2014年 · 第127卷第17期

Abstract：Background The Global Initiative for Chronic Obstructive Lung Disease (GOLD) presented a new ABCD group classification of chronic obstructive pulmonary disease (COPD).We aimed to examine the association of spirometric classification and the new GOLD classification with exacerbations,and to compare symptoms in different ways.Methods We investigated 848 patients with stable COPD from 24 hospitals.The annual frequencies of acute exacerbation and hospitalization were compared between the old and new classification.The symptom level was assessed using COPD assessment test (CAT) and modified British Medical Research Council (mMRC) questionnaire.Results A total of 848 patients were included in this study.According to spirometric classification,there were 32 patients of grade Ⅰ (3.8％),315 of grade Ⅱ (37.1％),366 of grade Ⅲ (43.2％),and 135 of grade Ⅳ (15.9％).According to GOLD 2011 classification,there were 59 patients of group A (7.0％),172 of group B (20.3％),55 of group C (6.5％),and 562 of group D (66.3％).In spirometric classification,the annual frequencies of acute exacerbation and associated hospitalization were respectively 1 (0-3) and 0 (0-2) for grade Ⅰ; 1 (0-5) and 0 (0-2) for grade Ⅱ; 2 (0-6) and 1 (0-3) for grade Ⅲ,and 3 (0-6) and 2 (0-3) for grade Ⅳ.In GOLD 2011,respectively 0 (0-3) and 0 (0-1) (group A),1 (0-4) and 0 (0-3) (group B),1 (0-5) and 0 (0-3) (group C),and 3 (0-6) and 1 (0-3) (group D).There were no significant difference between group B and C (Z=-1.347,P=0.178; Z=-0.772,P=0.440,respectively).The coincidence rate using mMRC=1 and CAT=10 as cutoff points was 86.6％ (734/848,x=0.706),compared with 77.9％ (661/848,K=0.60) using mMRC=2 and CAT=10.Conclusions Lung function test may be a better predictor of acute exacerbation and associated hospitalization of COPD.It is more appropriate to use mMRC=1 as cutoff point for assessing COPD symptoms。

Abstract：Background The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae has increasingly become a major contributor to nosocomial infections and can exhibit multiple antibiotic resistance.Previous studies have focused on the resistance genes in ESBL-producing strains,and the resistance-associated genetic environment of non-ESBL-producing strains has been ignored until now.Here,we investigated the occurrence and characteristics of non-ESBL-producing K.pneumoniae,which potentially carries unexpressed resistance genes.Methods K.pneumoniae strains were collected from five medical institutions in China from February 2010 to August 2013.The VITEK-2 ESBL detection system was used as a primary screen to identify the ESBL-producing phenotype,and the three primary types of ESBL-associated genes (CTX,SHV,and TEM) were detected by polymerase chain reaction (PCR) to confirm the strains presenting with a non-ESBL-producing phenotype.mRNA expression in the non-ESBL-producing strains was further screened by reverse-transcription PCR (RT-PCR) to validate their transcriptional efficiency.Results Out of 224 clinically isolated antibiotic-sensitive K.pneumoniae strains with a non-ESBL-producing phenotype,5 (2.2％) were identified to carry inactivated ESBL blaSHV genes with intact upstream promoter regions and resistance gene sequences.Interestingly,three of the five antibiotic-sensitive K.pneumoniae strains containing ESBL blaSHV genes still exhibited mRNA transcription of blasHv,while the other two exhibited no mRNA transcription.Conclusion These findings suggest that inactivated ESBL genes exist in non-ESBL-producing antibiotic-sensitive K.pneumoniae strains,which have the potential to transform the strain into an ESBL phenotype if an inappropriate application or overdose of antibiotics is implemented during clinical management。

