The Association Between Thymidylate Synthase Gene Polymorphisms and the Risk of Ischemic Stroke in Chinese Han Population.

Family history of hypertension, smoking, diabetes and alcohol consumption and atherosclerotic plaque were identified as common risk factors in IS. We aimed at investigating the relationship between Thymidylate Synthase (TS) gene polymorphisms and ischemic stroke (IS).This case-control research selected and genotyped three single nucleotide polymorphisms (SNPs)of TS( rs699517, rs2790, and rs151264360) with Sanger sequencing in Chinese Han population. We also adopted logistic regression analysis in genetic models for calculating odds ratios and 95% confidence intervals. Genotype-Tissue Expression(GTEx) database analyzed the tissue-specific expression and TS polymorphisms. The ischemic stroke patients showed higher low-density lipoprotein cholesterol and total homocysteine (tHcy). It was found that patients with the TT genotype of rs699517 and GG genotype of rs2790 had larger degrees of tHcy than those with CC + CT genotypes and AA + AG genotypes, respectively. The genotype distribution of the three SNPs did not deviate from Hardy-Weinberg equilibrium (HWE). Haplotype analysis showed that T-G-del was the major haplotype in IS, and C-A-ins was the major haplotype in controls. GTEx database indicated that the rs699517 and rs2790 increased the expression of TS in healthy human and associated with TS expression level in a single tissue. In conclusion: This study has shown that TS rs699517 and rs2790 were significantly related to ischemic stroke patients.

Effects of selenium-enriched yeast dietary supplementation on egg quality, gut morphology and caecal microflora of laying hens.

Selenium (Se) is an essential micronutrient for humans and animals and is a powerful antioxidant that can promote reproductive and immune functions. The purpose of this study was to evaluate the effects of supplemental dietary selenium-enriched yeast (SeY) on egg quality, gut morphology and microflora in laying hens. In total, 100 HY-Line Brown laying hens (45-week old) were randomly allocated to two groups with 10 replicates and fed either a basal diet (without Se supplementation) or a basal diet containing 0.2 mg/kg Se in the form of SeY for 8 weeks. The Se supplementation did not have a significant effect on egg quality and intestinal morphology of laying hens. Based on the 16S rRNA sequencing, SeY dietary supplementation effectively modulated the cecal microbiota structure. An alpha diversity analysis demonstrated that birds fed 100 mg/kg SeY had a higher cecal bacterial diversity. SeY dietary addition elevated Erysipelotrichia (class), Lachnospiraceae (family), Erysipelotrichaceae (family) and Ruminococcus_torques_group (genus; p < .05). Analysis of microbial community-level phenotypes revealed that SeY supplementation decreased the microorganism abundance of facultatively anaerobic and potentially pathogenic phenotypes. Overall, SeY supplementation cannot significantly improve intestinal morphology; however, it modulated the composition of cecal microbiota toward a healthier gut.

Extracellular Vesicles as Delivery Shippers for Noncoding RNA-Based Modulation of Angiogenesis: Insights from Ischemic Stroke and Cancer.

Ischemic stroke and systemic cancer are two of the leading causes of mortality. Hypoxia is a central pathophysiological component in ischemic stroke and cancer, representing a joint medical function. This function includes angiogenesis regulation. Vascular remodeling coupled with axonal outgrowth following cerebral ischemia is critical in improving poststroke neurological functional recovery. Antiangiogenic strategies can inhibit cancer vascularization and play a vital role in impeding cancer growth, invasion, and metastasis. Although there are significant differences in the cause of angiogenesis across both pathophysiological conditions, emerging evidence states that common signaling structures, such as extracellular vesicles (EVs) and noncoding RNAs (ncRNAs), are involved in this context. EVs, heterogeneous membrane vesicles encapsulating proteomic genetic information from parental cells, act as multifunctional regulators of intercellular communication. Among the multifaceted roles in modulating biological responses, exhaustive evidence shows that ncRNAs are selectively sorted into EVs, modulating common specific aspects of cancer development and stroke prognosis, namely, angiogenesis. This review will discuss recent advancements in the EV-facilitated/inhibited progression of specific elements of angiogenesis with a particular concern about ncRNAs within these vesicles. The review is concluded by underlining the clinical opportunities of EV-derived ncRNAs as diagnostic, prognostic, and therapeutic agents.

