2013年 · 第126卷第17期

For over 100 years,medical education has achieved continuous development and progress all over the world.Flexner's report in 1910 brought modern science into the curricula of medical schools.In the 1960s,problem-based learning (PBL) was born in Canada and quickly achieved wide use.From the beginning of the 21st century,with increasing specialization in medicine,the "silo effect" has become more apparent.The inequality in healthcare and low efficiency of the entire health system has become prominent problems.These have brought about new challenges for medical education—how to implement accountable medical education so as to rectify the current situation.Therefore,"competency-based" medical education,as an important feature of the third generation medical education reform,has gradually become the trend.1However,currently in most medical schools in China,PBL is still flourishing,which indicates that we are still at the second generation of medical education reform。

Abstract：Background The relationship between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) remains largely unknown.This study aimed to explore the association of COPD with CAD,especially with multivessel disease (VD).Methods The data of 354 patients who underwent multi-detector computed tomography (MDCT) for suspected CAD were analyzed.Luminal narrowing was defined as at least one lesion 50％ or greater stenosis.The analysis of serum biochemistry profile and spirometrywere performed on all eligible patients,and the diagnosis of COPD was defined as the criteria of Global Initiative for Chronic Obstructive Lung Disease.Results Patients with CAD had a significantly higher complication of COPD than those without CAD (11.8％ vs.3.7％,P ＜0.001).Comparing with patients without COPD,those with COPD were more likely to have multi-VD,proportion of smoking and high C-reactive protein (CRP) (P ＜0.001).Multivariate Logistic regression analysis revealed that the multi-VD was significantly correlated with COPD (P=0.012) and CRP (P=0.015).Conclusions There was a high complication of COPD in patients with CAD,and COPD may be a critical risk factor for CAD,especially for multi-VD.CAD and COPD were closely associated and the interplay of systemic inflammation might in part explain the relationship between them。

Abstract：Background Pneumonia is the most common cause of morbidity and mortality in lung transplant (LT) recipients.The aim of the present study was to evaluate the incidence,etiology,risk factors and prognosis of pneumonia in LT recipients.Methods The LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011.Data collected included demographic data,underlying disorders,time and type of transplant,follow-up information,date of last follow-up,and patient status.A retrospective analysis was made of observational data that were prospectively collected.Results Twenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period.Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days (1-2104 days),the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946 days) post-transplantation.Bacteria,virus and fungi accounted for 62％,16％ and 15％ of the microbial pathogens,respectively.The most frequent were Pseudomonas aeruginosa (20％),cytomegalovirus (CMV) (15％),and Aspergillus fumigatus (10％).A total of 29％ (11/38) of pneumonias occurred in the first month post-LT,and then the incidence decreased gradually.The incidence of CMV pneumonia was 25％ (7/28) with a median time of 97 days (10-971 days).More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection.The incidence of pulmonary tuberculosis (TB) was 18％ (5/28),and the history of TB was a risk factor for TB relapse.There were 58％ (7/12) of recipients who died of infection,and 71％ (5/7) of these died in the first year after LT.Conclusions Pneumonia is still a major cause of morbidity and mortality in LT recipients.The most frequent microorganisms were Pseudomonas aeruginosa,CMV,and Aspergillus fumigates.The incidence of CMV pneumonia decreases with a delayed median time of onset.More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection.LT recipients are at high risk for TB,and the history of TB is a risk factor for TB relapse。

