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As CO2 emissions are sharply increasing, processes for converting CO2 into value-added products are becoming more desirable. Ruthenium-based catalysts are the most active for CO2 methanation; howev...

Objectives The present study aimed to investigate the difference in target lesion failure (TLF) at 3 years after double kissing (DK) crush stenting versus provisional stenting (PS) for unprotected left main distal bifurcation (UPLMb) lesions. Background The multicenter and randomized DKCRUSH-V (Double Kissing Crush versus Provisional Stenting for Left Main Distal Bifurcation Lesions: The DKCRUSH-V Randomized Trial) study showed fewer 1-year TLF after DK crush for UPLMb lesions compared with PS. The study reports the 3-year clinical outcome of the DKCRUSH-V study. Methods A total of 482 patients with UPLMb lesions who were randomly assigned to either the DK crush group (DK group) or PS group in the DKCRUSH-V study were followed for 3 years. The primary endpoint was the occurrence of a TLF at 3 years. Stent thrombosis (ST) was the safety endpoint. Patients were classified by lesion’s complexity and NERS (New Risk Stratification) II or SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score. Results At 3 years, TLF occurred in 41 (16.9%) patients in the PS group and in 20 (8.3%) patients in the DK group (p = 0.005), mainly driven by increased target vessel myocardial infarction (5.8% vs. 1.7%; p = 0.017) and target lesion revascularization (10.3% vs. 5.0%; p = 0.029). Definite or probable ST rate at 3 years was 4.1% in the PS group and 0.4% in the DK group (p = 0.006). Notably, DK crush was associated with a significant reduction in both primary and secondary endpoints for patients with complex lesions or at high risk. Conclusions Provisional stenting for UPLMb lesions was associated with significantly increased rates of TLF and ST over 3 years of follow-up. Further randomized study is warranted to confirm the benefits of DK crush stenting for complex UPLMb lesions. (Double Kissing and Double Crush versus Provisional T Stenting Technique for the Treatment of Unprotected Distal Left Main True Bifurcation Lesions: A Randomized, International, Multi-center Clinical Trial; ChiCTR-TRC-11001213).

BACKGROUND: Melatonin is a hormone naturally produced by the pineal gland in the brain. In addition to modulating circadian rhythms, it has pleiotropic biological effects including antioxidant, immunomodulatory, and anti-cancer effects. Herein, we report that melatonin has the ability to decrease the growth and metastasis of androgen-dependent prostate cancer. METHODS: To evaluate the anti-cancer effect of melatonin on androgen-sensitive prostate cancer in vitro or in vivo, the effects of cell proliferation, apoptosis, migration and invasion were analyzed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry, Transwell assay, and immunohistochemistry (IHC), respectively. Next, the interaction between androgen receptor (AR) and SUMO specific protease 1 (SENP1) was detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting, and confirmed by luciferase reporter assay. Furthermore, the Small Ubiquitin-like Modifier (SUMO) proteins are a group of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. (SUMOylation) of histone deacetylases 1 (HDAC1) was measured by proximity ligation assay (PLA). RESULTS: The treatment of melatonin cripples the transcriptional activity of AR, which is essential for the growth of the androgen-dependent prostate cancer cell, LNCaP. The lower activity of AR was dependent on melatonin induced SUMOylation of HDAC1, which has been established as a key factor for the transcriptional activity of AR. Mechanistically, the effect of melatonin on AR was due to the decreased SENP1 protein level and the subsequent increased HDAC1 SUMOylation level. The overexpression of SENP1 abrogated the anti-cancer ability of melatonin on LNCaP cells. CONCLUSIONS: These findings indicate that melatonin is a suppressor of androgen-dependent prostate cancer tumorigenesis.

Electrolytic systems of a symmetric, an asymmetric and a two-compartment were established in the present work to investigate the effect of the external electric field distribution on α-Ni(OH)2 electrochemical-synthesis from a NiCl2 solution. Results demonstrate the sample particle size increased in the order of symmetric, two-compartment and asymmetric systems, with a sharpened diffraction peak of the (1 0 1), (0 1 5) and (1 1 0) plane, and a broadened diffraction peak of (0 0 3) plane. However, the reversibility of the redox reactions and the energy transferred in the redox reactions in the electrodes assembled by the samples from the three electrolytic systems increased based on the contrary order. In terms of the electrolysis process, the energy consumption per unit mass increased in the order of symmetric, two-compartment and asymmetric systems. The catholyte pH for both symmetric and asymmetric systems were more stable than that for the two-compartment system. The external electric filed distribution affected the transportation of Ni2+ from the anolyte to the catholyte. At the end of electrolysis, the Ni2+ concentration in the anolyte of two-compartment system was obviously higher than that of symmetric and asymmetric systems.

Background: Although stent underexpansion on intravascular ultrasound (IVUS) has been a major predictor for adverse outcomes in previous studies, these studies have primarily focused on angiographic restenosis or repeat revascularization with short-term follow-up. This study sought to evaluate the long-term benefit of different criteria for IVUS-defined optimal stent expansion on hard clinical outcomes. Methods: From the pooled data of 2 randomized trials, IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) and ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions) that compared IVUS- versus angiography-guided drug-eluting stent implantation, a total of 1254 patients with IVUS-guided drug-eluting stent implantation into 1484 long lesions (implanted stent length, ≥28 mm) were included. Different criteria for IVUS-defined optimal stent expansion based on minimum stent area (MSA) as an absolute measure or MSA relative to reference lumen area were applied and validated. The primary end point was composite of cardiac death, target lesion–related myocardial infarction, or stent thrombosis at 3 years. Results: The rate of the primary end point was lower in patients with optimal stent expansion versus those without optimal stent expansion according to 3 IVUS-defined optimal stent expansion criteria: MSA >5.5 mm 2 (0.5% versus 2.2%; hazard ratio, 0.21 [95% CI, 0.06–0.75]; P =0.008), MSA >5.0 mm 2 (0.6% versus 2.6%; hazard ratio, 0.24 [95% CI, 0.09–0.68]; P =0.003), and MSA/distal reference lumen area >90% (0.5% versus 2.4%; hazard ratio, 0.32 [95% CI, 0.12–0.88]; P =0.019). Achieving other relative expansion criteria, MSA/distal reference lumen area >100% or 80% or MSA/average reference lumen area >90% or 80%, was not associated with a reduction in hard clinical events. Conclusions: In patients undergoing IVUS-guided drug-eluting stent implantation for long lesions, achieving optimal stent expansion of MSA >5.5 mm 2 , >5.0 mm 2 , or MSA/distal reference lumen area >90% was associated with improved long-term hard clinical outcomes.

