Application of adaptive chaotic dung beetle optimization algorithm to near-infrared spectral model transfer.

A new transfer approach was proposed to share calibration models of the hexamethylenetetramine-acetic acid solution for studying hexamethylenetetramine concentration values across different near-infrared (NIR) spectrometers. This approach combines Savitzky-Golay first derivative (S_G_1) and orthogonal signal correction (OSC) preprocessing, along with feature variable optimization using an adaptive chaotic dung beetle optimization (ACDBO) algorithm. The ACDBO algorithm employs tent chaotic mapping and a nonlinear decreasing strategy, enhancing the balance between global and local search capabilities and increasing population diversity to address limitations observed in traditional dung beetle optimization (DBO). Validated using the CEC-2017 benchmark functions, the ACDBO algorithm demonstrated superior convergence speed, accuracy, and stability. In the context of a partial least squares (PLS) regression model for transferring hexamethylenetetramine-acetic acid solutions using NIR spectroscopy, the ACDBO algorithm excelled over alternative methods such as uninformative variable elimination, competitive adaptive reweighted sampling, cuckoo search, grey wolf optimizer, differential evolution, and DBO in efficiency, accuracy of feature variable selection, and enhancement of model predictive performance. The algorithm attained outstanding metrics, including a determination coefficient for the calibration set (Rc2) of 0.99999, a root mean square error for the calibration set (RMSEC) of 0.00195%, a determination coefficient for the validation set (Rv2) of 0.99643, a root mean squared error for the validation set (RMSEV) of 0.03818%, residual predictive deviation (RPD) of 16.72574. Compared to existing OSC, slope and bias correction (S/B), direct standardization (DS), and piecewise direct standardization (PDS) model transfer methods, the novel strategy enhances the accuracy and robustness of model predictions. It eliminates irrelevant background information about the hexamethylenetetramine concentration, thereby minimizing the spectral discrepancies across different instruments. As a result, this approach yields a determination coefficient for the prediction set (Rp2) of 0.96228, a root mean squared error for the prediction set (RMSEP) of 0.12462%, and a relative error rate (RER) of 17.62331, respectively. These figures closely follow those obtained using DS and PDS, which recorded Rp2, RMSEP, and RER values of 0.97505, 0.10135%, 21.67030, and 0.98311, 0.08339%, 26.33552, respectively. Unlike conventional methods such as OSC, S/B, DS, and PDS, this novel approach does not require the analysis of identical samples across different instruments. This characteristic significantly broadens its applicability for model transfer, which is particularly beneficial for transferring specific measurement samples.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

An Indacenodithienothiophene-Based Wide Bandgap Small Molecule Guest for Efficient and Stable Ternary Organic Solar Cells.

The strategic and logical development of the third component (guest materials) plays a pivotal and intricate role in improving the efficiency and stability of ternary organic solar cells (OSCs). In this study, a novel guest material with a wide bandgap, named IDTR, is designed, synthesized, and incorporated as the third component. IDTR exhibits complementary absorption characteristics and cascade band alignment with the PM6:Y6 binary system. Morphological analysis reveals that the introduction of IDTR results in strong crystallinity, good miscibility, and proper vertical phase distribution, thereby realizing heightened and balanced charge transport behavior. Remarkably, the novel ternary OSCs have exhibited a significant enhancement in photovoltaic performance. Consequently, open-circuit voltage (VOC), short-circuit current (JSC), and fill factor (FF) have all witnessed substantial improvements with a remarkable power conversion efficiency (PCE) of 18.94% when L8-BO replaced Y6. Beyond the pronounced improvement in photovoltaic performance, superior device stability with a T80 approaching 400 h is successfully achieved. This achievement is attributed to the synergistic interplay of IDTR, providing robust support for the overall enhancement of performance. These findings offer crucial guidance and reference for the design and development of efficient and stable OSCs.

Interfacial Rivet to Fill Structural Defects: A Spacer Engineering Gift for 3D Solar Cells.

