Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

The intake of cruciferous vegetables and the risk of ovarian cancer: a systematic review and dose-response meta-analysis.

INTRODUCTION: The link between cruciferous vegetables (CVs) and ovarian cancer (OC) is still uncertain. This meta-analysis intended to investigate the association between CVs consumption and the risk of OC, as well as to conduct a dose-response analysis to determine the degree of correlation between them. METHODS: We systematically searched PubMed, Web of Science, Embase, and Cochrane Library databases between database creation and October 2023. The present meta-analysis has been duly registered and assigned the registration number CRD42023470299. This study followed the PRISMA guidelines. The statistical analysis was performed using Stata 14.0 software. RESULTS: There were a total of 7 cohort studies and 7 case-control studies with 7,269 cases and 742,952 subjects. The combined relative risk (RR) of the highest intake of CVs was 0.90 (95% confidence intervals [CIs]: 0.84-0.96; I2=54.7%; P=0.007) compared to the lowest intake of CVs. The odds ratio (OR) was 0.97 (95% CIs: 0.86-1.08; P=0.192) for case-control studies, and the RR was 0.79 (95% CIs: 0.67-0.91; P=0.167) for cohort studies. The intake of CVs and the risk of OC were linearly correlated. Adding 15 grams of CVs to the diet each day decreased the likelihood of developing OC by almost 4% (RR=0.963, 95% CIs: 0.905-1.025; P=0.235). CONCLUSIONS: Consumption of CVs may be linked to a lower risk of OC.

Invasion and Propagation of White Spot Syndrome Virus: Hijacking of the Cytoskeleton, Intracellular Transport Machinery, and Nuclear Import Transporters.

The pathogenesis of white spot syndrome virus (WSSV) is largely unclear. In this study, we found that actin nucleation and clathrin-mediated endocytosis were recruited for internalization of WSSV into crayfish hematopoietic tissue (Hpt) cells. This internalization was followed by intracellular transport of the invading virions via endocytic vesicles and endosomes. After envelope fusion within endosomes, the penetrated nucleocapsids were transported along microtubules toward the periphery of the nuclear pores. Furthermore, the nuclear transporter CqImportin α1/ß1, via binding of ARM repeat domain within CqImportin α1 to the nuclear localization sequences (NLSs) of viral cargoes and binding of CqImportin ß1 to the nucleoporins CqNup35/62 with the action of CqRan for docking to nuclear pores, was hijacked for both targeting of the incoming nucleocapsids toward the nuclear pores and import of the expressed viral structural proteins containing NLS into the cell nucleus. Intriguingly, dysfunction of CqImportin α1/ß1 resulted in significant accumulation of incoming nucleocapsids on the periphery of the Hpt cell nucleus, leading to substantially decreased introduction of the viral genome into the nucleus and remarkably reduced nuclear import of expressed viral structural proteins with NLS; both of these effects were accompanied by significantly inhibited viral propagation. Accordingly, the survival rate of crayfish post-WSSV challenge was significantly increased after dysfunction of CqImportin α1/ß1, also showing significantly reduced viral propagation, and was induced either by gene silencing or by pharmacological blockade via dietary administration of ivermectin per os. Collectively, our findings improve our understanding of WSSV pathogenesis and support future antiviral designing against WSSV. IMPORTANCE As one of the largest animal DNA viruses, white spot syndrome virus (WSSV) has been causing severe economical loss in aquaculture due to the limited knowledge on WSSV pathogenesis for an antiviral strategy. We demonstrate that the actin cytoskeleton, endocytic vesicles, endosomes, and microtubules are hijacked for WSSV invasion; importantly, the nuclear transporter CqImportin α1/ß1 together with CqRan were recruited, via binding of CqImportin ß1 to the nucleoporins CqNup35/62, for both the nuclear pore targeting of the incoming nucleocapsids and the nuclear import of expressed viral structural proteins containing the nuclear localization sequences (NLSs). This is the first report that NLSs from both viral structure proteins and host factor are elaborately recruited together to facilitate WSSV infection. Our findings provide a novel explanation for WSSV pathogenesis involving systemic hijacking of host factors, which can be used for antiviral targeting against WSSV disease, such as the blockade of CqImportin α1/ß1 with ivermectin.

Risk of progression to hypertension across baseline blood pressure in nonhypertensive participants among rural Chinese adults: a prospective study.

OBJECTIVES: To assess the risk of progression to hypertension across baseline blood pressure (BP) level among rural Chinese adults. METHODS: A population-based sample of 24 052 rural Chinese adults aged at least 35 years and free from hypertension at baseline were followed up from 2004-2006 to 2008. Incident hypertension was defined as SBP of at least 140 mmHg, DBP of at least 90 mmHg, current use of antihypertensive medication, or all. RESULTS: During a median follow-up of 28 months, 26.5% participants developed clinical hypertension, most of which were untreated and uncontrolled. The cumulative incidence of hypertension in participants with optimal, normal, and high-normal BP was 21.2, 25.2, and 32.4%, respectively. The higher incidence of hypertension (per 100 person-years) was obviously observed in higher BP category at baseline among both older and younger groups (both P for trend <0.05). Compared with optimal BP, the adjusted hazard ratios of participants with normal and high-normal BP for incident hypertension were 1.16 (95% confidence interval 1.08-1.24) and 1.28 (95% confidence interval 1.20-1.36), respectively. In addition, older age, men, Mongolian ethnicity, alcohol drinking, family history of hypertension, BMI, and change in BMI during follow-up were also independently associated with incident hypertension. CONCLUSION: There was a stepwise increase in risk of progression to hypertension across baseline BP level. This information could help us define a population at high risk of progression to hypertension, to underscore the importance of frequent BP monitoring, and early interventions in rural Chinese adults.