia , Humans , Linguistics , Aphasia/diagnosis , Language , China
6.
Clin Neurophysiol ; 158: 43-55, 2024 02.
Article En | MEDLINE | ID: mdl-38176157

OBJECTIVE: This study aimed to explore the effect of catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met to post-stroke cognitive impairment (PSCI) and the interaction with transcranial direct current stimulation (tDCS). METHODS: Seventy-six patients with PSCI were randomly assigned to Group (1) (n = 38) to receive anodal tDCS of left dorsolateral prefrontal cortex or Group (2) (n = 38) to receive sham stimulation. The intensity of the tDCS was 2 mA, and the stimulations were applied over the left DLPFC for 10 sessions. The Montreal Cognitive Assessment (MoCA) and backward digit span test (BDST) were assessed before, immediately after, and one month after stimulation. RESULTS: After stimulation, patients in the tDCS group showed better improvement in both MoCA and BDST than those in the sham group. The results of GLMs also supported the main effects of tDCS on general cognitive function and working memory. Then we found that COMT genotype may have a main effect on the improvement of MoCA and BDST, and there may be an interaction between COMT genotype and tDCS in enhancing BDST. In contrast, BDNF genotype showed no significant main or interaction effects on any scales. CONCLUSIONS: These findings demonstrate that tDCS can improve cognition after stroke. Gene polymorphisms of COMT can affect the efficacy of tDCS on PSCI, but BDNF may not. SIGNIFICANCE: This study found that COMT Val158Met has an interaction on the efficacy of prefrontal tDCS in cognitive function, which provides reference for future tDCS research and clinical application.


Cognitive Dysfunction , Stroke , Transcranial Direct Current Stimulation , Humans , Transcranial Direct Current Stimulation/methods , Catechol O-Methyltransferase/genetics , Brain-Derived Neurotrophic Factor/genetics , Prefrontal Cortex/physiology , Cognition , Cognitive Dysfunction/genetics , Cognitive Dysfunction/therapy , Stroke/complications , Stroke/genetics , Stroke/therapy , Double-Blind Method
7.
Neural Regen Res ; 19(8): 1772-1780, 2024 Aug 01.
Article En | MEDLINE | ID: mdl-38103244

JOURNAL/nrgr/04.03/01300535-202408000-00031/figure1/v/2023-12-16T180322Z/r/image-tiff Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3ß/ß-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3ß/ß-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3ß/ß-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.

8.
Am J Speech Lang Pathol ; 33(2): 800-813, 2024 Mar 07.
Article En | MEDLINE | ID: mdl-38099824

PURPOSE: This study aimed to explore how well persons with anomic aphasia communicate information during discourse regarding quantity, quality, and efficiency compared to neurotypical controls, to investigate the influence of discourse tasks on informativeness and efficiency and to examine impact factors like aphasia severity and cognitive ability. METHOD: Language samples of four discourse tasks from 31 persons with anomic aphasia and 31 neurotypical controls were collected from Mandarin AphasiaBank. Correct information unit (CIU) analysis measures including the total number of CIUs, percentage of CIUs, CIUs per minute, and words per minute were calculated. Group differences and the effects of discourse tasks on informativeness and efficiency were investigated. Correlations of CIU analysis measures with aphasia severity and cognitive ability were examined. RESULTS: Persons with anomic aphasia showed lower efficiency in conveying information than controls. They underperformed controls on all CIU analysis measures when executing story narrative tasks. Discourse tasks influenced the informativeness and efficiency of both groups. Neurotypical controls delivered the greatest quantity of information most efficiently when narrating stories. Persons with anomic aphasia exhibited reduced quantity of information during procedural discourse and displayed superior information quality in sequential-picture descriptions. Discourse information may be impacted by aphasia severity and cognitive ability, with varying effects depending on the task. CONCLUSIONS: Persons with anomic aphasia are inefficient in communicating discourse messages and perform poorly on all measures in story narratives. When measuring discourse information, the effects of discourse tasks and factors like aphasia severity and cognitive ability should be considered.


