Contribution of NKX2-3 Polymorphisms to Inflammatory Bowel Diseases: A Meta-Analysis of 35358 subjects

AbstractPolymorphisms in NKX2-3 gene have been inconsistently associated with Crohn's disease (CD) and ulcerative colitis (UC). To generate large-scale evidence on whether NKX2-3 polymorphisms are associated with CD or UC susceptibility we have conducted a meta-analysis of 17 studies involving 17329 patients and 18029 controls. A significantly increased CD or UC risk was observed in persons carrying a G allele at rs10883365 polymorphism (A/G) compared with those with a A allele. (OR = 1.226, 95%CI: 1.177–1.277 and OR = 1.274, 95%CI: 1.175–1.382 respectively). In the subgroup analysis, a significantly increased CD risk was found in both Europeans and Asians. For rs11190140 polymorphism (C/T) and CD risk, the risk estimate for the allele contrast was OR = 1.201 (1.136–1.269). This meta-analysis provided a robust result that persons with a G or T allele may have a moderately increased risk of CD and suggested that rs10883365 polymorphism was also a candidate gene polymorphism for UC susceptibility.</jats:p

Characteristics of fecal mercury and methylmercury and risks to captive golden snub-nosed monkeys (Rhinopithecus roxellana) and rhesus macaques (Macaca mulatta) in China

Environmental pollution is widespread and poses significant risks to both human populations and diverse animal species. As part of conservation initiatives, many endangered animals are housed in zoos and breeding centers close to human activities, potentially exposing them to health threats arising from environmental contamination, such as mercury (Hg). By analyzing non-invasive fecal samples from 13 Chinese zoos, we assessed total mercury (THg) and methylmercury (MeHg) exposure in two non-human primate species: the endangered species golden snub-nosed monkey (Rhinopithecus roxellana), and the most widely distributed rhesus macaque (Macaca mulatta). The concentration of THg in golden snub-nosed monkeys (mean ± s.d.: 76.7 ± 35.6 ng/g; median: 71.8 ng/g, range: 11.2–200.0 ng/g, n = 71) was significantly higher than that in rhesus macaques (mean ± s.d.: 32.3 ± 54.7 ng/g; median: 17.5 ng/g, range: 7.4–409.0 ng/g, n = 98). No significant differences were observed in both MeHg and MeHg % between these two species. Age and sex did not predict fecal Hg. Among adults, approximately 85 % of sampled individuals exhibited hazard quotient (HQ) values exceeding 1, indicating mercury poses a health risk to captive primate populations. The average HQ for golden snub-nosed monkeys was 2.98 ± 1.68 (range: 0.46–8.21, n = 43), while for rhesus macaques was 1.84 ± 1.64 (range: 0.61–12.49, n = 71). Our findings suggest that conservation efforts for captive primates may be compromised by Hg pollution, particularly in golden snub-nosed monkeys. Further investigation and ongoing biomonitoring from an ecotoxicological perspective, are crucial to ensuring the health of captive primate populations

Colchicine for preventing stroke in patients with and without intracranial atherosclerotic stenosis: a prespecified analysis of a randomized clinical trialResearch in context

Summary: Background: The effect of colchicine on subsequent stroke among patients with and without symptomatic intracranial artery stenosis (sICAS) and whether age modifies such effect are not known. Methods: In this prespecified subgroup analysis of CHANCE-3, a randomized, double-blind, placebo-controlled clinical trial conducted at 244 centers in China between 11 August 2022 and 13 April 2023 (ClinicalTrials.gov number, NCT05439356), we included 7567 patients with ischemic stroke or transient ischemic attack and assessments of intracranial arteries at baseline. The primary efficacy outcome was a new stroke at 90 days. The main secondary outcome was a combined vascular event including ischemic stroke, hemorrhagic stroke, TIA, myocardial infarction, and vascular death. The primary safety outcome was any serious adverse event within 90 days. Findings: In patients with sICAS, 141 (10.5%) patients on colchicine and 115 (8.5%) on placebo had recurrent stroke within 90 days (adjusted HR 1.30, 95% CI 1.01–1.69; p = 0.04); in patients without sICAS, the corresponding event rates were 4.2% and 5.2% (adjusted HR 0.80, 95% CI 0.62–1.05; p = 0.10) (adjusted interaction p = 0.01). A significant interaction was also observed between sICAS status and the effect of colchicine on the secondary outcome of combined vascular events (adjusted p = 0.02). The interaction was more apparent in the elderly patients (adjusted p < 0.001). In the elderly patients with sICAS (n = 1648), the risk of stroke was higher in the colchicine group (n = 829, 50.3%) compared to the placebo group (n = 819, 49.7%) (adjusted HR 1.58, 95% CI 1.13–2.20; p < 0.001). There was no interaction of status of sICAS with treatment groups on primary safety outcome of any serious adverse event (p = 0.54). In patients with sICAS, 24 (1.8%) patients on colchicine and 7 (0.5%) on placebo had diarrhea within 90 days (p = 0.002). In patients without sICAS, diarrhea occurred in 43 (1.8%) patients on colchicine and in 20 (0.8%) patients on placebo (p = 0.004). Interpretation: The effect of colchicine on subsequent stroke within 90 days may differ according to the presence of sICAS. Aging might be associated with an increased risk of early recurrent stroke in the patients with sICAS receiving colchicine treatment. Future prospective studies are needed to confirm these results. Funding: National Key R&D Program of China, National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. China Kunming Pharmaceuticals supplied colchicine and placebo. Guangdong Wesail Biotech Co. provided assistance in measurement of hsCRP levels

Safety and efficacy of low-intensity versus standard monitoring following intravenous thrombolytic treatment in patients with acute ischaemic stroke (OPTIMISTmain): an international, pragmatic, stepped-wedge, cluster-randomised, controlled non-inferiority trial

Background: The universally accepted best practice protocol for monitoring patients who receive intravenous thrombolysis for acute ischaemic stroke was established in the 1990s. However, the protocol is burdensome for nurses, disrupts the sleep of patients, and is potentially less relevant in patients at low risk of symptomatic intracerebral haemorrhage. We aimed to assess whether implementing a low-intensity monitoring protocol would be as safe and effective as standard high-intensity monitoring for patients with acute ischaemic stroke at low risk. Methods: OPTIMISTmain was an international, pragmatic, multicentre, stepped-wedge, cluster-randomised, controlled, non-inferiority, blinded-endpoint trial conducted at hospitals (clusters) in eight countries. It was designed to test the non-inferiority of a low-intensity monitoring protocol to a standard protocol among consecutive adults with acute ischaemic stroke who were clinically stable with mild to moderate neurological impairment (score </p