Elevated levels of ß2-microglobulin in cerebrospinal fluid in adult patients with viral encephalitis/meningitis.

BACKGROUND: Increased cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) values are attributed to immune activation, lymphoid cell turnover and release of tissue destruction in the central nervous system (CNS). We investigated plasma and CSF ß2-MG levels in adult patients with viral encephalitis/meningitis and their correlations with clinical parameters. METHOD: CSF samples from 26 patients with viral encephalitis/meningitis were collected. Moreover, 24 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 22 enrolled patients and 20 healthy individuals were collected. The ß2-MG levels were measured by immunoturbidimetry on an automatic biochemical analyzer. Clinical data were extracted from an electronic patient documentation system. RESULT: CSF levels of ß2-MG, adenosine deaminase (ADA), white blood cell (WBC), lactate dehydrogenase (LDH), protein and lactate were significantly increased in patients with viral encephalitis/meningitis respectively (p < 0.001, p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.013). In contrast, no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were weakly correlated with WBC (r = 0.426, p = 0.030), lymphocyte percentage (r = 0.599, p = 0.018), ADA (r = 0.545, p = 0.004) and LDH (r = 0.414, p = 0.036), but not with lactate (r = 0.381, p = 0.055), protein (r = 0.179, p = 0.381) and plasma levels of ß2-MG (r = -0.156, p = 0.537) in viral encephalitis/meningitis patients. CONCLUSION: CSF ß2-MG may be a potential inflammatory marker for viral encephalitis/meningitis in adult patients diagnosed with viral encephalitis/meningitis.

The novel HLA-B*54:01:12 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*54:01:12 differs from HLA-B*54:01:01:01 by one nucleotide in exon 2.

Graph analysis of cortical reorganization after virtual reality-based rehabilitation following stroke: a pilot randomized study.

Introduction: Stroke is the leading cause of functional disability worldwide. With the increase of the global population, motor rehabilitation of stroke survivors is of ever-increasing importance. In the last decade, virtual reality (VR) technologies for rehabilitation have been extensively studied, to be used instead of or together with conventional treatments such as physiotherapy or occupational therapy. The aim of this work was to evaluate the GestureCollection VR-based rehabilitation tool in terms of the brain changes and clinical outcomes of the patients. Methods: Two groups of chronic patients underwent a rehabilitation treatment with (experimental) or without (control) complementation with GestureCollection. Functional magnetic resonance imaging exams and clinical assessments were performed before and after the treatment. A functional connectivity graph-based analysis was used to assess differences between the connections and in the network parameters strength and clustering coefficient. Results: Patients in both groups showed improvement in clinical scales, but there were more increases in functional connectivity in the experimental group than in the control group. Discussion: The experimental group presented changes in the connections between the frontoparietal and the somatomotor networks, associative cerebellum and basal ganglia, which are regions associated with reward-based motor learning. On the other hand, the control group also had results in the somatomotor network, in its ipsilateral connections with the thalamus and with the motor cerebellum, which are regions more related to a purely mechanical activity. Thus, the use of the GestureCollection system was successfully shown to promote neuroplasticity in several motor-related areas.

[Seasonal Regulation of Soil Microbial Carbon and Phosphorus Metabolisms in an Apple Orchard: Evidence from the Enzymatic Stoichiometry Method].

