Long-term outcomes of left atrial appendage closure with or without concomitant pulmonary vein isolation:a propensity score matching analysis based on CLACBAC study.

BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.

Improved in situ analysis of lead isotopes in low-Pb melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry.

RATIONALE: In situ Pb isotope analyses of tiny melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) are crucial for exploring the origins of mafic lavas. However, quantitative use of this technique with low-Pb (<10 ppm) melt inclusions is difficult due to their low 204 Pb content and 204 Hg interference. METHODS: Pb isotopic ratios of various reference glasses and olivine-hosted melt inclusions were determined using LA-MC-ICP-MS. Multiple ion counters were used to simultaneously determine signal intensities of all Pb isotopes and 202 Hg. An Hg signal-removal smoothing device reduced its signal in the gas blank by >80%. Instrumental mass bias was corrected using the standard-sample bracketing method. RESULTS: With 24-90 µm diameter laser spots, 2-4 Hz repetition rates, and 2.5-4 J cm-2 energy fluence, the analytical precisions of 20x Pb/204 Pb ratios (x = 6, 7, 8) for standards BHVO-2G, ML3B-G, NIST 614, NKT-1G, T1-G, GOR132-G, and StHs6/80-G were <1.0% (2RSD) when 208 Pb signals >100 000 cps. The Wangjiadashan melt inclusions have 206 Pb/204 Pb = 17.14-18.44, 207 Pb/204 Pb = 15.28-15.66, and 208 Pb/204 Pb = 37.12-38.68. CONCLUSIONS: The described method improves the precision and accuracy of in situ Pb isotope analysis in low-Pb melt inclusions using LA-MC-ICP-MS. The Pb isotopic compositions of the Wangjiadashan melt inclusions indicate the coexistence of LoMu and EMII+young HIMU components in the mantle source of weakly alkaline basalts.

Evaluation of Patients with Angiographically-Confirmed Coronary Artery Disease to Investigate the Association Between Epicardial Fat Thickness and Atrial Fibrillation.

BACKGROUND Epicardial fat thickness (EFT) is increasingly recognized as an independent risk factor of the presence, severity, and recurrence of atrial fibrillation (AF). We investigated the associations between EFT and AF prevalence and identified its correlation with other risk factors. MATERIAL AND METHODS A total of 199 participants who underwent coronary angiography and had confirmed coronary artery disease (CAD) were enrolled in this study. The EFT was measured by echocardiography and the association of EFT with other AF risk factors was evaluated by multivariate logistic regression analysis. RESULTS The EFT was significantly higher in patients with comorbidity of AF and CAD than those with CAD alone (6.86±1.96 mm vs 5.91±1.71 mm, P<0.001). Logistic regression analysis indicated that EFT was a predictive factor of the occurrence of AF in CAD, after adjusting for body mass index (BMI), systolic blood pressure (SBP), left circumflex artery (LCX) stenosis, LA diameter, B-type natriuretic peptide (BNP), creatinine (Cr), and blood urea nitrogen (BUN). LA diameter, SBP, and LCX stenosis are also independent risk factors for CAD complicated by AF. Correlation analysis revealed significant positive linear correlations between EFT and BMI (P<0.01), EFT, and LA diameter (P<0.05), as well as positive correlations between LA diameter and BNP, Cr, or BUN. CONCLUSIONS Epicardial fat thickness is a strong predictor for AF prevalence in patients with CAD, independent of other AF risk factors such as LA diameter, BMI, and SBP, while LA diameter, SBP, and LCX stenosis are also independent AF risk factors for CAD.

Higher FT4 level within the normal range predicts the outcome of cryoballoon ablation in paroxysmal atrial fibrillation patients without structural heart disease.

