The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

The Polo-Like Kinase 1-Mammalian Target of Rapamycin Axis Regulates Autophagy to Prevent Intestinal Barrier Dysfunction During Sepsis.

The intestines play a crucial role in the development of sepsis. The balance between autophagy and apoptosis in intestinal epithelial cells is dynamic and determines intestinal permeability. The present study focused on the potential role of autophagy in sepsis-induced intestinal barrier dysfunction and explored the mechanisms in vivo and in vitro. Excessive apoptosis in intestinal epithelia and a disrupted intestinal barrier were observed in septic mice. Promoting autophagy with rapamycin reduced intestinal epithelial apoptosis and restored intestinal barrier function, presenting as decreased serum diamine oxidase (DAO) and fluorescein isothiocyanate-dextran 40 (FD40) levels and increased expression of zonula occludens-1 (ZO-1) and Occludin. Polo-like kinase 1 (PLK1) knockdown in mice ameliorated intestinal epithelial apoptosis and the intestinal barrier during sepsis, whereas these effects were reduced with chloroquine and enhanced with rapamycin. PLK1 also promoted cell autophagy and improved lipopolysaccharide-induced apoptosis and high permeability in vitro. Moreover, PLK1 physically interacted with mammalian target of rapamycin (mTOR) and participated in reciprocal regulatory crosstalk in intestinal epithelial cells during sepsis. This study provides novel insight into the role of autophagy in sepsis-induced intestinal barrier dysfunction and indicates that the PLK1-mTOR axis may be a promising therapeutic target for sepsis.

PLK1 protects intestinal barrier function in sepsis: A translational research.

BACKGROUND: Sepsis and its related complications are very challenging in the intensive care unit, among which intestinal barrier injury is a general manifestation. Polo-like kinase 1 (PLK1) is widely studied in cancer, while its role in sepsis is poorly understood. In this study, the efficiency of PLK1 as a marker of intestinal barrier function as well as a predictor of mortality in sepsis was evaluated. METHODS: The level of serum PLK1 was measured in septic patients (n = 51) and controls (n = 20); subsequently, its correlation with serum diamine oxidase (DAO), d-lactate, and endotoxin levels and its ability topredict mortality were analysed. The survival rate and barrier injury degree were also assessed in septic mice. RESULTS: Serum PLK1 levels were elevated in septic patients, were negatively correlated with serum DAO, d-lactate, and endotoxin levels, and had a high predictive value for 28-day mortality in patients. The serum PLK1 level in non-survivors was lower. The expression of PLK1 in the intestine was decreased in septic mice, and overexpression or inhibition of PLK1 alleviated or aggravated intestinal barrier injury, respectively, as evaluated by Chiu's score, serum levels of DAO and d-lactate, and expression of tight junction proteins. Overexpressing PLK1 also decreased the 72-hour death rate of septic mice. Further study also revealed the negative correlation of PLK1 and IL-6 in patients, and increasing or interfering with PLK1 expression reduced or increased the serum IL-6 level in mice. CONCLUSIONS: PLK1 plays a critical role in intestinal barrier function during sepsis, providing a novel perspective for sepsis therapy in the clinic.

PLK1 protects intestinal barrier function during sepsis by targeting mitochondrial dynamics through TANK-NF-κB signalling.

BACKGROUND: Intestinal barrier integrity in the pathogenesis of sepsis is critical. Despite an abundance of evidence, the molecular mechanism of the intestinal barrier in sepsis pathology remains unclear. Here, we report a protective role of polo-like kinase 1 (PLK1) in intestinal barrier integrity during sepsis. METHODS: Mice with PLK1 overexpression (CAG-PLK1 mice) or PLK1 inhibition (BI2536-treated mice) underwent caecal ligation and puncture (CLP) to establish a sepsis model. The intestinal barrier function, apoptosis in the intestinal epithelium, mitochondrial function and NF-κB signalling activity were evaluated. To suppress the activation of NF-κB signalling, the NF-κB inhibitor PDTC, was administered. The Caco-2 cell line was chosen to establish an intestinal epithelial injury model in vitro. RESULTS: Sepsis destroyed intestinal barrier function, induced excessive apoptosis in the intestinal epithelium, and disrupted the balance of mitochondrial dynamics in wild-type mice. PLK1 overexpression alleviated sepsis-induced damage to the intestinal epithelium by inhibiting the activation of NF-κB signalling. PLK1 colocalized and interacted with TANK in Caco-2 cells. Transfecting Caco-2 cells with TANK-SiRNA suppressed NF-κB signalling and ameliorated mitochondrial dysfunction, apoptosis and the high permeability of cells induced by lipopolysaccharide (LPS). Furthermore, TANK overexpression impaired the protective effect of PLK1 on LPS-induced injuries in Caco-2 cells. CONCLUSION: Our findings reveal that the PLK1/TANK/NF-κB axis plays a crucial role in sepsis-induced intestinal barrier dysfunction by regulating mitochondrial dynamics and apoptosis in the intestinal epithelium and might be a potential therapeutic target in the clinic.

