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Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O-arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1β production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation. Compared with the clinical drugs hydrocortisone and indomethacin, as well as commercially available CAP agonists GTS-21 and pnu282987, 3k and 3q possessed greater potency against MSU-induced IL-1β production. Meanwhile, these molecules possessed less cytotoxicity against promonocytic THP-1 macrophages when compared with colchicine. This work reports a concise strategy for direct modification of 2-pyridone moiety from natural Lycodine alkaloids, and provides novel frameworks for discovering CAP activators and drugs for gout arthritis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jun-Cheng Su and Ji-Hong Gu reports financial support was provided by National Natural Science Foundation of China. Jun-Cheng Su reports financial support was provided by Guangxi Natural Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sulfur dioxide (SO 2 ) is a significant gas signaling molecule in organisms, and viscosity is a crucial parameter of the cellular microenvironment. They are both involved in regulating many physiological processes in the human body. However, abnormalities in SO 2 and viscosity levels are associated with various diseases, such as cardiovascular disease, lung cancer, respiratory diseases, neurological disorders, diabetes and Alzheimer's disease. Hence, it is essential to explore novel and efficient fluorescent probes for simultaneously monitoring SO 2 and viscosity in organisms., Results: We selected quinolinium salt with good stability, high fluorescence intensity, good solubility and low cytotoxicity as the fluorophore and developed a highly sensitive ratiometric probe QQD to identify SO 2 and viscosity changes based on Förster resonance energy transfer/twisted intramolecular charge transfer (FRET/TICT) mechanism. Excitingly, compared with other probes for SO 2 detection, QQD not only identified HSO 3 - /SO 3 2- with a large Stokes shift (218 nm), low detection limit (1.87 μM), good selectivity, high energy transfer efficiency (92 %) and wide recognition range (1.87-200 μM), but also identified viscosity with a 26-fold fluorescence enhancement and good linearity. Crucially, QQD was applied to detect HSO 3 - /SO 3 2- and viscosity in actual water and food samples. In addition, QQD had low toxicity and good photostability for imaging HSO 3 - /SO 3 2- and viscosity in cells. These results confirmed the feasibility and reliability of QQD for HSO 3 - /SO 3 2- and viscosity imaging and environmental detection., Significance: We reported a unique ratiometric probe QQD for detecting HSO 3 - /SO 3 2- and viscosity based on the quinolinium skeleton. In addition to detecting HSO 3 - /SO 3 2- and viscosity change in actual water and food samples, QQD could also monitor the variations of HSO 3 - /SO 3 2- and viscosity in cells, which provided an experimental basis for further exploration of the role of SO 2 derivatives and viscosity in biological systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.7 macrophage. The results of the anti-inflammatory efficacy and action mechanism of compounds 7l and 8c indicated that they significantly reduced the release of IL-6, IL-1β and TNF-α. Further studies revealed that they can strongly inhibit the activation of NF-κB and MAPK signal pathways. The LPS-induced acute liver injury mice model studies not only confirmed their anti-inflammatory efficacy in vivo but also could effectively relieve the liver injury in mice. The results suggest that compounds 7l and 8c might serve as lead compounds to develop therapeutic drugs for treatment of inflammation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cheng-xue Pan reports financial support was provided by National Natural Science Foundation of China. Jun-Cheng Su reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Receptor-interacting protein kinase 1 (RIPK1) contributes to necroptosis. Our previous study showed that pharmacological or genetic inhibition of RIPK1 protects against ischemic stroke-induced astrocyte injury. In this study, we investigated the molecular mechanisms underlying RIPK1-mediated astrocyte injury in vitro and in vivo. Primary cultured astrocytes were transfected with lentiviruses and then subjected to oxygen and glucose deprivation (OGD). In a rat model of permanent middle cerebral artery occlusion (pMCAO), lentiviruses carrying shRNA targeting RIPK1 or shRNA targeting heat shock protein 70.1B (Hsp70.1B) were injected into the lateral ventricles 5 days before pMCAO was established. We showed that RIPK1 knockdown protected against OGD-induced astrocyte damage, blocked the OGD-mediated increase in lysosomal membrane permeability in astrocytes, and inhibited the pMCAO-induced increase in astrocyte lysosome numbers in the ischemic cerebral cortex; these results suggested that RIPK1 contributed to the lysosomal injury in ischemic astrocytes. We revealed that RIPK1 knockdown upregulated the protein levels of Hsp70.1B and increased the colocalization of Lamp1 and Hsp70.1B in ischemic astrocytes. Hsp70.1B knockdown exacerbated pMCAO-induced brain injury, decreased lysosomal membrane integrity and blocked the protective effects of the RIPK1-specific inhibitor necrostatin-1 on lysosomal membranes. On the other hand, RIPK1 knockdown further exacerbated the pMCAO- or OGD-induced decreases in the levels of Hsp90 and the binding of Hsp90 to heat shock transcription factor-1 (Hsf1) in the cytoplasm, and RIPK1 knockdown promoted the nuclear translocation of Hsf1 in ischemic astrocytes, resulting in increased Hsp70.1B mRNA expression. These results suggest that inhibition of RIPK1 protects ischemic astrocytes by stabilizing lysosomal membranes via the upregulation of lysosomal Hsp70.1B; the mechanism underlying these effects involves decreased Hsp90 protein levels, increased Hsf1 nuclear translocation and increased Hsp70.1B mRNA expression., (© 2023. The Author(s).)

