Association of baseline hemoglobin A1c levels with bleeding in patients with non-ST-segment elevation acute coronary syndrome underwent percutaneous coronary intervention: insights of a multicenter cohort study from China.

OBJECTIVE: To investigate the association between baseline hemoglobin A1c (HbA1c) levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI). METHODS: This observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1, 2010 to December 31, 2014. Based on baseline HbA1c levels, the patients were divided into the group with HbA1c < 7% ( n = 4740) and the group with HbA1c ≥ 7% (n = 1543). The primary outcomes are major bleeding (BARC grades 3-5) and all-cause death during follow-up. RESULTS: Of patients enrolled, 4705 (74.9%) were male, and 2143 (34.1%) had a history of diabetes mellitus, with a mean (SD) age of 64.13 (10.32) years. The median follow-up duration was 3.21 years. Compared with the patients with HbA1c < 7%, the risk of major bleeding events during follow-up was higher in patients with HbA1c ≥ 7% (adjusted hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.01-2.44; P = 0.044), while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels (adjusted HR = 0.88; 95% CI: 0.66-1.18; P = 0.398). CONCLUSIONS: Compared with the lower baseline HbA1c levels, the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI, though higher baseline HbA1c levels were not associated with the higher risk in all-cause death.

Association of Parenteral Anticoagulation Therapy With Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Without Invasive Therapy: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project.

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

Differentially expressed genes involved in immune pathways from yellowhead catfish (Tachysurus fulvidraco) after poly (I:C) challenge.

Yellowhead catfish (Tachysurus fulvidraco) is an important aquaculture fish species in China with a high market value. Infectious diseases pose serious threats in farmed fish species, and although vaccines can prevent certain infections, they rely on potent adjuvants. In this study, we analyzed the transcriptomic profiles of spleens from poly (I:C)-treated T. fulvidraco. We obtained 46,362,922 reads corresponding to 490,926 transcripts and 318,059 genes. Gene annotation using different databases and subsequent differential gene expression analyses led to the identification of 5587 differentially expressed genes (DEGs), of which 2473 were up-regulated and 3114 were down-regulated in poly (I:C)-treated fish. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs revealed the significant dysregulation of immune- and cancer-related genes in the spleens of poly (I:C)-treated fish. Notably, several components of JAK-STAT, MAPK, and p53 signaling pathways were significantly dysregulated in response to poly (I:C) treatment. Quantitative real-time PCR (qRT-PCR) analysis of 11 randomly selected immune response genes confirmed the reliability of our findings. In conclusion, our findings provide novel insight into the immune responses of T. fulvidraco and suggest that poly (I:C) may represent a promising adjuvant of fish vaccines.

The association of baseline N-terminal pro-B-type natriuretic peptide with short and long-term prognosis following percutaneous coronary intervention in non-ST segment elevation acute coronary syndrome with multivessel coronary artery disease: a retrospective cohort study.

BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.

Association of in-hospital intensive statins dosage and death in arteriosclerotic cardiovascular disease with percutaneous coronary intervention: insights of multicentre cohort from China.

PURPOSE: In-hospital statin dosage-related effect remains unknown for patients with arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the associations of different in-hospital intensive statins dosages with the prognosis for patients in the era of percutaneous coronary intervention (PCI). METHODS: From January 2010 to December 2014, consecutive ASCVD patients receiving PCI were enrolled from five centres in China. All the enrolled patients were classified into high-dose (40 mg atorvastatin or 20 mg rosuvastatin) or low-dose (20 mg atorvastatin or 10 mg rosuvastatin) intensive statin group. In-hospital all-cause death was the primary outcome. RESULTS: Of the 7008 patients included in this study, 5248 received low-dose intensive statins (mean age, 64.28 ± 10.39; female, 25.2%), whereas 1760 received high-dose intensive statins (mean age, 63.68 ± 10.59; female, 23.1%). There was no significant difference in the in-hospital all-cause death between the two groups (adjusted OR, 1.27; 95% CI, 0.43-3.72; P = 0.665). All-cause death was similar between the two groups during the 30-day follow-up period (adjusted HR, 1.28; 95% CI, 0.55-2.97; P = 0.571). However, the high-dose intensive statins were tightly associated with the reduction in in-hospital dialysis (adjusted OR, 0.11; 95% CI, 0.01-0.81; P = 0.030). Besides, primary analyses were confirmed by subgroup analyses. CONCLUSIONS: The in-hospital high-dose intensive statins are not associated with the lower risk of in-hospital or 30-day all-cause death among ASCVD patients undergoing PCI. Given the robust beneficial effect of high-dose intensive statins with in-hospital dialysis, an individualized high-dose intensive statin therapy can be rational in specified populations.