A Retrospective Comparative Study of Endoscopic Treatment of Gastrocnemius Contracture using the Modified Soft Tissue Release Kit.

Background and Objectives: This study aimed to evaluate the effectiveness and safety of endoscopic gastrocnemius recession using the self-developed Modified Soft Tissue Release Kit. Materials and Methods: This retrospective review followed up 22 patients (34 feet) who underwent endoscopic surgery and 20 patients (30 feet) who received open surgery between January 2020 and January 2022. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the maximum ankle dorsiflexion angle were evaluated preoperatively and at the last follow-up. Postoperative complications were recorded. Patient satisfaction was surveyed at the last follow-up. The comparison between quantitative data was analyzed with the Wilcoxon signed-rank test. The comparison between qualitative data was analyzed with the chi-square test. Results: There was no significant difference in the baseline characteristics between the two groups. The AOFAS score in the endoscopic group increased from 50 (18) points preoperatively to 90 (13) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.7 (2.8) degrees to 10.6 (3.6) degrees. The AOFAS score in the open group improved from 47 (15) points preoperatively to 90 (18) points at the last follow-up; the maximum ankle dorsiflexion angle increased from -7.6 (4.0) degrees to 10.7 (3.3) degrees. The change values of the AOFAS scores in the endoscopic and open groups were 39 (15) and 40.5 (11) points, respectively, and there was no significant difference between them. The change values of the maximum ankle dorsiflexion angles in the endoscopic and open groups were 19.5 (4.3) and 19.1 (4.9) degrees, respectively, and there was no significant difference between them. There were no complications, such as sural nerve injury, in both groups. There was no significant difference between the two groups in satisfaction with the surgical outcome. Conclusions: Endoscopic gastrocnemius recession using the Modified Soft Tissue Release Kit can significantly improve the foot function with significant mid-term efficacy and high safety.

Long non-coding RNA AWPPH enhances malignant phenotypes in nasopharyngeal carcinoma via silencing PTEN through interacting with LSD1 and EZH2.

Evidence has emerged identifying long noncoding RNAs (lncRNAs) as important regulators of various cancers including nasopharyngeal carcinoma (NPC). LncRNA AWPPH is an oncogene recently identified in several cancers. However, the underlying role of AWPPH in NPC is still unclear and thus worth exploring. In this study, AWPPH expression was markedly upregulated in NPC cells. Further, loss- and gain-of-function assays indicated that AWPPH facilitates cell proliferation and migration and hinders apoptosis in NPC cells. Moreover, cytoplasmic AWPPH was predicted to share a common RNA-binding protein, IGF2BP1, with LSD1. The interaction between IGF2BP1 and both AWPPH and LSD1 mRNA was verified in NPC cells, and AWPPH stabilized LSD1 mRNA to enhance the expression of LSD1 in NPC through such interactions. Furthermore, nuclear AWPPH repressed PTEN expression through recruiting EZH2 and LSD1 to the PTEN promoter in NPC cells. Final rescue assays demonstrated that silenced PTEN could reverse the suppressive influence of AWPPH depletion on the progression of NPC. Collectively, our study shows that AWPPH inhibits PTEN expression to drive NPC progression through interacting with LSD1 and EZH2, providing potential biomarkers for NPC treatment.

Serum sex hormone-binding globulin is associated with symptomatic late-onset hypogonadism in aging rural males: a community-based study.

Background To investigate whether serum levels of sex hormone-binding globulin (SHBG) and testosterone are associated with symptomatic late-onset hypogonadism (SLOH) in middle-aged and elderly rural Chinese males. METHODS: A population-based cross-sectional study was conducted in Zhejiang rural communities. A total of 965 men (aged 40-80 years) were admitted to the aging males' symptoms (AMS) scale and related physical examinations including body mass index (BMI) and waist circumference were conducted. Serum total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG) and serum lipid levels were measured separately. Serum level of bioavailable testosterone (Bio-T) was calculated. RESULTS: A total of 965 participants were divided into two groups, symptomatic late-onset hypogonadism (SLOH) group (n = 202) (AMS score ≥27) and control group (n = 763), according to total AMS score. Men in the SLOH group were older (61.57±9.06 vs 54.95±8.27 years) and had a smaller waist circumference (81.06±6.89 vs 82.54±6.60 cm) than those in the control group. Moreover, a relatively higher level of SHBG and lower levels of FT, Bio-T, triglyceride (TG) and total cholesterol (T-CHOL) were found in the SLOH group compared with that in the control group (P < 0.05). Receiver operating characteristic curves (ROC) analysis showed that age (AUC = 0.702, P < 0.001) and SHBG (AUC = 0.617, P < 0.001) were potential predictive indicators for SLOH diagnosis, with the best cut-off values of 59 years for age and 44.40 nmol/L for SHBG. CONCLUSIONS: SHBG might be a potential predictor in men with hypogonadism, whereas BMI had no proportionality to the measurement of AMS. Age and SHBG should be used for SLOH diagnosis.