Studies of the Papuan region have provided fundamental insights into the evolutionary processes generating its exceptional biodiversity, but the influence of geological processes merits further study. Lying at the junction of five tectonic plates, this region has experienced a turbulent geological history that has not only produced towering mountains allowing elevational specialization and island archipelagos with varying degrees of isolation promoting vicariance, but also active margins where land masses have collided and been subsequently rifted apart creating a mosaic of intermixed terranes with vastly different geological histories. Asterophryine frogs are a hyperdiverse clade representing half the world's microhylid diversity (over 360 species) centered on New Guinea and its satellite islands. We show that vicariance facilitated by geological history explains this far and wide distribution of a clade that should have poor dispersal abilities. We recovered a mainland tectonic unit, the East Papua Composite Terrane (EPCT), as the center of origin for Asterophryinae and no fewer than 71 instances of what appear to be long-distance dispersal events, 29 of which are between mainland regions, with 42 from the mainland to the islands, some presently as far as 200 km away from source populations over open ocean. Furthermore, we find strong support for a "Slow and Steady" hypothesis for the formation of the northern margin of New Guinea by many separate accretion events during the Miocene, over other major geological alternatives, consistent with the 20 M year age of the clade and arrival via the EPCT. In addition, the historical biogeography of our frogs strongly supports an affiliation of the Louisiade Archipelago and Woodlark Island with the Owen Stanley Range on the EPCT, and the recent proximity of the large New Britain Island. Our results show that Asterophryinae did not have to repeatedly and independently disperse across large ocean barriers to the offshore islands, against the predictions of island biogeography theory, but that the current distribution can be explained through vicariance and short-distance oceanic dispersal as historical land connections disappeared and islands slowly became separated from each other. We show that islands have a life history, changing in distance from other land masses, with consequent opportunities for dispersal, isolation, and cladogenesis of their biotas. More broadly, we can begin to see how the geological history of the Papuan region can result in the rapid accumulation and staggering number of extant species., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

The data provided here are related to the article "Resolving the Deep Phylogeny: Implications for Early Adaptive Radiation, Cryptic, and Present-day Ecological Diversity of Papuan Microhylid Frogs" [1]. The dataset is based on 233 tissue samples of the subfamily Asteroprhyinae, with representatives from all recognized genera, in addition to three outgroup taxa. The sequence dataset contains over 2400 characters per sample for five genes: three nuclear (Seventh in Absentia (SIA), Brain Derived Neurotrophic Factor (BDNF), Sodium Calcium Exchange subunit-1 (NXC-1)), and two mitochondrial loci (Cytochrome oxidase b (CYTB), and NADH dehydrogenase subunit 4 (ND4)); and is 99% complete. New primers were designed for all loci and accession numbers for the raw sequence data are provided. The sequences are used with geological time calibrations to produce time-calibrated Bayesian inference (BI) and Maximum Likelihood (ML) phylogenetic reconstructions using BEAST2 and IQ-TREE. Lifestyle data (arboreal, scansorial, terrestrial, fossorial, semi-aquatic) were collected from the literature and field notes and used to infer ancestral character states for each lineage. Collection location and elevation data were used to verify sites where multiple species or candidate species co-occur. All sequence data, alignments, and associated metadata (voucher specimen number, species identification, type locality status, global positioning system [GPS] coordinates, elevation, site with species list, and lifestyle) as well as the code to produce all analyses and figures are provided., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (© 2023 The Authors.)

