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中华内分泌代谢杂志
中华内分泌代谢杂志

宁光

月刊

1000-6699

cjem@vip.163.com

021-64315587

200025

上海市瑞金二路197号

中华内分泌代谢杂志/Journal Chinese Journal of Endocrinology and MetabolismCSCD北大核心CSTPCD
查看更多>>1985年创刊，中华医学会主办。本刊是反映我国当代及与国外合作的，在内分泌代谢病学领域内临床与科研最新成果的高级学术刊物。在强调刊文的先进性、科学性与新颖性的同时，也十分重视临床的实用性和论文的可读性。本刊设指南与共识、述评、专论、论坛、临床研究、基础研究、综述、讲座、临诊应对、当年学术进展与动态、临床经验交流、新药研究、学术争鸣及国外期刊论文评论等栏目。本刊的读者对象主要为各级从事临床和基础内分泌代谢病学工作的医、教、研人员及研究生，以及内、外、儿、妇科以及神经、泌尿、老年、营养等相关科室的人员。
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    肥胖绝经后女性脂肪分布与股骨颈强度综合指数相关性

    张万丽王金娣路迪迪刘盼...
    93-97页
    查看更多>>摘要：目的 探讨肥胖绝经后女性脂肪分布与股骨颈强度综合指数相关性。 方法 选取非低体重绝经后女性293例，完善实验室检查、人体成分分析仪以及双能X线骨吸收仪检查，根据体重指数(body mass index, BMI)将研究对象分为正常BMI组(18.5 kg/m2≤BMI<24.0 kg/m2, 91例)、超重组(24.0 kg/m2≤BMI<28.0 kg/m2, 115例)和肥胖组(BMI≥28.0 kg/m2, 87例)，并对测量结果进行分析研究。 结果 绝经后女性肥胖组所有部位骨密度(bone mineral density, BMD)均高于正常BMI组和超重组(P<0.005)，肥胖组压缩强度指数(compression strength index, CSI)，弯曲强度指数(bending strength index, BSI)和冲击强度指数(impact strength index, ISI)均显著低于正常BMI组(P<0.001,P＝0.008, P＝0.001)。肥胖组中腰围、腰臀比、总脂肪量、四肢脂肪量、躯干脂肪量是CSI、BSI和ISI独立于年龄、空腹血糖、BMI的危险因素(P<0.05)。内脏脂肪等级与中国内脏脂肪指数是LSI、BSI和ISI的危险因素(P<0.05)。 结论 绝经后肥胖女性股骨颈强度综合指数降低，此人群皮下脂肪与内脏脂肪均与股骨颈强度综合指数负相关。 Objective To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women. Methods A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m2≤BMI<24.0 kg/m2, n=91), the overweight group(24.0 kg/m2≤BMI<28.0 kg/m2, n=115), and the obese group(BMI≥28.0 kg/m2, n=87). The measurement results were analyzed. Results In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group(P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group(P<0.001,P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI(P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI(P<0.05). Conclusion The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

    肥胖绝经后女性骨强度股骨颈强度综合指数脂肪分布皮下脂肪内脏脂肪

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    2型糖尿病患者血红蛋白水平与骨密度及骨质疏松之间的关系