Abstract：Background Previous studies reported interleukin-27 (IL-27),interferon-γ (IFN-γ),or adenosine deaminase (ADA) alone plays a helpful role in diagnosing tuberculous pleural effusion (TPE).The present study aims at comparing the diagnostic accuracy of pleural IL-27,IFN-γ,and ADA,and investigate the diagnostic accuracy of the combination of IL-27,IFN-γ,or/and ADA for differentiating TPE from pleural effusions with the other etiologies.Methods The concentrations of IL-27,IFN-γ and ADA were simultaneously determined in pleural fluids and sera from 40 patients with TPE; 26 with malignant pleural effusion,seven with infectious pleural effusion,and eight with transudative pleural effusion by enzyme linked immunosorbent assay and colorimetric method.The corresponding biochemical indexs were also simultaneously determined.Results The concentrations of pleural IL-27 and IFN-γ in the tuberculous group were significantly higher than those in the malignant,infectious,and transudative groups.The concentrations of ADA in TPE were significantly higher than those in MPE or transudative effusions,while much lower than those in infectious effusions.Among these three biomarkers,IL-27 was the most effective for TPE diagnosis,with the cut off value of 900.8 ng/L.IL-27 had a high sensitivity of 95％ and specificity of 97.6％ for differential diagnosis of TPE from non-TPEs.Combinations of IL-27,IFN-γ and ADA measurements further increased the sensitivity or specificity up to 100％.Conclusions Compared to non-TPEs,IL-27,IFN-γ and ADA all simultaneously increased in TPE; and among these three rapid detection methods,IL-27 appeared to be the best for distinguishing tuberculous from non-TPEs,especially from MPE.Combinations of the three markers (IL-27,IFN-γ and ADA) yielded the highest sensitivity and specificity.These findings suggest that the applications of a new biomarker,IL-27,alone or with IFN-γ and ADA,may contribute to more efficient diagnosis strategies in the management of tuberculous pleurisy。

Abstract：Background It has been widely demonstrated that endothelial progenitor cells are involved in several diseases and that they have therapeutic implications.In order to define the altered pulmonary vascular homeostasis in chronic obstructive pulmonary disease,we sought to observe the level and functions of circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease.Methods The total study population included 20 patients with chronic obstructive pulmonary disease and 20 control subjects.The number of circulating endothelial progenitor cells (CD34+/CD133+/VEGFR-2+ cells) was counted by flow cytometry.Circulating endothelial progenitor cells were also cultured in vitro and characterized by uptake of DilacLDL,combining with UEA-I,and expression of von Willebrand factor and endothelial nitric oxide synthase.Adhesion,proliferation,production of nitric oxide,and expression of endothelial nitric oxide synthase and phosphorylated-endothelial nitric oxide synthase were detected to determine functions of circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease.Results The number of circulating endothelial progenitor cells in the chronic obstructive pulmonary disease group was lower than in the control group:(0.54±0.16)％ vs.(1.15±0.57)％,P ＜0.05.About 80％ of adherent peripheral blood mononuclear cells cultured in vitro were double labeled with Dil-acLDL and UEA-1.The 92％ and 91％ of them were positive for von Willebrand factor and endothelial nitric oxide synthase,respectively.Compared with the control,there were significantly fewer adhering endothelial progenitor cells in chronic obstructive pulmonary disease patients:18.7±4.8/field vs.45.0±5.9/field,P ＜0.05.The proliferation assay showed that the proliferative capacity of circulating endothelial progenitor cells from chronic obstructive pulmonary disease patients was significantly impaired:0.135±0.038 vs.0.224±0.042,P＜0.05.Furthermore,nitric oxide synthase (112.06±10.00 vs.135.41±5.38,P ＜0.05),phosphorylated endothelial nitric oxide synthase protein expression (88.89±4.98 vs.117.98±16.49,P ＜0.05) and nitric oxide production ((25.11±5.27) μmol/L vs.(37.72±7.10) μmol/L,P ＜0.05) were remarkably lower in endothelial cells from the chronic obstructive pulmonary disease group than the control.Conclusion Circulating endothelial progenitor cells were decreased and functionally impaired in patients with chronic obstructive pulmonary disease。

Abstract：Background The correct diagnosis of sputum smear-negative pulmonary tuberculosis in AIDS patients is very important to their therapy.We aimed to assess the value of the computed tomography (CT) and clinical findings in predicting smearnegative pulmonary tuberculosis in AIDS patients.Methods A total of 121 AIDS patients suspected of smear-negative pulmonary tuberculosis by clinical and radiographic findings were recruited.Pulmonary tuberculosis was diagnosed in 57 (47.1％) patients.The CT and clinical predictors were selected to diagnose AIDS-related pulmonary tuberculosis through univariate and multivariate Logistic analysis.Results Multivariate analysis showed that five variables,including weight loss,presence of miliary nodules,necrotic lymph node,Iobular consolidation,tree-in-bud sign,were independent predictors of pulmonary tuberculosis in AIDS patients.Predicted scores based on the five variables were used to identify pulmonary tuberculosis.If the predicted score of 3 was taken as the ideal cut-off point in the diagnosis of AIDS-related smear-negative pulmonary tuberculosis,the sensitivity,specificity,positive predictive value,negative predictive value,and accuracy were 84.2％,81.2％,80.0％,85.2％,and 82.6％,respectively.Conclusion The prediction method based on five key factors of clinical and CT findings are useful in guiding the diagnosis of smear-negative pulmonary tuberculosis in AIDS patients。

