Targeting a cardiac abundant and fibroblasts-specific piRNA (CFRPi) to attenuate and reverse cardiac fibrosis in pressure-overloaded heart failure.

Cardiac fibrosis under chronic pressure overload is an end-stage adverse remodeling of heart. However, current heart failure treatments barely focus on anti-fibrosis and the effects are limited. We aimed to seek for a cardiac abundant and cardiac fibrosis specific piRNA, exploring its underlying mechanism and therapeutic potential. Whole transcriptome sequencing and the following verification experiments identified a highly upregulated piRNA (piRNA-000691) in transverse aortic constriction (TAC) mice, TAC pig, and heart failure human samples, which was abundant in heart and specifically expressed in cardiac fibroblasts. CFRPi was gradually increased along with the progression of heart failure, which was illustrated to promote cardiac fibrosis by gain- and loss-of-function experiments in vitro and in vivo. Knockdown of CFRPi in mice alleviated cardiac fibrosis, reversed decline of systolic and diastolic functions from TAC 6 weeks to 8 weeks. Mechanistically, CFRPi inhibited APLN, a protective peptide that increased in early response and became exhausted at late stage. Knockdown of APLN in vitro notably aggravated cardiac fibroblasts activation and proliferation. In vitro and in vivo evidence both indicated Pi3k-AKT-mTOR as the downstream effector pathway of CFRPi-APLN interaction. Collectively, we here identified CFPPi as a heart abundant and cardiac fibrosis specific piRNA. Targeting CFRPi resulted in a sustainable increase of APLN and showed promising therapeutical prospect to alleviate fibrosis, rescue late-stage cardiac dysfunction, and prevent heart failure.

A nomogram model based on the combination of the systemic immune-inflammation index, body mass index, and neutrophil/lymphocyte ratio to predict the risk of preoperative deep venous thrombosis in elderly patients with intertrochanteric femoral fracture: a retrospective cohort study.

OBJECTIVES: Deep vein thrombosis (DVT) has been considered as a frequent and serious consequence of intertrochanteric femoral fractures in the elderly. Several negative repercussions of DVT can be considerably mitigated by its timely recognition and treatment. The current work was aimed at exploring the factors independently predicting DVT among cases suffering from intertrochanteric femoral fractures and validate their predictive usefulness in diagnosing DVT. METHODS: Between April 2017 and July 2022, clinical information from 209 cases showing preoperative DVT for femoral intertrochanteric fractures were retrospectively evaluated. In patients with femoral intertrochanteric fractures, logistic regression analysis with a backward stepwise method was adopted for detecting independent predictors for the diagnosis of preoperative DVT. Using multivariate logistic regression, a nomogram prediction model was developed and verified with the testing group. RESULTS: According to multivariate logistic regression model, body mass index (BMI) (OR 0.79, 95% CI 0.63-0.99, P = 0.042), neutrophil/lymphocyte ratio (NLR) (OR 7.29, 95% CI 1.53, 34.64, P = 0.0012), and systemic immune-inflammation index (SII) (OR 6.61, 95% CI 2.35, 18.59, P = 0.001) were independent predictors for DVT before surgery among cases developing intertrochanteric femoral fracture. AUC values were 0.862 and 0.767 for training and testing groups, separately, while their mean errors in the calibration curve were 0.027 and 0.038 separately. Decision curve analysis (DCA) curve revealed a high value of clinical application for both groups. CONCLUSION: Upon admission, BMI, NLR, and SII are independent predictors of DVT before surgery among cases developing intertrochanteric femoral fractures. Additionally, the nomogram based on the BMI, NLR, and SII can assist clinicians in determining if preventive and symptomatic therapies are required to improve DVT prognosis and reduce its associated mortality.

Impact of Virtual Operating Room Tours on Relieving Perioperative Anxiety in Adult Patients: A Systematic Review.

