Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose-response meta-analysis.

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71-0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65-0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60-0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02-1.20). CONCLUSIONS: This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.

Macrophage-NLRP3 Activation Promotes Right Ventricle Failure in Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) often results in death from right ventricular failure (RVF). NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)-macrophage activation may promote RVF in PAH. Objectives: Evaluating the contribution of the NLRP3 inflammasome in RV macrophages to PAH RVF. Methods: Rats with decompensated RV hypertrophy (monocrotaline [MCT] and Sugen-5416 hypoxia [SuHx]) were compared with compensated RV hypertrophy rats (pulmonary artery banding). Echocardiography and right heart catheterization were performed. Macrophages, atrial natriuretic peptides, and fibrosis were evaluated by microscopy or flow cytometry. NLRP3 inflammasome activation and cardiotoxicity were confirmed by immunoblot and in vitro strategies. MCT rats were treated with SC-144 (a GP130 antagonist) or MCC950 (an NLRP3 inhibitor). Macrophage-NLRP3 activity was evaluated in patients with PAH RVF. Measurements and Main Results: Macrophages, fibrosis, and atrial natriuretic peptides were increased in MCT and SuHx RVs but not in left ventricles or pulmonary artery banding rats. Although MCT RV macrophages were inflammatory, lung macrophages were antiinflammatory. CCR2+ macrophages (monocyte-derived) were increased in MCT and SuHx RVs and highly expressed NLRP3. The macrophage-NLRP3 pathway was upregulated in patients with PAH with decompensated RVs. Cultured MCT monocytes showed NLRP3 activation, and in coculture experiments resulted in cardiomyocyte mitochondrial damage, which MCC950 prevented. In vivo, MCC950 reduced NLRP3 activation and regressed pulmonary vascular disease and RVF. SC-144 reduced RV macrophages and NLRP3 content, prevented STAT3 (signal transducer and activator of transcription 3) activation, and improved RV function without regressing pulmonary vascular disease. Conclusions: NLRP3-macrophage activation occurs in the decompensated RV in preclinical PAH models and patients with PAH. Inhibiting GP130 or NLRP3 signaling improves RV function. The concept that PAH RVF results from RV inflammation rather than solely from elevated RV afterload suggests a new therapeutic paradigm.

Effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced GIST.

BACKGROUND: Currently, the effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced gastrointestinal stromal tumors (LA-GIST) remains unclear. This study aims to investigate the relationship between changes in skeletal muscle and postoperative complications, survival and tumor response in patients with LA-GIST during neoadjuvant therapy with imatinib. METHODS: We retrospectively analyzed pre- and post-treatment computed tomography images of 57 GIST patients who underwent radical surgery after neoadjuvant therapy with imatinib from January 2013 to March 2019. Skeletal muscle index (SMI) was measured at the L3 vertebral level in all patients. A cut-off value (SMI < 52.3 cm2/m2 and < 38.6 cm2/m2 for men and women, respectively) published in a previous study was used to define sarcopenia. Based on gender, we defined ΔSMI (%)/250 days above 9.69% for men and ΔSMI (%)/250 days above 7.63% for women as significant muscle loss (SML). Factors associated with postoperative complications and tumor response were analyzed using logistic regression, and predictors affecting patient prognosis were analyzed using Cox regression. RESULTS: Of the 57 patients, sarcopenia was present before and after neoadjuvant therapy in 20 (35.09%) and 28 (49.12%) patients, respectively. It was not associated with immediate or long-term clinical outcomes. However, patients with SML during neoadjuvant therapy had a higher incidence of postoperative complications (60.00% vs. 25.00%, p = 0.008), worse pathological regression (44.00% vs. 75.00%, p = 0.017) and worse 3-year survival (Male, 68.75% vs. 95.45%, p = 0.027; Female, 66.67% vs. 100.00%, p = 0.046) than patients without SML. CONCLUSION: The development of SML during neoadjuvant therapy in LA-GIST patients, rather than pre- and post-treatment sarcopenia, is a major prognostic factor for the long-term prognosis and is also associated with recent postoperative complication rates and pathological regression.

Combined exposure to multiple metals on cardiovascular disease in NHANES under five statistical models.