Abstract：Background Intra-abdominal hypertension (IAH) is common in acute respiratory distress syndrome (ARDS) patients and when resulting in decrease of chest wall compliance will weaken the effect of positive end expiratory pressure (PEEP).We investigated the effect of PEEP titrated by transpulmonary pressure (Ptp) on oxygenation and respiratory mechanics in ARDS patients with IAH compared with PEEP titrated by ARDSnet protocol.Methods ARDS patients admitted to the intensive care unit (ICU) of the Zhongda Hospital were enrolled.Patients were ventilated with volume control mode with tidal volume of 6 ml/kg under two different PEEP levels titrated by Ptp method and ARDSnet protocol.Respiratory mechanics,gas exchange and haemodynamics were measured after 30 minutes of ventilation in each round.IAH was defined as intra-abdominal pressure of 12 mmHg or more.Results Seven ARDS patients with IAH and 8 ARDS patients without IAH were enrolled.PEEP titrated by Ptp were significant higher than PEEP titrated by ARDSnet protocol in both ARDS patients with IAH ((17.3±2.6) cmH2O vs.(6.3±1.6)cmH2O and without IAH ((9.5±2.1) cmH2O vs.(7.8±1.9) cmH2O).Arterial pressure of O2/fraction of inspired oxygen (PaO2/FiO2)was much higher under PEEP titrated by Ptp when compared with PEEP titrated by ARDSnet protocol in ARDS patients with IAH ((27.2±4.0) cmHg vs.(20.9± 5.0) cmHg.But no significant difference of PaO2/FiO2 between the two methods was found in ARDS patients without IAH.In ARDS patients with IAH,static compliance of lung and respiratory system were higher under PEEP titrated by Ptp than by ARDSnet protocol.In ARDS patients with IAH,central venous pressure (CVP) was higher during PEEP titrated by Ptp than byARDSnet protocol.Conclusion Positive end expiratory pressure titrated by transpulmonary pressure was higher than PEEP titrated by ARDSnet protocol and improved oxygenation and respiratory mechanics in ARDS patients with IAH。

Abstract：Background Exhaled nitric oxide (NO) is a noninvasive biomarker of airway inflammation in pulmonary diseases.Hydrogen sulfide (H2S),as the third member of the gasotransmitter family,is involved in the pathophysiological process in lung diseases.H2S also exists in exhaled breath and can be sampled non-invasively.The study investigated the level of exhaled H2S in patients with chronic obstructive pulmonary disease (COPD) and its correlation with exhaled NO.Methods Levels of exhaled NO and H2S,lung function,and cell differential counts in induced sputum were studied in 19patients with acute exacerbation of COPD (AECOPD),19 patients with stable COPD and seven healthy smoke controls.Results Exhaled H2S levels were similar in patients with AECOPD (10.0 parts per billion (ppb),8.0-13.0 ppb),stable COPD (10.0 ppb,9.0-12.0 ppb),and healthy controls (9.0 ppb,8.0-16.0 ppb) (P ＞0.05).Exhaled NO levels were similar in patients with AECOPD (155.0 ppb,129.0-190.0 ppb),stable COPD (154.0 ppb,133.0-175.0 ppb) and healthy controls (165.0 ppb,112.0-188.0 ppb) (P ＞0.05).Exhaled H2S levels correlated positively with exhaled NO in all healthy controls and patients with COPD (r=0.467,P ＜0.01).No significant correlation was found between the exhaled H2S level and percentage of predicted FEV1 (P ＞0.05) and proportion of different cell types in induced sputum (P ＞0.05).Conclusions There is a correlation between exhaled H2S and exhaled NO.The role of exhaled H2S in airway inflammation in COPD still needs further investigation。

