Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Lung-PNet: An Automated Deep Learning Model for the Diagnosis of Invasive Adenocarcinoma in Pure Ground-Glass Nodules on Chest CT.

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

Cuproptosis-related lncRNAs ovarian cancer: Multi-omics analysis of molecular mechanisms and potential therapeutic targets.

Ovarian cancer (OV) is an aggressive malignancy that poses a significant threat to the health and lives of women. Cuproptosis is a newly discovered form of programmed cell death that offers a promising therapeutic target, although its significance in cancer progression remains uncertain. In this study, we established a prognostic model of OV with six cuproptosis-related long non-coding RNAs (lncRNAs), including CTC.246B18.8, LINC00337, RP11.568N6.1, RP11.158I9.8, RP11.678G14.3 and CYP4F26P, based on the data of The Cancer Genome Atlas (TCGA). Lower risk scores were associated with favorable prognosis. In addition, a negative outcome was associated with high expression of CTC.246B18.8. According to the ESTIMATE algorithm, CTC.246B18.8 was negatively correlated with the ImmuneScore, and positively with immune checkpoints, immune cell infiltration, and tumor mutation burden (TMB). Moreover, gene set enrichment analysis (GSEA) revealed that pathways related to immunosuppression are likely activated in response to CTC-246B18.8 overexpression. Furthermore, CTC-246B18.8 expression was also associated with the sensitivity to various chemotherapy drugs. The expression patterns of the above lncRNAs were verified in ovarian tumor cell lines (SK-OV-3, COC1, and A2780) and normal ovarian epithelial cells (IOSE - 80). Six cuproptosis-related genes (CRGs), including ATP7B, MTF1, SLC31A1, DLD, ATP7A and DLAT, were differentially expressed between CTC-246B18.8high and CTC-246B18.8low patient groups, and exhibited organ-specific expression patterns pan-cancer. Small molecule drugs that target these CRGs were predicted, and potential candidates included DIAMIDE, bathocuproine disulfonate, D-penicillamine, etc. To summarize, our findings provide molecular insights into the role of cuproptosis in OV, and the signature lncRNAs and CRGs should be investigated further as immunotherapy biomarkers of OV.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue.

BACKGROUND: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. METHODS: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). CONCLUSION: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Association between spirometry pattern, left ventricular diastolic function, and mortality.

BACKGROUND: Spirometric abnormalities have been related to incident heart failure in general population, who generally have preserved left ventricular ejection fraction (LVEF). We aimed to investigate the association between spirometric indices, cardiac functions and clinical outcomes. METHODS: Subjects presenting with exertional dyspnoea and received spirometry and echocardiography were eligible for this study. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)/FVC ratio were measured to define the spirometry patterns: normal (FEV1/FVC ≥ 70%, FVC ≥ 80%), obstructive (FEV1/FVC < 70%, FVC ≥ 80%), restrictive pattern (FEV1/FVC ≥ 70%, FVC < 80%) and mixed (FEV1/FVC < 70%, FVC < 80%). The diastolic dysfunction index (DDi) was the counts of the indicators, including septal e' velocity <7 cm/s, septal E/e' > 15, pulmonary artery systolic pressure > 35 mmHg and left atrial dimension >40 mm. RESULTS: Among a total of 8669 participants (65.8 ± 16.3 years, 56% men), 3739 (43.1%), 829 (9.6%), 3050 (35.2%) and 1051 (12.1%) had normal, obstructive, restrictive and mixed spirometry pattern, respectively. Subjects with restrictive or mixed spirometry pattern had higher DDi and worse long-term survival than those with obstructive or normal ventilation. FVC but not FEV1/FVC was predictive of 5-year mortality, independent of age, sex, renal function, LVEF, DDi, body mass index, and comorbidities (hazard ratio, 95% confidence intervals: .981, .977-.985). Furthermore, there was an inverse nonlinear relationship between FVC and DDi, suggesting the declined FVC may mediate 43% of the prognostic hazard of left ventricular diastolic dysfunction. CONCLUSIONS: The restrictive spirometry pattern or the declined FVC was associated with left ventricular diastolic dysfunction, which aggravated the long-term mortality in the ambulatory dyspnoeic subjects.

