Risk factors of peripheral venous catheter-related complication and infection in children with bronchopneumonia.

OBJECTIVE: To investigate the risk factors associated with the peripheral venous catheter-related complication and infection in children with bronchopneumonia. METHODS: A total of 185 patients were divided into case group (n = 114) and control group (n = 71) according to the presence of catheter-related infection and complications related to indwelling needle. We performed a multivariate logistic regression analysis to explore the risk factors associated with the infection. RESULTS: Age was divided into 4 categories (0 < age ≤ 1, 1 < age ≤ 3, 3 < age ≤ 6, age > 6). The case group had a higher percentage of patients with 0 < age ≤ 1 than the control group (21% vs. 9.7%) and the age distribution was significant different between the two groups (P = 0.045). The case group had a longer retention time than the control group (≥ 3 days: 56% vs. 35%, P < 0.001). The results of binary logistics regression analysis revealed that the indwelling time and indwelling site were the factors that influenced the complications or bacterial infection. Among the three indwelling sites, the hand is more prone to infection and indwelling needle-related complications than the head (OR: 2.541, 95% CI 1.032 to 6.254, P = 0.042). The longer the indwelling time, the more likely the infection and indwelling needle related complications (OR: 2.646, 95% CI 1.759 to 3.979, P< 0.001). CONCLUSION: Indwelling time and indwelling site are the influencing factors of complications or bacterial infection, which should be paid more attention to prevent the catheter-related infection in children with bronchophenumonia.

Glyphosate exposure affected longevity-related pathways and reduced survival in asian honey bees (Apis cerana).

Glyphosate (N-(phosphonomethyl)glycine, GLY) ranks among the most extensively used and effective herbicides globally. However, excessive GLY utilization poses a substantial threat to the survival of honey bees (Apis cerana). Here we monitored the survival status of A. cerana treated with GLY, and conducted transcriptome sequencing of the bee gut and head to further explore potential GLY influences at the molecular level. We observed that the mortality rate of bees increased as GLY concentration escalated. Pivotal pathways emerged in response to the GLY treatment, with a substantial number of differentially expressed genes enriched in the longevity regulating pathway - multiple species. This strongly suggested that GLY may influence the physiological behavior of bees by impacting this particular pathway. Moreover, our analysis revealed a notable reduction in the enzymatic activities of CYP450 and AChE in both the bee head and intestines of when exposed to GLY. Conversely, the enzymatic activity of superoxide dismutase (SOD) in the head remained unaffected, whereas in the intestines, it exhibited a significant increase. Additionally, prophenol oxidase (PPO) and glutathione-S-transferases (GSTs) displayed contrasting trends in enzymatic activity in both organs. This study offers valuable insights into how GLY impacted the survival of A. cerana.

Evaluation of the pharmacokinetics and cardiotoxicity of doxorubicin in rat receiving nilotinib.

Doxorubicin (DOX) is a potent chemotherapy drug with a narrow therapeutic window. Nilotinib, a small-molecule Bcr-Abl tyrosine kinase inhibitor, was reported to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) transmembrane transporters. The present study aimed to investigate nilotinib's affection on the steady-state pharmacokinetics, disposition and cardiotoxicity of DOX. A total of 24 male Sprague-Dawley rats were randomized into four groups (6 in each) and received the following regimens: saline, intravenous DOX (5mg/kg) alone, and DOX co-administrated with either 20 or 40mg/kg nilotinib. Blood was withdrawn at 12 time points till 72h after DOX injection and the concentrations of DOX and its metabolite doxorubicinol (DOXol) in serum and cardiac tissue were assayed by LC-MS-MS method. To determine the cardiotoxicity, the following parameters were investigated: creatine kinase, lactate dehydrogenase, malondialdehyde, and superoxide dismutase. Histopathological examination of heart section was carried out to evaluate the extent of cardiotoxicity after treatments. The results showed that pretreatment of 40mg/kg nilotinib increased the AUC0-t and Cmax of DOX and DOXol. However, their accumulation in cardiac tissue was significantly decreased when compared with the group that received DOX alone. In addition, biochemical and histopathological results showed that 40mg/kg nilotinib reduced the cardiotoxicity induced by DOX administration. In conclusion, co-administration of nilotinib increased serum exposure, but significantly decreased the accumulation of DOX in cardiac tissue. Consistent with in vitro profile, oral dose of 40mg/kg nilotinib significantly decreased the cardiotoxicity of DOX in rat by enhancing P-gp activity in the heart.