The microhylid frogs of the New Guinea region are the largest and most ecologically diverse subfamily (Asterophryinae) of one of the largest anuran families in the world and can live in communities of up to 20 species. While there has been recent progress in resolving the phylogenetic relationships of Asterophryinae, significant uncertainties remain, impeding further progress in understanding the evolution of microhabitat use, parental care, and life history variation in this group. In particular, the early divergences at the base of the tree remain unclear; as does the monophyly of some genera; and recent studies have discovered that species with wide geographic distribution are instead cryptic species complexes. In this study, we fortified geographic sampling of the largest previous phylogenetic effort by sequencing an additional 62 taxa and increased data quality and quantity by adding new layers of data vetting and by filling in previously incomplete loci to the five gene dataset (2 mitochondrial, 3 nuclear protein-coding genes) to obtain a dataset that is now 99% complete in over 2400 characters for 233 samples (205 taxa) of Asterophryinae and 3 outgroup taxa, and analyzed microhabitat use data for these taxa from field data and data collected from the literature. Importantly, our sampling includes complete community complements at 19 sites as well as representatives at over 80 sites across New Guinea and its offshore islands. We present a highly resolved molecular phylogeny which, for the first time, has over 95% of nodes supported (84% highly supported) whether using Maximum Likelihood or Bayesian Inference, allowing clarification of all genera (whether monophyletic or clearly not), their sister genera relationships, as well as an age estimate for the Asterophryinae at approximately 20MYA. Early generic diversification occurring between 17 and 12 MYA gave rise to a surprising diversity of about 18 genera as well as the 5 putative microhabitat types. Our tree reveals extensive cryptic diversity calling any widespread taxa into doubt, and clearly demonstrates that complex multispecies communities of Asterophryinae are ecologically diverse, are numerous, and of ancient origin across New Guinea. We discuss the implications of our phylogeny for explaining the explosive diversification of Asterophryinae as the result of adaptive radiation, niche conservatism, and non-adaptive radiation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To explore the feasibility and accuracy of 0-1 h high sensitivity cardiac troponin I (hs-cTnI) concentration and its changes in judging non-ST segment elevation myocardial infarction (NSTEMI), and to investigate the feasibility of a simplified process. Methods: Patients with acute chest pain and suspected NSTEMI who were admitted to the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were selected. Hs-cTnI test was carried out for the selected patients at the time of visit (0 h) and 1 h after visit. According to the 0-1 h hs-cTnI diagnostic process and threshold standard recommended by European Society of Cardiology (ESC) guidelines in 2015, the laboratory adjudication was determined. Cardiologists who did not participate in the project design and did not know the results of hs-cTnI test performed the clinical judgment according to the routine diagnosis and treatment process of emergency department. Taking clinical judgment as the gold standard, the diagnostic efficacy of 0-1 h hs-cTnI concentration and its change recommended by the guidelines for judging NSTEMI in Chinese population was analyzed. The guide process was simplified. Under the condition of not considering the time of chest pain, the guideline threshold was used for test and judgement, and the diagnostic efficacy of the simplified process was evaluated. Results: A total of 1 534 patients were enrolled in the study, aged (62±12) years and 952 (62.1%) patients were male. Among them, 402 patients (26.2%) were clinically diagnosed as NSTEMI and 1 132 patients (73.8%) were diagnosed as non-NSTEMI. According to the diagnosis and determination process recommended by the guidelines, NSTEMI was excluded in 672 patients (42.8%), and 464 patients (30.2%) were diagnosed as NSTEMI. The consistency rate with clinical determination reached 92.4% (1 050/1 136), the sensitivity of excluding diagnosis was 99.5% (95% CI : 98.0%-99.9%), the negative predictive value was 99.7% (95% CI: 98.8%-99.9%), and the negative likelihood ratio was 0.008 (95% CI : 0.002-0.335). The diagnostic specificity was 92.6% (95% CI : 90.9%-94.0%), the positive predictive value was 81.9% (95% CI: 78.0%-85.2%), and the positive likelihood ratio was 12.739 (95% CI : 10.356-15.670). According to the simplified process, NSTEMI was excluded in 675 patients (44.0%), and 463 patients (30.2%) were diagnosed as NSTEMI. The consistency rate with clinical judgment was 92.4% (1 051/1 138), the sensitivity of exclusion diagnosis was 99.3% (95% CI: 97.6%-99.8%), the negative predictive value was 99.6% (95% CI: 98.6%-99.9%), and the negative likelihood ratio was 0.012 (95% CI: 0.004-0.389). The diagnostic specificity was 92.6% (95% CI: 90.9%-94.0%), the positive predictive value was 81.9% (95% CI: 78.0%-85.2%), and the positive likelihood ratio was 12.705 (95% CI: 10.328-15.630). There was no significant difference in diagnostic efficacy between the simplified process and the recommended process (all P >0.05). Conclusion: The diagnostic process for judging NSTEMI according to the 0-1 h hs-cTnI concentration and its change criteria recommended by the 2015 ESC guidelines is applicable in the Chinese population and remains highly accurate in judging NSTEMI without considering the duration of chest pain at the time of presentation.