BACKGROUND: It is well-documented that heavy metals are associated with cardiovascular disease (CVD). However, there is few studies exploring effect of metal mixture on CVD. Therefore, the primary objective of present study was to investigate the joint effect of heavy metals on CVD and to identify the most influential metals in the mixture. METHODS: Original data for study subjects were obtained from the National Health and Nutrition Examination Survey. In this study, adults with complete data on 12 kinds of urinary metals (antimony, arsenic, barium, cadmium, cobalt, cesium, molybdenum, mercury, lead, thallium, tungsten, and uranium), cardiovascular disease, and core covariates were enrolled. We applied five different statistical strategies to examine the CVD risk with metal exposure, including multivariate logistic regression, adaptive elastic net combined with Environmental Risk Score, Quantile g-computation, Weighted Quantile Sum regression, and Bayesian kernel machine regression. RESULTS: Higher levels of cadmium, tungsten, cobalt, and antimony were significantly associated with Increased risk of CVD when covariates were adjusted for multivariate logistic regression. The results from multi-pollutant strategies all indicated that metal mixture was positively associated with the risk of CVD. Based on the results of multiple statistical strategies, it was determined that cadmium, tungsten, cobalt, and antimony exhibited the strongest positive correlations, whereas barium, lead, molybdenum, and thallium were most associated with negative correlations. CONCLUSION: Overall, our study demonstrates that exposure to heavy metal mixture is linked to a higher risk of CVD. Meanwhile, this association may be driven primarily by cadmium, tungsten, cobalt, and antimony. Further prospective studies are warranted to validate or refute our primary findings as well as to identify other important heavy metals linked with CVD.

The association between pregnancy and COVID-19: A systematic review and meta-analysis.

OBJECTIVES: The purpose of this study was to compare and determine whether there were any differences in clinical outcomes between pregnant and non-pregnant women who had been infected with COVID-19. METHODS: A literature search was performed in 9 databases on November 20, 2021. The relative risk (RR) with 95% confidence interval (95% CI) was used to estimate the effect of pregnancy on COVID-19 outcomes. The I square value was used to assess heterogeneity, and the random or the fixed-effects model were adopted. Sensitivity and publication bias analyses were performed. RESULTS: This study included 8 published studies with 859,278 COVID-19 female patients. The incidences of fever and cough among pregnant women with COVID-19 were 19.07% and 28.79%, respectively. Pregnancy was associated with significantly increased risks of intensive care unit (ICU) admission (RR = 2.23, 95% CI = 1.58-3.16) and ventilation (RR = 2.13, 95% CI = 1.06-4.28), but was not associated with a statistically significant increase in mortality. CONCLUSIONS: Our results suggest that pregnant women with COVID-19 have a significantly higher probability of being hospitalized to the ICU and ventilation than non-pregnant women with COVID-19. To avoid these adverse outcomes, pregnant women should take precautions (for example, reduce going out, maintain social distance, and wear a mask) to avoid COVID-19 infection. Finally, additional research into the fetal outcomes is required to better investigate the impact of COVID-19 on pregnancy.

The molecular mechanisms of oxygen-sensing in human ductus arteriosus smooth muscle cells: A comprehensive transcriptome profile reveals a central role for mitochondria.

The ductus arteriosus (DA) connects the fetal pulmonary artery and aorta, diverting placentally oxygenated blood from the developing lungs to the systemic circulation. The DA constricts in response to increases in oxygen (O2) with the first breaths, resulting in functional DA closure, with anatomic closure occurring within the first days of life. Failure of DA closure results in persistent patent ductus arteriosus (PDA), a common complication of extreme preterm birth. The DA's response to O2, though modulated by the endothelium, is intrinsic to the DA smooth muscle cells (DASMC). DA constriction is mediated by mitochondrial-derived reactive oxygen species, which increase in proportion to arterial partial pressure of oxygen (PaO2). The resulting redox changes inhibit voltage-gated potassium channels (Kv) leading to cell depolarization, calcium influx and DASMC constriction. To date, there has not been an unbiased assessment of the human DA O2-sensors using transcriptomics, nor are there known molecular mechanisms which characterize DA closure. DASMCs were isolated from DAs obtained from 10 term infants at the time of congenital heart surgery. Cells were purified by flow cytometry, negatively sorting using CD90 and CD31 to eliminate fibroblasts or endothelial cells, respectively. The purity of the DASMC population was confirmed by positive staining for α-smooth muscle actin, smoothelin B and caldesmon. Cells were grown for 96 h in hypoxia (2.5% O2) or normoxia (19% O2) and confocal imaging with Cal-520 was used to determine oxygen responsiveness. An oxygen-induced increase in intracellular calcium of 18.1% ± 4.4% and SMC constriction (-27% ± 1.5% shortening) occurred in all cell lines within five minutes. RNA sequencing of the cells grown in hypoxia and normoxia revealed significant regulation of 1344 genes (corrected p < 0.05). We examined these genes using Gene Ontology (GO). This unbiased assessment of altered gene expression indicated significant enrichment of the following GOterms: mitochondria, cellular respiration and transcription. The top regulated biologic process was generation of precursor metabolites and energy. The top regulated cellular component was mitochondrial matrix. The top regulated molecular function was transcription coactivator activity. Multiple members of the NADH-ubiquinone oxidoreductase (NDUF) family are upregulated in human DASMC (hDASMC) following normoxia. Several of our differentially regulated transcripts are encoded by genes that have been associated with genetic syndromes that have an increased incidence of PDA (Crebb binding protein and Histone Acetyltransferase P300). This first examination of the effects of O2 on human DA transcriptomics supports a putative role for mitochondria as oxygen sensors.