[Effects of long-term moderate-small intensity aerobic exercise on differential expression of proteome in left ventricular muscle of rats].

Objective: To investigate the effects of long-term moderate-small intensity aerobic exercise on the differential expression of proteome in left ventricular muscle of rats, and to screen the target proteins sensitive to moderate-small intensity aerobic exercise stimulation. This study will enrich the basic theory of exercise and fitness and provide new ideas and experimental basis for the rehabilitation treatment of chronic cardiovascular disease. Methods: Twenty male SD rats were randomly divided into exercise group and control group (n=10). The treadmill training model of long-term moderate-small intensity aerobic exercise was established, and the whole protein samples of left ventricular muscle were extracted and separated by two-dimensional gel electrophoresis (2-DE). The two-dimensional gel electrophoresis map was analyzed by Bio PD quest image analysis software. The protein spots with differential expression more than 5 times or down-regulated over 80% after exercise were identified by tandem time-of-flight mass spectrometry (ULGRAFL-FLEX-TOF/TOF). Results: Compared with the group C, the heart weight index of the group E was increased by 32.0%, and the difference was significant (P＜0.05). Compared with the group C, there were 71 protein spots expression were up-regulated≥2 times or down-regulated≥50% in the group E. 4 protein spots expression were up-regulated≥5 times or down-regulated≥80% were identified by mass spectrometry, 3 proteins and 1 unknown protein were identified. Conclusion: After long-term moderate-small intensity aerobic exercise, the rats heart had a good adaptive change, and the proteome of left ventricular muscle changed significantly. Long-term moderate-small intensity aerobic exercise can effective enhance the ability of myocardial antioxidation.

Metformin protects high glucose­cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway.

Tissue damage in diabetes is at least partly due to elevated reactive oxygen species production by the mitochondrial respiratory chain during hyperglycemia. Sustained hyperglycemia results in mitochondrial dysfunction and the abnormal expression of mitochondrial genes, such as NADH: Ubiquinone oxidoreductase subunit A13 (NDUFA13). Metformin, an AMP­activated protein kinase (AMPK) activator, protects cardiomyocytes from oxidative stress by improving mitochondrial function; however, the exact underlying mechanisms are not completely understood. The aim of the present study was to investigated the molecular changes and related regulatory mechanisms in the response of H9C2 cardiomyocytes to metformin under high glucose conditions. H9C2 cells were subjected to CCK­8 assay to assess cell viability. Reactive oxygen species generation was measured with DCFH­DA assay. Western blotting was used to analyze the expression levels of NDUFA13, AMPK, p­AMPK and GAPDH. Reverse transcription­quantitative PCR was used to evaluate the expression levels of mitochondrial genes and transcription factors. It was observed that metformin protected H9C2 cardiomyocytes by suppressing high glucose (HG)­induced elevated oxidative stress. In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis­related transcription factors [peroxisome proliferator­activated receptor­gamma coactivator­1α, nuclear respiratory factor (NRF)­1, and NRF­2] in the metformin + HG group compared with the HG group. Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG­induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis.

[Study on 4 weeks medium intensity aeraobic exercise induce the difference expression of the proteomics in rat atrial muscle].

