Background and Purpose— Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods— We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results— The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13–1.46], 1.19 [95% CI, 1.05–1.35], and 1.30 [95% CI, 1.07–1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50–0.87] and 0.68 [95% CI, 0.51–0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20–1.56] and 1.53 [95% CI, 1.16–2.01]). Conclusions— Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.

Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1) is believed to function as a tumor suppressor, while Phosphoinositide-3-Kinase Regulatory Subunit 2 (PIK3R2) as a tumor driver. However, there is no systematic pan-cancer analysis of them. The pan-cancer study comprehensively investigated the gene expression, genetic alteration, DNA methylation, and prognostic significance of PIK3R1 and PIK3R2 in 33 different tumors based on the TIMER, GEPIA, UALCAN, HPA, cBioPortal, and Kaplan–Meier Plotter database. The results indicated that PIK3R1 is lowly expressed in most tumors while PIK3R2 is highly expressed in most tumors, and abnormal gene expression may be related to promoter methylation. Moreover, not only mutations, downregulation of PIK3R1 and upregulation of PIK3R2 were found to be detrimental to the survival of most cancer patients as well. Furthermore, the expression of both PIK3R1 and PIK3R2 was associated with the level of immune infiltration in multiple tumors, such as breast invasive carcinoma. Our study conducted a comparatively comprehensive analysis of the role of PIK3R1 and PIK3R2 in a variety of cancers, contributing to further study of their potential mechanisms in cancer occurrence and progression. Our findings suggested that PIK3R1 and PIK3R2 could serve as prognostic markers for several cancers.

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Mismatch between circulating influenza B viruses and vaccine strains occurs frequently. In a randomized, double-blind, controlled phase III clinical study, healthy children aged 6-35 months were randomized into three groups at a ratio of 2:1:1, received two doses of quadrivalent influenza vaccines (QIVs) or licensed trivalent influenza vaccines (TIVs). The primary objective was to evaluate the non-inferiority immunogenicity of QIV compared with the two TIVs, containing B/Victoria or B/Yamagata strain. Safety information was collected for 28 days after each vaccination. Serious adverse events (SAEs) were monitored for 6 months after the second vaccination. A total of 2146 subjects (QIV: 1069, TIV-Vic: 540, TIV-Yam: 537) were enrolled in this study. QIV was found non-inferior to TIVs for shared strains (A/ H1N1 and A/H3N2) and corresponding BY strain based on hemagglutination inhibition (HI) antibodies 28 days after the second dose of vaccination. The resulted geometric mean titer (GMT) ratios (QIV/TIV) were 0.98 (0.89, 1.07) for H1N1, 0.95 (0.85, 1.05) for H3N2 and 0.89 (0.81, 0.98) for BY. And the seroconversion rate differences (QIV-TIV) were −0.46% (−3.24%, 2.31%) for H1N1, −1.95% (−5.54%, 1.65%) for H3N2 and −3.58% (−8.11%, 0.95%) for BY. The BV strain in QIV did not reach the noninferiority criteria, with GMT of 1:52.25 (vs. 1:61.02 of TIV-Vic) and seroconversion rate of 59.49% (vs. 66.85% of TIV-Vic). No increased safety concerns occurred in QIV group. Candidate QIV can provide good protection for children aged 6 to 35 months, and its immunogenicity and safety were proved. Clinical Trials Registration: ClinicalTrials.gov number: NCT03859141.

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