A beige-pigmented, Gram-strain-negative, aerobic, rod-shaped, non-flagellated and non-gliding bacterium, designated strain lm94

Enriched environment (EE) is an important animal experimental paradigm to decipher gene-environment interaction. It is thought to be efficient in aiding recovery from certain metabolism disorders or cognitive impairments. Recently, the effects of EE during adolescence in mice gradually draw much attention. We first established an EE model in adolescent mice, dissected lipid metabolism, and further examined baseline level of anxiety and depression by multiple behavioral tests, including open field test (OFT), elevated zero maze (EZM), tail suspension test (TST), and forced swimming test (FST). EE mice exhibited lower weights, lower cholesterol than standard housing (SH) mice. Behaviorally, EE mice traveled more distance and had higher velocity than SH mice in OFT and EZM. Besides, EE mice showed reduced anxiety levels in OFT and EZM. Furthermore, EE mice also had less immobility time than SH mice in TST and FST. Thus, these results suggest that EE during adolescence has metabolic and behavioral benefits in mice.

In this paper, a stress sensor based on chipless RFID tags is proposed. The pressure sensor is a resonant type chipless tag based on the RCS and consists of several half-wavelength C-shaped resonators etched on the dielectric support layer of varying lengths. Through stretching or compression, the identity resonant unit and the sensor resonant unit change, the sensor resonant unit according to the generated resonance frequency to obtain the size of the stretching force or compression force. Identity resonant unit generates resonant frequency, and its position on the spectrum is used as the identity information of the corresponding label, thus being recognized. Simulation results show that the stress sensor has the sensitivity of 0.316GHz/mm, and has the advantages of simple structure, independent control of sensing information and identity coding information, high sensitivity and high stability of identity information in the sensing process.

Two-dimensional metals offer intriguing possibilities to explore the metallic and other related properties in systems with reduced dimensionality. Here, following recent experimental reports of synthesis of two-dimensional metallic gallium (gallenene) on insulating substrates, we conduct a computational search of gallenene structures using the Particle Swarm Optimization algorithm, and identify stable low energy structures. Our calculations of the critical temperature for conventional superconductivity yield values of ∼7 K for gallenene. We also emulate the presence of the substrate by introducing the external confining potential and test its effect on the structures with unstable phonons.

Based on the Wigner function in local equilibrium, we derive hydrodynamical quantities for a system of polarized spin-1/2 particles: the particle number current density, the energy-momentum tensor, the spin tensor, and the dipole moment tensor. Comparing with ideal hydrodynamics without spin, additional terms at first and second order in the Knudsen number $\text{Kn}$ and the average spin polarization $\chi_s$ have been derived. The Wigner function can be expressed in terms of matrix-valued distributions, whose equilibrium forms are characterized by thermodynamical parameters in quantum statistics. The equations of motions for these parameters are derived by conservation laws at the leading and next-to-leading order $\text{Kn}$ and $\chi_s$., Comment: 8 pages, no figure

The incorporation of charged functional groups is effective to modulate the activity of molecular complexes for the CO

The present study aimed to evaluate long-term cardiac survival benefit for intravascular ultrasound (IVUS)- versus angiography-guided long drug-eluting stent (DES) implantation.Although the long-term benefit of IVUS guidance for DES implantation has been reported from recent randomized trials, this benefit was primarily driven by the reduction in repeat revascularization. Thus, it remains uncertain whether IVUS guidance improved survival during long-term follow-up.We pooled the data of 2 randomized trials (IVUS-XPL [Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions] and ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions]) and compared IVUS guidance versus angiography guidance in 2,577 patients with long lesions treated with an implanted stent length ≥28 mm. The primary end point was cardiac death at 3 years.A 3-year clinical follow-up was completed in 96%. The primary end point of cardiac death occurred in 12 patients (1.0%) in the IVUS-guided group vs 28 patients (2.2%) in the angiography-guided group (HR: 0.43; 95% CI: 0.22-0.84; P = 0.011). In addition, target lesion-related myocardial infarction occurred in 3 patients (0.2%) in the IVUS-guided group and in 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95% CI: 0.09-1.22; P = 0.081), stent thrombosis developed in 3 patients (0.2%) in the IVUS-guided group and 9 patients (0.7%) in the angiography-guided group (HR: 0.33; 95% CI: 0.09-1.23; P = 0.082), and ischemia-driven target lesion revascularization was observed in 47 patients (3.8%) in the IVUS-guided group and 80 patients (6.5%) in the angiography-guided group (HR: 0.57; 95% CI: 0.40-0.82; P = 0.002).In this post hoc pooled patient-level analysis, the use of IVUS-guided long DES implantation compared with angiography-guided stent implantation improved long-term patient cardiac survival.

We have numerically studied the evolution of the heavy ions that expand in a cold background plasma at a large scale. Two typical collective behaviors of the heavy ions are identified with the conditions where only the traversing heavy ion's initial total mass is different. Our work has demonstrated that a difference in the initial total mass of the moving heavy ions is able to induce completely different collective behaviors of the plasma. The simulation is performed via the hybrid model, in which the ions and electrons are treated as classical particles and mass-less fluid, respectively. Due to the imbalance of the electric and magnetic force on the heavy ions, these particles will evolve into different collective patterns at the later time. These patterns manifest a rather different stopping behavior of the moving ions and an opposite drifting direction of the electron fluid at the rim of the expanding plasma. Further numerical and analytical calculations show that the imbalance depends not only on the number densities of the plasma ions, but also on the spatial variations of the magnetic fields. Our work reveals that the collective behavior of the heavy ions is highly non-linear, and the non-linearity is able to induce different phenomena in the evolution of the system at a large scale., 8 pages, 8 figures

We have implemented a GPU version of the Jefimenko's equations -- JefiGPU. Given the proper distributions of the source terms $\rho$ (charge density) and $\mathbf{J}$ (current density) in the source volume, the algorithm gives the electromagnetic fields in the observational region (not necessarily overlaps the vicinity of the sources). To verify the accuracy of the GPU implementation, we have compared the obtained results with that of the theoretical ones. Our results show that the deviations of the GPU results from the theoretical ones are around 5\%. Meanwhile, we have also compared the performance of the GPU implementation with a CPU version. The simulation results indicate that the GPU code is significantly faster than the CPU version. Finally, we have studied the parameter dependence of the execution time and memory consumption on one NVIDIA Tesla V100 card. Our code can be consistently coupled to RBG (Relativistic Boltzmann equations on GPUs) and many other GPU-based algorithms in physics., Comment: 21 pages, 8 figures, 4 tables

The realization of low-dimensional ferroelectrics is both fundamentally intriguing and practically appealing, to be used in nanoscale devices. Here, GeS and SnS nanowires are predicted to be one-dimensional (1D) ferroelectrics with inversion symmetry spontaneously broken by soft optical modes. Despite the low dimensionality, the estimated Curie point for GeS nanowires is above room temperature, benefiting experimental detection and suggesting realistic applications. To this end, further aspects of these 1D ferroelectrics are also examined, revealing the domain wall localization, switchable carrier mobility, and practically effective shieling by confining the nanowires inside the carbon nanotubes, all together potentially useful for nanoscale ferroelectric devices of broad interest.

