Leukocyte-poor platelet-rich plasma and leukocyte-rich platelet-rich plasma promote myoblast proliferation through the upregulation of cyclin A, cdk1, and cdk2.

Muscle injuries are common among athletes and often treated with platelet-rich plasma (PRP). However, whether the leukocyte concentration affects the efficacy of PRP in treating muscle injuries remains unclear. This study investigated the effects of leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP) on myoblast proliferation and the molecular mechanisms underlying these effects. Myoblasts were treated with 0.5% LP-PRP, 0.5% LR-PRP, 1% LP-PRP, or 1% LR-PRP for 24 h. The gene expression of the LP-PRP- and LR-PRP-treated myoblasts was determined using RNA sequencing analysis. Cell proliferation was evaluated using an bromodeoxyuridine (BrdU) assay, and cell cycle progression was assessed through flow cytometry. The expression of cyclin A, cyclin-dependent kinase 1 (cdk1), and cdk2 was examined using Western blotting. The expression of myoblast determination protein 1 (MyoD1) was examined through Western blotting and immunofluorescence staining. The LP-PRP and LR-PRP both promoted the proliferation of myoblasts and increased differential gene expression of myoblasts. Moreover, the LP-PRP and LR-PRP substantially upregulated the expression of cyclin A, cdk1, and cdk2. MyoD1 expression was induced in the LP-PRP and LR-PRP-treated myoblasts. Our results corroborate the finding that LP-PRP and LR-PRP have similar positive effects on myoblast proliferation and MyoD1 expression.

Association of Coffee and Tea Intake with Bone Mineral Density and Hip Fracture: A Meta-Analysis.

Background and Objectives: Osteoporosis is characterized by low bone mass and high bone fragility. Findings regarding the association of coffee and tea intake with osteoporosis have been inconsistent. We conducted this meta-analysis to investigate whether coffee and tea intake is associated with low bone mineral density (BMD) and high hip fracture risk. Materials and Methods: PubMed, MEDLINE, and Embase were searched for relevant studies published before 2022. Studies on the effects of coffee/tea intake on hip fracture/BMD were included in our meta-analysis, whereas those focusing on specific disease groups and those with no relevant coffee/tea intake data were excluded. We assessed mean difference (MD; for BMD) and pooled hazard ratio (HR; for hip fracture) values with 95% confidence interval (CI) values. The cohort was divided into high- and low-intake groups considering the thresholds of 1 and 2 cups/day for tea and coffee, respectively. Results: Our meta-analysis included 20 studies comprising 508,312 individuals. The pooled MD was 0.020 for coffee (95% CI, -0.003 to 0.044) and 0.039 for tea (95% CI, -0.012 to 0.09), whereas the pooled HR was 1.008 for coffee (95% CI, 0.760 to 1.337) and 0.93 for tea (95% CI, 0.84 to 1.03). Conclusions: Our meta-analysis results suggest that daily coffee or tea consumption is not associated with BMD or hip fracture risk.

Study on the Application of Nitrogen-Doped Holey Graphene in Supercapacitors with Organic Electrolyte.

We present a facile low-cost method to produce nitrogen-doped holey graphene (N-HGE) and its application to supercapacitors. A composite of N-HGE and activated carbon (AC) was used as the electrode active material in organic-electrolyte supercapacitors, and the performances were evaluated. Melamine was mixed into graphite oxide (GO) as the N source, and an ultra-rapid heating method was used to create numerous holes during the reduction process of GO. X-ray photoelectron spectra confirmed the successful doping with 2.9-4.5 at.% of nitrogen on all samples. Scanning electron micrographs and Raman spectra revealed that a higher heating rate resulted in more holes and defects on the reduced graphene sheets. An extra annealing step at 1000 °C for 1 h was carried out to further eliminate residual oxygen functional groups, which are undesirable in the organic electrolyte system. Compared to the low-heating-rate counterpart (N-GE-15), N-HGE boosted the specific capacity of the supercapacitor by 42 and 22% at current densities of 0.5 and 20 A/g, respectively. The effects of annealing time (0.5, 1, and 2 h) at 1000 °C were also studied. Longer annealing time resulted in higher capacitance values at all current densities due to the minimized oxygen content. Volumetric specific capacitances of 49 and 24 F/cm3 were achieved at current densities of 0.5 and 20 A/g, respectively. For the high-power-density operation at 31,000 W/kg (or 10,000 W/L), an energy density as high as 11 Wh/kg (or 3.5 Wh/L) was achieved. The results indicated that N-HGE not only improved the conductivity of the composite supercapacitors but also accelerated ion transport by way of shortened diffusion paths through the numerous holes all over the graphene sheets.