Abstract：Background Excessive daytime sleepiness (EDS) is often associated with obstructive sleep apnea hypopnea syndrome (OSAHS) and contributes to a number of comorbidities in these patients.Therefore,eady detection of EDS is critical in disease management.We examined the association between Epworth Sleepiness Scale (ESS) and multiple sleep latency test (MSLT) and diagnostic accuracy of ESS in assessing EDS in OSAHS patients.Methods The ESS,MSLT and overnight polysomnography were administered to 107 Chinese patients to assess EDS and its correlations with polysomnographic parameters.The diagnostic accuracy of ESS in classifying EDS (mean sleep latency (MSL) ＜10 minutes) was evaluated by calculating the area under ROC curve.Results As the severity of OSAHS increased,MSL decreased with increase in ESS score.Conversely,patients with worsening EDS (shorter MSL) were characterized by advanced nocturnal hypoxaemia and sleep disruption compared to those with normal MSL,suggesting EDS is associated with more severe OSAHS.There was a negative correlation between ESS score and MSL and both moderately correlated with some polysomnographic nocturnal hypoxaemic parameters.The area under ROC curve of ESS for identifying EDS was 0.80 (95％ C/:0.71 to 0.88) and ESS score ＞12provided the best predictive value with a sensitivity of 80％ and specificity of 69％.Conclusion The ESS score moderately correlates with MSL and our ROC study supports ESS as a screening strategy for assessing EDS in OSAHS。

Abstract：Background Genioglossal dysfuntion takes an important role in pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent hypoxia (CIH) is the major pathological origin.Recent studies have suggested genioglossal injury induced by CIH might be improved by adiponectin.The aim of this study was to investigate the effects of adiponectin on genioglossus contractile properties in rats exposed to CIH.Methods Thirty-nine healthy male Wistar rats were randomly divided into three groups:normal control (NC),CIH and adiponectin supplement (CIH+Ad) with 13 rats in each.Rats in NC were kept breathing normal air,while rats in CIH and CIH+Ad experienced the same CIH environment eight hours per day for 35 successive days.Rats in CIH+Ad were given intravenous adiponectin of 10 μg twice a week for 30 successive days.Rats in the NC and CIH were injected with normal saline as a control.After 35 days' CIH exposure,the levels of serum adiponectin and genioglossus contractile properties were compared.Results Serum adiponectin level was significantly lower in CIH than in NC (1210 ng/ml vs.2236 ng/ml).Serum adiponectin level in CIH+Ad (1844 ng/ml) was significantly higher than CIH but lower than NC.Twitch tension,time to peak tension,half relaxation time and tetanic tension were significantly lower in CIH than NC and improved in CIH+Ad.All mean tetanic fatigue indices decreased more rapidly in the first 20 seconds than during the subsequent 100 seconds.Tetanic fatigue indices in NC and CIH+Ad were significantly higher compared to CIH.Conclusions CIH could lead to hypoadiponectinaemia,impaired genioglossus contractile properties and decreased fatigue resistance in rats.Such changes could be partially offset by supplementation of adiponectin。

Abstract：Background Obstructive sleep apnea hypopnea syndrome,characterized by chronic intermittent hypoxia (CIH),is closely correlated with genioglossus dysfunction.CIH has been identified to mediate mitochondrial damage in genioglossus.It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction.This study aimed to investigate the role of ERS in CIH-induced genioglossus injury,as well as the possible intervention effect of adiponectin (Ad) supplement in rats.Methods Forty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A,n=15) as a control or CIH (groups B and C,n=15,respectively).Throughout the exposure period,intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B.After 35-day exposure,genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection,following blood sampling.Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus.Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA).Results Significant hypoadiponectinemia was revealed in group B only (P ＜0.05).Compared to those in groups A and C,expressions of markers involved in ERS,such as glucose regulated protein 78 (GRP78),p-PERK,phosphorylated eukaryotic initiation factor 2α (p-elF2α),phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1α (p-IRE1α),spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6),were significantly enhanced in group B (all P ＜0.01); while no significant difference was shown between groups A and C (all P ＞0.05).ERS-associated apoptotic pathways were remarkably activated in group B.The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP),B-cell lymphoma/leukemia associatied X protein (BAX)and caspase-12 were significantly elevated (all P ＜0.01).Transvenous adiponectin supplement improved the above CIH-induced pathological changes in group C.Conclusion Beyond hypoadiponectinemia,CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus,which could be significantly improved by adiponectin supplement。