As a continuation to our research, a series of novel Bcr-Abl inhibitors incorporated with 6-phenyl-1H-indazol-3-amine as hinge binding moiety (HBM) were developed based on confirmation analysis. Biological results indicated that these compounds exhibited an enhanced inhibition against Bcr-AblWT and Bcr-AblT315I in kinases assays, along with improved anti-proliferative activities in K562 cell assays. In particular, compound Y9 displayed comparable potency with that of imatinib. It potently inhibited Bcr-AblWT and Bcr-AblT315I kinases with IC50 of 0.043 μM and 0.17 μM, respectively. Furthermore, compound Y9 inhibited the proliferation of K562 and K562R cells with IC50 of 1.65 μM and 5.42 μM, respectively. Therefore, 6-phenyl-1H-indazol-3amine as HBM, combined with flexible linker, is a successful strategy contribute to research on T315I mutant resistance, and compound Y9 could be served as a starting point for further optimization.

Background: Only a limited number of studies considered the combined chemo-radiation therapy after surgery for treating locally advanced rectal cancer. Comparative studies on laparoscopic and open procedures indicated that laparoscopy surgery may be associated with fewer postoperative complications. Despite encouraging results from rectal cancer patients who received neoadjuvant chemo-radiotherapy prior to laparoscopic surgery, the acceptance of this procedure remains controversial, and conflicting evidence exists only in the form of retrospective trials. Objectives: Since laparoscopic surgery was introduced into clinical practice to treat rectal cancer after neoadjuvant chemo-radiotherapy, it has been discussed controversially whether laparoscopic surgery can be performed as effectively as an open procedure. To overcome the biases inherent in any nonrandomized comparison, we analyzed the propensity-matched analysis and randomized clinical trial. In this study, we set out to determine whether laparoscopic resection was non-inferior to open resection in treatment outcomes of rectal cancer after neoadjuvant chemo-radiotherapy. Method: Publications on laparoscopic surgery in comparison with open thoracotomy in treatment outcomes of rectal cancer after neo-adjuvant chemo-radiotherapy to November 2017 were collected. Summary hazard ratios (HRs) of endpoints of interest such as 3-OS (overall survival), 3-DFS (disease-free survival), and individual postoperative complications were analyzed in all trials. By using fixed- or random-effects models according to the heterogeneity, meta-analysis Revman 5.3 software was applied to analyze combined pooled HRs. Results: A total of 6 trials met our inclusion criteria. The pooled analysis of 3-DFS showed that laparoscopic surgery did not improve disease -free survival, compared with open thoracotomy (OR =1.48, 95% CI 0.95 – 2.29; P = 0.08), as well with the 3-OS (OR=0.96, 95%CI=0.66-1.41, P=0.084). The pooled result of duration of surgery indicated that laparoscopic surgery had a tendency towards a longer surgery time (SMD= 43.96, 95% CI 34.04– 53.88; P 0.00001) and a shorter hospital stay (SMD= -0.97, 95% CI -1.75– -0.18; P=0.02). However, no significant differences between laparoscopic surgery and open thoracotomy were observed in terms of the meta-analysis on the number of removed lymph nodes (SMD =-0.37, 95% CI -0.1.77 – 1.03; P = 0.60), blood loss (SMD =-21.30, 95% CI -0.48.36 – 5.77; P = 0.12), positive circumferential resection margin (OR =0.73, 95% CI 0.22– 2.48; P = 0.61) or postoperative complications (OR =0.89, 95% CI 0.67 – 1.17; P = 0.40) l. Conclusions: The current data supported the concept that laparoscopic surgery had correlated with a longer operative time but a shorter hospital stay, without superior advantages in short-term survival rates or oncologic efficiency for locally treating advanced rectal cancer after neoadjuvant chemoradiotherapy. However, prospective investigation on long-term oncological results from laparoscopic surgery is required in the future to verify the benefits of laparoscopic surgery over open surgery after chemo-radiation therapy for treating locally advanced rectal cancer.

Antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remain challenging. This study aims to explore the best antithrombotic strategy for AF patients after PCI based on a network meta-analysis. This study was registered in PROSPERO (CRD42018093928). The PubMed, Cochrane, and EMBASE databases were searched to identify clinical trials concerning antithrombotic therapy for AF patients with PCI from inception to April 2018. Pairwise and network meta-analysis were conducted to compare clinical outcomes of different antithrombotic therapy. The primary endpoint was major bleeding. Fifteen studies including 16,382 patients were identified with follow-up ranging from 3 to 12 months. Non-vitamin K oral anticoagulants (NOAC) plus P2Y12 inhibitor ranked first with a reduced risk of major bleeding compared with vitamin K antagonist (VKA) plus dual antiplatelet therapy (OR: 0.57, 95% CI: 0.43-0.75) but with no significant difference compared with VKA plus single platelet therapy (OR: 0.85, 95% CI: 0.62-1.16). Similar thrombotic events were evident among these groups. Subgroup analysis showed that VKA plus aspirin exhibited a similar risk of major bleeding compared with VKA plus clopidogrel (OR: 0.94, 95% CI: 0.73-1.23) but was associated with increased risks of ischaemic stroke (OR: 2.10, 95% CI: 1.33-3.32) and all-cause death (OR: 1.77, 95% CI: 1.15-2.74) versus VKA plus clopidogrel. In AF patients undergoing PCI, NOAC plus P2Y12 inhibitor and VKA plus clopidogrel, but not VKA plus aspirin, were associated with reduced risk of major bleeding compared with the recommended VKA-based triple therapy, while thrombotic events were similar among these treatments.

Background Oscillatory shear stress (OSS) occurs in areas where atherosclerosis is prevalent. Toll-like receptor 2 (TLR2) has been associated with mechanical-stress-mediated activation of signalling pathways that may lead to inflammation, apoptosis, and atherosclerosis. Nonetheless, the mechanism underlying the connection between TLR2 and OSS is not fully understood. The purpose of this study was to investigate the link between OSS and TLR2 in human umbilical vein endothelial cell (HUVECs). Methods Monolayer endothelial cells were stimulated or not stimulated by OSS. Protein expression was determined by western blotting and immunofluorescent staining. Endothelial function was assessed by using dihydroethidium assay, RT-PCR, immunofluorescent staining and western blotting. The carotid artery of rats was ligated for 1 week, and a section exposed to OSS was excised and analysed. Results In vitro, the expression of TLR2 in HUVECs was activated by OSS. Additionally, OSS increased apoptosis, inflammatory changes, and oxidative stress in HUVECs, and these effects were reversed by down-regulation the expression of TLR2. We proved that OSS regulates the inflammatory response of endothelial cells through the TLR2–TAK1–IKK2 pathway. In the rats with carotid artery ligation, TLR2, TAK1 and phospho-IKK2 amounts increased at the site of OSS. Significance According to our results, the OSS-mediated HUVECs injury may be associated with an increase in TLR2 expression. Accordingly, strategies designed to reduce TLR2 expression or inhibit TLR2 activation may be an effective approach to reduce the incidence of atherosclerosis.