The combination of 2D and 3D perovskites to passivate surfaces or interfaces with a high concentration of defects shows great promise for improving the efficiency of perovskite solar cells (PSCs). Constructing high-quality perovskite film systems by precisely modulating 2D perovskites with good morphologies and growth sites on 3D perovskite films remains a formidable challenge due to the complexity of spacer-engineered surface reactions. In this study, phase-pure 2D (HA)2(MA)n-1PbnI3n+1 perovskites with a controlled number of layers (n) are separated on a large scale and exploited as interface rivets to optimize 3D perovskite films, resulting in tunable film structural defects and grain boundaries. The optimized PSCs system benefits from a reduction in non-radiative recombination, resulting in improved optical performance, higher mobility, and lower trap density. The corresponding device achieves a champion power conversion efficiency (PCE) of more than 25%, especially for voltage (VOC) and fill factor (FF). The quality and uniformity of the perovskite films are further confirmed using large-area devices with an active area of 14 cm2, which exhibits a PCE of more than 21.24%. The high-quality thin-film system based on the 2D perovskites presented herein provides a new perspective for improving the efficiency and stability of PSCs.

Chlorogenic Acid Inhibited Epithelial-Mesenchymal Transition to Treat Pulmonary Fibrosis through Modulating Autophagy.

Chlorogenic acid (CGA), derived from dicotyledons and ferns, has been demonstrated with anti-inflammatory, anti-bacterial, and free radical-scavenging effects and can be used to treat pulmonary fibrosis (PF). However, the specific mechanism by which CGA treats PF needs to be further investigated. In this study, in vivo experiment was firstly performed to evaluate the effects of CGA on epithelial-mesenchymal transition (EMT) and autophagy in bleomycin (BLM)-induced PF mice. Then, the effects of CGA on EMT and autophagy was assessed using transforming growth factor beta (TGF-ß) 1-induced EMT model in vitro. Furthermore, autophagy inhibitor (3-methyladenine) was used to verify that the inhibitory mechanism of CGA on EMT was associated with activating autophagy. Our results found that 60 mg/kg of CGA treatment significantly ameliorated lung inflammation and fibrosis in mice with BLM-induced PF. Besides, CGA inhibited EMT and promoted autophagy in mice with PF. In vitro studies also demonstrated that 50 µM of CGA treatment inhibited EMT and induced autophagy related factors in TGF-ß1-induced EMT cell model. Moreover, the inhibitory effect of CGA on autophagy and EMT in vitro was abolished after using autophagy inhibitor. In conclusion, CGA could inhibit EMT to treat BLM-induced PF in mice through, activating autophagy.

Clinical characteristics and outcome correlates of Chinese patients with takotsubo syndrome: Results from the first Chinese takotsubo syndrome registry.

OBJECTIVE: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS). METHODS: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients. RESULTS: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049). CONCLUSION: We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events.

Utility of Circulating Free DNA Fragmentomics in the Prediction of Pathological Response after Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

BACKGROUND: A "Watch and Wait" (W&W) approach has become an alternative to surgery for locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). Precise prediction of pathological complete response (pCR) will improve patient selection for W&W. We investigated the utility of cell-free DNA (cfDNA) fragmentomics in predicting pCR. METHODS: We recruited 119 LARC patients and evaluated nCRT response by pCR status and pathological or MRI tumor regression grade (mrTRG). Plasma samples before, during, and after nCRT were applied to deep targeted-panel sequencing, with 103 patients having complete samples. cfDNA fragment and 5'-end motif profiles were used to construct elastic-net logistic regression models to predict non-pCR. Predictive performance was measured by area under the receiver operator characteristic curve (AUC), sensitivity, and specificity. RESULTS: In the training cohort, the model based on 5'-end motif profile plus mrTRG achieved the highest cross-validation AUC (0.92, 95% CI, 0.91-0.93). The AUC in a testing cohort was 0.96 (95% CI, 0.90-1.00). The models based on 5'-end motif profile alone or in combination with mrTRG both maintained good predictive ability for patients without detectable circulating tumor DNA (AUC 0.94, 95% CI, 0.93-0.95; AUC 0.95, 95% CI, 0.94-0.96). In an external validation cohort, the model trained with a local 5'-end motif profile obtained an AUC of 0.878 (95% CI, 0.801-0.956) in discriminating colorectal cancer from healthy subjects. CONCLUSIONS: The combination of a 5'-end motif profile with mrTRG has the potential to predict the response to nCRT, and therefore may improve the patient selection for a W&W approach.

Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection.

