ObjectiveTo evaluate whether AN69 ST membrane would prolong filter lifetime in continuous renal replacement therapy (CRRT) without anticoagulation in patients with high risk of bleeding.Methods A single-center, prospective, randomized, double-blind control trial with crossover design was conducted. From March 1st to December 31st in 2013, patients who were admitted to Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University meeting CRRT treatment indications, but could not receive systemic anticoagulation because of high risk of bleeding were studied. The selected patients were randomly divided into two groups according to a random number table, and four filters consisting of two AN69 ST100 membrane filters (A) and two traditional AN69 M100 membrane filters (B) were used for them. GroupⅠ with the filter order of A-B-A-B, and groupⅡ with the order of B-A-B-A. The clinical data of patients was recorded in detail, and conventional AN69 ST and AN69 membrane filter lifetime, their influence on coagulability, and the incidence of bleeding complications were compared.Results Seventeen patients were enrolled, with 10 in groupⅠ, and 7 in groupⅡ. The basic medical characteristics including gender, age, acute physiology and chronic health evaluationⅡ (APAECHⅡ) score, sequential organ failure score (SOFA), Acute Renal Injury Network (AKIN) stage, activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), platelet count (PLT), and use of mechanical ventilation were not significantly different between two groups. But the use of vasoactive drug was more frequent in groupⅡcompared with that of groupⅠ[100.0% (7/7) vs. 30.0% (3/10),χ2 = 8.330,P = 0.010]. AN69 ST filter lifetime (n =34) was (15.92±2.10) hours, there was no statistically significant difference compared with that of AN69 membrane (t = 0.088,P = 0.942), filter lifetime of which (n = 34) was (16.12±1.38) hours. It was also found by Kaplan-Meier survival analysis that there was no significant difference between the two membrane filter lifetime (χ2=1.589,P =0.208). Logistic regression analysis showed that the life of the first filter was not correlated with coagulation indicators, including APTT, PT, INR, and PLT [APTT: odds ratio (OR) = 0.977, 95% confidence interval (95%CI) = 0.892-1.071, P = 0.623; PT:OR = 1.001, 95%CI = 0.901-1.109,P = 0.988; INR:OR = 1.078, 95%CI = 0.348-3.340,P = 0.896;PLT:OR = 0.996, 95%CI = 0.974-1.019,P = 0.735]. The application rate of vasoactive drugs, which was different between two groups for basic medical indications showed no effect on filter life time (OR = 2.541, 95%CI = 0.239-26.955,P = 0.439). Reasons of clotting in filters were also analyzed, and it was found that blood coagulation in the filter ranked the top (88.2%), and the other reasons were catheter-related problems, death, and unscheduled transport. No difference in blood coagulation function was found in both groups after treatment for 12 hours, and there was no bleeding complication.ConclusionDuring the CRRT without systemic anticoagulant, both surface-treatment with polyethyleneimine AN69 and AN69 ST membrane cannot prolong filter lifetime.

