Immunomodulatory functions of the circ_001678/miRNA-326/ZEB1 axis in non-small cell lung cancer via the regulation of PD-1/PD-L1 pathway.

High-throughput circular RNA (circRNA) sequencing identified circRNA_001678 (circ_001678) as an upregulated circRNA in non-small cell lung cancer (NSCLC) tissues. Hence, the current study sought to investigate the function and the underlying mechanism of circRNA_001678 in immune escape of NSCLC. Briefly, commercially purchased NSCLC cell lines were adopted for in vitro experiment to evaluate the effects of circ_001678 over-expression or knockdown on cell biological functions, including proliferation, migration and invasive abilities. In addition, the effects of circ_001678 on the in vivo tumorigenicity ability were evaluated for verification. Accordingly, we uncovered that circ_001678 over-expression augmented NSCLC progression in vitro and enhanced tumorigenicity ability in vivo. The interaction between circ_001678 and miR-326 predicted online was verified by means of luciferase and RNA pull-down assays. Furthermore, circ_001678 could sponge miR-326 to up-regulate ZEB1. On the other hand, the tumor-promoting effects of circ_001678 could be inhibited by anti-PD-L1/PD-1 treatment. Mechanistically, circ_001678 led to the activation of the PD-1/PD-L1 pathway to promote CD8+ T cell apoptosis, thereby inducing NSCLC cell immune escape via regulation of the miR-326/ZEB1 axis. To conclude, our findings revealed that circ_001678 sponges miR-326 to up-regulate ZEB1 expression and induce the PD-1/PD-L1 pathway-dependent immune escape, thereby promoting the malignant progression of NSCLC.

Enhanced Acetone Sensing Properties Based on Au-Pd Decorated ZnO Nanorod Gas Sensor.

The mature processes of metal oxide semiconductors (MOS) have attracted considerable interest. However, the low sensitivity of metal oxide semiconductor gas sensors is still challenging, and constrains its practical applications. Bimetallic nanoparticles are of interest owing to their excellent catalytic properties. This excellent feature of bimetallic nanoparticles can solve the problems existing in MOS gas sensors, such as the low response, high operating temperature and slow response time. To enhance acetone sensing performance, we successfully synthesized Au-Pd/ZnO nanorods. In this work, we discovered that Au-Pd nanoparticles modified on ZnO nanorods can remarkably enhance sensor response. The Au-Pd/ZnO gas sensor has long-term stability and an excellent response/recovery process. This excellent sensing performance is attributed to the synergistic catalytic effect of bimetallic AuPd nanoparticles. Moreover, the electronic and chemical sensitization of noble metals also makes a great contribution. This work presents a simple method for preparing Au-Pd/ZnO nanorods and provides a new solution for the detection of acetone based on metal oxide semiconductor.

Highly Sensitive and Selective Toluene Gas Sensors Based on ZnO Nanoflowers Decorated with Bimetallic AuPt.

Efficient sensors for toluene detecting are urgently needed to meet people's growing demands for both environment and personal health. Metal oxide semiconductor (MOS)-based sensors have become brilliant candidates for the detection of toluene because of their superior performance over gas sensing. However, gas sensors based on pure MOS have certain limitations in selectivity, operating temperature, and long-term stability, which hinders their further practical applications. Noble metals (including Ag, Au, Pt, Pd, etc.) have the ability to enhance the performance of MOS-based sensors via surface functionalization. Herein, ZnO nanoflowers (ZNFs) modified with bimetallic AuPt are prepared for toluene detection through hydrothermal method. The response of a AuPt@ZNF-based gas sensor can reach 69.7 at 175 °C, which is 30 times, 9 times, and 10 times higher than that of the original ZNFs, Au@ZNFs, and Pt@ZNFs, respectively. Furthermore, the sensor also has a lower optimal operating temperature (175 °C), good stability (94% of previous response after one month), and high selectivity towards toluene, which is the result of the combined influence of the electronic and chemical sensitization of noble metals, as well as the unique synergistic effect of the AuPt alloy. In summary, AuPt@ZNF-based sensors can be further applied in toluene detection in practical applications.

