1-磷酸鞘胺醇受体3参与巨噬细胞迁移及脓毒症诱导的心肌损伤

目的探讨巨噬细胞中1-磷酸鞘胺醇受体(sphingosine 1-phosphate receptor,S1PR)的表达及其作用,观察干预S1PR3(S1P3)对脂多糖诱导的心肌损伤的影响。方法传代培养小鼠Ana-1巨噬细胞,给予脂多糖(lipopolysaccharide,LPS,100 ng/ml)刺激或S1P3特异性抑制剂CAY-10444(10μmol/L)干预,细胞随机分为对照组、LPS组、CAY-10444组、CAY-10444预处理2h+LPS组,Transwell小室观测巨噬细胞迁移,蛋白免疫印迹检测巨噬细胞S1PR的表达,并检测p-Akt/Akt蛋白水平。在体实验,6~8周龄雄性C57/B6小鼠,随机分为对照组、LPS组、CAY-10444组、CAY-10444干预+LPS组,每组12只,LPS(10 mg/kg)腹腔注射,或CAY-10444 1 mg/kg于LPS诱导后30 min腹腔注射干预,24 h后取心脏组织HE染色观察病理改变,免疫组化染色观察巨噬细胞浸润程度以及炎症因子的表达情况,实时荧光定量PCR检测心肌损伤标记分子BNP、巨噬细胞表面分子F4/80、炎症因子TNF-α、IL-1β、IL-6的mRNA水平。结果与对照组比较,LPS诱导巨噬细胞大量迁移S1P3蛋白表达增加(P0.01),p-Akt Ser473/Akt表达上调(P0.01);与LPS组相比,S1P3抑制剂CAY-10444干预后再给予LPS刺激,巨噬细胞迁移被抑制(P0.01),p-Akt Ser473/Akt表达也降低(P0.01);在体实验,LPS诱导小鼠后BNP mRNA水平明显上调(P0.01),同时F4/80以及炎症因子TNF-α、IL-1β、IL-6的mRNA水平上调(P0.01),HE染色可见心肌损伤及炎细胞浸润,免疫组化染色法显示F4/80及炎症因子的大量阳性表达(P0.01);使用S1P3抑制剂后,与LPS组比较,心肌损伤减轻免疫组化中巨噬细胞减少(P0.01),炎症因子表达降低(P0.01),BNP mRNA水平降低(P0.01),F4/80以及TNF-α、IL-1β、IL-6的mRNA水平也明显降低(P0.01)。结论抑制巨噬细胞S1P3表达可抑制巨噬细胞的迁移并提示p-Akt/Akt与了这一过程,此外,S1P3抑制剂的干预可有效减轻LPS诱导的心肌损伤。     

老年2型糖尿病并发ACS患者血清GGT与慢血流-无复流的相关性及其对预后的影响

目的探讨老年2型糖尿病(T2DM)并发急性冠脉综合征(ACS)患者血清γ谷氨酰胺转肽酶(GGT)水平与经皮冠状动脉介入(PCI)治疗术后冠脉慢血流-无复流的相关性及其对预后的影响。方法选取188例诊断为ACS并行急诊PCI的老年T2DM患者,根据TIMI血流分级和校正的TIMI血流帧计数(c TFC)方法评价冠脉血流分为正常血流组(156例)和慢血流-无复流组(32例),分析GGT及其他危险因素与冠脉慢血流-无复流的相关性和主要不良心血管事件(MACE)的发生率。结果慢血流-无复流组的血清GGT水平高于正常血流组[(49±18)U/L vs.(31±13)U/L,P0.01]。相关分析结果显示,血清GGT与冠脉慢血流-无复流呈正相关(r=0.389,P0.01)。血清GGT与PCI术后冠脉慢血流-无复流、住院期间及术后12个月MACE独立相关(分别OR=1.093,95%CI:1.058~1.129,P0.01;OR=1.047,95%CI:1.012~1.082,P0.05及OR=1.058,95%CI:1.028~1.089,P0.01)。结论老年T2DM并发ACS患者血清GGT水平与冠脉慢血流-无复流相关,血清GGT可能是预测冠脉风险的评价指标。     