    谭娟刘媛媛朱永芳李红...
    98-103页
    查看更多>>摘要：目的 研究2型糖尿病(type 2 diabetes mellitus, T2DM)患者血红蛋白水平与骨密度及罹患骨质疏松风险之间的关系。 方法 采用横断面方法研究2019年9月至2020年9月在南京医科大学附属淮安第一医院内分泌及老年医学科住院的T2DM患者364例。根据双能X线吸收法测定的股骨颈骨密度三分位数水平分为低值组、中值组及高值组。比较3组间一般资料、实验室检查、糖尿病慢性并发症及合并症的差异。多因素logistic回归模型分析血红蛋白水平与骨密度及罹患骨质疏松风险之间的关系，最后根据年龄、体重指数(body mass index, BMI)、糖尿病病程、估算肾小球滤过率(estimated glomeruar filtration rate, eGFR)、糖化血红蛋白(glycosylated hemoglobin, HbA1C)、总胆固醇(total cholesterol, TC)、三酰甘油(triglyceride, TG)、高密度脂蛋白胆固醇(high-density lipoprotein-cholesterol, HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein-cholesterol, LDL-C)、血尿酸(uric acid, UA)进行交互作用和分层分析。 结果 调整年龄、BMI、糖尿病病程后，血红蛋白水平与绝经后女性骨密度及罹患骨质疏松风险差别无统计学意义(所有P>0.05)。调整年龄、BMI、糖尿病病程、eGFR后，与血红蛋白<130 g/L组相比，血红蛋白≥130 g/L组50岁及以上男性患者，血红蛋白水平与股骨颈骨密度呈正相关(β＝0.057, 95%CI 0.014～0.100, P＝0.011)，而与髋部骨密度、腰椎L1-L4骨密度及罹患骨质疏松风险均差异无统计学意义(所有P>0.05)。最后分层分析显示在年龄、BMI、糖尿病病程、eGFR、HbA1C、TC、TG、HDL-C、LDL-C、UA亚组中，交互作用未发现分层变量间差异有统计学意义(所有交互作用P>0.05)。 结论 50岁及以上男性T2DM患者，高血红蛋白水平可能是股骨颈骨密度的保护因素。 Objective To explore the association of hemoglobin(HGB) levels with bone mineral density(BMD) and osteoporosis in patients with type 2 diabetes mellitus(T2DM). Methods A cross-sectional study was conducted in 364 patients with T2DM who were hospitalized in the Department of Endocrinology and Geriatrics of the Affiliated Huaian No. 1 People′s Hospital of Nanjing Medical University from September 2019 to September 2020. Participants were stratified into tertiles(lower, middle, and upper) according to femoral BMD determined by dual-energy X-ray absorptiometry. Demographic characteristics, medical history, chronic diabetes complications, and comorbid conditions were compared among the 3 groups. The association between hemoglobin levels and BMD/osteoporosis was examined using multivariable logistic regression analyses. Interaction and stratified analyses were conducted according to age, body mass index(BMI), duration of diabetes, estimated glomerular filtration rate(eGFR), glycosylated hemoglobin(HbA1C), total cholesterol(TC), triglycerides(TG), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C) and uric acid(UA). Results After adjusting for age, BMI, and duration of diabetes, there were no significant differences observed in the association between hemoglobin levels and BMD or osteoporosis among postmenopausal women with T2DM(all P>0.05). After adjusting for age, BMI, duration of diabetes, and eGFR, men aged≥50 years with hemoglobin≥130 g/L showed a positive association between hemoglobin level and femoral neck BMD compared to those with hemoglobin<130 g/L(β=0.057, 95%CI 0.014-0.100, P=0.011). However, no significant associations were observed between hemoglobin level and BMDs at the total hip or lumbar spine(L1-L4), nor the risk of osteoporosis(all P>0.05). Stratified analyses revealed no significant differences in the subgroups classified based on age, BMI, diabetes duration, eGFR, HbA1C, TC, TG, HDL-C, LDL-C, and UA(all interaction P>0.05). Conclusion In males aged 50 and above with T2DM, elevated hemoglobin levels may be a protective factor for femoral neck bone density.

    血红蛋白贫血糖尿病,2型骨密度骨质疏松

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    血清维生素D状况对妊娠女性子代胎儿期长骨发育的影响

    姜楠李美娟李欣徐莹...
    104-107页
    查看更多>>摘要：目的 探究血清维生素D状况对妊娠女性子代胎儿期长骨发育的影响。 方法 回顾性收集2018年7月至2020年6月在我院产前诊断中心就诊的第1胎妊娠女性1 193例，均行产前胎儿超声检查与血清维生素D水平检测，根据第1次检测维生素D后的给药剂量分为基础剂量组(维生素D3，1 600 IU/d，口服)、足量补充组(维生素D2注射液60万U/2周，肌肉注射)，比较两组妊娠女性在治疗12周和24周时血清25-(OH)D水平及妊娠女性其胎儿长骨生长情况，采用多因素logistic回归分析胎儿长骨长度的相关影响因素。 结果 足量补充组相比基础剂量组在治疗8周、治疗12周、治疗24周均能明显提升妊娠女性血清25-(OH)D水平。两组妊娠女性在给予治疗12周[(4.93±0.75) cm对(4.61±0.73) cm，P<0.05]和治疗24周[(7.92±0.84) cm对(7.25±0.92) cm，P<0.05]，足量补充组相比基础剂量组更能增加胎儿的长骨长度，尤以治疗24周时两组长骨的差异更为明显。母亲身高、基础维生素D水平、孕24周维生素D水平与胎儿长骨长度呈正相关。 结论 孕妇应保持相对较高的基础维生素D水平，并在孕期重视维生素D水平对胎儿的影响，足量补充维生素D对胎儿长骨发育具有重要意义。 Objective To investigate the effect of maternal serum vitamin D on fetal long bone development. Methods A retrospective collection of 1 193 first-time pregnant women who visited our hospital′s prenatal diagnosis center from July 2018 to June 2020 was conducted. All underwent prenatal fetal ultrasound examination and serum vitamin D level detection. Based on the dosage of vitamin D administered after the first vitamin D test, participants were divided into the basic dosage group(vitamin D3, 1 600 IU/d, orally) and the adequate supplementation group(vitamin D2 injection 600 000 IU/2 weeks, intramuscular injection). The serum 25-(OH)D levels of the two groups of pregnant women were compared at 12 and 24 weeks of treatment, as well as the long bone growth of their fetuses. Multivariable logistic regression analysis was used to analyze the factors influencing fetal long length. Results Compared to the basic dosage group, the adequate supplementation group showed a significant increase in serum 25-(OH)D levels in pregnant women at 8 weeks, 12 weeks, and 24 weeks of treatment. The adequate supplementation group also significantly increased fetal long bone length at 12 weeks[(4.93±0.75) cm vs(4.61±0.73) cm, P<0.05] and 24 weeks of treatment [(7.92±0.84) cmvs(7.25±0.92) cm, P<0.05], with the difference between the two groups being more pronounced at 24 weeks of treatment. Maternal height, basal vitamin D level, and vitamin D level at 24 weeks of gestation were positively correlated with fetal long bone length. Conclusion Pregnant women should maintain a relatively high level of basal vitamin D, and pay attention to the effect of vitamin D level on the fetus. A sufficient amount of vitamin D supplementation is of great significance for the long bone development of the fetus.