Inhibitory role of bone marrow mesenchymal stem cells-derived exosome in non-small-cell lung cancer: microRNA-30b-5p, EZH2 and PI3K/AKT pathway.

Exosomal microRNA (miRNA) exerts potential roles in non-small-cell lung cancer (NSCLC). The current study elucidated the role of miR-30b-5p shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC-related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR-30b-5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs-derived exosomes overexpressing miR-30b-5p were used to establish subcutaneous tumorigenesis models to study the effects of miR-30b-5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC-exo-miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC-exo-miR-30b-5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR-30b-5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC-exo-miR-30b-5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC-derived exosomes-loaded miR-30b-5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis.

In Silico Prediction of Human Organ Toxicity via Artificial Intelligence Methods.

Unpredicted human organ level toxicity remains one of the major reasons for drug clinical failure. There is a critical need for cost-efficient strategies in the early stages of drug development for human toxicity assessment. At present, artificial intelligence methods are popularly regarded as a promising solution in chemical toxicology. Thus, we provided comprehensive in silico prediction models for eight significant human organ level toxicity end points using machine learning, deep learning, and transfer learning algorithms. In this work, our results showed that the graph-based deep learning approach was generally better than the conventional machine learning models, and good performances were observed for most of the human organ level toxicity end points in this study. In addition, we found that the transfer learning algorithm could improve model performance for skin sensitization end point using source domain of in vivo acute toxicity data and in vitro data of the Tox21 project. It can be concluded that our models can provide useful guidance for the rapid identification of the compounds with human organ level toxicity for drug discovery.

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.

Optical coherence tomography-assisted interventional treatment of a woven coronary artery: a case report.

BACKGROUND: A woven coronary artery is a rare feature on coronary angiography. Distinguishing woven-like change and recanalization of an occluded artery is difficult. CASE PRESENTATION: A 59-year-old man was admitted to the hospital for chest tightness. Coronary angiography showed a woven coronary artery at the middle segment of the left anterior descending branch (LAD). The middle segment of the right coronary artery (RCA) exhibited 99% occlusion. A 3.5 × 26-mm drug-eluting stent was implanted in the middle segment of the RCA. One week later, we examined the LAD using optical coherence tomography (OCT). Considering the patient's medical history and the results of OCT, a 2.7 × 38-mm drug-eluting stent was inserted into the LAD. Re-examination by OCT indicated that the stent was well attached to the wall, with no dissection at the edge of the stent. Antiplatelet therapy and statin-based plaque stabilization were continued. No obvious abnormality was found during follow-up one year later. CONCLUSIONS: OCT can help distinguish woven-like change and recanalization of an occluded coronary artery. The evaluation and formulation of treatment strategies for a woven coronary artery are important.

Nomogram for predicting opioid-induced nausea and vomiting for cancer pain patients.

OBJECTIVE: Opioid-induced nausea and vomiting are frequently observed as an adverse effect in the treatment of cancer-related pain. The factors that affect OINV in cancer patients remain unclear. In this study, we developed a nomogram for predicting the occurrence of OINV in this population using retrospective clinical data. METHODS: We collected data from 416 cancer pain patients, 70% of whom used the training set to analyze demographic and clinical variables. We used multivariate logistic regression to identify significant factors associated with OINV. Then, we construct a prediction nomogram. The validation set comprises the remaining 30%. The reliability of the nomogram is evaluated by bootstrap resampling. RESULTS: Using multivariate logistic regression, we identified five significant factors associated with OINV. The C-index was 0.835 (95% confidence interval [CI], 0.828-0.842) for the training set and 0.810 (95% CI, 0.793-0.826) for the validation set. The calibrated curves show a good agreement between the predicted and actual occurrence of OINV. CONCLUSION: In a retrospective study based on five saliency-found variables, we developed and proved a reliable nomogram model to predict OINV in cancer pain patients. Future prospective studies should assess the model's reliability and usefulness in clinical practice.