CCNB2 expression correlates with worse outcomes in breast cancer patients: a pooled analysis.

Cyclin B2 (CCNB2) is upregulated in Breast Cancer (BC) and associated with worse relapse-free survival (RFS). However, its correlation with other clinical outcomes in BC was yet to be clarified. Therefore, this study aimed to explore the clinical significance of CCNB2 in BC. A comprehensive search was performed in PrognoScan and Gene Expression Omnibus (GEO) databases by searching the keywords of CCNB2 and breast cancer. Pooled hazard ratios (HRs) of overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and disease-free survival (DFS), and their corresponding 95 percent confidence intervals (CI) were calculated. Sensitivity analysis by omitting one study at a time and publication bias assessment by Egger's test and Begg's test were conducted. The clinical outcomes were externally verified via Kaplan-Meier Plotter. All of the statistical analyses were performed through STATA 17.0, and P values of less than 0.05 were taken to be statistically significant. Seven records with 1,074 participants were included for OS, with HR of 1.71 (95 percent CI = 1.24-2.35). Verification through Kaplan-Meier Plotter online tool based on 1,897 patients showed an HR of 1.75 (95 percent CI = 1.45-2.12, P < .01). For RFS, 11 records with 1,253 participants were included with the pooled HR of 1.37 (95 percent CI: 1.10-1.71). Verification based on 4,929 patients found and HR of 1.97 (95 percent CI = 1.78-2.19, P < .01). Regarding DMFS, the pooled HR of 10 records with 1,395 participants was 1.60 (95 percent CI: 1.24-2.05) and verification based on 2,765 patients revealed an HR of 1.97 (95 percent CI = 1.68-2.31, P < .01). For DSS, four records with 689 participants were included for DSS, with HR of 1.38 (95 percent CI = 0.59-3.24). The HR of DFS was 1.60 (95 percent CI: 0.46-5.51) after pooling 3 records with 379 participants. High expression of CCNB2 in BC is associated with worse OS, RFS, and DMFS, but not with DSS and DFS. More well-designed studies from different populations and different BC types are still needed.

Occupational therapy needs of patients with thoracic cancer at the time of diagnosis: findings of a dedicated rehabilitation service.

PURPOSE: Guidelines recommend screening patients with cancer to identify their rehabilitation needs. To help quantify this area of need and associated workload from an occupational therapy perspective in patients with thoracic cancer, we report the experiences of a dedicated rehabilitation service. METHODS: Consecutive patients were screened soon after diagnosis using items associated with occupational performance in the Sheffield Profile for Assessment and Referral for Care questionnaire. Those reporting predetermined levels of distress underwent a full occupational therapy evaluation; this generated a problem list from which individualised goals and interventions were instigated. RESULTS: Of 540 patients screened, 273 (51 %) reported levels of distress which warranted a full occupational therapy assessment. Of these, 260 (95%) reported a total of 681 problems (median of 4 [2-5] per patient). Mostly these lay within the domain of self care (553, 78%) in the categories of transfers, functional mobility and bathing/showering. A total of 646 goals (median of 2 [1-3] per patient) were formulated, resulting in 652 individual interventions, most frequently the provision of equipment (79%) or advice (32%) and referral to another professional/agency (23%). Patients considered that most goals were achieved (98%) and that the provision of equipment was useful (97%). CONCLUSIONS: About half of patients with thoracic cancer screened have occupational therapy needs around the time of diagnosis. Problems are mostly in the area of self-care, with equipment provision the most frequent intervention provided. Future work should examine the efficacy of occupational therapy interventions further.