Genetic diversity influences the fitness of species and provides variation for adaptation. Garcinia paucinervis Chun et How (Clusiaceae) is an endangered species with important ecological, medicinal and ornamental values endemic to Southwest China and Northern Vietnam, whose populations were severely fragmented in island habitats and population sizes were influenced by human. The assessment of genetic variation of G. paucinervis is anticipated to provide essential information for efficient conservation strategies. In this study, a suite of population genetics tests and analyses were used to investigate genetic diversity and structure of the 11 natural populations (a total of 360 individuals) of G. paucinervis in Guangxi and Yunnan Provinces, China, based on genotypes at 14 loci. Our results revealed a low to moderate genetic diversity in G. paucinervis remnants (HE = 0.487, I = 0.924, AR = 3.420). The global inbreeding coefficient (FIS = 0.004) showed significant deviation from Hardy–Weinberg equilibrium, implying that the risk of inbreeding depression accompanied by heterozygote deficiency was probably due to severe habitat fragmentation and decreasing population sizes. Significant bottlenecks were detected in two populations. There has been little recent exchange of genes between most of the population pairs. Mantel test revealed that the genetic distance was not related to the geographical distance, suggesting a limitation of gene flow. A population from Yunnan Province could be classified as an independent cluster separated from the other populations, which should be considered as a prior conservation unit.

BACKGROUND This case-control study compared the short-term clinical efficacy of natural orifice specimen extraction surgery (NOSES) using a prolapsing technique and the conventional laparoscopic-assisted approach for low rectal cancer. AIM To further explore the application value of the transanal placement of the anvil and to evaluate the short-term efficacy of NOSES for resecting specimens of low rectal cancer, as well as to provide a theoretical basis for its extensive clinical application. METHODS From June 2015 to June 2018, 108 consecutive laparoscopic-assisted low rectal cancer resections were performed at our center. Among them, 26 specimens were resected transanally using a prolapsing technique (NOSES), and 82 specimens were resected through a conventional abdominal wall small incision (LAP). A propensity score matching method was used to select 26 pairs of matched patients, and their perioperative data were analyzed. RESULTS The baseline data were comparable between the two matched groups. All 52 patients underwent the surgery successfully. The operative time, blood loss, number of harvested lymph nodes, postoperative complication rate, circumferential margin involvement, postoperative follow-up data, and postoperative anal function were not statistically significant. The NOSES group had shorter time to gastrointestinal function recovery (2.6 ± 1.0 d vs 3.4 ± 0.9 d, P = 0.006), shorter postoperative hospital stay (7.1 ± 1.7 d vs 8.3 ± 1.1 d, P = 0.003), lower pain score (day 1: 2.7 ± 1.8 vs 4.6 ± 1.9, day 3: 2.0 ± 1.1 vs 4.1 ± 1.2, day 5: 1.7 ± 0.9 vs 3.3 ± 1.0, P < 0.001), a lower rate of additional analgesic use (11.5% vs 61.5%, P = 0.001), and a higher satisfaction rate in terms of the aesthetic appearance of the abdominal wall after surgery (100% vs 23.1%, P < 0.001). CONCLUSION NOSES for low rectal cancer can achieve satisfactory short-term efficacy and has advantages in reducing postoperative pain, shortening the length of postoperative hospital stay, and improving patients’ satisfaction in terms of a more aesthetic appearance of the abdominal wall.

Exosomes, the nanosized vesicles released from various cell types, contain many bioactive molecules, such as proteins, lipids, and nucleic acids, which can participate in intercellular communication in a paracrine manner or an endocrine manner, in order to maintain the homeostasis and respond to stress adaptively. Currently, exosomes have already been utilized as diagnostic biomarkers and therapeutic tools in cancer clinical trials. There has also been great progress in cell and animal exosomes studies of coronary artery disease (CAD). Emerging evidence suggests that exosomes released from endothelial cells, smooth muscle cells, adipose cells, platelets, cardiomyocytes, and stem cells have been reported to play crucial roles in the development and progression of CAD. Moreover, it has been showed that exosomes released from different cell types exhibit diverse biological functions, either detrimental or protective, depending on the cell state and the microenvironment. However, the systematic knowledge of exosomes in CAD at the patient level has not been well established, which are far away from clinical application. This review summarizes the basic information about exosomes and provides an update of the recent findings on exosome-mediated intercellular communication in the development and progression of CAD, which could be helpful for understanding the pathophysiology of CAD and promoting the further potential clinical translation.

Objectives The aim of the present study was to evaluate the angiographic efficacy, clinical safety, and effectiveness of the Restore paclitaxel-coated balloon in a randomized trial designed to enable the approval of the new device in China. Background Drug-coated balloon (DCB) angioplasty offers an effective treatment for in-stent restenosis. Restore is a new DCB with a SAFEPAX shellac-ammonium salt excipient that can avoid drug washing off during catheter delivery to the target lesion site. Methods In the noninferiority RESTORE ISR China (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis) trial, eligible patients with first occurrence of drug-eluting stent ISR were randomized to the Restore DCB or SeQuent Please DCB in a 1:1 ratio stratified by diabetes. Angiographic and clinical follow-up was planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment late loss. Results Between May 2016 and July 2017, a total of 240 subjects at 12 sites were randomized to either the Restore group (n = 120) or the SeQuent Please group (n = 120). Nine-month in-segment late loss was 0.38 ± 0.50 mm with Restore versus 0.35 ± 0.47 mm with SeQuent Please; the 1-sided 97.5% upper confidence limit of the difference was 0.17 mm, achieving noninferiority of Restore compared with SeQuent Please (p for noninferiority = 0.02). Both DCBs had similar 1-year rates of target lesion failure (13.3% vs. 12.6%; p = 0.87). Conclusions In this head-to-head randomized trial, the Restore DCB was noninferior to the SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis; NCT02944890)

Background Intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation is associated with fewer major adverse cardiovascular events compared with angiography guidance for patients with individual lesion subset. However, the beneficial effect on major adverse cardiovascular event outcome of IVUS guidance over angiography guidance in all-comers who undergo DES implantation still remains understudied. Objectives This study aimed to determine the benefits of IVUS guidance over angiography guidance during DES implantation in all-comer patients. Methods A total of 1,448 all-comer patients who required DES implantation were randomly assigned (1:1 ratio) to either an IVUS guidance or angiography guidance group. The primary endpoint was target-vessel failure (TVF) at 12 months, including cardiac death, target-vessel myocardial infarction, and clinically driven target-vessel revascularization (TVR). The procedure was defined as a success if all IVUS-defined optimal criteria were met. Results At 12 months follow-up, 60 TVFs (4.2%) occurred, with 21 (2.9%) in the IVUS group and 39 (5.4%) in the angiography group (hazard ratio [HR]: 0.530; 95% confidence interval [CI]: 0.312 to 0.901; p = 0.019). In the IVUS group, TVF was recorded in 1.6% of patients with successful procedures, compared with 4.4% in patients who failed to achieve all optimal criteria (HR: 0.349; 95% CI: 0.135 to 0.898; p = 0.029). The significant reduction of clinically driven target-lesion revascularization or definite stent thrombosis (HR: 0.407; 95% CI: 0.188 to 0.880; p = 0.018) based on lesion-level analysis by IVUS guidance was not achieved when the patient-level analysis was performed. Conclusions The present study demonstrates that IVUS-guided DES implantation significantly improved clinical outcome in all-comers, particularly for patients who had an IVUS-defined optimal procedure, compared with angiography guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions [ULTIMATE]; NCT02215915)