Correlation between decreased plasma miR-29a and vascular endothelial injury induced by hyperlipidemia.

BACKGROUND: Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model. METHODS: The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D3 combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule­1 (sICAM-1). CONCLUSION: The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.

Effects of Surgical Timing of Facial Nerve Decompression for Patients With Severe Bell's Palsy.

Context: Bell's palsy is a form of idiopathic, facial nerve palsy. Initial treatment includes the use of oral corticosteroids and/or antiviral agents, but facial paralysis may persist. Some surgeons suggest that surgical decompression of the facial nerve can be a beneficial, but the optimal surgical approach, extent of nerve decompression, and timing of surgery remain unclear. Objective: This study intended to evaluate the efficacy of delayed, facial nerve decompression for severe Bell's palsy (BP) and to explore the relationship of opportunity timing for operations, with postoperative recovery for facial nerve function. Design: The research team performed a retrospective study. Setting: The study took place at Beijing Tiantan Hospital of Capital Medical University in Beijing, China. Participants: Participants were 45 patients who had been diagnosed with BP between 2015 and 2021 and who had undergone facial nerve decompression using the transmastoid approach, between 30 and 180 days after the onset of BP. According to the operation's timing, the research team divided the participants into three groups, consisting of participants who underwent surgery: (1) at 30-60-days after BP onset-19 participants, (2) at 61-90 days after BP onset-18 participants, and (3) at more than 90 days after BP onset-8 participants. Outcome Measures: The research team: (1) analyzed participants' demographic and preoperative and postoperative clinical characteristics, (2) compared the surgical outcomes with participants' House-Brackmann (HB) scales, and (3) analyzed the factors affecting the recovery of facial nerve function using logistic regression. Results: Decompression surgery was effective for 29 participants (64.4%), with similar rates for participants who underwent surgery after 30-60 days (73.7%) and 61-90 days (77.8%), but the surgery' success was significantly higher for those groups than for participants who underwent surgery after >90 days (12.5%), with P = .008 and P = .003, respectively. Multivariate logistic regression analysis showed that disease duration was the only factor significantly associated with the effectiveness of surgery (odds ratio = 120.337; 95% confidence interval 2.997-4832.267, P = .011). Conclusions: For patients with severe Bell's palsy with ineffective conservative treatment, surgery performed 30 to 90 days after the onset of paralysis can have therapeutic benefits, whereas surgery performed after 3 months is relatively ineffective.

Adaptive Bitline Voltage Countermeasure for Neighbor Wordline Interference in 3D NAND Flash Memory-Based Sensors.

Three-dimensional NAND flash memory is widely used in sensor systems as an advanced storage medium that ensures system stability through fast data access. However, in flash memory, as the number of cell bits increases and the process pitch keeps scaling, the data disturbance becomes more serious, especially for neighbor wordline interference (NWI), which leads to a deterioration of data storage reliability. Thus, a physical device model was constructed to investigate the NWI mechanism and evaluate critical device factors for this long-standing and intractable problem. As simulated by TCAD, the change in channel potential under read bias conditions presents good consistency with the actual NWI performance. Using this model, NWI generation can be accurately described through the combination of potential superposition and a local drain-induced barrier lowering (DIBL) effect. This suggests that a higher bitline voltage (Vbl) transmitted by the channel potential can restore the local DIBL effect, which is ever weakened by NWI. Furthermore, an adaptive Vbl countermeasure is proposed for 3D NAND memory arrays, which can significantly minimize the NWI of triple-level cells (TLC) in all state combinations. The device model and the adaptive Vbl scheme were successfully verified by TCAD and 3D NAND chip tests. This study introduces a new physical model for NWI-related problems in 3D NAND flash, while providing a feasible and promising voltage scheme as a countermeasure to optimize data reliability.

Improving the photoresponse performance of monolayer MoS2photodetector via local flexoelectric effect.