HBV endemicity in Mexico is associated with HBV genotypes H and G

Hepatitis B virus(HBV)genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics,progression,severity of disease and antiviral response.Herein,we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico.HBV genotype H is predominant among the Mexican population,but not in Central America.Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence,apparently due to a rapid resolution of the infection,low viral loads and a high prevalence of occult B infection.During chronic infections,genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities,such as obesity,alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus.Hepatocellular carcinoma prevalence is low.Thus,antiviral therapy may differ significantly from the standard guidelines established worldwide.The high prevalence of HBV genotype G in the Americas,especially among the Mexican population,raises new questions regarding its geographic origin that will require further investigation.     

Harnessing the potential of gene editing technology using CRISPR in inflammatory bowel disease

The molecular scalpel of clustered regularly interspersed short palindromic repeats/CRISPR associated protein 9(CRISPR/Cas9) technology may be sharp enough to begin cutting the genes implicated in inflammatory bowel disease(IBD) and consequently decrease the 6.3 billion dollar annual financial healthcare burden in the treatment of IBD. For the past few years CRISPR technology has drastically revolutionized DNA engineering and biomedical research field. We are beginning to see its application in gene manipulation of sickle cell disease,human immunodeficiency virus resistant embryologic twin gene modification and IBD genes such as Gatm(Glycine amidinotransferase, mitochondrial),nucleotide-binding oligomerization domain-containing protein 2, KRT12 and other genes implicated in adaptive immune convergence pathways have been subjected to gene editing, however there are very few publications. Furthermore,since Crohn's disease and ulcerative colitis have shared disease susceptibility and share genetic gene profile, it is paramount and is more advantageous to use CRISPR technology to maximize impact. Although, currently CRISPR does have its limitations due to limited number of specific Cas enzymes, off-target activity,protospacer adjacent motifs and crossfire between different target sites. However,these limitations have given researchers further insight on how to augment and manipulate enzymes to enable precise gene excision and limit crossfire between target sites.     

Abdominal compartment syndrome:Often overlooked conditions in medical intensive care units

Intra-abdominal hypertension(IAH)and abdominal compartment syndrome are well recognized entities among surgical patients.Nevertheless,a number of prospective and retrospective observational studies have shown that IAH is prevalent in about half of the critically ill patients in the medical intensive care units(ICU)and has been widely recognized as an independent risk factor for mortality.It is alarming to note that many members of the critical care team in medical ICU are not aware of the consequences of untreated IAH and the delay in making the diagnosis leads to increased morbidity and mortality.Frequently it is underdiagnosed and undertreated in this patient population.Elevated intraabdominal pressure decreases the blood flow to the kidneys and other abdominal viscera and also results in reduced cardiac output and difficulties in ventilating the patient because of increased intrathoracic pressure.When intraabdominal hypertension is not promptly recognized and treated,it leads to abdominal compartment syndrome,multiorgan dysfunction syndrome and death.Large volume fluid resuscitation is very common in medical ICU patients presenting with sepsis,shock and other inflammatory conditions like pancreatitis and it is one of the major risk factors for the development of intra-abdominal hypertension.This article presents an overview of the epidemiology,definitions,risk factors,pathophysiology and management of IAH and abdominal compartment syndrome in critically ill medical ICU patients.     