BACKGROUND: Accumulated evidence has indicated that a high-normal FT4 level is an independent risk factor for the clinical progression of AF. However, the association between elevated FT4 concentration within the normal range and AF recurrence after cryoballoon ablation in China is unknown. METHODS: This retrospective and observational study included 453 AF patients who underwent cryoballoon ablation from January 2016 to August 2018. Patients were classified into quartiles based on preprocedural serum FT4 concentration. The clinical characteristics of the patients and the long-term rate of AF recurrence after ablation were assessed. RESULTS: After a mean follow-up period of 17.4 ± 9.0 months, 91 (20.1%) patients suffered from AF recurrence. The AF recurrence rate by FT4 quartile was 17.7%, 19.0%, 21.4%, and 22.3% for participants with FT4 in quartile 1, 2, 3, and 4, respectively (p < .001). On multivariate Cox regression, FT4 concentration (HR: 1.187, 95% CI: 1.093-1.290, p < .001) and left atrial diameter (HR: 1.052, 95% CI: 1.014-1.092, p = .007) were significant predictors of AF recurrence. When stratifying for AF type, the rate of postoperative recurrence was independently increased as FT4 concentration increased in paroxysmal AF, but not in persistent AF (p < .001 in paroxysmal AF and p = .977 in persistent AF). CONCLUSION: Higher FT4 level within the normal range predicted the outcome of cryoballoon ablation in Chinese paroxysmal AF patients without structural heart disease.

Recurrent atrial fibrillation after initial cryoballoon ablation: New perspectives for intensive ablation in right superior pulmonary vein ostium for atrial fibrillation.

A significant proportion of patients with recurrent atrial fibrillation (AF) require repeat radiofrequency (RF) ablation after cryoballoon (CB) ablation. However, little is known about the pulmonary vein (PV) potential reconnection to left atrium and localization of gaps in the initial lesion sets following cryoablation in patients with recurrent AF. The data of 29 consecutive patients with repeat RF ablation for recurrent AF were analyzed. During the second ablation procedures, PV foci of AF were explored in 116 PVs by the CARTO system. All patients had complete PV isolation from initial cryoablation procedure. The fluoroscopy duration, mean cryoablation time and mean cryoablation frequency were lowest for the right superior pulmonary vein (RSPV) (58.69 ± 9.18 s, 185.10 ± 49.25 s and 1.07 ± 0.26; p = 0.024, p = 0.042 and p = 0.032). A significantly higher incidence of conduction gaps per patient was found for the RSPVs compared to the other PVs (p < 0.05 or p < 0.01). For RSPVs, it seemed that gaps were predominantly located at the anterior segment (22 gaps) and inferior segment (22 gaps). RSPV reconnection was independently related to a lower risk of major adverse events after the second ablation during follow up in the study patients (HR 0.275, 95%CI 0.078-0.967, p = 0.044). AF recurrence in patients after cryoablation is significantly associated with conduction gaps in the anterior and inferior segments of RSPVs. Various ablation strategies of close touch of CB on anterior and inferior segments of RSPV ostium, more freezing time and frequency for RSPV may help achieving durable PV isolation during follow up.

Acute left atrial ridge lesion after cryoballoon ablation: How does this affect left atrial appendage closure combined procedure?

BACKGROUND: Acute left atrial ridge (LAR) lesions have been observed following atrial fibrillation (AF) ablation. However, LAR lesions had not yet been quantitatively evaluated and their influence on procedure combining cryoballoon (CB) ablation with left atrial appendage closure (LAAC) remained to be explored. METHODS: The profile of LAR lesions was measured by transesophageal echocardiography (TEE) in 117 consecutive nonvalvular AF patients, who underwent the combined procedure of CB ablation and LAAC. We thoroughly investigated how LAR lesions correlated with baseline variables and clinical outcomes. RESULTS: A total of 95 out of 96 available TEE images presented prominent acute LAR lesions. In terms of dimensions, there was a greater change in width (Δwidth = 3.6 ± 2.3 mm) than the thickness (Δthickness = 2.6 ± 3.5 mm), and the outer ostium was narrowed (Δouter ostium diameter = -3.4 ± 4.0 mm), while the inner ostium remained unchanged. A higher nadir temperature when freezing the left superior pulmonary vein (LSPV) led to an LAR lesion with a two times greater width (adjusted odds ratio = 1.16; 95% confidence interval, 1.02-1.31). In the evaluation of LAAC outcomes, four patients implanted with Watchman devices had minimal residual flow at the inferior border, while two implanted with LAmbre devices developed residual flow at the LAR side. Clinical outcomes were similar between groups divided by lesion size. CONCLUSION: Acute LAR lesions frequently occurred following the CB ablation combined procedure, and lesion width positively correlates with LSPV nadir temperature. The presence of these lesions affects the measurement of pacifier devices but has little impact on that of occluder devices.

Efficacy and safety of cryoballoon ablation for Chinese patients over 75 years old: A comparison with a younger cohort.

INTRODUCTION: Cryoballoon ablation (CBA) results in satisfactory outcomes for drug-resistant atrial fibrillation (AF) patients. However, the efficacy and safety of CBA have not yet been tested in the Chinese elderly population. Therefore, this study compared the recurrence of AF and complications of CBA in patients ≥75 years and <75 years. METHODS: A total of 677 patients (<75 years, n = 550; ≥ 75 years, n = 127) with paroxysmal (n = 603) or persistent (n = 74) non-valvular drug-resistant AF were included. The efficacy was assessed by the recurrence of AF, and the safety was evaluated by peri- and post-procedural complications. RESULTS: The CHA2DS2-VASc (2.6 ± 1.7 vs 4.8 ± 1.6, P < .01) and HAS-BLED (1.8 ± 0.8 vs 2.0 ± 0.8, P = .01) scores were significantly higher in the elderly group. The instant pulmonary vein isolation success rate was comparable (99.11% younger vs 98.98% older, P = .99). After a mean follow-up time of 12.8 ± 9.6 months, the 1-year freedom from AF rate was 80.6% vs 85.8% in the older and younger groups, respectively, while the survival analysis showed a nonsignificant difference in the rate of freedom from AF (log-rank P = .46). Cox regression showed that age was not a predictive factor for AF recurrence and was not dichotomized (hazard ratio [HR] = 0.868, 95% confidence interval [CI] 0.509-1.481; P = .6046) or continuous (HR = 0.990, 95% CI, 0.968-1.012, P = .3642). Similar complications rates were observed, including stroke (1.0% younger vs 0.93% older, P = .95) and major hemorrhagic events (1.2% younger vs 0% elder, P = .25). CONCLUSIONS: The efficacy and safety profiles of CBA in patients older than 75 years are comparable with those in younger patients.

In situ determination of trace elements in melt inclusions using laser ablation inductively coupled plasma sector field mass spectrometry.

RATIONALE: In situ trace element analysis of melt inclusions by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) provides important geochemistry information. However, the precision and accuracy of this technique are affected by many factors, such as matrix effect, laser conditions, and calibration method. In addition, many previous LA-ICP-MS studies ablated entire melt inclusions along with their host minerals and obtained trace element composition by deconvoluting the mixed ablation signal, which may induce much uncertainty. METHODS: A 193 nm ArF laser ablation system combined with inductively coupled plasma sector field mass spectrometry (ICP-SF-MS) was used to investigate matrix effect, laser conditions, choice of external calibration standards, and data reduction strategy for in situ analysis of 36 major and trace elements in six common silicate reference glasses. The validity of the protocol presented here was demonstrated by measuring trace elements in olivine-hosted melt inclusions. Instead of ablating entire melt inclusions along with their host minerals, melt inclusions were polished to the surface to avoid laser ablating the mineral host. RESULTS: The calibration lines calculated from the calibration standards should cross the coordinate origin, especially for low-concentration elements (<10 ppm). As the laser crater size increased from 17 to 33 µm, the precision was improved from <20% to <8% (2RSD), and accuracy was improved from ±20% to better than ±10%. Most measured trace elements in Dali melt inclusions are consistent with those in their host rocks. For mobile elements (Ba, Sr, Pb), melt inclusions display much smaller variations than their host rocks. CONCLUSIONS: A simple but accurate approach for in situ analysis of trace elements in melt inclusions by LA-ICP-SF-MS has been established, which should greatly facilitate the wider application of in situ trace element geochemistry to melt inclusion studies.