ObjectiveTo investigate the extracorporeal clearance rate of imipenem in severe infection patients in the mode of continuous vena-venous hemofiltration (CVVH) during continuous renal replacement therapy (CRRT), in order to approach if the concentration of imipenem in plasma could achieve effective levels of anti-infection, and to explore the effect of time and anticoagulation measure on imipenem clearance during CRRT treatment.Methods A prospective observational study was conducted. All adult severe infection patients complicating acute kidney injury (AKI) in the Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University from March 2013 to September 2014, who were prescribed imipenem as part of their required medical care, and CRRT for treatment of AKI were enrolled. 0.5 g doses of imipenem was administered intravenously every 6 hours or 8 hours according to random number table, and infused over 0.5 hour. The unfractionated heparin was used for anticoagulation in the patients without contraindications, and no anticoagulation strategy was used in the patients with high risk of bleeding. At 24 hours after first time of administration, postfilter venous blood and ultrafiltrate samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 5, 6, and 8 hours after imipenem administration. The concentration of imipenem in above samples was determined with liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS).Results A total of 25 patients were enrolled. Thirteen patients received imipenem intravenously every 6 hours, and 12 patients, every 8 hours. The anticoagulation was conducted with heparin in 13 cases, and 12 cases without anticoagulation. The intra-day precision, inter-day precision, matrix effect, and recovery rate in low, medium, and high concentration of plasma and ultrafiltrate, and the stability of samples under different conditions showed a good result, the error of accuracy was controlled in the range of±15%. With the application of Prismaflex blood filtration system and AN69-M100 filter, under the mode with CVVH, the total clearance rate of imipenem was (8.874±2.828) L/h when the actual dose of replacement fluid was (31.63±1.48) mL·kg-1·h-1, the total CRRT clearance rate of imipenem in vitro was (2.211±0.539) L/h, which accounting for (30.1±15.7)% of the total drug clearance. In 6 hours interval dosage regimen, the percentages of the time> 4×minimum inhibitory concentration (MIC) at specific 4×MIC of 2, 4, 6, and 8μg/mL of imipenem were more than 40% of the dosing interval. But in the 8 hours interval dosage regimen, when the level was above the 4×MIC of 4μg/mL, maintaining time would drop below 40% of the dosing interval, with significant differences compared with that in 6 hours interval dosage regimen [4×MIC = 2μg/mL: (60.84±20.25)%vs. (94.01±12.46)%,t = 4.977,P = 0.001; 4×MIC = 4μg/mL: (39.85±15.88)% vs. (68.74±9.57)%,t = 5.562, P = 0.000; 4×MIC = 6μg/mL: (27.58±13.70)% vs. (53.97±8.36)%,t = 5.867,P = 0.000; 4×MIC = 8μg/mL:(18.87±12.43)% vs. (43.48±7.83)%,t = 5.976,P = 0.000]. No significant change in sieving coefficient of imipenem was found within a short time (6 hours), which indicated that there was no effect of anticoagulation on clearance of imipenem by AN69-M100 filter, and no statistical significance was found with repeated measure analysis (F = 0.186, P> 0.05).ConclusionsThe clearance rate of imipenem is increased significantly in vitro under the mode of CVVH with the actual dose of replacement fluid was (31.63±1.48) mL·kg-1·h-1 in severe infective patients with severe sepsis complicating AKI, affecting the level of plasma drug concentration, need to adjust the dosage regimen. When the time of the dosing interval was shortened, the concentration of imipenem in patients' plasma could be increased significantly. In a short period of time, the sieving coefficient of imipenem through AN69 filter is not affected by anticoagulation measures and time cleaning efficiency will not decline.

Objective:To investgate the ease effects of local injection of ursolic acid both on orthodontic tooth movement distance and tooth root resorption in the rats, and to clarify its mechanism.Methods:Ninety-six male Wistar rats were used to establish models of orthodontic tooth movement.After the successful establishment of models,all the model rats were randomly divided into 0 (control group),0.5,1.0 and 2.0 mmol·L-1 ursolic acid groups (n=24).The rats were locally injected with different doses of ursolic acid into the palatal submucosal area adjacent to the right upper first molar ,once per 3 d,each time 50μL.The rats were respectively sacrificed on the days 1,3,5,7,10,14,21 and 28,then the distances of tooth movement were measured.HE staining was used to observe the morphologic changes of the root tissue of rats.Results:The tooth movement distances of rats in control,0.5,1.0,and 2.0 mmol· L-1 ursolic acid groups were increased with the prolongation of time (P<0.01).Compared with control group,the tooth movement distances of rats in 0.5 mmol·L-1 ursolic acid group 3,7,14,21 and 28 d after forcing had statistical significance (P<0.05 or P<0.01 );the tooth movement distances of rats in 1.0 and 2.0 mmol· L-1 ursolic acid groups 1 d after treatment had no statistical significance (P>0.05),but at the other time points,the tooth movement distances of rats had statistical significance (P<0.01).The tooth movement distances of rats had statistical significance between 0.5,1.0 and 2.0 mmol·L-1 ursolic acid groups 5,7,10,14,21 and 28 d after forcing (P<0.05 or P<0.01).The morphological results showed that the resorption pits were found on the surface of tooth root with the prolongation of loading time;in addition,with the increasing of the doses of ursolic acid, the absorption of root surface was relieved. Conclusion:Local injection of ursolic acid at the doses of 0.5,1.0 and 2.0 mmol·L-1 can reduce the distance of orthodontic tooth movement in the rats, and the distance of tooth movement in the rats is reduced with the increasing of its doses,and ursolic acid has the ease effect on the orthodoutic tooth root resorption.