Strain engineering is an effective means of modulating the optical and electrical properties of two-dimensional materials. The flexoelectric effect caused by inhomogeneous strain exists in most dielectric materials, which breaks the limit of the materials' non-centrosymmetric structure for piezoelectric effect. However, there is a lack of understanding of the impact on optoelectronic behaviour of monolayer MoS2photodetector via local flexoelectric effect triggered by biaxial strain. In this paper, we develop a probe tip (Pt)-MoS2-Au asymmetric Schottky barrier photodetector based on conductive atomic force microscopy to investigate the impact of flexoelectric effect on the photoresponse performance. Consequently, when the probe force increases from 24 nN to 720 nN, the photocurrent, responsivity and detectivity increase 28.5 times, 29.6 times and 5.3 times at forward bias under 365 nm light illumination, respectively. These results indicate that local flexoelectric effect plays a critical role to improve the photoresponse performance of photodetector. Our approach suggests a new route to improve the performance of photodetectors by introducing local flexoelectric polarization field, offering the potential for the application of strain modulated photoelectric devices.

A simplified multiplex methylated DNA testing for early detection of colorectal cancer in stool DNA.

BACKGROUND: ColoDefense1.0 assay has demonstrated its excellent sensitivity and specificity for early detection of colorectal cancer (CRC) by detecting the methylation levels of SDC2 and SEPT9, while exhibited limitations on relatively large sample capacity required and limited detection throughput by applying triplicate PCR reactions for each sample. In this study, ColoDefense1.0 was simplified and optimized into ColoDefense2.0 in a single PCR reaction. METHODS: A total 529 stool specimens were collected, and 244 CRC patients, 34 patients with advanced adenomas (AA), 64 with small polyps (SP) and 187 control subjects were divided in training and validation cohorts. Methylation levels of SEPT9 and SDC2 were examined by qPCR reactions in triplicate or single. RESULTS: The stool DNA quantity stored in preservative buffer at 37 °C up to 7 days exhibited no significant decrease. In the training cohort, when the number of replicates reduced from 3 to 1, the overall performance of ColoDefense2.0 was identical to that of ColoDefense1.0, showing sensitivities of 71.4% for AA and 90.8% for all stage CRC with a specificity of 92.9%. In the validation cohort, sensitivities of SP, AA and CRC using ColoDefense2.0 were 25.0%, 55.0% and 88.2%, increased from 14.1% (20.3%), 40.0% (40.0%) and 79.4% (67.6%) using SDC2 (SEPT9) alone; along with an overall specificity of 90.2%, decreased from 94.1% (95.1%) using SDC2 (SEPT9) alone. CONCLUSION: The simplified ColoDefense test maintained the overall performance while reduced the number of PCR reactions to 1/3, and provided an effective and convenient tool to detect early CRC and precancerous lesions and potentially improve the compliance of screening.

Long noncoding RNA LINC00982 upregulates CTSF expression to inhibit gastric cancer progression via the transcription factor HEY1.

Upregulating the expression of long noncoding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and cathepsin F (CTSF) in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration, and invasion assays. The relationship between LINC00982, YRPW motif 1 (HEY1), and CTSF was examined by RNA-binding protein immunoprecipitation, luciferase assay, and chromatin immunoprecipitation, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, whereas its overexpression impaired the proliferative, migratory, and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter, LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the antitumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. All these taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential antitumor target for gastric cancer.NEW & NOTEWORTHY We identified LINC00982 as a promising antitumor target for the treatment of patients with gastric cancer. We also determined a regulatory network involved in the pathophysiology of gastric cancer wherein LINC00982 could bind to HEY1 to impair its binding to cathepsin F (CTSF) promoter and hence promote CTSF expression, which aids in better understanding of molecular mechanisms related to gastric tumorigenesis.

ELK4 promotes the development of gastric cancer by inducing M2 polarization of macrophages through regulation of the KDM5A-PJA2-KSR1 axis.