PURPOSE: To evaluate the effects of virtual operating room tours on perioperative anxiety in adult patients. DESIGN: This study was a systematic review of randomized controlled trials (RCTs). METHODS: PubMed, Cochrane Library, Embase, Web of Science, Proquest, Scopus, SinoMed, CNKI, and WanFang were systematically searched for English and Chinese RCTs published up to November 18, 2021, for studies on the effectiveness of virtual operating room tours in reducing perioperative anxiety in adult patients (>18 years of age). Primary and secondary outcomes were perioperative anxiety levels and understanding level of perioperative information and patient satisfaction, respectively. The data were synthesized using a qualitative method. FINDINGS: Five studies were found eligible for inclusion; 3 studies showed a significant decrease in perioperative anxiety levels in patients of the virtual operating room tours group. Furthermore, the overall satisfaction, understanding of perioperative information, and preoperative preparedness were significantly enhanced respectively in 3 studies. CONCLUSIONS: This study showed the effectiveness of virtual operating room tour on alleviating perioperative anxiety on adult patients. Furthermore, the satisfaction and understanding of perioperative information in intervention group improved owing to these tours. Future quantitative studies are needed to support these findings.

Clinical Symptoms Affect Treatment and Prognosis in Pediatric Patients with Congenital Pulmonary Airway Malformation: A Propensity Score Matching Retrospective Cohort Study.

OBJECTIVES: Surgery for asymptomatic congenital pulmonary airway malformation patients is still debatable at this time. This study aims to investigate the safety and efficacy of surgery for asymptomatic patients, as well as the factors influencing the symptoms of this group of patients. METHODS: An institutional database was sampled for congenital pulmonary airway malformation patients. Patients were divided into the symptomatic group and the asymptomatic group. Propensity score matching (PSM) analysis selected patients in each group to compare perioperative outcomes. A multivariable logistic regression analysis was performed to investigate the potential influences on symptomatic lesions. RESULTS: The asymptomatic group had better perioperative results than the symptomatic group, including shorter operating times (119.39 ± 49.42 min vs 100.73 ± 23.09 min, P = 0.031), shorter postoperative mechanical ventilation (2 h [0.5-46] vs 1 h [0.5-5], P = 0.002), shorter chest tube durations (4d [2-29] vs 3d [2-10], P = 0.007), and shorter postoperative hospital stays (10d [6-36] vs 8d [6-16], P < 0.001). With the conversion to thoracotomy and postoperative complications, there was no statistically significant difference between the two PSM-matched groups (P > 0.05). Age (p = 0.037), postnatal diagnosis (p = 0.018), and maximum cyst diameter (p = 0.032) were found to be independent variables associated with symptomatic lesions by multivariable logistic regression. CONCLUSIONS: Patients with congenital pulmonary airway malformation appear to have better perioperative outcomes before the beginning of symptoms. Symptomatic pulmonary lesions were associated with age, postnatal diagnosis, and maximum cyst diameter. LEVEL OF EVIDENCE: Level III.

Joint association of polycyclic aromatic hydrocarbons and heavy metal exposure with pulmonary function in children and adolescents aged 6-19 years.

Studies have reported associations between polycyclic aromatic hydrocarbon (PAH) or heavy metal (HM) exposure and respiratory diseases. However, evidence of their joint associations with pulmonary function, especially in children and adolescents aged 6-19 years, is lacking. We utilized cross-sectional data from 1,734 children and adolescents aged 6-19 years collected in the National Health and Nutrition Examination Survey 2007-2012 and analysed mixed PAH and mixed HM exposures and their joint association with pulmonary function by applying weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Multivariate linear regressions were carried out to determine the relationships between individual urinary PAH metabolites or blood HM levels and pulmonary function indices. We found that mixed PAHs and HMs were negatively related to forced expiratory volume in 1 s (FEV1) in subjects aged 6-12 years (all p values < 0.05). We found synergistic associations of PAH and HM exposure on pulmonary function impairment, mainly in children; lead (Pb) was the most damaging. In the analysis of individual PAH metabolites or HMs, Pb exposure was negatively associated with FEV1 values in all subgroups (all p values < 0.05). Thus, our findings indicate that increased PAH or HM exposure is associated with impairments to pulmonary function and that this association is more pronounced in children.

Association of increased risk of cardiovascular diseases with higher levels of perfluoroalkylated substances in the serum of adults.