Effects of white matter lesion grading on the cognitive function of patients with chronic alcohol dependence.

BACKGROUND: Alcohol dependence has become a major problem that poses a serious threat to public health. Long-term heavy alcohol consumption can lead to brain functional disorders. This study aimed to investigate the relationship of the severity of cerebral white matter lesions (WMLs), serum neurofilament light (NfL) and inflammatory factors, tumour necrosis factor alpha (TNF-α) and Interleukin-1ß (IL-1ß), with the cognitive function of patients with alcohol dependence. METHODS: A total of 118 patients were enrolled in this prospective study, and divided into alcohol-dependent and non-alcohol-dependent groups. The severity of WMLs was assessed using the Fazekas scale based on magnetic resonance imaging analysis. The expression levels of NfL, TNF-α and IL-1ß in the serum of the subjects were measured by enzyme-linked immunosorbent assay. The cognitive function and psychological status of the patients were assessed using the Minimum Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA). The severity of WMLs and the expression levels of serum NfL, TNF-α and IL-1ß in alcohol-dependent patients were analysed for their influence on cognitive function. This clinical trial was approved by China Clinical Trials Registry, and the trial number is ChiCTR2200066057 (http://www.chictr.org.cn/searchproj.aspx). RESULTS: The score of Fazekas scale was higher, and the MMSE score and MoCA score were lower in the alcohol-dependent group than those in the non-alcohol-dependent group. Moreover, the Fazekas score of the alcohol-dependent group was negatively correlated with the MMSE and MoCA scores. The serum NfL, TNF-α and IL-1ß levels were higher in the alcohol-dependent group than in the non-alcohol-dependent group, and the serum NfL, TNF-α and IL-1ß levels in the alcohol-dependent group were negatively correlated with the MMSE and MoCA scores. CONCLUSION: Alcohol-dependent patients have more severe cerebral WMLs and significant cognitive impairment, particularly in visuospatial and executive functions, attention, calculation, abstraction, delayed recall and orientation. Serum NfL, TNF-α and IL-1ß may be used as biomarkers to assess alcohol related cognitive decline.

Study on the Interaction between the Characteristics of Retinal Microangiopathy and Risk Factors for Cerebral Small Vessel Disease.

Objective: This study was designed to explore the characteristics of retinal microangiopathy in patients with cerebral small vessel disease (CSVD) and clarify its interaction with the risk factors for CSVD. Methods: Sixty patients with CSVD and 15 healthy individuals were enrolled. Demographic data, risk factors, and medical history were recorded, and magnetic resonance imaging was performed to detect and analyze the characteristics of retinal microangiopathy in the two groups. The interaction among retinal microangiopathy, vascular risk factors, and total imaging load of CSVD was compared. Results: (1) Hypertension, standard deviation of systolic blood pressure (SBPSD), standard deviation of blood glucose (SDBG), and atherogenic index of plasma (AIP) were independent vascular risk factors for CSVD. (2) Statistically significant differences in hypertension, SBPSD, SDBG, and AIP were observed between the two groups in terms of the total imaging burden of CSVD (p < 0.05). (3) Multivariate logistic linear regression showed that CSVD was associated with a wider central retinal vein equivalent (CRVE) (p = 0.015), a smaller arteriole-to-venule ratio (AVR) (p = 0.001), and a higher incidence of vessel tortuosity (p = 0.027). (4) When the total imaging burden of CSVD ranges from 0 to 4 points, the CRVE is larger, the AVR is smaller, and the incidence of vascular tortuosity is higher, with a statistically significant difference (p < 0.05). (5) The characteristics of retinal microangiopathy were correlated with hypertension, SBPSD, SDBG, and AIP (p < 0.05). (6) An association was observed between the characteristics of retinal microangiopathy and vascular risk factors and the total imaging burden of CSVD (p < 0.05). Conclusions: (1) Hypertension, SBP variability, BG fluctuation, and AIP are independent vascular risk factors for CSVD. (2) Retinal microvessels are changed in patients with CSVD, and venous dilatation, decreased arteriovenous ratio, and vascular tortuosity are the main characteristics of the disease. (3) The characteristics of retinal microangiopathy are interactively correlated with the total imaging load and risk factors for CSVD and can be used as indicators of the severity of CSVD.

