Development of simultaneous quantitation method for 20 free advanced glycation end products using UPLC-MS/MS and clinical application in kidney injury.

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N6-carboxyethyl-L-arginine (CEA), N6-carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N6-formyl-lysine, N6-carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease.

Microarray Expression Profile of Exosomal circRNAs from High Glucose Stimulated Human Renal Tubular Epithelial Cells.

Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.

Neural biomarker diagnosis and prediction to mild cognitive impairment and Alzheimer's disease using EEG technology.

BACKGROUND: Electroencephalogram (EEG) has emerged as a non-invasive tool to detect the aberrant neuronal activity related to different stages of Alzheimer's disease (AD). However, the effectiveness of EEG in the precise diagnosis and assessment of AD and its preclinical stage, amnestic mild cognitive impairment (MCI), has yet to be fully elucidated. In this study, we aimed to identify key EEG biomarkers that are effective in distinguishing patients at the early stage of AD and monitoring the progression of AD. METHODS: A total of 890 participants, including 189 patients with MCI, 330 patients with AD, 125 patients with other dementias (frontotemporal dementia, dementia with Lewy bodies, and vascular cognitive impairment), and 246 healthy controls (HC) were enrolled. Biomarkers were extracted from resting-state EEG recordings for a three-level classification of HC, MCI, and AD. The optimal EEG biomarkers were then identified based on the classification performance. Random forest regression was used to train a series of models by combining participants' EEG biomarkers, demographic information (i.e., sex, age), CSF biomarkers, and APOE phenotype for assessing the disease progression and individual's cognitive function. RESULTS: The identified EEG biomarkers achieved over 70% accuracy in the three-level classification of HC, MCI, and AD. Among all six groups, the most prominent effects of AD-linked neurodegeneration on EEG metrics were localized at parieto-occipital regions. In the cross-validation predictive analyses, the optimal EEG features were more effective than the CSF + APOE biomarkers in predicting the age of onset and disease course, whereas the combination of EEG + CSF + APOE measures achieved the best performance for all targets of prediction. CONCLUSIONS: Our study indicates that EEG can be used as a useful screening tool for the diagnosis and disease progression evaluation of MCI and AD.

Effects of forward and backward span trainings on working memory: Evidence from a randomized controlled trial.

Both forward and backward working memory span tasks have been used in cognitive training, but no study has been conducted to test whether the two types of trainings are equally effective. Based on data from a randomized controlled trial, this study (N = 60 healthy college students) tested the effects of backward span training, forward span training, and no intervention. Event-related potential (ERP) signals were recorded at the pre-, mid-, and post-tests while the subjects were performing a distractor version of the change detection task, which included three conditions (2 targets and 0 distractor [2T0D]; 4 targets and 0 distractor [4T0D]; and 2 targets and 2 distractors [2T2D]). Behavioral data were collected from two additional tasks: a multi-object version of the change detection task, and a suppress task. Compared to no intervention, both forward and backward span trainings led to significantly greater improvement in working memory maintenance, based on indices from both behavioral (Kmax) and ERP data (CDA_2T0D and CDA_4T0D). Backward span training also improved interference control based on the ERP data (CDA_filtering efficiency) to a greater extent than did forward span training and no intervention, but the three groups did not differ in terms of behavioral indices of interference control. These results have potential implications for optimizing the current cognitive training on working memory.

Interference of unilateral lower limb amputation on motor imagery rhythm and remodeling of sensorimotor areas.

Purpose: The effect of sensorimotor stripping on neuroplasticity and motor imagery capacity is unknown, and the physiological mechanisms of post-amputation phantom limb pain (PLP) illness remain to be investigated. Materials and methods: In this study, an electroencephalogram (EEG)-based event-related (de)synchronization (ERD/ERS) analysis was conducted using a bilateral lower limb motor imagery (MI) paradigm. The differences in the execution of motor imagery tasks between left lower limb amputations and healthy controls were explored, and a correlation analysis was calculated between level of phantom limb pain and ERD/ERS. Results: The multiple frequency bands showed a significant ERD phenomenon when the healthy control group performed the motor imagery task, whereas amputees showed significant ERS phenomena in mu band. Phantom limb pain in amputees was negatively correlated with bilateral sensorimotor areas electrode powers. Conclusion: Sensorimotor abnormalities reduce neural activity in the sensorimotor cortex, while the motor imagination of the intact limb is diminished. In addition, phantom limb pain may lead to over-activation of sensorimotor areas, affecting bilateral sensorimotor area remodeling.