The value on SUV-derived parameters assessed on 18F-FDG PET/CT for predicting mediastinal lymph node metastasis in non-small cell lung cancer.

PURPOSE: To explore valuable predictors for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from preoperative 18F-FDG PET/CT combined with clinical characteristics. METHODS: Data from 224 NSCLC patients who underwent preoperative 18F-FDG PET/CT scans in our hospital were collected. Then, a series of clinical parameters including SUV-derived features [SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] were evaluated. The best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Predictive analyses were performed using a Logistic regression model to determine the predictive factors for mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. After multivariate model construction, data of another 100 NSCLC patients were recorded. Then, 224 patients and 100 patients were enrolled to validate the predictive model by the area under the receiver operating characteristic curve (AUC). RESULTS: The mediastinal lymph node metastasis rates in 224 patients for model construction and 100 patients for model validation were 24.1% (54/224) and 25% (25/100), respectively. It was found that SUVmax of mediastinal lymph node ≥ 2.49, primary-tumor SUVmax ≥ 4.11, primary-tumor SUVpeak ≥ 2.92, primary-tumor SUVmean ≥ 2.39, primary-tumor MTV ≥ 30.88 cm3, and primary-tumor TLG ≥ 83.53 were more prone to mediastinal lymph node metastasis through univariate logistic regression analyses. The multivariate logistic regression analyses showed that the SUVmax of mediastinal lymph nodes (≥ 2.49: OR 7.215, 95% CI 3.326-15.649), primary-tumor SUVpeak (≥ 2.92: OR 5.717, 95% CI 2.094-15.605), CEA (≥ 3.94 ng/ml: OR 2.467, 95% CI 1.182-5.149), and SCC (< 1.15 ng/ml: OR 4.795, 95% CI 2.019-11.388) were independent predictive factors for lymph node metastasis in the mediastinum. It was found that SUVmax of the mediastinal lymph node (≥ 2.49: OR 8.067, 95% CI 3.193-20.383), primary-tumor SUVpeak (≥ 2.92: OR 9.219, 95% CI 3.096-27.452), and CA19-9 (≥ 16.6 U/ml: OR 3.750, 95% CI 1.485-9.470) were significant predictive factors for mediastinal lymph node metastasis in lung adenocarcinoma patients. The AUCs for the predictive value of the NSCLC multivariate model through internal and external validation were 0.833 (95% CI 0.769- 0.896) and 0.811 (95% CI 0.712-0.911), respectively. CONCLUSION: High SUV-derived parameters (SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, MTV and TLG) might provide varying degrees of predictive value for mediastinal lymph node metastasis in NSCLC patients. In particular, the SUVmax of mediastinal lymph nodes and primary-tumor SUVpeak could be independently and significantly associated with mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. Internal and external validation confirmed that the pretherapeutic SUVmax of the mediastinal lymph node and primary-tumor SUVpeak combined with serum CEA and SCC can effectively predict mediastinal lymph node metastasis of NSCLC patients.

Independently tunable multi-band terahertz absorber based on graphene sheet and nanoribbons.

A multi-band terahertz (THz) absorber based on graphene sheet and nanoribbons is proposed and investigated. In the studied frequency range, five absorption peaks are observed, with four originate from lateral Fabry-Perot resonance (LFPR) and one originates from guided-mode resonance (GMR). The LFPR and GMR peaks behave differently when geometric parameters are adjusted, which makes independent tuning possible. When period increases, the GMR peak red shifts and the frequencies of LFPR peaks remain almost unchanged. On the contrary, as nanoribbon width increases, the frequency of GMR remains almost unchanged while that of LFPRs decrease significantly. With increasing top dielectric layer thickness, the LFPR peaks blue shift while the GMR peak red shifts. In addition, the absorber has the merit of multi-band high absorptivity and frequency stability under large angle oblique incidence. The proposed terahertz absorber may benefit the areas of medical imaging, sensing, non-destructive testing, THz communications and other applications.