Transcriptome-wide identification of differentially expressed genes in Procambarus clarkii in response to chromium challenge.

Because of the high protein content and rich meat quality of crayfish Procambarus clarkii, it has become widely popular in China in recent years and has a high economic value. When P. clarkii is stimulated by heavy metals, it reacts to oxidation. P. clarkii has evolved antioxidant defense systems, including antioxidant enzymes such as catalase (CAT). The hexavalent form of Cr (VI) is a pathogenic factor that is of particular concern in aqueous systems because of its great toxicity to living organisms. In this study, we characterized the transcriptome of P. clarkii using a RNA sequencing method and performed a comparison between K2Cr2O7-treated samples and controls. In total, 34,237 unigenes were annotated. We identified 5098 significantly differentially expressed genes (DEGs), including 2536 and 2562 were significantly up-regulated and down-regulated, respectively. In addition, quantitative real time-PCR (qRT-PCR) confirmed the up-regulation of a random selection of DEGs. Our results contribute to a more comprehensive understanding of the antioxidant defense system used by P. clarkii in response to heavy metal stress.

Transcriptome analysis of differential expressed genes in hepatopancreas of Procambarus clarkii challenged with peptidoglycan.

Procambarus clarkii is one of the most economically important species in Chinese aquaculture, and is widely cultured. Infection of P. clarkii populations with bacterial pathogens causes high mortality and great economic loss, therefore disease control is of significant economic importance. P. clarkii is a model system for studying immune responses in invertebrates, and its immune system consists solely of the innate response. In the present study, we examined gene expression related to immune function in P. clarkii in response to pathogen challenge. The transcriptome of hepatopancreas tissue from P. clarkii challenged with peptidoclycan (PGN) was analyzed and compared to control specimens. After assembly and annotation, 48,661 unigenes were identified with an average length of 671.54 bp. A total of 2533 differentially expressed genes (DEGs) were obtained, including 765 significantly up-regulated unigenes and 1757 significantly down-regulated unigenes. Gene ontology (GO) analysis demonstrated 19 biological process subcategories, 16 cellular component subcategories, and 17 molecular function subcategories that were enriched among these DEGs. Enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed enrichment among immune responses pathways. Taken together, this study not only enriches the existing P. clarkii transcriptome database, but also elucidates immune responses of crayfish that are activated in response to PGN challenge.

A new bioactive steroidal ketone from the South China Sea sponge Xestospongia testudinaria.

A new steroidal ketone (1), with an ergosta-22,25-diene side chain, was obtained from the South China Sea marine sponge Xestospongia testudinaria. The structure of 1 was determined on the basis of detailed spectroscopic analysis and by comparison with literature. Compound 1 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC50 value of 4.27 ± 0.55 µM, which is comparable with the positive control oleanolic acid (IC50 = 2.63 ± 0.22 µM).

New laurane-type sesquiterpenoids from the Chinese red alga Laurencia okamurai Yamada.

Two new laurane-type sesquiterpenoids, debromo-3α-hydroperoxy-3-epiaplysin (1) and debromo-3ß-hydroperoxyaplysin (2), together with seven known related compounds (3-9), were isolated from the Chinese red alga Laurencia okamurai. Their structures were elucidated by detailed analysis of spectroscopic data and by comparison with the literature. In bioassay, compounds 2, 4, 8, and 9 exhibited significant PTP1B inhibitory activity with IC50 values ranging from 4.9 to 14.9 µg/ml.

Brominated polyunsaturated lipids with protein tyrosine phosphatase-1B inhibitory activity from Chinese marine sponge Xestospongia testudinaria.

