Correlation between protein C -1641A/-1654C haplotype and coagulation disorder in sepsis / 中华急诊医学杂志

Objective:To investigate the correlation between protein C -1641A/-1654C haplotype and coagulation disorder in Chinese Han septic patients.Methods:The genotypes of protein C gene -1641A>G (rs1799809) and -1654C>T (RS1799808) in septic patients were detected by direct sequencing, and their haplotypes were analyzed and divided into two groups according to the haplotype, -1641A/-1654C (AC) carriers and non-AC haplotype carriers. At the same time, unpaired t test or Mann-Whitney U test was used to compare the differences in coagulation/fibrinolytic parameters, including partial activated thrombin time, prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer levels, as well as APC levels between the two groups. Results:A total of 174 septic patients were included in this study, including 60 AC haplotype carriers and 114 non-AC haplotype carriers. Compared with non-AC haplotype carriers, AC haplotype carriers had significantly lower platelet counts, significantly longer partial activated thrombin time, and significantly decreased activated protein C levels. Other coagulation/fibrinolytic parameters including prothrombin time, internationally standardized ratio of prothrombin time, thrombin time, fibrinogen and D-dimer were not significantly different between the two groups.Conclusions:In this study, the protein C-1641A/-1654C haplotype was found to lead to decreased circulating activated protein C levels decreased platelet counts, and prolonged partial activated thrombin time in septic patients. These results suggest that the protein C-1641A/-1654C haplotype may directly affect the APC level and consequently influence the coagulation disorder of sepsis.

Correlation between single nucleotide polymorphism of TET2 gene and susceptibility and prognosis of sepsis / 中华急诊医学杂志

Objective@#To investigate the association of SNPs in TET2 gene with the susceptibility and prognosis of sepsis.@*Methods@#Ninety-nine patients diagnosed with sepsis and 107 controls were enrolled in the study. The septic patients were further divided into survivors (56 cases) and non-survivors (43 cases) according to the outcome of 28-day hospitalization. Patients without sepsis after major surgery were enrolled as the controls. The genotypes of the five loci (rs6839705, rs7670522, rs7679673, rs7698522 and rs10010325) with high minor allele frequency in the TET2 were screened according to the existing research reports and the SNP database of the NCBI website. The five loci were detected by TaqMan probe based allelic discrimination assays using real-time polymerase chain reaction (PCR). The data were calculated for genetic association study through χ2 test and Fisher’s exact probability method.@*Results@#There was no significant difference in genotype frequencies of the five tested SNPs in TET2 gene between septic patients and controls or between survivors and non-survivors in septic patients (P > 0.05). Furthermore, the allelic frequencies of the five SNPs between septic patients and controls or between survivors and non-survivors in septic patients also had no significant difference (P > 0.05).@*Conclusions@#This study showed that the five SNPs in TET2 gene (rs6839705, rs7670522, rs7679673, rs7698522, and rs10010325) were not associated with the susceptibility and prognosis of sepsis, which needs to be further confirmed by large-sample studies.

Correlation between single nucleotide polymorphism of TET2 gene and susceptibility and prognosis of sepsis / 中华急诊医学杂志

Objective To investigate the association of SNPs in TET2 gene with the susceptibility and prognosis of sepsis.Methods Ninety-nine patients diagnosed with sepsis and 107 controls were enrolled in the study.The septic patients were further divided into survivors (56 cases) and non-survivors (43 cases) according to the outcome of 28-day hospitalization.Patients without sepsis after major surgery were enrolled as the controls.The genotypes of the five loci (rs6839705,rs7670522,rs7679673,rs7698522 and rs10010325) with high minor allele frequency in the TET2 were screened according to the existing research reports and the SNP database of the NCBI website.The five loci were detected by TaqMan probe based allelic discrimination assays using real-time polymerase chain reaction (PCR).The data were calculated for genetic association study through x2 test and Fisher's exact probability method.Results There was no significant difference in genotype frequencies of the five tested SNPs in TET2 gene between septic patients and controls or between survivors and non-survivors in septic patients (P ＞ 0.05).Furthermore,the allelic frequencies of the five SNPs between septic patients and controls or between survivors and non-survivors in septic patients also had no significant difference (P ＞ 0.05).Conclusions This study showed that the five SNPs in TET2 gene (rs6839705,rs7670522,rs7679673,rs7698522,and rs10010325) were not associated with the susceptibility and prognosis of sepsis,which needs to be further confirmed by large-sample studies.

