Salmonella manipulates macrophage migration via SteC-mediated myosin light chain activation to penetrate the gut-vascular barrier.

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.

Challenges and opportunities in inflammatory bowel disease: from current therapeutic strategies to organoid-based models.

BACKGROUND: Inflammatory bowel disease (IBD) is an increasingly prevalent global health concern that has garnered substantial attention. However, the underlying mechanisms are still unclear and the current treatments have significant limitations. Intestinal organoids provide an in vitro model to explore the pathogenesis, test the therapeutic effects, and develop regenerative treatments as well as offer the potential to transform drug discovery of IBD. METHODS: To advance our understanding of the whole story of IBD spanning from the pathogenesis to the current therapeutic strategies and latest advancements, a comprehensive search of major databases including PubMed, Scopus, and Web of Science was conducted to retrieve original articles and reviews related to IBD, organoids, pathogenesis and therapy. RESULTS: This review deciphers the etiopathogenesis and the current therapeutic approaches in the treatment of IBD. Notably, critical aspects of intestinal organoids in IBD, such as their potential applications, viability, cell renewal ability, and barrier functionality are highlighted. We also discuss the advances, limitations, and prospects of intestinal organoids for precision medicine. CONCLUSION: The latest strides made in research about intestinal organoids help elucidate intricate aspects of IBD pathogenesis, and pave the prospective avenues for novel therapeutic interventions.

Dietary factors and the risk of atopic dermatitis: a Mendelian randomisation study.

Previous studies have revealed an association between dietary factors and atopic dermatitis (AD). To explore whether there was a causal relationship between diet and AD, we performed Mendelian randomisation (MR) analysis. The dataset of twenty-one dietary factors was obtained from UK Biobank. The dataset for AD was obtained from the publicly available FinnGen consortium. The main research method was the inverse-variance weighting method, which was supplemented by MR‒Egger, weighted median and weighted mode. In addition, sensitivity analysis was performed to ensure the accuracy of the results. The study revealed that beef intake (OR = 0·351; 95 % CI 0·145, 0·847; P = 0·020) and white bread intake (OR = 0·141; 95 % CI 0·030, 0·656; P = 0·012) may be protective factors against AD. There were no causal relationships between AD and any other dietary intake factors. Sensitivity analysis showed that our results were reliable, and no heterogeneity or pleiotropy was found. Therefore, we believe that beef intake may be associated with a reduced risk of AD. Although white bread was significant in the IVW analysis, there was large uncertainty in the results given the wide 95 % CI. Other factors were not associated with AD in this study.

A robust methodology for PEC performance analysis of photoanodes using machine learning and analytical data.

Machine learning (ML) is increasingly applied across various fields, including chemistry, for molecular design and optimizing reaction parameters. Yet, applying ML to experimental data is challenging due to the limited number of synthesized samples, which restricts its broader application in device development. In energy harvesting, photoanodes are crucial for solar-driven water splitting, generating hydrogen and oxygen. We explored electrodes like hematite and bismuth vanadate for photocatalytic uses, noting varied photoelectrochemical performances despite similar preparations. To understand this variability, we applied a data-driven ML approach, predicting photocurrent values and identifying key performance influencers even with limited experimental data in the research development of inorganic devices. We have utilized multiple machine learning algorithms to predict the target value in the calculation process, where the contributions of the dominant descriptors were unknown. We introduced a novel methodology, incorporating clustering to manage multicollinearity from correlated analytical data and Shapley analysis for clear interpretation of contributions to performance prediction. This method was validated on hematite and bismuth vanadate, showing superior predictability and factor identification, and then extended to tungsten oxide and bismuth vanadate heterojunction photoanodes. Despite their complexity, our approach achieved determination coefficients (R2) with a prediction accuracy over 0.85, successfully pinpointing performance-determining factors, demonstrating the robustness of the new scheme in advancing photodevice research.

Diabetes, glycemic profile and risk of vitiligo: A Mendelian randomization study.