Soil microbial carbon (C), nitrogen (N), and phosphorus (P) nutrient requirements and metabolic limitations are closely related to the availability of environmental nutrients. However, it is unclear how manure and chemical fertilization shift nutrient limitations for microbes in terms of the soil enzymatic stoichiometry in an apple orchard. Therefore, based on the long-term experiment located in an apple orchard established in 2008, this study applied the theory and method of soil enzyme stoichiometry to systematically investigate the effects of the combined application of manure and chemical fertilizers on soil C, N, and P turnover-related enzyme activities (ß-1,4-glucosidase, BG; leucine aminopeptidase, NAG; ß-1,4-N-acetylglucosaminidase, LAP; and acid or alkaline phosphatase, PHOS) and their stoichiometric characteristics and analyzed their relationships with environmental factors and microbial carbon use efficiency. The experiment was designed with four treatments, such as, no fertilization input as the control (CK), single application of chemical fertilizer (NPK), combined application of manure and chemical fertilizer (MNPK), and single application of manure (M). The results revealed that:① at different growth stages of fruit trees, the soil microbial biomass C (microC) content of manure fertilizer treatments (MNPK and M) was significantly higher than that of no manure fertilizer treatments (CK and NPK). The content of microbial biomass N (microN) in the NPK, MNPK, and M treatments increased by 89%, 269%, and 213%, respectively, compared with that in CK (P<0.05). ② Compared with those in the fertilization treatments, CK had higher leaf N and P contents (29.8 g·kg-1 and 2.17 g·kg-1) at the germination stage, and the leaf P content at the germination stage alone was significantly negatively correlated with soil available phosphorus (AP) content. ③ Soil enzyme stoichiometry analysis demonstrated that all data points in this study were above the 1:1 line, indicating that microbial communities had a strong phosphorus limitation. The range of vector length and angle was 0.56-0.79 and 59.3°-67.7°, respectively, in the growth period of fruit trees, and the vector angle was >45° in this study, which also reflected the strong phosphorus limitation of microorganisms. ④ RDA and random forest model analysis showed that organic carbon and available nitrogen (AN) were the main physical and chemical factors affecting vector length; AP, AN, and soil water content were the main physical and chemical factors affecting vector angle. Combined with SEM analysis, AN and dissolved organic carbon (DOC) directly affected microC and microN, AP directly affected microP and microN, DOC and AP directly affected vector length, and AP and microN directly affected vector angle. In addition, microbial carbon utilization was positively correlated with vector length and negatively correlated with vector angle. In summary, the combined application of manure and chemical fertilizers regulated microbial carbon and phosphorus metabolism by affecting soil carbon and phosphorus content at different growth stages of fruit trees, thereby affecting microbial carbon utilization. This study provides a scientific basis for manure and chemical fertilizers to improve soil quality and maintain soil health.

Texture-based brain networks for characterization of healthy subjects from MRI.

Brain networks have been widely used to study the relationships between brain regions based on their dynamics using, e.g. fMRI or EEG, and to characterize their real physical connections using DTI. However, few studies have investigated brain networks derived from structural properties; and those have been based on cortical thickness or gray matter volume. The main objective of this work was to investigate the feasibility of obtaining useful information from brain networks derived from structural MRI, using texture features. We also wanted to verify if texture brain networks had any relation with established functional networks. T1-MR images were segmented using AAL and texture parameters from the gray-level co-occurrence matrix were computed for each region, for 760 subjects. Individual texture networks were used to evaluate the structural connections between regions of well-established functional networks; assess possible gender differences; investigate the dependence of texture network measures with age; and single out brain regions with different texture-network characteristics. Although around 70% of texture connections between regions belonging to the default mode, attention, and visual network were greater than the mean connection value, this effect was small (only between 7 and 15% of these connections were larger than one standard deviation), implying that texture-based morphology does not seem to subside function. This differs from cortical thickness-based morphology, which has been shown to relate to functional networks. Seventy-five out of 86 evaluated regions showed significant (ANCOVA, p < 0.05) differences between genders. Forty-four out of 86 regions showed significant (ANCOVA, p < 0.05) dependence with age; however, the R2 indicates that this is not a linear relation. Thalamus and putamen showed a very unique texture-wise structure compared to other analyzed regions. Texture networks were able to provide useful information regarding gender and age-related differences, as well as for singling out specific brain regions. We did not find a morphological texture-based subsidy for the evaluated functional brain networks. In the future, this approach will be extended to neurological patients to investigate the possibility of extracting biomarkers to help monitor disease evolution or treatment effectiveness.

Kawasaki disease with peritonsillar abscess as the first symptom: A case report.