Arterial blood gas analysis aids early differential diagnosis and treatment of primary and secondary hypokalaemic periodic paralysis.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p<0.001); they had higher pH (p=0.046) and HCO3 levels (p=0.014) at baseline, and needed a higher dose of potassium supplement before the serum potassium level returned to normal (p=0.007) and a longer time to regain full muscle strength (p=0.004), compared with those with primary or thyrotoxic HypoPP. Emergent arterial blood gas analysis may aid early differential diagnosis of patients with primary and secondary HypoPP.

The Association of Body Mass Index With Mortality Among Pulmonary Hypertension Patients: A Systematic Review and Meta-Analysis of Cohort Studies.

Objective: To run a systematic review and meta-analysis of related studies on body mass index (BMI) and the risk of death among pulmonary hypertension (PH) patients, as well as, to shed light on the shape and strength of the dose-response association. Methods: Studies published up to Jun 2021 in scientific databases such as Scopus, and PubMed as well as Google Scholar were searched. Cohort studies that reported risk estimates for at least two categories of BMI or per certain increase in BMI in relation to mortality in PH patients were included. Summary relative risks were determined with random effects models. Non-linear relationship was discovered with dose-response analysis. Results: All in all, 15 cohort studies were selected. The number of participants was 127,215 out of which 73,999 were reported dead. The summary RR for mortality per a 5-unit increment in BMI was 0.83 (95% confidence interval 0.77-0.89; I2 = 75.6%, n = 9) among PH patients. There was a non-linear dose-response relation between BMI and mortality in PH patients (Pnon-linearity < 0.001), with the lowest risk being at BMI 32-38 kg/m2. Conclusion: Higher BMI is related to decreased risk of mortality among PH patients and the lowest point of the curve was seen at BMI 32-38.

Intermittent theta burst stimulation over the parietal cortex has a significant neural effect on working memory.

The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta-burst stimulation (iTBS) can improve WM. In this within-subject randomized controlled study, under the guidance of fMRI-identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K-score were then calculated to reflect neural and behavioral WM improvement. Repeated-measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere-by-iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated-measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.

Inhibition of LncRNA Vof-16 expression promotes nerve regeneration and functional recovery after spinal cord injury.

Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16 (lncRNA Vof-16) was upregulated after spinal cord injury, but its precise role in spinal cord injury remains unclear. Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis. PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus. The overexpression of lncRNA Vof-16 inhibited PC12 cell survival, proliferation, migration, and neurite extension, whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells. Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6, tumor necrosis factor-α, and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells. Furthermore, we established rat models of spinal cord injury using the complete transection at T10. Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury. At 7 days after spinal cord injury, rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension. At 8 weeks after spinal cord injury, rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb. Notably, lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-α and Caspase-3 expression in treated animals. Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends. These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis. The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury. The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

Reduced sensitivity to delayed time and delayed reward of the post-operative insular glioma patients in delay discounting.

Previous studies have shown that the insula is closely related to addiction, and the structure's role in delay discounting can be measured by a specific task, but the specific role of the insula has been less studied. In this study, we first conducted a lesion study in which we recruited healthy controls (n = 30) and patients with unilateral insula injury (n = 16) to complete a behavioral delay discounting task. Then we conducted a functional magnetic resonance imaging (fMRI) study, and a separate group healthy volunteers (n = 51) completed a delay discounting task during the fMRI scan. The lesion study showed a significant difference between the two groups in the delay discounting task, which revealed that insula injury was associated with impaired decision making. The fMRI study revealed choice-sensitive insula activation that was modulated by delayed time and delayed reward, indicating an important role of the insula in delay discounting. Overall, our results provide evidence for a role of the insular lobe in delay discounting and suggests that this structure may be considered an important factor in the future treatment and diagnosis of addiction disorders.

Downregulation of Long Noncoding RNA LINC00261 Attenuates Myocardial Infarction through the miR-522-3p/Trinucleotide Repeat-Containing Gene 6a (TNRC6A) Axis.