Atorvastatin Protects Against Cerebral Aneurysmal Degenerative Pathology by Promoting Endothelial Progenitor Cells (EPC) Mobilization and Attenuating Vascular Deterioration in a Rat Model.

BACKGROUND Endothelial injury is the early pathological change of cerebral aneurysm (CA) formation. In addition to its lipid-lowering activity, atorvastatin (ATR) also reportedly promotes vascular repair via mobilizing endothelial progenitor cells (EPC). Here, we investigated the influence of ATR on vascular worsening after CA induction in rats. MATERIAL AND METHODS Adult male Sprague-Dawley rats were randomly assigned to 3 groups: a control (CTR) group, a CA group, and a CA+ATR treatment group. Circulating EPC level and hematological and lipid profiles were measured 3 months after CA induction. Verhoeff-Van Gieson staining and transmission electron microscopy were performed to assess pathological changes in the artery wall. RT-PCR was also performed to evaluate the expression of inflammation-related genes in the aneurysmal wall. RESULTS ATR significantly restored the impaired level of circulating EPC without changing hematological and lipid profiles 3 months after CA induction. ATR markedly inhibited endothelial injury, media thinning, and CA enlargement, accompanied by reduced vascular inflammation. CONCLUSIONS Our preliminary results demonstrate that the mobilization of EPC and improvement of endothelial function by ATR contribute to the prevention of cerebral aneurysm. Further studies are warranted to investigate the detailed mechanism.

Quantitative volumetric analysis of primary glioblastoma multiforme on MRI and 11C-methionine PET: initial study on five patients.

To investigate the discrepancy between 11C-methionine (MET) positron emission tomography (PET) and MRI results in primary glioblastoma multiforme (GBM) through three-dimensional (3D) volumetric analysis, we retrospectively analysed patients with primary GBM who underwent preoperative 3D MRI and MET PET and were operated between June 2016 and January 2017. Tumour delineation and volumetric analysis were conducted using MRIcron software. Tumour volumes defined by MRI (VMRI) were manually drawn slice by slice in axial and sagittal or coronal images of enhanced T1 sequence, while metabolic tumour volumes were automatically segmented in MET PET (VMET) based on three (frontal, occipital and temporal) 3D reference volumes of interest (VOI). Discrepancies were evaluated in terms of both absolute volume and percentage on the combined images. MET PET contours contained and extended beyond MRI contours in all five patients; in a subset of cases, MET PET contours extended to the contralateral hemisphere. The discrepancy between MET uptake and MRI results was 27.67 cm3 (4.20-51.20 cm3), i.e. approximately 39.0% (17.4-64.3%) of the metabolic tumour volume was located outside the volumes of the Gd-enhanced area. Metabolic tumour volume is substantially underestimated by Gd-enhanced area in patients with primary GBM. Quantitative volumetric information derived from MET uptake is useful in defining tumour targets and designing individualised therapy strategies in primary GBM.

Simultaneous bilateral hypertensive basal ganglia hemorrhage.