Effect of transverse sinus variation on the clinical outcomes of atherosclerotic anterior circulation infarction.

Background: Hypoplasia of the transverse sinus (TS) is a common anatomical variation. The aim of this study was to investigate the effects of TS variation (i.e., TS hypoplasia) and no variation (i.e., TS symmetry) and their subgroups on the clinical outcomes of patients with atherosclerotic anterior circulation cerebral infarction (CI). Methods: A total of 75 patients were included in the study and were divided into the no TS variation group and the TS variation group. The TS variation group was further divided into the following subgroups: the TS variation with ipsilateral CI group and the TS variation with contralateral CI group. We retrospectively analyzed the correlations of the endpoint events of patients with large atherosclerotic anterior circulation infarction and TS no variant, and subgroups of TS variants. Results: We found that the diameter of the ipsilateral IJV in patients with TS variants were significantly smaller than those without TS variants, which was statistically significant (P<0.05). The differences in primary endpoint events, secondary endpoint events, and responsible vessel stenosis were not statistically significant when comparing the TS variant and no TS variant groups, and the TS variant subgroup (P>0.05). We found statistically significant differences in the National Institute of Health stroke scale (NIHSS) and Modified Rankin Scale (mRS) scores after 90 days of CI between the total anterior circulation infarct (TACI) TS variant group, the ipsilateral CI TS variant group, and the partial anterior circulation infarct (PACI) TS hypoplasia group and the ipsilateral CI TS variant group (P<0.05). There was a statistically significant difference (P<0.05) between the TS variant group with TACI, the TS variant group with ipsilateral CI, and the TS no variant group and the TS variant with contralateral CI group when comparing patients' mRS scores after 90 days of CI. Conclusions: The diameter of the internal jugular vein (IJV) ipsilateral to the TS variant was significantly smaller than that of the TS no variant. Patients with TACI in the TS variant group and one of its subgroups (the TS variant with ipsilateral CI group) had more severe clinical symptoms and a worse prognosis than patients in the same group with PACI.

Actinobacillus pleuropneumoniae exotoxin ApxI induces cell death via attenuation of FAK through LFA-1.

ApxI exotoxin is an important virulence factor derived from Actinobacillus pleuropneumoniae that causes pleuropneumonia in swine. Here, we investigate the role of lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), a member of the ß2 integrin family, and the involvement of the integrin signaling molecules focal adhesion kinase (FAK) and Akt in ApxI cytotoxicity. Using Western blot analysis, we found that ApxI downregulated the activity of FAK and Akt in porcine alveolar macrophages (AMs). Preincubation of porcine AMs with an antibody specific for porcine CD18 reduced ApxI-induced cytotoxicity as measured by a lactate dehydrogenase release assay and decreased ApxI-induced FAK and Akt attenuation, as shown by Western blot analysis. Pretreatment with the chemical compounds PMA and SC79, which activate FAK and Akt, respectively, failed to overcome the ApxI-induced attenuation of FAK and Akt and death of porcine AMs. Notably, the transfection experiments revealed that ectopic expression of porcine LFA-1 (pLFA-1) conferred susceptibility to ApxI in ApxI-insensitive cell lines, including human embryonic kidney 293T cells and FAK-deficient mouse embryonic fibroblasts (MEFs). Furthermore, ectopic expression of FAK significantly reduced ApxI cytotoxicity in pLFA-1-cotransfected FAK-deficient MEFs. These findings show for the first time that pLFA-1 renders cells susceptible to ApxI and ApxI-mediated attenuation of FAK activity via CD18, thereby contributing to subsequent cell death.

Exosomal miRNA-223-3p as potential biomarkers in patients with cerebral small vessel disease cognitive impairment.