A study on effects of immediate bone grafting at mandibular first molar fresh extraction socket on maintaining alveolar bone height after space closure / 中华口腔医学杂志

Objective@#To investigate the effect of immediate bone grafting at mandibular first molar extraction socket on maintaining alveolar bone height after space closure.@*Methods@#Thirty adult orthodontic patients who need to extract mandibular first molar, totally 38 target teeth, were included. The samples were divided into two groups randomly: graft group and non-graft group. All extraction space was closed orthodontically. Dental models of all patients were taken before extraction (T0), before space closure(T1) and after space closure (T2). The distance, time of the space closure and the velocity of tooth movement were recorded. Probing depth (PD) and clinical attachment level (CAL) at six sites (mesial buccal, buccal, mesial lingual, lingual, distal buccal and distal lingual) on adjacent teeth were measured before extraction (T0) and after space closure (T2). Cone-beam CT (CBCT) was taken at T0 and T2 to compare the changes of alveolar bone height at six sites on adjacent teeth using Invivo Dental 5.0 software.@*Results@#The extraction space in both graft group and non-graft group was closed successfully. However, the space in graft group was closed more slowly than in non-graft group. In graft group, PD and CAL at the six sites on both the second molar and the second premolar did not change significantly after space closure, and CBCT showed that the alveolar bone height of the second premolar had no significant difference after treatment. In non-graft group, alveolar bone height decreased in both adjacent teeth and periodontal attachment loss was found after space closure. On average, alveolar bone height and periodontal attachment of the second premolar decreased (0.75±0.16) mm and (0.64±0.15) mm, respectively. Meanwhile, alveolar bone height and periodontal attachment of the second molar decreased (0.79±0.23) mm and (0.80±0.24) mm, respectively.@*Conclusions@#Bone graft immediately after mandibular first molar extraction could delay alveolar bone resorption and preserve the periodontal attachment of the adjacent teeth during space closure. However, the procedure could slow down tooth movement.

Association of single nucleotide polymorphism in exon of transient receptor potential melastatin 2 gene with sepsis / 浙江大学学报·医学版

To investigate the association between single nucleotide polymorphism (SNP) in the 11th exon of transient receptor potential melastatin 2 (TRPM2) gene with the susceptibility and outcome of sepsis.A total of 119 septic patients and 112 normal subjects were enrolled from the First Affiliated Hospital, Zhejiang University School of Medicine. Among 119 septic patients, 62 died (fatal group) and 57 survived (survival group) within 28 days of disease onset. The genotypes of these individuals were detected using TaqMan allelic discrimination assays, and its correlations with susceptibility and outcome of sepsis were analyzed.There was no significant difference in genotype frequencies and allelic frequencies of TRPM2 SNP rs1556314 between septic patients and the controls (all>0.05). And no significant difference in genotype frequencies and allelic frequencies of TRPM2 SNP rs1556314 was observed between the survivors and fatal cases of septic patients (all>0.05).The TRPM2 SNP rs1556314 does not have significant association with sepsis, but this result need to be confirmed by large scale studies.

Studying the association of plasma S100A12 and noninfectious pulmonary complication in infants and young children following cardiopulmonary bypass / 中华急诊医学杂志