Current status of endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy

Endoscopic retrograde cholangiopancreatography(ERCP)in patients with surgically altered anatomy must be performed by a highly experienced endoscopist.The challenges are accessing the afferent limb in different types of reconstruction,cannulating a papilla with a reverse orientation,and performing therapeutic interventions with uncommon endoscopic accessories.The development of endoscopic techniques has led to higher success rates in this group of patients.Device-assisted ERCP is the endoscopic procedure of choice for high success rates in short-limb reconstruction;however,these success rate is lower in long-limb reconstruction.ERCP assisted by endoscopic ultrasonography is now popular because it can be performed independent of the limb length;however,it must be performed by a highly experienced and skilled endoscopist.Stent deployment and small stone removal can be performed immediately after ERCP assisted by endoscopic ultrasonography,but the second session is needed for other difficult procedures such as cholangioscopy-guided electrohydraulic lithotripsy.Laparoscopic-assisted ERCP has an almost 100%success rate in longlimb reconstruction because of the use of a conventional side-view duodenoscope,which is compatible with standard accessories.This requires cooperation between the surgeon and endoscopist and is suitable in urgent situations requiring concomitant cholecystectomy.This review focuses on the advantages,disadvantages,and outcomes of various procedures that are suitable in different situations and reconstruction types.Emerging new techniques and their outcomes are also discussed.     

Loss of BRCA1 expression leads to worse survival in patients with gastric carcinoma

AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 10.7% vs 20.5;Ⅰ/Ⅱ vs Ⅳ, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (Ⅰ/Ⅱ vs Ⅲ, 12.9% vs 16.9%;Ⅰ /Ⅱ vs Ⅳ, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 0% vs 12%;Ⅰ/Ⅱ vs Ⅳ, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and     

Assessment of chronic radiation proctopathy and radiofrequency ablation treatment follow-up with optical coherence tomography angiography: A pilot study

BACKGROUND Chronic radiation proctopathy(CRP) occurs as a result of pelvic radiation therapy and is associated with formation of abnormal vasculature that may lead to persistent rectal bleeding. While incidence is declining due to refinement of radiation delivery techniques, CRP remains one of the major complications of pelvic radiation therapy and significantly affects patient quality of life.Radiofrequency ablation(RFA) is an emerging treatment modality for eradicating abnormal vasculature associated with CRP. However, questions remain regarding CRP pathophysiology and optimal disease management.AIM To study feasibility of optical coherence tomography angiography(OCTA) for investigating subsurface vascular alterations in CRP and response to RFA treatment.METHODS Two patients with normal rectum and 8 patients referred for, or undergoing endoscopic RFA treatment for CRP were imaged with a prototype ultrahighspeed optical coherence tomography(OCT) system over 15 OCT/colonoscopy visits(2 normal patients, 5 RFA-na?ve patients, 8 RFA-follow-up visits). OCT and OCTA was performed by placing the OCT catheter onto the dentate line and rectum without endoscopic guidance. OCTA enabled depth-resolved microvasculature imaging using motion contrast from flowing blood, withoutrequiring injected dyes. OCTA features of normal and abnormal microvasculature were assessed in the mucosa and submucosa. Blinded reading of OCTA images was performed to assess the association of abnormal rectal microvasculature with CRP and RFA treatment, and rectal telangiectasia density endoscopic scoring.RESULTS OCTA/OCT images are intrinsically co-registered and enabled depth-resolved visualization of microvasculature in the mucosa and submucosa. OCTA visualized normal vascular patterns with regular honeycomb patterns vs abnormal vasculature with distorted honeycomb patterns and ectatic/tortuous microvasculature in the rectal mucosa. Normal arterioles and venules < 200 μm in diameter versus abnormal heterogenous enlarged arterioles and venules > 200μm in diameter were visualized in the rectal submucosa. Abnormal mucosal vasculature occurred in 0 of 2 normal patients and 3 of 5 RFA-na?ve patients,while abnormal submucosal vasculature occurred more often, in 1 of 2 normal patients and 5 of 5 RFA-na?ve patients. After RFA treatment, vascular abnormalities decreased, with abnormal mucosal vasculature observed in 0 of 8 RFA-follow-up visits and abnormal submucosal vasculature observed in only and 2 of 8 RFA-follow-up visits.CONCLUSION OCTA visualizes depth-resolved microvascular abnormalities in CRP, allowing assessment of superficial features which are endoscopically visible as well as deeper vasculature which cannot be seen endoscopically. OCTA/OCT of the rectum can be performed in conjunction with, or independently from endoscopy.Further studies are warranted to investigate if OCTA/OCT can elucidate pathophysiology of CRP or improve management.     