Evidence showing the association of perfluoroalkylated substance (PFAS) exposure with CVD risk is scarce. The objective of this study was to explore the relationships of CVD risk with mixed or individual serum PFAS levels among general adults. We analyzed combined data of 7904 adults who participated in the National Health and Nutrition Examination Survey 2003-2012 with a Bayesian kernel machine regression (BKMR) to examine the relationships of individual or mixed PFAS exposure with total CVD risk. A logistic regression model and restricted cubic spline (RCS) regression with multivariate adjustment were conducted to assess the relationships between individual serum PFAS levels and the risk of total CVD or its subtypes. A mediation model was applied to investigate how C-reactive protein (CRP) levels mediate the strength of the association. The BKMR results indicated a positive relationship between mixed PFAS exposure and total CVD risk; among the PFASs, perfluorooctane sulfonic acid (PFOS) had the highest posterior inclusion probability. As determined by logistic regression, a log-unit change in PFOS levels was positively related to a higher risk of heart attack and stroke in males (both P < 0.05). A nonlinear relationship was found between PFOS levels and stroke risk (P for nonlinearity = 0.04), as illustrated in the RCS plot. The mediation analysis showed that CRP levels mediated 8% and 1.2% of the relationship between serum PFOS and PFNA levels, respectively, and the prevalence of stroke. A significant relationship between higher serum PFAS concentrations and an increased risk of CVD was observed, mainly in males.

Engineering Multifunctional Hydrogel With Osteogenic Capacity for Critical-Size Segmental Bone Defect Repair.

Treating critical-size segmental bone defects is an arduous challenge in clinical work. Preparation of bone graft substitutes with notable osteoinductive properties is a feasible strategy for critical-size bone defects. Herein, a biocompatible hydrogel was designed by dynamic supramolecular assembly of polyvinyl alcohol (PVA), sodium tetraborate (Na2B4O7), and tetraethyl orthosilicate (TEOS). The characteristics of the supramolecular hydrogel were evaluated by rheological analysis, swelling ratio, degradation experiments, and scanning electron microscopy (SEM). In in vitro experiments, this TEOS-hydrogel had self-healing property, low swelling rate, degradability, good biocompatibility, and induced osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by upregulating the expression of Runx-2, Col-1, OCN, and osteopontin (OPN). In segmental bone defect rabbit models, the TEOS-containing hydrogel accelerated bone regeneration, thus restoring the continuity of bone and recanalization of the medullary cavity. The abovementioned results demonstrated that this TEOS-hydrogel has the potential to realize bone healing in critical-size segmental bone defects.

The relationship between multiple perfluoroalkyl substances and cardiorespiratory fitness in male adolescents.

Exposure to perfluoroalkyl substances (PFASs) is associated with a number of adverse health outcomes. However, the relationship between mixed and individual PFAS exposure and cardiorespiratory fitness (CRF) in adolescents remains unclear. We used cross-sectional data from 491 teenagers (aged 13-19 years) from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) and examined the association between mixed PFAS exposure and CRF via weighted quantile sum (WQS) regression. Maximal oxygen consumption (VO2max) was used to evaluate CRF. Multivariate linear regression was performed to investigate the relationship between each PFAS and VO2max as well as the relationship between PFAS exposure and the inflammation parameters and blood lipid content. Mediation analyses were performed to investigate possible explanations of the risk of low CRF due to PFAS exposure. The results showed that for males, mixed PFAS exposure was negatively related to VO2max (beta = - 0.80, 95% CI: - 1.53 to - 0.10, P = 0.028) and that of the PFASs, perfluorononanoic acid (PFNA) had the greatest influence on VO2max. In the individual PFAS analysis, PFNA was negatively related to VO2max in male adolescents (beta = - 1.49, 95% CI: - 2.65 to - 0.32, P = 0.013). Additionally, significant relationships among serum PFNA levels and total cholesterol and the white blood cell (WBC) count were found. Mediation analyses revealed that WBC count accounted for 24.18% of the variation between PFNA level and CRF. The present results provide epidemiological evidence that exposure to PFASs, mainly PFNA, is negatively associated with CRF, possibly via alterations in WBC count.

Low-level plasticizer exposure and all-cause and cardiovascular disease mortality in the general population.

