Objective:To explore the effect of probiotics on reducing ventilator-associated pneumonia (VAP) in sepsis patients.Methods:A total of 94 cases were randomly (random number) divided into the probiotic group ( n = 46) and the control group ( n = 48). All of the patients were given enteral nutrition therapy by nasogastric tube within 24-72 h after admission. And patients in the probiotic group were given live combined bifidobacterium, lactobacillus and enterococcus powder besides the regular therapy. The incidence of VAP, bacteremia, mortality, mechanical ventilation time and length of ICU stay were compared between the two groups. Results:Compared with the control group, the incidences of VAP and bacteremia in the probiotics group were significantly lower (χ 2=4.763, P=0.029; χ 2=4.438, P=0.035). There were no significant differences in 28-day mortality and the length of hospital stay between the two groups (χ 2=2.02, P=0.167; t=1.29, P=0.208). Mechanical ventilation time in the probiotics group was significantly shorter than that in the control group ( t=2.16, P=0.038). The Log-Rank test showed that the time of VAP-free in the probiotics group was significantly longer than that in the control group ( P < 0.05). After adjusting for APACHEⅡ score and age, COX proportional risk model analysis showed that the RR values of the probiotics group and the control group for 28-day VAP were 0.18 (95% CI: 0.12-0.74, P=0.025) and 0.21 (95% CI: 0.19-0.95, P=0.042), respectively. Conclusions:Probiotics treatment can reduce the incidence of VAP in sepsis patients.

OBJECTIVETo determine the potential urinary biomarkers of metabolic syndrome (MS) with early renal injury and establish diagnostic models by magnetic bead-based separation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).

METHODSParticipants were selected from the epidemiologic study on MS and renal involvement among residents in Pinggu district, Beijing. Eight-hour overnight urine samples were fractionated by means of magnetic bead-based weak cation exchange chromatography and subsequently analyzed with MALDI-TOF-MS. Wilcoxon test and random forests were used to screen differential protein peaks of MS patients with early renal injury, then combined with genetic algorithm and support vector machine, respectively, to establish diagnostic models.

RESULTSTotally 54 cases of MS without renal injury and 46 cases of MS with early renal injury were enrolled. Totally twenty protein peaks were up-regulated in the urine of MS patients with early renal injury by Wilcoxon test (P < 0.05); random forests algorithm revealed twelve protein peaks up-regulated in the urine of MS patients with early renal injury (importance value of mean decrease in accuracy > 0.005). Genetic algorithm based model showed 82.6% sensitivity, 84.3% specificity, and 83.5% accuracy by a 10-fold cross-validation in identifying MS patients with early renal injury; correspondingly, the support vector machine based model reported 89.2% sensitivity, 81.1% specificity and 85.5% accuracy. Four protein peaks were included in two diagnostic models with mass-to-charge ratios of 2756.98, 3019.11, 9077.04, and 10 054.26.

CONCLUSIONSThe urinary proteome patterns of MS with early renal injury were successfully established with magnetic bead-based separation and MALDI-TOF-MS technology. A series of urinary differential expressing protein peaks were identified with bioinformatics tools. Diagnostic models combining cluster of protein peaks are capable of differentiating MS patients with early renal injury from those without renal injury. The different urine protein excretion patterns revealed in this study provide urinary candidate biomarkers of MS patients with early renal injury for future identification and biological roles investigation.