Abstract：Background Aerobic exercise can improve symptoms,reduce airway inflammation,and even ameliorate airway remodeling in asthmatic animals and patients.However,previous studies have focused mainly on the effect of aerobic exercise on steroid-sensitive asthma (SSA).The goals of this study were to determine the effect of low-intensity aerobic exercise training on airway hyperresponsiveness,inflammation,and remodeling in a rat model of steroid-resistant asthma (SRA) and to identify the potential mechanisms underlying these effects.Methods Endotoxin-free ovalbumin with or without lipopolysaccharide were applied to establish rat models of SRA and SSA,respectively.Airway hyperresponsiveness,inflammation,remodeling,expression of interleukin (IL)-25,IL-33,thymic stromal lymphopoietin (TSLP),high mobility group box-1 (HMGB1),and IL-17 in bronchoalveolar lavage fluid (BALF),and the role of dexamethasone (DXM) were compared between these two asthmatic rat models.The effect of low-intensity aerobic exercise training and anti-HMGB1 treatment on airway hyperresponsiveness,inflammation,and remodeling in SRA rats also was evaluated.Results SRA rats developed neutrophil-dominated airway inflammation ((29.5±4.1)％ of the total cell numbers in BALF),whereas SSA rats developed eosinophil-dominated airway inflammation ((24.0±6.1)％ of the total cell numbers in BALF).Compared with SSA rats,SRA rats had more severe airway hyperresponsiveness,lower levels of IL-25 ((33.6±10.3) vs.(104.8±24.9) pg/ml),IL-33 ((87.5±25.0) vs.(226.6±40.7) pg/ml),and TSLP ((1 933.2±899.5) vs.(7 224.0±992.1) pg/ml),and higher levels of HMGB1 ((21.2±4.5) vs.(5.4±1.6) ng/ml) and IL-17 ((780.5±261.7) vs.(291.4±76.4) pg/ml) in BALF (all P ＜0.05).However,there was no significant difference in goblet cell hyperplasia,subepithelial collagen thickness,and airway smooth muscle remodeling between the two groups.Compared with control SSA rats,airway hyperresponsiveness,inflammation,and remodeling in SRA rats were less sensitive to DXM treatment.Anti-HMGB1 treatment attenuated airway hyperresponsiveness,inflammation,and remodeling in SRA rats to a certain extent and was accompanied by lower levels of IL-17 ((369.2±126.7) vs.(780.5±261.7) pg/ml in control SRA rats) in BALF (P ＜0.05).Low-intensity aerobic exercise training decreased the expression of both HMGB1 ((14.1±2.9) vs.(21.2±4.5) ng/ml in control SRA rats) and IL-17 ((545.3±148.6) vs.(780.5±261.7) pg/ml in control SRA rats) in BALF (all P ＜0.05) and was accompanied by improved airway hyperresponsiveness,inflammation,and remodeling in SRA rats (all P ＜0.05).Conclusions Low-intensity aerobic exercise training attenuated airway hyperresponsiveness,inflammation,and remodeling in a rat model of SPA.Decreased HMGB1 and IL-17 levels in BALF by aerobic exercise training at least partly contributed to the improvements of SPA。

Abstract：Background Obstructive sleep apnea hypopnea syndrome (OSAHS) is underdiagnosed.Screening patients at high risk of OSAHS is extremely important.Using the standard questionnaire to screen OSAHS is a practical method.This study aimed to evaluate the value of the STOP-Bang questionnaire (SBQ) in screening OSAHS in sleep-disordered breathing clinic by comparing it with the Epworth sleepiness scales (ESS),Berlin questionnaire,and STOP questionnaire.Methods In this study,212 patients at the sleep-disordered breathing clinic of the Peking Union Medical College Hospital between May 2011 and January 2012 were prospectively included.They were asked to fill in the SBQ,ESS,Berlin questionnaire,and STOP questionnaire before overnight polysomnography (PSG).Using PSG as gold standard,the sensitivities and specificities of SBQ were compared with those of ESS,Berlin questionnaire,and STOP questionnaire.Results There was no significance in applying ESS score ≥11 to screen OSAHS and detect moderate and severe OSAHS (P ＞0.05).SBQ was superior to Berlin questionnaire and STOP questionnaire in screening OSAHS and detecting the severity of OSAHS patients.The sensitivities of SBQ score ≥3 with apnea hypopnea index (AHI) ≥5/h,AHI ≥15/h,and AHI ≥30/h as gold standards were 94.9％,96.5％,and 97.7％,respectively.The specificities were 50.0％,28.6％,and 17.9％,respectively.The area upper curves were 0.815 (0.706-0.925,P ＜0.01),0.746 (0.665-0.828,P ＜0.01),and 0.751 (0.686-0.817,P ＜0.01),respectively.According to SBQ,the population was classified into high-risk group and low-risk group.The gender,BMI,neck circumference,AHI,LSpO2,and number of subjects ofAHI ≥5/h,AHI ≥15/h,and AHI ≥30/h of these two groups were significantly different.Conclusions The SBQ has superior predictive value compared with ESS,Berlin questionnaire,and STOP questionnaire.It should be used further in screening for OSAHS in the general population。