BACKGROUD: Previous observational studies have shown that vitiligo usually co-manifests with a variety of dysglycemic diseases, such as Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). Mendelian randomization (MR) analysis was performed to further evaluate the causal association between fasting plasma glucose, glycosylated hemoglobin (HbA1c), T1DM, T2DM and vitiligo. MATERIALS AND METHODS: We used aggregated genome-wide association data from the Integrative Epidemiology Unit (IEU) online database of European adults vitiligo; HbA1c data were from IEU. Fasting blood glucose data were obtained from the European Bioinformatics Institute (EBI). T1DM and T2DM data were from FinnGen. We used bidirectional two-sample and multivariate MR analyses to test whether dysglycemic measures (fasting blood glucose, HbA1c), diabetes-related measures (T1DM, T2DM) are causatively associated with vitiligo. Inverse variance weighting (IVW) method was used as the main test method, MR-Egger, Weighted mode and Weighted median were used as supplementary methods. RESULTS: We found no statistically significant evidence to support a causal association between dysglycemic traits and vitiligo, but in the correlation analysis of diabetic traits, our data supported a positive causal association between T1DM and vitiligo (p = 0.018). In the follow-up multivariate MR analysis, our results still supported this conclusion (p = 0.016), and suggested that HbA1c was not a mediator of T1DM affecting the pathogenesis of vitiligo. No reverse causality was found in any of the reverse MR Analyses of dysglycemic traits and diabetic traits. CONCLUSIONS: Our findings support that T1DM is a risk factor for the development of vitiligo, and this conclusion may explain why the co-presentation of T1DM and vitiligo is often seen in observational studies. Clinical use of measures related to T1DM may be a new idea for the prevention or treatment of vitiligo.

Differences in Comorbidities Explain Black-White Disparities in Outcomes After Femoropopliteal Endovascular Intervention.

BACKGROUND: Black adults have a higher incidence of peripheral artery disease and limb amputations than White adults in the United States. Given that peripheral endovascular intervention (PVI) is now the primary revascularization strategy for peripheral artery disease, it is important to understand whether racial differences exist in PVI incidence and outcomes. METHODS: Data from fee-for-service Medicare beneficiaries ≥66 years of age from 2016 to 2018 were evaluated to determine age- and sex-standardized population-level incidences of femoropopliteal PVI among Black and White adults over the 3-year study period. Patients' first inpatient or outpatient PVIs were identified through claims codes. Age- and sex-standardized risks of the composite outcome of death and major amputation within 1 year of PVI were examined by race. RESULTS: Black adults underwent 928 PVIs per 100 000 Black beneficiaries compared with 530 PVIs per 100 000 White beneficiaries (risk ratio, 1.75 [95% CI, 1.73-1.77]; P<0.01). Black adults who underwent PVI were younger (mean age, 74.5 years versus 76.4 years; P<0.01), were more likely to be female (52.8% versus 42.7%; P<0.01), and had a higher burden of diabetes (70.6% versus 56.0%; P<0.01), chronic kidney disease (67.5% versus 56.6%; P<0.01), and heart failure (47.4% versus 41.7%; P<0.01) than White adults. When analyzed by indication for revascularization, Black adults were more likely to undergo PVI for chronic limb-threatening ischemia than White adults (13 023 per 21 352 [61.0%] versus 59 956 per 120 049 [49.9%]; P<0.01). There was a strong association between Black race and the composite outcome at 1 year (odds ratio, 1.21 [95% CI, 1.16-1.25]). This association persisted after adjustment for socioeconomic status (odds ratio, 1.08 [95% CI, 1.03-1.13]) but was eliminated after adjustment for comorbidities (odds ratio, 0.96 [95% CI, 0.92-1.01]). CONCLUSIONS: Among fee-for-service Medicare beneficiaries, Black adults had substantially higher population-level PVI incidence and were significantly more likely to experience adverse events after PVI than White adults. The association between Black race and adverse outcomes appears to be driven by a higher burden of comorbidities. This analysis emphasizes the critical need for early identification and aggressive management of peripheral artery disease risk factors and comorbidities to reduce Black-White disparities in the development and progression of peripheral artery disease and the risk of adverse events after PVI.