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

Clinical features and outcomes of patients in different age groups with non-valvular atrial fibrillation receiving oral anticoagulants.

Background: Patients with non-valvular atrial fibrillation (NVAF) need prophylactically antithrombotic therapies to reduce the risk of stroke. We hypothesized that the prognostic benefits of prophylactic antithrombotic therapies outweighed the bleeding risk among very elderly (≥85 years old) patients. Methods: We analyzed clinical characteristics and outcomes of patients with NVAF in different age groups who had received different prophylactic antithrombotic therapies. We enrolled 3895 consecutive NVAF patients in the Macau Special Administrative Region (Macau SAR) of China from January 1, 2010, to December 31, 2018. Among 3524 patients [including 1252 (35.53%) very elderly patients] who completed the entire study, 2897 (82.21%) patients had a CHA2DS2-VASc score ≥ 2, 2274 (64.53%) had HAS-BLED score < 3, and 1659 (47.08%) had both of the above. The follow-up time was 3.80 (median, interquartile range 1.89-6.56) years. The primary outcome was the first occurrence of ischemic stroke, major bleeding, clinically relevant non-major gastrointestinal bleeding (CRNM-GIB), and all-cause mortality. Results: A total of 2012 patients (57.09%) received no antithrombotic (NAT), 665 (18.87%) received antiplatelet (AP) agents, 371 (10.53%) received vitamin K antagonist (VKA), and 476 (13.51%) received non-vitamin K antagonist oral anticoagulants (NOACs). Eventually, 610 (17.31%) patients experienced thromboembolic events, with 167 (4.74%) strokes and 483 (13.71%) transient ischemia attack (TIA)/strokes. Bleeding events occurred in 614 (17.42%) patients, with 131 (3.72%) major bleeding, 381 (10.81%) CRNM-GIB and 102 (2.89%) minor bleeding events. All-cause deaths occurred in 483 (13.71%) patients. Compared with patients receiving NAT, patients receiving NOACs and VKA had fewer strokes (hazard ratio [HR]: 0.038; 95 %CI 0.004-0.401; p  = 0.006 and HR: 0.544; 95 %CI 0.307-0.965; p  = 0.037, respectively), and lower all-cause mortality (HR: 0.270; 95 %CI 0.170-0.429; p  < 0.001 and HR: 0.531; 95 %CI 0.373-0.756; p  < 0.001, respectively). Of note, very elderly patients with NVAF receiving NOACs had fewer strokes (adjust hazard ratio [adjHR]: 0.042; 95 %CI 0.002-1.003; p  = 0.050) and lower all-cause mortality (adjHR: 0.308; 95 %CI 0.158-0.601; p  = 0.001). Meanwhile, despite higher CRNM-GIB events (adjHR: 1.736; 95 %CI 1.042-2.892; p  = 0.034), major bleeding events (adjHR: 1.045; 95 %CI 0.366-2.979; p  = 0.935) did not significantly increase. VKA neither reduced strokes (adjHR: 1.015; 95 %CI 0.529-1.948; p  = 0.963), nor improved all-cause mortality (adjHR: 0.995; 95 %CI 0.641-1.542; p  = 0.981) in very elderly patients with NVAF. Conclusions: Antithrombotic treatment (VKA and NOACs) reduces stroke and improves prognosis in patients in different age groups with NVAF. The prognostic benefits of NOACs outweigh their bleeding risks in very elderly patients with NVAF.

Growth Differentiation Factor-15 Based ABC (Age, Biomarkers, Clinical History)-AF (Atrial Fibrillation)-Bleeding Risk Score for Elderly Patients with Nonvalvular Atrial Fibrillation.