OBJECTIVE: To investigate the effect of moderate-intensity aerobic exercise on the differential expression of rat atrial muscle Proteomics and genes, which provide research basis for the rehabilitation of chronic cardiovascular diseases and exercise -induced cardiac remodeling research. METHODS: Twenty male SD rats were randomly divided into control group and experimental group (n=10) according to body weight. Rats in the experimental group were trained (6 days per week),which lasted for 4 weeks of moderate-intensity aerobic exercise at a rate of 24 m·min-1 for 40 min (load intensity equivalent to 60%~70% VO2max). The proteins were separated by two dimensional gel electrophoresis, and the tandem time-of- flight mass spectrometer technique was used to identify 13 candidate target protein spots. The expression levels of these 13 protein spots were up-regulated more than 5 times or down -regulated to below 1/5. The mRNA of six target proteins were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: By software analysis, the experimental group compared with the control group, there were 8 protein points which their expression reduced more than 4/5 and 5 protein points up-regulated more than 5 times, 13 proteins were identified by mass spectrometry protein spots, the final identification results acquired 8 proteins and a unknown protein of molecular mass 54 KDa, such as:pyruvate dehydrogenase E1α1, mitochondrial aconitate hydratase, protein disulfide isomerase A3, methylmalonic acid semialdehyde dehydrogenase, mitochondrial dihydrolipoic acid dehydrogenase, isovaleryl coenzyme A dehydrogenase, glutathione synthetase, mitogen-activated protein kinase 3 and so on. Compared with the control group, the mRNA expression of methylmalonic acid semialdehyde dehydrogenase in the atrial muscle of rats was decreased after 4 weeks of moderate aerobic exercise (P<0.05), the mRNA expression levels of mitochondria Ⅱ lipoic acid dehydrogenase, protein disulfide isomerase A3, mitochondrial aconitate hydratase and glutathione synthetase were decreased (P>0.05); The mRNA expression level of isopentenyl-CoA dehydrogenase was increased (P>0.05). The results indicated that the mRNA expression level was not completely consistent with the changes in mass spectrometry identification results. CONCLUSIONS: The 4 weeks moderate-intensity aerobic exercise induced ignificant changes of rats atrial muscle protemics. The majority of the 13 identified target proteins in this experiment are energy metabolism enzymes. The majority of the expression of the target protein and the mRNA expression in the atrial muscle is inconsistent and different. Exercise may affect the regulation of gene transcription or downstream translation and modification of these target proteins, resulting in the change of differential expression.

Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia.

BACKGROUND: Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance-based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model. METHODS: Eighty-four cancer cachexia patients, 33 pre-cachectic patients, 105 weight-stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model. RESULTS: Forty-six cancer cachexia patients, 22 pre-cachectic patients, 68 weight-stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre-cachectic patients, 37 weight-stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age-matched and sex-matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = -400.53 - 481.88 × log(Carnosine) -239.02 × log(Leucine) + 383.92 × log(Phenyl acetate), and the result showed 94.64% accuracy in the validation set. CONCLUSIONS: This metabolomics study revealed a distinct metabolic profile of cancer cachexia and established and validated a diagnostic model. This research provided a feasible diagnostic tool for identifying at-risk populations through the detection of serum metabolites.

Scutellarin protects against doxorubicin-induced acute cardiotoxicity and regulates its accumulation in the heart.

The clinical use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. The present study investigated the effects of scutellarin against DOX-induced cardiotoxicity in rats using pharmacodynamic and pharmacokinetic approaches. DOX (20 mg/kg) was injected intraperitoneally (i.p.) as a single dose, and scutellarin (5 mg/kg/day) was injected intravenously (i.v.) for 3 days. Rats treated with DOX showed acute cardiotoxicity as indicated by the elevated serum lactate dehydrogenase (LDH) activity (4057.8 ± 107.2 vs. 2032.7 ± 70.95), tissue malondialdehyde (MDA) level (2.083 ± 0.10 vs. 1.103 ± 0.09), cardiac troponin T (cTnT) concentration (0.1695 ± 0.0114 ng/mL), the decreased left ventricular ejection fraction (LVEF) (47.75 ± 15.79 vs. 78.72 ± 7.25) and left ventricular fractional shortening (LVFS) (20.66 ± 8.06 vs. 43.7 ± 6.76) compared with those of the control group. Cotreatment with scutellarin significantly decreased the LDH activity (2595.9 ± 72.73), MDA level (1.380 ± 0.06), cTnT concentration (0.0222 ± 0.0041 ng/m L), increased LVEF (76.70 ± 3.91) and LVFS (40.28 ± 3.68). Histopathological studies showed disruption of cardiac tissues in the DOX groups. Cotreatment with scutellarin reduced the damage to cardiac tissues. In the pharmacokinetic and tissue distribution study, scutellarin reduced the heart tissue exposure to DOX but did not change the AUC of plasma. These results suggest that scutellarin can protect against DOX-induced acute cardiotoxicity through its antioxidant activity and alterations of heart concentrations.