BACKGROUND: Myocardial infarction (MI) is cardiac tissue necrosis caused by acute and persistent ischemic hypoxia of the coronary arteries. This study is aimed at investigating the expression of long noncoding RNA (lncRNA) LINC00261 in MI and its effect on myocardial cells. METHODS: qRT-PCR was performed to detect the expression levels of LINC00261, miR-522-3p, and TNRC6A in normal and MI cells. Western blotting analysis was performed to detect the expression of TNRC6A protein. Viability and apoptosis of myocardial cells after MI with the knockout of LINC00261 or TNRC6A were detected. The relationships among miR-522-3p, LINC00261, and TNRC6A in cardiomyocytes were evaluated using a double luciferase reporter gene assay. Hypoxic preconditioning in normal cells was used to construct a simulated MI environment to investigate the effect of LINC00261 on apoptosis of cardiac cells. RESULTS: LINC00261 and TNRC6A were upregulated, while miR-522-3p was downregulated in coronary heart disease tissues with MI. Knockout of LINC00261 can increase the viability of cardiomyocytes and inhibit cell apoptosis. LINC00261 targets miR-522-3p in cardiomyocytes. In addition, miR-522-3p targets TNRC6A in cardiomyocytes. TNRC6A regulates cell viability and apoptosis of cardiomyocytes after MI, and TNRC6A-induced MI can be reversed by overexpression of miR-522-3p. CONCLUSIONS: LINC00261 downregulated miR-522-3p in cardiomyocytes after MI by directly targeting miR-522-3p. TNRC6A is the direct target of miR-522-3p. Our results indicated that LINC00261 might serve as a therapeutic target for the treatment of MI.

Protective effect of exosomes derived from bone marrow mesenchymal stem cells on rats with diabetic nephropathy and its possible mechanism.

OBJECTIVE: To investigate the effect of exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) on diabetic nephropathy (DN) rats and its possible mechanism. METHODS: Thirty rats were divided into the following three groups of 10 rats each: the NC group (normal rats), the DN group (rats with DN), and the BM group (DN rats injected with BMMSC-Exo). Blood glucose level, renal function, blood lipid level, and plasma viscosity of the rats were detected. Renal tissue morphology was observed using hematoxylin-eosin staining. Expression levels of JAK2 and STAT3 in rats' kidneys were measured by RT-PCR and western blot. RESULTS: The rats in the DN group had higher levels of blood glucose, blood lipids, and blood viscosity, worse renal function, and lower body weight than those in the NC group (all P<0.05). After treatment with BMMSC-Exos, rats in the BM group had markedly decreased levels of blood glucose, blood lipids, and blood viscosity, improved renal function, and higher body weight compared to those in the DN group (all P<0.05). The renal tissues in the NC group had intact structure, and no hyperplastic or hypertrophic cells were observed. In the DN group, the renal glomerulus and mesangial matrix were abnormal, and the capillary lumen and renal tubule lumen were depressed and blocked, accompanied by interstitial edema. Pathologic changes in the renal glomerulus and tubule in the BM group were less severe than those in the DN group. The DN rats had higher expression levels of JAK2 and STAT3 than normal rats, and the rats treated with BMMSC-Exos had lower levels of JAK2 and STAT3 compared to the DN rats (all P<0.05). CONCLUSION: BMMSC-Exo can achieve a good therapeutic effect in DN, which may be due to its ability to lower the blood glucose level, improve renal function, and inhibit JAK2/STAT3 expression.

Serum complement proteomics reveal biomarkers for hypertension disorder of pregnancy and the potential role of Clusterin.

INTRODUCTION: Hypertension disorder of pregnancy (HDP) is one of the leading causes of maternal and foetal illness. The aim of the current study was to identify and verify novel serum markers for HDP. METHODS: A label-free LC-MS/MS method was used to establish the serum proteomic profiles of 12 pre-HDP (before clinical diagnosis of HDP) pregnancies and verify prioritized candidates in the verification set of 48 pre-HDP pregnancies. These biomarkers were revalidated by ELISA in an independent cohort of 88 pre-HDP pregnancies. Subsequently, the candidate biomarkers were histologically analysed by immunohistochemistry, and function was evaluated in TEV-1 cells. RESULTS: We identified 33 proteins with significantly increased abundance and 14 with decreased abundance (peptide FDR ≤ 1%, P < 0.05). Complement was one of the top enriched components in the pre-HDP group compared with the control group. Three complement factors (CLU, CFHR5, and CRP) were significantly increased in the three sets, of which CLU was a critical factor for the development of HDP (OR = 1.22, P < 0.001). When these three factors and body weight were combined, the AUC was 0.74, with a sensitivity of 0.67 and specificity of 0.68 for HDP prediction compared with normal pregnancy. In addition, inflammation-induced CLU could inhibit the invasion of TEV-1 cells. CONCLUSIONS: Complement proteins may play an essential role in the occurrence of HDP by acting on trophoblast cells. CLU may be a high-risk factor for HDP, and the models combining candidates show reasonable screening efficiency of HDP in the first half of pregnancy.

Differential diagnosis and prospective grading of COVID-19 at the early stage with simple hematological and biochemical variables.