Utilization of and Outcomes Associated with Intravascular Ultrasound during Deep Venous Stent Placement among Medicare Beneficiaries.

PURPOSE: To evaluate temporal trends, practice variation, and associated outcomes with the use of intravascular ultrasound (US) during deep venous stent placement among Medicare beneficiaries. MATERIALS AND METHODS: All lower extremity deep venous stent placement procedures performed between January 1, 2017, and December 31, 2019 among Medicare beneficiaries were included. Temporal trends in intravascular US use were stratified by procedural setting and physician specialty. The primary outcome was a composite of 12-month all-cause mortality, all-cause hospitalization, or repeat target vessel intervention. The secondary outcome was a composite of 12-month stent thrombosis, embolization, or restenosis. RESULTS: Among the 20,984 deep venous interventions performed during the study period, 15,184 (72.4%) utilized intravascular US. Moderate growth in intravascular US use was observed during the study period in all clinical settings. There was a variation in the use of intravascular US among all operators (median, 77.3% of cases; interquartile range, 20.0%-99.2%). In weighted analyses, intravascular US use during deep venous stent placement was associated with a lower risk of both the primary (adjusted hazard ratio, 0.72; 95% confidence interval [CI], 0.69-0.76; P < .001) and secondary (adjusted hazard ratio, 0.32; 95% CI, 0.27-0.39; P < .001) composite end points. CONCLUSIONS: Intravascular US is frequently used during deep venous stent placement among Medicare beneficiaries, with further increase in use from 2017 to 2019. The utilization of intravascular US as part of a procedural strategy was associated with a lower cumulative incidence of adverse outcomes after the procedure, including venous stent thrombosis and embolization.

Trichostatin A inhibits dendritic cell maturation through down-regulating NF-κ B (p65) pathway.

BACKGROUND: Recent evidence suggested that histone deacetylase inhibitor (HDACi) could inhibit dendritic cell (DC) maturation. However, the mechanism is unclear. Here, we aimed to study whether Trichostatin A (TSA), the most widely studied HDACi, inhibits the maturation of DCs by down-regulating NF-κB (p65) pathway. METHODS AND RESULTS: Mouse bone marrow-derived DCs were cultured. Lipopolysaccharide (LPS) was applied as stimulation for maturation. Triptolide (TTL) was applied as p65 inhibitor. Microphotography and flow cytometry showed that TSA and p65 inhibitor separately inhibited the maturation of DCs stimulated by LPS from the aspects of cell morphology and cell phenotype. Mixed lymphocyte reaction test and ELISA showed that TSA and p65 inhibitor synergistically inhibited the proliferation of T lymphocytes stimulated by DCs, reduced the secretion of pro-inflammatory cytokine IL-12 and elevated the secretion of anti-inflammatory cytokine IL-10. Western blot and RT-qPCR showed that TSA down-regulated the expression of phosphorylated IκBα, phosphorylated-p65, Ikkß and Ikkγ, suggesting TSA down-regulates NF-κB (p65) pathway. CONCLUSIONS: TSA inhibits DC maturation through down-regulating NF-κB (p65) pathway.

Glymphatic clearance function in patients with cerebral small vessel disease.

