Molecular mechanism of the treatment of lung adenocarcinoma by Hedyotis Diffusa: an integrative study with real-world clinical data and experimental validation.

Background: With a variety of active ingredients, Hedyotis Diffusa (H. diffusa) can treat a variety of tumors. The purpose of our study is based on real-world data and experimental level, to double demonstrate the efficacy and possible molecular mechanism of H. diffusa in the treatment of lung adenocarcinom (LUAD). Methods: Phenotype-genotype and herbal-target associations were extracted from the SymMap database. Disease-gene associations were extracted from the MalaCards database. A molecular network-based correlation analysis was further conducted on the collection of genes associated with TCM and the collection of genes associated with diseases and symptoms. Then, the network separation SAB metrics were applied to evaluate the network proximity relationship between TCM and symptoms. Finally, cell apoptosis experiment, Western blot, and Real-time PCR were used for biological experimental level validation analysis. Results: Included in the study were 85,437 electronic medical records (318 patients with LUAD). The proportion of prescriptions containing H. diffusa in the LUAD group was much higher than that in the non-LUAD group (p < 0.005). We counted the symptom relief of patients in the group and the group without the use of H. diffusa: except for symptoms such as fatigue, palpitations, and dizziness, the improvement rate of symptoms in the user group was higher than that in the non-use group. We selected the five most frequently occurring symptoms in the use group, namely, cough, expectoration, fatigue, chest tightness and wheezing. We combined the above five symptom genes into one group. The overlapping genes obtained were CTNNB1, STAT3, CASP8, and APC. The selection of CTNNB1 target for biological experiments showed that the proliferation rate of LUAD A549 cells in the drug intervention group was significantly lower than that in the control group, and it was concentration-dependent. H. diffusa can promote the apoptosis of A549 cells, and the apoptosis rate of the high-concentration drug group is significantly higher than that of the low-concentration drug group. The transcription and expression level of CTNNB1 gene in the drug intervention group were significantly decreased. Conclusion: H. diffusa inhibits the proliferation and promotes apoptosis of LUAD A549 cells, which may be related to the fact that H. diffusa can regulate the expression of CTNNB1.

Cross-shore parallel tidal channel systems formed by alongshore currents.

Parallel tidal channel systems, characterized by commonly cross-shore orientation and regular spacing, represent a distinct class of tidal channel networks in coastal environments worldwide. Intriguingly, these cross-shore oriented channel systems can develop in environments dominated by alongshore tidal currents, for which the mechanisms remain elusive. Here, we combine remote sensing imagery analysis and morphodynamic simulations to demonstrate that the deflection of alongshore tidal currents at transitions in bed elevation determines the characteristic orientation of the parallel tidal channels. Numerical results reveal that sharp changes in bed elevation lead to nearly 90-degree intersection angles, while smoother transitions in bed profiles result in less perpendicular channel alignments. These findings shed light on the potential manipulation of tidal channel patterns in coastal wetlands, thus equipping coastal managers with a broader range of strategies for the sustainable management of these vital ecosystems in the face of climate change and sea level rise.

The association between O2-pulse slope ratio and functional severity of coronary stenosis: A combined cardiopulmonary exercise testing and quantitative flow ratio study.

Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.

Spatio-temporal evolution and driving factors of new urbanization in central China based on multi-source data.

Urbanization is an inevitable outcome of the development of human society to a certain stage, and it is also an irreversible pattern of the concentration degree of human society. Based on multi-source data such as remote sensing images, ecological environment and socio-economic data, the evaluation index system of new urbanization is constructed from multi-dimensions of population, economy, society, space and ecology. To explore the spatio temporal evolution and driving factors of urbanization in 80 prefecture-level cities in central China from 2013 to 2021 by using entropy method, spatial autocorrelation model and geographic detector. The results show that: (1) The level of new urbanization continues to grow, with the average value rising from 0.1562 in 2013 to 0.2557 in 2021, and the regional differences are obvious, forming a circle structure with Wuhan, Zhengzhou and other provincial capitals as the center and weakening radiation to surrounding cities. (2) The agglomeration of ecological urbanization is significant, and the agglomeration trend is gradually enhanced. The high-high agglomeration areas tend to Xinzhou City, most prefecture-level cities in Hubei Province and some prefecture-level cities in Southern Hunan Province, while the low-low agglomeration areas tend to Changzhi City, most prefecture level cities in Henan Province and some prefecture-level cities in Northern Anhui Province. (3) The night light index, total retail sales of consumer goods, investment in fixed assets, proportion of built-up areas and urban economic density are the main driving factors affecting the level of new urbanization. (4) The interaction of driving factors shows double factor enhancement and nonlinear enhancement effects.

