The relative and combined ability of stress hyperglycemia ratio and N-terminal pro-B-type natriuretic peptide to predict all-cause mortality in diabetic patients with multivessel coronary artery disease.

BACKGROUND: Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. METHODS: This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. RESULTS: During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566-3.008; P < 0.001; NT-proBNP: HR: 1.005; 95%CI 1.001-1.009; P = 0.009). Compared to patients in the first (SHR-L and NT-proBNP-L) group, patients in the fourth (SHR-H and NT-proBNP-H) group had the highest mortality risk (HR: 12.244; 95%CI 5.828-25.721; P < 0.001). The areas under the curve were 0.615(SHR) and 0.699(NT-proBNP) for all-cause mortality. Adding either marker to the original models significantly improved the C-statistic and integrated discrimination improvement values (all P < 0.05). Moreover, combining SHR and NT-proBNP levels into the original model provided maximal prognostic information. CONCLUSIONS: SHR and NT-proBNP independently and jointly predicted all-cause mortality in diabetic patients with MVD, suggesting that strategies to improve risk stratification in these patients should incorporate SHR and NT-porBNP into risk algorithms.

Bio-organic fertilizer facilitated phytoremediation of heavy metal(loid)s-contaminated saline soil by mediating the plant-soil-rhizomicrobiota interactions.

Bio-organic fertilizer (BOF) was effective to promote the phytoremediation efficiency of heavy metal(loid)s-contaminated saline soil (HCSS) by improving rhizosphere soil properties, especially microbiome. However, there existed unclear impacts of BOF on plant metabolome and plant-driven manipulation on rhizosphere soil microbiota in HCSS, which were pivotal contributors to stress defense of plants trapped in adverse conditions. Here, a pot experiment was conducted to explore the mechanisms of BOF in improving alfalfa (Medicago sativa)-performing phytoremediation of HCSS. BOF application significantly increased the biomass (150.87-401.58 %) to support the augments of accumulation regarding heavy metal(loid)s (87.50 %-410.54 %) and salts (38.27 %-271.04 %) in alfalfa. BOF promoted nutrients and aggregates stability but declined pH of rhizosphere soil, accompanied by the boosts of rhizomicrobiota including increased activity, reshaped community structure, enriched plant growth promoting rhizobacteria (Blastococcus, Modestobacter, Actinophytocola, Bacillus, and Streptomyces), strengthened mycorrhizal symbiosis (Leohumicola, Funneliformis, and unclassified_f_Ceratobasidiaceae), optimized co-occurrence networks, and beneficial shift of keystones. The conjoint analysis of plant metabolome and physiological indices confirmed that BOF reprogrammed the metabolic processes (synthesis, catabolism, and long-distance transport of amino acid, lipid, carbohydrate, phytohormone, stress-resistant secondary metabolites, etc) and physiological functions (energy supply, photosynthesis, plant immunity, nutrients assimilation, etc) that are associated intimately. The consortium of root metabolome, soil metabolome, and soil microbiome revealed that BOF facilitated the exudation of metabolites correlated with rhizomicrobiota (structure, biomarker, and keystone) and rhizosphere oxidative status, e.g., fatty acyls, phenols, coumarins, phenylpropanoids, highlighting the plant-driven regulation on rhizosphere soil microbes and environment. By compiling various results and omics data, it was concluded that BOF favored the adaptation and phytoremediation efficiency of alfalfa by mediating the plant-soil-rhizomicrobiota interactions. The results would deepen understanding of the mechanisms by which BOF improved phytoremediation of HCSS, and provide theoretical guidance to soil amelioration and BOF application.

An analysis of lncRNAs related to fiber quality and the discovery of their target genes in a Gossypium hirsutum line with Gossypium mustelinum introgression.