Donkey-hide gelatin, also called Ejiao (colla corii asini), is commonly used as a food health supplement and valuable Chinese medicine. Its growing popular demand and short supply make it a target for fraud, and many other animal gelatins can be found as adulterants. Authentication remains a quality concern. Peptide markers were developed by searching the protein database. However, donkeys and horses share the same database, and there is no specific marker for donkeys. Here, solutions are sought following a database-independent strategy. The peptide profiles of authentic samples of different animal gelatins were compared using LC-QTOF-MS/MS. Fourteen specific markers, including four donkey-specific, one horse-specific, three cattle-specific, and six pig-specific peptides, were successfully found. As these donkey-specific peptides are not included in the current proteomics database, their sequences were determined by de novo sequencing. A quantitative LC-QQQ multiple reaction monitoring (MRM) method was further developed to achieve highly sensitive and selective analysis. The specificity and applicability of these markers were confirmed by testing multiple authentic samples and 110 batches of commercial Ejiao products, 57 of which were found to be unqualified. These results suggest that these markers are specific and accurate for authentication purposes.

Objective: To systematically evaluate the efficacy of drug coated balloon (DCB) versus conventional balloon in the treatment of coronary de novo bifurcation lesions. Methods: The databases of PubMed, Embase, Cochrane Library, Web of science, CNKI (China National Knowledge Infrastructure), Wanfang database, VIP, China Biology Medicine disc, Chinese clinical trial registry, American clinical trial registry and cardiovascular related websites until September 2020 were retrieved for collecting the randomized controlled trials (RCT) comparing DCB versus conventional balloon in the treatment of coronary de novo bifurcation lesions. The risk of bias of included studies was assessed using the Cochrane risk assessment tool. The meta-analysis was performed by using Revman 5.3 and Stata 14.0 software. Results: Seven RCTs with a total of 613 patients were included in this meta-analysis. Among the included studies, 4 articles reached the low risk of bias, and the other 3 articles reached the medium risk of bias. The results of meta-analysis showed that there was no significant difference in the major adverse cardiac events ( RR =0.65, 95% CI 0.39-1.08, P =0.10), myocardial infarction ( RR =0.68, 95% CI 0.25-1.80, P =0.43), target lesion revascularization ( RR =0.94, 95% CI 0.53-1.67, P =0.83) between DCB group and conventional balloon group. Late lumen loss of side branch was less in the DCB group than that in the conventional balloon group ( WMD =-0.25, 95% CI -0.41--0.09, P <0.01) and the risk of side branch restenosis was also lower in the DCB group than that in the conventional balloon group ( RR =0.47, 95% CI 0.22-0.98, P <0.05). However, subgroup analysis showed that the conclusions of domestic studies and foreign studies on late lumen loss and side branch restenosis were inconsistent. The meta-analysis based on domestic literature showed that the risk of side branch restenosis after DCB treatment was lower compared with conventional balloon group ( RR =0.29, 95% CI 0.15-0.57, P <0.05), while this parameter derived from foreign literatures remained unchanged between two groups ( P =0.53). The meta-analysis results of domestic literature showed that late lumen loss in DCB group was less than that in conventional balloon group ( WMD =-0.32, 95% CI -0.51--0.13, P <0.05), but this phenomenon was not observed in foreign literatures ( P =0.30). Conclusions: The use of DCB in the treatment of coronary de novo bifurcation lesions has the potential to reduce the rate of restenosis and late lumen loss of side branch compared with conventional balloon group. However, due to the limitation on quantity, quality and results of published studies, more high-quality and large scale RCTs are still needed to confirm these findings.

