ShuiJing Wu

Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients

IntroductionFungal infection is increasingly common in critical illness with severe sepsis, but the influence of invasive fungal infection (IFI) on severe sepsis is not well understood. The aim of this study was to investigate the impact that IFI has on the outcomes of critically ill surgical patients with severe sepsis in China by means of matched cohort analysis; we also evaluated the epidemiologic characteristics of IFI in this population.MethodsRecords for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis.ResultsA total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both Gram-positive and Gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P < 0.001), high hospital costs (P = 0.038), and prolonged stay in the ICU (P < 0.001) and hospital (P = 0.020).ConclusionIFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources.

Increased Genomic Copy Number of DEFA1/DEFA3 Is Associated with Susceptibility to Severe Sepsis in Chinese Han Population

Background:Human neutrophil peptides 1–3 are endogenous cationic antimicrobial peptides implicated in host defense against microbes. The genes encoding human neutrophil peptides 1–3 (DEFA1/DEFA3) exhibit copy number variations. This study was designed to determine whether DEFA1/DEFA3 copy number variations conferred susceptibility to infection-induced complications such as severe sepsis. Methods:This case–control study was performed in 179 patients with severe sepsis and 233 healthy blood donors and was replicated in an independent cohort of 112 cases and 118 controls. Plasma levels of human neutrophil peptides 1–3, tumor necrosis factor-&agr;, interleukin-6, and interleukin-10 were detected. Results:The genotype of DEFA1/DEFA3 with more than eight copies was more frequent in patients with severe sepsis than in controls (55.9% vs. 31.3%; P = 1.13 × 10−6, odds ratio 2.77, 95% confidence interval 1.85–4.16). After adjustment for age and gender, logistic regression analysis confirmed the association of the genotype of more than eight copies with an increased risk of severe sepsis (P = 2.25 × 10−5, odds ratio 2.66, 95% confidence interval 1.69–4.19). This established association was replicated in a second age- and gender-matched case–control cohort (P = 0.02, odds ratio 1.90, 95% confidence interval 1.11–3.27). Furthermore, compared with those with fewer copies, the patients carrying more than eight copies of DEFA1/DEFA3 presented significantly lower plasma levels of human neutrophil peptides 1–3, tumor necrosis factor-&agr;, interleukin-6, and interleukin-10 (P = 0.039, 0.017, 0.030, and 0.029, respectively). Conclusions:DEFA1/DEFA3 is an important genetic component participating in host immune response to severe sepsis. A higher copy number of DEFA1/DEFA3 (>8 copies) is significantly associated with the risk of severe sepsis.

Effect of CYP3A4*1G on the fentanyl consumption for intravenous patient-controlled analgesia after total abdominal hysterectomy in Chinese Han population.

What is known and Objective:  Clinical investigations into postoperative intravenous patient‐controlled analgesia (PCA) have indicated interindividual differences in fentanyl consumption. Cytochrome P450 3A4 (CYP3A4) is the main metabolism enzyme of fentanyl, and single nucleotide polymorphisms within the CYP3A4 gene may contribute to the variability of fentanyl analgesic efficacy. The aim of this study was to investigate whether the most common genetic variation in Chinese, CYP3A4*1G, has an impact on the fentanyl consumption for intravenous PCA in Chinese Han women undergone abdominal total hysterectomy.

Lack of association between TREM-1 gene polymorphisms and severe sepsis in a Chinese Han population

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. Blocking of TREM-1 can protect against sepsis in mice. To date, the predisposition of TREM-1 gene polymorphisms to sepsis has not been reported. This study was designed to investigate whether TREM-1 genomic variations were associated with the development of severe sepsis. Three common polymorphisms (rs7768162, rs9471535, and rs2234237) within the TREM-1 gene were detected in 175 patients with severe sepsis and in 139 healthy control subjects. Neither allelic frequencies nor genotype distributions of the assayed single nucleotide polymorphisms were found to be significantly different between patients and controls as well as between surviving and nonsurviving patients in different models of inheritance. The distributions of estimated haplotype patterns were also comparable between the defined groups. The present findings suggest that the three studied polymorphisms within the TREM-1 gene may not play a major role in the predisposition to severe sepsis in a Chinese Han cohort. Further replication studies with large sample size to achieve sufficient power (80%) to dismiss these polymorphisms as candidate markers for severe sepsis are warranted.

Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients.

Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.