BACKGROUND: We tried to elaborate the molecular mechanism of ETS-like transcription factor 4 (ELK4) affecting gastric cancer (GC) progression through M2 polarization of macrophages mediated by lysine-specific demethylase 5A (KDM5A)-Praja2 (PJA2)-kinase suppressor of ras 1 (KSR1) axis. METHODS: GC expression dataset was obtained from GEO database, and the downstream regulatory mechanism of ELK4 was predicted. Tumor-associated macrophages (TAMs) were isolated from GC tissues. The interaction among ELK4, KDM5A, PJA2 and KSR1 was analyzed by dual luciferase reporter gene, ChIP and Co-IP assays. The stability of KSR1 protein was detected by cycloheximide (CHX) treatment. After TAMs were co-cultured with HGC-27 cells, HGC-27 cell biological processes were assessed through gain- and loss-of function assays. Tumorigenicity was detected by tumorigenicity test in nude mice. RESULTS: In GC and TAMs, ELK4, KDM5A and KSR1 were highly expressed, while PJA2 was lowly expressed. M2 polarization of macrophages promoted the development of GC. ELK4 activated KDM5A by transcription and promoted macrophage M2 polarization. KDM5A inhibited the expression of PJA2 by removing H3K4me3 of PJA2 promoter, which promoted M2 polarization of macrophages. PJA2 reduced KSR1 by ubiquitination. ELK4 promoted the proliferative, migrative and invasive potentials of GC cells as well as the growth of GC xenografts by regulating KSR1. CONCLUSION: ELK4 may reduce the PJA2-dependent inhibition of KSR1 by transcriptional activation of KDM5A to promote M2 polarization of macrophages, thus promoting the development of GC.

Reduction of miR-744 delivered by NSCLC cell-derived extracellular vesicles upregulates SUV39H1 to promote NSCLC progression via activation of the Smad9/BMP9 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Extracellular vehicles (EVs) are nano-sized particles containing proteins, lipids, and miRNAs secreted by various cells, which play important roles in the development of lung cancer by regulating a wide range of signaling pathways. This study focused on elucidating a potential mechanism by which EVs promote the development of NSCLC. METHODS: Expression levels of miR-744, SUV39H1, Smad9, and BMP4 in clinical tissue samples of NSCLC patients and cell lines were quantified by RT-qPCR and/or western blot analysis. The interaction between SUV39H1 and miR-744 was identified by dual-luciferase reporter assay. miR-744, SUV39H1, and BMP4 expression levels were modulated in A549 and H460 cells, in order to evaluate their effects on cell proliferation, colony formation and cell cycle. A NSCLC xenograft mouse model was used to verify the in vitro findings. NSCLC cell-derived EVs and normal bronchial epithelial cell-derived EVs were isolated and their roles in NSCLC development were evaluated in vivo and in vitro. RESULTS: miR-744 expression was lower in cancer cell-derived derived EVs than in normal lung epithelial cell-derived EVs. Reduced miR-744 expression in EVs upregulated SUV39H1 in NSCLC cells and further increased BMP4 levels to promote NSCLC development. BMP4 was upregulated in NSCLC cells upon suppression of Smad9 mediated by SUV39H1. Reduced miR-744 expression transferred from cancer cell-derived EVs into NSCLC cells enhanced cancer development. CONCLUSION: Overall, our findings unveiled a mechanism whereby miR-744 delivered by NSCLC-derived EVs upregulated SUV39H1, activating the Smad9/BMP9 axis and thus promoted cancer development.

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.