Hepatoprotective actions of melatonin: possible mediation by melatonin receptors

Melatonin,the hormone of darkness and messenger of the photoperiod,is also well known to exhibit strong direct and indirect antioxidant properties. Melatonin has previously been demonstrated to be a powerful organ protective substance in numerous models of injury; these beneficial effects have been attributed to the hormone’s intense radical scavenging capacity. The present report reviews the hepatoprotective potential of the pineal hormone in various models of oxidative stress in vivo,and summarizes the extensive literature showing that melatonin may be a suitable experimental substance to reduce liver damage after sepsis,hemorrhagic shock,ischemia/reperfusion,and in numerous models of toxic liver injury. Melatonin’s influence on hepatic antioxidant enzymes and other potentially relevant pathways,such as nitric oxide signaling,hepatic cytokine and heat shock protein expression,are evaluated. Based on recent literature demonstrating the functional relevance of melatonin receptor activation for hepatic organ protection,this article finally suggests that melatonin receptors could mediate the hepatoprotective actions of melatonin therapy.     

Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats

AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126     

Prevalence of coeliac disease in patients with autoimmune thyroiditis in a Turkish population

AIM:To investigate the prevalence of coeliac disease in a series of Turkish patients with autoimmune thyroiditis.METHODS:Sera from 136 consecutive patients with newly diagnosed autoimmune thyroiditis and 119 healthy blood donors were tested for IgA tissue transglutaminase antibody with enzyme-linked immunosorbent assay.Endoscopic mucosal biopsy from the second part of duodenum was performed in patients with positive antibody test.RESULTS:Eight patients(5.9%)and one control subject(0.8%)were positive for IgA tissue transglutaminase antibody(OR:7.38,95% CI:0.91-59.85,P = 0.04).Six patients and one control agreed to take biopsies.Histopathological examination revealed changes classified as Marsh Ⅲa in one,Marsh Ⅱ in one,Marsh Ⅰ in two,and Marsh 0 in two patients with autoimmune throiditis,and MarshⅠin one blood donor.CONCLUSION:Turkish patients with autoimmune thyroiditis have an increased risk of coeliac disease and serological screening may be useful for early detection of coeliac disease in these patients.Our findings need to be confirmed in a larger series of patients.     

Predisposing HLA-DQ2 and HLA-DQ8 haplotypes of coeliac disease and associated enteropathy in microscopic colitis

OBJECTIVE: To assess the presence of both genetic and serological markers of coeliac disease in patients with microscopic colitis, and whether there was associated enteropathy. METHODS: HLA-DQ2, HLA-DQ8, serum immunoglobulin A-antiendomysial and immunoglobulin A-anti-tissue transglutaminase antibodies were investigated in 59 patients with microscopic colitis. Seventy healthy subjects acted as the control group. Endoscopic biopsies from the distal duodenum were obtained in DQ2-positive or DQ8-positive patients. Patients with histological changes compatible with gluten-sensitive enteropathy were started on a gluten-free diet. RESULTS: Seventeen of 70 (24.3%) healthy controls were DQ2-positive. Twelve of 25 (48%) patients with lymphocytic colitis (P = 0.027 versus controls), and 11 of 34 (32.3%) with collagenous colitis (P = 0.38 versus controls) were DQ2-positive. There were no differences in the frequency of DQ8-positivity. The coeliac serology was positive in one patient. Duodenal biopsies were performed in 23 DQ2-positive and/or DQ8-positive patients. None had villous atrophy (Marsh III lesion) (0%; 95% confidence interval, 0-6.1). A Marsh type I lesion was found in four patients. Three of these patients were put on a gluten-free diet with disappearance of diarrhoea. CONCLUSIONS: The results suggest that there is an association of lymphocytic colitis with HLA-DQ2 genes, which might be relevant in the pathogenesis of this disease. The association of microscopic colitis with Marsh type III coeliac disease seems to be rare, making it unnecessary to routinely screen for coeliac disease in microscopic colitis patients.     

Association of coeliac disease with primary biliary cirrhosis in Poland

OBJECTIVES: In western and northern but not southern Europe, the prevalence of coeliac disease among patients with primary biliary cirrhosis (PBC) is higher than in the general population. We analysed the prevalence of coeliac disease among patients with PBC in Poland, a central European country. METHODS: In 115 patients with PBC, immunoglobulin A (IgA) antibodies against guinea-pig tissue transglutaminase (tTGA), monkey endomysium (EMA) and gliadin (AGA) were determined. In patients positive for tTGA and/or EMA, the DNA typing of HLA-DQB gene and small-bowel biopsy were performed. RESULTS: IgA EMA was found in one patient with PBC (0.9%, 95% CI 0-2.5%). tTGA was detected in seven patients (6%, 95% CI 1.8-10.3%). Small-bowel biopsy showed flat mucosa in one subject, who was EMA positive/tTGA negative/AGA negative, and normal histology in four tTGA-positive/EMA-negative patients. In the latter four patients, the positive tTGA result was caused by IgA reactivity to proteins other than transglutaminase. Prevalence of coeliac disease in our 115 patients with PBC was 0.9% (95% CI 0-1.9%). In one patient with silent coeliac disease presenting with the HLA-DQ2 allele, introduction of a gluten-free diet was followed by improvement in liver function tests, improvement in histology of the distal duodenum, and disappearance of EMA. CONCLUSIONS: Our results from Poland do not confirm a high prevalence of coeliac disease in PBC patients. Guinea-pig liver transglutaminase immunolinked assay cannot be used as a screening test for coeliac disease in PBC patients. A gluten-free diet may be helpful in restoration of liver function in patients with such an association.     

Thyroid function, autoimmune thyroiditis and coeliac disease in juvenile idiopathic arthritis

OBJECTIVES: Autoimmune diseases have been associated with some organ non-specific rheumatological disorders such as rheumatoid arthritis and systemic lupus erythematosus; however, few studies have been performed in an extensive cohort of children with juvenile idiopathic arthritis (JIA). Our objective was to evaluate the thyroid function and the prevalence of antithyroid antibodies, autoimmune thyroiditis and coeliac disease in children with JIA. METHODS: One hundred and fifty-one children (120 female, 31 male, median age 8.3 yr, range 2.4-16.9 yr) with JIA were evaluated. All patients underwent thyroid function tests (u-TSH, free T(4) and free T(3)), antithyroglobulin (TgA) and antiperoxidase (TPOA) antibodies, antigliadin, anti-endomysium and antitransglutaminase antibodies. All patients with raised thyroid stimulating hormone levels, low thyroid hormone levels or positive TPOA and/or TgA values had a thyroid high-resolution sonography examination. Coeliac disease was confirmed by jejunal biopsy if the specific antibodies profile was positive. One hundred and fifty-eight age- and sex-matched Caucasian children from the same geographical area acted as controls. RESULTS: Fourteen (9.3%) patients showed subclinical hypothyroidism, 17 (11.9%) patients showed autoimmune thyroiditis with nine patients also showing a non-homogeneous thyroid parenchyma at ultrasound evaluation. Coeliac disease was demonstrated in 10 (6.6%) patients. Compared with controls, JIA patients had higher prevalence of subclinical hypothyroidism (P < 0.01), autoimmune thyroiditis (P < 0.0001) and coeliac disease (P < 0.005). CONCLUSIONS: JIA children have an increased prevalence of autoimmune thyroiditis, subclinical hypothyroidism and coeliac disease. These data seem to suggest careful monitoring of thyroid function, thyroid autoantibodies and coeliac disease in JIA children.     