We evaluated simple laboratory variables to discriminate COVID-19 from bacterial pneumonia or influenza and for the prospective grading of COVID-19. Multivariate logistic regression and receiver operating characteristic curve were used to estimate the diagnostic performance of the significant discriminating variables. A comparative analysis was performed with different severity. The leukocytosis (P = 0.017) and eosinopenia (P = 0.001) were discriminating variables between COVID-19 and bacterial pneumonia with area under the curve (AUC) of 0.778 and 0.825. Monocytosis (P = 0.003), the decreased lymphocyte-to-monocyte ratio (P < 0.001), and the increased neutrophil-to-lymphocyte ratio (NLR) (P = 0.028) were predictive of influenza with AUC of 0.723, 0.895, and 0.783, respectively. Serum amyloid protein, lactate dehydrogenase, CD3+ cells, and the fibrinogen degradation products had a good correlation with the severity of COVID-19 graded by age (≥50) and NLR (≥3.13). Simple laboratory variables are helpful for rapid diagnosis on admission and hierarchical management of COVID-19 patients.

MiR-615 Regulates NSC Differentiation In Vitro and Contributes to Spinal Cord Injury Repair by Targeting LINGO-1.

LINGO-1(LRR and Ig domain-containing NOGO receptor interacting protein 1) is a viable target for spinal cord injury (SCI) repair due to its potent negative regulation in neuron survival and axonal regeneration. Although promising, the intracellular mechanism underlying LINGO-1 regulation is unclear. Here, we identified miR-615 as a potential microRNA (miRNA) that directly targets LINGO-1 by binding its 3'-untranslated region (3'-UTR) and caused the translation inhibition of LINGO-1. MiR-615 negatively regulated LINGO-1 during neural stem cell (NSC) differentiation and facilitated its neuronal differentiation in vitro. Interestingly, compared to the control, neurons differentiated from miR-615-treated NSCs were immature with short processes. Further results showed LINGO-1/epidermal growth factor receptor (EGFR) signaling may be involved in this process, as blockade of EGFR using specific antagonist resulted in mature neurons with long processes. Furthermore, intrathecal administration of miR-615 agomir in SCI rats effectively knocked down LINGO-1, increased neuronal survival, enhanced axonal extension and myelination, and improved recovery of hindlimbs motor functions. This work thus uncovers miR-615 as an effective miRNA that regulates LINGO-1 in NSC and SCI animals, and suggests miR-615 as a potential therapeutic target for traumatic central nervous system (CNS) injury.

Expression of long non-coding RNAs in complete transection spinal cord injury: a transcriptomic analysis.

Long non-coding RNAs (lncRNAs) are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes. To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury (SCI), the expression signatures of lncRNAs were profiled using RNA sequencing (RNA-seq) technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI. Results showed that 116 of 14,802 detected lncRNAs were differentially expressed, among which 16-including eight up-regulated (H19, Vof16, Hmox2-ps1, LOC100910973, Ybx1-ps3, Nnat, Gcgr, LOC680254) and eight down-regulated (Rmrp, Terc, Ngrn, Ppp2r2b, Cox6a2, Rpl37a-ps1, LOC360231, Rpph1)-demonstrated fold changes > 2 in response to transection SCI. A subset of these RNA-seq results was validated by quantitative real-time PCR. The levels of 821 mRNAs were also significantly altered post-SCI; 592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response, wound repair, and apoptosis, and were significantly enriched in 15 KEGG pathways, including cell phagocytosis, tumor necrosis factor alpha pathway, and leukocyte migration. Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model, and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment. We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury. This study was approved by the Administration Committee of Experimental Animals, Guangdong Province, China.

Evidence for the contribution of COMT gene Val158/108Met polymorphism (rs4680) to working memory training-related prefrontal plasticity.

BACKGROUND: Genetic factors have been suggested to affect the efficacy of working memory training. However, few studies have attempted to identify the relevant genes. METHODS: In this study, we first performed a randomized controlled trial (RCT) to identify brain regions that were specifically affected by working memory training. Sixty undergraduate students were randomly assigned to either the adaptive training group (N = 30) or the active control group (N = 30). Both groups were trained for 20 sessions during 4 weeks and received fMRI scans before and after the training. Afterward, we combined the data from the 30 participants in the RCT study who received adaptive training with data from 71 additional participants who also received the same adaptive training but were not part of the RCT study (total N = 101) to test the contribution of the COMT Val158/108Met polymorphism to the interindividual difference in the training effect within the identified brain regions. RESULTS: In the RCT study, we found that the adaptive training significantly decreased brain activation in the left prefrontal cortex (TFCE-FWE corrected p = .030). In the genetic study, we found that compared with the Val allele homozygotes, the Met allele carriers' brain activation decreased more after the training at the left prefrontal cortex (TFCE-FWE corrected p = .025). CONCLUSIONS: This study provided evidence for the neural effect of a visual-spatial span training and suggested that genetic factors such as the COMT Val158/108Met polymorphism may have to be considered in future studies of such training.