Effect of Yifei Qinghua Granule on the Tumor Microenvironment in Lung Cancer by Regulating the Inflammatory Pathway.

To investigate the mechanism of action of inflammatory molecules regulating the tumor microenvironment and anti-tumor through Yifei Qinghua granules and phloroglucinol-containing serum intervening in the changes of tumor microenvironment in vitro in the co-culture of lung cancer cells and bone marrow cells.  A549 lung adenocarcinoma cell line and ST2 bone marrow stromal cell line were selected and a transwell chamber was used to establish the co-culture system of the two kinds of cells. They were divided into normal saline, phloroglucinol, Qifei Qinghua granule, and phloroglucinol + Yifei Qinghua granule groups. They were given drug-containing serum interventions respectively. A549 cells and ST2 cells cultured separately were used as control. Flow cytometry was used to detect the proportions of MDSCs and Tregs in bone marrow cells of ST2 cells. ELISA was used to detect the levels of inflammatory factors in the culture supernatant. Western blot was used to detect the expressions of inflammatory pathways in A549 and ST2 cells. ST2 cells and A549 cells were co-cultured. The ratio of MDSCs and Treg in ST2 cells was increased. The levels of some inflammatory factors in the culture supernatant were increased. The expression level of the inflammatory pathway in ST2 cells was increased. However, the expression level of the inflammatory pathway in A549 cells had no obvious change. While Yifei Qinghua granule and phloroglucinol could partially reverse these changes. The combination of the two was more effective than a single drug. The conversion of cells to MDSCs and Treg was accelerated after the co-culture of ST2 cells and A549 cells. The combination of Yifei Qinghua granules with phloroglucinol can reshape the tumor microenvironment, prevent this phenomenon from occurring, reduce inflammatory secretion and inhibit tumor cell growth. This may be related to the inhibition of the expressions of TNF-α/IL-1- and NF-κB/STAT3 inflammatory pathways.

Synergistic effect of excellent carriers separation and efficient high level energy electron utilization on Bi3+-Ce2Ti2O7/ZnIn2S4 heterostructure for photocatalytic hydrogen production.

The separation of photogenerated carriers and the efficient utilization of high-level energy electrons (HLEEs) are the key processes for improving the performance of photocatalysts. Herein, Ce2Ti2O7/ZnIn2S4 (CTOZIS) and Bi3+-doped Ce2Ti2O7/ZnIn2S4 (BCTOZIS) photocatalyst were successfully synthesized through hydrothermal method. The photocatalytic hydrogen production of CTOZIS and BCTOZIS was 1233.7 µmol g-1 and 4168.5 µmol g-1 under visible light irradiation (λ ≥ 420 nm) within 5 h, which was 2.3 and 7.6 times than that of pure ZnIn2S4, respectively. X-ray photoelectron spectroscopy, photoluminescence spectroscopy and electrochemical characterization demonstrated that after Bi3+ doping, the electron-hole pairs recombination of BCTOZIS was inhibited, which may be ascribed to the establishment of a Z-scheme heterojunction and the presence of oxygen vacancy and Ce4+/Ce3+ redox center. The doping of Bi3+ resulted in the adjustment of the valence band position of Ce2Ti2O7 from 1.98 V to 1.92 V. This adjustment enabled direct transfer of HLEEs generated in Ce2Ti2O7 to the conduction band of ZnIn2S4 for hydrogen production with a wavelength below 423 nm. The synergistic effect of conventional Z-scheme electron transfer and the unique utilization of HLEEs boosted the photocatalytic performance of BCTOZIS. This study affords an innovative insight for designing visible-light-driven photocatalysts with high photocatalytic activity.

Novel noble-metal-free Co2P/CdIn2S4 heterojunction photocatalysts for elevated photocatalytic H2 production: Light absorption, charge separation and active site.

