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.

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.

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.

Association of D-dimer with long-term prognosis in type 2 diabetes mellitus patients with acute coronary syndrome.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM) accounts for more and more individuals worldwide. D-dimer has been demonstrated to be associated with cardiovascular diseases. The aim is to study the potential impact of D-dimer on the long-term prognosis of acute coronary syndrome (ACS) in the special population with type 2 DM. METHODS AND RESULTS: A total of 2265 consecutive patients with DM and ACS were eligible in the study. Patients were divided into four groups according to quartiles of D-dimer concentration. Univariate and multivariate Cox regression analysis were conducted to explore the prognostic value of D-dimer for future outcomes. Patients with higher level of D-dimer presented with higher percentage of major adverse cardiovascular events (MACEs) (23.7%), all-cause death (18.3%) and cardiovascular (CV) death (9.4%) in Quartile 4. In multivariate Cox regression analysis, D-dimer was demonstrated to be independently associated with MACEs, all-cause death and CV death. The prognostic value of D-dimer is still significant in subgroups of HbA1C <7% and ≥7%. In Kaplan-Meier analysis, higher D-dimer showed poorer prognosis in MACEs, all-cause death and CV death (all log rank p < 0.001). The area under the curve (AUC) by receiver operating characteristic (ROC) curve analysis is 0.609 for MACEs, 0.708 for all-cause death, 0.747 for CV death (p < 0.001). CONCLUSION: The present study demonstrated the independent predictive value of D-dimer for outcomes in DM patients with ACS. In addition, for the first time, we explored the prognostic value in different glucose control status.

The de Winter electrocardiographic pattern evolves to ST elevation in acute total left main occlusion: A case series.

The de Winter electrocardiographic (ECG) pattern was characterized by upsloping ST-segment depressions, tall and positive symmetrical T waves in precordial leads. This rare ECG pattern was recognized as an indication of proximal left anterior descending artery occlusion. Less commonly, this ECG pattern was reported in association with occlusion of other coronary artery segments. We present three cases of the de Winter pattern associated with acute total left main occlusion. This pattern may evolve to ST elevation within hours of presentation. Widespread upsloping ST-segment depressions from V2 -V6 , centered on V5 were observed in these patients.

Prognostic Significance of Preprocedural N-Terminal Pro-B-Type Natriuretic Peptide Assessment in Diabetic Patients With Multivessel Coronary Disease Undergoing Revascularization.

Background and Aims: The N-terminal pro-B-type natriuretic peptide (NT-proBNP) may predict adverse cardiovascular outcomes in patients with diabetes. However, its prognostic value in patients with multivessel disease (MVD) undergoing coronary revascularization remains unclear. This study aimed to evaluate the prognostic significance of preprocedural NT-proBNP levels in diabetic patients with MVD undergoing coronary revascularization. Methods: A total of 886 consecutive diabetic patients with MVD who underwent coronary revascularization were enrolled in this study. Patients were divided into quartiles according to their pre-procedural NT-proBNP levels. Kaplan-Meier curves and Cox regression analyses were performed to evaluate the risk of cardiovascular events, including all-cause death, cardiovascular death, myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE), according to the NT-proBNP quartiles. Results: During a median follow-up period of 4.2 years, 111 patients died (with 82 being caused by cardiovascular disease), 133 had MI, 55 suffered from stroke, and 250 experienced MACE. Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of all-cause death, cardiovascular death, MI, and MACE (log-rank test, P < 0.001, respectively). Multivariate Cox regression analysis revealed that NT-proBNP level was an independent predictor of adverse outcomes, including all-cause death (HR, 1.968; 95% CI, 1.377-2.812; P < 0.001), cardiovascular death (HR, 1.940; 95% CI, 1.278-2.945; P = 0.002), MI (HR, 1.722; 95% CI, 1.247-2.380; P = 0.001), and MACE (HR, 1.356; 95% CI, 1.066-1.725; P = 0.013). The role of NT-proBNP in predicting adverse outcomes was similar in patients with stable angina pectoris and acute coronary syndrome. Moreover, preprocedural NT-proBNP alone discriminated against the SYNTAX II score for predicting all-cause death [area under the curve (AUC), 0.662 vs. 0.626, P = 0.269], cardiovascular death (AUC, 0.680 vs. 0.622, P = 0.130), MI (AUC, 0.641 vs. 0.579, P = 0.050), and MACE (AUC, 0.593 vs. 0.559, P = 0.171). The addition of NT-proBNP to the SYNTAX II score showed a significant net reclassification improvement, integrated discrimination improvement, and improved C-statistic (all P < 0.05). Conclusion: NT-proBNP levels were an independent prognostic marker for adverse outcomes in diabetic patients with MVD undergoing coronary revascularization, suggesting that preprocedural NT-proBNP measurement might help in the risk stratification of high-risk patients.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

[Potential of Arbuscular Mycorrhizal Fungi, Biochar, and Combined Amendment on Sandy Soil Improvement Driven by Microbial Community].

Sandy soils are considered as a significant transition phase to desertification. The effective recovery of sandy soils is of great significance to mitigate the desertification process. Some studies have shown that arbuscular mycorrhizal (AM) fungi and biochar improved the sandy soil, but there have been very few studies regarding the combined effects of AM fungi and biochar amendments on sandy soil improvement. Additionally, the roles of the bacterial and fungal community during the process of sandy soil improvement remain unclear. A greenhouse pot experiment with four treatments, including a control (CK, no amendment), single AM fungi-assisted amendment (RI), single biochar amendment (BC), and combined amendment (BC_RI, biochar plus AM fungi), was set up. This study investigated the effects of different amendment methods on the Nitrariasi birica mycorrhizal colonization, biomass, nutrient (N, P, K, Ca, and Mg) content, soil organic carbon, soil nutrient (TN, TP, and TK) content, and soil water-stable aggregate composition. High throughput sequencing technology was used to investigate the roles of the bacterial and fungal communities during the process of sandy soil improvement. Combined with multiple analysis methods, the improvement mechanisms of different amendment methods were explored. The aim was to provide basic data and scientific basics for reasonably and effectively improving sandy soils. The results indicated that a significant mycorrhiza colonization was observed in the inoculation (RI and BC_RI) treatments, but there was no substantial difference in the mycorrhiza colonization with the RI and BC_RI. Compared with the CK, the shoot biomass and shoot element (N, K, Ca, and Mg) contents were significantly increased in the RI, and the shoot element (N, P, K, Ca, and Mg) contents were significantly increased in the BC and BC_RI; compared with the RI and BC, the root biomass and the root element (P, K, Ca, and Mg) contents were significantly increased in the BC_RI. Compared with the CK, the soil organic carbon contents were significantly increased in the BC and BC_RI, the soil TN contents were significantly increased by 152.54%, and the soil TP and TK contents were significantly decreased by 12.5% and 18.8%, respectively. The proportion of soil aggregates with particle sizes of 0.25-0.05 mm was the highest in each treatment, and the large particle size (>0.25 mm) soil aggregate was significantly increased in the BC_RI. Compared with the CK, the Sobs and Shannon indices of the bacterial/fungal community were significantly decreased in the RI and BC_RI. There was a difference in the microbial community compositions and abundance in the various treatments. The results of the RDA and network analysis were as follows:the effects of AM fungi, biochar, and combined amendment on the soil environment and microbial community structure were significant; in the different amendment treatments, the relationship of the microbial molecular ecological network was significantly changed, and the composition of the core species varied; compared with the RI, there was a higher network connection degree and a richer core species composition in the BC and BC_RI; moreover, the essential role of Rhizophagus intraradices was weaken and the core roles of the other microorganisms (especially bacterial species) were enhanced under the combined effects of biochar and AM fungi. The SEM results demonstrated that the application of AM fungi and biochar could directly affect the bacteria/fungi community structure, and further affect the plant growth and soil properties. The differences in the microbial community structure (especially the change in the microbial interaction) were the key driving factors that led to the difference in the soil improvement effectiveness. In summary, the effects of the different amendment methods on the improvement effectiveness of sandy soils varied. The microbial community played key roles in the process of sandy soil improvement, and there were potential advantages and applications in accelerating the ecological restoration of sandy soils under the combined AM fungi and biochar amendment.

Bivalirudin in patients undergoing percutaneous coronary intervention and independent predictors of postoperative adverse events in these patients: A real world retrospective study.

ABSTRACT: The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events.A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year.Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05).Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.

The Inhibitory Effects of Recombinant Hespintor Combined with Sorafenib on Transplanted Human Hepatoma in Nude Mice, and Transcriptional Regulation of Hespintor Based on RNA-Seq.

Objective: As targeted drugs, exogenous serpins could be introduced to patients to restore body balance. This study aimed to observe further the inhibitory effects of recombinant Hespintor (a Kazal-type serpin) combined with Sorafenib on transplanted human hepatoma tumors in nude mice specimens and to explore the possible transcriptional regulation by Hespintor. Methods: A model of human hepatoma tumors transplanted in nude mice was established, and the medication was administrated to observe the growth of the tumors. Four weeks after the drug administration, the tumors were removed to evaluate the inhibition effects of Hespintor on in-situ tumor growth and liver metastasis. The expression levels of MMP2, MMP9, Bax, Bcl-2, and caspase-3 in the tumor organizations were detected with Western blot. The target genes of the Hespintor were screened based on tissue RNA-Seq, and the regulatory network was constructed. Results: It was found that the recombinant Hespintor displayed a significant antitumor effect on the subcutaneous growth of MHCC97-H cells. Moreover, the therapeutic effects of the combination therapy were significantly better than those of single therapy. 10 target genes with significantly different expression by Hespintoron tumor tissue were identified. Finally, a visual regulatory networkwas constructed for target mRNA-pathway. Conclusions: The antitumor effect of Hespintor combined with Sorafenib in treating the subcutaneously implanted hepatocellular carcinoma tumors in nude mice was significant. The possible transcriptional regulation by Hespintor involved multiple signaling pathways, and it was not just the antitumor effect of uPA via its extracellular inhibitions.

Total synthesis of three natural phenethyl glycosides.

Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.

Botanical and Traditional Uses and Phytochemical, Pharmacological, Pharmacokinetic, and Toxicological Characteristics of Ziziphi Spinosae Semen: A Review.

Ziziphi Spinosae Semen (ZS, the seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) is used as a traditional Chinese medicine referred to as Suan zao ren (). This paper aims to provide a systematic review of its traditional uses and its botanical, phytochemical, pharmacological, pharmacokinetic, and toxicological characteristics. The future development and research prospects for ZS have also been discussed in detail. To date, over 150 compounds have been identified in this plant, including terpenoids, alkaloids, flavonoids, fatty acids, volatile oils, polysaccharides, and others. Both extracts and purified compounds have excellent biological activities, especially sedative and hypnotic effects. Other effects include ameliorating effect of learning and memory, anti-inflammation, antioxidation, blood pressure and lipid lowering, antiaging, and antitumor effects. Thus, this traditional Chinese medicine can be used to treat many diseases such as insomnia, forgetfulness, headaches, and dizziness. Although many of the traditional uses of ZS are well established, the relationship between structure and function still needs to be further studied. In order to better pave the way for research and the establishment of quality control standards for ZS, it will be very important to elucidate its pharmacological mechanisms of action and explore new clinical effects.

Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome.

BACKGROUND: The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS. METHODS: A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2). RESULTS: The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan-Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201-1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019). CONCLUSIONS: The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macacafascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3ß,5,6ß-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

A Novel Synthetic Steroid of 2ß,3α,5α-Trihydroxy-androst-6-one Alleviates the Loss of Rat Retinal Ganglion Cells Caused by Acute Intraocular Hypertension via Inhibiting the Inflammatory Activation of Microglia.

Neuroinflammation has been well recognized as a key pathological event in acute glaucoma. The medical therapy of acute glaucoma mainly focuses on lowering intraocular pressure (IOP), while there are still scarce anti-inflammatory agents in the clinical treatment of acute glaucoma. Here we reported that ß,3α,5α-trihydroxy-androst-6-one (sterone), a novel synthetic polyhydric steroid, blocked neuroinflammation mediated by microglia/macrophages and alleviated the loss of retinal ganglion cells (RGCs) caused by acute intraocular hypertension (AIH). The results showed that sterone significantly inhibited the morphological changes, the up-regulation of inflammatory biomarker ionized calcium-binding adapter molecule 1 (Iba-1), and the mRNA increase of proinflammatory tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in BV2 microglia and RAW264.7 macrophages. Moreover, immunofluorescence and western blotting analysis revealed that sterone markedly abrogated the nuclear translocation and phosphorylation of nuclear factor-κB (NF-κB) p65 subunit. Furthermore, sterone significantly suppressed the inflammatory microglial activation and RGCs' reduction caused by retinal ischemia/reperfusion (I/R) injury in a rat AIH model. These results suggest sterone may be a potential candidate in the treatment of acute glaucoma caused by microglial activation-mediated neuroinflammatory injury.

First total synthesis of a new phenylpropanoid glycoside: natural cytotoxic compound from Cirsium japonicum.

Phenylpropanoid glycoside compound 1, the natural anti-tumor compound isolated from the erial parts of Cirsium japonicum, was first totally synthesized using easily available materials in short, convenient route with overall yield of 13.9%.

The first total synthesis of anemarchalconyn and anemarcoumarin A.

Anemarchalconyn (1) and anemarcoumarin A (2), the natural bioactive compounds isolated from the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae), were first totally synthesized using easily available materials in short, convenient routes with overall yields of 32 and 48%.

Characteristics of coronary arterial lesions in patients with coronary heart disease and hypertension.