Abstract：Background Obstructive sleep apnea (OSA) has been recognized as an independent risk factor for systemic hypertension.The study investigated the functional consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced by angiotensin Ⅱ (Ang Ⅱ) and the possible signaling involving ERK1/2 and contractile proteins such as myosin light chain kinase (MLCK),myosin phosphatase targeting subunit (MYPT1) and myosin light chain (MLC).Methods Male Wistar rats were randomly divided into CIH group and normoxia group and exposed to either CIH procedure or air-air cycles.Phosphorylation of ERK1/2,MYPT1 and MLC was assessed by Western blotting following constrictor studies in the presence or absence of PD98059 (10 μmol/L).Results CIH-exposure resulted in more body weight gain and elevated blood pressure,which could be attenuated by pretreatment with PD98059.Endothelium-removed aortic rings from CIH rats exhibited higher constrictor sensitivity to Ang Ⅱ (Emax:(138.56±5.78)％ versus (98.45±5.31)％ of KCI; pD2:7.98±0.14 versus 8.14±0.05,respectively).CIH procedure exerted complex effects on ERK expressions (total ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2increased).CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC.In parallel to greater increases in phosphorylation of ERK1/2,MYPT1 and MLC,Ang Ⅱ-induced aortic constriction was significantly enhanced in CIH rats,which was largely reversed by PD98059.However vascular constriction of normoxia rats remained unchanged despite similar but smaller changing tendency of proteins phosphorylation.Conclusion These data suggest that CIH exposure results in aortic hyperresponsiveness to Ang Ⅱ,presumably owing to more activated ERK1/2 signaling pathway。

Abstract：Background Obstructive sleep apnea is a frequent medical condition consisting of repetitive sleep-related episodes of upper air ways obstruction and can lead to hypertension.Ang Ⅱ type 1 receptor (AT1R) played important roles in hypertension since it binds with Ang Ⅱ,controlling salt-water and blood pressure homeostasis.This study explores rat aorta AT1R expression during intermittent hypoxia (IH) and the signaling pathways involved.Methods A rat model and a cell model used a BioSpherix-OxyCycler A84 system and a ProOx C21 system respectively.The arterial blood pressure was recorded by a Nihon Kohden Polygraph System.Immunohistochemic was used to focus and analyze the expression of AT1R in rat aorta.Real-time PCR and Western blotting were used to explore the signaling pathways that participated in AT1R expression.Results In this study,we found that chronic intermittent hypoxia (CIH) induced AT1R transcription which increased the blood pressure in rat aorta compared to normoxia and to sustained hypoxia.The AT1R protein expression in the aorta was similar to the real-time PCR results.We explored the signaling mechanisms involved in the AT1R induction in both rat aorta and the aortic endothelial cells by real-time PCR and Western blotting.Compared to normoxia,CIH increased ERK1 mRNA transcription but not ERK2 or p38MAPK in the aorta; whereas sustained hypoxia (SH) upregulated ERK2 but not ERK1 or p38MAPK mRNA.In cells,IH induced AT1R expression with ERK1/2 phosphorylation but reduced p38MAPKs phosphorylation,whereas SH induced only ERK1/2 phosphorylation.The ERK1/2 inhibitor PD98059 attenuated the IHinduced AT1R increase but the p38MAPK inhibitor SB203580 did not.Conclusions Our results indicate that CIH induced the elevation of rat blood pressure and aorta AT1R expression.Moreover,AT1R expression in IH and sustained hypoxia might be regulated by different signal transduction pathways,highlighting a novel regulatory function through ERK1/2 signaling in IH。

Abstract：Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC),in whom chemotherapy had failed.Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS).This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC.Methods We systematically searched Medline,EmBase,the Cochrane Central Register of Controlled Trials,reference lists of articles,and proceedings of major meetings for relevant literature.Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis.The primary endpoints were OS and PFS.Results Of 182 relevant studies,12 were included in the final analysis,which consisted of 6844 patients with NSCLC.Overall,we noted that gefitinib therapy had an 8％ improvement in the OS as compared to the gefltinib-free therapy,but this difference was not statistically significant (HR,0.92; 95％ C/:0.85-1.00; P=0.051).Furthermore,gefltinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR,0.72; 95％ C/ 0.60-0.87,P=0.001).Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR,2.51; 95％ C/,1.67-3.78,P ＜0.001).Rashes,diarrhea,dry skin,pruritus,paronychia,and abnormal hepatic function were more frequent in the gefitinib therapy group.Conclusions Treatment with gefitinib had a clear effect on PFS and ORR,and it might contribute considerably to the OS.Furthermore,there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma。