Background: Growth differentiation factor-15 (GDF-15) is a strong predictor of bleeding in atrial fibrillation (AF) patients. The novel ABC (age, biomarkers, and clinical history), AF, and bleeding risk score outperforms HAS-BLED bleeding risk score for major bleeding (MB) in patients with AF receiving oral anti-coagulation in the clinical trial cohort. However, it has not been entirely externally validated. We aimed to refine and understand the application of the ABC-AF bleeding risk score in elderly (aged ≥65 years old) patients with nonvalvular atrial fibrillation (NVAF) for predicting the different types of bleeding events and anti-thrombotic treatments. Methods: We identified elderly patients with NVAF between March 2018 and December 2019 who were hospitalized for the first time after a diagnosis of NVAF. We measured the plasma concentration of the ABC biomarkers (growth differentiation factor 15 (GDF-15) and cardiac troponin-T (cTnT)) from enrolled patients. We collected their general information and follow up for one year until December 2020. During the follow-up period, information on the occurrence of bleeding events (major bleeding, clinically relevant nonmajor gastrointestinal bleeding (CRNM GIB), and minor bleeding events) was collected. Results: We enrolled 342 elderly NAVF patients; the ABC-AF bleeding and HAS-BLED scores were quantified. With an average of 1.5 years of follow-up, 6 patients had an intracranial hemorrhage; 57 patients had CRNM GIB; and 68 patients had minor bleeding events (36 fecal occult blood positive and 32 other minor bleeding events). The ABC-AF bleeding score yielded a C-index of 0.72 (95% CI 0.60-0.84) for predicting MB in elderly patients with NAVF, C-index of 0.69 (95% CI 0.57-0.82) by HAS-BLED score. Comparison of the incidence of bleeding events during follow-up and the predicted 1-year incidence of bleeding events by each bleeding risk score, ABC-AF bleeding, and HAS-BLED scores have similar value in predicting the risk for elderly patients with NAVF in different types of bleeding events, whether on oral anti-coagulation treatment (OAC) or non-OAC (P > 0.05). Conclusion: In elderly patients with NVAF, the biomarker-based ABC-AF bleeding score showed similar performance compared with the HAS-BLED bleeding risk score.

Ultrasensitive and affordable assay for early detection of primary liver cancer using plasma cell-free DNA fragmentomics.

BACKGROUND AND AIMS: Early detection of primary liver cancer (PLC), including HCC, intrahepatic cholangiocarcinoma (ICC), and combined HCC-ICC (cHCC-ICC), is essential for patients' survival. This study aims to develop an accurate and affordable method for PLC early detection and differentiating ICC from HCC using plasma cell-free DNA (cfDNA) fragmentomic profiles. APPROACH AND RESULTS: Whole-genome sequencings (WGS) were performed using plasma cfDNA samples from 192 patients with PLC (159 HCC, 26 ICC, 7 cHCC-ICC) and 170 noncancer controls (including 53 liver cirrhosis [LC] or HBV-positive) enrolled in the training cohort. An ensembled stacked model for PLC detection was constructed using the training cohort. The model performance was assessed in an independent test cohort (189 patients with PLC [157 HCC, 26 ICC, 6 cHCC-ICC], 164 noncancer controls [including 51 LC/HBV]). Our model showed excellent performance for cancer detection in the test cohort (AUC: 0.995, 96.8% sensitivity at 98.8% specificity). It showed excellent sensitivities in detecting early-stage PLC (I: 95.9%, II: 97.9%), small tumors (≤3 cm: 98.2%), and HCC (96.2%) or ICC (100%). The AUC for distinguishing PLC from LC/HBV reached 0.985 (96.8% specificity at 96.1% specificity). Promisingly, our model maintained consistent performances during the downsampling process, even using 1X coverage data (AUC: 0.994, 93.7% sensitivity at 98.8% specificity). A separate model showed potential for distinguishing ICC from HCC (AUC: 0.776). CONCLUSIONS: Our model, outperforming previous reports at a lower cost by solely using low-coverage WGS data, exhibits excellent clinical potential for ultrasensitive and affordable detection of PLC and its subtypes.

Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing.

BACKGROUND: Metastases are responsible for over 70% of deaths from lung adenocarcinomas. Previous large-scale studies of LUAD mainly focused on primary diseases. We aimed to comprehensively analyze the genomic landscape of metastatic LUADs and elucidate its clinical implications in the context of precision medicine. METHODS: We performed retrospective analyses on targeted sequencing data of 3,743 primary tumors and 934 metastases from 4,480 patients with lung adenocarcinomas, and PD-L1 immunohistochemical data of 1,336 primary tumors and 252 metastases from 1,588 LUAD patients. RESULTS: Metastases generally manifested significantly higher mutational burdens and chromosomal instability than primary lung adenocarcinomas. Clinically actionable alterations, including ALK mutations, ALK and ROS1 fusions, and MET copy number gains, were enriched in metastases, particularly metastases to some specific organs/tissues, such as lymph nodes, liver, and brain. PD-L1 expression decreased as the approximate metastatic distance increased. Additional data of paired primary tumors and metastases to lymph nodes and brain validated patterns of actionable alterations and candidates for metastatic drivers. Two evolutionary modes of metastatic dissemination, common origins and distinct origins, were identified in both types of primary-metastasis pairs. CONCLUSIONS: Our study showed heterogenous patterns of clinically actionable alterations, PD-L1 expressions, metastatic driver candidates, and evolutionary patterns among multiple types of metastases of lung adenocarcinomas, which may advise the planning of treatments and the identification of novel therapeutic targets.

