Altered attention networks in patients with thyroid dysfunction: A neuropsychological study.

Patients with thyroid dysfunction (31 hypothyroid, 32 subclinical hypothyroidism, 34 hyperthyroid, and 30 subclinical hyperthyroidism) and 37 euthyroid control subjects were recruited and performed the attention network test (ANT), which can simultaneously examine the alertness, orientation and execution control of the participants. Patients with hypothyroidism had abnormalities in the alerting network, and those with hyperthyroidism had impairments of the alerting and executive control networks. No attention networks deficit existed in patients with subclinical hyperthyroidism and subclinical hypothyroidism. The anxiety and depression scores of patients with thyroid dysfunction were significantly higher than those of the healthy control group. Covariance analysis demonstrated that interactions between group and Hamilton Anxiety Scale scores, group and HAMD score were not significant, but there was a significant main effect for group when analyzing the difference in values of the alerting network between groups. Further, the efficiency of the executive control network was negatively correlated with the T4 level in the hypothyroidism group, and positively correlated with the T4 level in the hyperthyroidism group. T4 or T3 level and efficiencies of the executive control network had a significant quadratic U-shaped relationship in all participants. In summary, the patients with four kinds of thyroid dysfunction exhibited different characteristics of ANT performance. Patients with thyroid dysfunction had various degrees of anxiety and depression disorders, but anxiety and depression disorders had no effect on the differences in the executive control network between the groups.

Helicid Reverses Lipopolysaccharide-Induced Inflammation and Promotes GDNF Levels in C6 Glioma Cells through Modulation of Prepronociceptin.

Helicid suppresses inflammatory factors and protects nerve cells in the hippocampus of rats with depression, but the mechanisms underlying its protective effects are unclear at present. In this investigation, we conducted gene silencing, Helicid intervention and rescue experiments to explore the protective actions of PNOC, the prepronociceptin gene known to regulate inflammatory processes, and Helicid on a C6 cell model of inflammation induced by LPS. Collective data from Western blots, ELISA, immunofluorescence and flow cytometry experiments showed that PNOC silencing or administration of Helicid led to reduced inflammatory factor levels, oxidative stress and expression of glial fibrillary acidic protein (GFAP), along with increased glial cell lines-derived neurotrophic factor (GDNF) expression. Furthermore, expression of p-Akt in the Akt signaling pathway was increased. Interestingly, overexpression of PNOC in the Helicid treatment group partially reversed the Helicid-induced changes in the above biochemical indexes. Our collective results provide strong evidence of Helicid-mediated regulation of the Akt signaling pathway through PNOC to improve cell inflammation and oxidative stress.

Antidiabetic potential of polysaccharides from Brasenia schreberi regulating insulin signaling pathway and gut microbiota in type 2 diabetic mice.

This study aimed to investigate the hypoglycemic activities and gut microbial regulation effects of polysaccharides from Brasenia schreberi (BS) in diabetic mice induced by high-fat diet and streptozotocin. Our data indicated that BS polysaccharides not only improved the symptoms of hyperglycemia and relieved metabolic endotoxemia-related inflammation but also optimized the gut microbiota composition of diabetic mice with significantly decreased Firmicutes/Bacteroidetes ratios. More importantly, altered gut microbiota components may affect liver glycogen and muscle glycogen by increasing the mRNA expression of phosphatidylinositol-3-kinase (PI3K) and protein kinase B (Akt) in the liver of mice through modulated the abundance of beneficial bacteria (Lactobacillus). Altogether, our findings, for the first time, demonstrate that BS polysaccharides may be used as a beneficial probiotic agent that reverses gut microbiota dysbiosis and the hypoglycemic mechanisms of BS polysaccharides may be related to enhancing the abundance of Lactobacillus to activate PI3K/Akt-mediated signaling pathways in T2DM mice.

Modelling of integrated scheduling problem of capacitated equipment systems with a multi-lane road network.

The coordination of different container-handling equipment is an important method for improving the overall efficiency of automated container terminals. In the real terminal, we should consider many real-life issues, such as the equipment capacity, the equipment collision, changing lanes in the multi-lane road, and choosing one of container-handling lanes for each container. This paper proposes the integrated scheduling problem of three container-handling equipment with the capacity constraint and the dual-cycle strategy, for simultaneously solving the equipment scheduling problem, the assignment problem of the container-handling lane and the conflict-free route planning problem of automated guided vehicles (AGVs). With the objective of minimizing the ship's berth time, we propose a mixed-integer programming model based on the space-time network representation method and two bilevel optimization algorithms based on conflict resolution rules. Finally, numerical experiments are conducted to verify the effectiveness of the proposed model and two bilevel optimization algorithms.

