2013年 · 第126卷第01期

Abstract：Background Neurofibromatosis type 1 (NF1) is the most common genetic syndrome predisposing patients to various tumors due to dysregulation of the Ras signaling pathway.Recent research has shown NF1 patients also suffer a spectrum of bone pathologies.The pathogenesis of NF1 bone diseases is largely unknown.There is no current treatment.By Nf1 heterozygote (Nf1+/-) mice and Nf1 conditional knockout mice,we and other groups demonstrated abnormal osteoblast and osteoclast function due to dysregulation of Ras signaling.However,the specific downstream effector pathways linked to NF1 abnormal osteoblastogenesis and osteoclastogenesis have not been defined.In this study,we investigated the Ras downstream effector related with NF1 bone disease.Methods We used Nf1+/+ and Nf1+/-mice as normal and NF1 models.Bone stromal cells extracted from Nf1+/+ and Nf1+/-mice were induced osteoclasts.The osteoclast cell was stained by tartrate resistant acid phosphatase staining.The osteoclast cell number was counted and the surface area of osteoclast cells was calculated under the microscope.The mRNA of mammalian target of rapamycin (mTOR) was determined by quantitative reverse-transcription-polymerase chain reaction.The presence of ribosomal protein S6 kinase was determined by Western blotting.Results Compared with Nf1+/+ mice,Nf1+/-mice had about 20％ more of osteoclast cells.These osteoclast cells werelarger in size with more nuclei.Hyperactive mTOR was detected in Nf1+/-osteoclast cells.Inhibition of mTOR signalingby rapamycin in Nf1+/-osteoclasts abrogated abnormalities in cellular size and number.Conclusion mTOR pathway inhibition may represent a viable therapy for NF1 bone diseases。

Abstract：Background Brain hypoplasia and mental retardation in Down syndrome (DS) can be attributed to a severe and selective disruption of neurogenesis.Secondary disruption of the transcriptome,as well as primary gene dosage imbalance,is responsible for the phenotype.MicroRNA (miRNA) expression is relatively abundant in brain tissue.Perturbed miRNA expression might contribute to the cellular events underlying the pathology in DS.Methods MiRNA expression profiles in the cerebrum of Ts65Dn mice,a DS model,were examined with a real-time RT-PCR array.MiRNA target gene expression was detected by real-time quantitative PCR and Western blotting.Based on the prediction of their cerebrum-specific targets,the functions of the misregulated miRNAs were annotated by Gene Ontology (GO) enrichment analysis.Results A total of 342 miRNAs were examined.Among them,20 miRNAs showed decreased expression in the brains of Ts65Dn mice,and some of these belonged to the same family.Two known targets of the miR-200 family,Lfng and Zeb2,were specifically selected to compare their expression in the cerebrum of Ts65Dn mice with those of euploids.However,no significant difference was found in terms of mRNA and protein expression levels of these genes.By enrichment analysis of the cerebrum-specific targets of each miRNA,we found that 15 of the differential miRNAs could significantly affect target genes that were enriched in the GO biological processes related to nervous system development.Conclusion Perturbed expression of multiple functionally cooperative miRNAs contributes to the cellular events underlying the pathogenesis of DS。

Abstract：Background The chronic obstructive pulmonary disease assessment test (CAT) is an easy to use health-related quality of life questionnaire,the modified Medical Research Council (mMRC) dyspnea scale is a classic dyspnea scale which is widely used,while the correlation between them is still not clear.This study investigated the use of the Chinese translation of CAT in chronic obstructive pulmonary disease patients and its correlation with the mMRC dyspnea scale.Methods The multicenter cross-sectional study was conducted in 329 hospitals throughout China from March 1 to April 30,2010.Chronic obstructive pulmonary disease patients completed both the assessment test and the dyspnea scale during a single study visit.Results Six thousand,four hundred and thirty-seven patients were evaluated; 74.9％ were male and the mean age was (64.9±10.0) years.Median test scores in dyspnea grades 0 to 4 were 14,16,22,26 and 32,respectively; these differences were statistically significant.The CAT score was moderately correlated with mMRC dyspnea grade (r=0.579,P ＜0.001).There was no significant difference in mean CAT score between males and females,and patients of high and low socioeconomic status.Pdmary analysis suggested that CAT scores were higher in older patients (＞65 years) than in younger patients (≤65 years) and increased with duration of formal education,but these findings were repudiated by further analysis of subgroups according to mMRC dyspnea grade.Conclusions There was no obvious confounding factor influencing use of the CAT in Chinese patients.CAT scores were moderately correlated with the mMRC dyspnea scale。