BACKGROUND: Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome, is an acute, self-limiting vasculitis of unknown aetiology that mainly involves the medium and small arteries and can lead to serious cardiovascular complications, with a 25% incidence of coronary artery aneurysms. Periton-Sillar abscesses are a rare symptom of KD and is easily misdiagnosed at its early stages. CASE SUMMARY: A 5-year-old boy who presented to a community hospital with a 3-d fever, difficulty in opening his mouth, and neck pain and was originally treated for throat infection without improvement. On the basis of laboratory tests, ultrasound of submandibular and superficial lymph nodes and computed tomography of the neck, the clinician diagnosed the periamygdala abscess and sepsis that did not resolve after antibiotic therapy. On the fifth day of admission, the child developed conjunctival congestion, prune tongue, perianal congestion and desquamation, and slightly stiff and swollen bunions on both feet. A diagnosis of KD was reached with complete remission after intravenous immunoglobulin treatment. CONCLUSION: Children with neck pain, lymph node enlargement, or airway obstruction as the main manifestations are poorly treated with intravenous broad-spectrum antibiotics. Clinicians should not rush invasive operations such as neck puncture, incision, and drainage and should be alert for KD when it cannot be explained by deep neck space infection and early treatment with aspirin combined with gammaglobulin.

Quantification of the Tissue Oxygenation Delay Induced by Breath-Holding in Patients with Carotid Atherosclerosis.

Carotid artery stenosis (CAS) is a common vascular disease with long-term consequences for the brain. Although CAS is strongly associated with impaired cerebral hemodynamics and neurodegeneration, the mechanisms underlying hemodynamic impairment in the microvasculature remain unknown. In this work, we employed functional near-infrared spectroscopy (fNIRS) to introduce a methodological approach for quantifying the temporal delay of the evoked hemodynamic response. The method was validated during a vasodilatory task (breath-holding) in 50 CAS patients and 20 controls. Our results suggest that the hemodynamic response to breath-holding can be delayed by up to 6 s in the most severe patients, a significant increase from the median 4 s measured for the control group (p = 0.01). In addition, the fraction of brain regions that responded to the task decreased as the CAS severity increased, from a median of 90% in controls to 73% in the most severe CAS group (p = 0.04). The presence of collateral circulation increases the response to breath-holding and decreases the average time delays across the brain, although the number of communicating arteries alone cannot predict these fNIRS-based hemodynamic variables (p > 0.09). Overall, this work proposes a method to quantitatively assess impaired cerebral hemodynamics in CAS patients.

2B and 3C Proteins of Senecavirus A Antagonize the Antiviral Activity of DDX21 via the Caspase-Dependent Degradation of DDX21.

Senecavirus A (SVA), also known as Seneca Valley virus, is a recently discovered picornavirus that can cause swine vesicular disease, posing a great threat to the global swine industry. It can replicate efficiently in cells, but the molecular mechanism remains poorly understood. This study determined the host's differentially expressed proteins (DEPs) during SVA infection using dimethyl labeling based on quantitative proteomics. Among the DE proteins, DDX21, a member of the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase (DDX) family, was downregulated and demonstrated inhibiting SVA replication by overexpression and knockdown experiment. To antagonize this antiviral effect of DDX21, SVA infection induces the degradation of DDX21 by 2B and 3C proteins. The Co-IP results showed that 2B and 3C did not interact with DDX21, suggesting that the degradation of DDX21 did not depend on their interaction. Moreover, the 3C protein protease activity was necessary for the degradation of DDX21. Furthermore, our study revealed that the degradation of DDX21 by 2B and 3C proteins of SVA was achieved through the caspase pathway. These findings suggest that DDX21 was an effective antiviral factor for suppressing SVA infection and that SVA antagonized its antiviral effect by degrading DDX21, which will be useful to guide further studies into the mechanism of mutual regulation between SVA and the host.

[Effect of Rehmanniae Radix Praeparata on energy metabolism in prefrontal cortex of rats with attention deficit hyperactivity disorder based on "static Yin and dynamic Yang" theory].