Antidepressant-like effects of helicid on a chronic unpredictable mild stress-induced depression rat model: Inhibiting the IKK/IκBα/NF-κB pathway through NCALD to reduce inflammation.

We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.

Value of peripheral neurotrophin levels for the diagnosis of depression and response to treatment: A systematic review and meta-analysis.

The neurotrophin hypothesis indicates that neurotrophic factors are important for the pathophysiology of major depressive disorder (MDD), with alterations in peripheral neurotrophin levels having potential clinical application for MDD. The present meta-analysis aimed to investigate the diagnostic value for MDD of peripheral neurotrophin levels in cross-sectional studies and the association between peripheral neurotrophin levels and the response to antidepressant treatment in longitudinal studies. Published studies in the PubMed and Web of Science databases were systematically searched up to February 2020. The search terms included depressive disorder, neurotrophic factor, serum/plasma and their synonyms. Human studies reporting on BDNF, GDNF, IGF-2, VEGF, NGF, FGF-2, and S100B levels in MDD patients were included. Data comparing MDD patients and healthy controls, and/or between responders and non-responders before and after antidepressant treatment were extracted. A random effects model was used to calculate standardized mean differences. A total of 177 original studies were identified, including 139 cross-sectional and 38 longitudinal studies. Significantly reduced BDNF and NGF levels and significantly elevated IGF-1, VEGF, and S100B levels were reported in MDD patients compared with healthy controls, while GDNF and FGF-2 levels were not significantly different. Furthermore, compared with non-responders, S100B levels at baseline and BDNF levels following treatment were significantly elevated in responders. In addition, there was a significantly elevated level of VEGF after treatment in responders only. In conclusions, alterations in peripheral neurotrophins levels were strongly associated with the biology and the treatment response of MDD. Further investigations are required to examine potential sources of heterogeneity.

MST4 modulates the neuro-inflammatory response by regulating IκBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice.

MST4 limits peripheral, macrophage-dependent inflammatory responses through direct phosphorylation of the adaptor TRAF6; though its role in neuro-inflammation is unclear. We investigated microglia expression of MST4 and whether is attenuates neuro-inflammatory response after cerebral ischemia-reperfusion injury in mice. Adult male C57BL6 mice were subjected to a 90-minute middle cerebral artery occlusion (MCAO) followed by a 72 -h reperfusing. The results showed that MST4 was involved in the pathological process after cerebral ischemia-reperfusion and was expressed in microglia. MST4-Adeno Associated Virus attenuated brain damage after MCAO and reduced expression of p-IκBα, p-ERK and p-JNK, while MST4 shRNA aggravated brain damage after MCAO and increased expression of p-IκBα, p-ERK and p-JNK. Our results show that MST4 inhibits neuro-inflammatory response in cerebral ischemia-reperfusion injury, improves neurological deficits, and reduces cerebral infarction volume in mice. Strategies to enhance MST4 in response to ischemic stroke may be a potential therapeutic strategy.

Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies.

This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies, including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway, anti-oxidative stress effects, enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway, increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway, and reducing the activity of the hypothalamic-pituitary-adrenocortical axis. We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning, shallow depth of stimulation, and difficulty in elucidating the neural circuit mechanism up- and down-stream of the stimulation target brain region.

Ultrafiltration isolation, hypoglycemic activity analysis and structural characterization of polysaccharides from Brasenia schreberi.

Brasenia schreberi (B. schreberi) is a rare and precious vegetable, which coat with a gelatinous mucilage. This study is aiming to investigate the relationship between structural characteristics and hypoglycemic activities of polysaccharides with different molecular weight (Mw) range. Three polysaccharides fractions, namely BSP-U100 (50-100 kDa), BSP-U50 (10-50 kDa) and BSP-U10 (<10 kDa), were isolated from B. schreberi mucilage using ultrafiltration method. Compared to other polysaccharide samples, only BSP-U100 had a triple helix structure and existed as the ordered structure in aqueous solution. Furthermore, BSP-U100 exhibited higher α-amylase (IC50 = 0.4414 mg/mL) and α-glucosidase (IC50 = 0.5993 mg/mL) inhibitory activity. A heteropolysaccharide BSP-1a, which average Mw was 83.98 kDa, was purified from BSP-U100 by DEAE Sepharose Fast Flow and Sephadex G-75 column. D-galactose (66.85%), d-glucose (2.05%) and D-mannose (1.65%) were three main monosaccharides of BSP-1a. Structural characterization of BSP-1a showed that BSP-1a might be a kind of L-D-pyranose type galactose and mainly composed of α-1 → 6-linked Galp, α-1 → 3-linked Manp and α-1 → 4-linked Glcp. This study provided a theoretical basis for the development and application of B. schreberi polysaccharides as a potential anti-diabetic supplement.