Design, synthesis and biological evaluation of inhibitors of cathepsin K on dedifferentiated chondrocytes.

Selective proteinase inhibitors have demonstrated utility in the investigation of cartilage degeneration mechanisms and may have clinical use in the management of osteoarthritis. The cysteine protease cathepsin K (CatK) is an attractive target for arthritis therapy. Here we report the synthesis of two cathepsin K inhibitors (CKIs): racemic azanitrile derivatives CKI-E and CKI-F, which have better inhibition properties on CatK than the commercial inhibitor odanacatib (ODN). Their IC50 values and inhibition constants (Ki) have been determined in vitro. Inhibitors demonstrate differential selectivity for CatK over cathepsin B, L and S in vitro, with Ki amounting to 1.14 and 7.21 nM respectively. We analyzed the effect of these racemic inhibitors on viability in different cell types. The human osteoblast-like cell line MG63, MOVAS cells (a murine vascular smooth muscle cell line) or murine primary chondrocytes, were treated either with CKI-E or with CKI-F, which were not toxic at doses of up to 5 µM. Primary chondrocytes subjected to several passages were used as a model of phenotypic loss of articular chondrocytes, occurring in osteoarthritic cartilage. The efficiency of CKIs regarding CatK inhibition and their specificity over other proteases were validated in primary chondrocytes subjected to several passages. Racemic CKI-E and CKI-F at 0.1 and 1 µM significantly inhibited CatK activity in dedifferentiated chondrocytes, even better than the commercial CatK inhibitor ODN. The enzymatic activity of other proteases such as matrix metalloproteinases or aggrecanases were not affected. Taken together, these findings support the possibility to design CatK inhibitors for preventing cartilage degradation in different pathologies.

Strontium isotope measurement of basaltic glasses by laser ablation multiple collector inductively coupled plasma mass spectrometry based on a linear relationship between analytical bias and Rb/Sr ratios.

RATIONALE: In situ strontium (Sr) isotope analysis of geological samples by laser ablation multiple collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) provides useful information about magma mixing, crustal contamination and crystal residence time. Without chemical separation, during Sr isotope analysis with laser ablation, many kinds of interference ions (such as Rb+ and Kr+ ) are on the Sr isotope spectrum. Most previous in situ Sr isotope studies only focused on Sr-enriched minerals (e.g. plagioclase, calcite). Here we established a simple method for in situ Sr isotope analysis of basaltic glass with Rb/Sr ratio less than 0.14 by LA-MC-ICP-MS. METHODS: Seven Faraday cups, on a Neptune Plus MC-ICP-MS instrument, were used to receive the signals on m/z 82, 83, 84, 85, 86, 87 and 88 simultaneously for the Sr isotope analysis of basaltic glass. The isobaric interference of 87 Rb was corrected by the peak stripping method. The instrumental mass fractionation of 87 Sr/86 Sr was corrected to 86 Sr/88 Sr = 0.1194 with an exponential law. Finally, the residual analytical biases of 87 Sr/86 Sr were corrected with a relationship between the deviation of 87 Sr/86 Sr from the reference values and the measured 87 Rb/86 Sr. The validity of the protocol present here was demonstrated by measuring the Sr isotopes of four basaltic glasses, a plagioclase crystal and a piece of modern coral. RESULTS: The measured 87 Sr/86 Sr ratios of all these samples agree within 100 ppm with the reference values. In addition, the Sr isotopes of olivine-hosted melt inclusions from the Emeishan large igneous province (LIP) were measured to show the application of our method to real geological samples. CONCLUSIONS: A simple but accurate approach for in situ Sr isotope measurement by LA-MC-ICP-MS has been established, which should greatly facilitate the wider application of in situ Sr isotope geochemistry, especially to volcanic rock studies.

[In Situ Infrared Spectroscopic Determination of Enzyme Activity].

A real-time infrared (IR) spectroscopy measurement is an effective means to obtain enzymatic information either in vitro or in living cells, as it can provide direct, continue test of biomacromolecule reactions. The principles of measurements are performed basing on the fact that the absorption bands in spectra of reactants and products are usually separated to each other and changed independently with time. Therefore, it is possible to measure the enzymatic efficiency at any reaction time according to the changes of characteristic band, from either reactant or product. That is, IR spectroscopy can be used to obtain intracellular structural information during the cells metabolic processes, as which can provide detailed and reliable scientific evidences. In this paper, we summarized the new developments of IR spectra in the in vitro enzymatic assay for several representative enzymes, as well the screening of enzyme inhibitors, which was further extended to the identical aspect by using living cells as detection model. Such important enzymatic examination closes to the physiological conditions without labeling, supplying structural information of the related biomolecules. The developing trends of IR spectra are discussed and the perspectives of it in the research area are also provided in this review.

Guiding atrial fibrillation ablation combined with left atrial appendage occlusion procedure by fluoroscopy with or without transesophageal echocardiography achieved comparable outcomes.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and can be treated with catheter ablation (CA) combined with left atrial appendage occlusion (LAAO). The study is designed to compare the safety and efficacy of guiding the combined procedure by digital subtraction angiography (DSA) with or without transesophageal echocardiography (TEE). METHODS: From February 2019 to December 2020, 138 patients with nonvalvular AF who underwent CA combined with LAAO procedure were consecutively included, and two cohorts were built according to intraprocedural guidance (DSA or DSA with TEE). Periprocedural and follow-up outcomes were compared with investigate the feasibility and safety between the two cohorts. RESULTS: 71 patients and 67 patients were included in the DSA cohort and TEE cohort, respectively. Age and gender were comparable, despite the TEE cohort having a higher proportion of persistent AF (37 [55.2%] vs. 26 [36.6%]) and hemorrhage history (9 [13.4%] vs. 0). The procedure time of the DSA cohort was significantly reduced (95.7 ± 27.6 vs. 108.9 ± 30.3 min, p = .018), with a nonsignificant longer fluoroscopic time (15.2 ± 5.4 vs. 14.4 ± 7.1 min, p = .074). And the overall incidence of peri-procedural complications was similar between cohorts. After an average of 24 months of clinical follow-up, only three patients in the TEE cohort had ≤3 mm residual flow (p = .62). Kaplan-Meier estimates showed nonsignificant differences between the cohorts for freedom from atrial arrhythmia (log-rank p = .964) and major adverse cardiovascular events (log-rank p = .502). CONCLUSIONS: Compared with DSA and TEE guidance, DSA-guided combined procedure could shorten the procedural time, while achieving similar periprocedural and long-term feasibility and safety.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial.

Background: Cryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). Objectives: This study sought to assess the performance of a novel liquid nitrogen-driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). Methods: This was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen-driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. Results: A total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. Conclusions: This premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of PAF.

[Effects of Green, Blue, and Blue-green Roofs on Runoff Quality].

Roofs occupy a great proportion of urban impervious surfaces, and the implementation of eco-roof construction in urban areas is beneficial to alleviate the ecological and environmental problems caused by rapid urbanization. In this study, different eco-roofs (i.e., 68.6%-90.7%, and 39.8%-54.5%, respectively. However, all the eco-roofs were sources of NO-3-N, DCr, DFe, and DNi. The blue roof was a sink of DCu (with a pollutant load reduction rate of 21.9%) and did not affect the cumulative load of PO3-4-P in runoff. However, the green roof and blue-green roof were the sources of PO3-4-P and DCu. The RQI value of the blue roof was the highest, followed by that of the blue-green roof and green roof. The RQI value of the green roof was significantly lower than that of the blue and blue-green roofs (P<0.05). These results indicated that the runoff quality of the blue roof was the best, whereas that of the green roof was the worst. Adding a storage layer to the green roofs could significantly improve the runoff quality. The results of this study provide scientific references for the selection and design of eco-roof facilities.

Tumor Microenvironments-Adaptive Apoptotic Effects of Cytidine 5'-monophosphate-Capped Gold Nanoclusters.

