Morning blood pressure surge and intracranial atherosclerotic plaque characteristics: a high-resolution magnetic resonance vessel wall imaging study.

OBJECTIVE: To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability. METHODS: A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association. RESULTS: Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects. CONCLUSION: Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup. ADVANCES IN KNOWLEDGE: This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI.

Influenza-existing drugs and treatment prospects.

Influenza is a century-old disease that continues to baffle humans by its frequently changing nature, seasonal epidemics, and occasional pandemics. Approximately 9% of the world's population is infected by the influenza virus annually. The emergence of novel strains because of rapid mutations as well as interspecies disease contamination, limits the efficiency of strain-specific vaccines. Anti-influenza drugs such as neuraminidase inhibitors, M2 ion channel inhibitors, etc. have become the first line of defense in prophylaxis and early containment of the disease. But the growing drug resistance due to drug-induced selective pressure has also limited the efficacy of those drugs. Because we can't predict the next strain types, their virulence, or the severity of the next epidemic/pandemic caused by influenza virus, we ought to gear up for the development of novel anti-influenza drugs with a broad spectrum of reactivity against all strains and subtypes, better bioavailability, easier administrative pathways, and lesser adverse effects. Various new compounds with each having significantly different target molecules and pharmacologic activity have shown potential against influenza virus strains in laboratory situations as well as clinical trials. We should also consider combination therapy to boost the efficacy of existing drugs. This review is aiming to succinctly document the recent signs of progress regarding anti-influenza drugs both in the market and under investigation.

Association between Short-Term Blood Pressure Variability and Intracranial Atherosclerotic Plaque Vulnerability: A High-Resolution Magnetic Resonance Imaging Study.

AIM: short-term blood pressure variability (BPV) as a risk factor of atherosclerosis and cardiovascular events has been investigated. However, its association with atherosclerotic plaque vulnerability remains unknown. The objective of this study was to determine the association between short-term BPV and intracranial atherosclerotic plaque vulnerability. METHODS: this is a cross-sectional analysis of 267 ischemic stroke patients with symptomatic intracranial atherosclerosis (mean age, 65±12 years old; 60.3% male), which were prospectively recruited in a comprehensive stroke center. Systolic and diastolic BP SD, CV, and BP variability ratio (BPVR) from 24 hours, daytime, and nighttime were calculated from 24-h ambulatory blood pressure monitoring, intracranial atherosclerotic plaque burden and vulnerability were evaluated by high-resolution magnetic resonance vessel wall imaging. Logistic regression analysis was used to locate the correlation between short-term BPV and plaque vulnerability. RESULTS: a total of 36.3% subjects presented with intraplaque hemorrhage (IPH) in this study. Multivariate logistic regression suggested that nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently after adjusted for cardiovascular risk factors, odds ratio (OR) and 95% confidence interval (CI) for per SD BPV changes were 1.418 (1.051, 1.914) and 0.731 (0.548, 0.976), respectively, and this association also independent of atherosclerosis burden and 24-h mean systolic BP level. Further subgroup analysis by age and hypertension history demonstrated that the statistical correlation could only establish in the elder, and subjects with hypertension. CONCLUSION: nighttime diastolic BP CV and 24-h BPVR were associated with intracranial IPH independently, especially in the elderly and subjects with hypertension.

Design, synthesis, in vitro and in vivo anti-respiratory syncytial virus (RSV) activity of novel oxizine fused benzimidazole derivatives.

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections. Currently, the only clinical anti-RSV drug is ribavirin, but ribavirin has serious toxic side effect and can only be used by critically ill patients. A series of benzimidazole derivatives were synthesized starting from 1,4:3,6-dianhydro-d-fructose and a variety of o-phenylenediamines. Evaluation of their antiviral activity showed that compound a27 had the highest antiviral activity with a half maximal effective concentration (EC50) of 9.49 µM. Investigation of the antiviral mechanism of compound a27 indicated that it can inhibit the replication of RSV by inhibiting apoptosis and autophagy pathways. Retinoic acid-inducible gene (RIG)-I, TNF receptor associated factor (TRAF)-3, TANK binding kinase (TBK)-1, interferon regulatory factor (IRF)-3, nuclear factor Kappa-B (NF-κB), interferon (IFN)-ß, Toll-like receptor (TLR)-3, interleukin (IL)-6 were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by compound a27. Decreased expression of RIG-I, IRF-3, IFN-ß, TLR-3, IL-6, interleukin (IL)-8, interleukin (IL)-10, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α was also found in vivo.