CONTEXT: Hypertension is the single most important risk factor for intracerebral hemorrhage (ICH) and often leads to solitary hematoma. Multiple spontaneous simultaneous ICH is not common, and bilateral hemorrhages occurred in symmetrical basal ganglia is extremely rare. Most reported cases accepted conservative treatment and suffered extremely poor outcome. CASE REPORT: A 57-year-old male became unconscious when having supper and was transported to our emergency room immediately. Non-contract CT brain scanning showed simultaneous bilateral hypertensive basal ganglia hemorrhage; he was treated by stereotactic aspiration and thrombolysis for both sides, with subsequent thrombolysis and clot aspiration through hematoma-indwelling catheter. The hematomas were almost totally cleared within a week. His condition improved gradually. Nearly 10 months after onset, he could chow and swallow food, controlling bowels and bladder all by himself, but need some help when feeding and using toilet. CONCLUSION: Simultaneous bilateral hypertensive basal ganglia hemorrhage is a devastating cerebrovascular disease with significant high morbidity and mortality. Stereotactic aspiration and thrombolysis is a safe and effective way to clear hematomas within short time, thus reducing the neurological impairment from hematoma mass effect and secondary brain injury, improving prognosis.

Arabidopsis C3H14 and C3H15 have overlapping roles in the regulation of secondary wall thickening and anther development.

Plant tandem CCCH zinc finger (TZF) proteins play diverse roles in developmental and adaptive processes. Arabidopsis C3H14 has been shown to act as a potential regulator of secondary wall biosynthesis. However, there is lack of direct evidence to support its functions in Arabidopsis. It is demonstrated here that C3H14 and its homologue C3H15 redundantly regulate secondary wall formation and that they additionally function in anther development. Plants with double, but not single, T-DNA mutants for C3H14 or C3H15 have few pollen grains and thinner stem secondary walls than the wild type. Plants homozygous for c3h14 and heterozygous for c3h15 [c3h14 c3h15(±)] have slightly thinner secondary walls than plants heterozygous for c3h14 and homozygous for c3h15 [c3h14(±) c3h15], and c3h14(±) c3h15 have lower fertility. Overexpression of C3H14 or C3H15 led to increased secondary wall thickness in stems and the ectopic deposition of secondary walls in various tissues, but did not affect anther morphology. Transcript profiles from the C3H14/15 overexpression and c3h14 c3h15 plants revealed marked changes in the expression of many genes associated with cell wall metabolism and pollen formation. Subcellular localization and biochemical analyses suggest that C3H14/15 might function at both the transcriptional and post-transcriptional levels.

Poplar PdC3H17 and PdC3H18 are direct targets of PdMYB3 and PdMYB21, and positively regulate secondary wall formation in Arabidopsis and poplar.

Wood biomass is mainly made of secondary cell walls, whose formation is controlled by a multilevel network. The tandem CCCH zinc finger (TZF) proteins involved in plant secondary wall formation are poorly understood. Two TZF genes, PdC3H17 and PdC3H18, were isolated from Populus deltoides and functionally characterized in Escherichia coli, tobacco, Arabidopsis and poplar. PdC3H17 and PdC3H18 are predominantly expressed in cells of developing wood, and the proteins they encode are targeted to cytoplasmic foci. Transcriptional activation assays showed that PdMYB2/3/20/21 individually activated the PdC3H17 and PdC3H18 promoters, but PdMYB3/21 were most significant. Electrophoretic mobility shift assays revealed that PdMYB3/21 bound directly to the PdC3H17/18 promoters. Overexpression of PdC3H17/18 in poplar increased secondary xylem width and secondary wall thickening in stems, whereas dominant repressors of them had the opposite effects on these traits. Similar alteration in secondary wall thickening was observed in their transgenic Arabidopsis plants. qRT-PCR results showed that PdC3H17/18 regulated the expression of cellulose, xylan and lignin biosynthetic genes, and several wood-associated MYB genes. These results demonstrate that PdC3H17 and PdC3H18 are the targets of PdMYB3 and PdMYB21 and are an additional two components in the regulatory network of secondary xylem formation in poplar.

R2R3-MYB gene pairs in Populus: evolution and contribution to secondary wall formation and flowering time.

