2013年 · 第126卷第21期

Abstract：Background Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies,which exert important roles in the process of type 1 diabetes mellitus (T1D).Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.Methods Two hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited.GADA and IA-2A were detected at the time of diagnosis,one year later,3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.Results During the course of acute-onset T1D,the majority of patients remained stable for GADA or IA-2A,however,a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity.The prevalence of GADA was 56.3％ at diagnosis,decreasing to 50.5％ one year later,and 43.3％ 3-5 years later while the corresponding prevalence of IA-2A were 32.8％,31.0％ and 23.3％,respectively.The median GADA titers were 0.0825 at diagnosis,declining to 0.0585 one year later and 0.0383 3-5 years later (P ＜0.001),while the corresponding median titers were 0.0016,0.0010,0.0014 for IA-2A,respectively.Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h)levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P ＜0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.Conclusion Our data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients。

Abstract：Background The association between IGF2BP2 and type 2 diabetes mellitus (T2DM) has been repeatedly confirmed among different ethnic populations.However,in several genome-wide association studies (GWAS) from the Chinese Han population,the gene IGF2BP2 has not been replicated.The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population.It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.Methods Two single-nucleotide polymorphisms (SNPs,rs4402960 and rs1470579) in IGF2BP2 were genotyped in Chinese Han population (3807 controls/4531 T2DM cases) by Illumina GoldenGate Indexing assay.The association between SNPs and T2DM was evaluated by multiple Logistic Regression analysis.A meta-analysis was used to estimate the effects of IGF2BP2 in 20854 Chinese Han individuals.Results rs1470579 and rs4402960 were confirmed to have strong association with T2DM in the Chinese Han population (rs1470579 P=-1.80x10-7,OR (95％ CI)=1.22 (1.14-1.32),rs4402960 P=7.46x10-9,OR (95％ CI)=1.26 (1.17-1.37),respectively).Moreover,11 studies for rs4402960 were included in the meta-analysis and 7 studies for rs1470579.The meta-analysis also showed the association between T2DM and IGF2BP2 (rs1470579 OR of 1.15 (95％ CI=1.10-1.19),P ＜0.0001 under an additive model and rs4402960 OR of 1.14 (95％ CI=1.10-1.18),P ＜0.0001 under an additive model).Conclusion IGF2BP2 was strongly associated with the risk of T2DM in Chinese Han population。

Abstract：Background Studies have shown that complications in type 1 diabetes mellitus (T1DM) in children are mainly due to oxidative stress (OS).Lipid peroxidation is the main marker of OS and iso-prostaglandin is a reliable biomarker of lipid peroxidation in type 2 diabetes mellitus (T2DM).However,there have been few studies on OS in T1DM children with hyperglycemia and glucose fluctuations.Methods We prospectively enrolled 23 newly diagnosed T1DM patients and 23 age and sex matched healthy controls in Beijing Children's Hospital from May 2010 to January 2011.They were treated with continuous subcutaneous insulin injection (CSII) and monitored by continuous glucose monitoring system (CGMS).Twenty-four-hour urine samples were collected to measure the concentration of 8-iso prostaglandin F2α (8-isoPGF2α).Samples taken from diabetic children were collected at days 8 to 10 after insulin treatment.Intraday glucose fluctuations were assessed by mean amplitude of glucose excursions (MAGE),largest amplitude of glycemic excursions (LAGE),standard deviation of blood glucose (SDBG) and number of glycemic excursions (NGE).The correlations between glucose parameters and the index of oxidative stress were analyzed.Results Urine 8-isoPGF2α in the T1DM group was higher than that in the control group ((967.70±412.68) ng vs.(675.23±354.59) ng,P=0.019).There was a correlation between urine 8-isoPGF2α level and MAGE (r=0.321,P=-0.039),a significant correlation between low-density lipoprotein and urine 8-isoPGF2α level (r=0.419,P=0.03).There was no significant correlation between urine 8-isoPGF2α level and blood pressure,glycosylated hemoglobin (HbA1c),fasting C-peptide or other lipid indices.Conclusion A correlation between urine 8-isoPGF2α levels and MAGE and low-density lipoprotein was found in children newly diagnosed with T1DM。