BACKGROUND: Plasticizers, also called phthalates, are a group of chemicals widely used in daily life. A previous report showed no significant association between phthalate metabolite concentrations and mortality. We investigated the association of urinary phthalate levels and individual phthalate metabolite levels with all-cause and cardiovascular disease (CVD) mortality after standardizing the phthalate concentration. METHODS: A total of 6,625 participants were recruited from a nationally representative sample of adults aged 40 years or older who were enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2014 and were followed up through December 31, 2015. Data were analyzed from January 2021 to June 2021. NHANES-linked updated National Death Index public access files were used to acquire information on mortality status and cause of death. The present study conducted extended follow-up of an earlier analysis. Cox proportional hazard models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of covariate-adjusted creatinine standardization urinary phthalate concentrations with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables. RESULTS: The mean ± standard deviation age of all participants in the final study was 59.9±12.6 years old, and 49.6% of the participants were male. The median follow-up time was 73 months (range 1-157 months). At the censoring date of December 31, 2015, 3,023 participants were identified as deceased (13.4%). A fully adjusted Cox model showed that a urinary di(2-ethylhexyl) phthalate (DEHP) concentration >= 83.4 ng/mL was associated with a slight increase in all-cause mortality (HR 1.27, 95% CI 1.03, 1.57, P for trend= 0.014) and CVD mortality (HR 2.19, 95% CI 1.35, 3.54, P for trend= 0.002). Similarly, urinary mono-2-ethyl-5-carboxypentyl phthalate (MECPP) levels >= 39.2 ng/mL were associated with increased CVD mortality (HR 2.33, 95% CI 1.45, 3.73, P for trend < 0.001). Restricted cubic spline analyses suggested linear associations of DEHP and MECPP levels with all-cause and CVD mortality. CONCLUSION: In this large nationally representative sample of American adults, high urinary DEHP and MECPP were significantly associated with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables.

Urinary levels of Phthalate metabolite mixtures and pulmonary function in adolescents.

Although an association between urinary phthalate (PAE) metabolites and respiratory symptoms and diseases has been reported, knowledge regarding its effect on pulmonary function is limited, especially in adolescents. Using cross-sectional data from 1389 adolescents (aged 10-19 years) in the 2007-2012 National Health and Nutrition Examination Survey, the association of mixed urinary PAE metabolites with pulmonary function was evaluated using the weighted quantile sum. Moreover, multivariate linear regression was performed to investigate associations between each urinary PAE metabolite and pulmonary function indicators and to estimate the interaction effects between urinary PAE metabolites and demographic characteristics. We found that mixed urinary PAE metabolites were negatively associated with forced expiratory volume at the 1 s (FEV1, p < 0.001) and forced vital capacity (FVC, p = 0.008) levels. In individual PAE metabolite analyses, mono (carboxynonyl) pthalate (MCNP), mono-n-butyl pthalate (MnBP), mono-isobutyl pthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-benzyl phthalate (MBzP) correlated negatively with both FVC and FEV1 values (Holm-Bonferroni corrected p < 0.05). Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was negatively associated with the FVC value. Significant interactions between sex and urinary MnBP or MBzP levels for the risk of FEV1 decrease in girls were found (p = 0.005), as was a significant interaction between sex and urinary MBzP level for the risk of FVC decline. Our findings suggest that higher PAE exposure is associated with respiratory dysfunction; the association is more pronounced among girls.

Associations of exposure to secondhand smoke with hypertension risk and blood pressure values in adults.

BACKGROUND: The effects of environmental chemical exposure on blood pressure (BP) have been confirmed, but the association between exposure to secondhand smoke (SHS) and hypertension risk and BP in the general population remains unknown. METHODS: Cross-sectional associations between SHS exposure and hypertension risk and BP values were evaluated using data for subjects who participated in the National Health and Nutrition Examination Survey (NHANES), 1999-2016. Logistic regression and linear regression were performed after adjusting for age, sex, race, alcohol consumption, poverty-to-income ratio (PIR), body mass index (BMI), estimated glomerular filtration rate, physical activity, diabetes, cardiovascular disease, and NHANES cycle. Restricted cubic spline models were created to display the potential nonlinear association between SHS and BP levels. RESULTS: Higher risk of hypertension was found at the highest SHS concentrations (OR = 1.13, 95% CI 1.04, 1.24, P for trend = 0.007). Additionally, SHS exposure had a strong positive association with systolic blood pressure (SBP) but was negatively associated with diastolic blood pressure (DBP). Furthermore, the nonlinear model result showed a significant association between SHS and SBP (P = 0.017); however, the nonlinear model result was not significant for SHS or DBP. CONCLUSIONS: Our results suggest a potential association between high SHS exposure and the risk of hypertension. Further research is needed to elucidate the underlying mechanisms.