In plants, the R2R3-MYB gene family contains many pairs of paralogous genes, which play the diverse roles in developmental processes and environmental responses. The paper reports the characterization of 81 pairs of Populus R2R3-MYB genes. Chromosome placement, phylogenetic, and motif structure analyses showed that these gene pairs resulted from multiple types of gene duplications and had five different gene fates. Tissue expression patterns revealed that most duplicated genes were specifically expressed in the tissues examined. qRT-PCR confirmed that nine pairs were highly expressed in xylem, of which three pairs (PdMYB10/128, PdMYB90/167, and PdMYB92/125) were further functionally characterized. The six PdMYBs were localized to the nucleus and had transcriptional activities in yeast. The heterologous expression of PdMYB10 and 128 in Arabidopsis increased stem fibre cell-wall thickness and delayed flowering. In contrast, overexpression of PdMYB90, 167, 92, and 125 in Arabidopsis decreased stem fibre and vessel cell-wall thickness and promoted flowering. Cellulose, xylose, and lignin contents were changed in overexpression plants. The expression levels of several genes involved in secondary wall formation and flowering were affected by the overexpression of the six PdMYBs in Arabidopsis. This study addresses the diversity of gene duplications in Populus R2R3-MYBs and the roles of these six genes in secondary wall formation and flowering control.

[Executive dysfunction in patients with temporal lobe epilepsy and its correlation with P300].

OBJECTIVE: To explore the changes of executive function in patients with temporal lobe epilepsy and analyze its correlation with P300 event-related potentials. METHODS: Fifty patients with temporal lobe epilepsy and 30 age, gender and education-matched healthy control subjects were assessed by neuropsychological tests, including Montreal cognitive assessment (MoCA), working memory, verbal fluency, trail making, digit span, digit symbol and Stroop color-word interference to detect P300 event-related potentials. RESULTS: In temporal lobe epilepsy group, the scores in MoCA, verbal and non-verbal working memory, verbal fluency, digit span, digit symbol and Stroop test were lower than those of the normal control group. And trail making tests A and B became prolonged (P < 0.05). Comparing with normal control group, temporal lobe epilepsy patients had prolonged latency [(332 ± 33)ms] and decreased P300 amplitude [(10 ± 8)µV] (P < 0.05). Comparing epileptogenic focus group on the left and right sides, there was statistically significant difference in verbal working memory (P < 0.05). There was a negative correlation of P300 latency and MoCA, non-verbal working memory, digit span and digit symbol test scores (r = -0.29--0.45, P < 0.05). And a positive correlation of P300 amplitude and MoCA, non-verbal working memory, digit symbol conversion and Stroop scores was also found (r = 0.37-0.47, P < 0.05). P300 amplitude was more relevant to overall cognitive level and executive functions. CONCLUSION: Temporal lobe is involved in the regulation of executive functions. Besides a wide range of cognitive impairment, temporal lobe epilepsy patients have a number of executive dysfunctions, including working memory, cognitive flexibility, attention and inhibitory control ability. And an impairment of verbal working memory is evident in left-sided lesion. Their manifestations include decreased latency and amplitude of P300 on executive function tests. Therefore these two objective parameters may be employed to evaluate the cognitive impairment in patients with temporal lobe epilepsy.

[Values of stereotactic guidance of intraoperative high-field magnetic resonance imaging for multiple intracranial lesions].

OBJECTIVE: To explore the diagnostic and therapeutic values of stereotactic guidance of intraoperative high-field magnetic resonance imaging (iMRI) for multiple intracranial lesions. METHODS: We retrospectively assessed 18 patients with multiple intracranial lesions undergoing stereotactic guidance of high-field iMRI between June 2011 and May 2013. The procedures included biopsy of stereotactic guidance (n = 6), stereotactic aspiration and drainage for brain abscess (n = 4), stereotactic aspiration and intracavitary irradiation with (32)P for mixed solid and cystic craniopharyngiomas (n = 3) and stereotactic hematoma evacuation (n = 5). RESULTS: For 6 cases with high-field iMRI stereotactic guidance, the target lesions were precisely predetermined and pathological specimens confirmed by clinical follow-up results. For 12 cases with multiple cystic lesions and multiple intracranial hematoma, aspiration of hematoma and liquids was satisfactory. And the course of clinical treatment was significantly shortened. And there was a lower incidence of postoperative complications. CONCLUSION: iMRI may guide precisely stereotactic surgery. And it has important clinical significance for confirming the diagnosis of multiple intracranial lesions and shortening their treatment courses.

Verapamil Attenuates the Severity of Tendinopathy by Mitigating Mitochondrial Dysfunction through the Activation of the Nrf2/HO-1 Pathway.

Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL-1ß) along with verapamil at a concentration of 5 µM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 µM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL-1ß. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.

Effects of dietary supplementation with tea polyphenols and probiotics on laying performance, biochemical parameters intestinal morphology and microflora of laying hens.