Using omics to breathe new life into our understanding of the ductus arteriosus oxygen response.

The ductus arteriosus (DA) connects the aorta to the pulmonary artery (PA), directing placentally oxygenated blood away from the developing lungs. High pulmonary vascular resistance and low systemic vascular resistance facilitate shunting of blood in utero from the pulmonary to the systemic circulation through the widely patent DA, thereby optimizing fetal oxygen (O2) delivery. With the transition from fetal (hypoxia) to neonatal (normoxia) oxygen conditions, the DA constricts while the PA dilates. This process often fails in prematurity, promoting congenital heart disease. Impaired O2-responsivness in the DA promotes persistent ductus arteriosus (PDA), the most common form of congenital heart disease. Knowledge of DA oxygen sensing has greatly advanced in the past few decades, however we still lack a complete understanding of the sensing mechanism. The genomic revolution of the past two decades has facilitated unprecedented discovery in every biological system. This review will demonstrate how multiomic integration of data generated from the DA can breathe new life into our understanding of the DA's oxygen response.

Clinical Features and Prognosis of Uncommon Metastatic Breast Cancer: A Retrospective Analysis of 82 Cases.

With the improvement of diagnostic techniques, numerous uncommon metastases derived from breast cancer were reported. However, very few studies explored the clinical characteristics and prognostic patterns of these patients. A total of 82 cases of uncommon metastatic breast cancer (MBC) registered at our hospital from January 1, 2010, to July 1, 2022, were selected for this retrospective study. The diagnoses of uncommon metastases were based on pathology, and the potential prognostic indicators (overall survival [OS], uncommon disease-free interval [uDFI], and remaining survival [RS]) were estimated. The uncommon metastases involved distant soft tissue, parotid gland, thyroid, digestive system, urinary system, reproductive system, bone marrow, and pericardium. Stepwise multivariate Cox regression analysis indicates age ≤ 35 is an independent risk factor of poor outcome of OS, uDFI, and RS in uncommon MBC patients. Meanwhile, uncommon metastasis combined with common visceral metastasis is an independent risk factor for poor RS of uncommon MBC patients, with a hazard ratio of 6.625 (95% confidence interval = 1.490-29.455, P = .013). Post hoc pairwise comparisons showed that uncommon MBC patients who developed bone-only metastasis survived longer than those concomitant with common visceral metastasis (P = .029). Although the incidence is low, uncommon MBC may involve multiple metastatic sites. The delayed diagnosis of uncommon metastases could lead to systemic progression of the disease. However, patients who only develop uncommon metastasis have a significantly better prognosis than that of those combined with common visceral metastasis. Even for those complicated by bone-only metastasis, active treatment of bone metastases can still achieve substantially longer survival.

Psychosocial interprofessional perinatal education: Design and evaluation of an interprofessional learning experience to improve students' collaboration skills in perinatal mental health.

BACKGROUND: Perinatal mental health disorders are one of the leading causes of maternal illness and suffering and care and services need to be well coordinated by an interprofessional team who are skilled in working collaboratively. AIM: The aim of this paper is to describe the design and evaluation of an innovative interprofessional education initiative to increase midwives and other health professional students' knowledge and skills in caring collaboratively for women with psychosocial issues in the perinatal period, including women experiencing domestic and family violence. METHODS: The Psychosocial Interprofessional Perinatal Education workshop was designed for midwifery, psychology, social work and medical students. It provided a simulated learning experience with case studies based on real life situations. Students undertook pre and post surveys to measure changes in students' perceptions of interprofessional collaboration and their experiences of participating in the interprofessional simulation-based learning activity. Quantitative survey data were analysed using paired t-tests and a qualitative content analysis was undertaken on the open-ended questions in the survey. FINDINGS: Comparison of pre and post surveys found students from all disciplines reported feeling more confident working interprofessionally following the workshop. The following categories were generated from analysis of the open ended survey data: Greater understanding of each others' roles; Recognising benefits of interprofessional collaboration; Building on sense of professional identity; Respecting each other and creating a level playing field; and Filling a pedagogical gap. CONCLUSION: Through this innovative, simulated interprofessional education workshop students developed skills essential for future collaborative practice to support women and families experiencing psychosocial distress.