    妊娠期维生素D胎儿长骨

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    体重指数与骨质疏松症之间的因果关系：一项孟德尔随机化研究

    任春蕊刘建凤安向莲杨栋梁...
    108-114页
    查看更多>>摘要：目的 应用孟德尔随机化(Mendelian randomization, MR)研究方法，探究体重指数(BMI)与骨质疏松症之间的因果关系。 方法 在全基因组关联研究(genome-wide association study，GWAS)汇总数据中选取与BMI密切相关的遗传变异作为工具变量，采用MR-Egger回归法、加权中位数法、逆方差加权法、简单模式、加权模式进行MR分析，通过计算OR值和95%CI评价BMI与骨质疏松症之间的因果关系，应用MR-APSS方法使基于MR的因果推断结果更加可靠，应用连锁不平衡评分(LDSC)回归评估遗传相关性，并进行水平多效性检验、异质性检验、留一法评价结果是否可靠，通过MR-PRESSO异常值测试减少异质性和水平多效性的影响。 结果 共纳入421个SNP，逆方差加权法为主要分析方法，计算的OR值和95%CI为0.994(95%CI 0.992～0.997)，表明BMI对骨质疏松症具有保护作用，MR-APSS方法显示BMI对骨质疏松症的影响具有统计学意义，LDSC回归显示BMI和骨质疏松症之间存在遗传相关性，MR-Egger回归截距显示工具变量不存在水平多效性，漏斗图显示工具变量不存在偏倚，留一法显示结果稳健。 结论 BMI和骨质疏松症之间可能存在负向因果关系，BMI是骨质疏松症的保护因素。 Objective To investigate the relationship between body mass index(BMI) and osteoporosis using Mendelian randomization analysis. Methods The genetic variation strongly related to BMI was selected as the instrumental variables in the collection data set of the genome-wide association study(GWAS). The MR-Egger regression, weighted median estimator(WME), inverse variance weighted(IVW), simple mode and weighted mode were used for Mendelian randomization(MR) analysis. The causal association between BMI and osteoporosis was evaluated by odds ratio and 95% confidence interval. The MR-APSS method was applied to make the causal inference results based on MR more reliable. The Linkage disequilibrium score regression was applied to evaluate the genetic correlation, and the horizontal pleiotropy test, heterogeneity test, and leave-one-out method were used to evaluate whether the results were reliable, The influence of heterogeneity and horizontal pleiotropy were reduced by the MR-PRESSO outlier test. Results A total of 421 SNPs were included, with inverse variance-weighted method as the main analysis approach. The calculated OR value and 95%CI were 0.994(95%CI 0.992-0.997), indicating a protective effect of BMI on osteoporosis. The MR-APSS method showed that the effect of BMI on osteoporosis was statistically significant. Linkage disequilibrium score regression demonstrated a genetic correlation between BMI and osteoporosis. MR-Egger regression intercept showed no horizontal pleiotropy of instrumental variables, and the funnel plot showed no bias in instrumental variables. Leave-one-out analysis confirmed robust results. Conclusion There may be a negative causal relationship between BMI and osteoporosis and BMI is a protective factor for osteoporosis.