Constructing heterojunctions is an effective and controllable approach that can boost the activity of photocatalysts. Inspiringly, this study explored a simple method that can be used to construct novel noble-metal-free Co2P/CdIn2S4 (CPCIS) heterojunction photocatalysts for photocatalytic hydrogen production. The heterojunction was formed by loading CdIn2S4 (CIS) nanoparticles on the surface of Co2P (CP). The structure, morphology, and optical property of the as-prepared samples were characterized by a series of tests. The DRS results showed that, the light absorption range of CPCIS was extended to the full visible light range and its light absorption intensity obviously was enhanced at 500-800 nm. The PL and photoelectrochemical tests manifested that the formed heterojunction promoted the separation of charges. The LSV results indicated that CP reduced the H2 evolution overpotential of the composites. Besides, CP could serve as active sites of H2 evolution in heterojunction composites. Interestingly, the H2-evolution rate for the optimum CPCIS (471.87 µmol h-1 g-1) was around 3.6 times than CIS-Pt. The elevated activity of CPCIS may mainly attribute to the following aspects: its enhanced light absorption, elevated charge separation and increased active site. More importantly, the photocatalytic activity of heterojunction composites didn't almost decrease after three cycles. This article delivers an idea that can be applied to form heterojunctions between CP and other sulfides for photocatalytic H2 production, easily extending to other transition metal phosphides.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer.

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION: The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).

Active sites modification and superior carriers separation synergistically boosted hydrogen production of Bi/Bi2MoO6/ZnIn2S4 non-noble metal S-scheme photocatalyst.

Novel Bi/Bi2MoO6/ZnIn2S4 is not only cost-effective compared to noble metals, but also shows superior hydrogen production. Comprehensive characterization illustrated that the S-scheme heterojunction and excellent photon utilization capability of the photocatalyst were the main factors that enhanced its hydrogen production performance. The X-ray photoelectron spectroscopy illustrated the elemental composition of the catalyst and the presence of Bi metal in ternary heterojunction. The photoluminescence and electrochemical characterization proved that S-scheme heterojunction Bi/Bi2MoO6/ZnIn2S4 promoted the separation of photogenerated carriers. The amount of hydrogen produced by Bi/Bi2MoO6/ZnIn2S4 was 2306.90 µmol g-1 under visible light illumination for 5 h. It was 4.3, 29.6 and 2.2 times more than those of ZnIn2S4, Bi2MoO6/ZnIn2S4 and Pt/ZnIn2S4, respectively. The excellent hydrogen production activity of the ternary complexes may be attributed to the following: (1) Bi/Bi2MoO6 could replace precious metals to enhance reactive sites of ZnIn2S4. (2) Metal Bi could produce surface plasmon resonance effect facilitating light absorption, and Bi acted as an electron bridge promoting charge transfer. (3) The charge transfer mechanism of S-scheme heterojunction and hot electrons injection process of Bi metal synergistically drove the photocatalytic hydrogen production. This work provides an innovative method for the construction of visible-light-driven photocatalysts without using precious metals.

Anatomical and Functional Discrepancy in Diabetic Patients With Intermediate Coronary Lesions　- An Intravascular Ultrasound and Quantitative Flow Ratio Study.

BACKGROUND: Data regarding the performance of computational fractional flow reserve in patients with diabetes mellitus (DM) remain scarce. This study sought to explore the impact of DM on quantitative flow ratio (QFR) and its association with intravascular ultrasound (IVUS)-derived anatomical references.Methods and Results: IVUS and QFR were retrospectively analyzed in 237 non-diabetic and 93 diabetic patients with 250 and 102 intermediate lesions, respectively. Diabetics were further categorized based on adequate (HbA1c <7.0%: 47 patients with 53 lesions) or poor (HbA1c ≥7.0%: 46 patients with 49 lesions) glycemic control. Lesions with QFR ≤0.8 or minimum lumen area (MLA) ≤4.0 mm2and plaque burden (PB, %) ≥70 were considered functionally or anatomically significant, respectively. PB increased, and MLA decreased stepwise across non-diabetics, diabetics with adequate glycemic control and those with poor glycemic control. In contrast, QFR was similar among the 3 groups. PB correlated significantly with the QFR for lesions in non-diabetics, but not for lesions in diabetics. DM was independently correlated with the functionally non-significant lesions (QFR >0.8) with high-risk IVUS features (MLA ≤4.0 mm2and PB ≥70; OR 2.053, 95% CI: 1.137-3.707, P=0.017). When considering the effect of glycemic control, HbA1c was an independent predictor of anatomical-functional discordance (OR 1.347, 95% CI: 1.089-1.667, P=0.006). CONCLUSIONS: Anatomical-functional discordance of intermediate coronary lesions assessed by IVUS and QFR is exacerbated in patients with diabetes, especially when glycemia is poorly controlled.

Construction of novel noble-metal-free MoP/CdIn2S4 heterojunction photocatalysts: Effective carrier separation, accelerating dynamically H2 release and increased active sites for enhanced photocatalytic H2 evolution.

Developing novel photocatalysts with high performance is significant for the practical application of photocatalytic H2 production. Herein, novel and noble-metal-free heterojunction photocatalysts contained CdIn2S4 nanoparticles and bulk MoP were prepared. The H2-production rate of optimal MoP/CdIn2S4 (MPCIS) composites achieved at 286.10 µmol g-1h-1, which was nearly 2.2 times that of CdIn2S4-1 %Pt (130.51 µmol g-1h-1). Electrochemical and PL results displayed that MoP cocatalyst could vastly boost the carrier separation efficiency of CdIn2S4. The high carrier separation efficiency maybe put down to the Fermi level rearrangement between MoP and CdIn2S4. The linear sweep voltammograms tests showed that, compared to CdIn2S4, CdIn2S4 with 30 %MoP (30MPCIS) has smaller Tafel slopes and lower H2 evolution overpotentials, which contributed to facilitate H2 release in kinetics. The 30MPCIS composites possess higher Cdl value and MoP has Pt-like electronic structure, so that MoP could offer abundant surface reaction sites of MPCIS composites for HER. Aforementioned results demonstrate that MoP may have great potential in replacing precious metal Pt for photocatalytic H2 production. It is expected that this study can provide new insights into developing the novel sulfide-based heterojunction photocatalysts with MoP as cocatalyst for resultful photocatalytic H2 generation.

Study on the Spatial Interaction between Urban Economic and Ecological Environment-A Case Study of Wuhan City.

In order to study the interactive relationship between urban economic and ecological environment, taking Wuhan as an example, Landsat and MODIS remote sensing satellite data and social and economic data were fused with multisource data, and multidimensional indicators were selected to construct the comprehensive evaluation index system of urban economic and ecological environment. The weights were determined by combining subjective and objective methods. Then, the decoupling elasticity coefficient method and spatial autocorrelation model were used to evaluate the dynamic relationship and spatial relationship between economic development and ecological environment in Wuhan from 2014 to 2020. The results showed that there was an interaction between the urban economic and the ecological environment in Wuhan. The ecological level index had a spatial effect, the adjustment of industrial structure had a positive effect on the improvement of the ecological level, and the improvement of the ecological level was also helpful to promote economic development. The typical districts of Huangpi District, Xinzhou District, Jiangxia District, Hannan District, Caidian District, and Hongshan District had superior location and ecological advantages, as well as high development potential. Lastly, on the basis of the empirical analysis results, policy suggestions are made from four aspects: regional differentiated construction, green development, energy consumption, and wetland construction.

Siah1 promotes the proliferation of NSCLC cells through ubiquitinating and stabilizing Notch1.

Seven in absentia homolog 1 (Siah1) has been shown plays important roles in the pathogenesis and development of multiple cancers. However, the functions and mechanisms of Siah1 in non-small cell lung cancer (NSCLC) remain unclear. In our study, we found that knock down of Siah1 could inhibit the proliferation of NSCLC cells, while over-expression of Siah1 had the opposite effects. Molecularly, the bioinformatics analysis determined that notch receptor 1 (Notch1) might be the potential target of Siah1. Subsequently, we identified that Siah1 acted as an E3 ligase to promote the ubiquitination and stabilization of Notch1 through the proteasome pathway. Furthermore, the results showed that the Siah1 expression was directly correlated with CTR9 in human NSCLC tissues. Finally, Siah1 could promote Akt phosphorylation through regulating Notch1, thus promoting the proliferation of NSCLC cells. In conclusion, our study demonstrated that Siah1 acts as an oncogene, can ubiquitinate and stabilize Notch1 by proteasome pathway, which promotes Akt phosphorylation and ultimately leads to NSCLC cell proliferation.