Assessment of atrial septal defect using 2D or real-time 3D transesophageal echocardiography and outcomes following transcatheter closure.

BACKGROUND: The assessment of interatrial septum (IAS) requires a standardized, systematic approach, including two-dimensional transthoracic echocardiography (2D TTE), 2D transesophageal echocardiography (2D TEE), and three-dimensional (3D) TEE. Although 2D TEE has been widely used for the preoperative assessment of atrial septal defect (ASD), its ability to provide reliable information is often limited due to the structural characteristics of IAS. The introduction of 3D TEE provides a unique "en face" view of IAS, which allows the visualization and accurate measurements of diameters, area, and rims of ASD. Hence, appropriate ASD imaging information is particularly important in successful transcatheter closure. METHODS: In this retrospective study, 2D TTE/TEE, and 3D TEE were performed before ASD closure, with 2D minimal and maximal diameters, areas, and residual rims being recorded. Adequate 3D TEE imaging data sets were collected and then analyzed. ASD related parameters were compared using different echocardiography. Patients who underwent ASD closure completed a clinical follow-up. RESULTS: The mean defect maximal diameter and aperture area by 3D TEE was significantly larger than that of the corresponding 2D TEE (P<0.05). There was no statistical difference in the minimal and maximal diameter or area by TEE for circular-shaped ASDs. For oval ASDs, mean minimal diameter on 2D TEE was larger than that on 3D TEE. The mean maximal diameter measured using 2D TEE was smaller than the 3D TEE measurement (16.0±7.1 vs. 19.8±8.6; P<0.05). For complex-shaped defects, there were statistical differences in minimal and maximal diameter between TEEs. Furthermore, 2D and 3D TEE had a longer superior vena cava (SVC) residual rim than did 2D TTE (P<0.05). The 3D TEE residual rims of the inferior vena cava (IVC) was significantly larger than the corresponding 2D TEE. There was a very strong correlation between the residual rim measurements using 3D and 2D TEE. However, the limits of agreement between 2D and real-time 3D TEE measurements were more apparent in the IVC rim group than in the other groups. CONCLUSIONS: Our study confirms the value of 3D TEE in assessing ASD shape and size reported by previous studies, and is also the first to accurately and systematically characterize ASD residual rim in complex ASDs.

3D transesophageal echocardiography assists in evaluating the morphology, function, and presence of thrombi of left atrial appendage in patients with atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) is significantly more likely to form thrombi in patients with atrial fibrillation (AFib). Two-dimensional transesophageal echocardiography (2D TEE) is considered the gold standard for assessing and studying LAA morphology and anatomy. However, 2D TEE can only visualize one plane at any given time. Real-time three-dimensional echocardiography (RT-3D TEE) imaging can preserve spatial and temporal resolution, which is a safe, accurate, and reproducible imaging modality. There are few reports of the usage of RT-3D TEE to study LAA in AFib patients. In our research, RT-3D TEE helps to provide detailed LAA information and identifying the presence or absence of thrombi from pectinate muscles in paroxysmal and long-standing AFib patients. METHODS: LAA morphology was analyzed in detail by 2D TEE and RT-3D TEE in 320 patients with paroxysmal or long-standing AFib. The LAA flow pattern, as maximal LAA emptying flow velocity (LAAeV), was retrieved from 2D and 3D TEE imaging. LAA morphological parameters, spontaneous echo contrast (SEC), and thrombi were also detected by 2D and 3D TEE in all patients. In addition, LAA lobes and types were classified according to the morphology by 3D TEE, and the relationship between LAA types and the incidence of thrombi was evaluated. RESULTS: Long-standing AFib had greater enlargement of LAAs (orifice diameters and area), significantly more severe SEC, and a higher thrombi clot incidence rate by 3D-TEE compared with paroxysmal AFib patients (P<0.05). In addition, cauliflower morphology in long-standing AFib patients was associated with a higher LAA thrombus (OR 2.1, 95% CI: 1.1-8.5, P=0.031) and increased prevalence of SEC. Moreover, the uncertainty of thrombi detection was significantly decreased by 3D TEE compared with 2D TEE (P<0.001), and the certainty of thrombi detection by 3D TEE also decreased slightly (P=0.06). CONCLUSIONS: RT-3D TEE is a safe and real-time option for the evaluation of LAA morphology and function. Long-standing AFib has greater LAA and SEC, as well as a higher incidence of thrombi than the paroxysmal group. Cauliflower LAA type was associated with a higher prevalence of SEC and thrombi.