Nilotinib reverses ABCB1/P-glycoprotein-mediated multidrug resistance but increases cardiotoxicity of doxorubicin in a MDR xenograft model.

The BCR-Abl tyrosine kinase inhibitor (TKI), nilotinib, was developed to surmount resistance or intolerance to imatinib in patients with Philadelphia-positive chronic myelogenous leukemia. Recent studies have shown that nilotinib induces potent sensitization to anticancer agents by blocking the functions of ABCB1/P-glycoprotein (P-gp) in multidrug resistance (MDR). However, changes in P-gp expression or function affect the cardiac disposition and prolong the presence of both doxorubicin (DOX) and doxorubicinol (DOXol) in cardiac tissue, thus, enhancing the risk of cardiotoxicity. In this study, we used a MDR xenograft model to evaluate the antitumor activity, tissue distribution and cardiotoxicity of DOX when co-administered with nilotinib. This information will provide more insight into the pharmacological role of nilotinib in MDR reversal and the risk of DOX cardiotoxicity. Our results showed that nilotinib significantly enhanced DOX cytotoxicity and increased intracellular rhodamine 123 accumulation in MG63/DOX cells in vitro and strongly enhanced DOX inhibition of growth of P-gp-overexpressing MG63/DOX cell xenografts in nude mice. Additionally, nilotinib significantly increased DOX and DOXol accumulation in serum, heart, liver and tumor tissues. Importantly, nilotinib induced a disproportionate increase in DOXol in cardiac tissue. In the co-administration group, CBR1 and AKR1A1 protein levels were significantly increased in cardiac tissue, with more severe necrosis and vacuole formation. These results indicate that nilotinib reverses P-gp- mediated MDR by blocking the efflux function and potentiates DOX-induced cardiotoxicity. These findings represent a guide for the design of future clinical trials and studies of pharmacokinetic interactions and may be useful in guiding the use of nilotinib in combination therapy of cancer in clinical practice.

Elucidation of fluoranthene degradative characteristics in a newly isolated Achromobacter xylosoxidans DN002.

Strain DN002 isolated from petroleum-contaminated soil was identified as Achromobacter xylosoxidans based on morphological and biochemical properties and 16S rRNA phylogeny, and investigated for its potential to utilize numerous polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene and pyrene as sole carbon and energy resource. Biodegradation studies showed that 500 mg(·)l(-1)fluranthene was degraded to 35.6 ± 0.3 mg(·)l(-1) by DN002 after 14 days incubation. During fluoranthene biodegradation, catechol 2,3 dioxygenase (C23O) activity was augmented 1.5 times more than catechol 1,2 dioxygenase (C12O), which indicated that C23O played a major role in fluoranthene degradation by DN002. Protein profiles were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and two-dimensional electrophoresis then analyzed by mass spectrometry induced by fluoranthene; a molecular mass range of 18 ∼ 66 kDa proteins were found upregulated compared with the uninduced control sample, including multiple isoenzymes of ß-oxidation and dehydrogenases as well as dioxygenases. Besides, some new proteins, i.e., dihydrolipoamide succinyltransferase and aldehyde dehydrogenase family proteins and isocitrate lyase were also synthesized.

[Adsorption characteristic and form distribution of silicate in lakes sediments].