Anomia , Aphasia , Humans , Anomia/diagnosis , Aphasia/diagnosis , Aphasia/psychology , Language , Narration , Cognition
9.
BMC Nephrol ; 24(1): 369, 2023 12 12.
Article En | MEDLINE | ID: mdl-38087232

OBJECTIVE: This study aimed to investigate the relationship between the consumption of fresh and salt-preserved vegetables and the estimated glomerular filtration rate (eGFR), which requires further research. METHODS: For this purpose, the data of those subjects who participated in the 2011-2012 and 2014 surveys of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and had biomarker data were selected. Fresh and salt-preserved vegetable consumptions were assessed at each wave. eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on plasma creatinine. Furthermore, a linear mixed model was used to evaluate associations between fresh/salt-preserved vegetables and eGFR. RESULTS: The results indicated that the median baseline and follow-up eGFRs were 72.47 mL/min/1.73 m² and 70.26 mL/min/1.73 m², respectively. After applying adjusted linear mixed model analysis to the data, the results revealed that compared to almost daily intake, occasional consumption of fresh vegetables was associated with a lower eGFR (ß=-2.23, 95% CI: -4.23, -0.23). Moreover, rare or no consumption of salt-preserved vegetables was associated with a higher eGFR (ß = 1.87, 95% CI: 0.12, 3.63) compared to individuals who consumed salt-preserved vegetables daily. CONCLUSION: Fresh vegetable consumption was direct, whereas intake of salt-preserved vegetables was inversely associated with eGFR among the oldest subjects, supporting the potential benefits of diet-rich fresh vegetables for improving eGFR.


Renal Insufficiency, Chronic , Vegetables , Humans , Glomerular Filtration Rate , Kidney Function Tests , Renal Insufficiency, Chronic/epidemiology , Longitudinal Studies , Sodium Chloride, Dietary , Creatinine
10.
BMJ Open ; 13(12): e078510, 2023 12 30.
Article En | MEDLINE | ID: mdl-38159939

OBJECTIVE: This study was to explore the changes in bacterial bloodstream infection (BSI) in patients with haematological malignancies (HMs) before and during SARS-CoV-2 pandemic. DESIGN: Retrospective cohort study between 2018 and 2021. SETTING: The largest haematological centre in southern China. RESULTS: A total of 599 episodes of BSI occurring in 22 717 inpatients from January 2018 to December 2021 were analysed. The frequencies of the total, Gram-negative and Gram-positive BSI before and during the pandemic were 2.90% versus 2.35% (p=0.011), 2.49% versus 1.77% (p<0.001) and 0.27% versus 0.44% (p=0.027), respectively. The main isolates from Gram-negative or Gram-positive BSI and susceptibility profiles also changed. The 30-day mortality caused by BSI was lower during the pandemic (21.1% vs 14.3%, p=0.043). Multivariate analysis revealed that disease status, pulmonary infection and shock were independent predictors of 30-day mortality. CONCLUSION: Our data showed that the incidence of total and Gram-negative organisms BSI decreased, but Gram-positive BSI incidence increased in patients with HMs during the pandemic along with the changes of main isolates and susceptibility profiles. Although the 30-day mortality due to BSI was lower during the pandemic, the new infection prevention strategy should be considered for any future pandemics.


Bacteremia , COVID-19 , Hematologic Neoplasms , Sepsis , Humans , SARS-CoV-2 , Pandemics , Bacteremia/microbiology , Retrospective Studies , COVID-19/epidemiology , Hematologic Neoplasms/complications
12.
IEEE Trans Biomed Eng ; 70(6): 1815-1825, 2023 06.
Article En | MEDLINE | ID: mdl-37015681

OBJECTIVE: This paper aimed to develop an orthosis to apply a compensating force to improve the stability of the glenohumeral joint without resisting arm movement. METHODS: The proposed orthosis was based on a parallelogram structure to provide a pair of compensating forces to the glenohumeral joint center. Theoretical analysis was used to evaluate the additional moments caused by glenohumeral joint center shifting. Then, an experimental evaluation platform, composed of a torque sensor, a force sensor, and a 3D printed arm, was set up to assess the additional moments and compensating force. Finally, the proposed orthosis was compared with the traditional orthosis to compare the subluxation reduction and the movement restriction when worn by stroke patients. RESULTS: There was only a maximum additional moment of 0.87 Nm for the glenohumeral center shifting. During 3D printed arm movement, the moment correlation coefficient between with and without the proposed orthosis was greater than 0.98, and the compensating force was larger than 90% of the arm weight. The proposed orthosis reduced subluxation by 12.5±3.5 mm, and the traditional orthosis reduced subluxation by 7.7±2.2 mm, indicating that the subluxation reduction of the proposed orthosis was more effective ( ). Meanwhile, the proposed orthosis's motion restriction joint was significantly smaller than traditional orthosis ( ). CONCLUSION: The proposed orthosis provided sufficient gravity compensation without resisting arm movement. SIGNIFICANCE: The proposed orthosis can improve the shoulder's stability during shoulder movement, potentially improving the rehabilitation effect of patients with shoulder subluxation.


