Author Correction: Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Spinal NGF induces anti-intrathecal opioid-initiated cardioprotective effect via regulation of TRPV1 expression.

Evidences from previous studies confirmed that intrathecal morphine preconditioning (ITMP) reduces the cardiac injury of ischemia-reperfusion (IR) via the central nervous system. However, the molecular mechanism is not fully understood. The breath of central nerve growth factor (NGF) during nociceptive transmission has been well documented, and little is known about the significance of NGF in myocardial injury of IR and intrathecal morphine-induced cardioprotection. To address these questions, we over-expressed or silenced NGF in the spinal cord by using intrathecal injection of lentivirus-NGF or shRNA respectively, accompanied by ITMP in the IR rat model. The levels of NGF and tropomyosin receptor kinase A (Trka) as well as transient receptor potential vanilloid 1 (TRPV1) in the T2-6 spinal cord were evaluated. The results showed that cardiac damage indicators induced by IR, including the increased infarct size, arrhythmia score and serum troponin levels were attenuated after ITMP. However, overexpression of spinal NGF significantly reversed these decreases, as well as reduced the expression and phosphorylation of TRPV1 that was elicited by ITMP. Conversely, silencing of spinal NGF enhanced ITMP-induced cardioprotective effects. Phosphorylation and expression of TRPV1 in the spinal cord were significantly decreased after regional NGF silencing. These findings suggested that the cardioprotective effects of ITMP may implement by mediating through spinal NGF expression, wherein it involves the nociceptor TRPV1. NGF may act as a potential therapeutic target in the development of new agents for the treatment of cardiac injury induced by IR.

miR­133b­5p contributes to hypoxic preconditioning­mediated cardioprotection by inhibiting the activation of caspase­8 and caspase-3 in cardiomyocytes.

In a previous study using a microRNA (miRNA/miR) microarray assay, we demonstrated that miR-133b-5p was upregulated in response to hypoxic preconditioning (HPC). The present study was designed to investigate the role of the miR­133b­5p in HPC­induced cardioprotection and the underlying mechanisms involving caspase­8 and caspase­3 apoptotic signaling. Adult rats were subjected to myocardial ischemia/reperfusion (I/R) injury with or without ischemic preconditioning (IPC), and the level of miR­133b­5p in myocardium was measured. Neonatal rat cardiomyocytes were isolated and subjected to hypoxia/reoxygenation (H/R) injury, with or without HPC. miR­133b­5p antagomir was transfected into the cardiomyocytes to observe whether it could block HPC­induced cardioprotection. Cellular injury was evaluated by detecting cell viability, lactate dehydrogenase (LDH) activity and apoptotic rate. Reverse transcription­quantitative polymerase chain reaction was used to measure the level of miR­133b­5p. The activation of caspase­8 and caspase­3 were measured by western blot analysis to detect the cleaved fragments as well as a colorimetric assay. Following myocardial I/R injury, the expression of miR­133b­5p was decreased in myocardium, while this decrease was restored by IPC. HPC protected neonatal rat cardiomyocytes against H/R injury by increasing cell viability, while reducing LDH release and cell apoptosis. These protective effects were coupled with the upregulation of miR­133b­5p. However, the knockdown of miR­133b­5p in the cardiomyocytes blocked HPC­mediated cardioprotection as reflected by the aggravation of cell injury and apoptosis. HPC upregulated miR­133b­5p level was markedly suppressed by the antagomir. In addition, the cleavage and activities of caspase­8 and caspase­3 were inhibited by HPC while reversed by knockdown of miR­133b­5p. Upregulation of miR­133b­5p contributes to HPC­mediated cardioprotection in cardiomyocytes, and the mechanism may be associated with inhibition of caspase­8 and caspase­3 apoptotic signaling.

Remifentanil preconditioning confers cardioprotection via c-Jun NH2-terminal kinases and extracellular signal regulated kinases pathways in ex-vivo failing rat heart.