BACKGROUND: Cerebrovascular disease is a common clinical illness. Many patients with cerebrovascular disease can be accompanied by cognitive impairment. The exosomal microRNA (miRNA)-223-3p is related to vascular endothelial injury, synaptic function, inflammatory response, and other mechanisms. In this study, we investigated the levels of plasma exosomal miRNA-223-3p in patients with cerebral small vessel disease (CSVD), in order to determine whether it could be used as a more accessible potential biomarker for the early diagnosis and treatment of CSVD. This study aimed to explore whether the development of cognitive impairment can be explained by differentially expressed miRNA-223-3p by detecting the level of miRNA-223-3p, which is abundant in peripheral blood exosomes related to cognitive impairment in CSVD. METHODS: The three groups of participants included 40 patients with CSVD cognitive impairment (CSVDCI), 38 patients with CSVD, and 35 normal controls (NC). The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of blood exosomal miRNA-223-3p. In addition, we also studied the relationship between exosomal miRNA-223-3p and blood Hcy and C-reactive protein (CRP). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of plasma exosomal miRNA-223-3p. RESULTS: The expression of exosomal miRNA-223-3p in CSVD increased, and the expression of miRNA-223-3p increased significantly with the occurrence of cognitive impairment. Exosomal miRNA-223-3p was positively correlated with the expression levels of Hcy and CRP in the blood. CONCLUSIONS: The expression of plasma exosomal miRNA-223-3p is associated with the development of cognitive impairment in patients with CSVD. It may be involved in the pathogenesis of CSVD and cognitive impairment, and can be used as a sensitive predictive biomarker.

A narrative review of multimodal imaging of white matter lesions in type-2 diabetes mellitus.

OBJECTIVE: To discuss the relevant studies about the structural and functional changes of the brain in patients with type-2 DM (T2DM) and white matter lesion (WML) in recent years, and to summarize them. BACKGROUND: T2DM is a common metabolic disease with increasing prevalence worldwide. This disease is closely related to central nervous system and vascular disease, and is considered a risk factor for white matter lesions in the brain. Compared to healthy individuals, WML patients with T2DM exhibit changes in brain perfusion, functional networks, nerve fiber structure, and brain tissue metabolism. METHODS: We analyzed recent studies related to structural and functional changes in the brain of patients suffering from T2DM and WML and summarized them. CONCLUSIONS: Multimodal magnetic resonance imaging (MRI) utilizes noninvasive and sensitive imaging techniques to provide multiparametric information in patients with T2DM to help in clinical practice. It features non-invasively and with high sensitivity assess the histomorphological and functional abnormalities of white matter in patients with T2DM using various parameters. We can use multimodal MRI methods to reflect the microscopic damage of neuromyelin structures and pathological changes of neuronal metabolic functions in WML in T2DM patients, and thus speculate the disease progression. This approach can be helpful for the early diagnosis and treatment of patients with such a disease who do not exhibit neurological deficit, to effectively improve their prognosis.

Safety of two common laparoscopic inguinal herniorrhaphy approaches: an updated systematic review with meta-analysis of randomized clinical trials.

BACKGROUND: Previous evidence indicated that total extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) are advantageous in efficacy of inguinal herniorrhaphy. Therefore, our aim in this study was to evaluate the association of the two laparoscopic approaches on safety of inguinal herniorrhaphy. METHODS: In this update study, we searched the Cochrane Library, EMBASE, PubMed, Scopus, and Web of Science and identified randomized clinical trials comparing complications in TEP and TAPP herniorrhaphy. We mainly used Peto odds ratio with 95% confidence interval (CI) for meta-analysis because of zero-cell. RESULTS: Fourteen eligible trials recruited 659 and 682 patients in TEP and TAPP respectively. In overall pooling, although TEP had a higher seroma rate than TAPP (Peto odds ratio =2.01; 95% CI, 1.39 to 2.91), it had a lower scrotal/cord edema rates at immediate postoperative (Peto odds ratio =0.22; 95% CI, 0.09 to 0.57) and 1 week after inguinal hernia repair (Peto odds ratio =0.58; 95% CI, 0.37 to 0.91) than TAPP. CONCLUSIONS: TEP and TAPP have their own advantages in inguinal herniorrhaphy. TAPP was associated with a lower seroma rate, and TEP was associated with a lower edema rate. Therefore, shared decision-making on laparoscopic inguinal herniorrhaphy with TEP and TAPP is still needed.

Imaging Diagnosis of Central Nervous System Damage in Patients with T2DM.

