Exploring the causal relationship between gut microbiota and frailty: a two-sample mendelian randomization analysis.

Background: Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition. Methods: Instrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results. Results: Bacteroidia (b = -0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = -0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses. Conclusion: Our findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.

Serial tissue Doppler imaging in the evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension among extremely preterm infants: a prospective observational study.

Objectives: To evaluate serial tissue Doppler cardiac imaging (TDI) in the evolution of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) among extremely preterm infants. Design: Prospective observational study. Setting: Single-center, tertiary-level neonatal intensive care unit. Patients: Infant born <28 weeks gestation. Main outcome measures: Utility of TDI in the early diagnosis and prediction of BPD-PH and optimal timing for screening of BPD-PH. Results: A total of 79 infants were included. Of them, 17 (23%) had BPD-PH. The mean gestational age was 25.9 ± 1.1 weeks, and mean birth weight was 830 ± 174 g. The BPD-PH group had a high incidence of hemodynamically significant patent ductus arteriosus (83% vs. 56%, p < 0.018), longer oxygen days (96.16 ± 68.09 vs. 59.35 ± 52.1, p < 0.008), and prolonged hospital stay (133.8 ± 45.9 vs. 106.5 ± 37.9 days, p < 0.005). The left ventricular eccentricity index (0.99 ± 0.1 vs. 1.1 ± 0.7, p < 0.01) and the ratio of acceleration time to right ventricular ejection time showed a statistically significant trend from 33 weeks (0.24 ± 0.05 vs. 0.28 ± 0.05, p < 0.05). At 33 weeks, the BPD-PH group showed prolonged isovolumetric contraction time (27.84 ± 5.5 vs. 22.77 ± 4, p < 0.001), prolonged isovolumetric relaxation time (40.3 ± 7.1 vs. 34.9 ± 5.3, p < 0.003), and abnormal myocardial performance index (0.39 ± 0.05 vs. 0.32 ± 0.03, p < 0.001). These differences persisted at 36 weeks after conceptional gestational age. Conclusions: TDI parameters are sensitive in the early evolution of BPD-PH. Diagnostic accuracy can be increased by combining the TDI parameters with conventional echocardiographic parameters. BPD-PH can be recognizable as early as 33-34 weeks of gestation.

Chemical Constituents from Berchemia polyphylla var. Leioclada.

One previously undescribed naphthoquinone-benzisochromanquinone dimer berpolydiquinone A (1), along with two previously undescribed naphthoquinone-anthraquinone dimers berpolydiquinones B and C (2-3), and one previously undescribed dimeric naphthalene berpolydinaphthalene A (4), were isolated from the stems and leaves of Berchemia polyphylla var. leioclada. The chemical structures of these compounds were determined using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), spectroscopic data, the exciton chirality method (ECM), and quantum chemical calculation. Notably, compounds (1-2 and 5) are dimeric quinones that share the same naphthoquinone moiety, specifically identified as 2-methoxystypandron. Compound (4) is a derivative of dimeric naphthalene with a symmetrical structure, which is a new structure type isolated from B. polyphylla var. leioclada for the first time. These findings suggest that B. polyphylla var. leioclada serves as a significant reservoir of structurally diverse phenolic compounds. This study provides a scientific foundation for regarding B. polyphylla var. leioclada as a potential source of "Tiebaojin".

Association between dietary antioxidant intakes and chronic respiratory diseases in adults.

Background: Chronic respiratory diseases (CRDs) pose a significant global health burden. Antioxidant-rich diets have been associated with improved lung health, but the specific relationship with CRDs remains unclear. Methods: This study examined the relationship between dietary antioxidant intakes and CRDs using data from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). Information on dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoid, were collected from the 2 24-h recall interviews to calculate composite dietary antioxidant index (CDAI). CRDs were determined based on self-reported physician diagnoses. To examine the relationship between CDAI and CRDs, multivariate logistic regression was used. To study potential non-linear correlations within these associations, restricted cubic spline (RCS) regression was performed. Results: The study involved 40 557 individuals. The median CDAI was -0.09 (-2.05, 2.25). We discovered those who were in the fourth quartile of CDAI scores had a 19% lower prevalence than those in the first quartile (OR = 0.81 [0.72-0.91], Ptrend < 0.01) after adjusting for all relevant covariates. The fourth quartile of CDAI was linked with a lower prevalence of emphysema (OR = 0.57 [0.40-0.81], Ptrend < 0.01) and chronic bronchitis (OR = 0.74 [0.62-0.88], Ptrend < 0.01). RCS regression showed that CDAI was non-linearly related to the prevalence of CRDs, with inflection points of 3.20 (P for non-linearity <0.01). The stratified analysis did not identify variables that significantly affected the results. Conclusion: Higher dietary antioxidant intakes were related with a lower prevalence of CRDs (particularly emphysema and chronic bronchitis) in general adults.

Anthraquinone-benzisochromanquinone dimers from the stems and leaves of Berchemia polyphylla.

Three new anthraquinone-benzisochromanquinone dimers polyphylldiquinones A-C (1-3), along with three known analogs floribundiquinone A-B (4-5) and 7-dehydroxyventiloquinone H (6), were isolated from the stems and leaves of Berchemia polyphylla. The chemical structures and absolute configurations of these compounds were determined using HR-ESI-MS, spectroscopic data, and electronic circular dichroism. Notably, compounds (1-5) are dimeric quinones that share the same benzisochromanquinone moiety, specifically identified as 7-dehydroxyventiloquinone H (6), which was the first time to report as a natural product. Compounds 1-2 and compounds 4-5 are two pairs of atropisomers respectively.

The relationship between albumin corrected anion gap levels and mortality in patients with asthma in the ICU.

Although previous studies have suggested that albumin-corrected anion gap (ACAG) may be a predictor of mortality in critically ill patients in intensive care unit (ICU), its utility in the context of asthma has not been definitively established. In this study, baseline data, albumin concentration, anion gap (AG) and 30-d mortality data were retrieved from the Medical Information Mart for Intensive Care IV database (MIMIC-IV) for patients with asthma in the intensive care unit. Receiver operating characteristic (ROC) curves were constructed to analyze the predictive ability of ACAG and AG. The risk of 30-day mortality among patients with ACAG and asthma was analyzed using a restricted cubic spline (RCS) plot. Decision curve analysis (DCA) was used to evaluate the clinical usefulness of ACAG as a prognostic factor for 30-day mortality. Subsequently, subgroup analysis was conducted to explore potential variations in the relationship between ACAG and 30-day mortality based on factors such as sex, age, whether the asthma was acute, and other co-morbidities. Our study reveals that ACAG is a significant independent predictor of 30-day mortality in asthmatic patients receiving intensive care. The area under the AUC curve for ACAG was found to be 0.703, which is higher than that of AG, indicating that ACAG has a better predictive ability for 30-day mortality in this population. Furthermore, higher levels of ACAG were found to be associated with increased risk of 30-day mortality in asthmatic patients. In addition, decision curve analysis (DCA) demonstrated that the net benefit of ACAG was greater than that of AG. These findings suggest that ACAG may be a valuable prognostic factor for predicting 30-day mortality in asthmatic patients in the ICU. Our study provides evidence that ACAG is associated with an increased risk of 30-d mortality and has better predictive value in patients with combined asthma who are admitted to the ICU than AG.

Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects.

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. RESULTS: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = - 0.355 for LV and - 0.318 for RV), and KEiEDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age. CONCLUSION: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Pan-cancer analysis of Krüppel-like factor 3 and its carcinogenesis in pancreatic cancer.

Background: Krüppel-like factor 3 (KLF3) is a key transcriptional repressor, which is involved in various biological functions such as lipogenesis, erythropoiesis, and B cell development, and has become one of the current research hotspots. However, the role of KLF3 in the pan-cancer and tumor microenvironment remains unclear. Methods: TCGA and GTEx databases were used to evaluate the expression difference of KLF3 in pan-cancer and normal tissues. The cBioPortal database and the GSCALite platform analyzed the genetic variation and methylation modification of KLF3. The prognostic role of KLF3 in pan-cancer was identified using Cox regression and Kaplan-Meier analysis. Correlation analysis was used to explore the relationship between KLF3 expression and tumor mutation burden, microsatellite instability, and immune-related genes. The relationship between KLF3 expression and tumor immune microenvironment was calculated by ESTIMATE, EPIC, and MCPCOUNTER algorithms. TISCH and CancerSEA databases analyzed the expression distribution and function of KLF3 in the tumor microenvironment. TIDE, GDSC, and CTRP databases evaluated KLF3-predicted immunotherapy response and sensitivity to small molecule drugs. Finally, we analyzed the role of KLF3 in pancreatic cancer by in vivo and in vitro experiments. Results: KLF3 was abnormally expressed in a variety of tumors, which could effectively predict the prognosis of patients, and it was most obvious in pancreatic cancer. Further experiments verified that silencing KLF3 expression inhibited pancreatic cancer progression. Functional analysis and gene set enrichment analysis found that KLF3 was involved in various immune-related pathways and tumor progression-related pathways. In addition, based on single-cell sequencing analysis, it was found that KLF3 was mainly expressed in CD4Tconv, CD8T, monocytes/macrophages, endothelial cells, and malignant cells in most of the tumor microenvironment. Finally, we assessed the value of KLF3 in predicting response to immunotherapy and predicted a series of sensitive drugs targeting KLF3. Conclusion: The role of KLF3 in the tumor microenvironment of various types of tumors cannot be underestimated, and it has significant potential as a biomarker for predicting the response to immunotherapy. In particular, it plays an important role in the progression of pancreatic cancer.

Endocardial Fibroelastosis as an Independent Predictor of Atrioventricular Valve Rupture in Maternal Autoimmune Antibody Exposed Fetus: A Systematic Review with Clinicopathologic Analysis.

BACKGROUND: Neonatal lupus (NL) is a clinical syndrome that develops in the fetus as a result of maternal autoimmune antibodies. Congenital complete heart block (CHB) is the most common manifestation, while extranodal cardiac manifestations of NL, such as endocardial fibroelastosis (EFE) and myocarditis, are rare but more serious. Less is known about this atrioventricular valve rupture due to valvulitis as a consequence of maternal autoantibodies. We have described a case of cardiac neonatal lupus with an antenatally detected CHB patient who developed mitral and tricuspid valve chordal rupture at 45 days of age. We compared the cardiac histopathology and the fetal cardiac echocardiographic findings of this case with another fetus that was aborted after being antenatally diagnosed with CHB but without valvar rupture. A narrative analysis after a systematic review of the literature regarding atrioventricular valve apparatus rupture due to autoimmune etiology along with maternal characteristics, presentation, treatment, and outcome have been discussed in this article. OBJECTIVES: To describe published data on atrioventricular valve rupture in neonatal lupus, including clinical presentation, diagnostic evaluation, management, and outcomes. METHODS: We conducted a PRISMA-compliant descriptive systematic examination of case reports that included accounts of lupus during pregnancy or in the newborn period that resulted in an atrioventricular valve rupture. We gathered information on the patient's demographics, the details of the valve rupture and other comorbidities, the maternal therapy, the clinical course, and the results. We also used a standardized method to evaluate the cases' quality. A total of 12 cases were investigated, with 11 cases drawn from 10 case reports or case series and 1 from our own experience. RESULTS: Tricuspid valve rupture (50%) is more common than mitral valve rupture (17%). Unlike mitral valve rupture, which occurs postnatally, the timing of tricuspid valve rupture is perinatal. A total of 33% of the patients had concomitant complete heart block, while 75% of the patients had endocardial fibroelastosis on an antenatal ultrasound. Antenatal changes pertaining to endocardial fibroelastosis can be seen as early as 19 weeks of gestation. Patients with both valve ruptures generally have a poor prognosis, especially if they occur at close intervals. CONCLUSION: Atrioventricular valve rupture in neonatal lupus is rare. A majority of patients with valve rupture had antenatally detected endocardial fibroelastosis in the valvar apparatus. Appropriate and expedited surgical repair of ruptured atrioventricular valves is feasible and has a low mortality risk. Rupture of both atrioventricular valves occurring at close intervals carries a high mortality risk.

Alzheimer's disease with sleep insufficiency: a cross-sectional study on correlations among clinical characteristics, orexin, its receptors, and the blood-brain barrier.

Previous studies have shown that reduced sleep duration, sleep fragmentation, and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling. At the same time, blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease. However, currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency. This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital. Patients were divided into two groups: those with insufficient sleep (sleep duration ≤ 6 hours, n = 19, age 61.58 ± 8.54 years, 10 men) and those with normal sleep durations (sleep duration > 6 hours, n = 31, age 63.19 ± 10.09 years, 18 men). Demographic variables were collected to evaluate cognitive function, neuropsychiatric symptoms, and activities of daily living. The levels of orexin, its receptor proteins, and several blood-brain barrier factors were measured in cerebrospinal fluid. Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains. Furthermore, levels of orexin and its receptors were upregulated in the cerebrospinal fluid, and the blood-brain barrier was destroyed. Both these events precipitated each other and accelerated the progression of Alzheimer's disease. These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation. Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.

Deep brain stimulation of the nucleus basalis of Meynert modulates hippocampal-frontoparietal networks in patients with advanced Alzheimer's disease.

BACKGROUND: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has shown potential for the treatment of mild-to-moderate Alzheimer's disease (AD). However, there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD. In addition, the mechanisms underlying the modulation of brain networks remain unclear. This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD. METHODS: Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months. Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale. Resting-state functional magnetic resonance imaging and positron emission tomography data were also collected. RESULTS: The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up. Interestingly, the MMSE score indicated clinical efficacy at 1 month of follow-up. At this time point, the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state. Additionally, the increased functional connectivity between the parahippocampal gyrus (PHG) and the parietal cortex was associated with cognitive improvement. Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections, which was related to improved cognitive performance. CONCLUSION: The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD, which may be related to the modulation of multi-network connectivity patterns, and the hippocampus plays an important role within these networks. TRIAL REGISTRATION: ChiCTR, ChiCTR1900022324. Registered 5 April 2019-Prospective registration. https://www.chictr.org.cn/showproj.aspx?proj=37712.

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension.

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes. METHODS: PAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded. RESULTS: 45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity. CONCLUSION: In this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

Applications of diffusion tensor imaging integrated with neuronavigation to prevent visual damage during tumor resection in the optic radiation area.

Background: Intracranial tumors involving the temporo-occipital lobe often compress or destroy the optic radiation (OpR), resulting in decreased visual function. The aim of this study is to explore the value of diffusion tensor imaging (DTI) tractography integrated with neuronavigation to prevent visual damage when resecting tumors involving the OpR and find potential factors affecting patients' visual function and quality of life (QOL). Methods: Our study is a cross-sectional study that included 28 patients with intracranial tumors in close morphological relationship with the OpR recruited between January 2020 and February 2022. The surgical incision and approach were preoperatively designed and adjusted according to the DTI tractography results and visual function scores. All patients underwent examinations of visual acuity (VA) and visual field index (VFI) and completed visual function and QOL scales at admission and 2 months after discharge. Logistic regression and linear regression analysis were conducted to evaluate clinical factors potentially affecting pre/postoperative OpR morphology, VA, VFI, visual function, and QOL. Results: Lesion size was the main factor found to affect visual function (ß = -0.74, 95%CI: -1.12~-0.36, P = 0.05), VA (left: ß = -0.11, 95%CI: -0.14~-0.08, P < 0.001; right: ß = -0.15, 95%CI: -0.17~-0.13, P < 0.001), and VFI (left: ß = -0.11, 95%CI: -0.14~-0.08, P < 0.001; right: ß = -0.14, 95%CI: -0.16~-0.12, P < 0.001). Lesion size, edema, and involvement of the lateral ventricle temporal horn were factors affecting OpR morphology and QOL. The 28 patients showed significantly improved VA, VFI, visual function, and QOL results (P < 0.05) 2 months after discharge. Conclusions: Combining DTI of OpR mapping and microscopic-based neuronavigation aided precise mapping and thus preservation of visual function in patients undergoing tumor resection. Potential clinical factors affecting patients' visual function and QOL scores were identified which are useful for assessing a patient's condition and predicting prognosis.

circRNA circ_0055724 Inhibits Trophoblastic Cell Line HTR-8/SVneo's Invasive and Migratory Abilities via the miR-136/N-Cadherin Axis.

Preeclampsia (PE) is one of the major causes of morbidity and mortality in pregnancy. According to recent research, circular RNAs (circRNA) may act as sponges for microRNAs (miRNAs) and modulate gene expression. Low expression of hsa_circ_0055724 (circ_0055724) in PE tissues was recently reported in literatures. However, its mechanism and function have not been reported. Therefore, we were committed to investigating the role and mechanism of circ_0055724 in PE. Our study first verified the low expression of circ_0055724 in PE tissues. Overexpression or knockdown of circ_0055724 enhances/weakens the trophoblast cell survival, migration, and invasion. Furthermore, CircInteractome predicted the binding sites of circ_0055724 and miR-136, while Starbase predicted miR-136 targeted N-cadherin. Luciferase reporter gene assay confirmed that circ_0055724 directly interacts with miR-136 and miR-136 directly interacts with N-cadherin. More results indicated that high expression of miR-136 and low expression of N-cadherin appeared in PE. Increased expression of circ_0055724 resulted in decreased miR-136 but increased N-cadherin expression. Hence, circ_0055724 and N-cadherin were positively correlated, while circ_0055724 and miR-136 had a negative correlation. In terms of mechanism, circ_0055724 may induce the expression of N-cadherin and regulate the proliferation, migration, and invasion of trophoblast cells through decreasing miR-136, which can be a promising biomarker for early diagnosis and prognosis of patients with PE.

Clinical Features and Potential Mechanisms Relating Neuropathological Biomarkers and Blood-Brain Barrier in Patients With Alzheimer's Disease and Hearing Loss.

Background: The aim of this study was to explore clinical features and potential mechanisms relating neuropathological biomarkers and blood-brain barrier (BBB) in Alzheimer's disease (AD) and hearing loss (HL). Materials and Methods: A total of 65 patients with AD were recruited and auditory function was assessed by threshold of pure tone audiometry (PTA). Patients were divided into AD with HL (AD-HL) and AD with no HL (AD-nHL) groups based on the standard of World Health Organization. Clinical symptoms were assessed by multiple rating scales. The levels of neuropathological biomarkers of ß amyloid1-42 (Aß1-42) and multiple phosphorylated tau (P-tau), and BBB factors of matrix metalloproteinases (MMPs), receptor of advanced glycation end products, glial fibrillary acidic protein, and low-density lipoprotein receptor related protein 1 were measured. Results: (1) Compared with AD-nHL group, AD-HL group had significantly impaired overall cognitive function and cognitive domains of memory, language, attention, execution, and activities of daily living (ADL) reflected by the scores of rating scales (P < 0.05). PTA threshold was significantly correlated with the impairments of overall cognitive function and cognitive domains of memory and language, and ADL in patients with AD (P < 0.05). (2) P-tau (S199) level was significantly increased in CSF from AD-HL group (P < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD. (3) MMP-3 level was significantly elevated in CSF from AD-HL group (P < 0.05), and was significantly and positively correlated with PTA threshold in patients with AD (P < 0.05). (4) In AD-HL group, P-tau (S199) level was significantly and positively correlated with the levels of MMP-2 and MMP-3 in CSF (P < 0.05). Conclusion: AD-HL patients have severely compromised overall cognitive function, multiple cognitive domains, and ADL. The potential mechanisms of AD-HL involve elevations of AD neuropathological biomarker of P-tau (S199) and BBB factor of MMP-3, and close correlations between P-tau (S199) and MMP-2/MMP-3 in CSF. Findings from this investigation highly suggest significance of early evaluation of HL for delaying AD progression, and indicate new directions of drug development by inhibiting neuropathological biomarkers of AD and protecting BBB.

High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. METHODS: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. RESULTS: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEiEDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEiEDV were independent predictors of RV remodelling index. CONCLUSIONS: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

Medical Management of Infants With Supraventricular Tachycardia: Results From a Registry and Review of the Literature.

Background: Several medication choices are available for acute and prophylactic treatment of refractory supraventricular tachycardia (SVT) in infants. There are almost no controlled trials, and medication choices are not necessarily evidence based. Our objective was to report the effectiveness of management strategies for infant SVT. Methods: A registry of infants admitted to hospital with re-entrant SVT and no haemodynamically significant heart disease were prospectively followed at 11 international tertiary care centres. In addition, a systematic review of studies on infant re-entrant SVT in MEDLINE and EMBASE was conducted. Data on demographics, symptoms, acute and maintenance treatments, and outcomes were collected. Results: A total of 2534 infants were included: n = 108 from the registry (median age, 9 days [0-324 days], 70.8% male) and n = 2426 from the literature review (median age, 14 days; 62.3% male). Propranolol was the most prevalent acute (61.4%) and maintenance treatment (53.8%) in the Registry, whereas digoxin was used sparingly (4.0% and 3.8%, respectively). Propranolol and digoxin were used frequently in the literature acutely (31% and 33.2%) and for maintenance (17.8% and 10.1%) (P < 0.001). No differences in acute or prophylactic effectiveness between medications were observed. Recurrence was higher in the Registry (25.0%) vs literature (13.4%) (P < 0.001), and 22 (0.9%) deaths were reported in the literature vs none in the Registry. Conclusion: This was the largest cohort of infants with SVT analysed to date. Digoxin monotherapy use was rare amongst contemporary paediatric cardiologists. There was limited evidence to support one medication over another. Overall, recurrence and mortality rates on antiarrhythmic treatment were low.