Fabrication of novel and noble-metal-free MoP/In2S3 Schottky heterojunction photocatalyst with efficient charge separation for enhanced photocatalytic H2 evolution under visible light.

Here, we synthesized a series of noble-metal-free MoP/In2S3 Schottky heterojunction photocatalysts through two-step synthesis. Morphology characterization revealed that In2S3 was deposited on metal-like MoP. The electrochemical experiment, photoluminescence (PL) and time-resolved transient PL results verify that electron-hole pairs separation efficiency of MoP-In2S3 composites has been immensely elevated compared to pristine In2S3. The effective separation of photocarriers is attributed to the appropriate Schottky energy barrier, band bending and Fermi level rearrangement between MoP and In2S3. Furthermore, the X-ray photoelectron spectra confirmed that electrons transferred from In2S3 to MoP in Schottky heterojunction. Importantly, MoP possesses active sites for H2 generation resulting from nearly zero binding for H atoms and low onset overpotentials. As expected, the 25 %MoP-In2S3 composites exhibited excellent photocatalytic activity (481.73 µmol·h-1·g-1), which was about 23 times than In2S3-1 %Pt (20.73 µmol·h-1·g-1). Hence, the enhanced photocatalytic performance was ascribed to not only the formed Schottky heterojunction leading to better charge separation, but also MoP as the active sites accelerated the surface proton reduction reaction. The research furnishes a thought that suitable semiconductors and metal-like were selected to construct high performance and low-cost Schottky heterojunction with efficient charge separation and active sites for resultful photocatalytic H2 generation.

Long-term prognostic value of dynamic function assessment of intermediate coronary lesion with computational physiology.

This study sought to investigate the dynamic functional changes of coronary intermediate lesions using quantitative flow ratio (QFR) and its implication on long-term clinical outcomes. Physiology-guided percutaneous coronary intervention in patients with angiographic intermediate lesions has been associated with favorable outcomes. This study consecutively enrolled 1130 patients with deferred intermediate lesions at baseline angiography and subsequently received second-time angiography between 9 months and 2 years later from two centers in China. The functional changes of intermediate lesions at angiographic follow-up (ΔQFR) were defined as (baseline QFR-follow-up QFR)/years. The primary outcome was vessel-oriented composite endpoint (VOCE), defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (ID-TVR) at angiographic follow-up for up to 5 years. Retrospective QFR assessment was available in 820 patients (996 intermediate lesions). QFR ≤ 0.80 at second-time angiography was associated with significantly higher 5-year VOCE (41.9% vs. 13.4%, p < 0.0001). In 777 intermediate lesions with baseline QFR > 0.80, mean ΔQFR was 0.03 ± 0.07 (median: 0.006; Q1: 0; and Q3: 0.04). The optimal cutoff of ΔQFR for predicting the primary outcome was 0.03 (area under the curve [AUC]: 0.68). The cumulative event rate of VOCE in patients with ΔQFR ≥ 0.03 was significantly higher than in those with ΔQFR < 0.03 (33.8% vs. 12.2%, p < 0.0001), driven by higher vessel-related MI and ID-TVR. The ΔQFR was a useful tool for evaluating the dynamic functional change of deferred intermediate lesions, as it demonstrates good prognostic value for long-term target vessel-related adverse events.

Impact of Arterial Remodeling of Intermediate Coronary Lesions on Long-Term Clinical Outcomes in Patients with Stable Coronary Artery Disease: An Intravascular Ultrasound Study.