Remifentanil preconditioning (RPC) exerts protection in normal hearts, but has not been investigated in heart failure. The aim of the present study was to evaluate the effect of RPC in a chronic failing rat heart model and the mechanisms involving mitogen-activated protein kinases (MAPK) and Bcl-2 protein family. The doxorubicin induced failing rat hearts were subjected to 30 min ischemia / 120 min reperfusion (IR) with or without RPC by using Langendorff apparatus. RPC was induced by three cycles of 5 min remifentanil / 5 min drug-free perfusion before IR, with three different concentrations: 25, 50 and 100 µg/l. An extracellular signal regulated kinases (ERK) inhibitor PD98059, p38MAPK inhibitor SB203580, c-Jun NH2-terminal kinases (JNK) inhibitor SP600125 were perfused at 10 min before RPC. Infarct size, cardiac function and protein kinase activity were determined. RPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by IR injury in failing heart. The JNK inhibitor SP600125 and ERK inhibitor PD98059 abolished the RPC mediated reduction effect on the infarct size and LDH activity after reperfusion. In addition, RPC increased the phosphorylation of JNK, ERK1/2 and the downstream GSK-3ß, as well as the Bcl-2/Bax ratio, while, these changes were completely reversed by SP600125 and PD98059. And of note, SB203580 had no effect. In conclusion, our results suggested that the activation of JNK and ERK pathways, by leading to inhibition of GSK-3ß and regulating Bcl-2 protein family, is a major mechanism that RPC confers cardioprotection in failing rat heart.

Effects of differential-phase remote ischemic preconditioning intervention in laparoscopic partial nephrectomy: A single blinded, randomized controlled trial in a parallel group design.

STUDY OBJECTIVE: There are two windows of protection for remote ischemic preconditioning (RIPC), an early (ERIPC) and a late-phase (LRIPC). While ERIPC has been well studied, works on LRIPC are relatively scarce, especially for the kidneys. We aimed to compare the effects of early-phase versus late-phase RIPC in patients with laparoscopic partial nephrectomy (LPN). DESIGN: A randomized controlled study SETTING: The Second Affiliated Hospital of Anhui Medical University, 1 May 2012 to 30 October 2013 PATIENTS: Sixty-five ASA 1 to 2 patients scheduled for LPN were located randomly to ERIPC group, LRIPC group and CON group (control). INTERVENTIONS: Three five-minute cycles of right upper limb ischaemia and reperfusion were performed after induction of anesthesia in ERIPC group. Patients in LRIPC group received similar treatment 24h before surgery, while control patients were not subjected to preconditioning. MEASUREMENTS: Serum neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) were evaluated before the induction of anesthesia (0h), 2h (2h) and 6h (6h) after surgery. Unilateral glomerular filtration rates (GFR) were assessed before and after surgery to evaluate overall renal function. MAIN RESULTS: Serum NGAL and CysC were significantly lower in ERIPC and LRIPC groups at 2h post-operation (P<0.001), 6h post-operation (P<0.001). Additionally, The GFR were significantly lower in ERIPC and LRIPC groups than in CON group at the 3rd month after surgery (P=0.019; P<0.001). Moreover, compared to the ERIPC group, concentration of NGAL and CysC in LRIPC group decreased to a greater extent, while GFR and the percentage of decrement was significantly less in the LRIPC group (P=0.016; P<0.001). CONCLUSIONS: Regardless of early-phase or late-phase intervention, limb remote ischemic preconditioning confers protection on renal ischemia-reperfusion injury in patients with laparoscopic partial nephrectomy, and the late-phase protection is more prominent.

Specific MicroRNAs comparisons in hypoxia and morphine preconditioning against hypoxia-reoxgenation injury with and without heart failure.

AIMS: Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. The present study aims to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes. MAIN METHODS: Chronic heart failure was established by injecting doxorubicin (2mg/kg/week) for 6weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart. Cellular injury was evaluated by detecting LDH release levels, cell variability and apoptotic rate. Dysregulated miRNAs in control, hypoxia preconditioning (HPC) and morphine preconditioning (MPC) groups under two conditions were quantified by microarray analysis. Fas protein expression was analyzed using Western Blotting analysis. KEY FINDINGS: Chronic heart failure was confirmed with lower ejection fraction (EF), and significant cellular injury. HPC could reverse the injury induced by H/R in normal heart rather than failed heart, otherwise, MPC significantly attenuated cellular injury dose dependently in both conditions. There was 12 miRNAs significantly altered after doxorubicin injection, 7 downregulated and 5 upregulated. miR-133b-5p, miR-6216, miR-664-1-5p and let7e-5p were differentially expressed after HPC and MPC treatments. The direct interaction between miR-133b-5p and target gene Fas were established. The Fas protein expression was manipulated by MPC not HPC affording protective effect against H/R injury. SIGNIFICANCE: We investigated that miR-133b-5p might play a particularly important role in the cardioprotective effect of MPC by regulating the target gene Fas.

Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells.

Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40-50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 µmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50 values (0.76 and 1.44 µmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects.

Remifentanil preconditioning protects rat cardiomyocytes against hypoxia-reoxygenation injury via δ-opioid receptor mediated activation of PI3K/Akt and ERK pathways.

Remifentanil preconditioning has been demonstrated to reduce myocardial ischemia reperfusion injury in rat hearts, while the mechanisms are not fully understood. This study investigated the protective effects of remifentanil against hypoxia-reoxygenation injury in adult rat cardiomyocytes and the mechanisms involving opioid receptors and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathways. Adult rat cardiomyocytes were pretreated with remifentanil at different concentrations and then subjected to 90min hypoxia followed by 120min reoxygenation. The δ- (naltrindole), κ- (nor-binaltorphimine), or µ-opioid receptor antagonist (CTOP), as well as ERK inhibitor (PD98059) or PI3K inhibitor (wortmannin) was added before remifentanil preconditioning, respectively. Remifentanil showed significant protective effects against hypoxia-reoxygenation injury by increasing cell survival (Trypan blue staining) while reducing LDH activity and cell apoptosis (Hoechst staining). These effects were markedly reversed by naltrindole and were partially blocked by nor-binaltorphimine. Pretreatment of either PD98059 or wortmannin also abolished the protective effects of remifentanil. Following remifentanil preconditioning, the phosphorylation level of Akt reached peak at 10min of reoxygenation. ERK phosphorylation, however, was subsequently enhanced at 120min of reoxygenation. The phosphorylation levels of Akt and ERK were both blocked by naltrindole, but not nor-binaltorphimine or CTOP. Wortmannin inhibited the phosphorylation of both Akt and ERK, whereas PD98059 suppressed the phosphorylation of ERK only. In conclusion, our results suggested that remifentanil protected adult rat cardiomyocytes from hypoxia-reoxygenation injury and its effects appears to be dependent on the δ-opioid receptor mediated activation of PI3K/Akt and subsequent ERK signaling pathways.

Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique.

BACKGROUND: Epidural anesthesia may attenuate the sympathetic hyperactivity and stress response from surgery. In this study, we compared the stress response, hemodynamic variables, and recovery profiles of patients undergoing total IV anesthesia (TIVA) and intraoperative dexmedetomidine with those receiving epidural anesthesia and TIVA. METHODS: Ninety patients undergoing elective open gastrectomy under TIVA were recruited. The dexmedetomidine group (group D, n = 30) received IV dexmedetomidine 0.6 µg/kg before the induction of general anesthesia, followed by dexmedetomidine 0.4 µg/kg/h until peritoneal closure. The control group (group C, n = 30) received volume-matched normal saline infusion as placebo. The epidural group (group E, n = 30) received epidural anesthesia with 0.375% ropivacaine combined with TIVA. The hemodynamic variables and recovery characteristics during emergence were evaluated. Blood samples for norepinephrine (NE), epinephrine (E), cortisol (Cor), and cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-10) were obtained before the administration of dexmedetomidine or epidural anesthesia (baseline), immediately after tracheal intubation, upon incision, at the time of celiac exploration, and at tracheal extubation. RESULTS: Compared with group E, there were no differences in the plasma concentration levels of NE, E, Cor, and cytokines (TNF-α, IL-6, and IL-10) in group D at all time points. The levels of NE and E in groups D and E were significantly lower than that in group C, at all time points following induction (all P < 0.0001 except at incision which were P = 0.001 and P = 0.004), and the level of Cor in groups D and E was significantly lower than that in group C at celiac exploration (P = 0.017 and P = 0.019) and immediately after tracheal extubation (P < 0.0001). The levels of TNF-α, IL-6, and IL-10 increased after the celiac exploration in the 3 groups. The levels of plasma TNF-α, IL-6, and IL-6/IL-10 ratio were higher in group C than in groups D and E at celiac exploration and tracheal extubation (all P < 0.0001 except at celiac exploration which were P = 0.005 and P =0.038 for TNF-α and P = 0.049 and P = 0.038 for IL-6/IL-10 ratio). In group D, the heart rate was significantly slower after commencing dexmedetomidine and remained significantly slower throughout the operative course (all P < 0.0001 except at tracheal extubation which was P = 0.032). The number of patients who required intervention because of intraoperative hypotension was significantly higher in group E (36.7%) compared with groups D and C (13.3% and 10.0%) (P = 0.037, P = 0.015). The times to eye opening and tracheal extubation were similar in all groups. There were fewer incidences of agitation in group D (6.7 %) than in group C (26.6%) (P = 0.038). CONCLUSIONS: When used in conjunction with TIVA, intraoperative dexmedetomidine blunts surgical stress responses to an extent comparable to combined epidural and general anesthesia without compromising hemodynamic stability and with minimal adverse effects during the intraoperative period.

MicroRNA-133b-5p Is Involved in Cardioprotection of Morphine Preconditioning in Rat Cardiomyocytes by Targeting Fas.

BACKGROUND: MicroRNAs (miRNAs) have been implicated in ischemia-reperfusion injury and ischemic preconditioning. Opioid pre- and postconditioning have powerful protective effects on the heart, but it is still not known whether miRNAs are involved in opioid-induced cardioprotection. The present study was designed to investigate the role of miRNAs in morphine preconditioning (MPC)-induced cardioprotection. METHODS: MiRNA microarray analysis was performed to examine the differentially expressed miRNAs caused by MPC in adult rat cardiomyocytes. A dual-luciferase reporter assay was performed to confirm the direct regulation of miR-133b-5p on the target gene Fas. MiR-133b-5p mimic or inhibitor was separately transfected into myocardial H9c2 cells to examine the role of miR-133b-5p in morphine-induced cardioprotection. RESULTS: MPC protected adult rat cardiomyocytes against hypoxia/reoxygenation (H/R) injury by reducing cell injury and death. MiRNA microarray data showed that a total of 39 miRNAs were differentially expressed after MPC treatment. A Dual-luciferase reporter assay confirmed that miR-133b-5p directly targets the Fas gene. After H/R injury, the decrease in miR-133b-5p and a contemporaneous rise in Fas mRNA and protein levels in adult rat cardiomyocytes were prevented by MPC treatment. In H9c2 cardiomyocytes, overexpression of miR-133b-5p reduced H/R-induced cell injury and apoptosis by inhibiting Fas expression. Knockdown of miR-133b-5p blocked morphine-mediated cardioprotection by reducing miR-133b-5p levels while enhancing the expression of Fas mRNA and protein. CONCLUSIONS: MPC causes a change in miRNA expression in rat cardiomyocytes. Morphine may protect cardiomyocytes against H/R injury through upregulation of miR-133b-5p by targeting Fas.

Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3ß pathway independent of PI3K/Akt.

Preconditioning against myocardial ischemia-reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3ß pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct size and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3ß. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3ß induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3ß in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3ß pathway independent of PI3K/Akt.

[Therapeutic efficacy of pegylated polymyxin E in the treatment of infection induced by gramnegative bacteria and the effect of reducing nephrotoxicity].

Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.

Two insulin receptors determine alternative wing morphs in planthoppers.

Wing polyphenism is an evolutionarily successful feature found in a wide range of insects. Long-winged morphs can fly, which allows them to escape adverse habitats and track changing resources, whereas short-winged morphs are flightless, but usually possess higher fecundity than the winged morphs. Studies on aphids, crickets and planthoppers have revealed that alternative wing morphs develop in response to various environmental cues, and that the response to these cues may be mediated by developmental hormones, although research in this area has yielded equivocal and conflicting results about exactly which hormones are involved. As it stands, the molecular mechanism underlying wing morph determination in insects has remained elusive. Here we show that two insulin receptors in the migratory brown planthopper Nilaparvata lugens, InR1 and InR2, have opposing roles in controlling long wing versus short wing development by regulating the activity of the forkhead transcription factor Foxo. InR1, acting via the phosphatidylinositol-3-OH kinase (PI(3)K)-protein kinase B (Akt) signalling cascade, leads to the long-winged morph if active and the short-winged morph if inactive. InR2, by contrast, functions as a negative regulator of the InR1-PI(3)K-Akt pathway: suppression of InR2 results in development of the long-winged morph. The brain-secreted ligand Ilp3 triggers development of long-winged morphs. Our findings provide the first evidence of a molecular basis for the regulation of wing polyphenism in insects, and they are also the first demonstration--to our knowledge--of binary control over alternative developmental outcomes, and thus deepen our understanding of the development and evolution of phenotypic plasticity.

Changes in smoking behavior and subsequent mortality risk during a 35-year follow-up of a cohort in Xi'an, China.

