缺硒:致甲状腺肿大 人体内的甲状腺激素有T3和T4两种类型,T3的生物活性远大于T4.生理状态下,甲状腺主要合成T4及少量的T3,而T3则主要在外周组织由脱碘酶将T4脱碘转化而来.当人体内硒浓度降低时,可引起外周组织和垂体中的脱碘酶活性降低,T4转化为T3受阻,T3生成减少.T3降低,对垂体促甲状腺素的反馈抑制减弱,导致促甲状腺素分泌增加,引起甲状腺肿大.

Objective:To investigate the relationship between family history of type 2 diabetes (T2D) and insulin re-sistance. Bioinformatic approach was used to identify the risk pathways in subjects with a family history (FH) of T2D, and then functions of key driver genes were analyzed using gene expression profiles from Gene Expression Omnibus (GEO). Methods: Gene expression data set was retrieved using GSE 25462 at NCBI GEO. The data set contained 26 normo-glycemic individuals with 1 or both parents having T2D (FH+) and 15 normoglycemic individuals with no one having dia-betes in first-degree relatives (FH-). Insulin sensitivity was assessed by the Bergman minimal model from intravenous glu-cose tolerance test. Gene expression in quadriceps muscle biopsies was analyzed to identify the differentially expressed genes associated with insulin resistance. Gene set enrichment analysis and identification of risk pathways were used to ex-plore the pathogenesis of T2D at molecular level. Results: Compared with FH-subjects, FH+subjects were insulin resis-tant as demonstrated by a 41%reduction in insulin sensitivity(P<0.05). A total of 202 genes showed differential expression in our analysis. Five biological pathways of gene set enrichment in FH+were identified, including hematopoiesis from mul-tipotent stem cells, hematopoiesis from pluripotent stem cells, role of JAK1 and JAK3 in c-cytokine signaling, antiprolifera-tive role of TOB in T cell signaling, and B cell development. Conclusions: Family history of T2D in normal subjects is associated with insulin resistance. Significantly enriched pathways identified by gene set enrichment analysis reveale that pathogenesis of T2D is associated with function of multipotent stem cells and immune status.

Objective To study the effect of glutathione (GSH)system on coronary artery lesion in type 2 diabetes mellitus (T2DM)patients .Methods Two hundred and thirty-six patients who un-derwent coronary angiography were divided into normal glucose tolerance (NGT ) group (n=126) and T2DM group (n= 110) .Their biochemical indexes were assayed and serum levels of GSH , GSH-Px and GR were meausred .Their coronary artery lesion was scored according to the Gensini scoring system .Results The serum levels of GSH ,GSH-Px and GR were significantly lower in T2DM group than in NGT group (3 .87 ± 1 .55 μg/L vs 4 .45 ± 1 .94 μg/L ,0 .29 ± 0 .05 ng/L vs 0.35 ± 0 .08 ng/L ,0 .19 ± 0 .07 ng/L vs 0 .26 ± 0 .08 ng/L ,P<0 .05) and negatively related with the Gensini score after adjustment for age ,BMI ,blood pressure ,blood lipids ,fasting glucose and insulin ,postprandial 2 h glucose and insulin ,HbA1c (P<0 .05 ,P<0 .01) ,indicating that the ser-um levels of GSH ,GSH-Px and GR could significantly influence the Gensini scores in T 2DM pa-tients .Conclusion Low serum levels of GSH ,GSH-PX and GR are negatively related with coro-nary artery lesion and are the independent factors for coronary artery lesion in T 2DM patients .

OBJECTIVEAdiponectin is a hormone that is mainly secreted by fat cells. Adiponectin has anti-inflammatory and anti-atherosclerotic effects, and a protective effect against ischemic brain injury, but the level of expression of adiponectin in brain tissue is unknown. In the current study, a mouse model of transient cerebral ischemia was used to determine the level of expression of adiponectin in ischemic brain tissue.METHODSSixty CD-1 mice underwent transient middle cerebral artery occlusion. The level of expression of adiponectin in mouse brain tissues 1 hour, 4 hours, 1 day, 3 days, and 7 days, after cerebral ischemia/reperfusion injury were determined using a real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry.RESULTSThe level of expression of adiponectin in mouse ischemic brain tissues increased after cerebral ischemia/reperfusion injury and was higher in the central area of ischemia than in the peripheral area. The level of expression of adiponectin occurred only in vascular endothelial cells. There was no significant change in the level of expression of adiponectin mRNA in brain tissue pre- and post-ischemia/reperfusion injury.CONCLUSIONAfter cerebral ischemia/reperfusion injury, adiponectin accumulated in the vascular endothelial cells of ischemic brain tissues, and non-endogenous adiponectin was generated. Circulating adiponectin accumulated in ischemic brain tissues through its role in adhering to damaged vascular endothelial cells.