Effect of Dexmedetomidine on Intestinal Barrier in Patients Undergoing Gastrointestinal Surgery-A Single-Center Randomized Clinical Trial.

INTRODUCTION: Gastrointestinal failure results in death in critically ill patients. This study aimed to explore the effect of dexmedetomidine (DEX) on intestinal barrier function and its mechanism in critically ill patients undergoing gastrointestinal surgery. METHODS: Patients undergoing gastrointestinal surgery were randomized into the DEX group (n = 21) or midazolam (MID) group (n = 21). Sufentanil was used for analgesia in both groups. In the DEX group, DEX was loaded (1 µg/kg) before sedation and infused (0.7 µg/kg/h) during sedation. In the MID group, MID was loaded (0.05 mg/kg) before sedation and infused (0.1 mg/kg/h) during sedation. The mean arterial pressure , heart rate , borborygmus resumption time , first defecation time, length of intensive care unit stay, and length of hospital stay were observed. The diamine oxidase (DAO), D-lactate , TNF-α, IL-6, and α7nAChR levels in plasma or hemocytes were detected before the start of sedation (0 h) and after sedation (24 h). RESULTS: No significant differences in age, sex, body mass index, Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were noted (P > 0.05). The mean arterial pressure between 0 h and 24 h showed no significant difference between the groups (P > 0.05), but the heart rate was significantly lower in the DEX group (P = 0.042). The borborygmus resumption time was significantly earlier in the DEX group (P = 0.034). The lengths of intensive care unit stay (P = 0.016) and hospital stay (P = 0.031) were significantly shorter in the DEX group. The TNF-α level in the DEX group was lower at 24 h than 0 h. The D-lactate level was significantly lower in the DEX group than the MID group at 24 h (P = 0.016). The expression of α7nAChR in the DEX group was significantly higher at 24 h than 0 h (P < 0.05). CONCLUSIONS: DEX maintained intestinal barrier integrity in patients undergoing gastrointestinal surgery through the cholinergic anti-inflammatory pathway.

Sepsis induces muscle atrophy by inhibiting proliferation and promoting apoptosis via PLK1-AKT signalling.

Sepsis and sepsis-induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell-based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo-like kinase 1 (PLK1) and phosphorylated protein kinase B (p-AKT) was decreased. Overexpression of PLK1 partly rescued LPS-induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS-induced atrophy in PLK1-overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1-AKT pathway. These findings enhance understanding of the mechanism of sepsis-induced skeletal muscle atrophy.

Sepsis induces variation of intestinal barrier function in different phase through nuclear factor kappa B signaling.

The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.

[Effects of dung beetles on decomposition of cattle dung in spring and autumn in a Seriphi-dium-dominated desert, China.] / ç²ªç”²è™«å¯¹ç»¢è’¿è’æ¼ æ˜¥ç§‹ä¸¤å­£ç‰›ç²ªåˆ†è§£çš„å½±å“.