The present study investigated the effect of Rehmanniae Radix Praeparata(RRP) on the energy metabolism of prefrontal cortex(PFC) of spontaneously hypertensive rats with attention deficit hyperactivity disorder(ADHD) based on the "static Yin and dynamic Yang" theory.Thirty spontaneously hypertensive male rats aged 3 weeks were randomly divided into a model group, a methylphenidate(MPH) group(2 mg·kg~(-1)), and an RRP group(2.4 g·kg~(-1)).Wistar-Kyoto(WKY) male rats of the same age were assigned to the normal group.Rats were treated with corresponding drugs twice per day, and those in the model group and the normal group received the same volume of 0.9% sodium carboxymethyl cellulose(CMC-Na) solution by gavage.The open-field test was performed to evaluate the spontaneous and impulsive behaviors of rats before treatment and on the 4~(th) week after treatment.Four weeks after treatment, PFC was isolated and mitochondria were prepared.The content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in the PFC was determined by high-performance liquid chromatography(HPLC), and energy charge(EC) was calculated.The parameters related to mitochondrial respiratory function were measured by the Clark oxygen electrode, specifically, state 3 respiration(ST3), state 4 respiration(ST4), and respiratory control rate(RCR).Enzymatic activities of succinate dehydrogenase(SDH), cytochrome C oxidase(COX), Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase were measured by chemical colorimetry.Mitochondrial permeability transition pore(mPTP) opening was measured by spectrophotometry.Protein expression of glucose transporter 1(GLUT1) and GLUT3 in PFC was tested by Western blot.Compared with the results in the model group, RRP could significantly reduce the total distance of movement, vertical times, and distance in the central area in the open field test(P<0.05 or P<0.01), increase the content of ATP and EC, decrease the content of AMP(P<0.05), elevate ST3 and RCR(P<0.05), potentiate activities of SDH, COX, Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase(P<0.05 or P<0.01), inhibit the opening of mPTP, and increase the expression levels of GLUT1 and GLUT3 proteins(P<0.05).It was inferred that RRP could inhibit hyperacti-vity and impulsivity by improving the energy metabolism disorder in PFC of ADHD rats, and its mechanism may be related to the improvement of mitochondrial respiratory function, potentiation of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, and mitochondrial respiratory enzymes, inhibition of the opening of mPTP, and up-regulation of the expression of glucose transporter proteins.This study initially reveals the biological connotation of the "static Yin and dynamic Yang" theory in ADHD.

B cell memory responses induced by foot-and-mouth disease virus-like particles in BALB/c mice.

A challenging but critical question is that new foot-and-mouth disease (FMD) vaccines should be to induce B cell memory to provide antibodies for long-term protection. The maintenance of B cell memory is dependent on long-lived plasma cells (LLPCs) and memory B cells. We developed a chimeric FMDV virus-like particles (FMDV-VLPs), fusing VP1-VP4 into HBcAg. In our study, we investigated if or how long B cell memory was induced by FMDV-VLPs in mice. The data showed that FMDV-VLPs can induce memory humoral responses with a high level of total IgG1, IgG2a, IgA, and FMDV-specific IgG antibodies in serum. The persistence of antibody levels in serum could depend on LLPCs. The proportion of LLPCs in CD19+ cells in bone marrow exhibited a dynamic trend with two peaks at 28 days post-immunization (dpi) and 72 dpi, respectively. Additionally, the proportion of memory B cells in CD19+ cells in the spleen increased significantly both at 7 days post primary immunization and at 7 days post -boost immunization. Of note, LLPCs together with memory B cells contribute to the production of FMDV-specific IgG and IgG1. The changes of LLPCs and memory B cells may be related to TNF-α, IL-6 and, CXCL12. Taken together, FMDV-VLPs could induce B cells memory responses. A further understanding of the mechanisms that FMDV-VLPs how we can manipulate the induction and maintenance of memory B cells and LLPCs will promote vaccine design and likely address several challenges to develop FMDV new vaccines in the future.