Objective To study the mechanism of adiponectin receptor(APNR) in protecting mouse brain by observing its expression in a mouse transient cerebral ischemia model .Methods Sixty CD-1 mice that underwent tMCAO were included in this study .Their brain tissue samples were taken before ischemia .Expression of APNR in mouse brain tissue samples taken before ischemia , and at 1 and 4 h ,and on days 3 and 7 after reperfusion was detected by RT-PCR ,Western blot and immunohistochemistry ,respectively .Results The expression level of APNR1 protein and mRNA was significantly higher in ischemic tissue at 4 h and on days 3 and 7 after reperfusion than before ischemia(P<0 .05 ,P<0 .01) .The expression level of APNR1 protein was similar in central is-chemic area and peripheral ischemic area .APNR1 was expressed in endothelial cells ,astrocytes and neurons .APNR2 was not expressed in brain tissue before and after ischemia .Conclusion The expression of APNR1 is up-regulated in ischemic brain tissue following ischemia-reperfusion inju-ry .Adiponectin may exert its brain protective effect via APNR1 .

CONTEXT It is widely reported that osteocalcin is negatively associated with fat mass. However, there are few reports describing its correlation with fat-free mass, particularly in women. OBJECTIVES The objective of the current study was to investigate the possible relationship between osteocalcin and fat-free mass in healthy, nonobese women. DESIGN AND SETTING This study was performed in a tertiary university teaching hospital. SUBJECTS A total of 504 healthy women aged 20-75 years were enrolled. MAIN OUTCOME MEASURES Body composition was measured using a bioelectronics impedance analyzer. The serum concentrations of total osteocalcin, estradiol, leptin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, IGF-I, fasting plasma glucose, and urinary N-terminal telopeptide of type I collagen were tested. The bone mineral densities (BMDs) at the lumbar spine and proximal femoral neck were measured by dual-energy X-ray absorptiometry. RESULTS The serum total osteocalcin level had a significant positive association with fat-free mass (r = 0.168, P = .007) after adjusting for age, fat mass, menopausal status, estradiol, fasting glucose, leptin, osteoprotegerin, receptor activator of nuclear factor-κB ligand, IGF-I, N-terminal telopeptide of type I collagen, BMDs, and waist and hip circumference. Analysis in pre- and postmenopausal women demonstrated that this association was only present in premenopausal women (r = 0.190, P = .005). The multiple stepwise regression analysis revealed that hip circumference, femoral neck-BMD, fat mass, leptin, osteocalcin, and age are the contributors to the changes in fat-free mass in premenopausal women (adjusted R(2) = 0.521, P < .001). CONCLUSION The serum level of total osteocalcin was positively associated with fat-free mass independent of age, fat mass, leptin, and other confounders in premenopausal women.

Objective To investigate the effect of Ganoderma lucidum polysaccharides on hyperthyroidism and liver injury in the mice model of Graves' disease(GD).Methods GD mice model was constructed by immunizing BALB/c mice with thyroid stimulating hormone receptor-A(TSHR-A).Serum thyroxine(T4),thyroid stimulating hormone receptor antibody(TRAb),and liver function parameters were measured,and correlation analysis was performed.The mice were intragastrically managed with pure water,low-dose Ganoderma lucidum polysaccharides(100 mg·kg-1·d-1) and high-dose Ganoderma lucidum polysaccharides(400 mg·kg-1·d-1) respectively,and the change of serum T4,TRAb,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP) were determined.ResultsSerum ALT,AST and ALP in mice with hyperthyroidism in model group were significantly higher than those in mice without hyperthyroidism in model group and mice in control group(P<0.05).Serum AST and ALP were positively significantly related to serum T4(r=0.585,P<0.05;r=0.744,P<0.05),but were not related to serum TRAb(P>0.05).Serum T4 and TRAb in model mice were not significantly changed after treatment with Ganoderma lucidum polysaccharides(P>0.05).Serum ALT and ALP in mice with hyperthyroidism in model group treated with low-dose Ganoderma lucidum polysaccharides were significantly superior to those in pure water group(P<0.05).Conclusion Ganoderma lucidum polysaccharides may not work on hyperthyroidism improvement in GD mice model,but can improve the liver injury caused by hyperthyroidism.

SummaryAimsTo study whether adiponectin (APN) could improve neurological outcomes in aged mice after ischemic stroke.MethodsAdeno‐associated virus carrying APN gene was injected into aged and young adult mice 7 days before transient middle cerebral artery occlusion (tMCAO). Atrophic volumes and neurobehavioral deficiencies were determined up to 28 days after tMCAO. Focal angiogenesis was determined based on blood vessel number in the ischemic regions.ResultsIncreased atrophic volume and more sever neurobehavioral deficits were found in the aged mice compared with young adult mice (P < 0.05). AAV‐APN gene transfer attenuated atrophic volume and improved neurobehavioral outcomes, along with increased focal angiogenesis in both aged and young adult mice, compared with control animals (P < 0.05). In addition, the attenuation of atrophic volume and the improvement in neurobehavioral outcomes were much more significant in aged mice than in young adult mice after AAV‐APN administration (P < 0.05). The number of microvessels in aged AAV‐APN mouse ischemic brain was higher than in young adult AAV‐APN treated mouse brain (P < 0.05).ConclusionsOur results demonstrate that APN overexpression reduces ischemic brain injury and improves neurobehavioral function recovery in aged mice than in young mice, suggesting APN is more beneficial in aged animals after ischemic stroke.

Introduction: Previous studies showed that adiponectin (APN) has benefits on acute phase of ischemic brain injury. However, its role for neurobehavior recovery after stroke remains unclear, especially in aged rodents. In this study, we explored whether hyperexpression of APN could improve long-term recovery after stroke in both young and aged mice. Methods: Adeno-associated viral vector carrying APN gene (AAV-APN) was stereotactically injected in the striatum of adult (3 months) and aged CD-1 mice (20-22 months). One week after injection, transient middle cerebral artery occlusion (tMCAO) was performed. Expression of APN and its receptors in adult and aged stroke mice was assessed by Real-time PCR,western blot and immunohistochemistry. Cortical atrophy volume, Neurobehavior tests, angiogenesis and neurogenesis were also explored. Expression of phospho-AMPK and VEGF were investigated by western blot to further study the mechanism of APN. Results: In both adult and aged mice after stroke, immunohistochemistry and western blot analysis showed that expression of APN and its receptor AdipoR1 was increased. Comparing to the AAV-GFP and saline treated mice, cortical atrophy volume was attenuated, neurobehavior recovery was improved and angiogenesis was increased in the AAV-APN transduced mice (p<0.05). In addition, the expression of phospho-AMPK and VEGF was increased in the AAV-APN transduced adult and aged mice after cerebral ischemia (p<0.05). Moreover, phospho-AMPK inhibitor compound C treated AAV-APN-transduced mice developed larger atrophy volume (p<0.05), and the number of microvessels was significantly decreased compared to the control mice (p<0.05). P-AMPK,VEGF protein levels and VEGF mRNA level in the AAV-APN-transduced mice with compound C treatment were significantly reduced (p<0.05). Conclusions: Our results showed that overexpression of APN attenuates brain atrophy, improves neurobehavior recovery in both adult and aged mice, which is mediated by VEGF up regulation and the AMPK signaling pathway. Our findings suggest that APN may have great potential for ischemic stroke, even in aged animals.

OBJECTIVES:Bisphenol A (BPA) exposure may promote obesity, but its effect on bone mineral density (BMD) has not been reported in humans. We aimed to examine the relationships between BPA exposure, body composition, serum estradiol, leptin, osteocalcin levels and BMDs in healthy premenopausal women. DESIGN AND METHODS:In this cross-sectional study, a total of 246 healthy premenopausal women aged 20 years and older with regular menstrual cycles were investigated. Body mass index (BMI), fat mass, fat-free mass and BMDs were measured by DXA. Serum estradiol, leptin, osteocalcin, urinary BPA and NTx levels were also tested. RESULTS:Urinary BPA levels were positively associated with fat mass (r=0.193, p=0.006) and leptin (r=0.236, p=0.001) but not with fat-free mass after adjusting for age and BMI. BPA was not associated with serum estradiol levels, BMDs, or bone resorption marker NTx and bone formation parameter osteocalcin, either. A multivariate stepwise regression analysis confirmed that serum leptin levels were positively influenced by fat mass (β=0.746, p<0.001) and BPA (β=0.127, p=0.01) but negatively correlated with fat-free mass (β=-0.196, p<0.001). However, the changes of BMDs at the lumbar spine (β=0.298, p<0.001) and femoral neck (β=0.305, p<0.001) were primarily explained by fat-free mass, and were irrelevant of the fat mass, leptin or BPA exposure. CONCLUSIONS:Although BPA exposure is related with increased amount of fat mass and elevated serum leptin levels, it has neutral effect on BMDs in premenopausal women, possibly due to the exclusive role of fat-free mass, which is unrelated to BPA in determining BMDs.

IDF公布的糖尿病流行病学数据显示:2011年全球糖尿病患病率达8.3％,患病总人数为3.66亿;预计到 2030年糖尿病患病率将上升至9.9％,患病总人数将超过5亿.我国目前糖尿病患病人数已超过9200万,随着我国社会老龄化程度的增加,老年人群占总人口比例不断增大,老年糖尿病患者也日益增多.面对庞大的老年糖尿病患病人群,制定更适合于老年人特点的疾病管理策略及更合理的个体化治疗方案无疑是一个挑战.

Medullary thyroid cancer (MTC) is characterized hy the secretion of calcitonin that is derived from parafollicular cells.20％-25％ of MTC are hereditary.Compared with other types of thyroid cancer,MTC is prone to recurrence,metastasis,and younger onset age.RET gene germline mutation accounts for the hereditary MTC,and somatic mutation is responsible for part of sporadic cases.A good correlation between phenotype and genotype is reported.We present in this article a case of medullary thyroid cancer patient with genetic diagnosis and treatment as well as postoperative follow-up together with RET gene screening results in her family members in order to call attention to the diagnosis and treatment of MTC.

OBJECTIVETo evaluate the therapeutic results of endoscopic orbital decompression for thyroid-associated ophthalmopathy.METHODThe records of nine patients (twelve orbits) received endoscopic orbital decompression for thyroid-associated ophthalmopathy were analyzed for changes in visual acuity, intraocular pressure, proptosis, corneal ulceration and movement. The follow-ups ranged from two months to thirty-six months.RESULTTwelve orbits (100%) had improvement in visual acuity (range 0.1-0.7). Ten orbits (83.3%) decreased in intraocular pressure (range 0.2-21.4 mm Hg). Eight orbits (66.70%) decreased in proptosis (one-five mm). The orbit with corneal ulcer was healed after decompression. Diplopia was cured in one of four patients.CONCLUSIONEndoscopic orbital decompression is a safe and effective procedure for the treatment of thyroid-associated ophthalmopathy.

正常情况下冠状动脉主干及其主要分支走行于心脏外膜下的脂肪组织内.当冠状动脉主干或其分支的某节段走行在心肌浅层中,这部分冠状动脉称作壁冠状动脉 (mural coronary artery,MCA),而覆盖在其上的心肌纤维称为心肌桥(myocardial bridging,MB).

Objective To investigate the influence of different glycometabolic states on the pathological changes of coronary artery in elderly patients with coronary arterosclerosis disease(CAD).Methods The biochemical parameters,severity of coronary artery stenosis and Gensini scores of the elderly CAD patients in different glycometabolic conditions were compared to observe the differences.Results High sensitivity C-reactive protein(hsC-RP) and homeostasis model assessment of insulin resistance(HOMA-IR) were higher in the impaired glucose regulation(IGR) group and the diabetes mellitus(DM) group than in the normal glucose tolerance(NGT) group(P<0.05).The severity of coronary artery stenosis and Gensini scores were positively associated with hs C-RP and HOMA-IR(P<0.05).The severity of coronary artery stenosis and Gensini scores were much higher in the IGR group and the DM group than in the NGT group(P<0.01).The prevalence of complex lesions and the triple vessel involvement were significantly higher in the DM group than in NGT group and IGR group(P<0.05).Conclusion Either IGR or DM may accelerate the pathological changes of coronary artery in elderly CAD patients.Glycemic control and insulin resistance and inflammation improvement may help to prevent severe cardiovascular events in this population.

Objective To investigate the expression of CXC-chemokine receptor 3(CXCR3) and its association with clinical features in papillary thyroid cancer.Methods Immunohistochemistry was used to detect the expression of CXCR3 in 48 papillary thyroid cancer,42 thyroid adenomas and 13 normal thyroid tissues.Results The positive rate of CXCR3 in papillary thyroid cancer tissues was significantly higher than that in thyroid adenomas and normal thyroid tissues(both P<0.05).The expression of CXCR3 was not significantly correlated with age,gender or the size of the tumor(all P>0.05),and was correlated with the degree of lymphatic metastasis(P<0.05).Conclusion CXCR3 is up-regulated in papillary thyroid cancer and associated with the progression of papillary thyroid cancer.CXCR3 may be a novel molecular marker to predict lymphatic metastasis and a new target to restrain metastasis.