To understand the decomposition of cattle dung in Seriphidium-dominated desert, the changes of dung physical and chemical properties were determined by setting different stacking times (0, 7, 29, 48, 58 h) in May (spring) and September (autumn), respectively. Mesh cage with different openings (no mesh cage, opening up and down, opening up, totally enclosed) were set up to explore the effects of different ecological functional groups of dung beetles on decomposition. The results showed that species richness of dung beetles in spring was significantly higher than that in autumn, and that the abundance of dung beetles in autumn was significantly higher than that in spring. The losses of moisture, total carbon, total nitrogen and total phosphorus in dung were mainly concentrated during 0-29 h in spring, being decreased by 39.4%, 13.9%, 32.1% and 26.7% at 29 h, respectively. Neutral detergent fiber and acid detergent fiber of the dung stacked for 58 h decreased significantly by 8.0% and 16.0% respectively. In autumn, moisture, neutral detergent fiber and acid detergent fiber decreased most rapidly during 0-7 h, being decreased by 85.6%, 10.2% and 20.2% at 7 h, respectively. The concentrations of neutral detergent fiber and acid detergent fiber increased during 7-58 h by 20.0% and 13.7%, respectively. The decomposition of total carbon, total nitrogen and total phosphorus mainly concentrated during 0-29 h, being reduced by17.5%, 55.0% and 64.8%, respectively. The mesh cage with different openings effectively prevented the entering of dung beetles from the corresponding ecological functional groups. With the increases of functional groups of dung beetles, the decomposition rate accelerated, with cattle dung of no mesh cage being significantly higher than other treatments. The species richness and abundance of dung beetles and the stacking time of dung significantly affected the decomposition of cattle dung.

Inhibition of miR-155 alleviates sepsis-induced inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling.

MicroRNA-155 (miR-155) is implicated in the pathological processes of sepsis. However, the function and regulatory mechanism of miR-155 in sepsis-induced inflammation and intestinal barrier dysfunction remain unknown. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). To reduce miR-155 expression, the mice were injected for three consecutive days with an miR-155 inhibitor (80 mg/kg) before CLP. The serum DAO concentration was measured by ELISA, and histological changes in the intestine were identified by H&E staining 24 h after CLP. FITC-dextran assays were used to evaluate intestinal permeability. MiR-155 gene expression was evaluated with RT-PCR, and relative protein expression was assessed by Western blotting. NCM460 cells were transfected with an miR-155 mimic/miR-155 inhibitor or pretreated with an NF-κB inhibitor before LPS treatment, and the cytokines levels, miR-155 gene expression and relative protein expression were measured. Sepsis increased miR-155, DAO and FITC-dextran levels and reduced Occludin and ZO-1 expression. Mice injected with the miR-155 inhibitor recovered from the damages. Transfection of NCM460 cells with the miR-155 mimic elevated the NF-κB (P65) and p-NF-κB (p-P65) localization and expression in the nucleus, which was reversed by the miR-155 inhibitor. Pretreatment with an NF-κB inhibitor suppressed inflammation, improved cell permeability to FITC-dextran and increased Occludin and ZO-1 levels. Transfection with the miR-155 inhibitor decreased TNF-α and IL-6 levels, reduced cell permeability to FITC-dextran and increased ZO-1 and Occludin expression. The effects induced by transfection with the miR-155 mimic, including elevated TNF-α and IL-6 levels, hyperpermeability to FITC-dextran and reduced ZO-1 and Occludin expression, were partly rescued by pretreatment with the NF-κB inhibitor. These findings reveal that the miR-155 inhibitor alleviates inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling during sepsis.

Prevention of underfeeding during enteral nutrition after gastrectomy in adult patients with gastric cancer: an evidence utilization project.

BACKGROUND: Enteral nutrition is commonly used in patients with gastric cancer after a partial or full gastrectomy since it is safe to use and nutrient delivery is in line with human physiological characteristics. However, enteral feeding often leads to deficiency, when the actual intake of the patient is lower than the target demand, which seriously affects the recovery of patients. OBJECTIVE: To implement the best practice for preventing and managing underfeeding during enteral nutrition, and to improve the nutritional status of patients with gastric cancer. METHODS: The current study was conducted following the Joanna Briggs Institute Practical Application of Clinical Evidence System program. Phase one referred to the development of the project, consisting of the generation of the best evidence, mainly based on literature review and discussions within a panel of experts. Phase two was the implementation of the project, including baseline audit, training of enteral nutrition and change of clinical practice. Phase three was a postimplementation reaudit. The intake of enteral nutrition was observed in the first 3 days, and feeding intolerance of enteral nutrition was observed within the first week of enteral nutrition. Data were collected using self-designed questionnaires. The nutritional status of patients was measured using Patient-Generated Subjective Global Assessment (PG-SGA) at admission, and 1 week after surgery. RESULTS: A total of 60 patients with gastric cancer and 10 registered nurses were enrolled in this study. The compliance rate for all audit criteria increased postimplementation. The feeding rate of enteral nutrition postimplementation was higher than the baseline audit on the third day, 54.29% (±12.01) vs. 42.89% (±10.63), and the incidence of underfeeding was lower (30%, n = 30) than the baseline audit (76.67%, n = 30). Furthermore, the feeding intolerance postimplementation (26.67%, n = 30) was lower than the baseline audit (76.67%, n = 30) within 1 week of enteral nutrition. The PG-SGA scores were not significantly different between the baseline audit and postimplementation on the day of admission, while the scores were lower postimplementation (12.90 ±â€Š1.47) compared with the baseline audit (14.00 ±â€Š1.82). CONCLUSION: In this study, we performed an audit of the clinical nursing quality, which can guide nurses to accurately identify obstacles to the implementation of enteral nutrition, and standardize the implementation and management process, thereby improving the quality of nursing and the nutritional status of patients. RELEVANCE TO CLINICAL PRACTICE: The evidence-based practice might optimize the enteral nutrition process, enhance the efficacy of enteral nutrition, and improve the nutritional status of patients. Medical staff should develop an individualized nutritional support protocol for patients based on the results of nutritional status assessments.

Baseline Serum Cystatin C Is a Potential Predictor for Acute Kidney Injury in Patients with Acute Pancreatitis.

AIMS: The study is aimed at studying the incidence of acute kidney injury (AKI) and exploring the potential predictor for AKI in patients with acute pancreatitis. METHODS: A retrospective study adopting a stratified cohort sampling design was performed in a cohort of patients (n = 237) diagnosed with acute pancreatitis without any renal injury. The following information including age, gender, serum creatinine, serum urea nitrogen, serum uric acid, serum cystatin C, fasting serum glucose, serum amylase, serum lipase, serum choline esterase, total protein, albumin, globulin, total bilirubin, direct bilirubin, total bile acids, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, gamma glutamyl transpeptidase, and alkaline phosphatase were collected from each patient when they were diagnosed with acute pancreatitis. Student t-test was conducted to figure out the difference between patients with and without AKI. Univariate and multivariate logistic regression analyses were used for investigating the predictors for AKI in patients with acute pancreatitis. RESULTS: 18 (7.6%) patients in total had developed AKI among the study group. Compared with patients without AKI (1.01 ± 0.26 mg/L), the level of baseline serum cystatin C (CYS-C) was significantly higher in patients with AKI (3.64 ± 2.17 mg/L, P < 0.001). Baseline serum CYS-C (OR = 203.594, P < 0.001) was the independent and significant predictor for AKI in patients with acute pancreatitis. AKI in patients with acute pancreatitis could be identified with a sensitivity of 88.9% at specificity of 100% (AUC = 0.948, 95% CI 0.879-1.000) by baseline serum CYS-C (cut-off value = 1.865 mg/L). CONCLUSIONS: Baseline serum CYS-C shall be adopted to predict the potential risk of AKI in patients with acute pancreatitis.

Plumbagin inhibits the proliferation and survival of esophageal cancer cells by blocking STAT3-PLK1-AKT signaling.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it requires novel treatment approaches and effective drugs. In the present study, we found that treatment with plumbagin, a natural compound, reduced proliferation and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent manner in vitro. The drug also effectively inhibited the viability of primary ESCC cells from fresh biopsy specimens. Furthermore, plumbagin-induced mitotic arrest and massive apoptosis in ESCC cells. Notably, the drug significantly suppressed the colony formation capacity of ESCC cells in vitro and the growth of KYSE150 xenograft tumors in vivo. At the molecular level, we found that exposure to plumbagin decreased both polo-like kinase 1 (PLK1) and phosphorylated protein kinase B (p-AKT) expression in both ESCC cell lines. Enforced PLK1 expression in ESCC cells not only markedly rescued cells from plumbagin-induced apoptosis and proliferation inhibition but also restored the impaired AKT activity. Furthermore, signal transducer and activator of transcription 3 (STAT3), a transcription factor of PLK1, was also inactivated in plumbagin-treated ESCC cells; however, the overexpression of a constitutively activated STAT3 mutant, STAT3C, reinstated the plumbagin-elicited blockade of PLK1-AKT signaling in ESCC cells. Taken together, these findings indicate that plumbagin inhibits proliferation and potentiates apoptosis in human ESCC cells in vitro and in vivo. Plumbagin may exert these antitumor effects by abrogating STAT3-PLK1-AKT signaling, which suggests that plumbagin may be a novel, promising anticancer agent for the treatment of ESCC.