Abstract：Background The experimental studies of venous thromboembolism (VTE) as an entity and the response of the pulmonary arterial endothelium after VTE are still rare.The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE.Methods Rats were allocated to the VTE (n=54) or control groups (n=9).The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis (DVT).One,four or seven-day-old thrombi were injected into the right femoral vein to induce DVT-pulmonary thromboembolism (DVT-PTE).The rats were sacrificed 1,4 or 7 days later (Dn (1,4,7) Pn(1,4,7) subgroups (n=6)),and the lungs were examined using light and electron microscopy.Results On gross dissection,the rate of DVT formation was higher on day 1 (D1Pn:100％,18/18) than day 4 (D4Pn:83％,15/18; x2=5.900,P=0.015) or day 7 (D7Pn:44％,8/18; x2=13.846,P=0.000).On gross dissection,the positive emboli residue rate in the pulmonary arteries was lower in the D1Pn subgroup (39％,7/18) than the D4Pn (73％,11/15;x2=3.915,P=0.048) and D7Pn subgroups (100％,8/8; x2=8.474,P=0.004); however,light microscopy indicated the residual emboli rate was similar in all subgroups.Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi.However,regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi.Conclusions This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation.The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi。

Abstract：Background Chronic intermittent hypoxia (CIH) has been associated with abnormalities in the liver,which is the most important organ for drug metabolism.This study aimed to investigate the effect of CIH on theophylline metabolism in mouse liver.Methods Eight C57BL/6J mice were exposed to CIH for 12 weeks.Eight C57BL/6J mice were exposed to room air as a control group.Serum levels of alanine aminotransferase and aspartate aminotransferase were measured.Liver histology was observed by light and electron microscopy.Total hepatic cytochrome P450 concentration was measured.Hepatocytes were isolated and incubated with 15 mg/ml theophylline for four hours.After incubation,the theophylline concentration in the supernatant was measured and the theophylline metabolism rate was calculated.Results CIH did not affect the serum transaminase levels.Livers from mice exposed to CIH showed hepatocellular edema,and liver cells had fuzzy rough endoplasmic reticulum under the electron microscope.The theophylline metabolism rate was significantly inhibited by CIH compared with controls; (16.60±2.43)％ vs.(21.58±4.52)％ (P=0.02).The total liver cytochrome P450 concentration in the CIH group was significantly lower than in the control group;(0.83±0.08) vs.(1.13±0.21) mol/mg microsomal protein (P=0.004).Conclusion CIH decreases theophylline metabolism by mouse hepatocytes,which may correlate with the downregulation of cytochrome P450 expression by CIH。

Abstract：Background The usual transbronchial coagulation techniques include microwave,argon plasma coagulation (APC),electrocautery and cryotherapy.However,there are serious clinical problems in the safety of each.By analyzing the experimental data and clinical observations,we observed the variable effects of different coagulation techniques via bronchofibroscopy,to look for an optimal interventional management of luminal bronchus diseases,and evaluate the safety and the equivalent point.Methods Four kinds of coagulation techniques under bronchoscopy were performed on the fresh bronchus of healthy sheep,and the pathologic changes in all groups were observed under the microscope.The different treatment parameters were as follows:microwave 60 W×1 second,3 seconds,5 seconds and 40 W×1 second,3 seconds,5 seconds; APC 40 W×1 second,3 seconds,5 seconds; electrocautery 40 W×1 second,3 seconds,5 seconds;cryotherapy 100 Ω×60 seconds,120 seconds.Results After treatment,ovine bronchial mucosa in all groups showed pathologic changes such as local necrosis and amotio of the mucosa lining epithelium,local submucosa coagulative necrosis or tissue defects,while inflammation in the surrounding tissue was not obvious.Under the same output power and action time,different methods had different outcomes.The damage by APC was the most superficial,microwave was the second,and electrocautery caused the worst damage.The study also found that effects of electrocautery at 40 W×3 seconds,microwave at 40 W×5 seconds or 60 W×3 seconds,APC at 40 W×5 seconds and cryotherapy at 100 Ω×120 seconds were the equivalent point conditions.The appearance included mucosa absence,partial submucosa absence,and collagen fiber coagulation in treatment areas.Conclusions Each coagulation technique has its own characteristic.It is very important to choose the appropriate power and action time of the suitable method according to the therapy requirement。

