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Objective·To explore the effects of hypertension and dyslipidemia on cognitive function in the elderly.Methods·A dynamic population cohort was established by using prospective cohort study methods. In 2019, a complete cohort was selected from residents aged 65 and above who voluntarily participated in a free physical examination program in a community in Shanghai, serving as the baseline cohort. In 2022, 512 community-dwelling elderly aged 67 to 93 were randomly selected from the same community as the follow-up cohort for the study. The collected date included residents′ health records, various physical examination measurements, and Mini-mental State Examination (MMSE) scale scores.Results·Of the 512 cases that were followed up, the valid sample size was reduced to 495 after data cleaning. According to the baseline and follow-up cognitive assessments and changes, the cases were categorized into three cognitive groups: the improvement group, the normal group, and the decline group. The prevalence of hypertension in the decline group was 43.14% higher than that in the improvement group and 24.39% higher than that in the normal group (66.67% in the decline group vs 23.53% in the improvement group, P=0.011; 66.67% in the decline group vs 42.28% in the normal group, P=0.040). Total cholesterol (TC) in the improvement group was lower than that in the normal group [improvement group (4.38±1.04) mmol/L vs normal group (5.11±1.12) mmol/L, P=0.009]. Additionally, TC in the decline group in 2022 was higher than that in 2019 [paired difference (0.46±0.87) mmol/L, 95% CI 0.08‒0.84, P=0.021]. LDL-Ch in the improvement group was lower than that in the normal group [improved group (2.51±0.92) mmol/L vs normal group (3.07±1.00) mmol/L, P=0.024], and their HDL-Ch in 2022 was higher than that in 2019 [paired difference (0.16±0.20) mmol/L, 95% CI 0.06‒0.26, P=0.005]. The results of multinomial Logistic regression showed: TC in the improved group was lower than that in the normal group [β=4.12, OR=61.64, 95% CI 1.52‒2494.07, P=0.029] and the decline group [β=5.88, OR=357.35, 95% CI 4.54‒28149.75, P=0.008]; the TAG [β=1.85, OR=6.34, 95% CI 1.05‒38.43, P=0.045], LDL-Ch [β=5.61, OR=274.06, 95% CI 3.65‒20567.57, P=0.011], and hypertension [β=1.90, OR=6.69, 95% CI 1.53‒29.16, P=0.011] in the decline group were higher than those in the improvement group; the age of the decline group was greater than that of the normal group [β=0.08, OR=1.08, 95% CI 1.00‒1.16, P=0.041], and the education level was lower than that of the normal group [β=1.22, OR=3.39, 95% CI 1.28‒8.94, P=0.014].Conclusion·Low TC and LDL-Ch and high HDL-Ch are beneficial to cognitive improvement. Conversely, hypertension, high TC, high TAG, high LDL-Ch, low education level, and advanced ages are risk factors for cognitive decline.

Several equipment clamps of main transformer in a nuclear power company were broken. Taking samples from the broken equipment clamps and the same batch of spare equipment clamps, the fracture causes were analyzed through macroscopic inspection, penetrant testing, metallographic analysis, micro morphology testing, crimping quality testing, conductivity testing and XRD testing. The main reason for the fracture is that the equipment clamp bears all kinds of stress under the condition of insufficient strength and performance degradation, and finally cracks appear at the weakest part of the weld, forming fracture. In order to avoid the occurrence of similar accidents, it is suggested to strengthen the metal supervision and strictly control the quality of the access equipment.