Shoulder Dislocation , Shoulder Joint , Humans , Shoulder , Shoulder Dislocation/therapy , Shoulder Dislocation/etiology , Orthotic Devices/adverse effects , Upper Extremity , Biomechanical Phenomena , Range of Motion, Articular
13.
Mol Cancer Res ; 21(7): 648-663, 2023 07 05.
Article En | MEDLINE | ID: mdl-36961398

The chemoresistance of temozolomide-based therapy is a serious limitation for lasting effective treatment of gliomas, while the underlying mechanisms remain unclear. In this study, we showed that downregulation of BASP1 correlated negatively with the response to temozolomide therapy and disease-free survival (DFS) of patients with gliomas. Silencing BASP1 significantly enhanced the temozolomide resistance of glioma cells both in vitro and in vivo through repair of temozolomide-induced DNA damage via activation of the FBXO32/NF-κB/MGMT axis in both MGMT-methylated and -unmethylated gliomas. We demonstrated that loss of BASP1 resulted in removal of TRIM37/EZH2 complex-induced repressive histone modifications, including H2A-ub and H3K27me3, but addition of WDR5/MLL complex-mediated active histone modifications, including H3K4me3 and H3K9ac, on the FBXO32 promoter, which elicited in FBXO32 upregulation and further activated NF-κB/MGMT signaling via ubiquitin-dependent degradation of IκBα. Importantly, treatment with OICR-9429, an antagonist of the WDR5-MLL interaction, impaired the FBXO32/NF-κB/MGMT axis-mediated repair of temozolomide-induced DNA damage, leading to significant apoptosis of BASP1-downregulated glioma cells. These findings shed light on the molecular mechanism underlying BASP1-mediated epigenetic transcriptional repression and may represent a potential strategy in the fight against temozolomide-resistant gliomas. IMPLICATIONS: BASP1 downregulation promotes temozolomide resistance in gliomas through WDR5/MLL complex-mediated epigenetic activation of the FBXO32/NF-κB/MGMT axis, providing new target for improving outcomes in patients with temozolomide-resistant gliomas.


Brain Neoplasms , Glioma , Humans , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Down-Regulation , Drug Resistance, Neoplasm/genetics , Epigenesis, Genetic , Glioma/drug therapy , Glioma/genetics , Glioma/metabolism , Muscle Proteins/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , SKP Cullin F-Box Protein Ligases/genetics , SKP Cullin F-Box Protein Ligases/metabolism , Temozolomide/pharmacology , Temozolomide/therapeutic use
14.
CNS Neurosci Ther ; 29(6): 1561-1570, 2023 06.
Article En | MEDLINE | ID: mdl-36786133

BACKGROUND: Post-ischemic stroke executive impairment (PISEI) is a serious obstacle for patients to returning to their society and is currently difficult to screen early and clinically ineffective. AIM: The aim of the study was to clarify whether functional near-infrared spectroscopy (fNIRS) can be used as a rapid screening tool for PISEI and to explore the efficacy of transcranial magnetic stimulation (TMS) in PISEI patients and the changes in brain function. METHODS: A single-blind, randomized controlled study design was used to detect hemodynamic differences by fNIIRS in 16 PISEI patients and 16 healthy subjects during the resting state and Stroop task, respectively. After 3 days, all subjects received a single TMS intervention and underwent simultaneous fNIRS testing for the Stroop task before and 3 days after the TMS intervention. RESULTS: PISEI patients had significantly higher HbO2 content in the left dorsolateral prefrontal cortex (DLPFC), the right pre-motor cortex (PMC) and the right primary sensorimotor cortex (SM1) during the Stroop task compared to the resting state (F = 141.966, p < 0.001), but significantly lower than healthy subjects (T = -3.413, p = 0.002). After TMS intervention, PISEI patients' time and error number scores on the Stroop test were significantly enhanced, and the functional activity of the above-mentioned brain regions was significantly more active than at baseline, while the strength of their functional connections with each other was markedly increased. CONCLUSIONS: fNIRS helped screen and diagnose PISEI. A single TMS session benefited PISEI patients with effects lasting 3 days, which may be attributed to activation of the left DLPFC, right PMC and right SM1 brain regions.


Ischemic Stroke , Sensorimotor Cortex , Humans , Transcranial Magnetic Stimulation/methods , Spectroscopy, Near-Infrared , Prospective Studies , Single-Blind Method , Prefrontal Cortex
15.
J Clin Med ; 12(4)2023 Feb 14.
Article En | MEDLINE | ID: mdl-36836034

This retrospective study aimed to derive the clinical phenotypes of ventilated ICU patients to predict the outcomes on the first day of ventilation. Clinical phenotypes were derived from the eICU Collaborative Research Database (eICU) cohort via cluster analysis and were validated in the Medical Information Mart for Intensive Care (MIMIC-IV) cohort. Four clinical phenotypes were identified and compared in the eICU cohort (n = 15,256). Phenotype A (n = 3112) was associated with respiratory disease, had the lowest 28-day mortality (16%), and had a high extubation success rate (~80%). Phenotype B (n = 3335) was correlated with cardiovascular disease, had the second-highest 28-day mortality (28%), and had the lowest extubation success rate (69%). Phenotype C (n = 3868) was correlated with renal dysfunction, had the highest 28-day mortality (28%), and had the second-lowest extubation success rate (74%). Phenotype D (n = 4941) was associated with neurological and traumatic diseases, had the second-lowest 28-day mortality (22%), and had the highest extubation success rate (>80%). These findings were validated in the validation cohort (n = 10,813). Additionally, these phenotypes responded differently to ventilation strategies in terms of duration of treatment, but had no difference in mortality. The four clinical phenotypes unveiled the heterogeneity of ICU patients and helped to predict the 28-day mortality and the extubation success rate.

16.
J Neuroinflammation ; 20(1): 50, 2023 Feb 25.
Article En | MEDLINE | ID: mdl-36829205

BACKGROUND: The repair of white matter injury is of significant importance for functional recovery after ischemic stroke, and the up-regulation of triggering receptors expressed on myeloid cells 2 (TREM2) after ischemic stroke is neuroprotective and implicated in remyelination. However, the lack of effective therapies calls for the need to investigate the regenerative process of remyelination and the role of rehabilitation therapy. This study sought to investigate whether and how moderate physical exercise (PE) promotes oligodendrogenesis and remyelination in rats with transient middle cerebral artery occlusion (tMCAO). METHODS: Male Sprague-Dawley rats (weighing 250-280 g) were subjected to tMCAO. AAV-shRNA was injected into the lateral ventricle to silence the Trem2 gene before the operation. The rats in the physical exercise group started electric running cage training at 48 h after the operation. The Morris water maze and novel object recognition test were used to evaluate cognitive function. Luxol fast blue staining, diffusion tensor imaging, and electron microscopy were used to observe myelin injury and repair. Immunofluorescence staining was applied to observe the proliferation and differentiation of oligodendrocyte precursor cells (OPCs). Expression of key molecules were detected using immunofluorescence staining, quantitative real-time polymerase chain reaction, Western blotting, and Enzyme-linked immunosorbent assay, respectively. RESULTS: PE exerted neuroprotective efects by modulating microglial state, promoting remyelination and recovery of neurological function of rats over 35 d after stroke, while silencing Trem2 expression in rats suppressed the aforementioned effects promoted by PE. In addition, by leveraging the activin-A neutralizing antibody, we found a direct beneficial effect of PE on microglia-derived activin-A and its subsequent role on oligodendrocyte differentiation and remyelination mediated by the activin-A/Acvr axis. CONCLUSIONS: The present study reveals a novel regenerative role of PE in white matter injury after stroke, which is mediated by upregulation of TREM2 and microglia-derived factor for oligodendrocytes regeneration. PE is an effective therapeutic approach for improving white matter integrity and alleviating neurological function deficits after ischemic stroke.