Efficacy and Safety of Intravenous Thrombolysis in Patients with Unknown Onset Stroke: A Meta-Analysis.

OBJECTIVES: Unknown onset stroke (UOS) is usually excluded from intravenous thrombolysis concerning the unclear symptom onset time. Attempts have been done to use thrombolytic therapy in these patients. The current meta-analysis was done to examine the efficacy and safety of intravenous thrombolysis in UOS. METHODS: PubMed, Web of Science, and Cochrane Library were searched for studies comparing thrombolysis with conservative therapy among UOSs. Data of good outcome (mRS, 0-2), mortality, and intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were extracted and analyzed using the Revman 5.2 software. RESULTS: In total, 8 studies with 1271 subjects (542 with thrombolysis and 729 with conservative therapy) were included in this meta-analysis. The data showed that patients receiving thrombolysis had a higher incidence of 90-day good outcome (P = 0.0005) than conservative therapy. The comparison of discharge (P = 0.89) and 90-day mortality (P = 0.10) in both groups did not find any significances. The incidences of ICH (P = 0.42) and sICH (P = 0.06) were relatively comparable between the two therapies. CONCLUSIONS: Intravenous thrombolysis is a better choice for UOS patients for its efficacy and safety. In addition, pretreatment imaging assessment is beneficial for improving the efficacy of thrombolytic therapy. However, it needs more supporting evidences for clinical use in the future.

Reversible Affective Symptoms and Attention Executive Control Network Impairment Following Thyroid Function Normalization in Hyperthyroidism.

INTRODUCTION: Affective symptoms and attention impairments are found in patients with hyperthyroidism. Our previous data have revealed that the patients with hyperthyroidism experience impairments of the attention networks, but it remains unclear whether these disorders persist after the treatment of hyperthyroidism. METHODS: Twenty healthy controls and 25 hyperthyroid patients were recruited and performed the attention network test (ANT) which can simultaneously examine the alertness, orientation and execution control components of the participants. The effect of treatment on affective symptom and attention networks impairments were examined in the patient group after 1-year anti-thyroid medication and reaching euthyroidism for at least 3 months. RESULTS: Anxiety and depression scores of patients with hyperthyroidism were significantly higher than those of the healthy control group. The patients with hyperthyroidism had impairments of the alerting and executive control networks. Meanwhile, the score of HAMA correlated significantly with thyroid hormone and TSH levels, and there was a negative significant correlation between the score of HAMD and TSH level in all subjects. There was a positive correlation between the value of the executive control network and thyroid hormones' levels in all subjects and in the hyperthyroidism group. Anxiety and depression symptoms were improved with methimazole treatment after euthyroidism was reached. The value of the executive control network no longer differed from that of healthy controls, but deficits in the alerting network of hyperthyroidism still persisted after treatment. CONCLUSION: The patients with hyperthyroidism existed affective symptoms and attention networks impairments. Affective symptoms and attention executive control network impairment were improved following thyroid function normalization in hyperthyroidism.

Oxygen therapy in patients with retinal artery occlusion: A meta-analysis.

BACKGROUND: Oxygen therapy has been widely used for RAO (retinal artery occlusion) patients; however, inconsistent results have been reported. METHODS: PubMed, Web of Science, EMBASE, Medline (OvidSP), Cochrane, China National Knowledge Infrastructure (CNKI), and Wanfang Database were examined. The primary endpoint was visual acuity (VA), and RevMan software 5.3 was used to statistically analyze the outcomes. RESULTS: Seven randomized controlled trials (RCTs) met the inclusion criteria. Patients who received oxygen therapy exhibited probability of visual improvement about 5.61 times compared with the control group who did not receive oxygen therapy (OR = 5.61; 95% CI, 3.60-8.73; p < 0.01). No statistically significant difference was observed between oxygen inhalation methods (Chi2 = 0.18, df = 1, p = 0.67), combined therapy (Chi2 = 0.21, df = 1, p = 0.64), or RAO type (Chi2 = 0.06, df = 1, p = 0.81). Conversely, 100% oxygen (Chi2 = 4.55, df = 1, p < 0.05) and hyperbaric oxygen (Chi2 = 4.55, df = 1, p < 0.05) significantly improved VA in RAO patients. Better effect was showed in period within 3 months (Chi2 = 5.76, df = 1, p < 0.05). The most effective treatment length was over 9 hours (Chi2 = 6.58, df = 1, p < 0.05). CONCLUSION: Oxygen therapy demonstrated beneficial effects in improving VA in RAO patients, particularly when patients were treated with 100% hyperbaric oxygen and for over 9 hours.