A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed definition of fatty liver disease (FLD) independent of excessive alcohol consumption (EAC) and hepatitis viral infection. Evidence on the mortality risk in different types of FLD [nonalcoholic FLD (NAFLD), alcoholic FLD (AFLD), and MAFLD] is sparse, hindering the identification of high-risk populations for preferential clinical surveillance. METHODS: A total of 11,000 participants in the Third National Health and Nutrition Examination Survey were enrolled. Participants were categorized into three groups [FLD( - ), MAFLD( - ), and MAFLD( +)] according to FLD and MAFLD criteria, and further categorized into six groups by EAC. Multivariate Cox proportional hazard model was used to estimate the risk of all-cause, cardiovascular-related, and cancer-related mortality. RESULTS: During a median follow-up of 23.2 years, a total of 3240 deaths were identified. Compared with FLD( - )/EAC( - ) participants, MAFLD( +) individuals had higher all-cause mortality risk [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.18-1.39] regardless of EAC status [MAFLD( +)/NAFLD: HR = 1.22, 95%CI = 1.11-1.34; MAFLD( +)/AFLD: HR = 1.83, 95%CI = 1.46-2.28], while not for MAFLD( - ) individuals. Furthermore, diabetes-driven-MAFLD had higher mortality risk (HR = 2.00, 95%CI = 1.77-2.27) followed by metabolic dysregulation-driven-MAFLD (HR = 1.30, 95%CI = 1.06-1.60) and overweight/obesity-driven-MAFLD (HR = 1.11, 95%CI = 1.00-1.22). Additionally, MAFLD( - ) participants with elevated fibrosis score were also associated with statistically significantly higher mortality risk (HR = 3.23, 95%CI = 1.63-6.40). CONCLUSIONS: Utilizing a representative sample of the US population, we proved the validity of MAFLD subtype and fibrosis score, rather than the traditional definition (NAFLD and AFLD), in the risk stratification of FLD patients. These findings may be applied to guide the determination of surveillance options for FLD patients.

Roles of IL-35-producing T and B cells in anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND: Interleukin 35 (IL-35) plays an anti-inflammatory in numerous autoimmune diseases. However, the potential roles of IL-35-producing T and B cells and serum IL-35 levels in the pathogenesis of myasthenia gravis (MG) and its association with disease activity in patients with MG remain unclear. METHODS: The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells among peripheral blood mononuclear cells were determined in 37 patients with anti-acetylcholine receptor (AChR) antibody-positive MG and 35 healthy controls (HCs) by performing a flow cytometry analysis. Serum IL-35 levels in participants were determined using an enzyme-linked immunosorbent assay. Further, the correlations between IL35 levels and disease activity were analysed. RESULTS: The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells were significantly lower in patients with anti-AChR antibody-positive MG than in HCs (p = 0.001 and p = 0.002, respectively). Furthermore, patients with thymoma and patients with generalized MG had lower percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells than those without thymoma and those with ocular MG (p = 0.001 and p = 0.003; p = 0.008 and p = 0.001, respectively). Interestingly, the suppression of IL-35 secretion correlated negatively with the activities of daily living scores of patients with MG (r = -0.4774, p = 0.0028) and the quantitative MG scores (r = -0.4656, p = 0.0037). The proportions of IL-35-producing T cells and B cells and serum levels of IL-35 increased after treatment. CONCLUSIONS: IL-35 may represent a potential biomarker for the clinical evaluation of MG.

Acute effect of high-definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial.

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called "conventional" tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg-1 min-1) were enrolled in this single-center, randomized, crossover, and sham-controlled trial. To test reliability, participants performed two time to exhaustion (TTE) tests (control conditions) on a cycle simulator with 80% of peak power until volitional exhaustion. Next, they randomly received HD-tDCS (2.4 mA), conventional (2.0 mA), or active sham tDCS (2.0 mA) over the motor cortex for 20-min before performing the TTE test. TTE, heart rate (HR), associative thoughts, peripheral (lower limbs), and whole-body ratings of perceived exertion (RPE) were recorded every minute. Outcome measures were reliable. There was no difference in TTE between HD-tDCS (853.1 ± 288.6 s), simulated conventional (827.8 ± 278.7 s), sham (794.3 ± 271.2 s), or control conditions (TTE1 = 751.1 ± 261.6 s or TTE2 = 770.8 ± 250.6 s) [F(1.95; 21.4) = 1.537; P = 0.24; η2p = 0.123]. There was no effect on peripheral or whole-body RPE and associative thoughts (P > 0.05). No serious adverse effect was reported. A single session of neither HD-tDCS nor conventional tDCS changed exercise performance and psychophysiological responses in athletes, suggesting that a ceiling effect may exist.