Background: Nirmatrelvir/Ritonavir is an orally administered anti-SARS-Cov-2 drug used in mild-to-moderate COVID-19 patients. Our retrospective cohort study aims to evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in severe hospitalized patients with Omicron infection, as well as in patients at high risk for progression to critical illness in real-world settings. Methods: A total of 350 patients received Nirmatrelvir/Ritonavir while 350 matched controls did not. Patients with confirmed COVID-19 were administered Nirmatrelvir 300 mg and Ritonavir 100 mg orally twice a day for 5 days, with the medication initiated on the first day after admission. The primary endpoint of the study was a composite outcome of hospitalization or death from any cause within 28 days. Secondary endpoints included the occurrence of adverse events and the evaluation of serum levels of IL-6 and viral load. Results: We documented the mortality risk from any cause within 28 days, viral load, serum IL-6 levels, and adverse events. Nirmatrelvir/Ritonavir reduced the 28-day risk of all-cause mortality by 86% (P =.011, hazard ratio (HR) = 0.14, 95% confidence interval (CI) = 0.03, 0.64). At baseline, the serum level of IL-6 was significantly higher in the antiviral treatment group compared to the control group (P <.001), but no significant difference (P =.990) was found between the two groups at discharge. In CKD patients undergoing hemodialysis, no significant worsening of renal function was observed in the Nirmatrelvir/Ritonavir treatment group compared to the control group. Conclusion: Nirmatrelvir/Ritonavir may reduce the 28-day risk of all-cause mortality in critically ill patients with COVID-19 and in patients at high risk for critical disease progression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear. RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models. RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07–1.27]) and CVD (HR, 1.09 [95% CI, 1.03–1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90–1.09]; HR for CVD, 1.04 [95% CI, 0.98–1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant. CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEA) and deoxynivalenol (DON) are two common mycotoxins produced by the genus Fusarium and have potential immunotoxic effects that may lead to a weak immune response against bacterial infections. Listeria monocytogenes (L. monocytogenes), a food-borne pathogenic microorganism ubiquitous in the environment, actively multiplies in the liver, where hepatocytes are capable of resistance through mediated innate immune responses. At present, it is not clear if ZEA and DON affect hepatocyte immune responses to L. monocytogenes infection or the mechanisms involved. Therefore, in this study, in vivo and in vitro models were used to investigate the effects of ZEA and DON on the innate immune responses of hepatocytes and related molecules after L. monocytogenes infection. In vivo studies revealed that ZEA and DON inhibited the toll-like receptors 2 (TLR2)/nuclear factor kappa-B (NFκB) pathway in the liver tissue of L. monocytogenes-infected mice, downregulating the expression levels of Nitric oxide (NO), in the liver and repressing the immune response. In addition, ZEA and DON inhibited Lipoteichoic acid (LTA)-induced expression of TLR2 and myeloid differentiation factor 88 (MyD88) in Buffalo Rat Liver (BRL 3A) cells in vitro, downregulating the TLR2/NFκB signaling pathway and resulting in the decreased expression levels of NO, causing immunosuppressive effects. In summary, ZEA and DON can negatively regulate NO levels through TLR2/NFκB, inhibiting the innate immune responses of the liver, and aggravate L. monocytogenes infections in mouse livers. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEA), a common mycotoxin in animal feed, is harmful to public health and causes huge economic losses. The potential target proteins of ZEA and its derivatives were screened using the PharmMapper database and the related genes (proteins) of the testis were obtained from Genecards. We obtained 144 potential targets of ZEA and its derivatives related to the testis using Venn diagrams. The PPI analysis showed that ZEA had the most targets in testis, followed by ZAN, α‐ZAL, β‐ZEL, α‐ZEL, and β‐ZAL. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses evaluated the metabolic and cancer pathways. We further screened four hub genes: RAC3, CCND1, EP300, and CTNNB1. Eight key biological processes were obtained by GO analysis, and four important pathways were identified by KEGG analysis. Animal and cell experimental results confirmed that ZEA could inhibit the expression of four key KEGG pathway protein components and four hub proteins that interfere with cell adhesion by inhibiting the focal adhesion structure of the testis, Leydig cells, and Sertoli cells. Collectively, our findings reveal that the destruction of the focal adhesion structure in the testis is the mechanism through which ZEA damages the male reproductive system. [ABSTRACT FROM AUTHOR]

The rodent Pig‐a assay has been used extensively as a potential regulatory assay for evaluating the in vivo mutagenicity of test substances. Although the assay can be conducted in different mammalian species, there have been only a few reports describing its use in humans, and rarely in genotoxicant‐exposed human populations. In this study, PIG‐A mutation frequencies (MFs) were evaluated in 36 azathioprine (AZA; human carcinogen)‐treated inflammatory bowel disease (IBD) patients and 36 healthy volunteers. IBD patients exhibited a slight but statistically higher MF (6.10 ± 4.44 × 10−6) than healthy volunteers (4.97 ± 2.74 × 10−6) (P = 0.0489). The estimated relative risk for the exposed patients was 1.22 which indicated that AZA is a risk factor for inducing PIG‐A mutation. However, the PIG‐A MF showed no associations with AZA treatment duration or total AZA exposure. In addition, we performed the cytokinesis‐block micronucleus test on the same samples. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in IBD patients (MN: 4.70 ± 2.86‰; NBUD: 1.89 ± 0.95‰) were significantly higher than in healthy volunteers (MN: 1.47 ± 0.77‰, P < 0.001; NBUD: 0.90 ± 0.58‰, P = 0.004). MN frequency also had significant correlations with AZA treatment duration (P = 0.011) and total AZA exposure (P = 0.018). Our findings indicate that AZA‐treated IBD patients have only a marginally significant increase in PIG‐A MF; in contrast, a much stronger AZA‐associated increase in genotoxicity was detected with the lymphocyte MN assay. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]