Abstract：Background Histone deacetylase inhibitors can regulate gene expression through modulation of the degree of acetylation of histone and non-histone,thus affecting cell proliferation,survival and chemosensitivity.Histone deacetylase inhibitors combined with paclitaxel may enhance the inhibitory effect of drugs on lung cancer cells.This study aimed to observe the effect of trichostatin A (TSA)/paclitaxel on the proliferation and apoptosis in human A549 lung adenocarcinoma cells,and to investigate its mechanism.Methods A549 cells were cultured in Dulbecco modified Eagle's medium (DMEM) in the presence of paclitaxel and the histone deacetylase inhibitor TSA,and the growth curve was obtained by trypan-blue exclusion assay and cell count.Apoptosis was assessed using Hoechst 33258 staining and flow cytometry analysis,and cell cycle was detected by flow cytometry analysis.The proteins poly ADP-ribose polymerase (PARP),caspase-3,survivin,and tubulin acetylation were detected by Western blotting.Results A significant reduction of proliferation was observed in A549 lung adenocarcinoma cells treated by paclitaxel or TSA.Combined treatment with TSA/paclitaxel caused the greatest inhibition of cell proliferation.The combined treatment with TSA and paclitaxel induced more severe apoptosis,and significantly more cells were arrested in Gz/M phase (P ＜0.05) then with a single drug.Using Western blotting,we demonstrated that treatment with TSA/paclitaxel led to synergistic increase in acetylated tubulin,PARP,caspase-3,and reduced the expression of survivin.Conclusion TSA and paclitaxel have a synergistic activity that can inhibit cell growth and induce apoptosis。

Abstract：Background It is believed that defects in upper airway neuromuscular control play a role in sleep apnea pathogenesis.Currently,there is no simple and non-invasive method for evaluating neuromuscular activity for the purpose of screening in patients with obstructive sleep apnea.This study was designed to assess the validity of chin surface electromyography of routine polysomnography in evaluating the neuromuscular activity of obstructive sleep apnea subjects and probe the neuromuscular contribution in the pathogenesis of the condition.Methods The chin surface electromyography of routine polysomnography during normal breathing and obstructive apnea were quantified in 36 male patients with obstructive sleep apnea.The change of chin surface electromyography from normal breathing to obstructive apnea was expressed as the percent compensated electromyography value,where the percent compensated electromyography value =(normal breath surface electromyography-apnea surface electromyography)/normal breath surface electromyography,and the percent compensated electromyography values among subjects were compared.The relationship between sleep apnea related parameters and the percent compensated electromyography value was examined.Results The percent compensated electromyography value of the subjects varied from 1％ to 90％ and had a significant positive correlation with apnea hypopnea index (R2=0.382,P ＜0.001).Conclusions Recording and analyzing chin surface electromyography by routine polysomnography is a valid way of screening the neuromuscular activity in patients with obstructive sleep apnea.The neuromuscular contribution is different among subjects with obstructive sleep apnea。

The endocrine changes of cancer patients on initial confirmed diagnosis and during chemotherapy have been gradually realized and clarified,as well as the dependences of different tumors on corresponding hormones.The prevalent endocrinotherapy suppresses tumor progression through downregulating dependent hormone level or completely inhibitting its combination with receptors.Because of the different and even antagonistic mechanisms,endocrinotherapy should not be used with chemotherapy at the same time,or it will reduce the chemotherapeutic efficacy,which is a widely accepted principle in clinic.On the other hand,kinds of hormone levels are downregulated during chemotherapy,which is the other format of using endocrinotherapy with chemotherapy at the same time,but this common phenomenon has not been paid enough attention to.Here,we systematically reviewed literatures suggesting that endocrine hormones might have an important chemosensitization role in cancer chemotherapy as follows。