BACKGROUND:The effective treatment for patients with resistant hyperthyroidism is difficult. METHODS:In this case report with 4-year follow-up data, we present 2 unusual cases of hyperthyroidism that were unresponsive to almost all antithyroid treatments including total thyroidectomy, but both were controlled with octreotide. RESULTS:Cases 1 and 2 were both middle-aged women. They presented thyrotoxicosis with a low serum concentration of TSH and thyroidal radioactive iodine uptake (RAIU). The underlying causes, such as thyroiditis, metastatic thyroid cancer and struma ovarii were explored. Iodine-induced hyperthyroidism, particularly factitious hyperthyroidism was highly suspected, but there was no direct evidence to establish these diagnoses. In spite of good compliance, their thyrotoxicosis could not be controlled with large doses of PTU or MMI. β-blocker, methylprednisolone, radio-iodine therapy and even thyroidectomy were all attempted and failed. Short-acting octreotide was first administered to case 1 and then to case 2. Thyroid function improved greatly within 3 days in both cases. The doses of octreotide were tapered down to twice a week with consistent efficacy. During the follow-up periods, case 1 required octreotide 0.1mg twice per week and case 2 is on thyroid replacement therapy due to hypothyroidism. The recurrences of hyperthyroidism in both cases were again rapidly controlled with the increased dose of octreotide in case 1 and re-started the usage of octreotide in case 2. CONCLUSIONS:The etiology of thyrotoxicosis in these 2 cases is not clear. In the absence of struma ovarii or wide-spread follicular thyroid cancer, factitious hyperthyroidism due to Munchausen syndrome should be considered first. The efficacy of the off-label use of octreotide in hyperthyroidism was highly effective (only) in these 2 cases.

1例42岁的女性有催乳素瘤病史2年.催乳素瘤诊断的确定是根据患者有高催乳素血症和溢乳症状.其它垂体激素TSH、FSH、LH、GH和ACTH的基线水平都在正常范围内.全面体格检查、神经系统检查及视野均为正常.MRI图像分析显示,垂体内有两个低信号病灶,与信号增强的正常垂体组织界限分明,未见视交叉受累,符合垂体微腺瘤(图1).患者用多巴胺激动剂治疗,催乳素水平降低至正常.鉴于内分泌评估正常,不需要经蝶骨垂体微腺瘤摘除手术,患者被纳入随访观察.

Endothelial dysfunction as well as abnormal thyroid hormone levels may be responsible for increased cardiovascular risk in Graves' disease (GD). Asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) are new markers of endothelial and myocardial dysfunction, respectively. The purpose of this study was to investigate the relationship among the serum levels of ADMA, NT-proBNP, and thyroid hormones in GD patients. This was a cross-sectional investigation conducted in a university teaching hospital. Two hundred and thirty-nine GD (Female: 182, Male: 57) patients and 81 normal controls were enrolled in this study. Serum levels of ADMA were positively related with FT3 (r = 0.584, P < 0.001), FT4 (r = 0.551, P < 0.001), and TRAb levels (r = 0.502, P < 0.001). Serum NT-proBNP levels were positively associated with FT3 (r = 0.243, P < 0.001) and FT4 levels (r = 0.274, P < 0.001), as well as heart rate (r = 0.271, P < 0.03). The elevation of serum ADMA and NT-proBNP levels were also observed in patients with controlled hyperthyroidism. It is thus concluded that serum ADMA and NT-proBNP levels were increased in GD patients. Future studies may determine the usefulness of these two biomarkers to detect early signs of endothelial dysfunction, vascular stiffness, and fluid volume in GD patients.

Lately, tremendous progress of hemoglobin A1c ( HbA1c) in the practice of monitoring and diagnosis of diabetes was witnessed, including the standardization of measurement of HbA1c, the emerging of estimated average glucose,its relationship with HbA1c and application in the monitering of diabetes,and application of HbA1c≥6.5% as diagnostic criteria of diabetes. However, since HbA1c can be affected by many factors,and its relationship with diabetic complications is not completely clear,reporting HbA1c as estimated average glucose,or using it as diagnostic criteria is yet to be further investigated.