Subacute functional connectivity correlates with cognitive recovery six months after stroke.

BACKGROUND AND PURPOSE: Cognitive impairment is a common consequence of stroke, and the rewiring of the surviving brain circuits might contribute to cognitive recovery. Studies investigating how the functional connectivity of networks change across time and whether their remapping relates to cognitive recovery in stroke patients are scarce. We aimed to investigate whether resting-state functional connectivity was associated with cognitive performance in stroke patients and if any alterations in these networks were correlated with cognitive recovery. METHODS: Using an fMRI ROI-ROI approach, we compared the ipsilesional, contralesional and interhemispheric functional connectivity of three resting-state networks involved in cognition - the Default Mode (DMN), Salience (SN) and Central Executive Networks (CEN), in subacute ischemic stroke patients (time 1, n = 37, stroke onset: 24.32 ± 7.44 days, NIHSS: 2.66 ± 3.45) with cognitively healthy controls (n = 20). Patients were reassessed six months after the stroke event (time 2, n = 20, stroke onset: 182.05 ± 8.17 days) to verify the subsequent reorganization of functional connections and whether such reorganization was associated with cognitive recovery. RESULTS: At time 1, patients had weaker interhemispheric connectivity in the DMN than controls; better cognitive performance at time 1 was associated with stronger interhemispheric and ipsilesional DMN connectivity, and weaker contralesional SN connectivity. At time 2, there were no changes in functional connectivity in stroke patients, compared to time 1. Better cognitive recovery measured at time 2 (time 2 - time 1) was associated with stronger functional connectivity in the DMN, and weaker interhemispheric subacute connectivity in the SN, both from time 1. CONCLUSIONS: Stroke disrupts the functional connectivity of the DMN, not only at the lesioned hemisphere but also between hemispheres. Six months after the stroke event, we could not detect the remapping of networks. Cognitive recovery was associated with the connectivity of both the DMN and SN of time 1. Our findings may be helpful for facilitating further understanding of the potential mechanisms underlying post-stroke cognitive performance.

Interleukin-27 levels in patients with myasthenia gravis.

Interleukin-27 (IL-27), which belongs to IL-12 family, influences the function of T cells (Tregs) through regulating the expression, and function of forkhead box P3 (FoxP3). In this study, we detected the IL-27 serum levels in 59 myasthenia gravis (MG) patients and 35 healthy controls (HCs). Among them, 32 MG patients received immunoglobulin intravenous (IVIG) injections (0.4 g/kg per day for 5 consecutive days). IL-27 levels were collected before and after the treatments and subjected to a comparative study. Finally, we assessed the correlations of IL-27 levels with the clinical characteristics of MG. As a result, serum IL-27 levels were significantly higher in MG patients than those in the HCs. Meanwhile, significant reduction was detected after the IVIG treatment. IL-27 levels positively correlated with both MG activities of daily living and quantitative MG score. IL-27 may participate in the pathogenesis of MG and can be used as an early marker for the diagnosis and prognosis of MG. In addition, IL-27 can be used as a target for MG treatment through the regulation of specific immune signaling and maintaining immune homeostasis.

Real-Time Monitoring of Neurocritical Patients with Diffuse Optical Spectroscopies.

Neurophysiological monitoring is an important goal in the treatment of neurocritical patients, as it may prevent secondary damage and directly impact morbidity and mortality rates. However, there is currently a lack of suitable non-invasive, real-time technologies for continuous monitoring of cerebral physiology at the bedside. Diffuse optical techniques have been proposed as a potential tool for bedside measurements of cerebral blood flow and cerebral oxygenation in case of neurocritical patients. Diffuse optical spectroscopies have been previously explored to monitor patients in several clinical scenarios ranging from neonatal monitoring to cerebrovascular interventions in adults. However, the feasibility of the technique to aid clinicians by providing real-time information at the bedside remains largely unaddressed. Here, we report the translation of a diffuse optical system for continuous real-time monitoring of cerebral blood flow, cerebral oxygenation, and cerebral oxygen metabolism during intensive care. The real-time feature of the instrument could enable treatment strategies based on patient-specific cerebral physiology rather than relying on surrogate metrics, such as arterial blood pressure. By providing real-time information on the cerebral circulation at different time scales with relatively cheap and portable instrumentation, this approach may be especially useful in low-budget hospitals, in remote areas and for monitoring in open fields (e.g., defense and sports).