MicroRNAs (miRNAs) are a novel class of～22-nt,non-coding,short single-stranded RNAs produced from endogenous genes by the sequential action of the RNase Ⅲ enzymes Drosha and Dicer.Increasing evidence shows that miRNAs play a critical role in regulating inflammatory and innate immunity.1,2 However,whether miRNAs are involved in the altered function of innate immune cells and ultimately contribute to the development of acute lung injury (ALI) remains largely unknown.It is worth studying the expression profiles of miRNAs in mouse lungs stimulated by lipopolysaccharide (LPS),which may be very important in the regulation of inflammatory mediators during ALI.In the present study,we investigated the expression profiles of miRNAs in LPS-induced ALI in mice。

Abstract：Background As the only active component in final treatment phase of Tip-Edge Plus technique,the activation of nickel-titanium orthodontic archwires is one of the factors that affect the torque expression.It is necessary to evaluate the mechanical properties of the nickel-titanium wire used in the final treatment phase in simulated oral environments to forecast the treatment outcomes.Methods The mechanical properties of 171 thermal nickel-titanium wires of 0.35 mm (0.014-in) in diameters with different deflection of 40 mm in length were investigated with three-point bending test.The samples were divided into 2 groups:as-received and bended groups.In the bended group,samples were divided into 7 subgroups according to the amounts of deflection and named by the canine angulations (-25°,-19°,-13°,-7°,-1°,+5°,+11°).The deflection of wires was made by inserting the wires into the deep tunnel of Tip-Edge Plus brackets positioned in plaster casts with different canine angulations to mimic the use of nickel-titanium wires in the final treatment phase.Immersed the bended group in artificial saliva (pH 6.8) and preserved at 37.0°C.Eight durations of incubation were tested:1 to 8 weeks.Three analogous samples of each group and subgroups were tested per week.Stiffness (YS:E) and the load-deflection characteristics of unloading plateau section were obtained.Results Significant changes in specific mechanical properties were observed in long-term immersed and large deflected wires compared with as-received groups.Both immersion time and deflection affected the mechanical properties of wires in the simulated oral environment,and the two factors had synergistic effect.In groups-25°,-19° and -13°,stiffness (YS:E) increased then decreased and average plateau force and ratio of variance decreased then increased correspondingly at specific time.Conclusions In the final treatment phase of Tip-Edge Plus technique,the mechanical properties of nickel-titanium wire are associated with the using time and amounts of deflection and it may affect treatment outcomes.As the main reason for wire deflection,canine crown angulation plays an important role in the wire performance.It may be wise to focus on the canine crown angulations and using time in clinic with Tip-Edge Plus technique and make proper adjustment to help to make sure the treatment outcomes。

Abstract：Background Thymectomy is an established treatment for myasthenia gravis (MG),and video-assisted thoracoscopic surgery (VATS) thymectomy has become an acceptable surgical procedure.This study aimed to compare the results of VATS thymectomy and open thymectomy and to identify the prognostic factors after thymectomy.Methods The clinical data of 187 consecutive thymectomies performed between July 2000 and December 2009 were retrospectively reviewed; 75 open thymectomies and 112 VATS thymectomies.Clinical efficacy and variables influencing outcome were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression analysis.Results The operative blood loss in the VATS group was significantly less than that in the open group ((62.14±55.43)ml vs.(137.87±165.25) ml,P ＜0.05).The postoperative crisis rate increased with the severity of preoperative MG and the prescription dose of anticholinesterase.Complete follow-up information of patients more than 12 months after the thymectomy was obtained on 151 cases,89 cases from the VATS group and 62 cases from the open group,with a mean follow-up period of 59.3 months,range from 12 to 117 months.Complete stable remission (CSR) was the end point for evaluation of the treatment results.The overall five-year CSR rate was 57.5％ Two good prognostic factors were identified; preoperative prescription of anticholinesterase alone (P=0.035) and non-thymomatous MG (P=0.003).The five-year CSR rate of the ocular type of MG reached a high level of 67.4％.Conclusions Thymectomy can achieve good long-term CSR in MG,and VATS is an ideal alternative method.High-dose prescription of anticholinesterase and the advanced stage by Myasthenia Gravis Foundation of America (MGFA) classification have higher risks of postoperative crisis.Preoperative prescription of anticholinesterase alone and non-thymomatous MG are good prognostic factors.Thymectomy should also be considered for the ocular type of MG。