Objective To examine the kinetics of plasma S100A12 and soluble receptor for advanced glycation end products (sRAGE) in infants and young children undergoing cardiopulmonary bypass ( CPB),and to investigate whether they could protective the occurrence of noninfectious pulmonary complication (NPC) after cardiac surgery.Methods This was a case-control study.The subjects included all children aged ＜3 years old who underwent cardiac surgery with CPB during the period from June 1st to July 31st 2011.The patient who showed pulmonary inflammation or had abnormal liver or renal function before surgery was excluded.The remain patients were divided into 2 groups according to whether they had developed NPC postoperatively.Twenty patients were grouped into NPC because they developed the complications of pleural effusion,chylothorax,partial lung collapse,pulmonary hypertensive crisis,airway disorders,pneumothorax,pneumomediastinum,or phrenic nerve palsy.Forty patients were categorized into the no-NPC group.Plasma concentrations of S100A12 and sRAGE were measured using ELISA at baseline,before CPB,immediately after CPB,1 h,12 h and 24 h after operation.Differences concentrations between two groups were analyzed with t test.A stepwise logistic regression analysis was used to indentify the independent risk factor for NPC.A P value ＜0.05 was considered statistically significant.Results Plasma levels of S100A12 and sRAGE dramatically increased immediately after CPB ( P ＜ 0.01 ).The levels of sRAGE dropped to lower than baseline level (P ＜0.05),while S100A12 was still at high level 24h after operation (P ＜0.01 ).Levels of S100A12 and sRAGE immediately after CPB in NPC group were significantly higher than the no-NPC group (P ＜ 0.05).Twenty-four hours after operation,levels of S100A12 were still higher in NPC group than no-NPC (P ＜ 0.01 ),while levels of sRAGE were similar in the two groups ( P ＞ 0.05 ).In the stepwise logistic regression analysis,plasma S100A12 level immediately after CPB remained as a independently predictor for postoperative NPC (OR =1.042,95％ CI:1.010 ～ 1.076,P =0.011 ).Levels of S100A12 immediately after CPB were positively associated with mechanical ventilation time ( r =0.47,P ＜ 0.01 ),duration of surgical Intensive Care Unit ( r =0.407,P =0.002) and hospital stay ( r =0.421,P =0.01 ).Conclusions Plasma levels of S100A12 and sRAGE were significantly increased immediately after CPB and the elevated plasma S100A12 immediately after CPB served as an early reliable biomarker of the occurrence and the prognosis of NPC after CPB in infants and young children.

Correlation of human β-defensin 1 gene polymorphism with fungal susceptibility to severe sepsis / 中华创伤杂志

Objective To investigate the correlation between gene polymorphism within human β defensin 1 (DEFB1) and fungal susceptibility to severe sepsis through case-control association study.Methods A total of211 patients with severe sepsis in ICU were enrolled in the present case control study. Sepsis in this study was diagnosed according to the definition of American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference in 1992 and 2002. Based on the development of fungal infection during ICU stay, all 211 patients were divided into fungal infection group (Group Ⅰ) and control group (Group C). Alleles and genotypes of-1816A/G, -390A/T, -52A/G, -44C/G and-20A/G within DEFB1 gene were assayed in all 211 patients by means of DNA direct sequencing, Allele-specific PCR amplifications or high-throughput site-specific TaqMan assay. Genetic analysis was employed to calculate the distribution frequency of haplotypes. The correlation between the genomic variations (allele,genotype and haplotype) and fungal infection was analyzed by Chi-square test or Fisher's exact test.Odds ratio (OR) was employed to reflect the correlation degree of genetic factor with fungal susceptibility to severe sepsis. Results Group Ⅰ enrolled 80 patients, of whom 43 pstients were male, at age of (60.81 ± 18.30) years. Group C enrolled 131 patients, of whom 80 patients were male, at mean age of (60.42 ± 17.03) years. No significant difference was found between two groups in aspect of gender and age (P＞0.05). The genetic locus of -1816A/G, -390A/T, -52A/G, -44C/G and -20A/G of both groups were in agreement with Hardy Weinberg equilibrium. No significant difference was found between two groups in the distribution of allelic frequencies and genotype frequencies (P ＞0.05). No significant difference was found in the distribution frequency of four common haplotypes of the above five genetic locus such as AAACG, ATGCA, GTGGG and ATACG (all P ＞ 0.05). Conclusions Genetic locus of -1816A/G, -390A/T, -52A/G, -44C/G and-20A/G within DEFB1 gene have no correction with fungal infections in severe sepsis, suggesting that DEFB1 gene polymorphism may not serve as a key genetic marker for the predisposition to fungal infection in severe sepsis.