KEY MESSAGE: Analysis of fiber quality lncRNAs and their target genes from a pair of Gossypium mustelinum near-isogenic lines provide new prospects for improving the fiber quality of Upland cotton. Long noncoding RNAs (lncRNAs) are an important part of genome transcription and play roles in a wide range of biological processes in plants. In this research, a pair of near-isogenic cotton lines, namely, a Gossypium mustelinum introgression line (IL9) with outstanding fiber quality and its recurrent Upland cotton parent (PD94042), were used as the experimental materials. Cotton fibers were selected for lncRNA sequencing at 17 and 21 days post-anthesis. A total of 2693 differentially expressed genes were identified. In total, 5841 lncRNAs were ultimately screened, from which 163 differentially expressed lncRNAs were identified. Target genes of the lncRNAs were predicted by two different methods: cis and trans. Some of the target genes were related to cell components, membrane components, plant hormone signal transduction and catalytic metabolism, and the results indicated that there might also be important effects on the development of fiber. Four differentially expressed target genes related to fiber quality (Gomus.D05G015100, Gomus.A05G281300, Gomus.A12G023400 and Gomus.A10G226800) were screened through gene function annotation, and the functions of these four genes were verified through virus-induced gene silencing (VIGS). Compared to the negative controls, plants in which any of these four genes were silenced showed significant reductions in fiber strength. In addition, the plants in which the Gomus.A12G023400 gene was silenced showed a significant reduction in fiber uniformity, whereas the plants in which Gomus.A05G281300 was silenced showed a significant increase in fiber fineness as measured via micronaire. Our results showed that these genes play different roles during fiber development, impacting fiber quality.

Prediabetes is Associated with Worse Long-Term Outcomes in Young Patients with Acute Coronary Syndrome.

Purpose: The incidence of prediabetes mellitus (pre-DM) is increasing among young individuals. Whether pre-DM can predict adverse cardiovascular events in acute coronary syndrome (ACS) patients remains controversial. This study aimed to investigate the impact of pre-DM on the long-term clinical outcomes of patients aged≤ 45 years with new-onset ACS. Patients and methods: A total of 1113 patients with new-onset ACS (aged≤ 45 years) who underwent percutaneous coronary intervention (PCI) were enrolled in this study. Patients were divided into three groups according to their glycemic status or history: normal glucose metabolism (NGM), prediabetes (pre-DM), and diabetes mellitus (DM). The primary endpoint was defined as a composite of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI), stroke, or unplanned repeat revascularization. Multivariate Cox regression analysis was performed to explore the association between abnormal glycemic status and MACE. Results: The prevalence of NGM, pre-DM, and DM were 45.9% (n=511), 27.0% (n=301), and 27.0% (n=301), respectively. During a median follow-up of 65 months, MACE occurred in 23.5% (n=120) of NGM, 29.2% (n=88) of pre-DM, and 34.6% (n=104) of DM (P=0.003). After multivariate adjustment, both pre-DM and DM significantly increased the risk of MACE compared with the NGM group (pre-DM: HR1.38, CI95% 1.05-1.83, P=0.023; DM: HR1.65, CI95% 1.27-2.16, P<0.001). Moreover, pre-DM had a similar impact on MACE as DM in young patients with ACS (P=0.162). Conclusion: Pre-DM was common among patients aged≤ 45 years with new-onset ACS. Pre-DM was associated with an increased risk of future MACE compared to NGM.

FT3/FT4 Enhances Risk Assessment in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Based on GRACE 2.0 Score.

Little is known about the association between the free triiodothyronine/free thyroxine (FT3/FT4) ratio and clinical outcomes in euthyroid patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI). A total of 1448 euthyroid patients with NSTE-ACS who underwent PCI were included in this prospective study. Multivariate Cox regression analysis revealed that there was a significantly increased risk of stroke (hazard ratio [HR] 11.380, 95% confidence interval [CI]: 1.386-93.410, P = .024) and major adverse cardiovascular and cerebrovascular events (MACCEs) (HR 3.364, 95% CI: 1.595-7.098, P = .001) in patients in lower FT3/FT4 tertiles. The combined model of FT3/FT4 ratio and the Global Registry of Acute Coronary Events (GRACE) score provided the added value of risk assessment by improving C-statistics, integrated discrimination improvement (IDI), and the net reclassification index (NRI) (all P < .05). Thus, in euthyroid patients with NSTE-ACS undergoing PCI, the FT3/FT4 ratio was not only an independent prognostic indicator of long-term MACCE but also enhanced risk discrimination when combined with the GRACE risk score, which suggests that the calculation of FT3/FT4 before and after PCI may contribute to risk stratification in this particular patient group.

Role of serum CAP1 protein in the diagnosis of patients with first-time acute myocardial infarction.