TM4SF19 aggravates LPS-induced attenuation of vascular endothelial cell adherens junctions by suppressing VE-cadherin expression.

Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases.

Long noncoding RNA ZNF800 suppresses proliferation and migration of vascular smooth muscle cells by upregulating PTEN and inhibiting AKT/mTOR/HIF-1α signaling.

BACKGROUND AND AIMS: Long noncoding RNAs (lncRNAs) have recently been implicated in many biological and disease processes, but the exact mechanism of their involvement in atherosclerosis is unclear. The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. This study aimed to investigate the potential effects of lncRNA ZNF800, a previously uncharacterized lncRNA, on VSMC proliferation and migration. METHODS: The expression of lncRNA ZNF800 in atherosclerotic plaque tissues was detected using reverse transcription-quantitative PCR (RT-qPCR), while the role and mechanism of lncRNA ZNF800 in proliferation and migration of VSMCs were investigated by CCK8 assay, transwell assay, scratch wound assay, RT-qPCR and Western blot. RESULTS: We found that lncRNA ZNF800 was significantly more abundant in atherosclerotic plaque tissues, and substantially suppressed the proliferation and migration of VSMCs. LncRNA ZNF800 had no effect on phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mRNA expression but dramatically increased the levels of PTEN protein. Enhanced lncRNA ZNF800 expression inhibited the activity of the AKT/mTOR/HIF-1α signaling pathway, downregulated the expression of vascular endothelial growth factor α (VEGF-α) and matrix metalloproteinase 1 (MMP1), and suppressed VSMC proliferation and migration. These inhibitory effects of lncRNA ZNF800 were abolished by knockdown of PTEN. The inhibitory effects of lncRNA ZNF800 on cell proliferation and migration and the expression of VEGF-α and MMP1 were exacerbated by HIF-1α knockdown in VSMCs. CONCLUSIONS: These findings demonstrated that lncRNA ZNF800 suppressed VSMC proliferation and migration by interacting with PTEN through a mechanism involving AKT/mTOR/HIF-1α signaling. Therefore, it may play a key atheroprotective role and represent a potential therapeutic target for atherosclerosis-related diseases.

[Influencing Factors and Prevation of Infection in Leukemia Patients after Allogeneic Peripheral Blood Stem Cell Transplantation].

OBJECTIVE: To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation. METHODS: A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed. RESULTS: Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P＜0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P＜0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P＜0.05). CONCLUSION: Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.

MLKL Aggravates Ox-LDL-Induced Cell Pyroptosis via Activation of NLRP3 Inflammasome in Human Umbilical Vein Endothelial Cells.

Atherosclerosis is a progressive chronic inflammation in the arterial walls. It is believed that the deposition of low-density lipoprotein (LDL) and its damage to endothelial cells play a vital role in atherosclerosis. Oxidized LDL (Ox-LDL) was confirmed to induce endothelial cell pyroptosis which plays an important role in intima inflammation and the development of atherosclerosis, but the underlying molecular mechanism needs to be explored. Here, we showed that ox-LDL upregulated the expression of mixed lineage kinase domain-like (MLKL) protein at both the mRNA and protein levels in endothelial cells, associated with the augment of pro-caspase-1 cleavage, interleukin-1ß (IL-1ß) maturation, pro-IL-1ß production, and lactate dehydrogenase (LDH) release. Overexpression of MLKL substantially aggravated ox-LDL-induced increasing levels of caspase-1, IL-1ß, pro-IL-1ß, and LDH. MLKL-induced caspase-1 activation and IL-1ß maturation were abolished by NLR family, pyrin domain-containing 3 (NLRP3) specific inhibitor MCC950, or extracellular high potassium concentration. Our findings indicated that MLKL is essential for regulation of ox-LDL-induced pyroptosis and inflammation through the activation of NLRP3 inflammasome, and suggested that MLKL could act as potential therapeutic targets to ameliorate atherosclerosis-related diseases.