Opioid use and adverse health effects in breast cancer survivors.

BACKGROUND: Little information exists on adverse effects related to opioid use in breast cancer survivors following active cancer treatment, and no studies included an age-matched comparison group. Thus, we examined opioid use and risk of falls, fractures, lung problems, and cardiovascular events in breast cancer survivors in the years following active cancer treatment along with a comparison group. METHODS: We conducted a longitudinal cohort study 33 989 breast cancer survivors and 157 609 age-matched women without cancer. Rates of adverse events, and multivariable hazards ratios for association between opioid use and the adverse health effects were calculated. RESULTS: Women with breast cancer had greater opioid use (60% vs 48%); longer median opioid duration (18 vs 16 days); and were prescribed stronger opioids than the matched cohort over 5.6 median years of follow-up. In multivariable models, the risk of falls was 12% higher (HR, 95% CI, 1.12 [1.07-1.17]), and fracture risk was 56% (HR = 1.56 [1.48-1.65]) greater in women with breast cancer who used opioids vs the matched cohort unexposed to opioids. In an analysis restricted to women with breast cancer, opioid use was strongly associated with the risk of falls (HR = 1.74 [1.63-1.85]); fractures (HR = 2.10 [1.95-2.27]); lung problems (HR = 1.53 [1.43-1.64]); and cardiovascular events (HR = 1.70 [1.39-2.08]) than opioid non-use. CONCLUSIONS: After active cancer treatment, opioid use and high dosage use were common in breast cancer survivors, and were associated with increased risk for falls, lung problems, fractures, and cardiovascular events. Findings underscore the need for careful monitoring of opioid use in these survivors and the exploration of alternative pain management strategies.

Quantum Criticality with Emergent Symmetry in the Extended Shastry-Sutherland Model.

Motivated by the novel phenomena observed in the layered material SrCu_{2}(BO_{3})_{2}, the Shastry-Sutherland model (SSM) has been extensively studied as the minimal model for SrCu_{2}(BO_{3})_{2}. However, the nature of its quantum phase transition from the plaquette valence-bond solid to antiferromagnetic phase is under fierce debate, posing a challenge to understand the underlying quantum criticality. Via the state-of-the-art tensor network simulations, we study the ground state of the SSM on large-scale size up to 20×20 sites. We identify the continuous transition nature accompanied by an emergent O(4) symmetry between the plaquette valence-bond solid and antiferromagnetic phase, which strongly suggests a deconfined quantum critical point (DQCP). Furthermore, we map out the phase diagram of an extended SSM that can be continuously tuned to the SSM, which demonstrates the same DQCP phenomena along a whole critical line. Our results indicate a compelling scenario for understanding the origin of the proposed proximate DQCP in recent experiments of SrCu_{2}(BO_{3})_{2}.

Regulation of glycolysis-derived L-lactate production in astrocytes rescues the memory deficits and Aß burden in early Alzheimer's disease models.

Aberrant energy metabolism in the brain is a common pathological feature in the preclinical Alzheimer's Disease (AD). Recent studies have reported the early elevations of glycolysis-involved enzymes in AD brain and cerebrospinal fluid according to a large-scale proteomic analysis. It's well-known that astrocytes exhibit strong glycolytic metabolic ability and play a key role in the regulation of brain homeostasis. However, its relationship with glycolytic changes and cognitive deficits in early AD patients is unclear. Here, we investigated the mechanisms by which astrocyte glycolysis is involved in early AD and its potential as a therapeutic target. Our results suggest that Aß-activated microglia can induce glycolytic-enhanced astrocytes in vitro, and that these processes are dependent on the activation of the AKT-mTOR-HIF-1α pathway. In early AD models, the increase in L-lactate produced by enhanced glycolysis of astrocytes leads to spatial cognitive impairment by disrupting synaptic plasticity and accelerating Aß aggregation. Furthermore, we find rapamycin, the mTOR inhibitor, can rescue the impaired spatial memory and Aß burden by inhibiting the glycolysis-derived L-lactate in the early AD models. In conclusion, we highlight that astrocytic glycolysis plays a critical role in the early onset of AD and that the modulation of glycolysis-derived L-lactate by rapamycin provides a new strategy for the treatment of AD.