This paper uses resting-state functional magnetic resonance imaging (rs-FMRI) to construct a whole-brain binary functional network through a complex brain network analysis theory based on graph theory to explore the functional network of patients with type 2 diabetes (T2DM). Changes in topological properties and their potential relationships with fasting blood glucose (FBG), glycated haemoglobin (HbAlc), and cognitive function scale, and further explore the diagnostic value of rs-FMRI technology for central nervous system damage in T2DM patients, for clinical diagnosis and treatment Provide objective radiological evidence. In the range of sparsity (Sp) of 0.05 to 0.50 and a step size of 0.01, compared with the random network, the resting brain functional networks in the T2DM group and the HC group have larger clustering coefficients and similar shortest paths. Length and small world index greater than 1, that is, both groups of resting brain functional networks have small world characteristics. The MoCA score of the T2DM group was positively correlated with the node degree (r = 0.400, p = 0.043) and the node efficiency (r = 0.452, p = 0.021) of the right straight back. FBG is positively correlated with the node degree of the left occipital gyrus (r = 0.422, p = 0.023); HbAlc is related to the node degree of the left occipital gyrus (r = 0.372, p = 0.043) and the node degree of the left occipital gyrus (r = 0.382, p = 0.037) was positively correlated with the node intermediary (r = 0.388, p = 0.034) at the back of the right cingulate gyrus. The topological properties of the resting brain function network of T2DM patients with negative MRI findings have changed compared with normal people, indicating that T2DM is an important factor leading to brain function damage, further explaining the rs-fMRI technology and complex brain networks based on graph theory Analysis theory can be used as an effective method to study the changes of brain function in T2DM patients.

Application of Hydrogen Proton Magnetic Resonance Technology Combined with Brain Neurometabolite Analysis in the Treatment of Cognitive Impairment Caused by Type 2 Diabetes Mellitus.

This study used hydrogen proton magnetic resonance imaging to detect the changes of white matter and the medial cortex in the prefrontal cortex of patients with type 2 diabetes, analyzed its relationship with cognitive function and blood glucose level, and discussed the recognition of patients with type 2 diabetes from the perspective of brain metabolism. We discuss the neural mechanisms affected by the disorder. The experiment recruited 65 volunteers, including 32 control subjects and 33 patients with type 2 diabetes. All volunteers underwent clinical cognitive function and psychological evaluation, including a simple intelligent mental state examination scale, digital breadth test, Raven intelligence test, Flanker paradigm experiment, connection test, auditory word learning test, depression self-evaluation scale, and anxiety self-rating scale. All subjects underwent multivoxel proton magnetic resonance scanning, and the spectral data were processed and metabolite concentration analysis was completed by Functool software. The detected regions of interest included the bilateral prefrontal white matter and bilateral prefrontal cortex. This study found that the N-acetylaspartate (NAA) and NAA/myo-inositol (MI) of the right prefrontal cortex were reduced, the right prefrontal white matter choline-containing compounds increased, and the MI of the bilateral prefrontal cortex increased in the type 2 diabetes group compared with the control group. The NAA value of the right prefrontal cortex in the type 2 diabetes group was negatively correlated with the glycated hemoglobin concentration. The study found that the right prefrontal cortex NAA value of patients with type 2 diabetes was negatively correlated with the glycated hemoglobin concentration, reflecting that recent blood glucose levels can affect the changes of brain metabolites, and reasonable control of blood glucose can effectively delay brain neurons caused by diabetes.

Autophagy is involved in assisting the replication of Bamboo mosaic virus in Nicotiana benthamiana.

Autophagy plays a critical role in plants under biotic stress, including the response to pathogen infection. We investigated whether autophagy-related genes (ATGs) are involved in infection with Bamboo mosaic virus (BaMV), a single-stranded positive-sense RNA virus. Initially, we observed that BaMV infection in Nicotiana benthamiana leaves upregulated the expression of ATGs but did not trigger cell death. The induction of ATGs, which possibly triggers autophagy, increased rather than diminished BaMV accumulation in the leaves, as revealed by gene knockdown and transient expression experiments. Furthermore, the inhibitor 3-methyladenine blocked autophagosome formation and the autophagy inducer rapamycin, which negatively and positively affected BaMV accumulation, respectively. Pull-down experiments with an antibody against orange fluorescent protein (OFP)-NbATG8f, an autophagosome marker protein, showed that both plus- and minus-sense BaMV RNAs could associate with NbATG8f. Confocal microscopy revealed that ATG8f-enriched vesicles possibly derived from chloroplasts contained both the BaMV viral RNA and its replicase. Thus, BaMV infection may induce the expression of ATGs possibly via autophagy to selectively engulf a portion of viral RNA-containing chloroplast. Virus-induced vesicles enriched with ATG8f could provide an alternative site for viral RNA replication or a shelter from the host silencing mechanism.