[Seed morphology and effects of sheep rumen digestion on seed germination of 28 Gramineae plants.] / 28ç§ç¦¾æœ¬ç§‘æ¤ç‰©ç§å­å½¢æ€å­¦ç‰¹å¾åŠå ¶èŒå‘å¯¹ç»µç¾Šç˜¤èƒƒæ¶ˆåŒ–çš„ååº”.

An experiment was undertaken to compare the morphological characteristics of seeds of 28 Gramineae plants which widely distributed in north Xinjiang and to study their digestion in the rumen of sheep. After determining their morphological characteristics including seed length, width, height, seed shape index, 100-seed mass, and seed germination percentage, seeds were put into nylon bags and then placed in the rumen of sheep through a fistula. The bags were removed at different times to determine the morphological characteristics and seed germination rates. The results showed that 23 plant seeds were all elliptic or flat types except for Melica scabrosa, Agrostis ma-tsumurae, Poa bulbosa, Phleum pratense and Triticum aestivum. 100-seed mass of T. aestivum (3.25 g) and Avena sativa (1.69 g) were >1 g, and the 100-seed mass of the other seeds ranged from 0.01-1 g, indicating they were all medium or small type seeds. The color of seed coat was deepened, seed structure was destructed, and the lengths of seed appendages, i.e., awn, lemma and glume were decreased with increasing digestion time. Seed length, width, height, 100-seed mass were decreased with increasing digestion time, but the changes were not significant compared with the non-digested seeds. The seed germination percentages were extremely decreased after sheep rumen digestion. After 6 h of sheep rumen digestion, the germination rates of the seeds of R. kamoji and A. sativa were decreased to 0, and part of the seeds of other 26 plants still had some vigor.

High-sensitivity cardiac troponin T: A biomarker for the early risk stratification of type-A acute aortic dissection?

BACKGROUND: High-sensitivity cardiac troponin is the most specific and sensitive biomarker of myocardial injury. However, no study has investigated whether the early concentration of high-sensitivity cardiac troponin is increased or is of value in predicting short-term prognosis in patients with type-A acute aortic dissection (AAD) in the emergency department. AIMS: To measure the high-sensitivity cardiac troponin T (hs-TnT) concentration in patients with type-A AAD upon hospital admission, and to assess its value in predicting short-term prognosis. METHODS: We enrolled consecutive patients with type-A AAD. Blood samples were collected on admission; hs-TnT concentrations were measured on the Elecsys 2010 system. High-sensitivity C-reactive protein (hs-CRP), D-dimer and other biochemical indicators were measured. Patients were divided into two groups according to hs-TnT concentration on admission (< or ≥0.014ng/mL). RESULTS: More than half (61.2%) of the 103 included patients had an hs-TnT concentration ≥0.014ng/mL. hs-TnT concentrations were significantly higher in those who died compared with survivors (0.292±0.516 vs. 0.069±0.154ng/mL; P=0.003). Multivariable Cox regression analysis suggested that hs-TnT is an independent factor for predicting in-hospital mortality risk (odds ratio: 2.202, 95% confidence interval: 1.111-4.367; P=0.024). Kaplan-Meier curves revealed a significant increase in hospital mortality in the hs-TnT(+) group compared with the hs-TnT(-) group (P=0.021). When hs-TnT was ≥0.042ng/mL, the sensitivity and specificity in predicting hospital short-term mortality were 70.8% and 76.4%, respectively. CONCLUSIONS: Our study suggests that hs-TnT concentration could be used as an early biomarker for the risk stratification of patients with type-A AAD in the emergency department; the relationship between hs-TnT concentration and long-term prognosis needs further investigation.

A broad-range survey of ticks from livestock in Northern Xinjiang: changes in tick distribution and the isolation of Borrelia burgdorferi sensu stricto.