Obstructive sleep apnea affects the psychological and behavioural development of children-a case-control study.

This study aims to investigate the effects of obstructive sleep apnea on paediatric psychological and behavioural abnormalities. A total of 1086 paediatric patients with obstructive sleep apnea and 728 sample snoring controls were enrolled in the study. Patients with obstructive sleep apnea underwent bilateral tonsillectomy plus adenoidectomy or adenoidectomy alone. Repeated Autism Behaviour Checklist, Spence Children's Anxiety Scale, and Children's Depression Inventory were performed to assess the autism symptoms, anxiety level and depressive symptoms before and after surgery. The score of Autism Behaviour Checklist in preschool children with obstructive sleep apnea was higher than that in control. In school children with obstructive sleep apnea, the score of Spence Children's Anxiety Scale was also higher. School children with obstructive sleep apnea with depressive symptoms were significantly higher than that in control. The scores of Autism Behaviour Checklist, Spence Children's Anxiety Scale, and Children's Depression Inventory in the obstructive sleep apnea group after surgery were significantly lower than that before surgery. Our study showed that the score of Spence Children's Anxiety Scale and Children's Depression Inventory had a close correlation with the illness course and hypoxia duration. The Spence Children's Anxiety Scale and Children's Depression Inventory scores are also closely associated with the Autism Behaviour Checklist score. These results suggest that obstructive sleep apnea may have a significant impact on autism symptoms, anxiety levels and depressive symptoms in children. We found that the longer the duration of the obstructive sleep apnea course and hypoxia, the greater the impact on anxiety level and depressive symptoms. The suspected autism symptoms, anxiety level and depressive symptoms in children with obstructive sleep apnea were also significantly correlated. Thus, early detection and timely treatment may often reverse the psychological and behavioural abnormalities caused by obstructive sleep apnea.

Unleashing the Potential of Internet Hospitals: An In-Depth Examination of Information Platform Functionality and Performance.

BACKGROUND: Internet hospitals (IHs) have rapidly developed as a promising strategy to address supply-demand imbalances in China's medical industry, with their capabilities directly dependent on information platform functionality. Moreover, a novel theory of "Trinity" smart hospital has provided advanced guidelines of IHs construction. OBJECTIVE: To explore the construction experience, construction models, and development prospects based on operational data from IHs. METHODS: Based on existing information systems and internet service functionalities, our hospital has built a "Smart Hospital Internet Information Platform (SHIIP)" for IHs operation, actively to expand online services, digitalize traditional healthcare, and explore healthcare services modes throughout the entire process and lifecycle. This article encompasses the platform architecture design, technological applications, patient service content and processes, healthcare professional support features, administrative management tools, and associated operational data. RESULTS: Our platform has presented a remarkable set of data, including 82,279,669 visits, 420,120 online medical consultations, 124,422 electronic prescriptions, 92,285 medication deliveries, 6,965,566 pre-diagnosis triages, 4,995,824 offline outpatient appointments, 2,025 medical education articles with a total of 15,148,310 views, and so on. These data demonstrate the significant role of IH as an indispensable component of our physical hospital services, with a deep integration between online and offline healthcare systems. CONCLUSIONS: Attributing to extreme convenience and improved efficiency, our IH has achieved a wide recognition and use from both the public and healthcare workers, and the upward trends in multiple data metrics suggest a promising outlook for its sustained and positive development in the future. Our pioneering exploration holds tremendous significance and serves as a valuable guiding reference for IHs construction and the progressive development of the internet healthcare sector.

Tuning Piezoelectricity via Thermal Annealing at a Freestanding Ferroelectric Membrane.