Abstract：Background Argon laser peripheral iridoplasty (ALPI) is proved to be effective in lowering intraocular pressure (IOP) of patients with mild acute primary angle closure (APAC).It is unclear whether this laser treatment is equally efficient in managing patients with severe APAC.This study aimed to evaluate the IOP-lowering efficacy of ALPI and laser peripheral iridotomy (LPI) on patients with refractory APAC,who have previously responded poorly to intensive medical therapy.Methods Thirty-six patients (8 men and 28 women) were identified as medically refractory APAC,who still had ocular pain,red eye,hazy cornea,closed anterior chamber (AC) angle,and IOP of not less than 21 mmHg after two days or more of anti-glaucoma medication.All enrolled patients underwent ophthalmologic examinations including measurement of visual acuity (VA),best corrected VA (BCVA),IOP,biomicroscopy,and gonioscopy followed by ALPI immediately in the APAC eye and LPI in both eyes.Results All patients were affected unilaterally,with average age of (54.6±11.7) (range,37.0-75.0) years old.The mean IOP value of the affected eyes dropped from (31.6±7.7) (range,21.0-39.0) mmHg at enrollment to (18.4±8.7) (range,10.0-27.0) mmHg 2 hours after ALPI.At follow-up day 7,the mean IOP value maintained at (14.8±4.2) (range,9.0-21.0)mmHg,which was significantly different (P=0.000) compared with baseline.The average decrease of IOP in the APAC eyes was (16.8±7.4) (range,12.0-21.0) mmHg.At follow-up three years later,the mean IOP of the APAC eyes stabilized at (16.3±3.2) (range,9.0-20.0) mmHg with at least 180° of AC angle opened.Conclusion ALPI and LPI lower the IOP of medically refractory cases of APAC though they have responded poorly to anti-glaucoma medication。

Abstract：Background The Da Vinci system is a newly developed device for colorectal surgery.With advanced stereoscopic vision,lack of tremor,and the ability to rotate the instruments surgeons find that robotic systems are ideal laparoscopic tools.Since conventional laparoscopic total mesorectal excision is a challenging procedure,we have sought to assess the utility of the Da Vinci robotic system in anterior resections for rectal cancer.Methods Between November 2010 and December 2011,a total of 22 patients affected by rectal cancer were operated on with robotic technique,using the Da Vinci robot.Data regarding the outcome and pathology reports were prospectively collected in a dedicated database.Results There were no conversions to open surgery and no postoperative mortality of any patient.Mean operative time was (220±46) minutes (range,152-286 minutes).The median number of lymph nodes harvested was (14.6±6.5) (range,8-32),and the circumferential margin was negative in all cases.The distal margin was (2.6±1.2) cm (range,1.0-5.5 cm).The mean length of hospital stay was (7.8+2.6) days (range,7.0-13.0 days).Macroscopic grading of the specimen was complete in 19 cases and neady complete in three patients.Conclusions Robotic anterior resection for rectal surgery is safe and feasible in experienced hands.Outcome and pathology findings are comparable with those observed in open and laparoscopy procedures.This technique may facilitate minimally invasive radical rectal surgery。