Abstract：Background Vitamin D status in relation to pancreatic cancer risks is still inconsistent.This study was performed to evaluate the association between vitamin D status and risk of pancreatic cancer using a meta-analysis approach.Methods A systemic review of all relevant literature in English was performed by searching Pubmed,Web of Science and Embase to identify eligible studies from the earliest available date to April 1,2012.The search terms "vitamin D","25-hydroxyvitamin D","pancreatic cancer" or "pancreatic neoplasms" were used to retrieve relevant papers.Inclusion criteria were:(1) the exposure of interest was intake of vitamin D or blood levels of vitamin D; (2) the outcome of interest was pancreatic cancer; (3) data on high and low intake or blood vitamin D in cases and controls were available; (4) odds ratio (OR) estimates with 95％ confidence interval (C/) were provided; (5) primary epidemiological data were provided reporting pancreatic cancer incidence.The combined OR values and their 95％ C/s were calculated via a meta-analysis.The potential presence of publication bias was estimated using Egger's regression asymmetry test.Results Nine studies with a total of 1 206 011 participants met the inclusion criteria.The test for heterogeneity showed there were significant differences among the included studies (l2=70.9％,P=0.001),so a randomized-effects model was used in the meta-analysis.The pooled OR of pancreatic cancer for the highest versus the lowest categories of vitamin D level was 1.14 (95％ C/ 0.896-1.451),and the Z-score for the overall effect was 1.06 (P=0.288),showing that there was no significant association between vitamin D levels and the risk of pancreatic cancer.Egger's test indicated there was a low possibility of publication bias in this study (P=0.348).Conclusion Dietary vitamin D or circulating concentrations of 25-hydroxyvitamin D are not associated with the risk of pancreatic cancer based on evidence from currently published studies。

Abstract：Background Numerous studies have evaluated the association between interleukin-18 (IL-18) promoter gene-607C/A (rs1946518) polymorphism and tuberculosis (TB) risk.However,the results remain apparently conflicting.The aim of this study was to investigate whether IL-18-607C/A polymorphism is associated with susceptibility to TB.Methods Publications addressing the association between the IL-18-607C/A polymorphism and TB risk were selected from the Pubmed,Cochrane Library,Embase,CNKI and Wanfang databases.Data were extracted from the studies by two independent reviewers.Statistical analysis was performed using RevMan 5.0.25 and STATA 11.0 software.Results Eight case-control studies with a total of 1166 TB patients and 1734 controls were retrieved.Meta-analysis results showed significant association between IL-18-607C/A polymorphism and TB risk in all comparisons of the A allele versus C allele (OR=1.17,95％ Cl 1.05-1.30,P=0.004),AA versus CC (OR=1.43,95％ CI 1.14-1.81,P=0.002),CA+AA versus CC (OR=1.20,95％ C/ 1.01-1.42,P=0.04) and AA versus CA+CC (OR=1.30,95％ C/ 1.07-1.58,P=0.007).In subgroup analysis by nationality,a significant association between IL-18-607C/A polymorphism and TB risk in the comparisons of A versus C,CA+AA versus CC and AA versus CA+CC (OR=1.22,95％ C/ 1.07-1.38,P=0.002;OR=1.31,95％ C/ 1.06-1.61,P=0.01; OR=1.32,95％ C/ 1.07-1.63,P=0.01,respectively) were found in Chinese population but not in Indian and Iranian populations.Conclusion This study suggests that the-607C/A polymorphism of IL-18 gene would be a risk factor for TB,especially in Chinese population.To further evaluate gene-to-gene and gene-to-environment interactions on-607C/A polymorphism and tuberculosis risk,more studies with thousands of patients are required。