Abstract：Background Glucosylceramide synthase (GCS),an enzyme responsible for ceramide glycosylation,plays an important role in multidrug resistance (MDR) in some tumors in vitro; however,its expression and clinicopathological significance in non-small cell lung cancer (NSCLC) remains unclear.Methods We evaluated GCS expression in 116 paired tumor and adjacent non-cancerous tissues and 50 frozen tissues from patients with NSCLC using immunohistochemistry and western blotting,and explored the correlation between GCS and NSCLC clinicopathological characteristics and prognosis.We observed the association between GCS and the MDR proteins P-glycoprotein (P-gp) and lung resistance-related protein (LRP) to determine the link between GCS and MDR at the histological level.Results GCS expression was significantly upregulated in NSCLC tumors compared with non-cancerous tissue.There was high GCS expression in 75/116 tumor specimens (64.7％) and 16/116 non-cancerous specimens (13.8％).High GCS expression was significantly associated with poor differentiation (P=0.01),lymph node metastasis (P=0.004),recurrence/ distant metastasis (P=0.006),and chemotherapy resistance (P=0.025).Multivariate analysis demonstrated that GCS immunopositivity was an independent risk factor for survival (P=0.018).P-gp was expressed in 80/116 tumors (69.0％) and in 12/116 non-cancerous tissue specimens (10.3％; P=0.001); LRP was expressed in 85/116 tumors (73.3％) and 19/116 non-cancerous tissue specimens (16.4％; P=0.001).Importantly,the results demonstrated that increased GCS expression in NSCLC cancer specimens correlated with increased expression of P-gp and LRP,molecules known to stimulate cancer cell MDR (r=0.612 and 0.503,P=0.01 and 0.035,respectively).Conclusion GCS upregulation might contribute to the development of NSCLC and could be a useful prognostic indicator and chemoresistance predictor for NSCLC patients。

Abstract：Background Outcomes in patients requiring coronary artery bypass graft (CABG) surgery have been improved with devices such as the intra-aortic balloon pump (IABP).Good coronary collateral circulation (CCC) has been shown to reduce mortality in patients with coronary artery disease (CAD).We aimed to investigate whether poor preoperative CCC grade is a predictor of in-hospital mortality in CABG surgery requiring IABP support.Methods Fifty-five consecutive patients who were undergoing isolated first time on-pump CABG surgery with IABP support were enrolled into this study and CCC of those patients was evaluated.Results Twenty-seven patients had poor CCC and 28 patients had good CCC.In-hospital mortality rate in poor CCC group was significantly higher than good CCC group (14 (50％) vs.4 (13％),P=0.013).Preoperative hemoglobin level (OR:0.752; 95％ CI,0.571-0.991,P=0.043),chronic obstructive pulmonary disease (OR:6.731; 95％ CI,1.159-39.085,P=0.034) and poor CCC grade (OR:5.750; 95％ CI,1.575-20.986,P=0.008) were associated with post-CABG in-hospital mortality.Poor CCC grade (OR:4.853; 95％ CI,1.124-20.952,P=0.034) and preoperative hemoglobin level (OR:0.624; 95％ CI,0.476-0.954,P=0.026) were independent predictors of in-hospital mortality after CABG.Conclusion Preoperative poor CCC and hemoglobin are predictors of in-hospital mortality after CABG with IABP support。