Chenyu Wang,* Xingwang Li,* Junjie Zhang, Zheng Ge, Hejin Chen, Junhong Hu Department of Anorectal, Huaihe Hospital of Henan University, Kaifeng, 475000, People’s Republic of China *These authors contributed equally to this work Background: Increasing evidence suggests the involvement of enhancer of zeste homologue 2 (EZH2) in chemoresistance of cancer treatment. Nevertheless, its function and molecular mechanisms in gastric cancer (GC) chemoresistance are still not well elucidated. Materials and methods: In the present study, we investigated the functional role of EZH2 in 5-fluorouracil (5-FU) resistance of GC cells and discovered the underlying molecular mechanism. Results: Results revealed that EZH2 was upregulated in 5-FU-resistant GC tissues and cell lines. High ZEH2 expression was correlated with poor prognosis of GC patients. EZH2 knockdown enhanced 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Moreover, EZH2 could epigenetically suppress FBXO32 expression. FBXO32 overexpression could mimic the functional role of downregulated EZH2 in 5-FU resistance. FBXO32 knockdown counteracted the inductive effect of EZH2 inhibition on 5-FU sensitivity of AGS/5-FU and SGC-7901/5-FU cells. Furthermore, EZH2 knockdown facilitated 5-FU sensitivity of 5-FU-resistant GC cells in vivo. Conclusion: In summary, EZH2 depletion overcame 5-FU resistance in GC by epigenetically silencing FBXO32, providing a novel therapeutic target for GC chemoresistance. Keywords: gastric cancer, 5-FU, enhancer of zeste homologue 2, FBXO32

In artery tree, endothelial function correlates with the distribution of shear stress, a dragging force generated by flowing blood. In laminar shear stress areas, endothelial cells (ECs) are available to prevent atherosclerosis, however, ECs in disturbed shear stress sites are featured with proinflammation and atherogenesis. Basic studies in the shear stress field that focused on the mechanosensors of ECs have attracted the interest of researchers. Among all the known mechanosensors, the primary cilium is distinctive because it is enriched in disturbed shear stress regions and sparse in laminar shear stress areas. The primary cilium, a rod liked micro-organelle, can transmit extracellular mechanical and chemical stimuli into intracellular space. In the cardiovascular system, primary cilia are enriched in disturbed shear stress regions, where blood flow is slow and oscillatory, such as the atrium, downstream of the aortic valve, branches, bifurcations, and inner curves of the artery. However, in the atrioventricular canal and straight vessels, blood flow is laminar, and primary cilia can barely be detected. Primary cilia in the heart cavity prevent ECs from mesenchymal transition and calcification by suppressing transforming growth factor (TGF) signaling. Besides, primary cilia in the vascular endothelium protected ECs against disturbed shear stress-induced cellular damage by triggering Ca2+influx as well as nitric oxide (NO) release. Moreover, primary cilia inhibit the process of atherosclerosis. In the current review, we discussed ciliogenesis, ciliary structure, as well as ciliary distribution, function and the coordinate signal transduction with shear stress in the cardiovascular system.

Climate change and invasive alien species threaten biodiversity. High temperature is a worrying ecological factor. Most responses of invasive plants aimed at coping with adversity are focused on the physiological level. To explore the molecular mechanisms underlying the response of an invasive plant (Sphagneticola trilobata L.) to high temperature, using a native species (Sphagneticola calendulacea L.) as the control, relevant indicators, including photosynthetic pigments, gas exchange, chlorophyll fluorescence, the antioxidant system, and related enzyme-coding genes were measured. The results showed that the leaves of S. calendulacea turned yellow, photosynthetic pigment content (Chl a, Chl b, Car, Chl) decreased, gas exchange (Pn) and chlorophyll fluorescence parameters (Fv/Fm, &Phi, PSII) decreased under high temperature. It was also found that high temperature caused photoinhibition and a large amount of ROS accumulated, resulting in an increase in MDA and relative conductivity. Antioxidant enzymes (including SOD, POD, CAT, and APX) and antioxidants (including flavonoids, total phenols, and carotenoids) were decreased. The qPCR results further showed that the expression of the PsbP, PsbA, and RubiscoL, SOD, POD, CAT, and APX genes was downregulated, which was consistent with the results of physiological data. Otherwise, the resistance of S. trilobata to high temperature was better than that of S. calendulacea, which made it a superior plant in the invasion area. These results further indicated that the gradual warming of global temperature will greatly accelerate the invasion area of S. trilobata.

Vascular smooth muscle cell (VSMC) phenotypic modulation plays an important role in the occurrence and development of in-stent restenosis (ISR), the underlying mechanism of which remains a key issue needing to be urgently addressed. This study is designed to investigate the role of plasma small extracellular vesicles (sEV) in VSMC phenotypic modulation. sEV were isolated from the plasma of patients with ISR (ISR-sEV) or not (Ctl-sEV) 1 year after coronary stent implantation using differential ultracentrifugation. Plasma sEV in ISR patients are elevated markedly and decrease the expression of VSMC contractile markers α-SMA and calponin and increase VSMC proliferation. miRNA sequencing and qRT-PCR validation identified that miRNA-501-5p was the highest expressed miRNA in the plasma ISR-sEV compared with Ctl-sEV. Then, we found that sEV-carried miRNA-501-5p level was significantly higher in ISR patients, and the level of plasma sEV-carried miRNA-501-5p linearly correlated with the degree of restenosis ( R 2 = 0.62 ). Moreover, miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers α-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. Mechanically, miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3. Notably, endothelial cells might be the major origins of miRNA-501-5p. Collectively, these findings showed that plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.

Two-dimensional field effect transistors (2D FETs) with high mobility semiconducting channels and low contact resistance between the semiconducting channel and the metallic electrodes are highly sought components of future electronics. Recently, 2D boron sheets (borophene) offer a great platform for realizing ideal 2D FETs but stable semiconducting phases still remain much unexplored. Herein, based on first-principles calculations and tight-binding model, we first clarify that α'-boron is the most stable semiconductor phase of boron sheets, while reveal the mechanism of metal-to-semiconductor transition from α- to α'-boron. Then we demonstrate that the carrier mobility in α'- and metastable β3S-boron should be very high, due to small effective masses of electrons and holes, as a good candidate material for 2D FETs. Considering further the lateral contacts between semiconducting α' and metallic borophene, we find that the α'- and β3S-boron sheet can form Ohmic contacts with selected metallic boron sheets, without Schottky barrier. The high energetic stability and excellent mobility properties of α'-boron sheet together with its good contact match to metallic borophene electrodes are promising for fully boron-based FETs in the real 2D atomically thin limit.