BACKGROUND: Treatment of coronary intermediate lesions remains a controversy, and the role of arterial remodeling patterns determined by intravascular ultrasound in intermediate lesion is still not well known. The aim of this study was to investigate the impact of arterial remodeling of intermediate coronary lesions on long-term clinical outcomes. METHODS: Arterial remodeling patterns were assessed in 212 deferred intermediate lesions from 162 patients after IVUS examination. Negative, intermediate, and positive remodeling was defined as a remodeling index of <0.88, 0.88∼1.0, and >1.0, respectively. The primary endpoint was the composite vessel-oriented clinical events, defined as the composition of target vessel-related cardiac death, target vessel-related myocardial infarction, and target vessel revascularization. Quantitative flow ratio was assessed for evaluating the functional significance of intermediate lesions. RESULTS: 72 intermediate remodeling lesions were present in 66 patients, whereas 77 negative remodeling lesions were present in 71 patients, and 63 positive remodeling lesions were present in 55 patients. Negative remodeling lesions had the smallest minimum lumen area (4.16 ± 1.03 mm2 vs. 5.05 ± 1.39 mm2 vs. 4.85 ± 1.76 mm2; P < 0.01), smallest plaque burden (63.45 ± 6.13% vs. 66.12 ± 6.82% vs. 71.17 ± 6.45%; P < 0.01), and highest area stenosis rate (59.32% ± 10.15% vs. 54.61% ± 9.09% vs. 51.67% ± 12.96%; P < 0.01). No significant difference was found in terms of quantitative flow ratio among three groups. At 5 years follow-up, negative remodeling lesions had a higher rate of composite vessel-oriented clinical event (14.3%), compared to intermediate (1.4%, P=0.004) or positive remodeling lesions (4.8%, P=0.06). After adjusting for multiple covariates, negative remodeling remained an independent determinant for vessel-oriented clinical event (HR: 4.849, 95% CI 1.542-15.251, P=0.007). CONCLUSION: IVUS-derived negative remodeling is associated with adverse long-term clinical outcome in stable patients with intermediate coronary artery stenosis.

Association of quantitative flow ratio-derived microcirculatory indices with anatomical-functional discordance in intermediate coronary lesions.

Discrepancy between coronary lesion severity and functional significance has always been a relevant issue in the management of patients undergoing coronary angiography and/or revascularization. We sought to investigate the relationship between quantitative flow ratio (QFR)-derived microcirculatory indices and anatomical-functional mismatch/reverse mismatch in intermediate coronary lesions. Intravascular ultrasound (IVUS) imaging and QFR were analyzed in 117 de novo intermediate coronary lesions. Lesions with QFR ≤ 0.8 were considered hemodynamically significant. Anatomical significance of the lesions was defined according to the best cutoff value of combined IVUS parameters for predicting QFR ≤ 0.8. QFR-derived microcirculatory indices including contrast-flow QFR minus fixed-flow QFR (cQFR-fQFR), hyperemic flow velocity and angiography-derived index of microcirculatory resistance (IMRangio) were calculated. The best cutoff values of IVUS parameters for predicting QFR ≤ 0.8 were minimum lumen area (MLA) 3.1mm2 and plaque burden (PB) 70%, with area under the curve of 0.635 and 0.703, respectively. The total discordance rate of lesion functional significance between IVUS and QFR assessments was 26.5%, with 21 lesions (17.9%) being classified as mismatch (MLA ≤ 3.1mm2 and PB ≥ 70% and QFR > 0.8) and 10 lesions (8.5%) as reverse-mismatch (MLA > 3.1 mm2 or PB < 70% and QFR ≤ 0.8). At multivariate analysis, IMRangio was identified as an independent predictor of mismatch (OR1.675, 95%CI:1.176-2.386, P = 0.004), whereas hyperemic flow velocity was identified as an independent predictor of reverse-mismatch (OR 1.233, 95%CI:1.073-1.416, P = 0.003). In intermediate coronary lesions, although MLA 3.1mm2 and PB 70% determined by IVUS are predictive of QFR-defined functional significance, the discordance rate remains substantial. QFR-derived microcirculatory indices are independently associated with anatomical-functional discordance between IVUS and QFR assessments.

Green Conversion of CO2 and Propargylamines Triggered by Triply Synergistic Catalytic Effects in Metal-Organic Frameworks.