Abstract：Background The diagnosis of liver fibrosis is a difficult task at any time using conventional clinical imaging.Intravoxel incoherent motion (IVIM) can be used to investigate both diffusion and perfusion changes in tissues.This study was designed to determine the value of IVIM in the diagnosis and staging of liver fibrosis.Methods IVIM examinations were performed on a GE 3.0T MR scanner in 25 patients with liver fibrosis and 25 healthy volunteers as the control group.Patients with liver fibrosis diagnosis were confirmed by pathology and staged on a scale of F0-4.The standard ADC values and the values of a biexponential model (slow ADC (Dslow),fast ADC (Dfast) and fraction of fast ADC (FF)) were measured in three liver regions per person.The mean standard ADC values,Dslow values,Dfast values and FF values from the study group were compared among the right posterior hepatic lobe,right anterior hepatic lobe and medial segment of the left lobe.Receiver Operating Characteristic (ROC) curves and independent-samples t-tests were used to calculate the mean standard ADC values,Dslow values,Dfast values and FF values from the study group and the control group.Spearman rho correlation analysis was used for the stage of liver fibrosis.The liver fibrosis stages between the groups F0-1 and F2-4,the groups F0-2 and F3-4 were compared.Results Among the liver fibrosis,there was no significant difference in the mean standard ADC values,Dslow values,Dfast values,and FF values obtained from the right posterior hepatic lobe,right anterior hepatic lobe and medial segment of the left lobe.Using ROC analysis,the Area Under the Curve (AUC) values of standard ADC,Dslow,Dfast,FF were all between 0.7 to 0.9.The mean standard ADC values,Dslow values,Dfast values and FF values of the liver in the study group were significantly lower than the values in the control group (P ＜0.05).As the stage of the fibrosis increased,the values decreased by Spearman rho correlation analysis.The mean values (standard ADC,Dslow,Dfast,and FF) of liver fibrosis stages between the groups F0-1 and F2-4,the groups F0-2 and F3-4 showed significant differences (P＜0.05).Conclusions IVIM can reflect the conditions of perfusion and diffusion in liver fibrosis and thus distinguish between normal liver and liver fibrosis.The IVIM technique may serve as a valuable tool for detecting and characterizing liver fibrosis,and monitoring its progression in a noninvasive manner。

Abstract：Background The mitochondrial displacement loop (D-loop) accumulates mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA).We previously identified disease riskassociated SNPs in the D-loop of chronic kidney disease (CKD) patients; in this study,we investigated the association of age-at-onset and D-loop SNPs in CKD patients.Methods The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008.The age-at-onset curve of the CKD patients was calculated using the KaplanMeier method at each SNP site,and compared using the log-rank test.Results The mean age of 119 CKD patients was (55.6±14.2) years,and 56.3％ were males.The mean estimated glomerular filtration rate (eGFR) was (81.2±12.4) ml·min-1·1.73 m-2,with 79.8％ (n=95) of patients having an eGFR ＜60 ml·min-1·1.73 m-2.All participants had an eGFR ＞30 ml·min-1·1.73 m-2.The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients.The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test.The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site (P=0.010).Conclusions Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients.Accordingly,the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease。

Abstract：Background Cavity reconstruction after benign bone tumor removal is varied and controversial.AIIograft is widely used but is associated with complications.New bone substitutes,such as calcium sulfate artificial bone,have been introduced for bone tumor operation.However,the bone healing response of artificial bone has not been compared with allograft bone.We therefore compared calcium sulfate grafts (study group) with bone allografts (control group) for the treatment of benign bone tumors.Methods We retrospectively reviewed 50 patients who underwent calcium sulfate reconstruction and 50 patients who underwent allograft cancellous bone reconstruction.The two groups were well matched.The mean follow-up time of the study group was 19.9 (12-55) months.We investigated bone healing response,complications,and factors affecting bone healing.Results At the last follow-up,84％ (42/50) of cases in the study group and 62％ (31/50) of cases in the control group had achieved clinical healing (P=0.013).The initial healing rate showed no significant difference between the two groups (100％ vs.96％,P=0.153).The mean healing times for calcium sulfate and allograft bone were 9.6 (3-42) months and 13.8 (3-36) months,respectively (P ＜0.01).Complications in the study group were minor and resolved.Implant volume was a significant factor affecting bone healing.Conclusion The calcium sulfate bone substitute showed a satisfactory healing outcome and safety profile in reconstruction of bone defects after benign bone tumor curettage,especially in smaller cavities。