ObjectiveTo explore the correlation between butylphthalide and plasma brain-type creatine kinase isoenzyme (CK-BB),endothelin (ET),calcitonin gene related peptide (CGRP) in patients with acute cerebral infarction (ACI).MethodsSixty patients with ACI were divided into treatment group and control group with 30 cases each by random digits table method.Both groups received normal treatment continuously for 7 days,and butylphthalide of 200 mg was added to treatment group for 3 times per day.The levels of plasma CK-BB,ET and CGRP of two groups before and after treatment were measured and compared.ResultsThe levels of plasma CK-BB,ET of two groups both decreased significantly after treatment,but CGRP rose obviously.It showed significant differences before and after treatment of both groups (P ＜0.01 or ＜ 0.05).The levels of plasma CK-BB,ET of treatment group after treatment were lower than those of control group in the same period [(216.48±36.95) U/L vs.(333.07±54.03) U/L,(83.33±26.48)ng/L vs.(98.46±31.46) ng/L,P ＜ 0.05 ].The level of plasma CGRP of treatment group after treatment was significantly higher than that of control group in the same period [ (44.16±13.28 ) ng/L vs.(36.42±12.31 )ng/L,P ＜ 0.05 ].ConclusionButylphthalide can reduce the plasma enzyme activity,balance ET and CGRP,extend the cerebral arteries to antagonize ET,improve cerebral ischemia and cerebral hypoxia,which can protect brain cells and endothelial cells.

Objective To study the expression of gravin in the keloid and to investigate its probable role in the pathogenesis of keloid. Methods Skin biopsy was performed and skin samples were obtained from 18 normal human controls and 25 patients with keloid. The mRNA expression of gravin in specimens was detected by real-time fluorescent RT-PCR, and double immunofluorescence analysis was used to investigate the distribution of gravin protein in skin tissues. Results As detected by real time PCR, the relative expression of gravin mRNA was remarkably reduced in comparison with normal skin (0.4565±0.1728 vs 0.0953±0.0664, P<0.01). Results of double staining indicated that, in normal skin, gravin was primarily distributed in the cytoplasm of fibroblasts; while in keloid, it was observed mainly in macrophages and sporadically in fibroblasts. Conclusions Compared with the normal skin, keloid shows a different expression intensity and distribution of gravin, which might contribute to the development of keloid by regulating the proliferation of fibroblasts and activation of macrophages.

Objective To detect the incidence of inherited metabolic diseases(IMD)and disorders of metabo-lism in 4 710 high - risk infants,as well as providing basis of clinical diagnosis and treatment by using urease pretreat-ment - gas chromatography - mass spectrometry(UP - GC - MS). Methods Samples were collected from high - risk infants with IMD,after removing urea,putting in internal standard,removing protein,vacuum drying and bis (trimethyl - silyl)trifluoroacetamide / trimethyl - chlorosilane derivativing,UP - GC - MS was used to analyze compo-sitions such as organic acids,amino acids,carbohydrates,pyridoxines,purines and pyrimidines,then metabolic analysis was proceeded to refer to the normal detection value of the healthy children,finally a metabolic diagnosis was made ba-sing on the clinical data such as the high - risk clinical manifestations and general biochemical tests and other special examinations. Results In the 4 710 cases,there were 98 cases of IMD(2. 1% ),326 cases of suspected IMD(6. 9% ), 2 610 cases of metabolic disorders(55. 4% ). There were 98 cases of IMD,including 57 cases of methylmalonic aciduria,12 cases of propionic acidemia,7 cases of glutaric aciduria,5 cases of hyperphenylalaninemia,maple syrup u-rine disease and multiple carboxylase defects each,4 cases of isovaleric acidemia and 3 cases of 4 - hydroxy butyric acid urine disease. Conclusions UP - GC - MS is a effective way to diagnose IMD and metabolic disorders of infants. Common IMD in Guangdong Province include methylmalonic aciduria,propionic academia,glutaric aciduria,hyperphe-nylalaninemia,maple syrup urine disease and multiple carboxylase defects. The results of the tests can provide effective guidance for diagnosis and treatment of suspected infants.