Myxobacteria are a prolific source of structurally diverse natural products, and one of the best-studied myxobacterial products is the siderophore myxochelin. Herein, we report two new compounds, myxochelins N ( 1 ) and O ( 2 ), that are nicotinic paralogs of myxochelin A, from the terrestrial myxobacterium Archangium sp. SDU34; 2 is functionalized with a rare 2-oxazolidinone. A precursor-feeding experiment implied that the biosynthesis of 1 or 2 was due to altered substrate specificity of the loading module of MxcE, which likely accepts nicotinic acid and benzoic acid instead of more conventional 2,3-dihydroxybenzoic acid. We also employed a phylogenomic approach to map the evolutionary relationships of the myxochelin biosynthetic gene clusters (BGCs) in all the available myxobacterial genomes, to pave the way for the future discovery of potentially hidden myxochelin derivatives. Although the biological function of 1 and 2 is unclear yet, this work underpins that even extensively studied BGCs in myxobacteria can still produce new chemistry.

Introduction/background: The purpose of this study was to compare the grip strength values obtained under 4 postures, and to identify the position providing the maximum grip strength value. We also explored the effects of different body positions on grip strength measurements and the significance of the selection of measurement position for guiding the screening and diagnosis of sarcopenia., Methodology: A total of 764 people (409 males and 355 females) participated in this study. Grip strength was measured in 4 positions: (1) standing with the elbow fully extended; (2) standing with arms raised; (3) sitting with the elbow flexed 90°; and (4) sitting with the elbow extended. Multiple linear regression model was used to compare the grip strength measurements obtained from these 4 positions by each hand when considering the influence of age, gender, body mass index, and other factors., Results: Both male and female grip strength values in the standing position with the elbow fully extended were significantly greater than those in other positions. In addition, the grip strength measured by standing posture was generally greater than measured by sitting posture. In contrast, grip strength values in the 2 sitting positions did not differ significantly. The grip strength of men was generally greater than that of women., Conclusions: The findings reveal that grip strength measured while standing with the elbow fully extended is greater than that measured while sitting, which is the posture currently recommended in clinical practice. Clinicians and researchers should choose the appropriate and optimal postures to measure grip strength., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between rs1053005 of signal conversion and transcription activator 3 (STAT3) and miR-452-3p, and the association between STAT3 gene polymorphism and noise-induced hearing loss (NIHL) . Methods: In December 2017, 1220 workers were selected from an automobile manufacturing factory, an energy company and a chemical fiber factory in Jiangsu Province who had occupational noise exposure and working age of more than 3 years. The workers with the mean hearing threshold of ≥26 dB (A) of the two ear high frequency (3000, 4000 and 6000 Hz) were defined as case group ( n =609) , and the rest were control group ( n =611) . Five single nucleotide polymorphism (SNP) sites of STAT3 (rs4796793, rs1053023, rs1053005, rs1053004 and rs3744483) were selected to explore the association between STAT3 gene polymorphism and NIHL by analyzing the points. The double luciferase reporter gene verified whether miR-452-3p was targeted to bind STAT3, and overexpressed miR-452-3p in HEI-OC1 cells to explore the mechanism of STAT3 expression regulation. Results: There was no significant difference in gender, age, smoking and drinking between the two groups ( P >0.05) . Compared with the control group[ (15.58±4.76) dB], the mean hearing threshold of the case group [ (37.50±12.39) dB] was higher, and the difference were statistically significant ( P <0.05) . Compared with the control group, the C alleles of rs1053023 and rs1053005 were higher in the case group ( OR =1.367, 1.370, P <0.05) . The risk of NIHL in men with TC/CC genotype were 1.545 and 1.531 times higher than that in men with TT genotype ( P <0.05) . Compared with the control group, the mRNA expression of STAT3 in the case group was significantly increased ( P <0.05) . The STAT3 mRNA expression of miR-452-3p group cells was significantly decreased ( P <0.05) . Conclusion: The rs1053023 and rs1053005 polymorphism of STAT3 are related to NIHL. The C alleles of rs1053023 and rs1053005 may be biomarkers of workers exposed to noise.