Abstract：Background Optic neuritis (ON) is often the first symptom of multiple sclerosis (MS) and neuromyelitis optica (NMO) while there has been very little research reported on ON combined with Sj(o)gren's syndrome (SS).The aim of this study is to provide different treatments and services for and NMO patients combined with SS.Methods Twenty-seven patients with ON combined SS were divided into two groups:corticosteroid group (C group,methylprednisolone sodium succinate,14 patients) and corticosteroid+ immunosuppressant group (C+I group,leflunomide,13 patients).ON relapse times in 1 year after treatment,number of patients who relapsed to NMO/MS in 1 years,visual acuity and retina nerve fiber layer (RNFL) thickness were measured.Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher's exact test was to compare proportions.Results ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse,and the patients are often hormone dependent.The patients are more likely anti-aquaporin-4 IgG seropositive (70.4％).They are liable to form a centrocecal scotoma and tubular vision.The times of relapse decreased in patients who used immunosuppressant,and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month followup period (P ＜0.05); however,the RNFL thickness at the four quadrants was not significantly different.Conclusions The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics.This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid。

Abstract：Background Vitamin D supplementation is believed to be beneficial in the treatment of patients with tuberculosis (TB),however,results from clinical trials have been inconclusive.Methods We performed a systematic literature search across MEDLINE,EMBASE,the Cochrane Central Register of Controlled Trials,Springer,EBSCO,ProQuest,HighWire Press,and Web of Science,published as of December 2013.We individually inspected citations and extracted data independently.We estimated pooled risk ratios (RR) and 95％ confidence intervals (CI) using random-effect models.We also assessed risk of bias using the Jadad scale and the quality of the evidence using GRADE.We included all randomized controlled trials comparing vitamin D with or without standard TB therapy or placebo.Results A total of five studies were analyzed in our meta analysis covering 841 newly-diagnosed TB cases.Patients receiving vitamin D supplementation had a 39％ reduced risk of sputum smear or culture positive after six weeks of antiTB treatment than those in the control group,although this is not statistically significant (pooled RR 0.61,95％ CI 0.24 to 1.56,P=0.30).Apart from an increased serum vitamin D level in the supplement group after eight weeks of treatment there was no evidence of any additional adverse effects related to vitamin D.Conclusions The meta analysis results indicate that vitamin D supplementation does not seem to have any beneficial effect in the treatment of TB.Future rigorous randomized controlled trials are needed to explore whether the supplementation of vitamin D could shorten treatment duration and to confirm whether the polymorphisms of vitamin D receptor have any potentially beneficial effect。

Abstract：Objective To have a better understanding of genetic contributions to the development of obstructive sleep apnea hypopnea syndrome (OSAHS) by reviewing studies on its genetic basis.Data sources A comprehensive search of the PubMed literature without restriction on the publication date was carried out using terms "obstructive sleep apnea" and "candidate genes" or "genetics".Study selection Articles were selected if they were an original research paper or meta analysis of the genetic factors of OSAHS.Results Four intermediate phenotypes were described and several candidate genes that may determine the expression and severity of OSAHS were reviewed.Conclusion Multiple gene-gene interactions occurring in genes that affect obesity,craniofacial structure,ventilator control and asleep-awake pattern may influence the expression of OSAHS in a suitable environment。

Abstract：Objective To review the studies investigating the increased risk of lung cancer in patients with idiopathic pulmonary fibrosis (IPF).Data sources Data cited in this review were obtained mainly from PubMed and Medline from 1999 to 2013 and highly regarded older publications were also included.Study selection We identified,retrieved and reviewed the information on the frequency,risk factors,anatomical features,histological types,clinical manifestations,computed tomography findings and underlying mechanisms of lung cancer in IPF patients.Results The prevalence rates of lung cancer in patients with IPF (4.8％ to 48％) are much higher than patients without IPF (2.0％ to 6.4％).The risk factors for lung cancer in IPF include smoking,male gender,and age.Lung cancers often occur in the peripheral lung zones where fibrotic changes are predominant.Adenocarcinoma and squamous cell carcinoma are the most common types of lung cancer in patients with IPF.Radiologic features of these patients include peripherally located,ill-defined mass mimicking air-space disease.The underlying mechanisms of the development of lung cancer in patients with IPF have not been fully understood,but may include the inflammatory response,epithelial injury and/or abnormalities,aberrant fibroblast proliferation,epigenetic and genetic changes,reduced cell-to-cell communication,and activation of specific signaling pathways.Conclusions These findings suggest that IPF is associated with increased lung cancer risk.It is necessary to raise the awareness of lung cancer risk in IPF patients among physicians and patients。