The realization of multifunctional nanomaterials is both fundamentally intriguing and practically appealing to be used in nanoscale devices. Here, a heterobilayer consisting of realistic 2D-material components of matching lattice symmetry, that is, one being the

Background Genetic polymorphisms of key proteins involved in clopidogrel absorption, metabolism, and action may contribute to variability in platelet inhibition in patients undergoing percutaneous coronary intervention (PCI), but their impacts on cardiovascular outcomes remain unclear. Purpose To examine the associations between genetic polymorphisms and cardiovascular outcomes in Chinese patients undergoing PCI and treated with clopidogrel and aspirin. Methods This prospective cohort study consecutively enrolled 2,453 post-PCI patients treated with clopidogrel and aspirin. Adenosine diphosphate-induced platelet aggregation was measured by light transmission aggregometry. A total of 40 single nucleotide polymorphisms (SNPs) of 18 genes selected according to published studies were investigated using an improved multiplex ligation detection reaction technique. The primary outcome was major adverse cardiovascular event (MACE), the composite of cardiovascular death, non-fatal myocardial infarction (MI), and ischemic stroke within one year after PCI. Results We restricted the analyses to the first 1,452 patients who had finished one-year follow-up and complete data on genotyping and platelet aggregation. 44 (3.03%) patients suffered MACE. Among the 40 SNPs, only the A-allele carriers of CYP2C19*2 had a significant higher risk of MACE (adjusted HR 2.05; 95% CI, 1.01–4.19; p=0.048) and platelet aggregation than non-A-carriers after adjusting age, sex, MI presentation, and left ventricular ejection fraction. CYP2C19*3, CYP2B6 rs3745274, and PEAR1 rs12041331 variants were also significantly associated with platelet aggregation (all p Conclusion About 54.2% of Chinese patients with PCI were A-allele carriers of CYP2C19*2, who face a two-fold higher risk of MACE than non-A-allele carriers in Chinese patients after PCI. It would help identify low clopidogrel responders and optimize antiplatelet therapy before drug administration. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Funding of China

Background The parasitoid wasp, Trichogramma dendrolimi, can enter diapause at the prepupal stage. Thus, diapause is an efficient preservation method during the mass production of T. dendrolimi. Previous studies on diapause have mainly focused on ecological characteristics, so the molecular basis of diapause in T. dendrolimi is unknown. We compared transcriptomes of diapause and non-diapause T. dendrolimi to identify key genes and pathways involved in diapause development. Results Transcriptome sequencing was performed on diapause prepupae, pupae after diapause, non-diapause prepupae, and pupae. Analysis yielded a total of 87,022 transcripts with an average length of 1604 bp. By removing redundant sequences and those without significant BLAST hits, a non-redundant dataset was generated, containing 7593 sequences with an average length of 3351 bp. Among them, 5702 genes were differentially expressed. The result of Gene Ontology (GO) enrichment analysis revealed that regulation of transcription, DNA-templated, oxidation-reduction process, and signal transduction were significantly affected. Ten genes were selected for validation using quantitative real-time PCR (qPCR). The changes showed the same trend as between the qPCR and RNA-Seq results. Several genes were identified as involved in diapause, including ribosomal proteins, zinc finger proteins, homeobox proteins, forkhead box proteins, UDP-glucuronosyltransferase, Glutathione-S-transferase, p53, and DNA damage-regulated gene 1 (pdrg1). Genes related to lipid metabolism were also included. Conclusions We generated a large amount of transcriptome data from T. dendrolimi, providing a resource for future gene function research. The diapause-related genes identified help reveal the molecular mechanisms of diapause, in T. dendrolimi, and other insect species.

IntroductionProvisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions.Methods and analysisThe DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis.Ethics and disseminationThe study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences.Trial registration numberNCT04242134.

Author's summary The current study showed that pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) was associated with target vessel failure (TVF) after PCI. When the prognostic value of post-PCI FFR was evaluated according to pre-PCI FFR value, the risk of TVF significantly decreased along with the increase of post-PCI FFR in the low pre-PCI FFR group, but not in the high pre-PCI FFR group. Our study results suggest that patient prognosis can be varied according to the level of physiologic indices, both before and after PCI, and the integration of both information can provide better risk stratification after PCI., Background and Objectives The influence of pre-intervention coronary physiologic status on outcomes post percutaneous coronary intervention (PCI) is not well known. We sought to investigate the prognostic implications of pre-PCI fractional flow reserve (FFR) combined with post-PCI FFR. Methods A total of 1,479 PCI patients with pre-and post-PCI FFR data were analyzed. The patients were classified according to the median values of pre-PCI FFR (0.71) and post-PCI FFR (0.88). The primary outcome was target vessel failure (TVF) at 2 years. Results The risk of TVF was higher in the low pre-PCI FFR group than in the high pre-PCI FFR group (hazard ratio, 1.82; 95% confidence interval, 1.15–2.87; p=0.011). In 4 group comparisons, the cumulative incidences of TVF at 2 years were 3.8%, 4.1%, 4.8%, and 10.2% in the high pre-/high post-, low pre-/high post-, high pre-/low post-, and low pre-/low post-PCI FFR groups, respectively. The risk of TVF was the highest in the low pre-/low post-PCI FFR group among the groups (p values for comparisons 0.05). When the prognostic value of the post-PCI FFR was evaluated according to the pre-PCI FFR, the risk of TVF significantly decreased with an increase in post-PCI FFR in the low pre-PCI FFR group, but not in the high pre-PCI FFR group. Conclusions Pre-PCI FFR was associated with clinical outcomes after PCI, and the prognostic value of post-PCI FFR differed according to the pre-PCI FFR. Trial Registration ClinicalTrials.gov Identifier: NCT04012281

Background Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. Trial design DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. Conclusions DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Background: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization. Methods: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1−RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1–5, and >5) and post-PCI FFR (≥0.94, 0.87–0.93, and ≤0.86). Results: After PCI, SYNTAX score was changed from 10.0 (Q1–Q3, 7.0–16.0) to 0.0 (Q1–Q3, 0.0–5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank P =0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank P =0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032–1.153]; P =0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898–1.045]; P =0.417). Conclusions: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04012281.

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg−1) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg−1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.