The fresh leaves of Metapanax delavayi (Araliaceae) have been used as a common wild vegetable for salad and soup, and also herbal tea by the local people living in its growing areas of Yunnan province, China. Detailed chemical investigation led to the identification of a new triterpenoid saponin, 3- O - α -L-arabinopyranosyl-28- O - β -D-glucopyranosyl-(1→6)- O - β -D-glucopyranosyl-3 β -hydroxyolean-12-ene-28,29-dioic acid ( 1 ) from the fresh leaves, together with 11 known compounds, including six triterpenoid saponins ( 2 - 7 ), two caffeoylquinic acid derivatives ( 8 - 9 ), and three flavonoid glycosides ( 10 - 12 ). Their structures were determined on the basis of spectroscopic analysis and acidic hydrolysis. Compounds 3 - 5 and 8 - 12 were isolated from M. delavayi for the first time. Moreover, the known saponins 3- O - β -D-xylopyranosyl-3 β -hydroxyolean-12-ene-28,29-dioic acid ( 3 ) and yiyeliangwanoside IV ( 5 ) exhibited protective effects on HepG2 cells damaged by the alcohol intakes, at a concentration of 1.0 µg/mL. The results indicated M. delavayi is an ideal dietary vegetable and herbal tea with potential hepatoprotective activity.[Formula: see text].

Objective: To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis. Methods: In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes. Results: Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P< 0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P< 0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P< 0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P< 0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P< 0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality ( HR (95 %CI ):4.739(2.272-9.885), P< 0.01), cardiovascular mortality ( HR (95 %CI ):7.258(2.237-23.548), P= 0.001) and MACCE ( OR (95 %CI ):4.143(2.031-8.453), P< 0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality ( HR (95 %CI ): 6.387(2.533-16.104), P< 0.01), cardiovascular mortality ( HR (95 %CI ): 10.848(2.586-45.506), P= 0.001) and MACCE ( OR (95 %CI ): 4.081(1.299-12.816), P= 0.016), while not for re-hospitalization for HF ( OR (95 %CI ):1.010(0.700-1.457), P= 0.957). Conclusions: Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.

Objective To investigate the relationships of blood pressure circadian rhythm and brain natriuretic peptide (BNP) with left ventricular hypertrophy (LVH) in patients with primary hypertension. Methods Totally 349 patients (74 with LVH and 275 without LVH) with primary hypertension were enrolled in this study.Echocardiography was performed to determine left ventricular mass index (LVMI) using the Devereux formula. The nocturnal blood pressure decline rate,24-hour blood pressure (24 h PP; especially 24 h mean systolic blood pressure,24 h SBP) and blood pressure index (PPI) were determined by 24 h-ambulatory blood pressure monitoring. These 349 hypertensive patients were divided into four groups including supper-dipper group (defined as≥;20%, n=7),dipper group (defined as 10%- 20%, n=77),non-dipper group (defined as 0- 10%, n=173),and anti-dipper group (defined as<0, n=92). The baseline demographic characteristics of patients were collected. Fasting blood sugar,blood lipids,blood urea nitrogen,serum cretinine,cystatin C,uric acid,and plasma BNP level were measured. Results The patients with LVH (n=74) had significantly higher percentage of grade 3 hypertension (85.1% vs. 46.9%;χ 2 =34.428,P<0.001),24 h SBP (134 mmHg vs. 129 mmHg; t=3.175,P=0.002)(1 mmHg=0.133 kPa),daytime-mean SBP (134 mmHg vs. 130 mmHg; t=2.197,P=0.029),night-mean SBP(132 mmHg vs. 121 mmHg; t=4.763,P<0.001),and 24 h PP(57 mmHg vs. 52 mmHg; t=4.120,P<0.001) and PPI (0.43 vs. 0.41; t=3.335,P=0.001) and lower nocturnal blood pressure decline rate [(1.30±8.02)% vs. (5.68±7.25)%; t=-4.510,P<0.001] than the non-LVH patients (n=275). The LVH hypertensive group had significantly higher BNP level (87.8 pg/ml vs. 28.8 pg/ml; t=2.170,P=0.034) and LVMI (135.1 g/m 2 vs. 88.7 g/m 2 ; t=15.285,P<0.001) than the control group. No significant difference was observed in the BNP level among supper-dipper,dipper,non-dipper and anti-dipper groups (P=0.137).However,the difference was statistically significant in the LVMI (P=0.001). Additionally,patients in the anti-dipper group had significantly higher LVMI than those in the dipper patients (100.3 g/m 2 vs. 86.3 g/m 2 ; t=4.335,P<0.001) and non-dipper (100.3 g/m 2 vs.93.7 g/m 2 ; t=1.987,P=0.048). Patients in the non-dipper group had significantly higher LVMI than those in the dipper group (93.7 g/m 2 vs. 86.3 g/m 2 ; t=2.693,P=0.008). The multivariate linear correation analysis and logistic regressions analysis suggested a significant correlation of LVMI with BNP and the grade of hypertension. Conclusion With the increasing of plasma BNP level,the left ventricular hypertrophy is closely related to abnormal blood pressure circadian rhythm and the grade of hypertension in primary hypertensive patients.