Abstract：Background Despite psycho-oncological concerns and studies having thrived these past decades,sparse reports illustrate to what extent Chinese cancer patients are involved and influenced by comorbid mental health problems.To investigate the mental health condition of cancer patient,as well as its possible impacts on prognosis,the first large-scale survey was performed in the west of China.Methods For standardizing and facilitating the assessment of mental illness in inpatients with cancer,a multidisciplinary rating flow was designed and established.On the basis of this system,between May 1st and 31st 2009,2279 cancer inpatients from nine medical centers received preliminarily screening executed by oncologists using screening scales Mental Health Screening Questionnaire (MHSQ),Zung self-rating depression scales (SDS),Zung self-rating anxiety scale (SAS),and posttraumatic stress disorder checklist-civilian version (PCL-C).Further analyses of the ones screened positively were conducted by psychiatrists applying corresponding symptom-rating scales (HAMA/HAMD/BPRS).We summarized the overall proportion of patients with impaired mental health based on the data acquired from preliminary screening,and then calculated occurrence rates of each clinical syndrome of mental disorder according to symptom conclusions.The impact of comorbid mental illness was evaluated through the follow-up scheduled 1 year later,by comparing the survival rate,progression of disease,and quality of life (QoL) between subgroup patients with or without clinical syndrome of mental disorder.Results In preliminary screenings,26.1％ (595/2279) yielded positive results.Further symptom conclusions confirmed 15.8％ (359/2279) with clinical syndrome of mental disorder.Regarding specific type of syndrome,the occurrence rates of depression,anxiety,psychotic symptoms,and stress-related disorders were 13.3％,10.2％,2.8％,and 1.4％,respectively.Follow-up assessments were successfully performed in 1918 subjects (84.2％).Further analyses indicated that although insignificant influence was observed in terms of 1-year survival rate and disease progression,cancer patients with a clinical syndrome of mental disorder obtained significantly lower levels (P ＜0.05) in five domains of QoL (scored by QLQ-C30).Conclusion In China,at least 26％ of cancer patients experienced impaired mental health,of which 60％ already had a detectable clinical syndrome of mental disorder,which could significantly undermine their QoL。

Abstract：Background Early detection with screening mammography can potentially reduce breast cancer mortality rates.To achieve an efficient screening,a peer review system provides a compensatory double-check reviewing,will hopefully to prevent the omission of detectable lesions and reduce unnecessary recall.Methods In 2009,4643 initial mammographic screenings reported by 74 screening radiologists had negative results with a recall rate of less than 5％.In the same year,2538 initial positives screened by 18 screening radiologists had a recall rate higher than 15％.Those 7181 randomized screenings were evenly distributed for reassessment by 39 reviewing radiologists.The disagreement of assessments between the reviewers and screening radiologists was recorded.The differential rate was defined as the number of the disagreements divided by the number of audited films reviewed by a screening radiologist.The equality of the differential rates for each screening radiologists with negative and positive assessments was compared by a Chi-square test.The performance of the 39 auditors was measured by the Kendall's tau statistic.P values less than 0.05 were considered statistically significant.Results The mean differential rate for screening radiologists of negative assessments was 6.7％ (P=-0.588),while 35.0％ for positive assessments were significant (P ＜0.001).The result indicated that most of the initial negative assessments reported by the screening radiologists were generally accepted by the reviewers but not the positive assessments.With respect to the 39 reviewers,there was no significant evidence for the association of the difference rates between negative and positive assessments.Nine reviewers were found to have their differential rate for negative and positive assessments larger than the average of the population.Eleven reviewers were found to have their differential rates smaller than the average for both.Thirteen reviewers had their differential rates smaller than the average for negative assessments but larger than the average for positive assessments.The opposite condition was found for six reviewers.The Kendall's tau statistic was 0.038 (P=0.735).Conclusions Reviewers usually agreed with the opinion of the initial screening doctors who reported negative findings.Therefore,a 5％ recall rate as the lower range of reviewing negatives may be still too high.The recall rate of more than 15％ was significantly related to improper interpretation,especially when the differential rate is 25％ or higher,a warning to the underperforming screening radiologist is recommended.An ideal reviewer should interpret films independently.Reviewers with tendencies to be followers or contrarians should not be enrolled in the reviewing system。