Abstract：Background Evidences show that subclinical chronic inflammation is involved in the pathogenesis of diabetic nephropathy.The aim of this study was to examine the relationship between serum C-reactive protein (CRP),serum uric acid,and albuminuria in Chinese type 2 diabetic patients.Methods A total of 1162 type 2 diabetic patients were recruited.All participants had relevant clinical and laboratory measurements.CRP was measured using a particle enhanced immunoturbidimetric assay.Results In the multiple linear regression model,natural log-transformed CRP (InCRP) and uric acid were independent predictors of natural log-transformed urinary albumin to creatinine ratio (InACR) (β=0.18,95％ CI 0.10-0.27,P ＜0.001 and β=0.18,95％ CI 0.09-0.27,P ＜0.001).The interaction of InCRP with uric acid was also associated with InACR (β=0.04,95％ CI 0.02-0.06,P ＜0.001).In the full-adjusted logistic regression model,the OR for albuminuria of the patients in the third tertile levels of CRP and uric acid was 3.94 compared with patients in the first tertile levels of CRP and uric acid (95％CI 1.73-8.94,P ＜0.001).Conclusions Elevated serum CRP and increased serum uric acid level were associated with albuminuria in Chinese type 2 diabetic patients.Moreover,CRP and uric acid had an interactive effect on albuminuria。

Abstract：Background The probability and risk of operations increase in patients with type 2 diabetes mellitus.For diabetic patients,blood glucose control is a key factor to improving the prognosis of surgery.During perioperative period,insulin therapy is usually advised to be used for surgical patients with type 2 diabetes.However,the insulin regimen which one is better remains controversial.In this study,we estimated the efficacy,safety and advantage of different insulin therapy strategy during perioperative period.Methods A total of 1086 cases of surgical patients with type 2 diabetes mellitus enrolled in the present study.According to the glucose level at admission,all patients were divided into relatively high glucose group (group A,fasting blood glucose (FBG) ＜13.9 mmol/L) and higher glucose group (group B,FBG ＞13.9 mmol/L).Patients in group A randomly accepted premixed insulin twice a day,or basal insulin plus oral medications,and were divided into group A1 and A2 respectively.Patients in group B randomly received premixed insulin twice daily,basal insulin plus oral hypoglycemic agents,or basal insulin plus preprandial insulin,and were divided into group B1,B2 and B3 respectively.The data of the preoperative preparation time,the daily doses of insulin used in different periods,postoperative incision healed installments,hypoglycemic events,the total hospitalization time,postoperative complications were all collected and statistically analyzed.Results Compared the main outcome measures in groups treated by premixed insulin therapy,both in preoperative preparation and postoperative period,the daily insulin dosage and the frequency of hypoglycemic events were decreased in groups treated by basal insulin therapy (P ＜0.05).The preoperative preparation time and the total hospitalization time in groups with basal insulin therapy were shorter than that in groups with premixed insulin therapy (P ＜0.05).The incision healing rate of stage Ⅰ,Ⅱ and Ⅲ among different therapy protocols were significantly different (P ＜0.05).Conclusions Basal insulin therapy could be used in diabetic patients undergoing elective major and medium surgery during whole perioperative period.Basal insulin therapy strategy,including a single injection of basal insulin and basal insulin plus preprandial insulin injection subcutaneously,is superior to premixed insulin therapy in the perioperative blood glucose management,and it could be viewed as the best choice in glucose control during perioperative period。