Adult ; Biomarkers ; urine ; Chromatography, Ion Exchange ; methods ; Female ; Humans ; Kidney Diseases ; etiology ; urine ; Male ; Metabolic Syndrome ; complications ; urine ; Middle Aged ; Proteome ; analysis ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; Urine ; chemistry

The present study was to evaluate feasibility of a limited sampling strategy (LSS) in the prediction of inhibited hepatic CYP3A activity with systemic clearance of midazolam (MDZ), a hepatic CYP3A activity phenotyping probe. Rats were pretreated with a serial doses of ketoconazole, a selective inhibitor on CYP3A. Blood samples were collected and detected for MDZ at specified time points after intravenous injection of MDZ. Stepwise regression analysis and a Jack-knife validation procedures were performed in one group of rats as training set to establish the most informative LSS model for accurately estimating the clearance of MDZ. Another group of rats with same treatment was used as validation set to estimate the individual clearance based on predictive equations derived from the training set. Bland-Altman plots showed a good agreement between the systemic clearance calculated from DAS (CLobs) and corresponding parameter that was derived from three LSS models (CLest). LSS models derived from two or three sampling time points, including 60, 90 min, 30, 60, 90 min and 30, 60, 120 min, exhibited a good accuracy and acceptable error for estimating the CLobs of MDZ to evaluate hepatic CYP3A activity, especially the 60, 90 min LSS model is most accurate and convenient. The results supported that limited plasma sampling to predict the systemic clearance of MDZ is easier than the usual method for estimating CYP3A phenotyping when the hepatic activity of CYP3A is reduced in the rat. The present study provided theoretical basis and laboratory evidence for LSS to clinically evaluate metabolizing function of liver and
Animals ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; genetics ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Injections, Intravenous ; Ketoconazole ; administration & dosage ; pharmacology ; Male ; Metabolic Clearance Rate ; Midazolam ; blood ; pharmacokinetics ; Phenotype ; Random Allocation ; Rats ; Rats, Wistar

This study was purposed to investigate the effect of ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT) on erythroid lineage hematopoiesis. The changes of ABO group, IgM and IgG antibody in 16 patients received ABO-incompatible allo-HSCT were detected. The results showed that ABO-incompatible allo-HSCT were successfully engrafted in 16 patients, and there was no difference in reconstitution of platelets and neutrophils between ABO-incompatible and ABO-compatible transplantation (p > 0.05). The time of erythroid lineage reconstitution was prolonged (p < 0.05), the disappearance time of isoagglutinins against donor-type RBC in major and bidirectional ABO-incompatible recipients was correlated with the time of erythroid lineage reconstitution. It is concluded that ABO-incompatible allo-HSCT may lead to prolong recovery of erythroid lineage hematopoiesis. Before transplantation, the removal of anti-donor isoagglutinins by plasmapheresis or transfusion of donor's erythrocytes for neutralizing the isoagglutinins against donor's erythrocytes in the recipients may facilitate RBC engraftment and reduce erythrocyte transfusion.
ABO Blood-Group System ; immunology ; Adult ; Blood Group Incompatibility ; blood ; immunology ; Erythrocytes ; immunology ; Female ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Transplantation, Homologous

Objective To analyze the stage characteristics in the exercise behavior improvement of college students and explore the role of Process in the exercise behavior change based on the transtheoretical model, providing basis for the stage-matched intervention for the exercise behavior of college students. Methods There were 932 students who completed the questionnaires, from 5 universities in Shanxi Province were selected by using a stratified random cluster sampling method. Descriptive analysis was used to describe the exercise behavior of college students. Variance analysis and multivariate Logistic regression model were used to analyze the difference of the process of with stage of change among college students’ physical exercise. Multivariate variance analysis was used to analyze how personal characteristics affect process of change. Results Among all participants, 89.4% students knew the importance of physical exercise, and 29.4% students were satisfied with their physical exercise condition. The distribution of students’ physical exercise stage showed an inverted U-shape with left-side peak, and there was a significant difference between gender( 2=54.657, P<0.001). There were significant stage characteristics in the process of students' exercise behavior, gender had a significant main effects on mutual aid relation(F=7.400, P=0.07)and conscious control (F=7.778, P=0.005), gender and grade had interaction effects on social release (F=3.614, P=0.013). Conclusions The college students' exercise behavior showed the characteristics of “knowing but not to do”, which conformed to the Transtheoretical model. It is essential to develop targeted phased exercise intervention strategies according to the relationship between change of phase and change of procedure.