Cyclization of propargylamines with CO2 to obtain 2-oxazolidone heterocyclic compounds is an essential reaction in industry but it is usually catalyzed by noble-metal catalysts with organic bases as co-catalysts under harsh conditions. We have synthesized a unique CuI /CuII mixed valence copper-based framework {[(CuI 6 I5 )Cu3 II L6 (DMA)3 ](NO3 )⋅9DMA}n (1) with good solvent and thermal stability, as well as a high density of uncoordinated amino groups evenly distributed in the large nanoscopic channels. Catalytic experiments show that 1 can effectively catalyze the reaction of propargylamines with CO2 , and the yield can reach 99 %. The turnover frequency (TOF) reaches a record value of 230 h-1 , which is much higher than that of reported noble-metal catalysts. Importantly, this is the first report of heterogeneously catalyzed green conversion of propargylamines with CO2 without solvents and co-catalysts under low temperature and atmospheric pressure. A mechanistic study reveals that a triply synergistic catalytic effect between CuI /CuII and uncoordinated amino groups promotes highly efficient and green conversion of CO2 . Furthermore, 1 directly catalyzes this reaction with high efficiency when using simulated flue gas as a CO2 source.

The association between intravascular ultrasound-derived echo-attenuation and quantitative flow ratio in intermediate coronary lesions.

BACKGROUND: The clinical relevance of moderate coronary stenosis is determined by its morphological characteristics and physiological significance. We investigated the relationship between high-risk plaque characteristics detected by intravascular ultrasound and functional significance assessed with quantitative flow ratio (QFR) in intermediate coronary lesions. METHODS: QFR was retrospectively analyzed in 352 intermediate lesions from 330 patients undergoing intravascular ultrasound examination. The functional significance was defined as QFR ≤0.8. High-risk plaque morphologies including plaque rupture, echo-lucent, echo-attenuation, and spotty calcification were identified, and attenuation indices including maximum angle, attenuation length, and superficial attenuation were determined. Clinically relevant echo-attenuation was defined as an attenuation with a minimum lumen area ≤4.0 mm2 and plaque burden ≥70%. RESULTS: The prevalence of echo-attenuation was higher (63.0% vs. 37.6%, P=0.001) and attenuation length was longer (12.8±10.3 vs. 8.0±5.8 mm, P=0.015) in lesions with QFR ≤0.8 compared to those with QFR >0.8, associated with a higher rate of clinically relevant echo-attenuation (35.2% vs. 10.4%, P<0.001). On multivariable analysis, the presence of echo-attenuation was an independent predictor of QFR ≤0.8 [odds ratio (OR) 3.162, 95% confidence interval (CI): 1.263-7.917, P=0.014], whereas attenuation length was weakly correlated with QFR value (ß=-0.185, B=-0.002, 95% CI: -0.004 to -0.001, P=0.001). Receiver-operating characteristic curve analysis revealed that the best cutoff of QFR in predicting clinically relevant echo-attenuation was 0.82 [area under the curve (AUC) =0.696, 95% CI: 0.616-0.775, P<0.001]. CONCLUSIONS: The presence of intravascular ultrasound-derived echo-attenuation confers an increased risk of QFR-defined functional significance in intermediate coronary lesions. KEYWORDS: Coronary artery disease; intermediate coronary lesion; quantitative flow ratio (QFR); intravascular ultrasound (IVUS); echo-attenuation.

Transcatheter closure for patent ductus arteriosus in patients with Eisenmenger syndrome: to do or not?

BACKGROUND: Patent ductus arteriosus (PDA) complicated by Eisenmenger syndrome (ES) remains to be a major cause of morbidity and mortality worldwide. Giving increasing evidences of benefit from targeted therapies, ES patients once thought to be inoperable may have increasing options for management. This study aims to explore whether PDA in patients with ES can be treated with transcatheter closure (TCC). METHODS: Between August 2014 and July 2016, four of fifteen PDA-ES patients whose Qp/Qs improved significantly and Qp/Qs > 1.5 after acute vasodilator testing with 100% oxygen were selected to receive TCC and pulmonary vasodilator therapy. PAH-targeted drugs were prescribed before and after occlusion for all. Trial occlusion was performed before permanent closure. RESULTS: The first TCC failed after initiation of PAH-targeted drugs for 6 months in four patients. After the medication was adjusted and extended to 12 months, TCC was performed for all without hemodynamic intolerances during perioperative period. Pulmonary artery systolic pressure (PASP) was significantly decreased (≥ 40%) immediately after TCC. During a mean follow-up of 48 ± 14.70 months, there were a further decrease of PASPs in two patients, the other two showed improved pulmonary vascular resistance, WHO functional class and six-minute walking distance despite deteriorated PASP. CONCLUSION: Some selected PDA-ES patients might benefit from TCC and combined PAH-targeted drugs play a crucial role.