Abstract：Background Congenital heart disease (CHD) is a diverse group of diseases determined by genetic and environmental factors.Considerable research has been done on genes associated with the development of the heart.Recently,focus is on the role of transcription factor NFATc1 in the development of proper valve and septa.As part of a larger study,high density single nucleotide polymorphism (SNP) scanning was used to explore the relationship between NFATc1 gene polymorphism and susceptibility to ventricular septal defect (VSD) in the Chinese Han population.Methods One hundred and ninety-two pediatric patients with congenital VSD and 192 matching healthy control subjects were studied.The haplotype reconstructions were calculated by PHASE2.0 software.Haploview software was used to perform linkage disequilibrium assessment and define haplotype blocks.The algorithm used for defining the blocks was the confidence interval method.Results The NFATc1 gene region can be divided into 11 haplotype blocks.Strong linkage disequilibrium existed within blocks 6,8,9,and 11.Three SNPs (rs7240256,rs11665469,and rs754505) within the NFATc1 gene had significant correlation with VSD by single marker association analysis.In addition,two haplotypes correlated with VSD.Conclusions NFATc1 is associated with the occurrence of VSD and it may be a predisposing gene to CHD in Han Chinese.This finding has set a direction for further genetic and functional studies。

Abstract：Background This meta-analysis evaluated the effect of noninvasive,positive pressure ventilation on severe,stable chronic obstructive pulmonary disease (COPD).Methods PUBMED,CNKI,Wanfang,EMBASE and the Cochrane trials databases were searched.Randomized controlled trials of patients with severe,stable COPD and receiving noninvasive positive pressure ventilation,compared with sham ventilation or no ventilation,were reviewed.The mortality,physiological and health related parameters were pooled to yield odds ratio (OR),weighted mean differences or standardized mean differences (SMD),with 95％ confidence interval (C/).Results Eight parallel and three crossover randomized controlled trials met the inclusion criteria.Pooled analysis for parallel,randomized controlled trials showed noninvasive positive pressure ventilation:(1) Did not affect the 12-or 24-month mortality (OR 0.82,95％ C/:0.48 to 1.41); (2) Improved the arterial carbon dioxide tension (SMD-0.88,95％C/:-1.43 to-0.34); (3) Did not improve forced expiratory volume in one second (SMD 0.20,95％ C/:-0.06 to 0.46),maximal inspiratory pressure (SMD 0.01,95％ C/:-0.28 to 0.29) or 6-minute walk distance (SMD 0.17,95％ C/:-0.16 to 0.50); (4) Subgroup analysis showed noninvasive positive pressure ventilation improved the arterial carbon dioxide tension in hypercapnic patients.Pooled analysis for crossover randomized controlled trials did not show improvement in arterial blood gas or forced expiratory volume in one second with noninvasive positive pressure ventilation.Conclusions Noninvasive positive pressure ventilation improves the arterial carbon dioxide tension but does not improve the mortality,pulmonary function,or exercise tolerance and should be cautiously used in severe stable chronic obstructive pulmonary disease。

Abstract：Background Surgery is regarded as the most effective treatment to relieve pain and reduce complications in chronic pancreatitis (CP).Two major strategies exist:duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD).Many studies suggest that DPPHR offers advantages during surgery and in the short-term; however,the long-term effects have not been thoroughly investigated.We analyzed the long-term outcomes of DPPHR and PD,over follow-up times of at least 1 year,to determine the optimal surgical treatment for CP.Methods We systemically reviewed all CP surgical treatment reports,and only included randomized controlled trials (RCT) comparing DPPHR and PD,excluding unqualified studies using several pre-specified criteria.When multiple publications of a single trial were found,the most comprehensive current data were selected.Characteristics of the study populations and long-term postoperative outcome parameters were collected.The quality of the studies and data was analyzed using RevMan 4.2 software.Results Five trials were qualified for meta-analysis,with 261 participants in total (114 in the DPPHR group and 147 in the PD group).There were no significant differences in the age,gender,or indications for surgery of each group.At the mean of 5.7-year (1-14 years) follow-up examination,DPPHR and PD resulted in equally effective pain relief,exocrine and endocrine function,and similar mortality rates (P ＞0.05); however,DPPHR patients had improved global quality of life and weight gain,and reduced diarrhea and fatigue (P ＜0.05).Conclusion DPPHR and PD result in equal pain relief,mortality,and pancreatic function; however,DPPHR provides superior long-term outcomes。