Platelet function testing guided antiplatelet therapy reduces cardiovascular events in Chinese patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: The PATROL study.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor has become the standard of care to reduce thrombotic events in patients with acute coronary syndrome or after percutaneous coronary intervention (PCI). The role of routine platelet function testing (PFT) in patients treated with DAPT after PCI remains controversial and evidence of PFT-guided antiplatelet therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI is limited. METHODS: We analyzed 1,353 consecutive STEMI patients undergoing primary PCI. PFT was performed 72 hr postprocedure using a vasodilator-stimulated phosphoprotein assay. The primary endpoint of major adverse cardio-cerebral events (MACCEs) was defined as a composite of all-cause death, cardiac death, nonfatal myocardial infarction, target vessel revascularization, and ischemic stroke. Patients with high platelet reactivity (HPR) were randomized to receive an intensified antiplatelet strategy by switching from clopidogrel to ticagrelor (HPR switch group) or to continue on clopidogrel (HPR nonswitch group). One-year clinical outcomes were compared among the groups. RESULTS: The baseline clinical characteristics were comparable across all groups (all p > .05). At the 1-year clinical follow-up, the primary endpoint of MACCE was significantly higher in the HPR nonswitch group than in the non-HPR and HPR switch groups (19.49% vs. 10.20% or 8.57%, p < .05), which was mainly caused by higher mortality (14.87% vs. 4.51% or 5.71%, p < .05). Major bleeding events were comparable across the groups. CONCLUSIONS: In STEMI patients with HPR, identified by vasodilator stimulated phosphoprotein (VASP)-determined PFT, switching clopidogrel to ticagrelor could significantly improve 1-year clinical outcomes without increasing the risk of bleeding.

Blockchain for Vehicular Internet of Things: Recent Advances and Open Issues.

The vehicular Internet of Things (IoT) comprises enabling technologies for a large number of important applications including collaborative autonomous driving and advanced transportation systems. Due to the mobility of vehicles, strict application requirements, and limited communication resources, the conventional centralized control fails to provide sufficient quality of service for connected vehicles, so a decentralized approach is required in the vicinity to satisfy the requirements of delay-sensitive and mission-critical applications. A decentralized system is also more resistant to the single point of failure problem and malicious attacks. Blockchain technology has been attracting great interest due to its capability of achieving a decentralized, transparent, and tamper-resistant system. There are many studies focusing on the use of blockchain in managing data and transactions in vehicular environments. However, the application of blockchain in vehicular environments also faces some technical challenges. In this paper, we first explain the fundamentals of blockchain and vehicular IoT. Then, we conduct a literature review on the existing research efforts of the blockchain for vehicular IoT by discussing the research problems and technical issues. After that, we point out some future research issues considering the characteristics of both blockchain and vehicular IoT.

Long non-coding RNA H19 is responsible for the progression of lung adenocarcinoma by mediating methylation-dependent repression of CDH1 promoter.

Lung adenocarcinoma is a common histologic type of lung cancer with a high death rate globally. Increasing evidence shows that long non-coding RNA H19 (lncRNA H19) and CDH1 methylation are involved in multiple tumours. Here, we tried to investigate whether lncRNA H19 or CDH1 methylation could affect the development of lung adenocarcinoma. First, lung adenocarcinoma tissues were collected to detect CDH1 methylation. Then, the regulatory mechanisms of lncRNA H19 were detected mainly in concert with the treatment of overexpression of lncRNA H19, siRNA against lncRNA H19, overexpression of CDH1 and demethylating agent A-5az in lung adenocarcinoma A549 cell. The expression of lncRNA H19 and epithelial-mesenchymal transition (EMT)-related factors as well as cell proliferation, sphere-forming ability, apoptosis, migration and invasion were detected. Finally, we observed xenograft tumour in nude mice so as to ascertain tumorigenicity of lung adenocarcinoma cells. LncRNA H19 and methylation of CDH1 were highly expressed in lung adenocarcinoma tissues. A549 cells with silencing of lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation by demethylating agent 5-Az had suppressed cell proliferation, sphere-forming ability, apoptosis, migration and invasion, in addition to inhibited EMT process. Silencing lncRNA H19 could reduce methylation level of CDH1. In vivo, A549 cells with silencing lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation exhibited low tumorigenicity, reflected by the smaller tumour size and lighter tumour weight. Taken together, this study demonstrates that silencing of lncRNA H19 inhibits EMT and proliferation while promoting apoptosis of lung adenocarcinoma cells by inhibiting methylation of CDH1 promoter.