BACKGROUND: Borreliosis is highly prevalent in Xinjiang Uygur Autonomous Region, China. However, little is known about the presence of Borrelia pathogens in tick species in this region, in addition Borrelia pathogens have not been isolated from domestic animals. METHODS: We collected adult ticks from domestic animals at 19 sampling sites in 14 counties in northern Xinjiang from 2012 to 2014. Ticks were identified to species by morphology and were molecularly analysed by sequences of mitochondrial 16S rDNA gene; 4-8 ticks of each species at every sampling site were sequenced. 112 live adult ticks were selected for each species in every county, and were used to culture Borrelia pathogens; the genotypes were then determined by sequences of the 5S-23S rRNA intergenic spacer and the outer surface protein A (ospA) gene. RESULTS: A total of 5257 adult ticks, belonging to four genera and seven species, were collected. Compared with three decades ago, the abundance of the five common tick species during the peak ixodid tick season has changed. Certain tick species, such as Rhipicephalus turanicus (Rh. turanicus), was found at Jimusaer, Yining, Fukang, and Chabuchaer Counties for the first time. Additionally, the sequence analyses showed that the Hyalomma asiaticum (Hy. asiaticum), Haemaphysalis punctata (Ha. punctata), and Dermacentor marginatus (D. marginatus) that were collected from different sampling sites (≥3 sites) shared identical 16S rDNA sequences respectively. For the tick species that were collected from the same county, such as Hy. asiaticum from Shihezi County and Rh. turanicus from Yining County, their 16S rDNA sequences showed genetic diversity. In addition, sixteen Borrelia isolates were found in Hy. asiaticum, Ha. punctata, D. marginatus and Rh. turanicus, which infested cattle, sheep, horse and camel in Yining, Chabuchaer, Shihezi and Shawan Counties. All of the isolates were genetically identified as B. Burgdorferi sensu stricto. CONCLUSIONS: Warmer and wetter climate may have contributed to the altered distribution and abundance of the five most common ticks in northern Xinjiang. The genetic analyses showed that certain tick species, such as Hy. asiaticum or Rh. turanicus, exhibit genetic commonness or diversity. Additionally, this study is the first to isolate B. burgdorferi sensu stricto in Hy. asiaticum asiaticum, H. punctata, D. nuttalli and D. marginatus ticks from domestic animals. These ticks may transmit borreliosis among livestock.

Admission hypoxia-inducible factor 1α levels and in-hospital mortality in patients with acute decompensated heart failure.

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a critical regulator for cellular oxygen balance. Myocardial hypoxia can induce the increased expression of HIF-1α. Our goals were to evaluate the value of HIF-1α in predicting death of patients with acute decompensated heart failure (ADHF) and describe the in vivo relationship between serum HIF-1α and N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels. METHOD: We included 296 patients who were consecutively admitted to the emergency department for ADHF. The primary end point was in-hospital death. The patients were categorized as HFrEF (patients with reduced systolic function) and HFpEF (patients with preserved systolic function) groups. RESULTS: In our patients, the median admission HIF-1α level was 2.95 ± 0.85 ng/ml. The HIF-1α level was elevated significantly in HFrEF patients and deceased patients compared with HFpEF patients and patients who survived. The HIF-1α level was positively correlated with NT-proBNP and cardiac troponin T levels, and negatively correlated with left ventricular ejection fraction and systolic blood pressure. Kaplan-Meier curves revealed a significant increase in in-hospital mortality in ADHF patients with higher HIF-1α levels. Multivariable Cox regression analysis showed that HIF-1α levels were not correlated with the short-term prognosis of ADHF patients. CONCLUSIONS: This is the first study to evaluate the circulating levels of HIF-1α in ADHF patients. Serum HIF-1α levels may reflect a serious state in patients with ADHF. Due to the limitations of the study, serum HIF-1α levels were not correlated with the in-hospital mortality based on regression analysis. Further studies are needed to demonstrate the diagnostic and/or prognostic role of HIF-1α as a risk biomarker in patients with ADHF.

Resuscitation with hydroxyethyl starch 130/0.4 attenuates intestinal injury in a rabbit model of sepsis.