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Objective To investigate the role of TNSALP gene detection in prenatal diagnosis of HPP. Method The clinical data and the results of complete exon sequencing of TNSALP gene in one neonate with low alkaline phosphatase (HPP) were analyzed retrospectively. Peripheral bloods from his family members were collected. The amniotic fluid cell in fetuses at 17 weeks was tested for candidate gene mutations by Sanger sequencing. Results Mainly manifestations in 6-day-old baby were multiple fractures, limb shortening and bending and dyspnea. He died of respiratory failure 9 days after birth. The serum alkaline phosphatase was decreased and serum calcium was decreased slightly; serum phosphorus, serum 25 hydroxyvitamin-D and parathyroid hormone were normal. X-ray showed that the whole body bone was very poorly mineralized, and the long diaphysis was enlarged with shape of a cup at the end and multiple fractures existed. Gene sequencing revealed a complex heterozygous missense mutation in the TNSALP gene, including the heterozygous missense mutation c.542C>T in exon sixth causing 181st amino acids changed from serine to leucine (p.S181L), and tenth exon heterozygous missense mutation in c.1016G>A causing 339th amino acid changed from glycine to glutamic acid (p.G339E). The parental phenotypes were normal. The c.542C>T mutation is inherited from his father and the c.1016G>A mutation is inherited from his mother. These two mutations were not detected in the fetus. Conclusion TNSALP gene analysis can be applied to the diagnosis and prenatal diagnosis of HPP.

Objective To explore the technique of maximum entropy model for extracting Oncomelania hupensis snail habi?tats in Poyang Lake zone. Methods The information of snail habitats and related environment factors collected in Poyang Lake zone were integrated to set up the maximum entropy based species model and generate snail habitats distribution map. Two Land?sat 7 ETM+remote sensing images of both wet and drought seasons in Poyang Lake zone were obtained,where the two indices of modified normalized difference water index(MNDWI)and normalized difference vegetation index(NDVI)were applied to ex?tract snail habitats. The ROC curve,sensitivities and specificities were applied to assess their results. Furthermore,the impor?tance of the variables for snail habitats was analyzed by using Jackknife approach. Results The evaluation results showed that the area under receiver operating characteristic curve(AUC)of testing data by the remote sensing?based method was only 0.56, and the sensitivity and specificity were 0.23 and 0.89 respectively. Nevertheless,those indices above?mentioned of maximum en?tropy model were 0.876,0.89 and 0.74 respectively. The main concentration of snail habitats in Poyang Lake zone covered the northeast part of Yongxiu County,northwest of Yugan County,southwest of Poyang County and middle of Xinjian County,and the elevation was the most important environment variable affecting the distribution of snails,and the next was land surface tem?perature(LST). Conclusions The maximum entropy model is more reliable and accurate than the remote sensing?based meth?od for the sake of extracting snail habitats,which has certain guiding significance for the relevant departments to carry out mea?sures to prevent and control high?risk snail habitats.

Objective To understand the epidemical patterns of schistosomiasis in Guichi District of Chizhou City，Anhui Province，in order to provide the reference for schistosomiasis control. Methods The annual data of schistosomiasis endemic situation in Guichi District from 1991 to 2011 were collected. The descriptive analysis was first conducted to describe the changes of schistosomiasis in local residents and the status of Oncomelania hupensis. An autoregressive integrated moving average （ARIMA）model was applied to fit and predict the tendency of schistosomiasis incidence in this region. Results The humanmorbidity increased with the increasing of the areas with snail habitats（P < 0.05），and four peaks（in 1992，1995，2005，2008）were detected. The difference of the area with snails among different types of snail habitats was statistically significant（F = 256.79，P < 0.05）. ARIMA（1，1，1）was determined to be the optimal model for analyzing the morbidity of schistosomiasis，and the short⁃term forecast of the morbidity in Guichi District from 2012 to 2015 showed that the predicted values were 0.017%，0.007%，0.012%，and 0.010%，respectively. Conclusions The endemic situation of schistosomiasis in Guichi District is controlled relatively well in the past two decades. However，the surveillance in the lake and marshland regions should be strengthened continuously to prevent the rebounding of the schistosomiasis endemic situation.