Exploratory analysis of the association between organophosphate ester mixtures with high blood pressure of children and adolescents aged 8-17 years: cross-sectional findings from the National Health and Nutrition Examination Survey.

Epidemiological studies on the effect of organophosphate esters (OPEs) on high blood pressure (BP) among children and adolescents are scant. Therefore, the main objective of the present study was to explore the effect of exposure to OPEs on high BP among children and adolescents. A total of 1340 participants were included in the current analyses. Multivariable logistic regression models were implemented to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to examine the association between OPE metabolites and high BP. We also assessed the modified effect of sex, age, and overweight/obesity on this association. Furthermore, quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) were exhibited to analyze the association between multiple OPE metabolite mixtures and high BP. After adjusting for covariates, the highest (vs. lowest) tertiles of bis (1-choloro-2-propyl) phosphate (BCPP), bis-2-chloroethyl phosphate (BCEP), and di-n-butyl phosphate (DBUP) were associated with 1.23 (95% CI: 0.83, 1.83), 1.27 (95% CI: 0.85, 1.92), and 1.01 (95% CI: 0.67, 1.53) odds ratios for high BP, respectively. In the Qgcomp, a quartile increase in OPE metabolite mixtures was weakly associated with an elevated risk of high BP (adjusted OR: 1.06, 95CI%: 0.81, 1.37). The results from BKMR showed a positive trend of association between OPE metabolite mixture on the risk of high BP. In conclusion, our study demonstrated that higher levels of BCPP, BCEP, and DBUP were weakly associated with high BP among US children and adolescents. Moderate evidence suggested OPE metabolite mixtures had positive joint effects on high BP. Consequently, longitudinal studies with repeated measurements are warranted to examine the relationships between multiple OPE metabolites and high blood pressure among children and adolescents.

Comparison of short-term efficacy and safety between total robotic and total 3D laparoscopic distal radical gastrectomy for gastric cancer in Enhanced Recovery After Surgery (ERAS) protocol: a propensity score matching study.

BACKGROUND: The application of Enhanced Recovery After Surgery (ERAS) protocol in gastrointestinal surgery has been widely accepted. The aim of this study was to compare the effect of ERAS in total robotic distal gastrectomy (TRDG) versus 3D total laparoscopic distal gastrectomy (3D-TLDG) for gastric cancer. METHODS: We retrospectively evaluated 73 patients underwent TRDG and 163 patients who received 3D-TLDG. The propensity score was used for matching analysis according to a 1:1 ratio, so that there was no significant difference in the baseline data between the two groups. The short-term effect and safety of the two groups were compared. RESULTS: The TRDG group had a less intraoperative bleeding (30.21 ± 13.78 vs. 41.44 ± 17.41 ml, P < 0.001), longer intraoperative preparation time (31.05 ± 4.93 vs. 15.48 ± 2.43 min, P < 0.001), shorter digestive tract reconstruction time (32.67 ± 4.41 vs. 39.78 ± 4.95 min, P < 0.001), shorter postoperative ambulation time (14.07 ± 8.97 vs. 17.49 ± 5.98 h, P = 0.007), shorter postoperative anal exhaust time (1.78 ± 0.79 vs. 2.18 ± 0.79 days, P = 0.003), shorter postoperative hospital stay (7.74 ± 3.15 vs. 9.97 ± 3.23 days, P < 0.001), lower postoperative pain score (P = 0.006) and higher hospitalization cost (89,907.15 ± 17,147.19 vs. 125,615.82 ± 11,900.80 RMB, P < 0.001) than the 3D-TLDG group. CONCLUSION: TRDG and 3D-TLDG under ERAS protocol are safe and feasible. Compared with 3D-TLDG, the TRDG has better intraoperative bleeding control effect and greater advantages in digestive tract reconstruction. After the combination of ERAS protocol, TRDG also has certain advantages in the recovery process of patients after surgery.

Association between household air pollution and all-cause and cause-specific mortality: a systematic review and meta-analysis.