Effects of transabdominal preperitoneal and totally extraperitoneal inguinal hernia repair: an update systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Compared with open herniorrhaphy, laparoscopic herniorrhaphy can yield more favorable clinical outcomes. However, previous studies failed to give definite answer for comparison between laparoscopic inguinal hernia repair approaches. This study aimed to systematically determine the differences in recurrence rate, duration of return to work, pain, surgery duration, and duration of hospital stay between transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) approach for inguinal hernia. METHODS: PubMed, Embase, and Cochrane Library (including the Cochrane Central Register of Controlled Trials) abstracts up to September 2017 were searched for randomized controlled trials (RCTs) comparing TAPP or TEP hernia repairing. The hernia recurrence rate, time to return to work, analgesic consumption, surgery duration, hospital stay, and the pain score were recorded with subgroup analysis of the hernia type. RESULTS: Sixteen RCTs that randomized 1519 patients with hernia into TEP and TAPP repair groups were analyzed in this study. The results revealed that TEP repair resulted in shorter hospital stay of primary cases (MD - 0.87, 95% CI - 1.67 to - 0.07) but was associated with a longer operative duration in recurrent hernia group (MD 3.35, 95% CI 0.16 - 6.54). CONCLUSIONS: TEP and TAPP have their own advantages. TEP repair reduces short-term postoperative pain more effectively than TAPP repair and results in shorter hospital stay of primary cases. In contrast, TAPP repair is correlated with shorter surgery duration. These findings show that shared decision-making regarding both approaches of laparoscopic hernia repair may be needed.

Homeostasis model assessment of insulin resistance in relation to the poor functional outcomes in nondiabetic patients with ischemic stroke.

Whether insulin resistance (IR) predicts worse functional outcome in ischemic stroke is still a matter of debate. The aim of the present study is to determine the association between IR and risk of poor outcome in 173 Chinese nondiabetic patients with acute ischemic stroke. This is a prospective, population-based cohort study. Insulin sensitivity, expressed by the homeostasis model assessment (HOMA) of insulin sensitivity (HOMA index = (fasting insulin × fasting glucose)/22.5). IR was defined by HOMA-IR index in the top quartile (Q4). Functional impairment was evaluated at discharge using the modified Rankin scale (mRS). The median (interquartile range) HOMA-IR was 2.14 (1.17-2.83), and Q4 was at least 2.83. There was a significantly positive correlation between HOMA-IR and National Institutes of Health Stroke Scale (r = 0.408; P<0.001). In multivariate analyses, patients in IR group were associated with a higher risk of poor functional outcome (odds ratio (OR) = 3.23; 95% confidence interval (CI) = 1.75-5.08; P=0.001). In multivariate models comparing the third and fourth quartiles against the first quartile of the HOMA-IR, levels of HOMA-IR were associated with poor outcome, and the adjusted risk of poor outcome increased by 207% (OR = 3.05 (95% CI 1.70-4.89), P=0.006) and 429% (5.29 (3.05-9.80), P<0.001). In a receiver operating characteristic curve (ROC) analysis of poor outcome, the area under the curve (AUC) increased from 0.80 to 0.84 (95% CI: 0.79-0.88) by adding HOMA-IR to clinical examination variables (P=0.02). High HOMA-IR index is associated with a poor functional outcome in nondiabetic patients with acute ischemic stroke.

Prognostic Utility of Fatty Acid-Binding Protein 4 in Patients with Type 2 Diabetes and Acute Ischemic Stroke.

The role of fatty acid-binding proteins (FABPs) in atherosclerosis has been investigated. The aim of this study was to verify the hypothesis that higher levels of serum fatty acid-binding protein 4 (FABP4) could be a prognostic factor in Chinese patients with type 2 diabetes (T2DM) and acute ischemic stroke (AIS). From September 2015 to August 2016, consecutive first-ever AIS patients combined with T2DM were included in this study. FABP4, NIH stroke scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcomes within 3 months. Multivariate analyses were performed using logistic regression models. We measured FABP4 in 329 patients. The median age of patients included in this study was 63 (IQR, 56-72) years and 45.9% were women. FABP4 serum levels were obtained at a median of 8.5 h (IQR, 4.0-14.0 h) after the stroke onset with a median value of 21.4 ng/ml (IQR, 15.6-28.2 ng/ml). In multivariable models, FABP4 remained an independent stroke severity predictor with an adjusted OR of 1.05 (95% CI, 1.02-1.09). In multivariate models comparing the third (odd ratio (OR), 2.25; 95% confidence interval (CI), 1.59-3.54) and fourth quartiles (OR, 3.75; 95% CI, 2.48-5.03) against the first quartile of the FABP4, levels of FABP4 were associated with poor functional outcome. At 3 months, 38 patients (11.6%; 95%CI, 8.1-15.0%) had died. The mortality distribution across the FABP4 quartiles ranged between 3.7% (first quartile) and 20.7% (fourth quartile). Elevation of FABP4 is associated with an increased risk of death and poor functional outcome events in patients with type 2 diabetes and acute ischemic stroke and is independent of other established clinical risk predictors and biomarkers.