Abstract：Objective We review the targets of the deep brain and the responsive neurostimulation system (RNS) to identify the best optimal stimulation parameters and the best mode of stimulation,whether cyclical,continuous,or smarter.Data sources This review is based on data obtained from published articles from 1950 to 2013.To perform the PubMed literature search,the following keywords were input:deep brain stimulation (DBS),RNS,and refractory epilepsy.Study selection Articles containing information related to brain stimulation or RNS for the treatment of refractory epilepsy were selected.Results The currently available treatment options for those patients who resist multiple antiepileptic medications and surgical procedures include electric stimulation,both direct and indirect,of brain nuclei thought to be involved in epileptogenesis.The number of potential targets has increased over the years to include the anterior nucleus of the thalamus,the centromedian nucleus of the thalamus,the hippocampus,the subthalamic nucleus,the caudate nucleus,and the cerebellum,among others.The results of a randomized controlled trial and the RNS trial were published to reveal the effectiveness.Conclusions Although statistically significant reductions in seizures have been observed using several different stimulation techniques,including vagus nerve stimulation,DBS,and RNS,these effects are currently only palliative and do not approach the efficacy comparable with that seen in resection in appropriately selected patients.More research is needed to determine optimal stimulation targets and techniques as well as to determine which epilepsy patients will benefit most from this technology。

Abstract：Objective This review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression.Data sources Relevant articles published in English were identified by searching in Pubmed from 1997 to 2013,with keywords "CXCL12","CXCR4" and "pancreatic cancer".Important references from selected articles were also retrieved.Study selection Articles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected.Results Pancreatic cancer has been one of the most lethal human malignancies,with median survival less than one year and overall 5-year survival only 6％.Tumor cells from pancreatic cancer express high level of CXCR4.CXCL12,the ligand for CXCR4,is extensively secreted by neighboring stromal cells and other distant organs.CXCL12 primarily binds to CXCR4,induces intracellular signaling through several divergent pathways,which are involved in progression and metastasis of pancreatic cancer.Conclusions CXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment,which may have effect on tumor proliferation,invasion,angiogenesis,metastasis and chemoresistance.CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer。

Asthma is a chronic inflammatory disease that affects 300 million people worldwide.Its prevalence ranges from 1％ to 18％ of the population in different countries,1The World Health Organization has estimated that 15 million disability-adjusted life years are lost annually due to asthma.Worldwide deaths from asthma are estimated at 250 000 per year。

Without adequate fluid replacement,patients with sepsis often experienced serious hypovolemia due to fever,vomiting,or diarrhea before admission.To make things worse,relative and absolute intravascular volume deficits could be exacerbated by sepsis-induced vasodilation,increased microvascular permeability and abnormal distribution of blood flow.1 Consequently,it led to poor tissue perfusion and facilitated the development of multiple organ failure.Therefore,fluid resuscitation is crucial for initial management of severe sepsis,by which the restoration and maintenance of adequate intravascular volume contribute greatly to hemodynamic stability,and attenuate poor perfusion-caused organ injuries.24 However,the choice of fluid remains controversial。

In serum,adiponectin can exist as either full-length form that can form trimers,hexamers and high molecular weight (HMW) multimers,or as globular adiponectin (gAd).Adiponectin-deficiency leads to an increase in proinflammatory mediators and an emphysemalike phenotype,1 also protects against tobacco-induced inflammation and the increased emphysema.2 The mechanism underlying this apparent paradox remains unclear.We therefore analyzed serum levels of adiponectin isoforms,thioredoxin (Trx)/thioredoxin reductase (TrxR) activity,tumor necrosis factor (TNF)-α,IL-6and 4-hydroxynonenal (4-HNE) in patients with chronic obstructive pulmonary disease (COPD) and in control individuals。

Once the ascending aorta gets involved and however farther the dissection extends,it is named type A dissection (TAD),in which the entry tear usually locates in the ascending aorta.But there exists a small subset with primary entry tear in the descending aorta and the dissection process extends back into the ascending aorta,which here we name primary retrograde type A dissection (PRTAD).Operative procedures are far more difficult and extensive for PRTAD and usually result in poor prognosis in the aspects of surgical mortality and survival rate during follow-up.1-3 Kato et al4 and Chang et al5 showed successful method of endovascular repair for PRTAD and recommended it as an alternative to the operative treatment.During March 2008 to August 2010,five continuous patients with PRTAD were admitted into our institution.We here introduce our preliminary experience with medical therapy and thoracic endovascular aortic repair (TEVAR)for treating PRTAD。