This study was conducted to investigate the effects of tea polyphenols (TP) and probiotics (PB) on the production performance, biochemical indices, and gut health of laying hens. A total of 400 Hy-line Brown layers (45 weeks old) were randomly assigned to 8 diet groups for 8-week feeding trial. Compared with the control basal diet (CT), dietary high dosage of TP and PB (HTP-PB) increased egg mass (P < 0.05). Supplementation with HTP-PB improved the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the malonic dialdehyde (MDA) content (P < 0.05) without affecting the contents of immunoglobulins in the serum. The combination of HTP and PB supplementation promoted the secretion of estradiol (E2) and progesterone (PROG) compared with treatment with TP or PB alone (P < 0.05). The combined use of HTP and PB induced higher jejunal villus height (VH) than the CT group (P < 0.05). Dietary TP and PB could optimize the functional network of intestinal microflora and the interactions between the intestinal microflora and the host. Therefore, the combined use of the high dosage of TP and PB affected laying performance, improved antioxidant capacity, and promoted intestinal health, which may be associated with regulation of the intestinal microbiota.

Bidirectional two-sample Mendelian randomization analyses support causal relationships between structural and diffusion imaging-derived phenotypes and the risk of major neurodegenerative diseases.

Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer's disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.

Classification and transfer learning of sleep spindles based on convolutional neural networks.

Background: Sleep plays a critical role in human physiological and psychological health, and electroencephalography (EEG), an effective sleep-monitoring method, is of great importance in revealing sleep characteristics and aiding the diagnosis of sleep disorders. Sleep spindles, which are a typical phenomenon in EEG, hold importance in sleep science. Methods: This paper proposes a novel convolutional neural network (CNN) model to classify sleep spindles. Transfer learning is employed to apply the model trained on the sleep spindles of healthy subjects to those of subjects with insomnia for classification. To analyze the effect of transfer learning, we discuss the classification results of both partially and fully transferred convolutional layers. Results: The classification accuracy for the healthy and insomnia subjects' spindles were 93.68% and 92.77%, respectively. During transfer learning, when transferring all convolutional layers, the classification accuracy for the insomnia subjects' spindles was 91.41% and transferring only the first four convolutional layers achieved a classification result of 92.80%. The experimental results demonstrate that the proposed CNN model can effectively classify sleep spindles. Furthermore, the features learned from the data of the normal subjects can be effectively applied to the data for subjects with insomnia, yielding desirable outcomes. Discussion: These outcomes underscore the efficacy of both the collected dataset and the proposed CNN model. The proposed model exhibits potential as a rapid and effective means to diagnose and treat sleep disorders, thereby improving the speed and quality of patient care.

D-mannose alleviates intervertebral disc degeneration through glutamine metabolism.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. METHODS: The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. RESULTS: In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. CONCLUSIONS: In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.

[Intraoperative magnetic resonance imaging-guided functional neuronavigation plus intraoperative neurophysiological monitoring for microsurgical resection of lesions involving hand motor area].

OBJECTIVE: To explore the methods and applications of intraoperative magnetic resonance imaging (iMRI)-guided functional neuronavigation plus intraoperative neurophysiological monitoring (IONM) for microsurgical resection of lesions involving hand motor area. METHODS: A total of 16 patients with brain lesions adjacent to hand motor area were recruited from January 2011 to April 2012. All of them underwent neuronavigator-assisted microsurgery. Also IONM was conducted to further map hand motor area and epileptogenic focus. High-field iMRI was employed to update the anatomical and functional imaging date and verify the extent of lesion resection. RESULTS: Brain shifting during the functional neuronavigation was corrected by iMRI in 5 patients. Finally, total lesion resection was achieved in 13 cases and subtotal resection in 3 cases. At Months 3-12 post-operation, hand motor function improved (n = 10) or remained unchanged (n = 6). None of them had persistent neurological deficit. The postoperative seizure improvement achieved Enge II level or above in 9 cases of brain lesions complicated with secondary epilepsy. CONCLUSION: Intraoperative MRI, functional neuronavigation and neurophysiological monitoring technique are complementary in microsurgery of brain lesions involving hand motor area. Combined use of these techniques can obtain precise location of lesions and hand motor functional structures and allow a maximum resection of lesion and minimization of postoperative neurological deficits.