Taking surface sediments from the Wuliangsuhai Lake and Daihai Lake as adsorbent, the isothermal adsorption experiments of silicate on sediments were carried out and the adsorption behavior was explained by Langmuir, Freundlich and Temkin crossover-type equations, then the form distribution characters of silicate were studied after adsorption in this work. The results showed that the adsorption behavior of silicate on the two lakes sediments can be linear fitting in the lower concentration dose (< or = 3.00 mg x L(-1)); the sediments from the Wuliangsuhai Lake behaved adsorbing silicate while the sediments from the Daihai Lake behaved releasing silicate under the experimental dose; all of the Langmuir, Freundlich and Temkin crossover-type equations can be used to explain the adsorption behavior of silicate on the two lakes sediments, and the native adsorption silicate (NAS) and equilibrium silicate concentration (ESC(0)) calculated by the three equations could be used to explain the sink and source effects of the sediments from the two lakes; the silicate form distribution in the sediments after adsorption indicated that silicate adsorbed on particles were mainly added on the form of IEF-Si, CF-Si, IMOF-Si and OSF-Si, and the IMOF-Si and OSF-Si had important potential bioavailability.

Evaluation of impact of Herba Erigerontis injection, a Chinese herbal prescription, on rat hepatic cytochrome P450 enzymes by cocktail probe drugs.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis. AIM OF THE STUDY: The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8ml/kg or 7.2ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5ml/kg, which contained caffeine (2.5mg/kg), tolbutamide (2.5mg/kg), chlorzoxazone (5mg/kg), midazolam (5mg/kg) and metoprolol (10mg/kg), was injected via the lingual vein to all rats. Then 0.8ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis. RESULTS: There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P<0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down. CONCLUSIONS: The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions.

Alleviation of the acute doxorubicin-induced cardiotoxicity by Lycium barbarum polysaccharides through the suppression of oxidative stress.

The present study aims to investigate whether Lycium barbarum polysaccharides (LBP) could protect against acute doxorubicin (DOX)-induced cardiotoxicity. Rats received daily treatment of either distilled water (4 ml/kg) or LBP (200mg/kg) for 10 days and then followed by an intravenous injection at day 7 of either saline (10 ml/kg) or DOX (10 mg/kg). DOX induced significantly myocardial damage in rats, which were characterized as conduction abnormalities, decreased heart-to-body weight ratio, increased serum CK, and myofibrillar disarrangement. DOX treatment also increased MDA and decreased SOD and GSH-Px activity in cardiac tissues. Pretreatment with LBP significantly reduced DOX-induced oxidative injury in cardiac tissue, suggesting by the fact that LBP significantly attenuated DOX-induced cardiac myofibrillar disarrangement and LBP was effective in decreasing the levels of serum CK and thus improving conduction abnormalities caused by DOX. LBP treatment significantly increased SOD and GSH-Px activity and decreased the MDA level of heart tissues damaged by DOX exposure in rats. Furthermore, the cytotoxic study showed that LBP protect against cytotoxicity of DOX in cardiac myoblasts H9c2 but dose not attenuate the anti-tumor activity of DOX. In summary, our evidence indicates that LBP elicited a typical protective effect on DOX-induced acute cardiotoxicity via suppressing oxidative stress.

Effects of quercetin on gene and protein expression of NOX and NOS after myocardial ischemia and reperfusion in rabbit.

Previous studies have suggested that reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) are involved in the pathophysiology of myocardial ischemia-reperfusion injury (MIRI). The NOX family of NADPH oxidases share the capacity to generate superoxide and ROS. Several studies have demonstrated that quercetin possesses a protective effect against MIRI. Our aim is to investigate the effects of quercetin on NOX2, eNOS, and iNOS after MIRI in rabbits. New Zealand rabbits were subjected to 30 min of myocardial ischemia followed by 12 h of reperfusion. They were then randomly assigned to four experimental groups: control, I/R (ischemia/reperfusion), quercetin (Que), I/R + Que. Gene and protein expression of NOX2, eNOS, and iNOS were compared. Both in real-time PCR and in the Western blotting studies, myocardial ischemia-reperfusion-induced NOX2 and iNOS expression were enhanced (P < 0.01) but eNOS mRNA and protein expression in I/R hearts were not significantly different from those in control (P < 0.01). Administration of quercetin reduced NOX2, eNOS, and iNOS mRNA and protein expression both in control and in I/R heart (P < 0.01). Gene and protein expression of NOX2 and iNOS were increased after MIRI. Quercetin not only inhibited myocardial ischemia-reperfusion-induced NOX2 and iNOS mRNA and protein expression but also inhibited eNOS mRNA and protein expression.