The correlation of PTPN4 expression with prognosis in breast cancer.

Precision medicine, applying knowledge of breast cancer's molecular subtypes, has improved the disease's prognosis. However, recurrence and chemoresistance are critical issues for breast cancer patients. PTPN4, a new potential therapeutic target, has not been studied sufficiently in breast cancer, and the potential role of PTPN4 in the prognosis of breast cancer patients is still unknown. In our study, data from 140 invasive breast cancer patients were retrospectively collected to identify the association between PTPN4 expression and clinical outcomes of these patients. The expressions of PTPN4 were detected by immunohistochemical analysis. Breast hyperplasia tissues showed higher expression of PTPN4. We found that PTPN4 expression was lower in breast cancer patients with relapse than in patients without relapse. Patients with an increased PTPN4 level had a significantly longer relapse-free survival and overall survival time. Decreased PTPN4 expression was an independent factor associated with relapse-free survival and overall survival, as shown by multivariate Cox regression analysis. The study found that PTPN4 is an attractive prognostic biomarker for predicting the clinical outcome and effective disease management of breast cancer patients.

Association between platelet glycoprotein Ia C807T gene polymorphism and ischemic stroke: a meta-analysis in a separate ethnic group.

Many studies have been examined the association of platelet glycoprotein (GP) Ia C807T polymorphism with ischemic stroke (IS) susceptibility. However, the results of these studies are inconsistent. To further assess the effects of GP Ia C807T polymorphism on the risk of IS, a meta-analysis was performed in a separate ethnic group. Relevant studies were identified using PubMed and Chinese databases through January 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, 13 studies contained 2438 IS cases and 2308 controls included. In the total analyses, a significantly elevated risk of IS was associated with all variants of GP Ia C807T in the Chinese population (T vs C: OR = 1.24, 95% CI = 1.09-1.40; TT vs CC: OR = 1.59, 95% CI = 1.17-2.15; TT and CT combined vs CC: OR = 1.32, 95% CI = 1.09-1.59; TT vs CC and CT: OR = 1.35, 95% CI = 1.04-1.76). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han and in South China. This meta-analysis provides the evidence that GP Ia C807T polymorphism may contribute to the IS development in the Chinese population, especially in South China, and further studies in other ethic groups are required for definite conclusions.

Association between FSP, CVHI, inflammatory cytokines and the incidence of primary stroke.

This case-control study was designed to establish a new risk-prediction model for primary stroke using Framingham stroke profile (FSP), cerebral vascular hemodynamic indexes (CVHI) and plasma inflammatory cytokines including hs-CRP, IL-6, TNF-α and Lp-PLA2. A total of 101 primary stroke patients admitted to Dongguan Houjie Hospital between August 2014 and June 2015 were assigned into the case group, and 156 age- and gender-matched healthy subjects from the Houjie Community were allocated into the control group. The prognostic values of FSP, CVHI and inflammatory cytokines including high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were assessed by multivariate logistic regression analysis. Seven risk-prediction models (FSP, CVHI, inflammatory cytokine, FSP+CVHI, FSP+inflammatory cytokine, CVHI+inflammatory cytokine, CVHI+FSP+inflammatory cytokine) were successfully established and the prognostic values were statistically compared by ROC curve and Z test. For FSP, the stroke risk was significantly elevated by 2.85 times when the FSP score was increased by 1 level (P=0.043), increased by 3.25 times for CVHI (P=0.036), 6.53 times for IL-6 (P=0.003), and 7.75 times for Lp-PLA2 (P=0.000). The sensitivity of FSP+CVHI+inflammatory cytokine and CVHI+inflammatory cytokine models was higher than 90%. For model specificity, the specificity of FSP+CVHI+inflammatory cytokine model alone exceeded 90%. FSP, CVHI, IL-6 and Lp-PLA2 are independent risk factors of stroke. Integrating IL-6 and Lp-PLA2 into the models can significantly enhance the risk prediction accuracy of primary stroke. Combined application of FSP+CVHI+inflammatory cytokine is of potential for risk prediction of primary stroke.