IL-10 polymorphism is associated with increased incidence of severe sepsis / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether three biallelic polymorphisms at positions -592, -819 and -1082 in the promoter region of the IL-10 gene are associated with increased incidence of severe sepsis.</p><p><b>METHODS</b>The IL-10 -592, -819 and -1082 polymorphisms were typed using polymerase chain reaction followed by digestion with the restriction enzymes RsaI, MaeIII and MnlI, respectively.</p><p><b>RESULTS</b>Patients with severe sepsis were more likely to have IL-10 -1082 allele 1, compared with controls (P < 0.05). Genotype distribution of the IL-10 -1082 polymorphism significantly differed between patients and controls (P < 0.05). However, the allele frequencies and genotype distribution of the IL-10 -1082 polymorphism did not differ between surviving and dead patients (P > 0.05). No significant differences in the genotype distribution and allele frequencies of the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with severe sepsis and healthy controls, nor between surviving and dead patients (P > 0.05).</p><p><b>CONCLUSIONS</b>The polymorphism at position -1082 in the promoter region of the IL-10 gene may be associated with susceptibility to severe sepsis. In contrast, the other two highly linked IL-10 polymorphisms are not associated with incidence or the outcome of severe sepsis.</p>

Differential expression of ?-and ?-defensin in human peripheral blood / 中华麻醉学杂志

Objective To examine the expression of a- and ?-defensin genes in human peripheral leukocytes. Methods Fifty-one healthy blood donors were studied. Peripheral leukocytes were stimulated by lipopolysaccharide ( LPS) 100 ng?ml-1 ex vivo. The level of defensin mRNA expression in the leukocytes were assessed after being incubated with LPS for 0 (baseline), 1, 3, 6, 12, 24 h by semi-quantitative RT-PCR. Southern blot analysis and sequencing were used to confirm the identity of defensin gene transcripts. Results Expression of ?-defensin 1-3 mRNA was detected in all donors studied, but no ?-defensin mRNA expression was detected in peripheral leukocytes before LPS-stimulation. Expression of ?-defensin-1 gene was detected in the leukocytes after being incuaated with LPS for 3 h in 45 of 51 donors (88.2% ) and ?-defensin-2 mRNA expression was positive in 20 donors (39.2 % ), but no ?-defensin-3 mRNA expression was detected. The levels of ?-defensin-1 and-2 mRNA peaked at 6 h and started decreasing at 12 h. In contrast there was no significant change in ?-defensin 1-3 mRNA in peripheral leukocytes after LPS-stimulation. Conclusion In human peripheral leukocytes ?-defensin-1 and-2 genes are induced transiently by LPS-stimulation;whereas ?-defensin 1-3 genes are constitutive. The induced expression of ?-defensin-1 and-2 genes show inter-individual variability.

Effects of cardiopulmonary bypass on plasma levels of procalcitonin and cytokines / 中华麻醉学杂志

ve To investigate the changes in perioperative levels of circulating procalcitonin (PCT), TNF-?, IL-6, IL-8 and IL-10 in patients undergoing valve replacement with cardiopulmonary bypass (CPB) .Methods Sixteen patients (7 male, 9 female) aged (38.5?5.1) years and weighing (42.9?10.2) kg, undergoing valve replacement under CPB were chosen in this study as CPB group and seven male patients aged (32.6?5.1) years and weighing (58.3?4.4) kg undergoing pericardectomy were enrolled in this study as non-CPB group. Patients with infection or immunodeficiency and those who had received corticosteroid and drugs which may affect immune function were excluded. Premedication consisted of intramuscular midazolam 0.1 mg/kg and morphine 0.1 mg/kg. Anesthesia was induced with midazolam 0.15mg/kg, fentanyl 8?g/kg and vecuronium 0.1mg/kg and maintained with 0.8%-1.2% isoflurane inhalation and intermittent iv boluses of fentanyl and vecuronium. Blood samples were taken from CVP line before induction of anesthesia, 5 min after tracheal intubation, before CPB, immediately after discontinuation of CPB, and on 1st, 3rd, 5th, 7th postoperative day for determination of plasma PCT, TNF-?, IL-6, IL-8, and IL-10 levels. Results In CPB group plasma TNF-?, IL-6, IL-8 and IL-10 levels increased significantly immediately after CPB and returned to the baseline levels on the 3rd postoperative day, while plasma PCT concentration increased significantly after operation and reached its peak level of (10.62?3. 51) ng/ml on the 1st postoperative day. In non-CPB group there was a similar trend of changes in PCT , IL-6, IL-8 and IL-10 but to a much lesser extent.Conclusions CPB leads to a pro- and anti-inflammatory response, as well as procalcitonin release. PCT may play an important role in the systemic inflammation induced by CPB.