Factors associated with gene aberration test status and treatment decision in patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer: A multicenter survey in China (CTONG 1506).

OBJECTIVES: This study investigated factors associated with (i) the likelihood of receiving a gene aberration test and (ii) the choice of treatment between chemotherapy and targeted therapy in patients with non-small cell lung cancer (NSCLC) in China. MATERIALS AND METHODS: This cross-sectional study analyzed data previously extracted from the medical charts of patients with unresectable Stage IIIB/IV nonsquamous NSCLC discharged from one of 12 tertiary hospitals in China between August 2015 and March 2016. Logistic regressions were applied to investigate factors associated with receiving a gene aberration test and the treatment decision. RESULTS: Data from 932 patients were analyzed. Patients were less likely to have a gene aberration test if they had a histologic subtype other than adenocarcinoma or a hospital waiting time for test results of >5 days. Patients were more likely to receive tyrosine kinase inhibitor (TKI) treatment than chemotherapy if they had a positive result for epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase gene aberration testing. EGFR positive patients were more likely to receive TKI treatment than chemotherapy if they did not have insurance for TKI or pemetrexed treatment, and more likely to receive chemotherapy than TKI treatment if they had a waiting time for test results of >5 days. EGFR wild-type/unknown patients receiving chemotherapy were more likely to receive pemetrexed if they attended a hospital in a developed area or had insurance for pemetrexed. CONCLUSION: In this real-world setting in China, the choice of first-line treatment for advanced NSCLC was appropriately guided by gene aberration testing for most patients. However, gene aberration testing and the treatment decision were influenced by practical factors such as hospital location, the waiting time for test results, and insurance coverage, which should be addressed to ensure optimal patient care.

Strategies to Improve Outcomes of Patients with EGRF-Mutant Non-Small Cell Lung Cancer: Review of the Literature.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) monotherapy has been regarded as the standard first-line treatment of advanced non-small cell lung cancer (NSCLC) in patients with sensitive epidermal growth factor receptor gene (EGFR) mutations. Acquired resistance is inevitable, however, which presents a challenge in the management of patients with such mutations. Here, we summarize the clinical evidence on treatment strategies for both EGFR TKI-naive and acquired EGFR TKI-resistant NSCLC. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing treatment strategies that are in use or in clinical development to improve the survival of patients who are EGFR TKI naive and EGFR TKI resistant. Various strategies have been explored to manage EGFR TKI resistance with the aim of prolonging the survival of patients with EGFR-mutant NSCLC. Combination strategies in the first-line treatment have been studied most to improve the benefit from EGFR TKI monotherapy and delay the occurrence of resistance. After failure of EGFR TKI monotherapy, continuation of EGFR TKI therapy combined with chemotherapy, immunotherapy, or targeted agents has been used to overcome the development of resistance. In addition, novel compounds designed to act on specific targets associated with EGFR TKI resistance have been in continued clinical development. Treatment regimens that are superior to EGFR TKI monotherapy in the first-line or to overcome acquired EGFR TKI resistance in patients with NSCLC and EGFR mutations still need to be developed. Results of ongoing studies will provide more insight into effective treatment strategies for patients with EGFR mutations.

Black hemostatic sponge based on facile prepared cross-linked graphene.

In this study, we demonstrate for the first time the remarkable hemostatic performance of a cross-linked graphene sponge (CGS) as a superb hemostat. The CGS can absorb plasma immediately (<40 ms) to form a blood cell layer and promotes subsequent clotting. The interaction between the interface of the CGS and blood cells reveals that the fast blood coagulation is primarily attributed to the enrichment of hemocytes and platelets on the wound surface. An in vitro dynamic whole-blood clotting test further highlights the effectiveness of the CGS. Considering the facile preparation, low cost, nontoxicity, and long shelf life of the portable black sponge, the CGS has great potential for trauma treatment.

Antibacterial adhesion of borneol-based polymer via surface chiral stereochemistry.

During its adhesion on external surfaces, a cell exhibits obvious inclination to different molecular chirality, which encourages us to develop a new type of antibacterial material catering to the "chiral taste" of bacteria. On the basis of the natural product borneol (a camphane-type bicyclic monoterpene), a series of borneol-based polymer, polyborneolacrylate (PBA), was successfully prepared and showed superior antibacterial adhesion properties resulting from the borneol isomers on material surface. The results of this study reveal that bacteria simply dislike this type of stubborn surface of PBA, and the PBA surface stereochemistry contributes to the interfacial antibacterial activities. The PBA polymers were evaluated as noncytotoxic and can be simply synthesized, demonstrating their great potential for biomedical applications.