硒治疗自身免疫性甲状腺疾病的荟萃分析

目的 评价元素硒治疗自身免疫性甲状腺疾病(AITD)的有效性和安全性.方法 通过5个数据库(MEDLINE,Cochrane Central Register of Controlled Trials,中国期刊全文数据库,中国生物医学文献数据库和维普数据库)检索所有研究元素硒治疗AITD的随机对照试验(RCT).由两名研究者独立筛选文献、提取数据和进行结果的统计分析.将结果数据形式一致的同类临床试验的结果进行荟萃分析,对不能荟萃分析的数据进行描述性分析.共纳入30项RCT,涉及2 963例AITD患者.结果 (1)与对照组相比,硒治疗组桥本甲状腺炎患者甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)水平明显下降[标准化均数差(SMD)=-1.35,95％ CI:-1.93～-0.67,P ＜0.000 01和SMD=-0.92,95％ CI:-1.53～-0.31,P＜0.01].(2)硒治疗组与对照组相比,Graves病患者促甲状腺激素受体抗体(TRAb)水平降低(均数差=-2.5,95％ CI:-2.99～-2.01,P＜0.000 01).(3)元素硒可以降低Graves病患者血清游离T3(FT3)和游离T4(FT4)水平(均数差=-1.57,95％ CI:-2.56～-0.58,P＜0.001和均数差=-3.74,95％ CI:-5.65～-1.82,P=0.000 01),但对桥本甲状腺炎患者FT3、FT4和促甲状腺激素的作用不明显(P均＞0.05).结论 对AITD患者使用200 μg∥d的元素硒治疗3～12个月,能够有效降低抗甲状腺自身抗体(TPOAb,TgAb和TRAb)的水平,并具有较好的安全性.     

Smoking and thyroid disorders--a meta-analysis

BACKGROUND: Smoking has been associated with Graves' disease, but it remains unclear if the association is present in other thyroid disorders. OUTCOME VARIABLES: Graves' disease, Graves' ophthalmopathy, toxic nodular goitre, non-toxic goitre, post-partum thyroid disease, Hashimoto's thyroiditis, or hypothyroidism. MATERIAL AND METHODS: A search of MEDLINE identified 25 studies on the association between smoking and thyroid diseases. RESULTS: In Graves' disease eight studies were available showing an odds ratio (OR) of 3.30 (95% confidence interval (CI): 2.09-5.22) in current smokers compared with never smokers. In ex-smokers there was no significant excess risk of Graves' disease (OR=1.41, 95% CI: 0.77-2.58). The OR associated with ever smoking in Graves' ophthalmopathy (4.40, 95% CI: 2.88-6.73, six studies) was significantly higher than in Graves' disease (1.90, 95% CI: 1.42-2.55, two-sided P-value <0.01). Ever smoking was not associated with toxic nodular goitre (OR=1.27, 95% CI: 0.69-2.33, three studies), while there was an increased risk of non-toxic goitre in smokers if men were excluded (OR=1.29, 95% CI: 1.01-1.65, eight studies). The risk associated with smoking was significantly lower in men than in women for both Graves' disease and non-toxic goitre. Hashimoto's thyroiditis and post-partum thyroid dysfunction were also associated with smoking while the association with hypothyroidism did not reach statistical significance. CONCLUSIONS: Cessation of smoking seems associated with a lower risk of Graves' disease than current smoking. Smoking increases the risk of Graves' ophthalmopathy beyond the risk associated with Graves' disease alone. Smoking cessation may lead to a decrease in morbidity from Graves' disease, especially in women.     

Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease

OBJECTIVE: Autoimmune thyroid disease (AITD) is a common disorder especially in women, and both genetic and environmental factors are involved in its pathogenesis. We wanted to gain more insight into the contribution of various environmental factors. Therefore, we started a large prospective cohort study in subjects at risk of developing AITD, for example healthy female relatives of AITD patients. Here we report on their baseline characteristics. SUBJECTS: Only first- or second-degree female relatives of patients with documented AITD were included. MEASUREMENTS: Smoking habits, oestrogen use, pregnancy history and iodine exposure were assessed by questionnaires, and correlated to the thyroid function and antibody status. RESULTS: Of 803 subjects, 440 came from families with more than one patient with documented AITD. Of these families, 33% had documented cases of both Graves' disease and Hashimoto's thyroiditis. Although the subjects were in self-proclaimed good health, 3.6% were found to have hypothyroidism (overt disease in 1.3%) and 1.9% had hyperthyroidism (overt disease in 0.4%). These patients were older than the euthyroid subjects and were mostly positive for thyroid peroxidase (TPO) antibodies. Oestrogen use was associated with a lower rate of hyperthyroidism [relative risk (RR) 0.169; 95% confidence interval (CI) 0.06-0.52], whereas having been pregnant was associated with a higher relative risk for hyperthyroidism (RR 6.88; 95% CI 1.50-30.96). Of the 759 euthyroid subjects, 24% had TPO antibodies. Smoking and oestrogen use were negatively correlated with the presence of TPO antibodies. In the euthyroid subjects, TPO antibody titre correlated positively with TSH levels (r = 0.386; P < 0.001). CONCLUSIONS: The high prevalence of evidence for autoimmune thyroiditis at baseline supports the importance of genetic factors in its pathogenesis. The co-occurrence of Hashimoto's thyroiditis and Graves' disease within one family suggests a common genetic basis for these diseases. Oestrogen use is associated with a lower risk, and pregnancy with a higher risk for developing hyperthyroidism. The positive correlation between TPO antibody titres and TSH levels in euthyroid subjects suggests that TPO antibodies are indeed a marker of future thyroid failure.     

Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves' disease,Hashimoto's thyroiditis and type 1 diabetes mellitus

OBJECTIVE: The vitamin D endocrine system plays a role in the regulation of (auto)immunity and cell proliferation. Vitamin D 1alpha-hydroxylase (CYP1alpha) is one of the key enzymes regulating both systemic and tissue levels of 1,25-dihyroxyvitamin D(3) (1,25(OH)(2)D(3)). Administration of 1,25(OH)(2)D(3), whose serum levels were found to be reduced in type 1 diabetes and thyroid autoimmunity, prevents these diseases in animal models. We therefore investigated a recently reported CYP1alpha polymorphism for an association with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. DESIGN AND METHODS: Four hundred and seven Caucasian pedigrees with one offspring affected by either type 1 diabetes (209 families), Graves' disease (92 families) or Hashimoto's thyroiditis (106 families) were genotyped for a C/T polymorphism in intron 6 of the CYP1alpha gene on chromosome 12q13.1-13.3 and transmission disequilibrium testing (TDT) was performed. Subsets of affected offspring stratified for HLA-DQ haplotype were compared using chi(2) testing. RESULTS: There was no deviation from the expected transmission frequency in either type 1 diabetes mellitus (P=0.825), Graves' disease (P=0.909) or Hashimoto's thyroiditis (P=0.204). However, in Hashimoto's thyroiditis the CYP1alpha C allele was significantly more often transmitted to HLA-DQ2(-) patients (27 transmitted vs 14 not transmitted; TDT: P=0.042) than expected. The C allele was less often transmitted to HLA-DQ2(+) patients (9 transmitted vs 12 not transmitted; TDT: P=0.513), although the difference was not significant (chi(2) test: P=0.143). A similar difference was observed in type 1 diabetes between offspring with high and low risk HLA-DQ haplotypes (chi(2) test: P=0.095). CONCLUSIONS: The CYP1alpha intron 6 polymorphism appears not to be associated with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. A potential association in subsets of patients with type 1 diabetes and Hashimoto's thyroiditis should be further investigated as well as its functional implications.     