The adhesion of monocytes to endothelial cells is one of the early stages in the development of atherosclerosis. The expression of type IV collagenases, which include matrix metalloproteinase (MMP)-2 and MMP-9, in monocytes is hypothesized to play an important role in monocyte infiltration and transformation into foam cells. The aim of the present study was to examine the effects of monocyte-endothelium interactions on the expression levels of type IV collagenases and their specific inhibitors in monocytes, and to investigate the roles of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in this process. Monocytes were single-cultured or co-cultured with endothelial cells. The expression of the type IV collagenases, MMP-2 and MMP-9, and their specific inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, in monocytes was determined by immunohistochemistry followed by image analysis. The expression levels of MMP-2 and MMP-9 were found to be low in the single-culture monocytes, but increased significantly when the monocytes and endothelial cells were co-cultured. However, treatment with monoclonal TNF-α or IL-1β antibodies partially inhibited the upregulated expression of MMP-2 and MMP-9 in the co-cultured monocytes. Expression of TIMP-1 and TIMP-2 was observed in the single monocyte culture, and a small increase in the expression levels was observed when the monocytes were co-cultured with endothelial cells. Therefore, monocyte-endothlium interactions were shown to increase the expression of type IV collagenases in monocytes, resulting in the loss of balance between MMP-2 and -9 with TIMP-1 and -2. In addition, TNF-α and IL-1β were demonstrated to play important roles in this process.

Objective: To generate systemic expression human cellular glutathione peroxidase-1 (GPx-1) (198Leu) transgenic mice model in order to investigate the functional variants in GPx-1 gene in oxidative stress-related diseases., Methods: After linearization with BamnH I and Acc I, the transgenic construct GPx-1 (198Leu) was microinjected into the zygotes of C57BL/6J mice to generate transgenic mice, whose genotype was detected by PCR with specific primers. The GPx-1 gene expression profile was determined by Western blotting., Results: 13 transgenic founder mice were successfully generated. Western blotting result showed that the protein expression level of 4 transgenic mice in hearts were higher than that of wild type mice., Conclusion: Human GPx-1PSL transgenic mice was successfully established. This kind of animal model is of significance for making further researches on oxidative stress-related diseases.

Background: Viral myocardial disease (VMD) is a common disease inducing heart failure. It has not been clear the roles of mitochondrial damage in the pathological changes of cardiomyocytes in VMD., Methods: Myocardial tissues and lymphocytes were collected from 83 VMD patients. Control groups included 12 cases of healthy accidental death with myocardial autopsy and 23 healthy blood donors. The mouse model of viral myocarditis (VMC) was established by Coxsackie virus B3 infection and myocardial tissues and skeletal muscle were collected. Mitochondrial DNA (mtDNA) deletion rate was quantitatively determined using polymerase chain reaction., Results: There was significantly difference of myocardial mitochondrial DNA deletion rate between VMD or VMC group and control group (P<0.05). Moreover, the loss of mitochondrial membrane phospholipids was significantly different between VMD or VMC group and control group. In VMC mice, there were negative correlations between myocardial mtDNA3867 deletion rate and left ventricular peak systolic pressure (LVPSP) (r = -0.66, P<0.05), and between myocardial mtDNA3867 deletion rate and +dp/dtmax (r = -0.79, P<0.05), while there was positive correlation between myocardial mtDNA3867 deletion rate and -dp/dtmax (r = 0.80, P<0.05)., Conclusion: Mitochondrial damage is an important pathophysiological mechanism leading to myocardial injury and cardiac dysfunction. The mitochondrial damage in the skeletal muscle and lymphocytes reflect a "window" of myocardial mitochondrial damage.