Abstract：Background Depot medroxyprogesterone acetate (DMPA) as a hormonal contraceptive is highly effective and widely used,but it may reduce bone mineral density (BMD) and increase the risk of osteoporosis.We compared BMD between users of intramuscular DMPA and nonhormonal subjects.Methods The study included 102 women aged between 16 and 18 years using DMPA for 24 months and 97 women aged between 16 and 18 years using nonhormonal contraception as nonusers control group.BMD of the lumbar spine and femoral neck was measured every 12 months for 24 months using dual-energy X-ray absorptiometry,comparing mean BMD changes in DMPA users and nonusers.Results There were no significant differences between groups at baseline in age,gynecologic age,body mass index (BMI),lumbar spine BMD and femoral neck BMD,etc.At 24 months of DMPA treatment,the mean percentage change from baseline in lumbar spine and femoral neck BMD values had decreased by 1.88％ and 2.32％,respectively.The mean lumbar spine and femoral neck BMD in DMPA group at 24 months were not significantly different compared to baseline (P=-0.212 and P=0.106,respectively).In comparison,in nonhormonal control group,there was a trend toward increasing BMD.At 24 months of observation,the mean percentage change from baseline in lumbar spine and femoral neck BMD had increased by 2.08％ and 1.46％,respectively.There were no significant difference compared to baseline (P=-0.160 and P=-0.288,respectively).Mean BMD at the spine and femoral neck did not differ significantly between DMPA users and nonusers over 12-month,but the BMD values at both anatomical sites were significantly lower in DMPA users compared with nonusers after 24-month treatment (P=-0.009 and P=-0.009,respectively).Conclusion The evidence of our study suggested that the use of DMPA for short-term (＜12-month) has no significant effects on BMD at spine and femoral neck,but long-term exposure to DMPA may prevent the bone mass accrual in adolescents。

Abstract：Background Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops.Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types,its role in cytokine-induced pancreatic β-cell apoptosis remains unclear.The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis.Methods After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1,RINm5F (rat insulinoma cell line) cells were exposed to cytokines,interferon (IFN)-γ alone,IFN-γ+interleukin (IL)-1β,IFN-y+IL-1β+tumor necrosis factor (TNF)-α respectively.Pancreatic β-cell apoptosis was assessed by using MTT,FACS,and caspase-3 activity assays.Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS),NF-κB and Fas were analyzed by RT-PCR.Results Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-γ alone,IFN-γ+IL-1β and IFN-γ+TNF-α+IL-1β mediated apoptosis.Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein.Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels.Conclusion Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway。

Abstract：Background Oxidative Stress and p38 mitogen-activated protein kinase (p38MAPK) play a vital role in renal fibrosis.Pioglitazone can protect kidney but the underlying mechanisms are less clear.The purpose of this study was to investigate the effect of pioglitazone on oxidative stress and whether the severity of oxidative stress was associated with the phosphorylation level of p38MAPK.Methods Rat mesangial cells were cultured and randomly assigned to control group,high glucose group and pioglitazone group.After 48-hour exposure,the supernatants and ceils were collected.The protein levels of p22phox,p47phox,phosphorylated p38MAPK,total p38MAPK were measured by Western blotting.The gene expressions of p22phox,p47phox were detected by RT-PCR.The levels of intracellular reactive oxygen species (ROS) were determined by flow cytometry.The levels of superoxide dismutase (SOD) and maleic dialdehyde (MDA) in the supernatant were determined respectively.Results Compared with the control group,the expression levels of p22phox,p47phox,phospho-p38 and ROS significantly increased,activity of SOD decreased in high glucose group,while the level of MDA greatly increased (P ＜0.01).Pioglitazone significantly suppressed p22phox,p47phox expressions and oxidative stress induced by high glucose.The expressions of p22phox,p47phox,phospho-p38MAPK and ROS generation were markedly reduced after pioglitazone treatment (P ＜0.05).The activity of SOD in the the supernatant increased (P ＜0.05),while the level of MDA decreased greatly by pioglitazone (P ＜0.05).The level of oxidative stress was associated with the phosphorylation level of p38MAPK (P ＜0.01).Conclusion Pioglitazone can inhibit oxidative stress through suppressing NADPH oxidase expression and p38MAPK phosphorylation。

Abstract：Background Currently,migration has become one of the risk factors of high burden of tuberculosis in China.This study was to explore the influence of mass migration on the dynamics of Mycobacterium (M.) tuberculosis in Beijing,the capital and an urban area of China.Methods Three hundred and thirty-six M.tuberculosis strains from the Changping district,where the problem of urban migrants was more pronounced than in other Beijing regions,were genotyped by Spoligotyping,large sequence polymorphisms (LSPs 105 and 181),and variable number tandem repeat (VNTR) typing.Based on the genotype data,the phylogeny of the isolates was studied.Results In Changping district,the proportion of Beijing lineage M.tuberculosis isolates amounted to 89.0％ (299/336),among which 86.6 ％ (252) belonged to the modern lineage.The frequency of modern Beijing lineage strains is so high (around 75％ (252/336)) that associated risk factors affecting the tuberculosis epidemic cannot be determined.The time to the most recent common ancestor (TMRCA) of the Beijing lineage strains was estimated to be 5073 (95％ CI:4000-6200) years.There was no significant difference in the genetic variation of Beijing isolates from urban migrants and local residents.Conclusions The clone of modern Beijing lineage M.tuberculosis,which is dominant in the Beijing area,most likely started to expand with the five thousand-year-old Chinese civilization.In the future,with the urbanization in the whole of China,modern Beijing lineage M.tuberculosis may gain the larger geographical spread。

Abstract：Background Decreasing the intracranial pressure has been advocated as one of the major protective strategies to prevent spinal cord ischemia after endovascular aortic repair.However,the actual changes of cerebrospinal fluid (CSF) pressure and its relation with spinal cord ischemia have been poorly understood.We performed CSF pressure measurements and provisional CSF withdrawal after thoracic endovascular aortic repair,and compared the changes of CSF pressure in high risk patients and in patients with new onset paraplegia and paraparesis.Methods Four hundred and nineteen patients were evaluated for the risk of spinal cord ischemia after thoracic endovascular aortic repair.Patients with identified risk factors before the procedure constituted group H and received prophylactic sequential CSF pressure measurement and CSF withdrawal.Patients who actually developed spinal cord ischemia constituted group P and received rescue CSF pressure measurements and CSF withdrawal.Results Among the 419 patients evaluated,17 were graded as high risk.Four patients actually developed spinal cord ischemia after endovascular repair.The incidence of spinal cord ischemia in this investigation was 0.9％.The patients who actually developed spinal cord ischemia had no identified risk factors and had elevated CSF pressure,ranging from 15.4 to 30.0 mmHg.Six of the 17 patients graded as high risk had elevated CSF pressure:＞20 mmHg in two patients and ＞15 mmHg in four patients.Sequential CSF pressure measurements and provisional withdrawal successfully decrease CSF pressure and prevented symptomatic spinal cord ischemia in high-risk patients.However,these measurements could only successfully reverse the neurologic deficit in two of the patients who actually developed spinal cord ischemia.Conclusions Cerebrospinal fluid pressure was elevated in patients with spinal cord ischemia after thoracic endovascular aortic repair.Sequential measurements of CSF pressure and provisional withdrawal of CSF decreased CSF pressure effectively in high risk patients and provided effective prevention of spinal cord ischemia.Risk factor identification and prophylactic measurements play the key role in prevention of spinal cord ischemia after thoracic endovascular aortic repair。

Type 1 diabetes (T1D) is a chronic,multifactorial autoimmune disorder that is characterized by the progressive immune destruction to pancreatic β cells,which begins years before clinical onset.The latest survey showed that there are nearly 100 million patients with diabetes in China.1 At present,the therapy of this disease can not be carried out effectively aiming at etiology.Patients with T1D rely on insulin replacement treatment and bear huge risks of long-term complications and severe hypoglycemia。