Objective: To compare the clinical effect of conventional polyvinyl chloride (PVC) endotracheal tube with silicone wire reinforced endotracheal tube to prevent ventilator-associated pneumonia (VAP) in mechanical ventilation patients. Methods: A total of 240 mechanical ventilation patients in the ICU were enrolled in this study, which were divided into two groups, PVC endotracheal intubation group (PVC group, n=113) and wire reinforced endotracheal intubation group (WR group, n=127). Gender, age, APACHEⅡ score, one-time success rate of intubation, intubation time, the rate of changing endotracheal, ventilation time, rate of tracheotomy and the incidence of VAP were compare between the two groups. Predictive factors for VAP were identified by the univariate and multivariate analyses in step-wise logistic regression model. Results: The rate of changing endotracheal tube in the PVC group was lower than that in the WR group (χ²=5.785, P=0.016); the mechanical ventilation time in the PVC group was shorter than that in the WR group (t=2.180, P=0.018); and compared with the WR group, the PVC group had significantly lower incidence of VAP (χ²=6.215, P=0.012). The univariate analysis showed that the selection of PVC endotracheal tube, APACHE Ⅱ score and mechanical ventilation time were the significant risk factors for VAP (P < 0.05). Multivariate analysis showed that the different selection of endotracheal tube and mechanical ventilation time were independent influencing factors of VAP (P < 0.05). Conclusions PVC tracheal tube can effectively reduce the incidence of VAP in patients with mechanical ventilation.

ObjectiveWe conducted a two-sample Mendelian randomization （MR） study to assess the causal relationship between circulating isoleucine， leucine and valine levels and the risk of peripheral atherosclerosis. MethodsBased on the large-scale genome-wide association study （GWAS） database， single nucleotide polymorphisms （SNPs） closely related to the circulating levels of isoleucine， leucine and valine were identified as instrumental variables （IVs）. Two-sample MR analysis applying the inverse variance weighted （IVW） method and the weighted median estimator （WME） method were performed to estimate the causal relationship between the risk of peripheral atherosclerosis and the exposure with more than three SNPs that were available as IVs. The pleiotropy was evaluated by using the MR-Egger regression and MR-PRESSO method， and the leave-one-out method was used in sensitivity analysis. ResultsFour， one and one SNPs were identified as IVs for circulating isoleucine， leucine and valine levels， respectively. For isoleucine， the IVW model demonstrated there was no evidence of heterogeneity among the IVs （P=0.715）， and there was a significant causal relationship between the increase of circulating isoleucine level and a higher risk of peripheral atherosclerosis risk. Per every 1 elevated standard deviation （SD） of circulating isoleucine level resulted in increasing 31% of peripheral atherosclerosis risk （OR=1.31， 95%CI： 1.07‒1.61）. Similarly， the OR（95%CI） was 1.33 （1.04‒1.71） in the WME model. The MR-Egger regression and MR-PRESSO analysis indicated no evidence of pleiotropy in IVs （all P>0.05）. The result of the leave-one-out sensitivity analysis was stable. The Wald ratio model displayed that the causal relationship between circulating leucine and valine levels and the risk of peripheral atherosclerosis was not statistically significant. The OR （95%CI） for leucine and valine was 1.13 （0.78‒1.63） and 1.11 （0.82‒1.50）， respectively. ConclusionThere is a significant causal relationship between the increase of circulating isoleucine level and a higher peripheral atherosclerosis risk. The causal relationships between circulating leucine and valine levels and the risk of peripheral atherosclerosis need to be further confirmed in future studies.

OBJECTIVETo explore F (13) A gene mutation in a pedigree with hereditary coagulation factor XIII (FXIII) deficiency.