OBJECTIVE: The aim of this study was to investigate the correlations between risk factors such as hypertension and the complex degrees of coronary arterial lesions (CAL). METHODS: We selected 462 patients with coronary heart disease (CHD) with confirmed the stenosis (≥50 %) in at least one major coronary artery on coronary angiography and divided them into the "CHD with hypertension" group (CHD-HT, n = 306) and the CHD group (n = 156). The characteristics of CAL and the occurrence of 2-year postoperative major adverse cardiac cerebrovascular events (MACCE) in the two groups were observed. RESULTS: The mean SYNTAX scores (SS) was higher in the CHD-HT group than in the CHD group (P < 0.05). The proportions of complex, calcified, and diffused long lesions in the PCI patients' target vascular lesions, as well as the total MACCE incidence, were significantly higher in the CHD-HT group than in the CHD group (P < 0.05). Logistic multifactor regression analysis showed that age, male sex, hypertension, diabetes, hyperlipidemia, and previous history of myocardial infarction were positively correlated with the SS (P < 0.05). CONCLUSIONS: The patients with CHD-HT exhibited complicated and diffused CAL, and arterial hypertension can be considered as a risk factor for the complexity of coronary lesions in patients with ischemic heart disease.

Characterization of a Synthetic Steroid 24-keto-cholest-5-en-3ß, 19-diol as a Neuroprotectant.

BACKGROUND: Neuroactive steroids represent promising candidates for the treatment of neurological disorders. Our previous studies identified an endogenous steroid cholestane-3ß, 5α, 6ß-triol (Triol) as a novel neuroprotectant. AIM: We aimed to identify a potent candidate for stroke treatment through a screening of Triol analogs. METHODS: Hypoxia- and glutamate-induced neuronal injury models in vitro, middle cerebral artery occlusion (MCAO)-induced cerebral ischemia model in vivo, fluorescein diacetate (FDA) for alive and propidium iodide (PI) for dead staining, LDH assay, and calcium imaging techniques were used. RESULTS: 24-keto-cholest-5-en-3ß, 19-diol (Diol) showed the most potent neuroprotective effect among the screened structurally related compounds. FDA and PI staining showed that Diol concentration dependently increased the survival rate of cerebellar granule neurons (CGNs) challenged with glutamate or hypoxia, with an effective threshold concentration of 2.5 µM. Consistently, the quantitative LDH release assay showed the same concentration-dependent protection in both models. Diol, at 10 µM, potently decreased glutamate- and hypoxia-induced LDH release from 51.6 to 18.2% and 62.1 to 21.7%, respectively, which values are close to the normal LDH release (~16-18%). Moreover, we found Diol effectively decreased MCAO-induced infarction volume in mice from ~23% to 7%, at a dose of 6 mg/kg. We further explored the underlying mechanism and found that Diol attenuated NMDA-induced intracellular calcium ([Ca(2+) ]i ) increase in cortical neurons, suggesting a negative modulatory effect on NMDA receptor. CONCLUSION: Taken together, we identified Diol as a potent neuroprotectant. It may represent a novel and promising neuroprotectant for stroke intervention.

Expression of tissue factor in rabbit pulmonary artery in an acute pulmonary embolism model.

BACKGROUND: Tissue factor (TF) is the initiation factor of the extrinsic coagulation pathway, and plays a critical role in the process of thrombosis. This study aimed to investigate the expression of TF and to explore their clinical effect on the pulmonary artery after acute pulmonary thromboembolism. METHODS: Thirty-four Japanese white rabbits (Level II animals) supplied by Tianjin Medical University were randomly assigned into: group A, specimens of the pulmonary artery taken 3 hours after pulmonary embolism (n=8); group B, specimens of the pulmonary artery taken 8 hours after pulmonary embolism (n=8); group C, specimens of the pulmonary artery taken 24 hours after pulmonary embolism (n=8); and control group, pseudo-operations performed without injection of autologous blood clots (n=10). The animal model of pulmonary thrombo-embolism was established by injection of autologous blood clots into the jugular vein through a 5F catheter, and was confirmed by digital subtraction angiography. The mRNA expression of TF in different parts of the pulmonary artery was accessed by RT-PCR. The q test was used if there was a significant difference in a given continuous variable among the three groups assessed by ANOVA. The experiment equipment was supplied by the State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, the Chinese Academy of Medical Sciences and Peking Union Medical College. RESULTS: The TF expression in the specimen adjacent to emboli was stable at 3, 8 or 24 hours after embolism. The mRNA expression of TF at 3 and 8 hours after embolism was lower in the specimens taken from the distal end of the morbid pulmonary artery than those adjacent to emboli. While at 24 hours after embolism, there were similar mRNA levels in specimens either adjacent or distal to emboli. CONCLUSION: The high level of TF expression in pulmonary artery tissue adjacent to emboli could lead to locally increased coagulation activity, indicating the necessity of initiating anti- coagulation treatment as soon as possible after acute pulmonary embolism.