Evidence for Assimilatory Nitrate Reduction as a Previously Overlooked Pathway of Reactive Nitrogen Transformation in Estuarine Suspended Particulate Matter.

Suspended particulate matter (SPM) contributes to the loss of reactive nitrogen (Nr) in estuarine ecosystems. Although denitrification and anaerobic ammonium oxidation in SPM compensate for the current imbalance of global nitrogen (N) inputs and sinks, it is largely unclear whether other pathways for Nr transformation exist in SPM. Here, we combined stable isotope measurements with metagenomics and metatranscriptomics to verify the occurrence of dissimilatory nitrate reduction to ammonium (DNRA) in the SPM of the Pearl River Estuary (PRE). Surprisingly, the conventional functional genes of DNRA (nirBD) were abundant and highly expressed in SPM, which was inconsistent with a low potential rate. Through taxonomic and comparative genomic analyses, we demonstrated that nitrite reductase (NirBD) in conjunction with assimilatory nitrate reductase (NasA) performed assimilatory nitrate reduction (ANR) in SPM, and diverse alpha- and gamma-proteobacterial lineages were identified as key active heterotrophic ANR bacteria. Moreover, ANR was predicted to have a relative higher occurrence than denitrification and DNRA in a survey of Nr transformation pathways in SPM across the PRE spanning 65 km. Collectively, this study characterizes a previously overlooked pathway of Nr transformation mediated by heterotrophic ANR bacteria in SPM and has important implications for our understanding of N cycling in estuaries.

Pulmonary vascular volume is associated with DLCO and fibrotic score in idiopathic pulmonary fibrosis: an observational study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease that primarily occurs in elderly individuals. However, it is difficult to diagnose and has a complex disease course. High-resolution computed tomography (HRCT) and lung function testing are crucial for its diagnosis and follow-up. However, the correlation of HRCT findings with lung function test results has not been extensively investigated. METHODS: This study retrospectively analysed the medical records and images of patients with IPF. Patients with evident emphysema and lung cancer were excluded. The diagnosis of all the included cases was confirmed following a discussion among specialists from multiple disciplines. The correlation of HRCT findings, including fibrotic score, HRCT lung volume, pulmonary artery trunk (PA) diameter and pulmonary vascular volume (PVV), with lung function test parameters, such as forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), was analysed. RESULTS: A total of 32 patients were included. Higher fibrotic and PVV scores were significantly correlated with lower DLCO (r = - 0.59, p = 0.01; r = - 0.43, p = 0.03, respectively) but not with FVC. Higher PVV score significantly correlated with higher fibrotic score (r = 0.59, p < 0.01) and PA diameter (r = 0.47, p = 0.006). CONCLUSION: Our study demonstrated the structural and functional correlation of IPF. The extent of lung fibrosis (fibrotic score) and PVV score were associated with DLCO but not with FVC. The PA diameter, which reflects the pulmonary artery pressure, was found to be associated with the PVV score.

Percutaneous transluminal angioplasty and stenting of post-irradiated stenosis of subclavian artery.

BACKGROUND/PURPOSE: The therapeutic efficacy of percutaneous transluminal angioplasty and stenting (PTAS) of post-irradiated stenosis of subclavian artery (PISSA) was not well clarified. This retrospective study was designed to evaluate the technical safety and outcome of the patients of severe symptomatic PISSA accepted PTAS. METHODS: Between 2000 and 2019, 16 cases with 17 lesions of symptomatic and medically refractory PISSA accepted PTAS were included. We evaluated their technical success, peri-procedural complications and diffusion-weight imaging (DWI) of brain magnetic resonance imaging (MRI), results of symptom relief, and long-term stent patency. RESULTS: The stenosis of the 17 stenotic lesions were 81.2 ± 11.1%. The most common symptom of the 16 patients was dizziness (14/16, 87.5%). All successfully accepted PTAS without neurological complication and had symptom relief after PTAS (17/17, 100%). Of the 12 patients accepted pre-procedural and early post-procedural MRI follow-up, 2 patients had an asymptomatic tiny acute embolic infarct in the territory of vertebrobasilar system. In a 51.9 ± 54.9 months follow-up, all patients had no severe restenosis and no recurrent vertebrobasilar ischemic symptoms. CONCLUSION: For patients with PISSA and medically refractory ischemic symptoms, PTAS can be an effective alternative management.