Prospective evidence of the associations of smoking cessation with chronic obstructive pulmonary disease (COPD) and other causes of death in Asia is scarce. Previous studies, which were mostly based on baseline smoking behavior only, were subject to sick-quitter bias and misclassification resulting from changes in smoking behavior during follow-up. We followed up a cohort for 18 years (1976-1994) to assess changes in smoking behavior and then for an additional 17 years (1994-2011) to examine the relationships of continuing to smoke and new quitting with mortality risk in 1,494 Chinese people (961 men, 533 women). Of the baseline current smokers, 38.7% quit between 1976 and 1994. From 1994 to 2011, a total of 488 persons (359 men, 129 women) died. Ever smokers had increased risks of lung cancer, coronary heart disease, thrombotic stroke, and COPD, with dose-response relationships. For all tobacco-related mortality, the relative risk for new quitters compared with continuing smokers was 0.68 (95% confidence interval: 0.46, 0.99) for those who had quit 2-7 years previously and 0.56 (95% confidence interval: 0.37, 0.85) for those who had quit 8 years or more previously. The corresponding relative risks were 0.69 and 0.45 for lung cancer, 0.78 and 0.51 for coronary heart disease, 0.76 and 0.84 for thrombotic stroke, and 0.89 and 0.61 for COPD, respectively. Smoking increased tobacco-related deaths, and particularly deaths from COPD, in China, whereas quitting at middle age (at approximately 50 years of age) substantially reduced the risks of death from these causes. The benefits of smoking cessation were underestimated in previous studies that did not use repeated measures.

Secondhand smoke exposure predicted COPD and other tobacco-related mortality in a 17-year cohort study in China.

BACKGROUND: Prospective evidence on the association between secondhand smoke (SHS) and COPD and ischemic stroke is scarce. METHODS: We prospectively examined the relationship between SHS and major tobacco-related deaths, particularly COPD and stroke, in 910 Chinese (439 men, 471 women) who never smoked from a 17-year follow-up study in Xi'an, China. SHS exposure was defi ned as exposure to another person's tobacco smoke at home or in the workplace. RESULTS: At baseline among the 910 subjects, 44.2% were exposed to SHS at home, 52.9% in the workplace, and 67.1% at home, work, or both. From March 1, 1994, to July 1, 2011, 249 (150 men,99 women) died within 14,016 person-years. Those who were exposed to SHS had increased mortality due to coronary heart disease (adjusted relative risk [RR], 2.15; 95% CI, 1.00-4.61), ischemic stroke (RR, 2.88; 95% CI, 1.10-7.55), lung cancer (RR, 2.00; 95% CI, 0.62-6.40), COPD (RR, 2.30;95% CI, 1.06-5.00), and all causes (RR, 1.72; 95% CI, 1.29-2.20), with significant dose-response relationships between cumulative SHS exposure at home and work and the increased risk of cause-specific and total mortality (P for linear trend ranged from .045 to , .001). CONCLUSIONS: This study shows dose-response relationships between SHS and major tobacco-related mortality and provides new evidence to support causation for COPD and ischemic stroke.

In situ ligand and complex transformation of an iron(III) Schiff base complex: structural evidence and theoretical calculations.

A C-C coupling reaction has been achieved at room temperature by in situ ligand transformation. The iron(III) complexes before and after the in situ transformation, [FeNaL(1)(2)(H(2)O)(4)](2)·2H(2)O (1) (H(2)L(1) = (Z)-2-(2-hydroxyl)benzylideneamino) and [FeL(2)](2)·7.5H(2)O (2) (H(3)L(2) = (E)-2-(2-hydroxyl-benzylideneamino)-3-hydroxyl-3-(2-hydroxyphenyl), have been studied by elemental analyses, FT-IR, UV-vis, TGA and X-ray single crystal diffraction analysis. The proposed mechanism of this in situ transformation has been determined based on structural evidence and theoretical calculations using the density functional theory (DFT) M06 method.

Triglyceride and coronary heart disease mortality in a 24-year follow-up study in Xi'an, China.

PURPOSE: To study whether serum triglyceride (TG) was associated with coronary heart disease (CHD) mortality. METHODS: A cohort analytic study carried out in a machinery factory in Xi'an, China on 1696 subjects aged 35 years or above (1124 men and 572 women) examined in 1976 and followed up till 2000. RESULTS: At baseline, the mean serum total cholesterol (TC) and triglyceride (TG) was 4.64 and 1.16 mmol/L in men, 4.62 and 1.10 mmol/L in women, respectively. Three hundred six (239 men, 67 women) had died within 37,781 person-years of follow-up, with 49 CHD deaths (36 male, 13 female). The relative risk (95% confidence interval) of CHD mortality per mmol/L increase in TG was 2.13 (1.46-3.17) after adjusting for age, marital status, occupation, education, systolic blood pressure and TC. Dose-response relationship between TG levels by tertiles and CHD risk was found. Stratified analyses showed TG was an independent predictor for CHD mortality in subjects with lower or higher TC. CONCLUSIONS: Chinese had lower levels of TC and TG than Western populations. This study provides new evidence that TG is an independent risk factor of CHD in subjects with lower or higher TC levels, and supports the lowering of cut-off value for elevated triglyceride.