Antiviral Activity of 3D, a Butene Lactone Derivative Against Influenza A Virus In Vitro and In Vivo.

Influenza A virus is a highly variable and contagious respiratory pathogen that can cause annual epidemics and it poses an enormous threat to public health. Therefore, there is an urgent need for a new generation of antiviral drugs to combat the emergence of drug-resistant strains of the influenza virus. A novel series of butene lactone derivatives were screened and the compound 3D was selected, as it exhibited in vitro potential antiviral activity against A/Weiss/43 H1N1 virus with low toxicity. In addition, 3D dose-dependently inhibited the viral replication, expression of viral mRNA and viral proteins. 3D exerted a suppressive effect on A/Virginia/ATCC2/2009 H1N1 and A/California/2/2014 H3N2 in vitro. The time-of-addition analysis indicated that 3D suppressed H1N1 in the early stage of its life cycle. A/Weiss/43 H1N1-induced apoptosis in A549 cells was reduced by 3D via the mitochondrial apoptosis pathway. 3D could decrease the production of H1N1-induced pro-inflammatory cytokines that are induced by H1N1 in vitro and in vivo. The administration of 3D reduced lung lesions and virus load in vivo. These results suggest that 3D, which is a butene lactone derivative, is a promising agent for the treatment of influenza A virus infection.

Screening and pharmacodynamic evaluation of the antirespiratory syncytial virus activity of steroidal pyridine compounds in vitro and in vivo.

Respiratory syncytial virus (RSV) causes serious lower respiratory tract infections and there are currently no safer or more effective drugs available. It is important to find novel medications for RSV infection. A series of steroidal pyridines were synthesized for screening and evaluation of their antiviral activity and investigation of their antiviral mechanism of action. Compound 3l had the highest antiviral activity, with a half-maximal effective concentration (EC50 ) of 3.13 µM. Compound 3l was explored for its effects in vitro on RSV 2 h before infection (pretreatment), at the time of infection (competition), and 2 h after infection (postinfection). Toll-like receptor (TLR)-3, retinoic acid-inducible gene (RIG)-I, interleukin (IL)-6, and interferon (IFN)-ß were suppressed at the cellular level. Mouse lung tissue was subjected to hematoxylin and eosin (HE) staining and immunohistochemistry, which showed that RSV antigen and M gene expression could be reduced by compound 3l. Decreased expression of TLR-3, RIG-I, IL-6, IFN-ß, and IL-10 was also found in vivo. The results indicated that compound 3l exerted its antiviral effects mainly through inhibition of viral replication and downregulation of inflammatory factors.

Incremental value of plaque enhancement in predicting stroke recurrence in symptomatic intracranial atherosclerosis.

PURPOSE: To investigate the association between plaque enhancement and stroke recurrence in subjects with intracranial atherosclerosis. METHODS: Ischemic stroke patients with symptomatic intracranial atherosclerosis were prospectively included and followed in a comprehensive stroke center. Pre- and post-contrast vessel wall images were used to evaluate plaque enhancement. Other established suggestive imaging markers were also acquired simultaneously. Univariate- and multivariate-adjusted Cox proportional hazard regression models were used to determine the association between plaque enhancement and stroke recurrence. Finally, receiver operating characteristic (ROC) curves were used to demonstrate the predictive value of different imaging markers. RESULTS: Of the 60 subjects included, 12 (20.0%) patients presented with ipsilateral stroke recurrence during the median 12-month follow-up. Cox proportional hazard regression models indicated that plaque enhancement was an independent risk factor associated with stroke recurrence after adjusted covariates, with a hazard ratio (HR) of 14.24 and 95% confidence interval (95% CI) (1.21, 168.11), p = 0.04. In addition, border zone infarction was also statistically significant in predicting stroke recurrence in multi-variable regression (HR = 3.80; 95% CI = 1.04, 13.80; p = 0.04). Collateral status was in marginal significance (HR = 0.25; 95% CI = 0.06, 1.08; p = 0.06). ROC analysis indicated that the area under the curve and 95% CI to identify stroke recurrence are 0.67 (0.51, 0.82) for plaque enhancement and 0.71 (0.54, 0.88) for infarction pattern and collateral status and may increase to 0.82 (0.70, 0.93) by combining the three markers above. CONCLUSION: Plaque enhancement is independently associated with stroke recurrence in subjects with intracranial atherosclerosis and has added value to hemodynamic indicators in predicting stroke recurrence.