Tuning the ferroelectric domain structure by a combination of elastic and electrostatic engineering provides an effective route for enhanced piezoelectricity. However, for epitaxial thin films, the clamping effect imposed by the substrate does not allow aftergrowth tuning and also limits the electromechanical response. In contrast, freestanding membranes, which are free of substrate constraints, enable the tuning of a subtle balance between elastic and electrostatic energies, giving new platforms for enhanced and tunable functionalities. Here, highly tunable piezoelectricity is demonstrated in freestanding PbTiO3 membranes, by varying the ferroelectric domain structures from c-dominated to c/a and a domains via aftergrowth thermal treatment. Significantly, the piezoelectric coefficient of the c/a domain structure is enhanced by a factor of 2.5 compared with typical c domain PbTiO3. This work presents a new strategy to manipulate the piezoelectricity in ferroelectric membranes, highlighting their great potential for nano actuators, transducers, sensors and other NEMS device applications.

NtMYB1 and NtNCED1/2 control abscisic acid biosynthesis and tepal senescence in Chinese narcissus (Narcissus tazetta).

Chinese narcissus (Narcissus tazetta var. chinensis cv. 'Jinzhanyintai') is one of the 10 most famous traditional flowers of China, having a beautiful and highly ornamental flower with a rich fragrance. However, the flower longevity affects its commercial appeal. While petal senescence in Narcissus is ethylene-independent and abscisic acid-dependent, the regulatory mechanism has yet to be determined. In this study, we identified a R2R3-MYB gene (NtMYB1) from Narcissus tazetta and generated oeNtMYB1 and Ntmyb1 RNA interference mutants in Narcissus as well as an oeNtMYB1 construct in Arabidopsis. Overexpressing NtMYB1 in Narcissus or Arabidopsis led to premature leaf yellowing, an elevated level of total carotenoid, a reduced level of chlorophyll b, and a decrease in photosystem II fluorescence (Fv/Fm). A dual-luciferase assay and chromatin immunoprecipitation-quantitative PCR revealed that NtMYB1 directly binds to the promoter of NtNCED1 or NtNCED2 and activates NtNCED1/2 gene expression both in vitro and in vivo. Moreover, overexpressing NtMYB1 accelerated abscisic acid biosynthesis, up-regulated the content of zeatin and abscisic acid, and down-regulated the level of ß-carotene and gibberellin A1, leading to petal senescence and leaf yellowing in Narcissus. This study revealed a regulatory process that is fundamentally different between non-photosynthetic organs and leaves.

Analysis of Multimorbidity of Moderate to Severe Allergic Rhinitis in Children: A Real-World Study.

INTRODUCTION: Allergic rhinitis (AR) in children is associated with various comorbidities, posing challenges for treatment and management. There have been few investigations of these multimorbidities in Chinese children with AR. Here, we investigated the prevalence of multimorbidities in children with moderate to severe AR and analyzed the influencing factors using real-world data. METHODS: In total, 600 children who visited the outpatient clinic of our hospital and were diagnosed with moderate-severe AR were prospectively enrolled. All children underwent allergen detection and electronic nasopharyngoscopy. Parents or guardians completed a questionnaire that included age, sex, mode of delivery, feeding pattern, and familial history of allergy. The multimorbidities investigated included atopic dermatitis (AD), asthma, allergic conjunctivitis (AC), chronic rhinosinusitis (CRS), adenoid hypertrophy (AH), tonsil hypertrophy (TH), recurrent epistaxis, and recurrent respiratory tract infections (RRTIs). RESULTS: The AR multimorbidities reported in children were as follows: recurrent epistaxis (46.5%), AC (46.3%), AD (40.7%), asthma (22.5%), RRIs (21.3%), CRS (20.5%), AH (19.7%), and TH (12.5%). In univariate logistic regression analysis, age (<6 years), birth mode, familial history of allergy, and single dust mite allergy were associated with AR multimorbidity (p < 0.05). Multivariate logistic regression revealed that a familial history of allergy was an independent risk factor for AC (odds ratio [OR] = 1.539, 95% confidence interval [CI]: 1.104-2.145) and AH (OR = 1.506, 95% CI: 1.000-2.267) (p < 0.05). Age (<6 years) was independently associated with the risk of AD (OR = 1.405, 95% CI: 1.003-1.969) and RRTIs (OR = 1.869, 95% CI: 1.250-2.793) (p < 0.05), cesarean section with AR and CRS risk (OR = 1.678, 95% CI: 1.100-2.561), and single dust mite allergy with asthma (OR = 1.590, 95% CI: 1.040-2.432) and CRS (OR = 1.600, 95% CI: 1.018-2.515) risk (p < 0.05). Further, non-dust mite allergy was independently associated with AR and CRS (OR = 2.056, 95% CI: 1.084-3.899). CONCLUSION: AR was found to be accompanied by different comorbidities, including both allergic and non-allergic comorbidities, complicating disease treatment. These findings demonstrated that age (<6 years), familial history of allergy, types of allergens, and cesarean section were risk factors for different multimorbidities associated with AR.