Fanconi syndrome (FS) is a disorder that is mainly characterized by aminoaciduria,hypophosphatemia,phosphaturia,and renal hyperglycosuria,and occasionally associated with renal tubular acidosis.The disease was originally thought to be either inherited or acquired,but to date the pathogenesis of FS remains unclear.1 Therefore,FS is often misdiagnosed in clinical practice,and many cases have been incorrectly diagnosed as osteoporosis.Moreover,even in cases where the disease is correctly diagnosed,many clinicians are not familiar with FS due to the complex clinical manifestation and only understand it as an organspecific disease.2 Only a few cases have been reported to date in the literature,which describe it as a rare disease.In this study,we collected 27 cases in General Hospital of Tianjin Medical University over the past 18 years.Based on a comprehensive assessment of 10 patients using bone,kidney,and muscle biopsies,we developed a novel treatment strategy and assessed the efficacy in a subset of patients。

Diffuse malignant pleural mesothelioma (DMPM)is a rare thoracic malignancy,but its incidence is dramatically increasing worldwide as a result of widespread use of asbestos).1 The World Health Organization classifies DMPM into three types:epithelioid,sarcomatoid,and biphasic types.DMPM remains suffering poor prognosis and the diagnosis should always be based on adequate,representative tissue samples。

Morgagni's hernia is a rare type of diaphragmatic hernia.It is hardly developed to an incarcerated hernia.It is often misdlagnosed as pneumothorax or effusion.Computed tomography and upper GI contrast studies make contribution to the diagnosis.Transabdominal approach or laparoscopy and thoracoscopy are efficient therapies for the hernia。

To the editor:Acute myocardial infarction (AMI) and acute myeloid leukemia (AML) are two intensive and life threatening diseases.Recent human studies demonstrated that C reactive protein (CRP),the best characterized biomarker of inflammation,contributed to increase cardiovascular risk1 and AML.2 Moreover,CRP could stimulate the generation of reactive oxygen species (ROS),3 which have been detected in a variety of diverse pathologic states,including atherosclerosis,and acute myeloid malignancies。

To the editor:Sufentanil has the same analgesia effect compared with the fentanyl.Although sufentanil has the same adverse effects of skeletal muscle rigidity with fentanyl,sufentanil's halflife is greatly shortened.1 These adverse effects are rarely reported in medical intensive care unit (MICU) patients.We found that patients with chest and abdominal wall muscle rigidity attributed to intravenous analgesia with sufentanil can be identified by observing mechanical ventilator graphics。

To the editor:Targetoid hemosiderotic hemangioma (THH),also known as Hobnail Hemangioma (HH) is characterized by a violaceous to brown targetoid lesion.The classic histological presentation of THH is that of ectatic vascular lumina mainly in the superficial and mid-dermis lined by a single layer of endothelial cells with hobnail appearance.We report here a case of THH in China with distinctive clinical features。

To the editor:A 51-year-old man presented with a 7-year history of painful purple plaques on the left back.The lesions went ulceration and healed after some treatment.The lesions would recur every spring and improve in the fall and winter.One month ago,he again developed these lesions,which gradually increased to palmsized plaques.A physical examination revealed multiple ulcers,ranging in size from 8 cm×2.5 cm to 1 cm× 1 cm,some of the lesions had dark crusts on the left back and bilateral axillary and inguinal multiple lymphadenopathy.His serum albumin level was 34.7 g/L (normal range,35-55 g/L).A T-cell subset analysis showed the following:CD3,84.20％ (normal range,66.9％-83.1％);CD4,57.40％ (normal range,33.19％-47.85％);CD8,17.40％ (normal range,20.4％-34.7％);and CD4/CD8 ratio,3.30 (normal range,0.97-2.31).The serum level of interleukin-2 receptor was 3704.0U/ml (normal range,223-710 U/ml).Vascular ultrasonography showed atherosclerotic plaques in the lower limbs.Computed tomography (CT) performed using the mediastinal aortic window showed nodular tissue in the upper abdomen and chest.Histopathological examination of the lesions on the left back showed epithelioid granulomas in the dermis and subcutaneous fat,with multinucleated giant cells and lymphocytic infiltration.No acidfast bacteria were detected.On the basis of the above findings,we diagnosed sarcoidosis of the ulcerative type。

To the editor:We here present a rare case of müllerian adenosarcoma arising in pelvic endometriosis and the changes of serum CA125 level during the course of malignant changes.Serum CA125 was found being persistently abnormal during the course of endometriosis progression;and the fluctuation of CA125 seemed be relative to disease condition and could reflect the response to treatment。