Anion-Guided Stepwise Assembly of High-Nuclearity Lanthanide Hydroxide Clusters.

The ability to construct complex molecular architectures with precise control is critical for realizing molecule-based materials and functions. Using the assembly of a 60-metal complex of ErIII with histidine as an example, we demonstrate the rational assembly of otherwise synthetically elusive polynuclear lanthanide hydroxide clusters directed by the combined set of I- and CO3 2- as templates. We succeeded in the stepwise transformation starting from Er12 to Er60 by way of two key intermediates Er34 and Er48 . The Er12 , Er34 , and Er48 core motifs represent respectively 1/6, 1/2, and 3/4 of the complete sodalite cage of Er60 . This work, representing a rare example of rationally constructing high-nuclearity lanthanide clusters guided by judiciously chosen templates, is expected to stimulate more future efforts for the controllable synthesis of complex molecular or supramolecular architectures with unprecedented structural sophistication and possibly useful properties.

Integrated analysis of methylation-driven genes and pretreatment prognostic factors in patients with hepatocellular carcinoma.

BACKGROUND: The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and then construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients. METHODS: The gene methylation, gene expression dataset and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Methylation-driven genes were screened with a Pearson's correlation coefficient less than - 0.3 and a P value less than 0.05. Univariable and multivariable Cox regression analyses were performed to construct a risk score model and identify independent prognostic factors from the clinical parameters of HCC patients. The least absolute shrinkage and selection operator (LASSO) technique was used to construct a nomogram that might act to predict an individual's OS, and then C-index, ROC curve and calibration plot were used to test the practicability. The correlation between clinical parameters and core methylation-driven genes of HCC patients was explored with Student's t-test. RESULTS: In this study, 44 methylation-driven genes were discovered, and three prognostic signatures (LCAT, RPS6KA6, and C5orf58) were screened to construct a prognostic risk model of HCC patients. Five clinical factors, including T stage, risk score, cancer status, surgical method and new tumor events, were identified from 13 clinical parameters as pretreatment-independent prognostic factors. To avoid overfitting, LASSO analysis was used to construct a nomogram that could be used to calculate the OS in HCC patients. The C-index was superior to that from previous studies (0.75 vs 0.717, 0.676). Furthermore, LCAT was found to be correlated with T stage and new tumor events, and RPS6KA6 was found to be correlated with T stage. CONCLUSION: We identified novel therapeutic targets and constructed an individual prognostic model that can be used to guide personalized treatment in HCC patients.

Phylogenetically divergent bacteria consortium from neutral activated sludge showed heightened potential on bioleaching spent lithium-ion batteries.

Recycling of spent lithium-ion batteries (LIBs) has become a global issue because of the potential environment risks raised by spent LIBs as well as high valuable metal content remaining in them. Although bioleaching is an environmentally friendly method to recover metals from spent LIBs, the commonly utilized bioleaching bacterial consortia or strains enriched/isolated from acidic environments cannot be applied at large scales owing to their long leaching cycle and poor tolerance to organic compounds. Here, two bioleaching consortia were enriched in 60 days from neutral activated sludge and were identified phylogenetically divergent from the documented bioleaching bacteria. The results showed that the novel consortia shortened the leaching cycle almost by half when compared to the previous reported consortia or strains, of which one consortium dominated by Acidithiobacillus ferrooxidans displayed high bioleaching efficiency on LiMn2O4, as 69.46% lithium (Li) and 67.60% manganese (Mn) were leached out in seven days. This consortium was further domesticated using cathodic materials for 100 days and proved consisted of three mixotrophs and two chemoautotrophs, three of which were novel species from the genera Sulfobacillus and Leptospirillum. More genes coding for proteins that utilize organic compounds were annotated in the metagenomic assembled genomes (MAGs) than previously reported. A mutualistic relationship between mixotrophs and chemoautotrophs was suggested to help the consortium surviving under either organic- rich or shortage environments. The results discovered that novel bioleaching bacteria with shorter leaching cycle and higher tolerance to organics could be enriched from non-acidic environments, which showed high potential for the metal recovering from spent LIBs or other organic-rich environments.