OBJECTIVE: Improvement of mucosal barrier function and reduction of bacterial translocation are important in the management of sepsis. The mechanisms that underlie the protective effects of colloids on the intestinal mucosal barrier are unclear. The study aims to investigate the effect of fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 against intestinal mucosal barrier dysfunction in a rabbit model of sepsis. MATERIALS AND METHODS: Thirty healthy rabbits were randomly and equally divided into a sham-operated control, a sepsis model, or a sepsis + HES treatment group. The sepsis model and sepsis + HES treatment groups were subjected to a modified colon ascendens stent peritonitis (CASP) procedure to induce sepsis. Four hours after the CASP procedure, fluid resuscitation was performed with 6% HES 130/0.4. Arterial and superior mesenteric vein blood samples were collected 4 and 8 h after the CASP procedure for blood gas analysis and measuring tumor necrosis factor-α, interleukin-10, and D-lactate levels. The rabbits were euthanized 8 h after CASP, and sections of the small intestine were stained to evaluate histopathological changes. RESULTS: Respiratory rate and blood pressure were stable during the resuscitation period. Fluid resuscitation with 6% HES 130/0.4 alleviated pathological changes in the abdominal cavity, improved blood gas parameters and inflammatory mediator levels, decreased plasma D-lactate levels, and reduced intestinal mucosal injury compared with the non-treated sepsis model. CONCLUSIONS: Fluid resuscitation with 6% HES 130/0.4 protects against intestinal mucosal barrier dysfunction in rabbits with sepsis, possibly via mechanisms associated with improving intestinal oxygen metabolism and reducing the release of inflammatory mediators.

Effect of atorvastatin on the expression of gamma-glutamyl transferase in aortic atherosclerotic plaques of apolipoprotein E-knockout mice.

BACKGROUND: Gamma-glutamyl transpeptidase (GGT) is now considered to be one of the risk factors for cardiovascular disease. However, whether statins can alter GGT levels in arterial atheromatous plaque has not yet been studied. Therefore, the aim of this study is to determine whether statins can effectively decrease the expression of GGT in arterial atheromatous plaques. METHODS: We randomly divided 45 apolipoprotein E-knockout (ApoE KO) male mice into three groups: normal diet (ND) group,high-cholesterol diet (HCD) group and high-cholesterol diet and atorvastatin (HCD + Ato) group. We fed high-cholesterol food to the HCD and HCD + Ato group. After eight weeks, atorvastatin 5 mg•kg-1•d-1 was given to HCD + Ato group mice. The serum GGT-1, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell-adhesion molecule-1 (VCAM-1) levels were measured at end of 16 weeks by using ELISA methods. The expressions of GGT-1, ICAM-1 and VCAM-1 in aorta were measured by RT-PCR and Western Blot. RESULTS: The ApoE KO mice with HCD were associated with a marked increase in plasma lipid, inflammatory factors, GGT-1, ICAM-1 and VCAM-1. The expressions of GGT-1, ICAM-1 and VCAM-1 in HCD aortic tissue were increased. At the HCD + Ato group were treated with atorvastatin, the levels of lipid, GGT-1, ICAM-1 and VCAM-1 were suppressed. Meanwhile, the expressions of GGT-1, ICAM-1 and VCAM-1 were significantly decreased in the whole aorta plaques. CONCLUSIONS: The effect of statins on the expression of GGT in aorta plaque was firstly observed in animal model. The research shows that statins can significantly decrease the expression of GGT in aortic atherosclerotic plaques.

The relationship between serum hypoxia-inducible factor 1α and coronary artery calcification in asymptomatic type 2 diabetic patients.

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1), a master regulator of oxygen homeostasis, is a heterodimer consisting of HIF-1α and HIF-1ß subunits, and is implicated in calcification of cartilage and vasculature. The goal of this study was to determine the relationship between serum HIF-1α with coronary artery calcification (CAC) in patients with type 2 diabetes. METHODS: The subjects were 405 (262 males, 143 females, age 51.3 ± 6.4 years) asymptomatic patients with type 2 diabetes mellitus. Serum HIF-1α and interleukin-6 (IL-6) levels were measured by ELISA. CAC scores were assessed by a 320-slice CT scanner. The subjects were divided into 4 quartiles depending on serum HIF-1α levels. RESULTS: Average serum HIF-1α was 184.4 ± 66.7 pg/ml. Among patients with higher CAC scores, HIF-1α levels were also significantly increased (p <0.001). HIF-1α levels positively correlated with CRP, IL-6, UKPDS risk score, HbA1c, FBG, and CACS, but did not correlate with diabetes duration, age, and LDL. According to the multivariate analysis, HIF-1α levels significantly and independently predict the presence of CAC. ROC curve analysis showed that the serum HIF-1α level can predict the extent of CAC, but the specificity was lower than the traditional risk factors UKPDS and HbA1c. CONCLUSION: As a marker of hypoxia, serum HIF-1α level may be an independent risk factor for the presence of CAC. These findings indicate that elevated serum HIF-1α may be involved in vascular calcification in patients with type 2 diabetes mellitus.