In the present work, cytidine 5'-monophosphate capped gold nanoclusters (AuNCs@CMP) are reported as a catalyst for redox reactions, which show both oxidase- and excellent peroxidase-like activity. When employing 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate in the presence of hydrogen peroxide (H2O2), the maximum velocity (Vmax) was 175 × 10-8 M s-1in vitro. Besides, the AuNCs@CMP exhibited high catalytic activity for reactive oxygen species (ROS) generation with H2O2. Particularly, they also displayed excellent catalytic activity for ROS generation in tumor cells, being activated and promoted by the tumor microenvironment (TME). Consequently, the AuNCs@CMP show an excellent antitumor effect on HeLa and SW480 cells as assayed by flow cytometry. The antitumor mechanism of AuNCs@CMP was attributed to the high ROS generation based on the specific environments of the TME. Therefore, the present study provides TME-adaptive AuNCs@CMP with excellent mimetic peroxidase activity, producing significant ROS to kill the tumor cells in TME.

Full length transcriptomes analysis of cold-resistance of Apis cerana in Changbai Mountain during overwintering period.

Apis cerana in Changbai Mountain is an ecological type of Apis cerana, which is an excellent breeding material with cold-resistant developed by long-term natural selection under the ecological conditions. However, the physiological and molecular mechanisms of Changbai Mountain population under cold stress are still unclear. In this study, the Nanopore sequencing was carried out for the transcriptome of Apis cerana in Changbai Mountain in the coldest period of overwintering, which will provide a reference to the cold-resistant mechanism. We determined 5,941 complete ORF sequences, 1,193 lncRNAs, 619 TFs, 10,866 SSRs and functional annotations of 11,599 new transcripts. Our results showed that the myosin family and the C2H2 zinc finger protein transcription factor family possibly have significant impacts on the response mechanism of cold stress during overwintering. In addition, the cold environment alters genes expression profiles in honeybees via different AS and APA mechanisms. These altered genes in Hippo, Foxo, and MARK pathways help them counter the stress of cold in overwinter period. Our results might provide clues about the response of eastern honeybees to extreme cold, and reflect the possible genetic basis of physiological changes.

Prognostic Value of Arm Circumference for Cardiac Damage and Major Adverse Cardiovascular Events: A Friend or a Foe? A 2-Year Follow-Up in the Northern Shanghai Study.

Background: The high prevalence of cardiovascular diseases globally causes a great social burden and much individual suffering. The effective recognition of high-risk subjects is critical for primary prevention in the general population. In the elderly cohort, anthropometric measurements may have different prognostic values. Our study aimed to find convincing anthropometric measures to supplement conventional risk factors for major adverse cardiovascular events (MACEs) in the elderly cohort. Materials and Methods: A total of 1,576 elderly participants (44.5% male, aged 72.0 ± 6.0 years) recruited into the Northern Shanghai Study (2014-2015) were followed up between 2016 and 2017. Following the standard guideline for cardiovascular risk evaluation, all conventional cardiovascular risk factors were assessed. The body measures were made up of body weight, body height, hip circumference, waist circumference, and middle-upper arm circumference (MUAC). Organ damage (OD) markers for cardiac, vascular, and renal diseases will be evaluated by the standardized methods. Results: After the average 571 (±135) days of follow-up, a total of 90 MACEs (5.7%) occurred, i.e., 13 non-fatal myocardial infarction, 68 non-fatal stroke, and 9 cardiovascular deaths. Univariable COX survival analysis revealed that only MUAC could validly predict MACEs among anthropometric characters [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.82-0.96]. In Kaplan-Meier analysis, the group of high MUAC showed the lowest MACE risk (log-rank p = 0.01). Based on OD analysis, MUAC was independently linked to higher risk of left ventricular hypertrophy (LVH) in women and left ventricular diastolic dysfunction (LVDD) in both men and women. In adjusted COX analysis, only MUAC indicated statistical significance, but all other anthropometric parameters such as BMI, waist circumference, and waist-to-hip ratio (WHR) did not indicate significance. The higher level of MUAC remained a protective factor in fully adjusted models (HR: 0.73; 95% CI: 0.59-0.91), with p-values markedly significant in men (HR: 0.69; 95% CI: 0.49-0.97) and marginally significant in women (HR: 0.0.77; 95% CI: 0.59-1.01). After considering all factors (i.e., cardiovascular risk factors, MUAC, BMI, and WHR), the fully adjusted COX regression analysis demonstrated that the increased MUAC level was linked to decreased MACE risk in both men (HR: 0.57; 95% CI: 0.37-0.88) and women (aHR: 0.64; 95% CI: 0.46-0.93). Conclusion: Despite being associated with a higher rate of cardiac damage, higher MUAC independently and significantly conferred protection against the MACE, in the elderly cohort.