Feasibility of the transcatheter mitral valve repair for patients with severe mitral regurgitation and endangered heart failure.

BACKGROUND: The transcatheter edge-to-edge mitral valve repair using MitraClip has been a safe and effective treatment for severe mitral regurgitation (MR). In patients with severe MR and cardiogenic shock under hemodynamic supporting devices, emergent surgical mitral valve interventions carry extremely high risk for peri-operative morbidities and mortalities. The feasibility and efficacy of emergent MitraClip to rescue patients in critical conditions remains elucidate. METHODS: Patients with severe MR and high or prohibitive surgical risks were referred for MitraClip procedures. Emergent MitraClip were conducted in patients with unstable hemodynamics and under mechanical or inotropic support. The hemodynamic measures, transthoracic echocardiography, transesophageal echocardiography, and blood tests were performed before MitraClip procedures. Procedural success was defined as having mild mitral regurgitation immediately after MitraClip, and patients were free from in-hospital mortality. Clinical and echocardiographic outcomes were followed by telephones and clinics. RESULTS: Among 50 consecutive patients (74.7 ± 11.2 years, 74% male), 8 emergent MitraClip procedures were conducted to rescue patients with cardiogenic shock. Extracorporeal membrane oxygenations were used in 2 patients and intra-aortic balloon pump were applied in 4 patients (50%). Compare to those who underwent elective procedures, patients underwent emergent MitraClip had higher surgical risk profile (EuroSCORE II 34.8% vs 5.1% and STS score 19.7% vs 5.1%), poorer renal function and higher right atrial pressure. There was no peri-procedural death, myocardial infarction, stroke or any adverse events requiring emergent cardiac surgery in both groups. Mild mitral regurgitation was achieved in 87.5% patients from the emergent group and 95.2% patients in the elective group (P = 0.514). The Kaplan-Meier analysis showed patients who underwent emergent procedures have poorer long-term survival rate as compare to those who received elective procedures. (P value = 0.008). CONCLUSION: When open-heart surgery is not feasible, trans-catheter mitral valve repair is an alternative way to rescue patients in cardiogenic shock status.

[A new cembranoid diterpene from Olibanum].

Five compounds were isolated from the alcohol extract of Olibanum by MCI, silica gel, ODS, and Sephadex LH-20 column chromatographies and preparative high-performance liquid chromatography(HPLC). On the basis of spectral data and literature data, the compounds were identified as:(1S,3R,4S,7R,11S,12R)-1:12,4:7-diepoxisonane-8(19)-ene-3,11-diol(1), boscartin A(2),(+)-resinolin(3),(+)-5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one(4), and acerogenin A(5). Compound 1 is a new compound, and compounds 3-5 were isolated from Olibanum for the first time. The structure of compound 1 was determined by spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1 and 2 were tested for PC12 neurotoxicity, and the results showed that they were both safe compounds.

[A new sesquiterpene from Chloranthus henryi].

Eight sesquiterpenes were isolated and purified from the ethanol extract of Chloranthus henryi by column chromatographies over silica gel, ODS and Sephadex LH-20,and preparative HPLC. Their chemical structures were established by spectral data and physiochemical properties as(1S,6S,8S,10R)-8-ethoxy-10-methoxychlomultin C(1),tianmushanol(2),multistalide A(3),myrrhterpenoid N(4),1α,9α-dihydroxy-8,12-expoxy-eudesma-4,7,11-trien-6-one(5),4ß,10α-aromadendranediol(6),oplopanone(7),10α-hydroxycadinan-4-en-3-one(8). Among them, compound(1) was a new compound, and compounds 2-8 were isolated from Chloranthus henryi for the first time.