Abstract：Objective To review the current evidence about the prevalence of obstructive sleep apnea in patients with Marfan's syndrome,and discuss some proposed potential mechanisms for this relationship.Data sources The data in this review were mainly from Medline and PubMed articles published in English from 1990 to 2013.The search term was "Marfan's syndrome and sleep apnea".Study selection Clinical evidence about the epidemiology of obstructive sleep apnea in patients with Marfan's syndrome; the mechanism that causes obstructive sleep apnea; interventional therapy for patients with Marfan's syndrome,and coexisting obstructive sleep apnea.Results A high prevalence of obstructive sleep apnea exists in patients with Marfan's syndrome.The potential reasons are craniofacial abnormalities and lax upper airway muscles,which lead to high nasal airway resistance and upper airway collapse.Obstructive sleep apnea mechanically deteriorates aortic dilatation and accelerates progression of aortic aneurysms.The condition is reversible and rapid maxillary expansion and adequate continuous positive airway pressure therapy are possible effective therapies to delay the expansion of aortic diameter in patients with Marfan's syndrome.Conclusions Obstructive sleep apnea is strongly associated with Marfan's syndrome.Craniofacial abnormalities and lax upper airway are the main mechanisms.Untreated obstructive sleep apnea accelerates progression of aortic dissection and rupture.Effective therapies for obstructive sleep apnea could postpone the aortic dilatation in patients with Marfan's syndrome。

Abstract：Objective To review the current crosslinking strategies for acelluar matrix scaffold,laying the foundation for subsequent experiment.Data sources Data were mainly obtained from recent papers published in PubMed or indexed by Web of Science,with keyword like crosslinking.Results Various crosslinking strategies,including chemical,physical and biological methods,have been introduced to facilitate the performance of fresh acellular matrix.Chemical crosslinking reagents,involved in synthetic and naturally derived agents,need to be eliminated before implantation in case of their potential biotoxicity,although several crosslinking agents with less toxicity and specific characteristics have been developed.Physical crosslinking methods present to be safe,additive-free and relatively controllable for rapid surface functionalization with no consideration of remaining radioactivity.Biological crosslinking strategies have attracted great interest,and have been demonstrated to enhance collagen-based crosslinking since their preparations do not need toxic or potentially biologically contaminated substances and can be carried out under physiological conditions.Conclusions Kinds of crosslinking methods with its potential advantages have been developed to modify raw acelluar matrix,of which the performance are promising after being crosslinked by several crosslinking treatments.Further preclinical and clinical evaluations should be taken to vertify their safety and efficacy for the tissues and organs substitutes in tissue and regenerative medicine。

Abstract：Objective The objective of this article was to review the current advances in diagnostic methods for Acanthamoeba keratitis (AK).Data sources Data used in this review were retrieved from PubMed (1970-2013).The terms "Acanthamoeba keratitis" and "diagnosis" were used for the literature search.Study selection Data from published articles regarding AK and diagnosis in clinical trials were identified and reviewed.Results The diagnostic methods for the eight species implicated in AK were reviewed.Among all diagnostic procedures,corneal scraping and smear examination was an essential diagnostic method.Polymerase chain reaction was the most sensitive and accurate detection method.Culturing of Acanthamoeba was a reliable method for final diagnosis of AK.Confocal microscopy to detect Acanthamoeba was also effective,without any invasive procedure,and was helpful in the early diagnosis of AK.Conclusion Clinically,conjunction of various diagnostic methods to diagnose AK was necessary。

Abstract：Objective This review aimed at understanding pregnancy-induced changes in the maternal immune response and mechanisms for the establishment of feto-maternal tolerance.Data sources Articles cited in this review were obtained from PubMed in English from 2000 to 2014,and the search string included keywords such as feto-maternal tolerance,dendritic cells,macrophage,T regulatory cells,natural killer cells,cytokines and hormone.Study selection Articles regarding altered maternal immune response,including the proliferation and differentiation of the altered cells,and the production of cytokines and regulation of hormones in the feto-maternal interface were retrieved,reviewed and analyzed.Results The changes in immune cells and cytokines in the local uterine microenvironment and peripheral blood are correlated with the establishment of feto-maternal tolerance.The endocrine system regulates the maternal immune system,promoting modifications during pregnancy.In these regulatory networks,every factor is indispensible for others.Conclusions The integration and balance of these immune factors during pregnancy give rise to an environment that enables the fetus to escape rejection by the maternal immune system.This progress is complicated,and needs more comprehensive exploration and explanation。