A new brominated polyunsaturated lipid, methyl (E,E)-14,14-dibromo-4,6,13-tetradecatrienoate (1), along with three known related analogues (2-4), were isolated from the Et2O-soluble portion of the acetone extract of Chinese marine sponge Xestospongia testudinaria treated with diazomethane. The structure of the new compound was elucidated by detailed spectroscopic analysis and by comparison with literature data. Compound 3 exhibited significant inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a key target for the treatment of type II diabetes and obesity, with an IC50 value of 5.30 ± 0.61 µM, when compared to the positive control oleanolic acid (IC50 = 2.39 ± 0.26 µM).

[Review on the secondary metabolites from Xestospongia sponges and their bioactivities].

The genus Xestospongia is one of the most widespread genera of sponges, containing abundant secondary metatolites with novel structures and potent bioactivities. The main structure types of secondary metatolites found in this genus are alkaloids, quinines, terpens, steroids, lipids, polyketones, etc. These metatolites exhibit a variety of bioactivities, such as cytotoxic, antibacterial and antiviral activities. This paper reviews the progress in the chemistry and pharmacological activities of the second metabolities from sponges of Xestospongia, especially for recent five years, with the aim for further research.

Hainanerectamines A-C, alkaloids from the Hainan sponge Hyrtios erecta.

Two new indole alkaloids, hainanerectamines A (1) and B (2), and one new ß-carboline alkaloids, hainanerectamines C (4), along with five known related alkaloids (3, 5-8), have been isolated from the Hainan marine sponge Hyrtios erecta. The structures of new compounds 1, 2 and 4 were determined by detailed analysis of their 1D and 2D NMR spectra and by comparison of their spectroscopic data with those of related model compounds. Compounds 2-4 exhibited moderate inhibitory activity against Aurora A, a member of serine/threonine kinase family involving in the regulation of cell division and a new target in cancer treatment, with IC50 values of 24.5, 13.6, and 18.6 µg/mL, respectively.

Thunberol, a new sterol from the Chinese brown alga Sargassum thunbergii.

A new sterol, named thunberol (1), along with four known analogs, 24-ethylcholesta-4,24(28)-dien-3-one (2), stigmasta-5,28-dien-3ß-ol (3), cholesta-5,14-dien-3ß-ol (4), and cholesta-5,23-dien-3ß,25-diol (5), were isolated from the brown alga Sargassum thunbergii collected from East China Sea. The structures of these metabolites were elucidated on the basis of detailed spectroscopic analysis and by comparison with the literature data. Thunberol (1) exhibited significant inhibitory activity against protein tyrosine phosphatase 1B, a potential drug target for the treatment of Type-II diabetes and obesity, with an IC50 value of 2.24 µg/ml.

New isoquinolinequinone alkaloids from the South China Sea nudibranch Jorunna funebris and its possible sponge-prey Xestospongia sp.

Two new renieramycin-type bistetrahydroisoquinolinequinone alkaloids, fennebricins A (1) and B (5), and one new isoquinolinequinone alkaloid, N-formyl-1,2-dihydrorenierol (7), were isolated from the skin of the South China Sea nudibranch Jorunna funebris and its possible sponge-prey Xestospongia sp., together with eight known metabolites, including three bistetrahydroisoquinolinequinones (2-4) and five isoquinolinequinones (8-12). Their structures were elucidated by analysis of spectroscopic data including 1D and 2D NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS) and by comparison with data for related known compounds. All the metabolites except for 7 occurred simultaneously in the two animals, supporting recent ecological studies that the nudibranch J. funebris preys on the sponge of the genus Xestospongia.

Brominated polyunsaturated lipids from the Chinese sponge Xestospongia testudinaria as a new class of pancreatic lipase inhibitors.

Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded a library of brominated polyunsaturated lipids including eight new compounds, named xestonarienes A-H (3-10) and thirteen known analogues (11-23). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by comparison with literature data. The isolated lipids were evaluated for their inhibitory activity against pancreatic lipase (PL), an essential enzyme for efficient fat digestion and the major metabolite, 14, exhibited a marked inhibitory activity (IC50 = 3.11 µM), similar to that of the positive control Orlistat (IC50 = 0.78 µM). The preliminary structure-activity relationships on the series of compounds clearly evidenced that a terminal (E)-enyne functionality, a diyne within the chain, and methyl ester group are all key functional groups for the activity of this class of PL inhibitors. Further biological investigation on compound 14 revealed a significant decrease in the plasma triglyceride level following an oral lipid challenge in C57BLKS/J male mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to 1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity for brominated polyunsaturated lipids and the obtained results qualify compound 14 as a potent and bioavailable drug candidate for a mild and safe treatment to prevent and reduce obesity.