Recently, a growing number of epidemiological studies have examined the relationship between household air pollution (HAP) and all-cause and cause-specific mortality. While the results were not entirely consistent, the current study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol to conduct a comprehensive review and meta-analysis. Data sources were PubMed, Web of Science, Embase, and Cochrane Library for studies published up to 12 May 2022. The pooled relative risks (RRs) with 95% confidence intervals (CI) were used to estimate the effect of household air pollution on all-cause and cause-special mortality. Then I square value (I2) was used to assess heterogeneity, and random-effects model was used as the pooling method. Seventeen studies were included in the quantitative analysis. Our results showed a significant association between household air pollution and increased risks of all-cause mortality (RR = 1.12, 95% CI = 1.06-1.19) and cardiovascular disease mortality (RR = 1.13, 95% CI = 1.04-1.24). Similarly, the associations between household air pollution and mortality from other specific causes (respiratory, ischemic heart disease, stroke, and total cancer) were positive, although they were not statistically significant. The study suggests that exposure to household air pollution increases the risk of all-cause mortality and cardiovascular disease mortality. In addition, our results found a trend of increased mortality from the respiratory system, ischemic heart disease, stroke, and total cancer, with household air pollution.

Combined exposure to multiple dioxins and dioxin-like polychlorinated biphenyls on hypertension among US adults in NHANES: a cross-sectional study under three statistical models.

Dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) are mainly released as by-products of human activities, often in the form of mixtures, and the potential harm on human health deserves attention. Therefore, our study aimed to analyze the combined effect of dioxins and DL-PCB exposures on hypertension (HTN) among US adults. Data of eligible participants were acquired from the National Health and Nutrition Examination Survey (NHANES). Multiple logistic regression models with adjustment for covariates were applied to explore the associations between 13 persistent organic pollutants (POPs) and HTN. Stratified analyses and interaction analyses were then conducted by age and gender. Finally, the combined effects of dioxins and DL-PCBs on HTN were assessed by the weighted quantile sum (WQS) model and the Bayesian kernel machine regression (BKMR) model. A total of 976 adults were included in our study, of whom 397 had HTN. Spearman correlations indicated positive correlations among 13 POPs. And most of them (except PCB28, PCB66, and 1,2,3,4,7,8,9-hpcdf) had significant effects on HTN. The result of WQS revealed that mixed exposure to dioxins and DL-PCBs was significantly associated with increased risk of HTN (OR: 2.205; 95% CIs: 1.555, 3.127). The BKMR model also presented a positive trend of HTN risk with exposure to multiple dioxins and DL-PCBs. And 1,2,3,4,6,7,8,9-ocdd may be the main factor for this positive association. Considering the limitations of our cross-sectional study with the small sample, further prospective studies are necessary to validate our findings.

A Systematic Review and Meta-analysis of the Association Between SARS-CoV-2 Vaccination and Myocarditis or Pericarditis.

INTRODUCTION: There have been reports of potential negative cardiovascular effects from the COVID-19 vaccine, such as myocarditis or pericarditis. This study sought to ascertain the risk of myocarditis/pericarditis after COVID-19 vaccination by conducting an extensive meta-analysis of published cases. METHODS: A systematic literature search was conducted in 7 online databases by March 31, 2022. Heterogeneity was tested by I2 index. RR and 95% CI were pooled through either random-effect or fixed-effect models. Sensitivity analysis and publication bias were also conducted. RESULTS: A total of 11 studies with 58,620,611 subjects were included. COVID-19 vaccination correlated with an increased risk of myocarditis or pericarditis (RR=2.04; 95% CI=1.33, 3.14). In addition, an increased risk of myocarditis or pericarditis in people who received the second dose of COVID-19 vaccine compared with that in those who received only the first dose of COVID-19 vaccine was also found (RR=4.06; 95% CI=2.08, 7.92). An increased incidence of pericarditis or myocarditis was noted predominantly in those who received BNT162b2 and mRNA-1273 vaccines (RR=2.19; 95% CI=1.46, 3.29 and RR=4.15; 95% CI=1.87, 9.22, respectively). DISCUSSION: Study results indicate that a higher incidence of myocarditis or pericarditis was found after COVID-19 vaccination. In addition, the risk of developing myocarditis or pericarditis was greater after the second dose than after the first dose. Nevertheless, the risks of myocarditis and pericarditis in COVID-19 vaccine recipients are still significantly lower than the health risks observed in patients with COVID-19. Therefore, the benefits and harms must be carefully assessed to determine the best management option for patients who are in the high-risk group of myocarditis or pericarditis.

Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site IQ Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus.

Background As partial pressure of oxygen (pO2) rises with the first breath, the ductus arteriosus (DA) constricts, diverting blood flow to the pulmonary circulation. The DA's O2 sensor resides within smooth muscle cells. The DA smooth muscle cells' mitochondrial electron transport chain (ETC) produces reactive oxygen species (ROS) in proportion to oxygen tension, causing vasoconstriction by regulating redox-sensitive ion channels and enzymes. To identify which ETC complex contributes most to DA O2 sensing and determine whether ROS mediate O2 sensing independent of metabolism, we used electron leak suppressors, S1QEL (suppressor of site IQ electron leak) and S3QEL (suppressor of site IIIQo electron leak), which decrease ROS production by inhibiting electron leak from quinone sites IQ and IIIQo, respectively. Methods and Results The effects of S1QEL, S3QEL, and ETC inhibitors (rotenone and antimycin A) on DA tone, mitochondrial metabolism, O2-induced changes in intracellular calcium, and ROS were studied in rabbit DA rings, and human and rabbit DA smooth muscle cells. S1QEL's effects on DA patency were assessed in rabbit kits, using micro computed tomography. In DA rings, S1QEL, but not S3QEL, reversed O2-induced constriction (P=0.0034) without reducing phenylephrine-induced constriction. S1QEL did not inhibit mitochondrial metabolism or ETC-I activity. In human DA smooth muscle cells, S1QEL and rotenone inhibited O2-induced increases in intracellular calcium (P=0.02 and 0.001, respectively), a surrogate for DA constriction. S1QEL inhibited O2-induced ROS generation (P=0.02). In vivo, S1QEL prevented O2-induced DA closure (P<0.0001). Conclusions S1QEL, but not S3QEL, inhibited O2-induced rises in ROS and DA constriction ex vivo and in vivo. DA O2 sensing relies on pO2-dependent changes in electron leak at site IQ in ETC-I, independent of metabolism. S1QEL offers a therapeutic means to maintain DA patency.

Association of sugar-sweetened beverages with the risk of colorectal cancer: a systematic review and meta-analysis.

The association between sugar-sweetened beverages intake and colorectal cancer (CRC) remains controversial. A metaanalysis was performed to clarify the correlation between sugar-sweetened beverages and CRC risk/mortality. A systematic literature search was conducted in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Sinomed (CBM), Wanfang Data Knowledge Service Platform, and China Science and Technology Journal VIP database. Articles were restricted to be available in any language until March 31, 2022. The highest exposed categories were used to calculate the pooled relative risks (RR) values. Pooled relative risks (RR) and 95% confidence intervals (CI) were used to estimate the association of sugar-sweetened beverages with CRC risk and mortality. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic. A total of 17 studies (6 case-control and 11 cohort) involving 557,391 subjects were included in this meta-analysis. The pooled RRs for CRC incidence and mortality among people taking sugar-sweetened beverages were 1.17 (95% CI: 1.07-1.28) and 1.13 (95% CI: 0.99-1.29), respectively. In subgroup analysis, a correlation was found in the distal colon with a pooled RR of 1.41 (95% CI: 1.10-1.80). There was no correlation in the proximal colon with a pooled RR of 1.58 (95% CI: 0.79-3.17). We found statistically significant associations between CRC incidence and sugar-sweetened beverages intake in North America and Oceania, with pooled RRs of 1.16 (95% CI: 1.00-1.33) and 1.32 (95% CI: 1.13-1.55), respectively. In sensitivity analysis, after excluding each study and calculating heterogeneity and effect sizes, there was still a correlation between sugar-sweetened beverages intake and CRC risk. This meta-analysis suggests that sugar-sweetened beverages intake may increase CRC risk, independent of CRC mortality. Whether CRC risk increases with increased sugar-sweetened beverage intake needs further investigation in the future. This meta-analysis aimed to indicate the relationship between sugar-sweetened beverages intake and the risk and mortality of colorectal cancer. A total of 17 studies involving 557,391 subjects were included. The results showed that sugar-sweetened beverages may increase the risk of colorectal cancer but may not be associated with colorectal cancer mortality.