[Research progress on chemical constituents from Chloranthus plants and their biological activities].

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.

[A new labdane-type diterpenoids from Callicarpa nudiflora].

The purpose of the research is to study the bioactive constituents of Callicarpa nudiflora. From the 65% ethanol extract of C. nudiflora leaves, ten compounds were isolated by macroporous adsorption resin, Sephadex LH-20, ODS, silica gel, and preparative HPLC. These compounds were identified as callicapene M6(1), sterebin A(2), isomartynoside(3), crenatoside(4), luteolin-7-O-neohesperidoside(5), apigenin-7-O-ß-D-neohesperidoside(6), isoacteoside(7), acteoside(8),(7R)-campneoside I(9), and(7S)-campneoside I(10) on the basis of NMR, HR-ESI-MS, and optical rotation data. Compound 1 was obtained as a new compound. Compounds 2 and 4 were isolated from the genus Callicarpa for the first time. Compounds 9 and 10 were isolated from C. nudiflora for the first time.

[Chemical constituents of sesquiterpenes from Chloranthus multistachys].

With repeated silica gel, octadecyl silica(ODS), and Sephadex LH-20 column chromatography, normal-phase and reverse-phase high performance liquid chromatography(HPLC), etc., a pair of new enantiomers and 5 known compounds were separated from the 95% ethanol extract of Chloranthus multistachys. These compounds were identified by the nuclear magnetic resonance spectroscopy(including 1 D-NMR and 2 D-NMR), single-crystal X-ray diffraction, circular dichroism(CD) spectroscopy, mass spectrometry(MS), and some other methods as(1R,4R,5R,8S,10R)-chloraeudolide H(1 a),(1S,4S,5S,8R,10S)-chloraeudolide H(1 b), hydroxyisogermafurenolide(2), 4α-hydroxy-5α,8ß(H)-eudesm-7(11)-en-8,12-olide(3), chloraniolide A(4), chlorantene D(5), 4α,8ß-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide(6). Compounds 1 a and 1 b are a pair of new eudesmane-type sesquiterpene enantiomers, and compounds 2-4 were isolated from C. multistachys for the first time.

Effect of Acoustic Cardiography-guided Management on 1-year Outcomes in Patients With Acute Heart Failure.

BACKGROUND: The electromechanical activation time (EMAT) normalized by cardiac cycle length (%EMAT) and the third heart sound (S3) strength, as measured by automated acoustic cardiography, are predictive of postdischarge adverse events in patients with acute heart failure (AHF). The aim of this study was to evaluate whether the acoustic cardiography-guided management improves outcomes in patients with AHF when it is compared with the conventional therapy. METHODS AND RESULTS: This prospective single-blind study randomized 225 patients with AHF (74.1 ± 14.5 years of age, 26.2% women, and left ventricular ejection fraction 38.4 ± 14.4%) before discharge to the EMAT-guided group (n = 114) with the postdischarge treatment goals to reduce %EMAT to < 15% and S3 < 5, and the symptom-guided group (n = 111) to adjust medications without knowledge of the results of acoustic cardiography. The primary endpoints were rehospitalization for heart failure and total mortality during 1-year follow-up. The 2 groups were well matched in age and predischarge %EMAT and S3 strength. After a mean follow-up period of 238.1 ± 140.8 days, a significant reduction in the primary endpoints was seen in the EMAT-guided group compared with the symptom-guided group (43 events vs 61 events, P = 0.0095). Kaplan-Meier curves demonstrated significant differences in the time to first event, favoring the EMAT-guided group in the total study population (n = 225, hazard ratio and 95% confidence interval: 0.61, 0.42-0.91, log-rank P = 0.0129), as well as in the prespecified subgroup of patients with predischarge %EMAT > 15% (n = 85; 0.32, 0.16-0.65, P = 0.0008). CONCLUSIONS: In patients hospitalized due to AHF, EMAT-guided postdischarge management was superior to the conventional symptoms-driven therapy in terms of 1-year outcomes (ClinicalTrials.gov number NCT01298232).