METHODSThe FXIII deficiency was diagnosed by clot solubility test and other standard laboratory clotting tests. All exons, exon-intron boundary sequences of F(13) A gene were amplified by PCR and the products were sequenced directly. Any mutation identified by direct sequencing was confirmed by reverse sequencing. The mutation identified in the proband was screened in the family members.

RESULTSThe assays of PT, Qiulan, fibrinogen leveling, platelet counts, bleeding time were normal and the clot solubility test was positive in the proband. The homozygous deletion of 33 nucleotides (127067de133) in exon 10 of F(13) A gene which resulted in deletion of 11 amino acids in FXIIII A protein with 720aa residues was identified in the proband. Family studies showed that the mutation was inherited from the parents both of whom carried the heterozygous deletion mutation.

CONCLUSIONThe homozygous 127067de133 mutation of F(13) A gene is responsible for the disorder of the pedigree.

Adolescent ; Factor XIII ; genetics ; Factor XIII Deficiency ; genetics ; Heterozygote ; Homozygote ; Humans ; Male ; Pedigree ; Sequence Deletion

BACKGROUNDAngiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

METHODSTwo-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA).

RESULTSPAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels correlated significantly with PAR in overall patients (r = 0.109, P < 0.001). During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L).

CONCLUSIONSAT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

Aged ; Aged, 80 and over ; Angiotensin Receptor Antagonists ; therapeutic use ; Blood Platelets ; drug effects ; Blotting, Western ; Cell Line ; Cyclooxygenase 2 ; blood ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Platelet Aggregation ; drug effects ; Real-Time Polymerase Chain Reaction ; Tetrazoles ; therapeutic use ; Thrombosis ; blood ; drug therapy ; Thromboxane B2 ; blood ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

BACKGROUNDKnee osteoarthritis (KOA) is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling, stiffness, and movement disorders. The therapeutic goal is to alleviate or eliminate pain, correct deformities, improve or restore joint functions, and improve the quality of life. This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA.

METHODSThis multi-center, randomized, double-blind, double-dummy, parallel controlled trial, started from December 2011 to May 2014, was carried out in 6 cities, including Beijing, Shanghai, Chongqing, Changchun, Chengdu, and Nanjing. A total of 432 patients with KOA were divided into three groups (144 cases in each group). The groups were treated, respectively, with Zhuanggu joint capsules combined with celecoxib capsule simulants, Zhuanggu joint capsules combined with celecoxib capsules, and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively. The improvement of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment. Intergroup and intragroup comparisons of quantitative indices were performed. Statistically significant differences were evaluated with pairwise comparisons using Chi-square test (or Fisher's exact test) and an inspection level of α = 0.0167.

RESULTSFour weeks after treatment, the total efficacies of Zhuanggu group, combination group, and celecoxib group were 65%, 80%, and 64%, respectively, with statistically significant differences among the three groups (P = 0.005). Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu (P = 0.005) and celecoxib (P = 0.003) groups. The difference between the latter two groups was not statistically significant (P > 0.0167). Four weeks after discontinuation, the efficacies of the three groups were 78%, 95%, and 65%, respectively, with statistically significant differences (P < 0.0001). Intergroup pairwise comparisons revealed that the efficacy of the combination group was significantly better than that of the Zhuanggu and the celecoxib groups (P < 0.0001). The difference between the latter two groups was not statistically significant (P > 0.0167). The incidences of adverse events in Zhuanggu group, combination group, and celecoxib group were 8.5%, 8.5%, and 11.1%, respectively, with insignificant differences (P > 0.05).

CONCLUSIONSZhuanggu joint capsules alone or combined with celecoxib showed clinical efficacy in the treatment of KOA. The safety of Zhuanggu joint capsules alone or combined with celecoxib was acceptable.

TRIAL REGISTRATIONChinese Clinical Trial Registry, ChiCTR-IPR-15007267; http://www.medresman.org/uc/project/projectedit.aspx?proj=1364.

Adult ; Aged ; Celecoxib ; administration & dosage ; adverse effects ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy