2014年 · 第127卷第20期

Abstract：Background Stroke is now the most prevalent and debilitating disease affecting diabetic population in China.The study aimed to investigate the prevalence of stroke and metabolic disorders in the middle-aged and elderly Chinese with type 2 diabetes.Methods A total of 4 629 subjects with type 2 diabetes (males:1 917; females:2 712) aged ＞ 40 years from Shijingshan district,Beijing,China from November 2011 to August 2012 were included in the study.Data on demographic information,lifestyle,history of diabetes mellitus,stroke,coronary heart disease,hypertension,and dyslipidemia were collected.The oral glucose tolerance test or a standard meal test was performed.Non-fatal stroke was reported by the subjects.The 2-tailed test was used,and P ＜0.05 was regarded as statistically significant.Results Prevalence of stroke in the subjects with type 2 diabetes was 5.5％.The prevalence of smoking,overweight or obesity,hypertension,and dyslipidemia was 41.0％,65.8％,67.4％,and 52.0％ in males,and 2.2％,65.5％,69.5％,and 57.6％ in females.Multivariate Logistic regression analysis showed that increased age,hypertension,diabetic duration,and overweight or obesity were positively correlated with stroke in the population with type 2 diabetes,whereas highdensity lipoprotein cholesterol level was negatively correlated with stroke.After adjustment for age and gender,the odds ratio values of stroke in subjects having 1,2 or ＞3 of 4 risk factors,including smoking,overweight or obesity,hypertension and dyslipidemia,were 2.302 (95％ CI:0.789-6.712),4.089 (95％ CI:1.470-11.373),6.023 (95％ CI:2.176-16.666),compared with subjects without any of the above 4 risk factors.Conclusions The prevalence of stroke was higher in middle-aged and elderly Chinese with type 2 diabetes than that in the general population.With the aggregation of risk factors,the prevalence of stroke increased。

Abstract：Background Copious evidence from epidemiological and laboratory studies has revealed that sleep status is associated with glucose intolerance,insulin resistance,thus increasing the risk of developing type 2 diabetes.The aim of this study was to reveal the interaction of sleep quality and sleep quantity on glycemic control in patients with type 2 diabetes mellitus.Methods From May 2013 to May 2014,a total of 551 type 2 diabetes patients in Tianjin Metabolic Diseases Hospital were enrolled.Blood samples were taken to measure glycosylated hemoglobin (HbA1c),and all the patients completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire to evaluate their sleep status."Good sleep quality" was defined as PQSI ＜5,"average sleep quality" was defined as PQSI 6-8,and "poor sleep quality" was defined as PQSI ＞8.Poor glycemic control was defined as HbA1c ＞7％.Sleep quantity was categorized as ＜6,6-8,and ＞8 hours/night.Short sleep time was defined as sleep duration ＜6 hours/night.Results In the poor glycemic control group,the rate of patients who had insufficient sleep was much higher than that in the other group (x2=11.16,P=0.037).The rate of poor sleep quality in poor glycemic control group was much greater than that in the average control group (x2=9.79,P=0.007).After adjusted by gender,age,body mass index,and disease duration,the adjusted PSQI score's OR was 1.048 (95％ CI 1.007-1.092,P=0.023) for HbA1c level.The sleep duration's OR was 0.464 (95％ CI 0.236-0.912,P=0.026) for HbA1c level.One-way analysis of variance showed that the poor sleep quality group had the highest homeostasis model assessment-insulin resistance (P ＜0.01).Conclusions Inadequate sleep,in both quality and quantity,should be regarded as a plausible risk factor for glycemic control in type 2 diabetes.Poor sleep might bring much more serious insulin resistance and could be the reason for bad glycemic control.A good night's sleep should be seen as a critical health component tool in the prevention and treatment of type 2 diabetes.It is important for clinicians to target the root causes of short sleep duration and/or poor sleep quality。

Abstract：Background The importance of polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear.The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.Methods Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy.DNA samples were isolated from peripheral blood collected before treatment.The three single nucleotide polymorphisms (SNPs) (rs1801131,rs1801133,rs2274976) genotypes of the MTHFR gene were determined by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).Results The average response rate for chemotherapy was 46.7％.Homozygous genotypes rs2274976G/G (x2=22.7,P ＜0.01) and rs1801131A/A (x2=14.3,P=0.008) were over-represented in responsive patients.Carriers of the rs2274976A allele genotypes (G/A and A/A) and of the rs1801131C allele genotypes (A/C and C/C) were prevalent in nonresponsive patients.In the haplotype association analysis,there was a significant difference in global haplotype distribution between the groups (x2=20.69,P=0.000 124).Conclusions These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population.Well-designed,comprehensive,and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted。

Abstract：Background H9N2 avian influenza viruses (AIVs) have repeatedly caused infections in mammals even humans in many countries.The purpose of our study was to evaluate the acute lung injury (ALI) caused by H9N2 viral infection in mice.Methods Six-to eight-week-old female SPF C57BL/6 mice were infected intranasally with 1x104 MID50 of A/HONG KONG/2108/2003 [H9N2 (HK)] virus.Clinical signs,pathological changes,virus titration in tissues of mice,arterial blood gas,and cytokines in bronchoalveolar lavage fluid (BALF) and serum were observed at different time points after AIV infection.Results H9N2-AIV-infected mice exhibited severe respiratory syndrome,with a mortality rate of 50％.Lung histopathological changes in infected mice included diffuse pneumonia,alveolar damage,inflammatory cellular infiltration,interstitial and alveolar edema,and hemorrhage.In addition,H9N2 viral infection resulted in severe progressive hypoxemia,lymphopenia,and a significant increase in interleukin 1,interleukin 6,tumor necrosis factor,and interferon in BALF and serum.Conclusions The results suggest that H9N2 viral infection induces a typical ALl in mice that resembles the common features of ALl.Our data may facilitate the future studies of potential avian H9N2 disease in humans。

Abstract：Background The use of post-enucleation adjuvant therapy to decrease the extraocular relapse rate is frequently considered,but there is much controversy about the indications for adjuvant therapy.The aim of this retrospective study was to observe the treatment and prognosis for different degrees of invasion of eye tissue in retinoblastoma (RB) and identify the indications for post-enucleation adjuvant therapy.Methods We recruited 537 children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2012 in our hospital,and divided them into three groups according to their number of histopathologic risk factors:0 factor,1 factor,or ＞2 factors.Histopathologic high-risk factors included invasion of the optic nerve posterior to the ethmoid plate (including optic nerve stumps) and extensive invasions of the choroid,sclera,anterior chamber,iris,and ciliary body.Treatment was delivered accordingly,and the prognosis of different degrees of histopathologic invasion was observed.The subjects were followed up for 6 months to 7 years (average follow-up time:35 months).Statistical analysis was analyzed using x2test.P ＜0.05 was considered significant.Results Of the 537 RB patients who received enucleation,25 died (overall survival:95.3％).Of the 369 (68.7％) with no histopathologic risk factors,1 died of recurrence,with a mortality rate of 0.3％,whereas of the 168 (31.3％) with histopathologic risk factors,26 had recurrences and 24 died (mortality rate:14.3％; P=0.000).Of the 93 patients (17.3％),each of whom had a single risk factor,nine had recurrences,16 died (8.6％).Of the 75 patients (14％) with two or more high-risk factors,16 died (21.3％).These differences were statistically significant between the three (P=0.000).Conclusion Chemotherapy is recommended for patients with histopathologic risk factors,especially those with two or more histopathologic risk factors。

Abstract：Background Bilateral transpedicular screw fixation in conjunction with interbody fusion is widely used to treat lumbar degenerative diseases; however,there are some disadvantages of using this fixation system.This study comparatively analyzes the results of unilateral and bilateral pedicle screw fixation combined with transforaminal lumbar interbody fusion (TLIF) for one-level lumbar degenerative diseases.Methods Sixty-six cases with one-level lumbar degenerative diseases were studied.The patients were divided according to surgical approach into a unilateral group (Group A) and a bilateral group (Group B).The patients were evaluated for pain by visual analog scale (VAS) and Oswestry Disability Index (ODI).Operating time,blood loss,duration of hospitalization,and complication rate were also evaluated.Patients were examined at 1,3,6,and 12 months postoperatively and every year thereafter.Results Group A patients' average preoperative VAS and ODI scores were 7.03 ± 0.98 and (64.22±6.38)％,respectively,significantly decreased to 2.91 ± 0.88 and (14.42±2.08)％,respectively,at the last follow-up (P =0.000).In Group B,the average preoperative VAS and ODI scores were 6.79±0.86 and (63.22±4.70)％,respectively,significantly decreased to 3.12±0.96 and (14.62±2.08)％,respectively,at the last follow-up (P=0.000).No significant difference in the duration of hospitalization was found between groups.Operating time and blood loss of (125.9±13.0) minutes and (211.4±28.3) ml,respectively,in Group A were significantly less than (165.2±15.3) minutes and (258.6±18.3) ml,respectively,in Group B (P=-0.000).All patients achieved good bone union and had no pseudarthrosis at the last follow-up.Conclusions There are no clinical differences between unilateral and bilateral pedicle screw fixation combined with TLIF for one-level lumbar degenerative diseases.Unilateral fixation reduces operating time,bleeding,and cost of hospitalization。

Abstract：Background In haploidentical hematopoietic stem cell transplantation (HSCT),the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD.However,the successful application of modified DLI depended not only on the reduction of severe GVHD,but also on the preservation of graft-versus-leukemia (GVL) effect.Therefore,this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for ＜6 weeks on GVL effect after modified DLI in haploidentical HSCT.Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively.Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for ＜6 weeks.Results First,compared with prophylaxis for ＜6 weeks,prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6％ vs.69.0％,P ＜0.001).Besides,prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P ＜0.001).Second,prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P ＜0.05),reduced the therapeutic application of immunosuppressive agents (P=0.019),but increased the incidence of chronic GVHD (P＜0.05).Third,prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients,as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P ＜0.05).Conclusions In haploidentical HSCT,prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect,but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for ＜6 weeks.This strategy will probably improve the safety and efficacy of modified DLI further。

Abstract：Background The hippocampus and amygdala exhibit structural and functional alterations in patients with depression.The objective of this study was to investigate the structural and functional relationships between these core regions.Methods Based on the severity of their condition,60 patients and 20 healthy controls were equally divided into four groups (mild group,moderate group,major group and health controls group),scanned by T1-MR,functional magnetic resonance imaging (fMRI),and susceptibility weighted imaging (SWI).Structural image,BOLD image,and SWl image were collected for processing and analysis.The characteristics of the depression and controls were checked by analysis of variance test,and the difference between groups was checked by Dunnett's test.Results The volume of hippocampus and amygdala varied with the severity of the condition.The signal obtained under the stimulation of negative events was linearly decreased in the mild,moderate and major groups revealed by fMRI.The length and diameter of the lateral ventricle vein was reduced in the mild group,whereas the number of branches increased.In the moderate and major groups,the reduction in the length,diameter and increase in the number of branches of the lateral ventricle vein were greater.Conclusion The alterations of the volume,fMRI,and cerebral veins in these core regions may account for the causal relationship between structure and function。

Abstract：Background Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue perfusion.Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis.However,it has side effects that limit its therapeutic utility in vivo,especially at high concentrations.This study aimed to investigate whether an intramuscular injection of a genetically engineered zinc finger VEGF-activating transcription factor modulates the endothelial progenitor cells (EPC) and promotes therapeutic angiogenesis in a hindlimb ischemia model with type 1 diabetes.Methods Alloxan (intravenous injection) was used to induce type Ⅰ diabetes in C57BL/6 mice (n=58).The ischemic limb received ZFP-VEGF (125 μg ZFP-VEGF plasmid in 1％ poloxamer) or placebo (1％ poloxamer) intramuscularly.Mice were sacrificed 3,5,10,or 20 days post-injection.Limb blood flow was monitored using laser Doppler perfusion imaging.VEGF mRNA and protein expression were examined using real-time PCR and ELISA,respectively.Capillary density,proliferation,and apoptosis were examined using immunohistochemistry techniques.Flow cytometry was used to detect the EPC population in bone marrow.Two-tailed Student's paired t test and repeated-measures analysis of variance were used for statistical analysis.Results ZFP-VEGF increased VEGF mRNA and protein expression at 3 and 10 days post-injection,and increased EPC in bone marrow at day 5 and 20 post-injection compared with controls (P＜0.05).ZFP-VEGF treatment resulted in better perfusion recovery,a higher capillary density and proliferation,and less apoptosis compared with controls (P＜0.05).Conclusions Intramuscular ZFP-VEGF injection promotes therapeutic angiogenesis in an ischemic hindlimb model with type 1 diabetes.This might be due to the effects of VEGF on cell survival and EPC recruitment。

Abstract：Background Epidemiologic studies have reported inconsistent results regarding tea consumption and the risk of pancreatic cancer.This study aimed to investigate whether tea consumption is related to the risk of pancreatic cancer.Methods We searched Medline,EMBASE,ISI Web of Science,and the Cochrane library for studies published up to November 2013.We used a meta-analytic approach to estimate overall odds ratio (OR) and 95％ confidence interval (CI) for the highest versus the lowest tea consumption categories.Results The summary OR for high versus no/almost never tea drinkers was 1.04 (95％ CI:0.91-1.20),with no significant heterogeneity across studies (P=0.751;I2=0.0％).The OR was 0.99 (95％ CI:0.77-1.28) in males and 1.01 (95％ CI:0.79-1.29) in females.The OR was 1.07 (95％ CI:0.85-1.34) in Asian studies,1.05 (95％ CI:0.84-1.31) in European studies,and 0.98 (95％ CI:0.72-1.34) in the US studies.The OR was 0.87 (95％ CI:0.69-1.10) without adjustment for a history of diabetes and 1.16 (95％ CI:0.97-0.39) after adjustment for a history of diabetes.The OR was 0.90 (95％ CI:0.72-1.12) without adjustment for alcohol drinking and 1.16 (95％ CI:0.96-1.39) after adjustment for alcohol drinking.The OR was 0.97 (95％ CI:0.76-1.25) without adjustment for BMI and 1.07 (95％ CI:0.87-1.31) after adjustment for BMI.Conclusion This systematic meta-analysis of cohort studies dose not provide quantitative evidence that tea consumption is appreciably related to the risk of pancreatic cancer,even at high doses。

It is generally believed that genotype and adult lifestyle elements are primary risks of diabetes mellitus. However, increasing evidence demonstrates that early life malnutrition during the period of gestation andJor lactation may increase our susceptibility to some metabolic diseases in later life and the underlying mechanism is not very clear. Recently, epigenetics is hypothesized to be the important molecular basis of the imbalanced early life nutrition and glucose metabolism disorders. The fundamental mechanism is that early developmental nutrition can regulate epigenetic modifications of some genes associated with development and metabolism. MicroRNAs (miRNAs) are recognized as an important epigenetic modification and they are a major class of small noncoding RNAs (about 20-22 nucleotides) which can mediate posttranscriptional regulation of target genes with cell differentiation and apoptosis。

Abstract：Background Given the pace with which standards of care have changed,timely assessment of their impact on routine clinical practice and patient outcomes is needed.In coordination with the Chinese Diabetes Society (CDS),we developed a quantitative survey to explore the implementation of standards of care for type 2 diabetes (T2D) in China.Methods A national online survey of physicians involved in the management of T2D in China was conducted over a 4-week period in 2012.Completed responses were obtained from 1 028 physicians.Participants responded to 52 questions designed to capture information relating to their demographic and clinical practice profiles.The questionnaire was divided into three sections:basic information,diagnosis practices and screening methods on main complications,and treatment and control practices.The questionnaire was developed in conjunction with the CDS.Results Overall,83％ of surveyed physicians were at least "aware" of the CDS guidelines on standards of care for T2D.Level of awareness was directly related to hospital grade,specialty,geographic location,professional rank and participation in CDS training.The 2-hour oral glucose tolerance test was reported as the most ever-used approach across all three hospital grades and physician specialties,with a usage rate of 97％.Respondents selected their choice of primary treatment for newly diagnosed T2D patients.Just over half (52％) indicated the use of oral anti-diabetic drugs (OAD) monotherapy,in line with CDS recommendations.However,OAD use varied considerably between different regions and city tiers.Despite hemoglobin A1c being defined as the gold standard for glucose control,it was not universally measured,with more physicians indicating routine use of glucose before fasting and glucose non-fasting.Conclusion The standards-of-care analysis has provided important insights into the current management of T2D among physicians in China across different geographical regions,hospital grades,specialties,professional statuses,and levels of CDS guideline awareness and training。

Abstract：Background Insulin injection therapy is one of the most effective treatments for type 2 diabetes mellitus (T2DM).Many people with T2DM in western countries resist starting insulin therapy; whether the same is true in China is unknown.This survey-based study assessed acceptance and rejection of insulin therapy among individuals with T2DM in China and selfreported reasons for these therapy choices.It also examined what methods may be useful for increasing the rate of insulin acceptance.Methods A multi-center,cross-sectional survey was conducted between April and July 2010 to a convenience sample of inpatients and outpatients at 50 medical centers across 29 administrative divisions in China.Data were collected on sociodemographic and T2DM characteristics,therapy regime,and attitudes toward insulin therapy.Results A total of 6 043 patients were surveyed,and 5 961 complete questionnaires (98.6％) were used in the analysis.Just over half the respondents (3 460,58.0％) reported negative attitudes to insulin therapy,including 2 508 of the 4 469 patients (56.1％) whose physicians had recommended it to them.Of the patients counseled to use insulin,800 (17.9％) were unwilling to start therapy and cited the following reasons:inconvenience (64.3％); concerns over addiction (24.6％);pain (14.3％); side effects (14.1％); and high cost (13.6％).Logistic regression suggested that respondents would be more willing to undertake insulin therapy if they had received diabetes education,had positive attitudes to the treatment,had higher glycosylated hemoglobin level,or had suffered diabetes for a longer period or with more complications.Conclusions Patients with T2DM in China are often resistant to insulin therapy if they have been diagnosed with the disease for a relatively short time or if the disease has been relatively mild.Educating patients on the benefits of insulin therapy,not only at the initial diagnosis with T2DM but also when insulin therapy becomes necessary,will likely increase their willingness to undertake it。

Abstract：Background Type Ⅱ diabetes mellitus usually related to visceral and other organ (ectopic) fat.The purpose of this study was to detect hepatic and pancreatic fat infiltration in type Ⅱ diabetes mellitus patients using 3.0T magnetic resonance (MR) and to compare the performance of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL-Quant)with single-voxel proton spectroscopy (H1-MRS).Methods The study protocol was approved by our Institutional Review Board.Written informed consent was obtained from each subject in this study.We prospectively performed IDEAL-Quant and single-voxel proton spectroscopy with an echo time of 35 ms on 24 type Ⅱ diabetes patients and 10 healthy volunteers.The hepatic proton density fat fraction (HPDFF) and pancreatic proton density fat fraction (PPDFF) were calculated,compared,and analyzed by t-tests and Spearman's correlation.Results The HPDFF and PPDFF measured with IDEAL-Quant were significantly different between the healthy volunteers and type Ⅱ diabetes patients (th=9.377,P=0.000; tp=2.813,P=0.008).The HPDFF and PPDFF measured with MRS were also significantly different between the healthy volunteers and type Ⅱ diabetes patients (th=5.342,P=0.000; tp=2.63,P=-0.013).The HPDFF and PPDFF measured by the two methods were in good agreement (rh=0.854,P=0.000; rp=0.774,P=-0.000).The HPDFF and PPDFF were not significantly correlated with each other (rMRS=0.203,p=0.248; rIDEAL-Quant=0.301,P=-0.084).The PPDFF measured with IDEAL-Quant was associated with body mass index (r=0.377,P=0.028).Conclusion IDEAL-Quant is a nice method for hepatic and pancreatic fat detection,and it can be applied in clinical practice。

Abstract：Background The International Association of Diabetes and Pregnancy Study Group (IADPSG) recommended new diagnostic criteria for gestational diabetes mellitus (GDM) after extensive analyses of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.Unfortunately,there was no data from mainland of China in this study.We evaluated the feasibility of IADPSG criteria for GDM diagnosis in China.Methods A large prospective study was conducted.We reviewed medical records of a total of 25 674 pregnant women who underwent GDM screening and diagnosis between January 1,2005 and December 31,2012 in the Peking University First Hospital.The prevalence of gestational glucose metabolism abnormalities was calculated according to different cut off values defined by the National Diabetes Data Group (NDDG) or the IADPSG,and the incidence of adverse pregnancy outcomes related to GDM was analyzed.Results According to the cut off values of NDDG and IADPSG criteria,the prevalence of gestational glucose metabolism abnormalities was 8.4％ and 18.9％ (P ＜0.01) respectively,and the prevalence of cesarean section (52.5％ vs.46.0％,P ＜0.01),macrosomia (7.5％ vs.6.3％,P ＜0.05),neonatal hypoglycemia (1.6％ vs.1.0％,P ＜0.01),and perinatal death (0.5％ vs.0.2％,P ＜0.01); the prevalence was significantly lower when IADPSG criteria were applied.The prevalence of macrosomia,cesarean section,neonatal hypoglycemia,pregnancy induced hypertension,etc.was also higher in the GDM group than in the normal group.The prevalence of cesarean section (62.3％) and macrosomia (14.8％) was the highest in untreated mild GDM patients.Conclusions Our results indicated that treatment/intervention of women with GDM identified by IADPSG criteria was related to significantly lower risk of multiple adverse pregnancy outcomes.Such findings provide support for applying IADPSG criteria in China。

Abstract：Background Systemic sclerosis (SSc) is an autoimmune disease that has three major components:inflammation,fibrosis,and vasculopathy.T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be critical for autoimmune disease pathogenesis.The role of Th17 and Treg in SSc is still unclear.The aim of this study was to detect the presence of Th17s and CD4+CD25+ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis.Methods Th17s (CD4 and IL-17 positive) and CD4+CD25+ Tregs (CD4,CD25 and Foxp3 positive) in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry.The differences between SSc and control patients were analyzed.Clinical parameters,including disease duration,duration of the second symptoms,Modified Rodnan Skin Score (MRSS),anti-topoisomerase I antibody,anti-U1 ribonucleoprotein (RNP) antibody,systemic involvements,pulmonary function test (PFT) and high resolution computed tomography (HRCT) score were prospectively collected following EUSTAR (EULAR scleroderma trial and research group) protocols.The correlations between the experimental and clinical data were investigated.Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls (8.74％ vs.4.41％,P ＜0.001).The amount of Th17 was positively correlated with disease duration (R=0.531,P=0.013) and duration of the second symptoms (R=0.505,P=0.023).The ratio of CD4+CD25+ Treg in SSc patients also significantly differed from the healthy controls (3.04％ vs.2.24％,P=0.018).Elevated Tregs were more frequently observed in patients with a high interstitial lung disease (ILD) score on computed tomography (24/36) compared with patients with normal ILD scores (4/12,P=0.043).Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity (DLCO) (24/34) compared with patients with normal DLCO (4/11,P=0.042).Conclusions T cell abnormalities are remarkable in systemic sclerosis.Th17s proliferate and their numbers increase with lengthened disease duration.Th17s might participate in both inflammation and fibrosis by secreting IL-17.CD4+CD25+ Tregs also proliferate in SSc and may play important roles in promoting fibrosis。

Abstract：Background Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) plays a pivotal role in this process.Recently identified pro-angiogenic factor,semaphorin4D (Sema4D) also promotes angiogenesis and enhances invasive proliferation in some tumors.Furthermore,tumor-associated macrophages (TAMs) can increase the expression of HIF-1α and Sema4D in cancer cells and thus influence tumor growth and progression.The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-1α and the impact of biologic behavior in colon cancer cells.Methods Immunohistochemistry was used to analyze HIF-1α and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples.The relationship between their expression and clinicopathological factors was analyzed.Furthermore,macrophage-tumor cell interactions,such as metastasis,angiogenesis,were also studied using in vitro co-culture systems.Statistical analysis was performed using SPSS 17.0 software (SPSS Inc.,USA).Differences between two groups were analyzed with Student's t test.Results HIF-1α (58％) and Sema4D (60％) were expressed at a significantly higher level in tumors than in normal tissues (P ＜0.01,for both).Furthermore,HIF-1α and Sema4D expression was significantly correlated with lymphatic metastasis,specific histological types and TNM stages (P ＜0.05),but not with age and tumor size (P ＞0.05).Sema4D expression was correlated with that of HIF-1α (r=0.567,P ＜0.01).TAMs markedly induced HIF-1α and Sema4D expression in colon cancer cells and subsequently increased their migration and invasion.Conclusions HIF-1α and Sema4D expression are closely related to lymphatic metastasis,specific histological types and TNM stages in colon cancer.Furthermore,TAMs promote migration and invasion of colon cancer cells and endothelial tube formation,possibly through up-regulation of HIF-1α and Sema4D。

Abstract：Background Short-term outcomes of the Wallis system in the treatment of lumbar degenerative disease (LDD) have been shown to be effective,whereas there is a paucity of studies on the mid-long-term effects of the treatment of the Wallis system.This study was to evaluate the mid-long-term effects of the Wallis dynamic stabilization system in the treatment of LDD.Methods A total of 26 patients who received the treatment of the Wallis system between February 2008 and January 2009 were included in the study,with 14 patients (Group 1) with L4/5 disc herniation and 12 patients (Group 2) with L5/S1 disc herniation and L4/5 intervertebral disc degeneration (IDD).Visual analog scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical outcomes and lumbar x-rays and MRI were obtained to observe imaging changes before and after operation.Results The mean follow-up period was (63.50±2.12) months.The mean ODI and VAS scores decreased obviously three months and five years after operation (P ＜0.05).In Groups 1 and 2,L4/5 Cobb angle and range of motion (ROM) decreased and L4/5 posterior disc height increased at the last follow-up (P ＜0.05).There were no statistically significant changes in L4/5 anterior disc height and L3/4 University of California at Los Angeles grading before and after operation.There was no statistically significant change in Pfirrmann grading system of L4/5 IDD in Group 2 before and after operation.Adjacent segment degeneration at the last follow-up was found in two patients (2/26,7.69％) and Modic changes in L4/5 endplates were detected in one patient (1/26,3.85％).Conclusions The mid-long-term effects of the Wallis system in the treatment of LDD were satisfied.The Wallis system,as a dynamic stabilization system,which can preserve some ROM of the fixed segment,sustain the lumbar stabilization,and prevent adjacent segment disease and fixed segment degeneration,is an effective instrument to treat LDD。

Abstract：Background The effects of donor characteristics on CD34+ cell dose remain controversial.Recently,we developed a novel haploidentical transplant protocol,in which mixture allografts of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (G-BM) and G-CSF-mobilized peripheral blood (G-PB) were used.The aim of this study was to investigate the effects of donor characteristics on CD34+ cell dose in mixture allografts of G-BM and G-PB.Methods A total of 162 healthy adult donors,who underwent bone marrow harvest and peripheral blood collection between January 2009 and November 2010 in Peking University People's Hospital,were prospectively investigated.G-CSF was administered subcutaneously at a dose of 5 μg/kg once a day for 5-6 consecutive days.Bone marrow and peripheral blood stem cells were harvested on the fourth day and fifth day,respectively.A final total CD34+ cell dose less than 2× 106 cells/kg recipient body weight was considered a poor mobilization.Results Of the 162 donors,31 (19.1％) did not attain this threshold.The obtained median CD34+ cell doses in bone marrow,peripheral blood,and mixture allografts were 0.83×106/kg,2.40×106/kg,and 3.47×106/kg,respectively.Multiple regression analysis showed that donor age had a significant negative effect on CD34+ cell dose in either G-BM,or G-PB,or mixture allografts of G-BM and G-PB.And a 1-year increase in age was associated with a 5.6％ decrease in the odds of achieving mobilization cutoff.No significant correlation was found for donor gender,body mass index (BMI),and weight.Conclusion Donor age is the only factor among the four parameters,including age,gender,weight,and BMI,that influence CD34+ cell dose in mixture allografts of G-BM and G-PB,and younger donors should be chosen to obtain sufficient CD34+ cells for transplantation。

Abstract：Background Dendritic cells (DCs) can recognize the pathogen-associated molecular patterns (PAMP) of Aspergillus fumigatus (A.fumigatus),activating the immune response.During A.fumigatus infection,a Th and Treg response induced in the fungi-pulsed DCs is not yet well understood.Methods In this study,bone marrow-derived dendritic cells (BMDCs) were separated and proliferated from C57BL/6 mice.A.fumigatus pulsed DCs were generated and cultured with CD4+ T cells derived from the spleen of C57BL/6 mice in vitro.CD4+ T cells differentiation after co-culture were analyzed by flow cytometry,ELISA,and real-time PCR analysis.Results The A.fumigatus pulsed DCs exhibited increased Th1 and Treg frequency,Th1-related cytokines (IFN-γ and IL-12),Treg-related cytokines (TGF-β) and T-bet,and Foxp3 mRNA levels compared with the control group.There was no significant difference between A.fumigatus pulsed DCs group and the control group about Th17 and Th2 frequency.Conclusions The inactivated conidia of A.fumigatus were able to activate BMDCs and made them capable of triggering T cell responses in vitro.A.fumigatus loaded DCs was a weak inducer of Th17 and Th2,but induced a strong Th1 and Treg response。

Abstract：Background The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice.Danggui-shaoyao-san (DSS) is a traditional Chinese medicine (TCM) prescription which has long been used for pain treatment and possesses antioxidative,cognitive enhancing and antidepressant effects.We raise the hypothesis that DSS exerts analgesic effect for orthodontic pain via inhibiting the activations of neuron and microglia.Methods DSS was given twice a day from day 5 prior to experimental tooth movement (ETM).Directed face grooming and vacuous chewing movements (VCM) were evaluated.Immunofluorescent histochemistry and Western blot analysis were used to quantify the Iba-1 (microglia activation) and Fos (neuronal activation) expression levels in the trigeminal spinal nucleus caudalis (Vc).Results ETM significantly increased directed face grooming and VCM which reached the peak at post-operative day (POD) 1 and gradually decreased to the baseline at POD 7.However,a drastic peak increase of Fos expression in Vc was observed at 4 hours and gradually decreased to baseline at POD 7; while the increased Iba-1 level reached the peak at POD 1 and gradually decreased to baseline at POD 7.Furthermore,pre-treatment with DSS significantly attenuated the ETM induced directed face grooming and VCM as well as the Fos and Iba-1 levels at POD 1.Conclusion Treatment with DSS had significant analgesic effects on ETM-induced pain,which was accompanied with inhibition of both neuronal and microglial activation。

Stroke has become one of the secondary worldwide mortal diseases that burdens the family and the society both emotionally and economically. The announcement of China's Ministry of Health in 2008 showed that stroke had been the first cause of death in urban and rural residents. Traditional therapies such as thrombolysis, anti-platelets, and rehabilitation showed limited effects. Replacement therapy with stem cells promises to be a good solution due to its possible thorough therapy for the damaged brain area, reconstruction of neuronal circuitry, and probable long-term efficacy. Previous studies demonstrated that stem ceils have played crucial roles in various kinds of tissue repair and immune disorders such as cardiovascular diseases, skeletal diseases, arthritis diseases, and lupus erythematodes。

To the editor: Neonatal diabetes mellitus (NDM) is one kind of monogenic diabetes which usually presents within 6 months after birth and needs insulin treatment for at least 2 weeks.1 For transient neonatal diabetes mellitus (TNDM), all patients will go into remission phase but nearly half the patients have the risk of developing diabetes again.2 About 70% of all TNDM is 6q24 TNDM, which is related to imprint disorder causing hypomethylation on chromosome 6q24。