The dysregulation of adenylate cyclase-associated protein 1 (CAP1) is associated with a variety of inflammatory conditions. Here, we aimed to assess the role of serum CAP1 protein in predicting acute myocardial infarction (AMI), and to explore its effect and mechanism in vascular endothelial cells injury. ELISA was utilized to detected CAP1 protein expression in serum from 70 patients with first-time AMI at 0, 6, 12, 24, 48 hours and 7 days of the onset of chest pain. Receiver operating characteristic (ROC) curve analysis was administered to analyze the diagnostic power of CAP1 for AMI. The CCK-8 and 5-BrdU assays were applied to measure cell proliferation and inflammation in a model of oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVEC). Luciferase reporter gene assay and Western blotting were used to assess the activity of NF-κB pathway. Results showed that serum CAP1 protein expression was upregulated in patients with first-time AMI, its expression was highest at 12 hours of the onset of chest pain. CAP1 protein was positively associated with the levels of cTnI and ox-LDL. CAP1 showed a relatively high diagnostic accuracy in patients with first-time AMI compared with cTnI, and CAP1 combined with cTnI had superior diagnostic value than CAP1 and cTnI alone. The expression of CAP1 protein was increased in supernatants of ox-LDL induced HUVEC in a dose- and time-dependent manner. CAP1 inhibited cell proliferation but promoted inflammation, and induced the activation of NF-κB pathway in vitro. To sum up, increased serum CAP1 expression might serve as a novel diagnostic biomarker for patients with first-time AMI, the mechanism might be related to its induction of NF-κB pathway activation causing abnormal proliferation and inflammation and thus mediating vascular endothelial cell injury.

Synthesis of 1,3,5-triphenyl-1,2,4-triazole derivatives and their neuroprotection by anti-oxidative stress and anti-inflammation and protecting BBB.

Acute ischemic stroke (AIS) is a serious cardiovascular and cerebrovascular disease; Oxidative stress and neuroinflammation are important factors which destroy blood-brain barrier (BBB) in AIS. In the study, a series of 1,3,5-triphenyl-1,2,4-triazole derivatives were designed and synthesized; the optimal compound 9 was obtained by screening their anti-oxidant and anti-inflammatory effects; the neuroprotection effect of compound 9 was evaluated with a rat middle cerebral artery occlusion (MCAO) model. Subsequently, the mechanism of neuroprotection were explored via Western blot. The results prompt compound 9 maybe exert anti-AIS neuroprotection by inhibiting oxidative stress and neuroinflammation inhibition by inhibiting Keap1, COX-2 and iNOS. At the same time, it can protect BBB by reducing glycocalyx degradation and matrix metallopeptidase-9 levels. Its LD50 > 1000 mg/kg on mice and hERG channel inhibition IC50 > 30 µM, which lower acute toxicity and hERG channel inhibition would make compound 9 a promising stroke treatment candidate.

Multiomics reveals Claroideoglomus etunicatum regulates plant hormone signal transduction, photosynthesis and La compartmentalization in maize to promote growth under La stress.

Rare earth elements (REEs) have been widely used in traditional and high-tech fields, and high doses of REEs are considered a risk to the ecosystem. Although the influence of arbuscular mycorrhizal fungi (AMF) in promoting host resistance to heavy metal (HM) stress has been well documented, the molecular mechanism by which AMF symbiosis enhances plant tolerance to REEs is still unclear. A pot experiment was conducted to investigate the molecular mechanism by which the AMF Claroideoglomus etunicatum promotes maize (Zea mays) seedling tolerance to lanthanum (La) stress (100 mg·kg-1 La). C. etunicatum symbiosis significantly improved maize seedling growth, P and La uptake and photosynthesis. Transcriptome, proteome, and metabolome analyses performed alone and together revealed that differentially expressed genes (DEGs) related to auxin /indole-3-acetic acid (AUX/IAA) and the DEGs and differentially expressed proteins (DEPs) related to ATP-binding cassette (ABC) transporters, natural resistance-associated macrophage proteins (Nramp6), vacuoles and vesicles were upregulated. In contrast, photosynthesis-related DEGs and DEPs were downregulated, and 1-phosphatidyl-1D-myo-inositol 3-phosphate (PI(3)P) was more abundant under C. etunicatum symbiosis. C. etunicatum symbiosis can promote plant growth by increasing P uptake, regulating plant hormone signal transduction, photosynthesis and glycerophospholipid metabolism pathways and enhancing La transport and compartmentalization in vacuoles and vesicles. The results provide new insights into the promotion of plant REE tolerance by AMF symbiosis and the possibility of utilizing AMF-maize interactions in REE phytoremediation and recycling.