Electrocardiogram-based sleep analysis for sleep apnea screening and diagnosis.

PURPOSE: Despite the increasing number of research studies of cardiopulmonary coupling (CPC) analysis, an electrocardiogram-based technique, the use of CPC in underserved population remains underexplored. This study aimed to first evaluate the reliability of CPC analysis for the detection of obstructive sleep apnea (OSA) by comparing with polysomnography (PSG)-derived sleep outcomes. METHODS: Two hundred five PSG data (149 males, age 46.8 ± 12.8 years) were used for the evaluation of CPC regarding the detection of OSA. Automated CPC analyses were based on ECG signals only. Respiratory event index (REI) derived from CPC and apnea-hypopnea index (AHI) derived from PSG were compared for agreement tests. RESULTS: CPC-REI positively correlated with PSG-AHI (r = 0.851, p < 0.001). After adjusting for age and gender, CPC-REI and PSG-AHI were still significantly correlated (r = 0.840, p < 0.001). The overall results of sensitivity and specificity of CPC-REI were good. CONCLUSION: Compared with the gold standard PSG, CPC approach yielded acceptable results among OSA patients. ECG recording can be used for the screening or diagnosis of OSA in the general population.

Knockdown of Nemo­like kinase promotes metastasis in non­small­cell lung cancer.

The evolutionarily conserved serine/threonine kinase Nemo­like kinase (NLK) serves an important role in cell proliferation, migration, invasion and apoptosis by regulating transcription factors among various cancers. In the present study, the function of NLK in human non­small cell lung cancer (NSCLC) was investigated. Immunohistochemical analysis and western blotting demonstrated that NLK expression was significantly reduced in NSCLC tissues compared with corresponding peritumoral tissues. Statistical analysis revealed that decreased NLK expression was associated with the presence of primary tumors, tumor node metastasis (TNM) staging, differentiation, lymph node metastasis, and E­cadherin and vimentin expression. Univariate analysis indicated that NLK expression, differentiation, lymph node metastasis, TNM stage, and E­cadherin and vimentin expression affected the prognosis of NSCLC. Cox regression analyses revealed NLK expression and TNM as independent factors that affected prognosis. Kaplan­Meier survival analysis revealed that patients with NSCLC and low NLK expression had relatively shorter durations of overall survival. In vitro, NLK overexpression inhibited A549 ncell migration and invasion as determined by wound healing and Transwell migration assays, respectively. Additionally, immunofluorescence staining indicated that downregulation of NLK expression could induce epithelial­mesenchymal transition in NSCLC. NLK knockdown significantly decreased the expression of the epithelial marker E­cadherin, and markedly increased that of ß­catenin and the mesenchymal marker vimentin. Furthermore, NLK was reported to directly interact with ß­catenin as determined by a co­immunoprecipitation assay. Collectively, the results of the present study indicated that decreased NLK expression could promote tumor metastasis in NSCLC.

Inhibition effects of Yuxiao San combined with cisplatin on transplanted tumor growths via upregulation of nm-23 and downregulation of K-ras in Lewis lung cancer mice.