[Total triterpenes of Euphorbium alleviates rheumatoid arthritis via Nrf2/HO-1/GPX4 pathway].

This study aims to investigate the effect and mechanism of total triterpenes of Euphorbium in treating rheumatoid arthritis(RA). The rat model of RA was established with Freund's complete adjuvant(FCA). Male rats were randomly assigned into control, model, Tripterygium glycosides(7.5 mg·kg~(-1)), and low-, medium-, and high-dose total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1), respectively) groups, with 10 rats in each group. In other groups except the control group, 0.2 mL FCA was injected into the right hind toe. Rats in the intervention groups were administrated with corresponding drugs by gavage, and the control group and the model group with the same volume of 0.5% CMC-Na solution once a day. During the treatment period, the swelling degree of the hind paw was measured and the arthritis was scored until day 30. At the end of drug administration, the pathological changes of the joint tissue were observed by hematoxylin-eosin staining. The content of malondialdehyde(MDA), glutathione(GSH), and Fe~(2+) and the activity of superoxide dismutase(SOD) in the joint tissue were measured by biochemical colorimetry. RT-PCR was performed to determine the mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), and acyl-CoA synthetase long chain family member 4(ACSL4) in the joint tissue. Western blot was employed to determine the protein levels of Nrf2, Kelch-like ECH-associated protein 1(Keap1), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), SOD2, GPX4, and ACSL4 in the joint tissue. The results showed that the treatment with Tripterygium glycosides(7.5 mg·kg~(-1)) and total triterpenes of Euphorbium(32, 64, and 128 mg·kg~(-1)) alleviated the swelling degree of bilateral hind limbs, decreased the arthritis score, reduced joint tissue lesions and the content of MDA and Fe~(2+) in the joint tissue, and increased GSH content and SOD activity. Furthermore, the interventions up-regulated the protein and mRNA levels of Nrf2 and GPX4, down-regulated the protein and mRNA levels of ACSL4, and up-regulated the protein levels of Keap1, NQO1, HO-1, and SOD2 in the Nrf2/HO-1/GPX4. In summary, the total triterpenes of Euphorbium can treat RA by inhibiting lipid peroxidation and abnormal ferroptosis, which may involve the Nrf2/HO-1/GPX4 signaling pathway.

Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis.

A visible light-induced Co-catalyzed highly regio- and stereoselective reductive coupling of vinyl azaarenes and alkynes has been developed. Notably, Hünig's base together with simple ethanol has been successfully applied as the hydrogen sources instead of commonly used Hantzsch esters in this catalytic photoredox reaction. This approach has considerable advantages for the straightforward synthesis of stereodefined multiple substituted alkenes bearing an azaarene motif, such as excellent regioselectivity (>20 : 1 for >30 examples) and stereoselectivity (>20 : 1 E/Z), broad substrate scope and good functional group compatibility under mild reaction conditions, which has been utilized in the concise synthesis of natural product monomorine I. A reasonable catalytic reaction pathway involving protolysis of the cobaltacyclopentene intermediate has been proposed based on the mechanistic studies.