MRI-based comparative study of different mild cognitive impairment subtypes: protocol for an observational case-control study.

INTRODUCTION: Amnestic mild cognitive impairment (aMCI) and vascular mild cognitive impairment (VaMCI) comprise the 2 main types of mild cognitive impairment (MCI). The first condition generally progresses to Alzheimer's disease, whereas the second is likely to develop into vascular dementia (VD). The brain structure and function of patients with MCI differ from those of normal elderly individuals. However, whether brain structures or functions differ between these 2 MCI subtypes has not been studied. This study is designed to analyse neuroimages of brain in patients with VaMCI and aMCI using multimodality MRI (structural MRI (sMRI), functional MRI and diffusion tensor imaging (DTI)). METHODS AND ANALYSIS: In this study, 80 participants diagnosed with aMCI, 80 participants diagnosed with VaMCI, and 80 age-matched, gender-matched and education-matched normal controls (NCs) will be recruited to the Hongqi Hospital of Mudanjiang Medical University, Heilongjiang, China. All participants will undergo neuroimaging and neuropsychological evaluations. The primary outcome measures will be (1) microstructural alterations revealed by multimodal MRIs, including sMRI, resting-state functional MRI and DTI; and (2) a neuropsychological evaluation, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Memory and Executive Screening (MES), trail making test, Stroop colour naming condition and Clinical Dementia Rating (CDR) scale, to evaluate global cognition, memory function, attention, visuospatial skills, processing speed, executive function and emotion, respectively. TRIAL REGISTRATION NUMBER: NCT02706210; Pre-results.

Involvement of NF-κB in regulation of Actinobacillus pleuropneumoniae exotoxin ApxI-induced proinflammatory cytokine production in porcine alveolar macrophages.

Actinobacillus pleuropneumoniae is a crucial respiratory pathogen that causes fibrinous, hemorrhagic, necrotizing pleuropneumonia in pigs. A. pleuropneumoniae exotoxins (ApxI to IV) are the major virulence factors contributing to A. pleuropneumoniae pathogenesis. Previously, we demonstrated that ApxI induces the expression of proinflammatory cytokines in porcine alveolar macrophages (PAMs) via the mitogen-activated protein kinases (MAPKs) p38 and cJun NH2-terminal kinase (JNK). Nonetheless, the role of nuclear factor (NF)-κB-a transcription factor widely implicated in immune and inflammatory responses-in ApxI-elicited cytokine production has yet to be defined. In the present study, we examined the involvement of NF-κB in ApxI-elicited production of interleukin (IL)-1ß, IL-8, and tumor necrosis factor (TNF)-α in PAMs and investigated the correlation between NF-κB and MAPK (p38 and JNK) pathways in this event. The results of Western blot analysis, confocal microscopy, and a DNA binding activity assay revealed that the classical NF-κB pathway was activated by ApxI, as evidenced by the decreased levels of IκB and subsequent NF-κB translocation and activation in ApxI-stimulated PAMs. Moreover, the blocking of ApxI-induced NF-κB activation significantly attenuated the levels of mRNA and protein secretion of IL-1ß, IL-8, and TNF-α in PAMs. Notably, the attenuation of JNK activation by a specific inhibitor (SP600125) reduced ApxI-induced NF-κB activation, whereas a p38 blocker (SB203580) had no effect on the NF-κB pathway. Further examination revealed that the level of phosphorylation at serine 536 on the NF-κB p65 subunit was dependent on JNK activity. Collectively, this study, for the first time, demonstrates a pivotal role of NF-κB in ApxI-induced IL-1ß, IL-8, and TNF-α production; JNK, but not p38, may positively affect the activation of the classical NF-κB pathway.