BACKGROUND Provisional side branch (SB) stenting is correlated with target vessel myocardial infarction (TVMI) in patients with coronary bifurcation lesions. However, the mechanisms underlying this association remain unknown. OBJECTIVES To determine the correlation between SB lesion length with vulnerable plaques and TVMI using optical coherence tomography (OCT). BACKGROUND The correlation between SB lesion length with vulnerable plaques and TVMI is unknown. METHODS A total of 405 patients with 405 bifurcation lesions who underwent preprocedure OCT imaging of both the main vessel (MV) and the SB were enrolled. Patients were divided into long SB lesion (SB lesion length ≥10 mm) and short SB lesion (SB lesion length

BACKGROUND Colorectal cancer is one of the most common cancers globally. In China, its prevalence ranks fourth and fifth among females and males, respectively. Presently, treatment of rectal cancer follows a multidisciplinary comprehensive treatment approach involving surgery, radiotherapy, chemotherapy, and targeted therapy. With deepening theoretical and molecular research on colorectal cancer, randomized controlled trials (RCTs) on colorectal cancer have made significant progress. However, many RCTs have shortfalls. AIM To investigate the RCTs of global colorectal cancer spanning from 2008 to 2018. To provide suggestions for conducting Chinese RCTs of colorectal cancer. METHODS PubMed and Web of Science databases were searched to obtain RCTs of colorectal cancer carried out between January 1, 2008, and January 1, 2018. The bibliometric method was used for statistical analysis of the publication years, countries/regions, authors, institutions, source journals, quoted times, key words, and authors. RESULTS Colorectal cancer RCTs showed an upward trend between 2008 to 2018; the top 10 research institutions in the included literature were from the United States, the United Kingdom, and other countries with a high incidence of colorectal cancer. Most of the related research journals are sponsored by European and American countries. The 15 most cited studies involved international multicenter clinical research, having few participants from Chinese research institutions. Network visualization using key words showed that RCTs on colorectal cancer focus on screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life, and prognosis. The result of the coauthorship network analysis showed that Chinese researchers are less involved in international exchanges compared to those from leading publication countries. CONCLUSION High-quality RCTs are increasingly favored by leading international journals. However, there is still a large gap in clinical research between China and leading countries. Researchers should implement standardized and accurate clinical trials, strengthen international multicenter cooperation, and emphasize quality control.

Background The parasitoid insect Trichogramma dendrolimi can successfully enter diapause at the prepupal stage. Thus, diapause is an efficient preservation method during the mass production of T. dendrolimi . Previous studies on diapause have focused mostly on ecological characteristics, so the molecular mechanism of diapause in T. dendrolimi is mostly unknown. In this study, we compared transcriptomes of diapause and non-diapause T. dendrolimi to identify genes involved in the development of diapause. Results Transcriptome sequencing was performed using different samples, including diapause prepupae, pupae after diapause, normal prepupae, and pupae. This initially yielded a total of 87,022 unigenes with an average length of 1,604 bp. By removing redundant sequences and those without significant BLAST hits, a non-redundant dataset was generated, containing 7,593 sequences with an average length of 3351 bp. Among the differentially expressed genes, 1,204 were specifically expressed during the diapause stage, and 820 were significantly up-regulated. The result of GO enrichment analysis revealed that binding, oxidation−reduction process, and ribosome biogenesis were significantly affected. Ten genes were selected for validation using a quantitative real-time PCR (qPCR). The changes showed the same trend between the qPCR and RNA-Seq results. Based on previous studies and our data, several genes were identified to be involved in diapause, including UDP-glucuronosyltransferase ; Glutathione-S-transferase , ATGs , zinc finger protein genes, cell cycle-related genes, Trehalase , trehalose transporter , hsp68 , p53, and DNA damage-regulated gene 1 ( pdrg1 ), and genes related to lipid metabolism were also included. Conclusions In this study, we generated a great amount of transcriptome data from T. dendrolimi , providing a resource for gene function research. The diapause-related genes that we identified establish a valuable basis for future studies on the molecular mechanisms of diapause, not only for T. dendrolimi, but for other species as well.

Aim The present study aimed to assess the benefits of two-stent techniques for patients with DEFINITION criteria-defined complex coronary bifurcation lesions. Methods and results In total, 653 patients with complex bifurcation lesions at 49 international centres were randomly assigned to undergo the systematic two-stent technique (two-stent group) or provisional stenting (provisional group). The primary endpoint was the composite of target lesion failure (TLF) at the 1-year follow-up, including cardiac death, target vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). The safety endpoint was definite or probable stent thrombosis. At the 1-year follow-up, TLF occurred in 37 (11.4%) and 20 (6.1%) patients in the provisional and two-stent groups, respectively [77.8%: double-kissing crush; hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30–0.90; P = 0.019], largely driven by increased TVMI (7.1%, HR 0.43, 95% CI 0.20–0.90; P = 0.025) and clinically driven TLR (5.5%, HR 0.43, 95% CI 0.19–1.00; P = 0.049) in the provisional group. At the 1 year after indexed procedures, the incidence of cardiac death was 2.5% in the provisional group, non-significant to 2.1% in the two-stent group (HR 0.86, 95% CI 0.31–2.37; P = 0.772). Conclusion For DEFINITION criteria-defined complex coronary bifurcation lesions, the systematic two-stent approach was associated with a significant improvement in clinical outcomes compared with the provisional stenting approach. Further study is urgently warranted to identify the mechanisms contributing to the increased rate of TVMI after provisional stenting. Study registration http://www.clinicaltrials.com; Identifier: NCT02284750.

Background The aim of this bibliometric analysis was to evaluate the clinical trials of randomized controlled trials (RCTs) of colorectal cancer all the world over the past decade. Methods The PubMed and Web of Science database were searched to obtain a randomized controlled trial of colorectal cancer from January 1, 2008 to January 1, 2018.The included literatures were analyzed with the bibliometric analysis. Results In the past 10 years, Randomized controlled trials of colorectal cancer have shown an upward trend; Most of the top ten research institutions in the literature are from the USA, the UK and other regions which has the high incidence of colorectal cancer; Most of the related research journals are also sponsored by European and American countries; the frequently cited top 15 literatures are mostly international multi-center clinical research, and there are fewer participants in Chinese research institutions. By keyword co-occurrence, colorectal cancer research mostly involves screening, disease-free survival, drug treatment, surgical methods, clinical trials, quality of life and prognosis; The results of the co-authorship network analysis show that Chinese researchers are less involved in international cooperation. Conclusions High-quality randomized controlled trials are increasingly favored by top international journals. However, there is still a large gap in clinical research between China and abroad. Researchers should gradually implement the standardization and accuracy of clinical trials, strengthen international multi-center cooperation and emphasize quality control.

Background This study investigated and analyzed rectal cancer-related clinical trials registered on Chinese Clinical Trial Registry (Chi-CTR) by the end of 2018. We aimed to discuss the characteristics and developmental trends. Methods The Chi-CTR database was searched and all clinical trials related to rectal cancer extracted. The time limit for the search was from the establishment of the data library to December 31, 2018. The characteristics of registered clinical trials were then analyzed. Results A total of 70 clinical trials were retreived. Beijing, Shandong, and Guangzhou accounted for 47.1% of the total number of registered clinical trials. Sichuan and Sun Yat-sen Universities having the highest number of registrations. The registration status of the 55 trials was prospective registration. The top sources of funding were self-financing (41.4%), hospital funding (22.9%) and local finance (15.7%). Out of the 43 randomized controlled trials, 39 were either blank or missing in the blinded section. The sample size of clinical trials was high in 100 to 199 cases. Only eight of the 70 trials were multicenter clinical trials. Conclusions Relevant departments should increase the registration of clinical trials, increase the awareness of registration, and promote the development of high-quality clinical trials. At the same time, researchers should raise the awareness of clinical trial registration, and actively carry out multi-center clinical trials.