Few studies have focused on the connection between glymphatic dysfunction and cerebral small vessel disease (CSVD), partially due to the lack of non-invasive methods to measure glymphatic function. We established modified index for diffusion tensor image analysis along the perivascular space (mALPS-index), which was calculated on diffusion tensor image (DTI), compared it with the classical detection of glymphatic clearance function calculated on Glymphatic MRI after intrathecal administration of gadolinium (study 1), and analyzed the relationship between CSVD imaging markers and mALPS-index in CSVD patients from the CIRCLE study (ClinicalTrials.gov ID: NCT03542734) (study 2). Among 39 patients included in study 1, mALPS-index were significantly related to glymphatic clearance function calculated on Glymphatic MRI ( r  = -0.772~-0.844, p < 0.001). A total of 330 CSVD patients were included in study 2. Severer periventricular and deep white matter hyperintensities (ß = -0.332, p < 0.001; ß = -0.293, p < 0.001), number of lacunas (ß = -0.215, p < 0.001), number of microbleeds (ß = -0.152, p = 0.005), and severer enlarged perivascular spaces in basal ganglia (ß = -0.223, p < 0.001) were related to mALPS-index. Our results indicated that non-invasive mALPS-index might represent glymphatic clearance function, which could be applied in clinic in future. Glymphatic clearance function might play a role in the development of CSVD.

Arabidopsis MADS-box factor AGL16 is a negative regulator of plant response to salt stress by downregulating salt-responsive genes.

Sessile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS-box transcription factor AGL16 acting as a negative regulator in stress response in Arabidopsis. Loss-of-AGL16 confers resistance to salt stress in seed germination, root elongation and soil-grown plants, while elevated AGL16 expression confers the opposite phenotypes compared with wild-type. However, the sensitivity to abscisic acid (ABA) in seed germination is inversely correlated with AGL16 expression levels. Transcriptomic comparison revealed that the improved salt resistance of agl16 mutants was largely attributed to enhanced expression of stress-responsive transcriptional factors and the genes involved in ABA signalling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter of HKT1;1, HsfA6a and MYB102 and represses their expression. Genetic analyses with double mutants also support that HsfA6a and MYB102 are target genes of AGL16. Taken together, our results show that AGL16 acts as a negative regulator transcriptionally suppressing key components in the stress response and may play a role in balancing stress response with growth.

Incidence, predictors and clinical impact of permanent pacemaker insertion in women following transcatheter aortic valve implantation: Insights from a prospective multinational registry.

OBJECTIVES: To describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women. BACKGROUND: Data on pacemaker insertion complicating TAVR in women are scarce. METHODS: The Women's International Transcatheter Aortic Valve implantation (WIN-TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no-PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)-2 efficacy and safety endpoints. RESULTS: Out of 1019 patients, 922 were included in the analysis. Post-TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre-existing right bundle branch block (RBBB) was associated with a high risk of post-TAVR PPI (OR 3.62, 95% CI 1.85-7.06, p < 0.001), while implantation of balloon-expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30-0.74, p < 0.001). Post-TAVR PPI prolonged in-hospital stay by a median of 2 days (11 [9-16] days in PPI vs. 9 [7-14] days in no-PPI, p = 0.005), yet risks of VARC-2 efficacy and safety endpoints at 1 year were similar in both groups (adj HR 0.95, 95% CI 0.60-1.52, p = 0.84 and adj HR 1.22, 95% CI 0.83-1.79, p = 0.31, respectively). CONCLUSION: Pacemaker implantation following TAVR is frequent among women and is associated with pre-existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1-year outcomes.

Preprocedural anemia in females undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI registry.