A seco-laurane sesquiterpene and related laurane derivatives from the red alga Laurencia okamurai Yamada.

A ring-cleaved sesquiterpene, named seco-laurokamurone, four laurane-type sesquiterpenes, laurepoxyene, 3ß-hydroperoxyaplysin, 3α-hydroperoxy-3-epiaplysin, and 8,10-dibromoisoaplysin, one laurokamurane-type sesquiterpene, laurokamurene D, and one bisabolane-type sesquiterpene, (5S)-5-acetoxy-ß-bisabolene, have been isolated from a re-collection of the red alga Laurencia okamurai Yamada, together with six other known sesquiterpenes. Their structures, including relative configuration, were elucidated by detailed analysis of spectroscopic data, and by comparison with data for related known compounds. In addition, on the basis of chemical conversions, degradation results, and biogenetic considerations, the absolute configurations of several of these compounds were also tentatively proposed. seco-Laurokamurone possesses an unprecedented carbon skeleton, formed from an oxidative cleavage of the laurokamurane skeleton, and laurokamurene D represents the fourth example of a laurokamurane-type sesquiterpene from a natural source. The in vitro antifungal activity of many of these compounds was evaluated against four fungi (Cryptococcus neoformans, Candida glabrata, Trichophyton rubrum, and Aspergillus fumigatus), as well as assessing cytotoxicity against HL-60 and A-549 human cancer cell lines. The compounds studied displayed moderate activities, relative to controls.

The prevalence and molecular spectrum of α- and ß-globin gene mutations in 14,332 families of Guangdong Province, China.

OBJECTIVE: To reveal the familial prevalence and molecular variation of α- and ß-globin gene mutations in Guangdong Province. METHODS: A total of 40,808 blood samples from 14,332 families were obtained and analyzed for both hematological and molecular parameters. RESULTS: A high prevalence of α- and ß-globin gene mutations was found. Overall, 17.70% of pregnant women, 15.94% of their husbands, 16.03% of neonates, and 16.83% of couples (pregnant women and their husbands) were heterozygous carriers of α- or ß-thalassemia. The regions with the highest prevalence were the mountainous and western regions, followed by the Pearl River Delta; the region with the lowest prevalence was Chaoshan. The total familial carrier rate (both spouses were α- or ß-thalassemia carriers) was 1.87%, and the individual carrier rates of α- and ß-thalassemia were 1.68% and 0.20%, respectively. The total rate of moderate-to-severe fetal thalassemia was 12.78% among couples in which both parents were carriers. CONCLUSIONS: There was a high prevalence of α- and ß-thalassemia in Guangdong Province. This study will contribute to the development of thalassemia prevention and control strategies in Guangdong Province.

A concise synthesis of xestospongic acid methyl ester with pancreatic lipase inhibitory activity.

Xestospongic acid methyl ester, a naturally brominated fatty acid with potent pancreatic lipase inhibitory activity in vitro, was synthesized from 5-hexynol in 30% total yield.

Chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms.

Opisthobranchs are slow-moving, brightly colored, and shell-less slug. Interestingly, these naked molluscs appear to be free of predation causing great interests to biologists, chemists, and pharmacologists as well. It is well documented that their ability to escape predation is realized by utilizing chemical substances as defensive allomones. Due to their extraordinary capacity to produce a variety of chemical defensive molecules and in particular, some of which exhibited promising pharmacological activities, opisthobranch molluscs became the hotspot of research subject in the recent years. The authors and co-workers have systematically investigated the possible diet relationship between the South China Sea opisthobranch molluscs and their related prey organisms, including sponges, corals, and algae in the last decade. A series of interesting results have been obtained concerning the chemistry and chemoecology of the studied marine organisms. The present review focuses on recent development dealing with chemistry, chemoecology, and bioactivity of the South China Sea opisthobranch molluscs and their dietary organisms. Some selected representative examples are described in detail.