Autoantibody tests in autoimmune thyroid disease: a case-control study.

Both positive antinuclear antibody (ANA) and anti-DNA antibodies have been reported in patients with autoimmune thyroid disease. We sought to determine the frequency of ANA and other autoantibodies in autoimmune thyroid disease versus control subjects. We measured ANA by 2 methods (mouse liver, HEp-2), anti-dsDNA, anti-Ro, anti-La, anti-Sm, anti-RNP, and anticardiolipin in 26 patients with Hashimoto's thyroiditis, 26 patients with Graves' disease, and 26 control patients. Positive ANA by either method were more common in patients with Graves' disease than in controls (p = 0.002 and 0.05). Although common (46.2%), ANA by HEp-2 method was not found significantly more often in patients with Hashimoto's thyroiditis than in controls. Evidence for systemic autoimmune diseases was not found: patients with autoimmune thyroid did not have autoantibodies other than ANA and did not differ from controls in rheumatologic symptoms. Positive ANA using the widely accepted HEp-2 method were commonly found in both Graves' disease and Hashimoto's thyroiditis. No evidence of subclinical systemic autoimmune disease was found, either by specific autoantibody tests or by increased frequency of rheumatologic symptoms or signs.     

The value of ultrasonography in predicting autoimmune thyroid disease.

Ultrasonography (US) may demonstrate a diffuse reduction in thyroid echogenicity (low-amplitude echoes) in autoimmune thyroid disease (AITD), which includes chronic lymphocytic thyroiditis and Graves' disease, as well as in subacute thyroiditis. The reported occurrence of this finding in AITD varies from 19% to 95%. To assess the validity of diffuse reduction in thyroid echogenicity as a predictor of AITD, 3,077 patients referred for US of the thyroid were examined prospectively with regard to reduced versus normal thyroid echogenicity. The most frequent reasons for referral were goiter, thyroid dysfunction, neck discomfort, and/or difficulty in swallowing. Ultrasonography demonstrated diffuse reduction in thyroid echogenicity in 485 patients. Of these, 452 patients had available records of fine-needle aspiration biopsy (FNAB), and were included in the study. From the remaining patients, with normal thyroid echogenicity, 100 consecutive patients were selected as controls. In 411 of the 452 study patients (90.9%) there was at least one laboratory finding consistent with possible AITD: cytology indicating lymphocytic thyroiditis, 287 of 363 patients (79.1%) with diagnostic specimens; elevated levels of peroxidase antibodies (TPOAb), 225 of 337 (66.8%); elevated thyrotropin (TSH) levels, 290 of 450 (64.4%); or low TSH levels, 79 of 450 (17.6%). The final diagnosis was: chronic autoimmune (Hashimoto's) thyroiditis in 352 patients; Graves' disease in 47 patients; subacute (granulomatous) thyroiditis in 7 patients; toxic nodular goiter in 3 patients; and toxic adenoma in 2 patients. In the remaining 41 patients, those without laboratory results consistent with AITD, the final diagnosis was colloid goiter in 37 and thyroid cancer in 4 patients. In the 100 controls, laboratory results were consistent with possible AITD in 14 patients: elevated TPOAb levels in 5 of 49 patients with retrieved antibody results; lymphocytic thyroiditis in 2 patients; elevated TSH levels in 2 patients; and low TSH levels in 2 patients. In these controls, the final diagnosis was: chronic autoimmune thyroiditis in 7; toxic nodular goiter in 6 patients, and toxic adenoma in 1 patient. The corresponding positive and negative predictive values of reduced thyroid echogenicity as an indicator of AITD were 399 of 452 (88.3% [95% CI, 85% to 91%]), and 93 of 100 (93.0% [95% CI, 88% to 98%]), respectively. Thus, diffuse reduction in thyroid echogenicity was a valid predictor of AITD.