OBJECTIVES: To assess the impact of anemia on clinical outcomes in female patients enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry. BACKGROUND: Anemia is highly prevalent among females who constitute half of TAVI candidates, yet, its clinical significance remains poorly investigated. METHODS: Patients were divided into three groups according to preprocedural hemoglobin (Hb) level: (1) no anemia (Hb ≥12 g/dl), (2) mild-to-moderate anemia (10 ≤ Hb <12 g/dl), and (3) severe anemia (Hb <10 g/dl). The primary outcome was the occurrence of Valve Academic Research Consortium (VARC)-2 efficacy endpoint, a composite of mortality, stroke, myocardial infarction (MI), hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. RESULTS: Hemoglobin level was available in 877 (86.1%) patients: 412 (47.0%) had no anemia, 363 (41.4%) had mild-to-moderate anemia, and 102 (11.6%) had severe anemia. The latter group had a higher prevalence of cardiovascular risk factors. Compared with patients without anemia, severe anemia was associated with a greater risk of VARC-2 efficacy endpoint (adj HR 1.71, 95% CI: 1.02-2.87, p = .04), all-cause death (adj HR 2.36, 95% CI: 1.31-4.26, p = .004) and a composite of death, MI or stroke (adj HR 1.88, 95% CI: 1.10-3.22, p = .02) at 1 year. Moreover, an increased risk of late mortality (adj HR 1.15, 95% CI: 1.02-1.30, p = .03) was observed with every 1 g/dl decrease in hemoglobin level. CONCLUSION: Severe anemia in females undergoing TAVI was independently associated with increased rates of VARC-2 efficacy endpoint and mortality at 1 year.

The therapeutic effects and safety of bright light therapy combined with escitalopram oxalate on insomnia in patients with poststroke depression.

INTRODUCTION: Bright light therapy (BLT) is known to treat depression and sleep disorders in clinical practice, but its efficacy on poststroke depression (PSD) has not been studied. OBJECTIVE: To investigate the therapeutic effects and safety of BLT combined with escitalopram oxalate (ESC) on insomnia in patients with PSD. METHODS: Ischemic stroke patients with depressive symptoms and a score of ≥8 on the Hamilton Depression Scale (HAMD-17) while meeting DSM-IV criteria were diagnosed as having PSD. A total of 112 PSD patients with symptoms of insomnia were randomly assigned to polytherapy (BLT plus ESC) and monotherapy (ESC only) groups. Each regimen continued for 6 weeks. The primary outcomes were a change in scores on the Pittsburgh Sleep Quality Index (PSQI) and a remission rate (PSQI ≤7 at the endpoint). The secondary outcomes included changes in the HAMD-17 and Barthel Index (BI) scores. Adverse effects were assessed by the Adverse Events Scale. RESULTS: The endpoint assessment included 106 patients (monotherapy, 54; polytherapy, 52). The mean changes in the PSQI scores for the monotherapy and polytherapy groups were 4.85 (1.47) and 5.87 (1.72) (P = 0.001), respectively. Compared to monotherapy, polytherapy improved PSQI remission rate (71.4% vs 50.0%; χ2 = 5.390; P = 0.020), and HAMD-17 score (6.70 [2.12] vs 4.75 [1.98]; P < 0.001). Both treatments improved BI score, with no statistical difference, and were well tolerated, with few significant differences in treatment-associated adverse events. CONCLUSION: BLT combined with ESC is effective and well tolerated for the treatment of PSD-associated insomnia.

Uric acid played a role in the association between gender and deep vein thrombosis in patients with stroke.

BACKGROUND AND AIMS: Gender-specific differences were found in serum uric acid (SUA) levels and the risk of isolated distal deep vein thrombosis (IDDVT). This study aimed to explore the association among gender, SUA, and IDDVT in stroke patients. METHODS AND RESULTS: Finally, 3404 patients were recruited and divided into two groups: IDDVT (n = 1233) and Non-IDDVT (n = 2171) groups. Propensity score matching (PSM) was conducted to match the patients. Binary logistic regression was adopted to explore the association between SUA and IDDVT, with the SUA divided into quartiles. After PSM, 975 patients were included in each group. Non-IDDVT group had a larger proportion of male than IDDVT group (64.9% vs. 52.7%, p < 0.001). Moreover, males showed higher SUA levels than females (316.7 ± 102.1 vs. 261.8 ± 94.0 µmol/L, t = 12.1, p < 0.001). The highest quartile of SUA (≥346 µmol/L) showed a lower risk of IDDVT (OR = 0.629, p = 0.001), while the lowest quartile (≤225 µmol/L) showed a higher risk of IDDVT (OR = 1.361, p = 0.022). CONCLUSION: In patients with stroke, SUA played a protective role in IDDVT. Females had a higher risk of IDDVT, which may be owing to the lower SUA levels than males. In clinical practice, more attention should be paid to the risk of IDDVT in females, especially those with lower SUA levels.