Nuclear factor-κB mediated lipopolysaccharide-induced mRNA expression of hepcidin in human peripheral blood leukocytes

Hepcidin is a known key modulator of iron homeostasis and an innate immune molecule secreted by the liver. The transcriptional mechanism of hepcidin in hepatocytes during inflammation is mediated via the IL-6/STAT3 pathway. Recently, hepcidin demonstrated an anti-inflammatory function in endotoxic mice, and a TLR4-dependent inducible expression of hepcidin was detected in myeloid cells. In this study, we explored the expression and signaling mechanism regulating hepcidin mRNA expression in peripheral blood leukocytes. The mRNA levels of hepcidin in peripheral blood leukocytes from patients with severe sepsis (n = 14) was significantly higher than those in healthy controls (n = 16;0.286 ± 0.065 vs 0.068 ± 0.025; P < 0.05). Ex vivo studies found hepcidin mRNA can be highly induced by challenge of 100 ng/ml LPS or 20 ng/ml TNF-α in peripheral blood leukocytes rather than IL-6, IL-1 and IFN-γ. Anti-TNF-α antibody significantly decreased the levels of hepcidin mRNA induced by LPS. Inhibitor of nuclear factor (NF)-κB rather than that of STAT3 completely abolished the inducibility of hepcidin mRNA in PBMCs and neutrophils. These results indicate that hepcidin mRNA expression in peripheral blood leukocytes induced by LPS depends on NF-κB, and TNF-α may be a key mediator in this procedure.

Theoretical study on electronic structures and spectroscopic regularities of ethylated single-walled carbon nanotubes

The electronic structures of a series of ethylated single-walled carbon nanotubes (SWCNTs) were studied using density; function theory (DFT) at B3LYP/6-31G(d) level. The bond vertical to the main axis of the SWCNT was predicted to be the most thermodynamically stable additive site by ethylene. The energy gaps of the ethylated SWCNTs decrease with the decrease in the symmetries after the addition. The C-C and C=C stretching vibrations in the IR spectra of the ethylated SWCNTs, compared with those in the IR spectra of the pristine SWCNTs, are red-shifted. The chemical shifts at 172.9 ppm of the bridged carbon atoms in the NMR spectrum of (3,3)-C2H4(v) (C36C2H4) are shifted downfield in comparison with those at 144.7 ppm of the same carbon atoms in (3,3) (C36). Meanwhile, (3,3)-C2H4(v) (C36C2H4) shows a weakened anti-aromaticity owing to a nuclear independent chemical shift (NICS) at 3.6 ppm, relative to the NICS value at 6.3 ppm of (3,3) (C36).

Genomic polymorphisms within alpha 7 nicotinic acetylcholine receptor and severe sepsis in Chinese Han population.

Alpha 7 nicotinic acetylcholine receptor, a kind of ligand‐gated ion channel mainly expressed in macrophages, plays a crucial role in improving survival in sepsis via suppressing proinflammatory cytokines. The predisposition of genomic polymorphisms within alpha 7 nicotinic acetylcholine receptor gene (CHRNA7) to sepsis has not been investigated. The current association study was performed to analyse six common genetic variations within 5′‐upstream region of CHRNA7 gene in 229 patients with severe sepsis and 267 controls. Neither allelic frequencies nor genotype distributions were significantly different between patients and controls, as well as between surviving and nonsurviving patients. The frequencies of estimated haplotypes were also comparable between above defined groups. The present study suggests that genomic polymorphisms in the 5′‐upstream region of CHRNA7 gene may not be a major risk factor for severe sepsis in Chinese Han population.

Polymorphisms of the HTR3B gene are associated with post-surgery emesis in a Chinese Han population.

The serotoninergic receptor 5‐hydroxytryptamine (serotonin) receptor 3 (HTR3) is instrumental in the regulation of nausea and emesis (vomiting).This study investigated whether common genomic variations of the A and B subunits of HTR3 (HTR3A, HTR3B) are associated with the incidence of post‐operative vomiting in a Chinese Han population.

Tai Chi Exercise for Patients with Chronic Heart Failure: A Meta-analysis of Randomized Controlled Trials.

Aim This meta-analysis aimed to update and evaluate evidence from randomized controlled trials of tai chi for patients with chronic heart failure. Method Both English and Chinese databases were searched from their inception to June 2, 2016 (PubMed, EMBASE, Cochrane Central Register of Controlled Trials for English publications and China Knowledge Resource Integrated, Wanfang, and Weipu databases for Chinese publication). Titles, abstracts, and full-text articles were screened against study inclusion criteria: randomized controlled trials studying tai chi intervention for patients with chronic heart failure. The meta-analysis was conducted with Revman 5.3 or STATA 12. Result Thirteen randomized controlled trials were included. Tai chi induced significant improvement in 6-min walking distance (51.01 m; 30.49–71.53; P < 0.00). Moreover, tai chi was beneficial for quality of life (−10.37 points; −14.43 to −6.32; P = 0.00), left ventricular ejection fraction (7.72%; 3.58–11.89; P = 0.003), and B-type natriuretic peptide (−1.01; −1.82 to −0.19; P = 0.02). Conclusion Despite heterogeneity and risk of bias, this meta-analysis further confirms that tai chi may be an effective cardiac rehabilitation method for patients with chronic heart failure. Larger, well-designed randomized controlled trials are needed to exclude the risk of bias.