Abstract：Background The change of glucose transporter 4 (GLUT4) expression could influence glucose uptake in the myocardial cells and then effect myocardial metabolism,which maybe one of the factor for the diabetes cardiovascular disease.This study aimed to explore the influence of glucose and insulin at different concentrations on H9c2 (2-1) cell proliferation and its GLUT4 expression in vitro,and evaluate the correlation between myocardial cells proliferation and GLUT4 expression.This might be helpful for understanding the relationship between glucose metabolism and cardiovascular disease.Methods According to glucose concentrations in culture medium,cultured H9c2 rat myocardial cells were divided into five groups:control group (NC,glucose concentration 5.0 mmol/L),low glucose group (LG,glucose concentration 0.1 mmol/L),high glucose group 1 (HG1,glucose concentration 10 mmol/L),high glucose group 2 (HG2,glucose concentration 15 mmol/L),high glucose group 3 (HG3,glucose concentration 20 mmol/L).Then according to different insulin concentrations in culture medium,each group was further divided into two subgroups:normal insulin subgroup (INSc,insulin concentration 3.8 mU/L),high insulin subgroup (INSh,insulin concentration 7.6 mU/L).H9c2 (2-1) cells were cultured for 1,2,3 days,the proliferation of cells were assayed by cell counting Kit-8 assay,the expressions of GLUT4 mRNA and protein were detected with RT-PCR and Western Blotting technique,and the relation between myocardial cells proliferation and GLUT4 expression was evaluated.Results Compared with NC group,cell proliferation (OD value) was lower in LG,HG2,HG3 group but higher in HG1 group on the second and the third day (P ＜0.05).There was a negative correlation between OD value and the glucose level in HG1,HG2,HG3 groups (P ＜0.05).OD value in INSc subgroups was lower than that in INSh subgroups (P ＜0.05).GLUT4 mRNA was lower in LG,HG2,HG3 groups than that in NC group (P ＜0.05).Compared with NC group,GLUT4 mRNA level in HG1 group was higher on the first day but lower on the second and third day (P ＜0.05).In HG1,HG2 and HG3 groups,GLUT4 mRNA level had a negative correlation with the level of glucose (P ＜0.05).GLUT4 mRNA in INSc subgroups was lower than that in INSh subgroups (P ＜0.05).The expression of GLUT4 protein was similar to that of GLUT4 mRNA.There was a positive correlation between H9c2 cell proliferation and GLUT4 expression (P ＜0.02).Conclusions Glucose levels could regulate glucose uptake in myocardial cells through influencing GLUT4 expression,and thus affected the cell proliferation and cell function.Insulin levels could affect the myocardial cell function by regulating GLUT4 expression.Effects of glucose and insulin on the myocardial cells proliferation might be mediated through regulating GLUT4 expression.There may be a mechanism of hyperglycemia pre-accommodation (HGPA) in myocardial cells mediated through regulation of GLUT4 expression。

Abstract：Background Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke.There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention.We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention.Methods This is a multicenter,randomized,parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months.Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen-depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules.The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded.The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination.Primary outcomes included all-cause mortality,any event of recurrent ischemic stroke/transient ischemic attack (TIA),hemorrhagic stroke,myocardial infarction and angina,and other noncerebral ischemia or hemorrhage.Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups.Comparison of median values between two groups was done by the Student t test,one-way analysis of variance (ANOVA),or non-parametric rank sum test.Results A total of 310 patients were enrolled,192 patients in the treatment group and 118 patients in the control group.Compared to the control group,the treatment group showed favorable outcomes in the Fg level,carotid IMT,the detection rate of vulnerable plaques,the volume of carotid plaques,NIHSS scores,and incidence of total vascular (6.78％ and 2.08％,respectively) and cerebral vascular events (5.93％ and 1.04％,respectively) (P ＜0.05).In the treatment group,the volume of carotid plaques was significantly related to the carotid IMT,the plaque diameter,width and number (P=0.000,0.000,0.000,0.022; F=13.51,2.52,11.33,-3.29,but there was a weak correlation with the Fg level (P=-0.056).After 1-year therapy,the incidence of overall vascular end points was reduced by 4.7％.Conclusion Long-term oral fibrinogen-depleting therapy may be beneficial for secondary ischemic stroke prevention。

Abstract：Background Hypertension is an important issue in Asia,responsible for up to 66％ of cardiovascular disease cases.This randomized controlled trial subgroup analysis compared telmisartan 80 mg (T80)/hydrochlorothiazide 25 mg (H25) singlepill combination with T80 monotherapy,specifically in Chinese and Korean patients.Methods Patients with grade 2/3 hypertension were randomized to receive telmisartan 40 mg (T40)/hydrochlorothiazide 12.5 mg (H12.5) combination or T40 monotherapy for one week,before uptitrating the dose to T80/H25 or T80,respectively,for the remaining 6 weeks.The primary endpoint was systolic blood pressure (SBP) mean change from baseline.Secondary endpoints included mean diastolic blood pressure (DBP) change from baseline,and blood pressure (BP) goal achievement.Adverse events were recorded.Results Of a total 888 patients who were treated,efficacy analyses for Chinese and Korean patients included 127 patients treated with T80/H25 and 54 patients treated with T80.At week 7,mean SBP reductions from baseline were -37.5 mmHg (1 mmHg=0.133 kPa) and-26.9 mmHg in the T80/H25 and T80 groups (adjusted mean difference,-10.6 mmHg; 95％ confidence interval (CO,-15.6 to-5.7).Mean DBP reductions were-19.0 and-14.1 mmHg in the T80/H25 and T80 groups (adjusted mean difference,-4.9 mmHg; 95％ CI,-8.0 to-1.8).In total,56.7％ of patients receiving T80/H25 achieved BP goal (＜140/90 mmHg) compared with 35.2％ receiving T80.SBP goal attainment (＜140 mmHg) and DBP goal attainment (＜90 mmHg) were also higher in the T80/H25 group compared with the T80 group (SBP:69.3％ vs.48.1％; DBP:62.2％ vs.46.3％).A small number of treatment-related adverse events were observed in both T80/H25 (nine patients,6.9％) and T80 monotherapy (two patients,3.6％) groups.Conclusions In Chinese and Korean patients with moderate-to-severe hypertension,treatment with T80/H25 provided large reductions in mean SBP and DBP,and high BP goal attainment rates.This once-daily combination is effective and well tolerated in this patient group.(ClinicalTrials.gov identifier NCT00926289)

Abstract：Background Cardiac surgery for congenital heart disease covers a wide spectrum from simple to complex cardiac and extracardiac malformations.Innovations in pediatric cardiac surgery and perioperative care over the past decades have allowed surgical correction or at least palliation in almost all complex congenital heart defects in the first years of life.Diaphragmatic paralysis (DP) due to phrenic nerve injury after congenital cardiac surgery is an important respiratory complication resulting with respiratory insufficiency,lung infections,prolonged hospital stay time and even death.Methods Between April 2001 and December 2010,among patients undergoing cardiac surgery for congenital heart disease,postoperative DP was diagnosed in 47/10 200 (0.46％) patients.Diaphragmatic placation was performed in 37/47 patients.DP was suspected in children who failed to wean from mechanical ventilation or in those with persistent respiratory distress when there is no cardiac cause.Decreased respiratory sounds in auscultation,paradoxical breathing during spontaneous ventilation and elevated hemidiaphragm on chest X-ray led us to use fluoroscopy,ultrasound and/or electromyogram (EMG).When chest X-rays did not have a diagnostic value in patients with persistent respiratory distress,bilateral DP was suspected and immediate fluoroscopy of EMG was performed for diagnosis.In all patients,diaphragmatic placation was performed using a thoracic approach,through the sixth or seventh intercostals space with lateral thoracotomy.Results A total of 47 patients (21 females and 26 males) with a median age of 7.21 months (range 0.27-71 months) were diagnosed DP after cardiac surgery.The incidence of DP was 0.46％ after cardiac surgery.The paralysed hemidiaphragm was left side in 26/47 (55.3％),right side in 17/47 (36.2％) and bilateral in 4/47 (8.5％) cases.The assisted ventilation time after cardiac surgery was (450±216) (116-856) hours.The median time from cardiac surgery to surgical placation was (24±14) (5-56) days.No patient died in this study.The follow-up period was (26.2±16.8) months.The position of the plicated diaphragm was normal on chest X-ray,in all plicated survivors within the 1st,6th and 12th months after discharge.Conclusions DP caused by phrenic nerve injury during surgical intervention for congenital heart disease is an important risk factor in terms of morbidity during the postoperative period.Diaphragmatic placation appears a good option,especially in newborns and small children,to wean patients from mechanical ventilation and to prevent long-term side effects of mechanical ventilation。

Abstract：Background Chronic kidney disease (CKD) is a growing public health problem with well-established risk factors.Other contributing factors,however,remain to be identified.Systemic inflammation in asthma plays a significant role in the development of other diseases.We therefore initiated a study to assess whether the growing prevalence of asthma is associated with an increase in the risk of CKD.Methods We conducted a retrospective cohort study using data from 3015 patients with asthma aged 14 years and older who were registered and followed up in Asthma Control Study at the Department of Respiratory Medicine of three medical centers from 2005 to 2011.History,asthma control test (ACT),and asthma stage were used to assess the traits of asthma.CKD was defined as proteinuria and/or reduced estimated glomerular filtration rate (eGFR) (＜60 ml·min-1·1.73 m-2) in two consecutive follow-up surveys.We used logistic regression models,adjusting for age,sex,and other confounding factor to determine associations between the traits of asthma and CKD.Kaplan-Meier curves were used to analyze patient outcomes.Results A total of 2354 subjects with complete data were recruited for this study with mean age (45.4±10.4) years.After 6 years of follow-up,9.6％ (n=227) of the analytic cohort developed proteinuria and 3.1％ (n=72) progressed to eGFR ＜60 ml·min-1·1.73 m-2.The patients with ＞20 years asthma history,not well-controlled or persistent asthma patients had higher incidence of proteinuria and reduced eGFR compared with patients with ＜20 years asthma history,at least well-controlled or remission asthma,respectively.The multivariable adjusted OR for proteinuria and reduced eGFR in participants with persistent asthma was 1.49; (95％ confidence interval (CI) 1.17-1.91) and 2.07 (95％ CI 1.34-4.42).Compared to patients with no asthma traits,there was a significant risk (OR,3.39; 95％ CI 1.36-8.73) for those who met all three traits,including asthma history ＞20 years,not well-controlled and persistent stage,after adjusting for potential confounding factors.Conclusions In this retrospective cohort study,we found that persistent asthma was associated with an increased risk of CKD,which was independent of obesity,diabetes,hypertension,and other well-established risk factors.Future studies should be directed to elucidate the mechanisms underlying the association between asthma and CKD。

Abstract：Background The aim of this research was to explore quality of life (QOL) and acceptance of disability and social support of colostomy patients as well as the relationship between these factors.Methods A descriptive,correlational study was conducted using four scales:the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and European Organization for Research and Treatment of Cancer Colorectal Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-CR38) scales,the Acceptance of Disability Scale (ADS),and the Social Relational Quality Scale (SRQS).A convenience sample of 111 colostomy patients from four hospitals in Guangzhou who underwent colostomy operation at least one month prior to the study and who visited the stoma clinic or association from August 2011 to February 2012 was evaluated for inclusion in the study.All statistical analyses were performed using SPSS 17.0 software (SPSS Inc.,Chicago,IL,USA).Results The patients' general health status was better than the reference level recommended by European Organization for Research and Treatment of Cancer,and the overall ADS score was average.The SRQS score was similar to that found in a Hong Kong study.The general health status and dimensions of QOL were significantly correlated with ADS and all of its dimensions (P ＜0.05).The general health status and dimensions of QOL were also significantly correlated with SRQS and all of its dimensions (P ＜0.05).Conclusions QOL,acceptance of disability,and social relational quality of colostomy patients were closely related.Our results emphasize that patients should work to form rational values and close bonds with families and friends to achieve a better QOL。

Abstract：Background Transient sublethal ischemia is known as ischemic preconditioning,which enables cells and tissues to survive subsequent prolonged lethal ischemic injury.Ischemic preconditioning exerts neuroprotection through phosphatidylinositol 3-kinase (PI3K)/Akt pathway.Cbl-b belongs to the Casitas B-lineage lymphoma (Cbl) family,and it can regulate the cell signal transduction.The roles of ubiquitin ligase Cbl-b and PI3K/Akt pathway and the relationship between them in oxygen-glucose deprivation preconditioning (OGDPC) in PC12 cells were investigated in the present study.Methods Oxygen and glucose deprivation (OGD) model in PC12 cells was used in the present study.The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay,nuclear staining with Hoechst 33258,and Western blotting were applied to explore the roles of Cbl-b and PI3K/Akt pathway and the relationship between them in OGDPC in PC12 cells.Results Cell viability was significantly changed by OGD and OGDPC.OGD significantly decreased cell viability compared with the control group (P ＜0.05),and preconditioning could rescue this damage was demonstrated by the increase of cell viability (P ＜0.05).The expression of Cbl-b was significantly increased after OGD treatment.However,the activation of Akt and GSK3β was greatly inhibited.Preconditioning could inhibit the increase of Cbl-b caused by OGD and increase the activation of Akt and GSK3β.LY294002,a specific inhibitor of PI3K,could effectively inhibit the increase of Akt and GSK3β after preconditioning treatment.It partly inhibited the decrease of Cbl-b expression after preconditioning treatment.Conclusion Ubiquitin ligase Cbl-b and PI3K/Akt pathway are differently involved in OGDPC in PC12 cells。

Abstract：Background Clostridium difficile-associated diarrhea (CDAD) is a major public health problem because of significant morbidity and mortality,and many clinicians pay attention to Lactobacillus as a potentially effective treatment.The purpose of this meta-analysis was to evaluate the efficacy of Lactobacillus in the prevention of CDAD.Methods The databases MEDLINE,the Cochrane Central Register of Controlled Trials,metaRegister of Controlled Trials,National Institutes of Health,CNKI,VIP,and Wanfang data were searched to locate all reported randomized controlled trials (RCT) from 1990 to December 2012.Only RCT in English and Chinese using Lactobacillus for the prevention of documented CDAD were considered for study inclusion.The data was analyzed by Review Manager and SPSS software.Results Seven placebo-controlled RCTs that evaluated the prevention of CDAD,which included 1486 subjects,accorded with inclusion and exclusion criteria.The mean age of the subjects ranged from 4.15 to 64.75 years and the proportion of male subjects ranged from 42.0％ to 59.1％.The total daily dose of Lactobacillus ranged from 1.2×109-1.2×1012 colonyforming units (CFU).A low risk of bias was attributed to two studies and four studies evaluated a medium-level risk of bias.The combined risk ratio (RR) of developing CDAD was significantly lower in subjects who received Lactobacillus compared with subjects who received placebo (RR 0.38,95％ confidence interval (CI) 0.22-0.67).A combination regimen of Lactobacillus acidophilus (L.acidophilus) and Lactobacillus casei (L.casei) (RR 0.05,95％ CI 0.01-0.36) showed significant effect sizes for the prevention of CDAD,while single regimens of Lactobacillus plantarum (L.plantarum)and Lactobacillus rhamnosus (L.rhamnosus) did not.Across all trials,positive significant effects of Lactobacillus were observed in the elderly subgroup (RR 0.05,95％ Cl 0.01-0.36).Whether the 1×1012-9×1012 CFU/d Lactobacillus could prevent CDAD significantly or not was unclear.Conclusion There is a sufficient evidence to recommend Lactobacillus (L.acidophilus and L.casei) as a prevention therapy for CDAD。

Clinical information of infections with the novel avian influenza A (H7N9) have been described elsewhere,1 but clinical variability,especially changes of mental status in the onset of infection,has rarely been reported in patients infected with H7N9.In this report,the initial clinical manifestations of three confirmed cases are summarized.Two of the patients were in critical condition。

To the editor:We successfully treated a case of 35-year-old female of severe rheumatic mitral valve stenosis with left atrial thrombus with mitral valve replacement,left atrial thrombus removal and tricuspid valve repair in puerperium.The patient had an uneventful hospital course and remains well。

To the editor:Recent evidence shows that renal sympathetic denervation can perform a promising role in attenuating the over-activity of sympathetic nerve system and treat related diseases.1-4 A 42 years old male patient suffering from 7 years history of paroxysmal palpitation was referred to our center.Basic heart disease was denied.The symptom was usually induced by exercise or intense emotion,which lasted about several minutes and was accompanied dizziness and fatigue。