A Brain-Inspired Decision-Making Linear Neural Network and Its Application in Automatic Drive.

Brain-like intelligent decision-making is a prevailing trend in today's world. However, inspired by bionics and computer science, the linear neural network has become one of the main means to realize human-like decision-making and control. This paper proposes a method for classifying drivers' driving behaviors based on the fuzzy algorithm and establish a brain-inspired decision-making linear neural network. Firstly, different driver experimental data samples were obtained through the driving simulator. Then, an objective fuzzy classification algorithm was designed to distinguish different driving behaviors in terms of experimental data. In addition, a brain-inspired linear neural network was established to realize human-like decision-making and control. Finally, the accuracy of the proposed method was verified by training and testing. This study extracts the driving characteristics of drivers through driving simulator tests, which provides a driving behavior reference for the human-like decision-making of an intelligent vehicle.

Analysis of signal detection configurations in optical time-stretch imaging.

Optical time-stretch (OTS) imaging is effective for observing ultra-fast dynamic events in real time by virtue of its capability of acquiring images with high spatial resolution at high speed. In different implementations of OTS imaging, different configurations of its signal detection, i.e. fiber-coupled and free-space detection schemes, are employed. In this research, we quantitatively analyze and compare the two detection configurations of OTS imaging in terms of sensitivity and image quality with the USAF-1951 resolution chart and diamond films, respectively, providing a valuable guidance for the system design of OTS imaging in diverse fields.

Arabidopsis MADS-box factor AGL16 negatively regulates drought resistance via stomatal density and stomatal movement.

Drought is one of the most important environmental factors limiting plant growth and productivity. The molecular mechanisms underlying plant drought resistance are complex and not yet fully understood. Here, we show that the Arabidopsis MADS-box transcription factor AGL16 acts as a negative regulator in drought resistance by regulating stomatal density and movement. Loss-of-AGL16 mutants were more resistant to drought stress and had higher relative water content, which was attributed to lower leaf stomatal density and more sensitive stomatal closure due to higher leaf ABA levels compared with the wild type. AGL16-overexpressing lines displayed the opposite phenotypes. AGL16 is preferentially expressed in guard cells and down-regulated in response to drought stress. The expression of CYP707A3 and AAO3 in ABA metabolism and SDD1 in stomatal development was altered in agl16 and overexpression lines, making them potential targets of AGL16. Using chromatin immunoprecipitation, transient transactivation, yeast one-hybrid, and electrophoretic mobility shift assays, we demonstrated that AGL16 was able to bind the CArG motifs in the promoters of the CYP707A3, AAO3, and SDD1 and regulate their transcription, leading to altered leaf stomatal density and ABA levels. Taking our findings together, AGL16 acts as a negative regulator of drought resistance by modulating leaf stomatal density and ABA accumulation.

Impact of Elevated Hemoglobin A1c Levels on Functional Outcome in Patients with Acute Ischemic Stroke.