Patients With Larger Left Atrial Appendage Orifice Presented Worse Prognosis Contributed by Acute Heart Failure After Left Atrial Appendage Closure.

Background Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P<0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P=0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P=0.010). Conclusions Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.

The chemical structure of the Hawaiian mantle plume.

The Hawaiian-Emperor volcanic island and seamount chain is usually attributed to a hot mantle plume, located beneath the Pacific lithosphere, that delivers material sourced from deep in the mantle to the surface. The shield volcanoes of the Hawaiian islands are distributed in two curvilinear, parallel trends (termed 'Kea' and 'Loa'), whose rocks are characterized by general geochemical differences. This has led to the proposition that Hawaiian volcanoes sample compositionally distinct, concentrically zoned, regions of the underlying mantle plume. Melt inclusions, or samples of local magma 'frozen' in olivine phenocrysts during crystallization, may record complexities of mantle sources, thereby providing better insight into the chemical structure of plumes. Here we report the discovery of both Kea- and Loa-like major and trace element compositions in olivine-hosted melt inclusions in individual, shield-stage Hawaiian volcanoes--even within single rock samples. We infer from these data that one mantle source component may dominate a single lava flow, but that the two mantle source components are consistently represented to some extent in all lavas, regardless of the specific geographic location of the volcano. We therefore suggest that the Hawaiian mantle plume is unlikely to be compositionally concentrically zoned. Instead, the observed chemical variation is probably controlled by the thermal structure of the plume.

Association Between Lipid Accumulation Product and Target Organ Damage in Elderly Population: The Northern Shanghai Study.

INTRODUCTION: Lipid accumulation product (LAP), calculated from waist circumference (WC) and triglycerides (TG), is a novel index that correlates cardiovascular disease. We aimed to investigate the relationship between LAP and target organ damage (TOD) in elderly Chinese community-dwelling individuals. MATERIALS AND METHODS: We enrolled 3363 participants whose age was ≥65 years old. TOD, including left ventricular hypertrophy (LVH), arterial stiffness (AS), lower extremity atherosclerotic (LEA), micro-albuminuria (MAU) and chronic kidney disease (CKD), was measured using standard methods. LAP was calculated as (WC-65) × TG in men and (WC-58) × TG in women. Both quartiles and continuation of LAP were analyzed. RESULTS: Age-sex adjusted partial correlation analysis showed that LAP was significantly associated with CVD risk factors. With the first quartile (Q1) as a reference, in univariate logistic regression, the fourth quartile (Q4) of LAP was associated with all TOD. In multivariate model, Q4 of LAP was only associated with an increased risk of AS (odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.37-2.58, P for trend < 0.001), MAU (OR = 1.33, 95% CI: 1.01-1.75, P for trend = 0.02) and CKD (OR = 2.39, 95% CI: 1.39-4.12, P for trend < 0.001). But, Q4 of LAP was not associated with an increased risk of LVH (OR = 1.19, 95% CI: 0.85-1.65, P for trend = 0.25) or LEA (OR = 0.87, 95% CI: 0.58-1.29, P for trend = 0.96). Similar associations were found when analyzed continuously. CONCLUSION: The novel metabolic parameter LAP is significantly and independently associated with an increased risk of arterial stiffness, chronic kidney disease and micro-albuminuria in Chinese community-dwelling elderly individuals.