Early versus late delayed percutaneous coronary intervention in elderly patients with ST-segment elevation myocardial infarction.

BACKGROUND AND OBJECTIVE: There are a substantial proportion of elderly patients with ST-segment elevation myocardial infarction (STEMI) miss the optimal time window (12 h from symptom onset) of primary percutaneous coronary intervention (PCI). For these patients, the ideal timing of delayed PCI remains undetermined. Therefore, this study compared the clinical outcomes of early versus late delayed PCI in elderly patients with STEMI. METHODS: From January 2014 to September 2019, 512 patients aged ≥ 65 years with STEMI who underwent delayed PCI after 12 h from symptom onset were included and then categorized into the early PCI group (12-48 h, n = 111) and late PCI group (48 h-28 days, n = 401) according to the timing of delayed PCI. Propensity score matching (PSM) was conducted to adjust the confounding factors between groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, cardiac death, recurrent myocardial infarction (MI), stroke, and ischemia-driven revascularization. RESULTS: During a mean follow-up of 77 months, 163 (31.8%) patients developed MACCE and 93 (18.2%) died. Early or late delayed PCI did not make a significant difference in clinical outcomes of MACCE (Before PSM: HR 0.773, 95% CI 0.520-1.149, P = 0.203; After PSM: HR 0.869, 95% CI 0.498-1.517, P = 0.622), all-cause death, cardiac death, recurrent MI, stroke, and ischemia-driven revascularization in both overall patients and the PSM cohorts. CONCLUSION: Early delayed PCI (12-48 h from symptom onset), for elderly patients with STEMI who present > 12 h after symptom onset is not associated with better long-term clinical outcomes compared with late delayed PCI (48 h-28 days).

Transcriptome, proteome and functional characterization reveals salt stress tolerance mechanisms in upland cotton (Gossypium hirsutum L.).

Uncovering the underlying mechanism of salt tolerance is important to breed cotton varieties with improved salt tolerance. In this study, transcriptome and proteome sequencing were performed on upland cotton (Gossypium hirsutum L.) variety under salt stress, and integrated analysis was carried out to exploit salt-tolerance genes in cotton. Enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed on differentially expressed genes (DEGs) obtained from transcriptome and proteome sequencing. GO enrichment was carried out mainly in the cell membrane, organelle, cellular process, metabolic process, and stress response. The expression of 23,981 genes was changed in physiological and biochemical processes such as cell metabolism. The metabolic pathways obtained by KEGG enrichment included glycerolipid metabolism, sesquiterpene and triterpenoid biosynthesis, flavonoid production, and plant hormone signal transduction. Combined transcriptome and proteome analysis to screen and annotate DEGs yielded 24 candidate genes with significant differential expression. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the candidate genes showed that two genes (Gh_D11G0978 and Gh_D10G0907) responded significantly to the induction of NaCl, and these two genes were further selected as target genes for gene cloning and functional validation through virus-induced gene silencing (VIGS). The silenced plants exhibited early wilting with a greater degree of salt damage under salt treatment. Moreover, they showed higher levels of reactive oxygen species (ROS) than the control. Therefore, we can infer that these two genes have a pivotal role in the response to salt stress in upland cotton. The findings in this research will facilitate the breeding of salt tolerance cotton varieties that can be grown on saline alkaline lands.

13-Cis Retinoic Acid Induces Neuronal Differentiation in Daoy (Medulloblastoma) Cells Through Epigenetic Regulation of Topoisomerase IIß.

Medulloblastoma (MB) is a malignant tumor of the cerebellum that occurs in children and infants. Abnormal neuronal differentiation can lead to brain tumors, and topoisomerase IIß (Top IIß) plays an important role in neuronal differentiation. The aim of this study was to investigate the molecular mechanism of 13-cis retinoic acid (13-cis RA) promoting the expression of Top IIß and inducing neuronal differentiation in human MB Daoy cells. The results showed that 13-cis RA inhibited the cell proliferation and induced cell cycle arrest in G0/G1 phase. The cells differentiated into a neuronal phenotype, with high expression of the neuronal marker microtubule-associated protein 2 (MAP2) and abundant Top IIß, and obvious neurite growth. Chromatin immunoprecipitation (ChIP) assay showed that histone H3 lysine 27 tri-methylation (H3K27me3) modification in Top IIß promoter decreased after 13-cis RA-induced cell differentiation, while jumonji domain-containing protein 3 (JMJD3) binding in Top IIß promoter increased. These results suggest that H3K27me3 and JMJD3 can regulate the expression of Top IIß gene, which is related to inducing neural differentiation. Our results provide new insights into understanding the regulatory mechanisms of Top IIß during neuronal differentiation and imply the potential application of 13-cis RA in the clinical treatment of MB.