BACKGROUND: The association between hemoglobin A1c (HbA1c) and clinical outcomes of acute ischemic stroke is uncertain. We aimed to evaluate the association between initial hemoglobin A1c level and clinical outcome after acute ischemic stroke. METHODS: A total of 408 patients with first-ever acute ischemic stroke were included in this study. We divided the patients into three groups according to HbA1c level: low HbA1c level (HbA1c <5.7%), moderate HbA1c level (HbA1c 5.7-6.4%), and high HbA1c level (HbA1c ≥6.5%). Poor neurological outcomes were defined as modified Rankin Scale (mRS) score of 2-6 at 3 months after stroke. The relation between HbA1c value and clinical outcomes were evaluated by using multivariate logistic regression analyses. RESULTS: Moderate HbA1c level was present in 126 (30.9%) patients and high HbA1c level in 129 (31.6%) patients. After adjustment for potential confounding variables, both patients in the high HbA1c level group (adjusted odds ratio [OR]: 2.387; 95% confidence interval [CI], 1.201-4.745; P = .013) and moderate HbA1c level group (adjusted OR: 1.797; 95% CI, 1.005-3.214; P = .048) had a significantly higher poor neurological outcomes than the group in the low HbA1c level. When separately analyzed according to with or without diabetes, the HbA1c level as continuous variable was also associated with poor functional outcome at 3 months in the diabetic patients (adjusted OR: 1.482, 95% CI, 1.013-2.167, P = .042), nor in nondiabetic group. CONCLUSIONS: Higher HbA1c on admission was an independent predictor of adverse functional outcome in ischemic stroke patients. Based on this point, tight glycemic control must be necessary for high-risk diabetic patients.

Clinical features and risk factors of neurological involvement in Sjögren's syndrome.

BACKGROUND: To investigated distinct manifestations of Sjögren's syndrome (SS) patients with neurological complications and the potential risk factors associated with neurological complications in SS, and to produce a disease evaluation and neurological involvement prediction for SS. METHODS: 566 patients who fulfilled the 2002 classification criteria for SS from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University were included in the cross-sectional study. Clinical, immunological and histological characteristics were surveyed, and potential risk factors for neurological complications were examined by multivariate analysis. RESULTS: Among 566 SS patients, 184 (32.5%) patients had neurological involvement, with more than 10% got limbs pain, limbs numbness and cerebral infarction, respectively. Of these 184 SS patients with neurological complications, secondary SS (sSS) patients had a higher prevalence of peripheral nervous system (PNS) involvement than primary SS (pSS) patients (31.1 vs. 19%). And sSS patients showed higher total ESSPRI score and higher prevalence of xerostomia and low C3, C4 levels with more liver, articular involvement and saliva gland atrophy, and more severe lymphocyte infiltration in salivary glands than pSS patients. As for the specific factors associated with neurological involvement, low C3 level were found to be significant in pSS or sSS patients who were younger 50 year old, and ANA positivity, cardiac involvement, saliva gland atrophy were demonstrated to be associated in elder pSS patients. And xerophthalmia was found to be associated in sSS patients. CONCLUSION: Low complement (C3) levels, xerophthalmia, ANA positive, cardiac involvement and labial salivary gland histological result were good ways to predict neurological complications in different subgroups of SS, which might provide insight into better clinical decision-making, especially at early stages of the disease.

Plasma long non-coding RNA BACE1 as a novel biomarker for diagnosis of Alzheimer disease.

BACKGROUNDS: Long non-coding RNA (LncRNA) have been reported to be involved in the pathogenesis of neurodegenerative diseases, but whether it can serve as a biomarker for Alzheimer disease (AD) is not yet known. METHODS: The present study selected four specific LncRNA (17A, 51A, BACE1 and BC200) as possible AD biomarker. RT-qPCR was performed to validate the LncRNA. Receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were applied to study the potential of LncRNA as a biomarker in a population of 88 AD patients and 72 control individuals. RESULTS: We found that the plasma LncRNA BACE1 level of AD patients was significantly higher than that of healthy controls (p = 0.006). Plasma level of LncRNA 17A, 51A and BC200 did not show a significant difference between two groups (p = 0.098, p = 0.204 and p = 0.232, respectively). ROC curve analysis showed that LncRNA BACE1 was the best candidate of these LncRNA (95% CI: 0.553-0.781, p = 0.003). In addition, no correlation was found for expression of these LncRNA in both control and AD groups with age or MMSE scale (p > 0.05). CONCLUSIONS: Our present study compared the plasma level of four LncRNA between AD and non-AD patients, and found that the level of the BACE1 is increased in the plasma of AD patients and have a high specificity (88%) for AD, indicating BACE1 may be a potential candidate biomarker to predict AD.