Traditional Chinese medicine applied to cancer therapy has a long history. This study aimed to investigate the effect and underlying mechanism of the traditional Chinese medicine, Yuxiao San, in combination with cisplatin, on Lewis lung cancer mice. Lewis lung cancer mouse models were were established in mice, and were randomly divided into model (normal saline + egg white), cisplatin (cisplatin injection + egg white), traditional Chinese medicine (Yuxiao San + egg white) and combined medication (Yuxiao San + cisplatin injection + egg white) groups. The weight and tumor size of mice was measured every 3 days, and the number of lung surface metastasis nodules were calculated after 14 days. Nucleoside diphosphate kinase (nm-23) and K-ras expression levels in tumor tissues were determined by immunohistochemical methods and reverse transcription- quantitative polymerase chain reaction. The results suggested that compared with the model group, cisplatin, traditional Chinese medicine and combined medication groups significantly inhibited growth of transplanted tumors, reduced the number of lung metastasis nodules, increased the inhibition rate of lung metastasis (P<0.05 or P<0.01), significantly increased tumor suppressor gene nm-23 expression and significantly downregulated oncogene K-ras expression. Among all groups, the effect of the combined medication group for inhibiting tumor growth was most favorable (P<0.01). Compared with the cisplatin group, nm-23 expression in the traditional Chinese medicine group and the combined medication group was significantly increased, and K-ras expression in the traditional Chinese medicine and combined medication groups was significantly reduced (P<0.01). To conclude, Yuxiao San and cisplatin injection effectively inhibited growth of the transplanted tumor. The underlying mechanism may be associate with nm-23 upregulation and K-ras downregulation. Therefore, the Yuxiao San and cisplatin injection may become a potential therapeutic strategy for tumor treatment.

Enhanced flux performance of polyamide composite membranes prepared via interfacial polymerization assisted with ethyl formate.

A novel thin film composite (TFC) polyamide reverse osmosis membrane was prepared via the interfacial polymerization of m-phenylene diamine (MPD) in aqueous phase and 1,3,5-trimesoyl chloride (TMC) in organic phase on a polysulfone ultrafiltration support by assisting with ethyl formate as a co-solvent added in the organic phase. The ethyl formate added in the organic phase is intended to form a narrow miscibility zone, which leads to the thicker reaction zone. The multi-layered loose polyamide structure with larger pore size was formed due to the thicker reaction zone and lower content of MPD. The enhanced hydrophilicity of the membrane was proved by the decreased water contact angle. Water flux was measured at 1.6 MPa with 2,000 ppm NaCl aqueous solution. Compared to the TFC membrane prepared without ethyl formate, the water flux across the TFC membrane with ethyl formate in the organic phase increased with the increased ethyl formate content (from 23 to 45 L/(m2 h)) and the salt rejection remained at a high level (>90%). The ethyl formate can be used as a co-solvent to effectively enhance the performance of the TFC membrane.

[Study on the Mechanism of Yiqi Chutan Recipe in the Treatment of Lung Cancer with Splenasthenic Syndrome].

Objective: To investigate the mechanism of Yiqi Chutan recipe( YCR) in the treatment of lung cancer with splenasthenic syndrome from the perspective of the endoplasmic reticulum stress( ERS). Methods: 60 mice were successfully modeled as Lewis lung cancer mice with spleen deficiency, which were randomly divided into model group( normal saline),cisplatin group( 1 mg / kg),low dose( 2 g/kg) YCR group, middle dose( 4 g/kg) YCR group,high dose( 8 g/kg) YCR group and the combined medication group( YCR 4 g/kg + cisplatin 1 mg / kg),with 10 mice in each group. The mice were killed after 14 days,the size and weight of tumor in mice were measured,morphological changes of tumor were observed by HE staining method, the expression of CHOP and DR5 protein in tumor tissue was detected by immunohistochemical method and Western blot method. Results: Compared with model group, the volume and weight of tumor in cisplatin group, middle dose YCR group, high dose YCR group and combined medication group were significantly decreased( P < 0. 01),and the tumor cells in transplanted tumor were large necrosis and the protein expression of CHOP and DR5 were increased significantly( P < 0. 01). The effect in treatment of lung cancer with splenasthenic syndrone in combined medication group was higher( P < 0. 05 or P < 0. 01). Conclusion: Yiqi Chutan recipe has different degrees of inhibition on lung cancer, the combined use of cisplatin can obviously improve the curative effect. The mechanism may be related to up-regulating the expression of CHOP and DR5 in endoplasmic reticulum stress-related proteins.