BACKGROUND Reports showed no change of 7-day mortality after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) between 2001 and 2011 in China. National rolling one-year interventional standardized training programme began in September 2009. However, the improvement in clinical outcome following STEMI PCI after 2011 remains unclear. METHODS AND RESULTS This multicentre MOODY registry study aimed to analyse the clinical improvement after STEMI PCI. Of a total of 9265 acute MI patients registered from 24 centres, 3142 STEMIs having a first medical contact time ≤12 hours and undergoing primary PCI were assigned to the Pre Group (n = 1014, between March 1999 and October 2010) or the Post Group (n = 2128, between 2010 November and 2016 October). The primary endpoint was in-hospital cardiac death. Study endpoints were also compared between trained and untrained operators and between experienced (≥50 primary PCIs/year) and inexperienced personnel. In-hospital death after PCI was 3.0% in the Pre Group, significantly higher than 1.6% in the Post Group (P = .035). The improvements in clinical outcome after PCI between the 2016 and Pre Groups were stably sustained through one-year follow-up. The significant reduction for in-hospital death was noted when primary PCI was performed by trained (1.4% vs 5.4%, P

To compare the differences in the clinical effect on post-stroke hand spasm among the combined treatment of penetrating acupuncture and kinesiotherapy, the simple application of penetrating acupuncture and the simple application of kinesiotherapy.A total of 105 patients with post-stroke hand spasm were randomized into a penetrating acupuncture group, a kinesiotherapy group and a combined treatment group, 35 cases in each one, of which, 2 cases were dropped out in either the combined treatment group and the penetrating acupuncture group, and 1 case dropped out in the kinesiotherapy group. The routine rehabilitation training, e.g. occupational therapy and Bobath exercise and medication were adopted in all of the three groups. In the penetrating acupuncture group, the penetrating needling technique was exerted from Hegu (LI 4) to Houxi (SI 3) and from Waiguan (TE 5) to Sidu (TE 9) on the affected side. In the kinesiotherapy group, the persistent movement or passive movement was exerted on the wrist joint, the metacarpophalangeal joints and the interphalangeal joints. In the combined treatment group, the penetrating acupuncture (the same as the penetrating acupuncture group) was exerted combined with kinesiotherapy (the same as the kinesiotherapy group). In each group, the treatment was given once a day, 30 min in each time, 6 treatments a week in total, with the interval of 1 day between the courses. The treatment for 2 weeks was as one course and 2 courses were required totally. Before and after treatment, the scores of hand spasm index, hand-wrist motor function and the activity of daily living (ADL) were compared in each group.After treatment, the scores of hand spasm index were reduced as compared with those before treatment in each group (Compared with the simple application of either penetrating acupuncture or kinesiotherapy, the combined treatment of them achieves the significant improvements in hand spasm degree, hand wrist motor function and ADL in patients with stroke.

Accumulating evidence suggested that lncRNA MALAT1 plays critical roles in the commencement and progression of malignant cancers. Nevertheless, the function of MALAT1 in colorectal cancer (CRC) remains largely unknown. In the present study, we reported that MALAT1 expression is significantly upregulated in CRC and correlated with advanced TNM stage, lymph node metastasis, and worse prognosis in patients. Functional assays revealed that MALAT1 knockdown reduced CRC cell growth and invasion abilities in vitro. Mechanistically, we discovered that MALAT1 may serve as a competing endogenous RNA (ceRNA) to miR-508-5p in CRC progression. Bioinformatics analysis and luciferase assays confirmed that RAB14 acts as a target of miR-508-5p. In addition, downregulation of RAB14 reduced the progression of CRC. Collectively, our findings indicated that MALAT1 could promote CRC progress by sponging miR-508-5p and enhancing RAB14 expression, which provides a therapeutic target in CRC treatment.

The accelerating research interest in graphene involving the use of Hummers method has generated non-negligible amount of wastewater containing residual graphite as well as Mn2+ . In this paper, we report the first example of using this wastewater as precursor to prepare Mn3 O4 /N-doped graphite (NG) composites through a facile solvothermal process. The mass fraction of Mn3 O4 in the composites was manipulated by adding various amounts of extra Mn2+ . The conversion of Mn2+ to Mn3 O4 nanoparticles and the N atoms doping were achieved by adding hydrazine hydrate and ammonia into the system. The as-obtained Mn3 O4 /NG composites were well characterized by SEM, TEM, EDS, Raman, XPS, TGA, XRD and N2 adsorption-desorption experiments and showed excellent catalytic performances as well as stability in the degradation of a model organic pollutant methylene blue (MB). Theoretical simulation was also carried out to illustrate the structural features of the Mn3 O4 /NG composite. This work presents a novel idea of designing functional materials from waste precursors.

We have developed a numerical framework for a full solution of the relativistic Boltzmann equations for the quark-gluon matter using the multiple Graphics Processing Units (GPUs) on distributed clusters. Including all the $2 \to 2$ scattering processes of 3-flavor quarks and gluons, we compute the time evolution of distribution functions in both coordinate and momentum spaces for the cases of pure gluons, quarks and the mixture of quarks and gluons. By introducing a symmetrical sampling method on GPUs which ensures the particle number conservation, our framework is able to perform the space-time evolution of quark-gluon system towards thermal equilibrium with high performance. We also observe that the gluons naturally accumulate in the soft region at the early time, which may indicate the gluon condensation., 32 pages, 12 figures

Epidermal growth factor receptor (EGFR), a member of the HER family, is closely related to the development of multiple cancers. Herein, we report the discovery of small molecule EGFR degraders based on the proteolysis targeting chimera (PROTAC) strategy. In the present study, 13 EGFR degraders containing pyrido[3,4-d] pyrimidine moiety were designed and synthesized. Promising PROTACs 2 and 10 induced degradation of EGFR in HCC827 cells with the DC50 values of 45.2 and 34.8 nM, respectively. Cellular protein-controlling machinery ubiquitin proteasome system (UPS) was involved in the degradation process. Furthermore, the degraders 2 and 10 could significantly induce the apoptosis of HCC827 cells and arrest the cells in G1 phase. These findings demonstrated that compounds 2 and 10 could serve as effective EGFRdel19-targeting degraders in HCC827 cells. v.

RB-2 and RB-4 are two structural analogs of polyacetylene from Radix Bupleuri that show antidepressant effects. However, no metabolic data are available to elucidate their systemic homeostasis. Mass spectrometry combined with liver microsomes and recombinant drug-metabolizing enzymes were performed to profile the biotransformations of RB-2/RB-4