Brain Injuries , Brain Ischemia , Ischemic Stroke , Stroke , White Matter , Rats , Male , Animals , Microglia/metabolism , White Matter/metabolism , Ischemic Stroke/metabolism , Brain Ischemia/metabolism , Diffusion Tensor Imaging , Rats, Sprague-Dawley , Stroke/metabolism , Infarction, Middle Cerebral Artery/metabolism , Brain Injuries/metabolism
17.
Heliyon ; 8(12): e11919, 2022 Dec.
Article En | MEDLINE | ID: mdl-36578417

Background and aims: China has the largest number of chronic kidney disease (CKD) patients. Current CKD definition has been challenged recently. We aim to reassess kidney function in healthy Chinese population, to provide a more appropriate reference range (RIs) for diagnosis, treatment, monitoring (or screening) of kidney disease and related research. Materials and methods: A total of 49627 apparently healthy people aged 18-94 years old were enrolled. Age and sex effects were explored for the kidney function indicators and RIs were calculated non-parametrically. Results: Albumin's limits were lower than the national RIs, with 5.7 g/L lower in upper limit (UL) and 0.4 g/L lower in lower limit (LL) [RIs: 39.6-49.3 vs 40-55]. The LL of estimate glomerular filtration rate (eGFR) was 80.4 mL/min/1.73 m2 or 63.3 mL/min/1.73 m2 at the age of <50 or ≥70 years, respectively. Notably, eGFR showed an approximately 0.7 mL/min/1.73 m2 decrease every year. In addition, eGFR increase 0.35 mL/min/1.73 m2 per standard deviation increase in blood glucose when uric acid (UA) exceed the RIs. Conclusion: UA was an important factor affecting eGFR. For healthy elderly in China, albumin's limits were lower than the national RIs, and LLs of eGFR were nearly 60 mL/min/1.73 m2. Using national RIs for healthy elderly may be overly stringent.

18.
Front Pediatr ; 10: 797836, 2022.
Article En | MEDLINE | ID: mdl-35386254

Background: The survival rate of children and adolescents with acute lymphoblastic leukemia (ALL) has progressively improved. However, ALL survivors often have adverse effects after treatment, such as an increased risk of obesity. Obesity has been associated with reduced survival. Objective: We investigated the relationship between obesity, adipocytokine levels, and ALL short-term outcomes. Methods: Weight and height were measured, and body mass index (BMI) was calculated at patient diagnosis and discharge. Leptin and Adiponectin levels and Minimal Residual Disease (MRD) were measured before therapy, at days 19 of remission-induction therapy, and at the end of remission-induction therapy (days 46). The relationship between BMI, adipocytokine levels, and MRD was then determined. Results: Compared to the normal BMI group, children with an abnormal increase in BMI had an increase in MRD at day 19 and 46 (P = 0.04 and P = 0.008), and showed a positive correlation (P = 0.014). In addition, we found a positive correlation between weight, hip circumference at diagnosis and at day 19, and MRD at day 46. Both BMI and fat concentric distribution affected the outcome of ALL children. A higher BMI was also associated with a significant increase in Leptin levels at diagnosis. Leptin resistance should be considered in ALL children with high BMI. Conclusion: BMI affects the outcome of ALL patients. Early interventions such as regular weight, height monitoring, and dietary assessments should be preferably initiated during remission-induction chemotherapy.

19.
Mol Biol Rep ; 49(7): 6199-6205, 2022 Jul.
Article En | MEDLINE | ID: mdl-35403941

BACKGROUND: The hematological phenotype and genotype analysis of hemoglobin New York (Hb New York) combined with α or ß thalassemia has been rarely reported, and whether there is any effect of Hb New York on thalassemia has not been well explored. METHODS AND RESULTS: In this study, peripheral blood samples from 346 Hb New York carriers were collected for blood cell parameter analysis. When comparing Hb New York heterozygotes, Hb New York combined with α0 thalassemia or α+ thalassemia, we found that the differences in hemoglobin (HGB), MCV and MCH values were statistically significant (P < 0.05). The HGB, MCV and MCH values of α thalassemia patients were not different from Hb New York combined with α thalassemia group (P > 0.05). When Hb New York heterozygotes were compared to Hb New York combined with ß0 thalassemia or ß+ thalassemia, the differences in MCV and MCH values were statistically significant (P < 0.05). However, the differences in MCV and MCH values were not statistically significant between Hb New York combined with ß thalassemia and ß thalassemia (P > 0.05). CONCLUSIONS: Our study shows that the hematological characteristics of Hb New York combined with thalassemia are similar to the corresponding thalassemia, and Hb New York does not aggravate the clinical manifestations of thalassemia.


Hemoglobins, Abnormal , alpha-Thalassemia , beta-Thalassemia , Hemoglobins, Abnormal/analysis , Hemoglobins, Abnormal/genetics , Heterozygote , Humans , beta-Thalassemia/genetics
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