Assessing local California trends in emergency physician opioid prescriptions from 2012 to 2020: Experiences in a large academic health system.

OBJECTIVES: There has been increased focus nationally on limiting opioid prescriptions. National data demonstrates a decrease in annual opioid prescriptions among emergency medicine physicians. We analyzed data from 2012 to 2020 from a large academic health system in California to understand trends in opioid prescribing patterns for emergency department (ED) discharged patients and assessed the potential impact of two initiatives at limiting local opioid prescriptions. METHODS: In 2012-2020, monthly ED visit data was used to evaluate the total number of outpatient opioid prescriptions and percent of ED visits with opioid prescriptions (as primary outcomes). Descriptive statistics, graphic representation, and segmented regression with interrupted times series were used based on two prespecified time points associated with intensive local initiatives directed at limiting opioid prescribing1) comprehensive emergency medicine resident education and 2) electronic health record (EHR)-based intervention. RESULTS: Between March 2012 and July 2020, a total of 41,491 ED discharged patients received an opioid prescription. The three most commonly prescribed drugs were hydrocodone (84.1%), oxycodone (10.8%), and codeine (2.8%). After implementing comprehensive emergency medicine resident education, the total number of opioid prescriptions, the percentage of opioid prescriptions over total ED visit numbers and the total tablet number showed decreasing trends (p's ≤ 0.01), in addition to the natural (pre-intervention) decreasing trends. In contrast, later interventions in the EHR tended to show attenuated decreasing trends. CONCLUSIONS: From 2012 to 2020, we found that total opioid prescriptions decreased significantly for discharged ED patients. This trend is seen nationally. However, our specific interventions further heightened this downward trend. Evidence-based legislation, policy changes, and educational initiatives that impact prescribing practices should guide future efforts.

[Chemical constituents of triterpenoids from Euphorbia resinifera].

The combination of normal-phase silica gel column chromatography, octadecyl silica(ODS) column chromatography, semi-preparative high performance liquid chromatography(HPLC), etc. was employed to isolate and purify the chemical components from Euphorbia resinifera, and 7 triterpenoids were separated from the ethanol extract of the medicinal materials. Their structures were identified by various spectroscopy methods as cycloartan-1,24-diene-3-one(1), cycloartan-1,24-diene-3-ol(2), 3ß-hydroxy-lanosta-8,24-diene-11-one(3), lnonotusane C(4), eupha-8,24-diene-3ß-ol-7,11-dione(5), eupha-24-methylene-8-ene-3ß-ol-7,11-dione(6), and eupha-8,24-diene-3ß,11ß-diol-7-one(7). Compounds 1 and 2 are new compounds, and compound 3 is obtained from nature for the first time.

Effects of high-fat diet on antioxidative status, apoptosis and inflammation in liver of tilapia (Oreochromis niloticus) via Nrf2, TLRs and JNK pathways.

Fatty liver injury (or disease) is a common disease in farmed fish, but its pathogenic mechanism is not fully understood. Therefore the present study aims to investigate high-fat diet (HFD)-induced liver injury and explore the underlying mechanism in fish. The tilapia were fed on control diet and HFD for 90 days, and then the blood and liver tissues were collected to determine biochemical parameter, gene expression and protein level. The results showed that HFD feeding signally increased the levels of plasma aminotransferases and pro-inflammatory factors after 60 days. In liver and plasma, HFD feeding significantly suppressed antioxidant ability, but enhanced lipid peroxidation formation, protein oxidation and DNA damage after 60 or 90 days. Further, the Nrf2 pathway and antioxidative function-related genes were adversely changed in liver of HFD-fed tilapia after 60 and/or 90 days. Meanwhile, HFD treatment induced apoptosis via initiating mitochondrial pathway in liver after 90 days. Furthermore, after 90 days of feeding, the expression of genes or proteins related to JNK pathway and TLRs-Myd88-NF-κB pathway was clearly upregulated in HFD treatment. Similarly, the mRNA levels of inflammatory factors including tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8 and IL-10 were also upregulated in liver of HFD-fed tilapia after 60 and/or 90 days. In conclusion, the current study suggested that HFD feeding impaired antioxidant defense system, induced apoptosis, enhanced inflammation and led to liver injury. The adverse influences of HFD in the liver might be due to the variation of Nrf2, JNK and TLRs-Myd88-NF-κB signaling pathways.