Association between blood ethylene oxide levels and the risk of cardiovascular diseases in the general population.

Ethylene oxide (EtO) is a highly reactive organic compound that is mainly used as a sterilizing agent. However, to date, the effects of EtO on the cardiovascular system are not clear. We aimed to explore the association between blood EtO levels and the risk of cardiovascular disease (CVD) in the general US population. We obtained information on blood levels of EtO and CVD outcomes in 3,410 participants from the National Health and Nutritional Examination Survey (NHANES) 2013-2014 and 2015-2016. Logistic regression models were applied to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between EtO and risk of all CVD as well as subtypes of CVD. Linear regression analyses were used to estimate the associations of EtO with potential mechanistic parameters of CVD, including blood pressure, blood lipid levels and inflammatory parameters. Higher blood levels of EtO were associated with an increased risk of all CVD (p for trend = 0.003), with an adjusted OR (95% CI) in the highest quartile of 1.94 (1.24, 3.02) compared with the lowest quartile as a reference. Higher concentrations of EtO were positively associated with the risk of angina (p for trend = 0.04) and heart attack (p for trend = 0.011). In addition, the concentration of EtO was positively associated with the levels of triglycerides, white blood cells, lymphocytes, monocytes, neutrophils and eosinophils (p = 0.003 for eosinophils and p < 0.001 for the others) and negatively associated with the level of high-density lipoprotein cholesterol (p < 0.001). We found that exposure to EtO was associated with angina, heart attack and all CVD in a large representative US population. Furthermore, EtO may induce CVD through the inflammatory response and abnormal fatty acid metabolism.

Metabonomic Study on the Plasma of High-Fat Diet-Induced Dyslipidemia Rats Treated with Ge Gen Qin Lian Decoction by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry.

Gegen Qinlian decoction (GGQLD) has a definite effect on T2DM in clinic, and it has the effect of lowering blood sugar, improving insulin resistance, and improving the blood lipid level of rats with dyslipidemia, but the intervention mechanism of GGQLD on dyslipidemia has not been clarified. The changes in endogenous metabolites in the plasma of high-fat diet-induced dyslipidemia rats treated with Ge Gen Qin Lian Decoction (GGQLD) were studied to elucidate the therapeutic effects and mechanism of action of GGQLD in dyslipidemia. Based on ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS), the metabolic profiles of rat serum samples were collected. The rat model of dyslipidemia was induced by a 60% fat-fed high-fat diet. After feeding the rats with a high-fat diet for 4 weeks, dyslipidemia appeared. After 5 weeks of GGQLD (14.85 g kg-1) administration, the metabonomics of rats' plasma samples in the normal group, model group, and administration group were analyzed. Mass profiler professional (MPP), SIMCA-P 14.1, and Graphpad prism 6.0 software were used combined with METLIN biological database and human metabolite database HMDB to screen and identify endogenous biomarkers. Metaboanalyst 4.0 software was used by combining with HMDB and KEGG databases; the enrichment and metabolic pathway of biomarkers were analyzed to explore the metabolic mechanism of dyslipidemia rats induced by high-fat diet and the intervention mechanism of Gegen Qinlian decoction. After 5 weeks of administration of GGQLD, the levels of serum TC and TG were significantly decreased (P < 0.05, P < 0.01), while HDL-C and LDL-C were not significantly affected. After administration, the food intake of rats in the administration group decreased gradually, and the change trend of body weight gradually slowed down. The metabonomics of rat plasma samples results showed that 23 potential biomarkers including α-linolenic acid, arachidonic acid, and lysophosphatidylcholine were significantly changed in positive ion mode. Studies have shown that GGQLD has a significant lipid-lowering effect on dyslipidemia rats induced by a high-fat diet, and its preventive mechanism is related to tryptophan metabolism, fatty acid biosynthesis, α-linolenic acid metabolism, arachidonic acid, and glycerophosphatidyl metabolism pathway.