Spatial Localization of Two Enzymes at Pickering Emulsion Droplet Interfaces for Cascade Reactions.

Developing biocatalytic cascades in abiological conditions is of utmost significance, but such processes often suffer from low reaction efficiency because of incompatible reaction environments and suppressed intermediate transportation. Herein we report a new type of biocatalytic cascade by localizing two different enzymes separately in the outer and inner interfacial layers of Pickering emulsion droplets. This versatile approach enables the localization of two enzymes in their preferred reaction microenvironments and simultaneously in nanoscale proximity of each other. The thus-designed interfacial biocatalytic cascades show outstanding catalytic efficiency in alkene epoxidation and thioether oxidation with in situ generation of hydrogen peroxide under mild conditions, 6.9-13.6 times higher than the catalytic efficiency of the free enzymes in solution and their multi-enzymatic counterparts. The remarkable interfacial effect of Pickering droplets was found to be responsible for the significantly enhanced cascading efficiency.

Genome-Wide Characterization and Functional Analysis of ABCG Subfamily Reveal Its Role in Cutin Formation in Cotton.

ATP-binding cassette transporter G (ABCG) has been shown to be engaged in export of broad-spectrum compounds with structural differences, but little is known concerning its role in cutin formation of cotton (Gossypium spp.). In this study, we conduct a genome-wide survey and detected 69, 71, 124 and 131 ABCG genes within G. arboretum, G. raimondii, G. hirsutum and G. barbadense, separately. The above ABCGs could be divided into four groups (Ia, Ib, Ic, II). Some ABCG genes such as GhABCG15, whose homologous gene transports cuticular lipid in Arabidopsis, was preferentially expressed in the development of fiber. A weighted gene co-expression network analysis (WGCNA) demonstrated that GhABCG expression was significantly associated with the amount of 16-Hydroxypalmitate (a main component of cutin precursor) in cotton fibers. Further, silencing of GhABCG15 by virus-induced gene silencing (VIGS) in cotton generated brightened and crinkled leaves as well as reduced thickness of cuticle and increased permeability. Chemical composition analysis showed the cutin content in GhABCG15-silenced leaves had decreased while the wax content had increased. Our results provide an insight for better understanding of the role of the Gossypium ABCG family and revealed the essential role of GhABCGs in cotton cutin formation.

Polysaccharides from apple pomace exhibit anti-fatigue activity through increasing glycogen content.

The polysaccharides were isolated from apple pomace by hot-water extraction, and their anti-fatigue activity was evaluated in C2C12 muscle myoblasts and male Kunming mice. The purified polysaccharides from apple pomace (PAP) have a molecular weight of 1.74 × 105 Da and were composed of mannose, rhamnose, glucose, galactose and arabinose. In C2C12 myoblasts, PAP showed no cytotoxicity in the concentrations of 0-300 µg/ml. PAP treatment increased the glycogen content, while the ATP content was not affected in C2C12 myoblasts. Further investigation found that the activity and gene expression of glycogen synthase, rather than glycogen phosphorylase, were upregulated by PAP treatment. The studies in vivo showed that PAP treatment did not affect the food intake and weight again in mice. Importantly, PAP prolonged the exhaustive swimming time, increased hepatic and skeletal muscle glycogen levels, and effectively inhibited the accumulation of blood lactic and blood urea nitrogen in mice. Taken together, the results suggested that PAP exhibit anti-fatigue activity in vitro and in vivo through increasing glycogen content.

Culprit vessel vs. immediate multivessel vs. out-of-hospital staged intervention for patients with non-ST-segment elevation myocardial infarction and multivessel disease.