The risk of intracranial infection in adults with hydrocephalus after ventriculoperitoneal shunt surgery: A retrospective study.

Infection remains the most significant complication of ventriculoperitoneal shunt (VPS) surgery. The objective of this study was to investigate intracranial infections complicating VPS surgery in adults with hydrocephalus. Patients who underwent VPS surgery for hydrocephalus between 2000 and 2016 were included. Clinical data and follow-up evaluations were examined and analysed retrospectively. A total of 502 patients with hydrocephalus who underwent VPS surgery were included. They were followed up for at least 2 years. Twelve patients with incomplete data were excluded. Four hundred and ninety patients were included in the final analysis. Twenty-five cases of intracranial infection occurred, accounting for 5.1% of patients with VPS surgery. The mean age of the patients was 57.1 ± 10.1 years (range, 39-72 years). The incidence of intracranial infection in patients over 60 years of age was higher than that in patients under 60 years of age (P = .007). Age (P = .007), diabetes (P = .026), skin infection (P = .028), bed-ridden (P = .007), and modified operation (P = .011) were highly correlated with the incidence of intracranial infection. The findings of this retrospective study show that age, diabetes, skin infection, bed-ridden, and modified operation of hydrocephalus significantly and independently correlated with the incidence of infection. Prospective studies are needed to assess the relationship between the incidence of infection and risk factors in patients with hydrocephalus after VPS.

Anomalous Symmetry Protected Topological States in Interacting Fermion Systems.

The classification and construction of symmetry protected topological (SPT) phases have been intensively studied in interacting systems recently. To our surprise, in interacting fermion systems, there exists a new class of the so-called anomalous SPT (ASPT) states which are only well defined on the boundary of a trivial fermionic bulk system. We first demonstrate the essential idea by considering an anomalous topological superconductor with time-reversal symmetry T^{2}=1 in 2D. The physical reason for this is that the fermion parity might be changed locally by certain symmetry action, but it is conserved if we introduce a bulk. Then we discuss the layer structure and systematical construction of ASPT states in interacting fermion systems in 2D with a total symmetry G_{f}=G_{b}×Z_{2}^{f}. Finally, potential experimental realizations of ASPT states are also addressed.

Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7.

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

Santin inhibits influenza A virus replication through regulating MAPKs and NF-κB pathways.

Influenza A virus (IAV) causes high morbidity and significant mortality worldwide. Given the limitations of existing vaccination and antiviral drugs, it is urgent to develop new anti-influenza drugs. Flavonoids are natural polyphenolic compounds with broad applications to treatments for influenza infection. In this study, we demonstrated that santin, a flavonoid compound, showed anti-influenza activity in MDCK and THP-1 cells. Mechanistic studies revealed that santin depressed the phosphorylation of p38 MAPK, JNK/SAPK, ERK, and NF-κB factor and subsequently attenuated the expression of inflammatory cytokines in IAV-infected cells. Thus, santin is a potential candidate for the future development of anti-IAV drugs.

Intermolecular C-H Amidation of (Hetero)arenes to Produce Amides through Rhodium-Catalyzed Carbonylation of Nitrene Intermediates.