Contexte: De nombreux choix de médicaments existent pour le traitement aigu et prophylactique de la tachycardie supraventriculaire (TSV) réfractaire chez les nourrissons. Or, il n'y a presque pas d'essais contrôlés à ce sujet, et les choix de médicaments ne sont pas nécessairement fondés sur des données probantes. Notre objectif était de faire état de l'efficacité des stratégies de prise en charge de la TSV chez les nourrissons. Méthodologie: Un registre des nourrissons admis à l'hôpital pour une TSV par réentrée, sans cardiopathie d'importance hémodynamique, a été tenu de façon prospective dans 11 centres de soins tertiaires à l'échelle mondiale. De plus, une revue systématique des études sur la TSV par réentrée chez le nourrisson a été effectuée dans MEDLINE et EMBASE. Des données sur les caractéristiques démographiques, les symptômes, les traitements aigus et d'entretien, et les résultats ont été recueillis. Résultats: Un total de 2 534 nourrissons ont été inclus : n = 108 du registre (âge médian de 9 jours [0-324 jours], 70,8 % de sexe masculin) et n = 2 426 de la revue de la littérature (âge médian de 14 jours; 62,3 % de sexe masculin). Le propranolol était le traitement de soins aigus (61,4 %) et d'entretien (53,8 %) le plus fréquent dans le registre, alors que la digoxine a été utilisée occasionnellement (respectivement dans 4,0 % et 3,8 % des cas). Dans la littérature, le propranolol et la digoxine étaient fréquemment utilisés en soins aigus (31 % et 33,2 %) et en traitement d'entretien (17,8 % et 10,1 %) (p < 0,001). Aucune différence n'a été observée entre les médicaments au chapitre de l'efficacité du traitement de soins aigus ou du traitement prophylactique. Le taux de récurrence était plus élevé dans le registre (25,0 %) que dans la littérature (13,4 %) (p < 0,001), et 22 (0,9 %) décès ont été signalés dans la littérature, mais aucun dans le registre. Conclusion: Il s'agit de la plus grande cohorte de nourrissons atteints de TSV analysée à ce jour. De nos jours, les cardiologues pédiatriques prescrivent rarement la digoxine en monothérapie. Peu de données probantes favorisent l'utilisation d'un médicament par rapport à l'autre. Dans l'ensemble, les taux de récurrence et de mortalité sous traitement antiarythmique étaient faibles.

A pilot study of differential gene expressions in patients with cough variant asthma and classic bronchial asthma.

BACKGROUND: Despite extensive exploration of asthma, the mechanism of asthma has not been fully elucidated. Cough variant asthma (CVA) is considered as precursor to classical asthma (CA). Comparative study between CA and CVA may be helpful in further understanding the pathogenesis of asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from CVA, CA and healthy adults. Each group consisted of five cases. Total RNA was extracted from the PBMCs. Agilent 4 × 44 K human genome oligo microarray was used to detect whole genome expression. Allogeneic clustering, Gene Ontology and KEGG analysis were performed to investigate differentially expressed genes (DEGs). Then, ten candidate genes were screened and verified by real-time PCR. RESULTS: Gene expressions were significantly different among the three groups, with 202 DEGs between the CA and the CVA groups. The Gene Ontology analysis suggested that the DEGs were significantly enriched in 'histone H4-K20 demethylation' and 'antigen processing and presentation of endogenous antigens'. HDC, EGR1, DEFA4, LTF, G0S2, IL4, TFF3, CTSG, FCER1A and CAMP were selected as candidate genes. However, the results of real-time PCR showed that the expression levels of FCER1A, IL4 and HDC in the cough variant asthma group were significantly different from those in the other two groups (p < 0.05). CONCLUSIONS: The pathogenesis of CVA and CA may be related to genes such as FCER1A, HDC and IL4. Further studies incorporating a larger sample size should be conducted to find more candidate genes and mechanisms.