Background and aims: The optimal interventional strategy remains undetermined in hemodynamically stable patients with NSTEMI and MVD. This study aimed to examine clinical prognosis among culprit vessel, immediate multivessel, and staged percutaneous coronary intervention (PCI) in patients with NSTEMI and MVD. Methods: This retrospective, observational, single-center study included 943 hemodynamically stable patients with NSTEMI and MVD who had undergone successful drug-eluting stent (DES) implantation from January 2014 to December 2019. Patients were categorized into culprit lesion-only PCI (CL-PCI), immediate multivessel PCI (MV-PCI), and out-of-hospital staged MV-PCI according to PCI strategy. The primary outcome was the composite of major adverse cardiac events (MACEs), including all-cause death, myocardial infarction (MI), or unplanned repeat revascularization. The secondary outcomes were all-cause death, cardiac death, MI, and unplanned repeat revascularization. Results: Over a median follow-up of 59 months, immediate MV-PCI was associated with a lower risk of all-cause death than CL-PCI (HR: 0.591, 95%CI: 0.364-0.960, P = 0.034). Out-of-hospital staged MV-PCI was associated with a reduced risk of MACE (HR: 0.448, 95%CI: 0.314-0.638, P < 0.001) and all-cause death (HR: 0.326, 95%CI: 0.183-0.584, P < 0.001) compared with CL-PCI. The above results were accordant after multivariate COX analysis and propensity score matching. MACE (HR: 0.560, 95%CI: 0.385-0.813, P = 0.002) and repeat revascularization (HR: 0.627, 95%CI: 0.400-0.982, P = 0.041) were significantly less likely to occur with out-of-hospital MV-PCI rather than immediate MV-PCI. However, the incidences of primary and secondary outcomes were comparable between immediate and staged PCI after confounder adjustment using multivariate regression and propensity score matching analysis. For subgroup analyses stratified by synergy between PCI with taxus and cardiac surgery score, staged MV-PCI was found to lower the risk of MACE compared with immediate MV-PCI in patients with more complex coronary disease. Conclusion: Hemodynamically stable patients with NSTEMI and MVD benefited from the strategy of MV-PCI. Patients with complex coronary anatomy treated with out-of-hospital staged MV-PCI rather than immediate MV-PCI had lower risks of MACE. These need to be confirmed in the future randomized study.

Case report: Individualized treatment of advanced breast cancer with the use of the patient-derived tumor-like cell cluster model.

Breast cancer is one of the most common tumors in women. Despite various treatments, the survival of patients with advanced breast cancer is still disappointing. Furthermore, finding an effective individualized treatment for different kinds of patients is a thorny problem. Patient-derived tumor-like cell clusters were reported to be used for personalized drug testing in cancer therapy and had a prediction accuracy of 93%. However, there is still a lack of case reports about its application in the individualized treatment of breast cancer patients. Here, we described four cases of individualized treatment for advanced breast cancer using the patient-derived tumor-like cell cluster model (PTC model). In these four cases, the PTC model showed a good predictive effect. The tumor size was reduced significantly or even disappeared completely through clinical, radiological, or pathological evaluation with the help of the PTC model for selecting an individualized therapy regimen. Furthermore, the drug sensitivity test results of the PTC model were consistent with pathological molecular typing and the actual clinical drug resistance of the patients. In summary, our case report first evaluated the application value of the PTC model in advanced breast cancer, and the PTC model might be used as an efficient tool for drug resistance screening and for selecting a better personalized treatment, although further study is needed to prove the validity and stability of the PTC model in drug screening.

Pro-angiogenic activity of isofuran.

Isofurans (IsoFs) are a series of novel discovered lipid peroxidation products. This study focused on the investigation of the angiogenic property of IsoF. MTT stain assay indicated that 1 µm IsoF had the most bioactivity in rat brain endothelial cells (RBECs). IsoF significantly promoted cellular proliferation and migration and remarkably decreased staurosporine-induced apoptosis by TUNEL assay in the RBECs. It successfully up-regulated rat aortic vascularization and choroid explant sprouting, extracellular regulated protein kinases (ERK)1/2, and triggered calcium release. RT-PCR examination indicated that IsoF up-regulated tumor necrosis factor (TNF)α, angiopoietin-1 receptor (Tie2), and vascular endothelial growth factor (VEGF)-A, but did not interfere with caspase 2 and VEGF-C in the RBECs. IsoF has pro-angiogenic activity. Calcium release and ERK1/2 phosphorylation may be involved in the signaling of the IsoF-induced up-regulation of TNFα, Tie2, and VEGF-A, which could be the molecular mechanism of the pro-angiogenic activity of the IsoF.

Staged revascularization vs. culprit-only percutaneous coronary intervention for multivessel disease in elderly patients with ST-segment elevation myocardial infarction.