Amide bond formation is one of the most important reactions in organic chemistry because of the widespread presence of amides in pharmaceuticals and biologically active compounds. Existing methods for amides synthesis are reaching their inherent limits. Described herein is a novel rhodium-catalyzed three-component reaction to synthesize amides from organic azides, carbon monoxide, and (hetero)arenes via nitrene-intermediates and direct C-H functionalization. Notably, the reaction proceeds in an intermolecular fashion with N2 as the only by-product, and either directing groups nor additives are required. The computational and mechanistic studies show that the amides are formed via a key Rh-nitrene intermediate.

ß-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke.

BACKGROUND: Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a protective mechanism for secondary inflammatory injury as well as a contributor to infection complications. Although stroke-induced hyperactivation of the sympathetic system is proved to facilitate SIDS, the involved endogenous factors and pathways are largely elusive. In this study, we aim to investigate the function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS. METHODS: Splenic ARRB2 expression and the sympathetic system activity were detected after establishing transient models of middle cerebral artery occlusion (MCAO). In addition, a correlation between ARRB2 expression and the sympathetic system activity was analyzed using a linear correlation analysis. Any SIDS reflected in monocyte dysfunction was investigated by measuring inflammatory cytokine secretion and neurological deficit scores and infarct volume were tested to assess neurological outcome. Further, ARRB2 expression in the monocytes was knocked down in vitro by siRNAs. Following the stimulation of noradrenaline and lipopolysaccharide, cytokine secretion and the nuclear factor-κB (NF-κB) pathway were evaluated to gain insight into the mechanisms related to the contribution of ARRB2 to adrenergic-induced monocyte dysfunction. RESULTS: Splenic ARRB2 expression was significantly increased after stroke and also showed a significant positive correlation with the sympathetic system activity. Stroke-induced monocyte dysfunction resulted in an increase of the interleukin-10 (IL-10) level as well as a decrease of the interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. Also, blockade of adrenergic-activity significantly reversed these cytokine levels, and blockade of adrenergic-activity improved stroke-induced neurological results. However, the improved neurological results had no significant correlation with ARRB2 expression. Furthermore, the in vitro results showed that the deficiency of ARRB2 dramatically repealed adrenergic-induced monocyte dysfunction and the inhibition of NF-κB signaling phosphorylation activity. CONCLUSIONS: ARRB2 is implicated in the sympathetic-triggered SIDS, in particular, monocyte dysfunction after stroke. Accordingly, ARRB2 may be a promising therapeutic target for the immunological management of stroke in a clinic.

Differential long noncoding RNA expressions in peripheral blood mononuclear cells for detection of acute ischemic stroke.

Long noncoding RNAs (lncRNAs) have been highlighted to be involved in the pathological process of ischemic stroke (IS). The purpose of the present study was to investigate the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs) of acute IS patients and to explore their utility as biomarkers of IS. Distinctive expression patterns of PBMC lncRNAs were identified by an lncRNA microarray and individual quantitative real-time PCR (qRT-PCR) in four independent sets for 206 IS, 179 healthy controls (HCs), and 55 patients with transient ischemic attack (TIA). A biomarker panel (lncRNA-based combination index) was established using logistic regression. LncRNA microarray analysis showed 70 up-regulated and 128 down-regulated lncRNAs in IS patients. Individual qRT-PCR validation demonstrated that three lncRNAs (linc-DHFRL1-4, SNHG15, and linc-FAM98A-3) were significantly up-regulated in IS patients compared with HCs and TIA patients. Longitudinal analysis of lncRNA expression up to 90 days after IS showed that linc-FAM98A-3 normalized to control levels by day 7, while SNHG15 remained increased, indicating the ability of lncRNAs to monitor IS dynamics. Receiver-operating characteristic (ROC) curve analysis showed that the lncRNA-based combination index outperformed serum brain-derived neurotrophic factor (BDNF) and neurone-specific enolase (NSE) in distinguishing IS patients from TIA patients and HCs with areas under ROC curve of more than 0.84. Furthermore, the combination index increased significantly after treatment and was correlated with neurological deficit severity of IS. The panel of these altered lncRNAs was associated with acute IS and could serve as a novel diagnostic method.