Abstract：Objective This review focuses on current knowledge of specific processes that drive chronic airway inflammation which are important in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and lung cancer.Data sources The data used in this review were obtained mainly from studies reported in the PubMed database (1997-2012) using the terms of COPD and lung cancer.Study selection Data from published articles about prevalence of COPD-lung cancer overlap and mechanism involved in lung cancer development in COPD were identified,retrieved and reviewed.Results COPD prevalence,morbidity and mortality vary and are directly related to the prevalence of tobacco smoking except in developing countries where air pollution resulting from the burning of biomass fuels is also important.COPD is characterized by a chronic inflammation of lower airway and,importantly,the presence of COPD increases the risk of lung cancer up to 4.5 fold among long-term smokers.COPD is by far the greatest risk factor for lung cancer amongst smokers and is found in 50％-90％ of patients with lung cancer.Conclusions Both COPD and lung cancer are tobacco smoking-associated chronic diseases that cluster in families and aggravate with age,and 50％-70％ of patients diagnosed with lung cancer have declined spirometric evidence of COPD.Understanding and targeting common pathogenic mechanisms for lung cancer and COPD would have potential diagnostic and therapeutic implications for patients with these lung diseases and for people at risk。

Asthma affects about 300 million people worldwide,placing an enormous strain on health resources in many countries.Evidence is increasing that asthma is a complex condition with different underlying pathophysiologies.1 Scientists around the world have devoted much effort to unveiling this heterogeneity,from phenotyping initially focused on combinations of clinical characteristics,towards endotypes evolving which link pathophysiological mechanism to subtypes of asthma.2The identification of these endotypes,either by matching biology,genetics and therapeutic responses with clinically defined phenotypes or through unbiased genomic approaches,remains limited.3 Moving forward,ongoing studies that expand on these insights into the molecular signatures should enhance our ability to define the endotypes and lead to more targeted approaches to asthma therapy.4

Pneumocystis jiroveci (P.jiroveci) pneumonia (PCP)in non-AIDS immunocompromised patients is much more critical than that in AIDS patients.1 Without treatment,mortality of PCP in immunocompromised patients approaches 100 percent,and there were no reports of spontaneous remissions of PCP without anti-PCP therapy.2 Here we report 2 non-AIDS immunocompromised patients in whom PCP developed and remitted without treatment. Case 1 A 31-year-old man was admitted to hospital because of mild cough and fever for 14 days (the maximum temperature of 37.8℃) and a little breathless for 2 days。

Pulmonary embolism (PE) is a potentially lethal disease.Syncope or seizure as a presenting symptom of PE is very difficult to diagnose.We report a patient with PE presenting recurrent transient loss of consciousness including both syncope and seizure. A previously healthy 51-year-old woman with unremarkable family history and personal history was referred to our hospital for evaluation of recurrent transient loss of consciousness.Half a month before admission,she had approximately 60 seconds of loss of consciousness with urinary and fecal incontinence when getting up in the morning.She had no tonic-clonic activity.She was brought to the local hospital.There in the afternoon she experienced another transient loss of consciousness the same as the previous episode in the morning。

To the editor:We read with a great interest the article by Cai et al.1 They described a good case of Klinefelter's syndrome (KS) with diabetes mellitus (DM).KS is a common abnormality of the sex chromosome,characterized by small testicles,sparse body hair,gynecomastia and hypogonadism in men with two or more X chromosomes.There has been an increased risk of DM,osteoporosis2 and autoimmune disease 3 for KS patients.We report a KS patient accompanying refractory asthma,DM and osteoporosis with a rib fracture. A 43-year-old man was admitted to our hospital for an acute exacerbation of asthma in November 2010.He has suffered from asthma from an age of 3 years,and has been steroid dependent in the past 5 years.Prednisone 20 mg/d alleviated his symptoms and reduced incidences of recurrent attacks.He had a past history of type 2 DM and rib fracture without any trauma。