Backgroundand objective: Studies have highlighted the significant role of staged percutaneous coronary intervention (PCI) for a multivessel disease (MVD) among patients with ST-elevation myocardial infarction (STEMI). However, the relative benefit of staged vs. culprit-only PCI for MVD in elderly patients with STEMI remains undetermined. Thus, the present study compared the clinical outcomes of staged and culprit-only PCI in this cohort. Methods: From January 2014 to September 2019, 617 patients aged ≥65 years with STEMI and MVD who underwent primary PCI of the culprit vessels within 12 h of symptom onset were enrolled. They were then categorized into the staged and culprit-only PCI groups according to intervention strategy. Propensity score matching (PSM) was conducted to adjust for confounding factors between groups. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, cardiac death, recurrent myocardial infarction (MI), stroke, and ischemia-driven revascularization. Results: During a mean follow-up of 56 months, 209 patients experienced MACCE and 119 died. Staged revascularization was associated with a lower risk of MACCE, all-cause death, and cardiac death than culprit-only PCI in both overall patients and the PSM cohorts. In contrast, there was no significant difference in stroke or ischemia-driven revascularization. Moreover, on multivariate Cox regression analysis, staged PCI was a significant predictor of a lower incidence of MACCE and all-cause death. Conclusion: In elderly patients with STEMI and MVD, staged PCI is superior to culprit-only PCI.

Prognostic performance of multiple biomarkers in patients with acute coronary syndrome without standard cardiovascular risk factors.

Background and aims: Acute coronary syndrome (ACS) without standard modifiable cardiovascular risk factors (SMuRFs) represents a special case of ACS. Multiple biomarkers have been shown to improve risk stratification in patients with ACS. However, the utility of biomarkers for prognostic stratification in patients with ACS without SMuRFs remains uncertain. The aim of the present study was to evaluate the prognostic value of various biomarkers in patents with ACS without SMuRFs. Methods: Data of consecutive patients with ACS without SMuRFs who underwent coronary angiography in Tianjin Chest Hospital between January 2014 and December 2017 were retrospectively collected. The primary outcome was the occurrence of major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, myocardial infarction and stroke. Seven candidate biomarkers analyses were analyzed using models adjusted for established risk factors. Results: During a median 5-year follow-up, 81 of the 621 patients experienced a MACE. After adjustment for important covariates, elevated fibrinogen, D-dimer, N-terminal proB-type natriuretic peptide (NT-proBNP), and lipoprotein (a) [Lp(a)] were found to be individually associated with MACE. However, only D-dimer, NT-proBNP and Lp(a) significantly improved risk reclassification for MACE (all P < 0.05). The multimarker analysis showed that there was a clear increase in the risk of MACE with an increasing number of elevated biomarkers and a higher multimarker score. The adjusted hazard ratio- for MACE (95% confidential intervals) for patients with 4 elevated biomarkers was 6.008 (1.9650-18.367) relative to those without any elevated biomarker-. Adding- the 4 biomarkers or the multimarker score to the basic model significantly improved the C-statistic value, the net reclassification index and the integrated discrimination index (all P < 0.05). Conclusion: Fibrinogen, D-dimer, NT-proBNP and Lp(a) provided valuable prognostic information for MACE when applied to patients with ACS without SMuRFs. The multimarker strategy, which combined multiple biomarkers reflecting different pathophysiological process with traditional risk factors improved the cardiovascular risk stratification.

Discovery of 1,2,4-triazole derivatives as novel neuroprotectants against cerebral ischemic injury by activating antioxidant response element.

Acute ischemic stroke is an important cause of death and long-term disability worldwide. In this work, we have synthesized a series of derivatives with 3,5­diaryl substituent triazole scaffolds. The derivatives showed favorable protective effective in SNP-induced oxidative stress model, of which compound 5 was the most active. In vivo experiments showed that compound 5 could ameliorate neurological deficits, attenuate infarction sizes, reduce malonaldehyde (MDA) level and increase superoxide dismutase (SOD) level in middle cerebral artery occlusion (MCAO) rats. Preliminary safety evaluation showed that compound 5 exhibited low acute toxicity in BALB/c mice (LD50 greater than 1000 mg/kg). Further investigation indicated that compound 5 was able to scavenge ROS, restore mitochondrial membrane potential and protect PC12 cells from SNP-induced apoptosis. Moreover, compound 5 could initiate transcription of antioxidant response element (ARE) and induced expressions of antioxidative enzymes. Collectively, compound 5 might have the potency of treating acute ischemic stroke.