    体重指数骨质疏松症孟德尔随机化

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    143例高钙危象的临床诊疗

    刘洋王先令郭清华杜锦...
    115-120页
    查看更多>>摘要：目的 本研究回顾性分析较大样本量高钙危象病例的病因、临床表现、急诊救治及病因治疗。 方法 分析2009年1月至2022年7月中国人民解放军总医院第一医学中心救治的高钙危象患者的一般资料、临床表现、病因、影像学检查、急诊救治、病因治疗、治疗前后血清学检查对比、病理免疫组化结果、随访转归。 结果 本研究共纳入143例高钙危象患者(男性84例，女性59例)，平均年龄为(53.51±16.60)岁。最常见罹患的是甲状旁腺功能亢进症(62/143)，其次是实体恶性肿瘤(57/143)，再次为多发性骨髓瘤(12/143)。患者临床表现为消化系统症状占76.91%，神经系统症状占63.60%，泌尿系统症状占58.76%，骨骼系统症状占55.23%，心血管系统症状占32.91%。143例患者中，经水化补液、降钙素、双膦酸盐、血液透析等急诊降钙治疗后高钙危象好转率为100%(143/143)，经病因治疗后高钙血症好转率为85.31%(122/143)。 结论 高钙危象的早期识别、急诊救治以及病因治疗非常重要。急诊有效的综合降钙措施可以使临床症状迅速缓解，为病因治疗创造条件。针对性病因治疗可以取得高钙血症的纠正或长期缓解。 Objective The study retrospectively analyzed the etiology, clinical manifestations, emergency treatment and etiological treatment of a large sample of cases with hypercalcemic crisis. Methods The clincial data of patients with hypercalcaemia cirisis who were administered in First Medical Center of Chinese PLA General Hospital from January 2009 to July 2022 were analyzed, inculding the general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, serological examination before and after treatment, pathological immunohistochemical findings and prognosis. Results A total of 143 hypercalcaemia crisis patients(84 males and 59 females) with a mean age of 53.51±16.60 were enrolled. The most common disease was hyperparathyroidism(62/143), followed by solid malignancy(57/143) and multiple myeloma(12/143). Patients presented with digestive system symptoms at 76.91%, followed by neurological symptoms at 63.60%, urinary system symptoms at 58.76%, musculoskeletal symptoms at 55.23%, and cardiovascular system symptoms at 32.91%. After emergency calcium-lowering treatment, the remission rate of hypercalcemic crisis in 143 patients was 100%(143/143), and after etiological treatment, the remission rate of hypercalcemia was 85.31%(122/143). Conclusion Early identification, emergency treatment and etiology treatment of hypercalcaemia crisis are essential. Effective treament with comprehensive calcium reduction can quickly relieve clinical symptoms and create opportunities for treatment for the cause. Targeted etiological interventions can lead to the correction or long-term remission of hypercalcemia.

    高钙危象急诊救治病因临床表现

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    男性和女性睾酮与非酒精性脂肪肝的孟德尔随机化研究

    沈涛黄鑫袁中尚管庆波...
    121-131页
    查看更多>>摘要：目的 采用两样本孟德尔随机化(Mendelian randomization, MR)方法探究男性和女性睾酮与非酒精性脂肪肝(nonalcoholic fatty liver disease, NAFLD)的因果关联。 方法 利用全基因组关联研究(genome-wide association study, GWAS)汇总数据，使用女性、男性睾酮(总睾酮、生物有效性睾酮)以及性激素结合球蛋白(sex hormone-binding globulin, SHBG)的遗传变异作为工具变量，采用逆方差加权法(inverse variance weighted, IVW)为主分析方法，同时结合基于其他模型假设下的6种单变量MR方法评估女性、男性睾酮(总睾酮、生物有效性睾酮)以及SHBG与NAFLD的因果关系。此外，应用芬兰生物银行(FinnGen)的NAFLD数据对探索性分析的结果进行验证。进一步采用Cochran′s Q检验，MR-Egger回归和留一法等方法进行敏感性分析，评估工具变量的异质性水平、基因多效性和稳定性。 结果 探索性分析IVW模型结果表明，女性生物有效性睾酮和SHBG与NAFLD具有因果关联，女性生物有效性睾酮水平每增加一个单位，NAFLD发病风险增高24%(OR＝1.24, 95%CI 1.07～1.43, P＝0.004)；女性SHBG每降低一个单位，NAFLD发病风险增高31%(OR＝0.69, 95%CI 0.57～0.83, P<0.001)。然而，男性睾酮(总睾酮，生物有效性睾酮)以及SHBG和女性总睾酮与NAFLD并未显示出因果关系。其他6种MR方法的结果与IVW法基本一致。外部验证数据的结果进一步证明了女性生物有效性睾酮和SHBG与NAFLD的因果关系。 结论 较高的女性生物有效性睾酮水平与较低的SHBG水平可能会增加NAFLD的发病风险。 Objective To investigate the causal association between testosterone and nonalcoholic fatty liver disease(NAFLD) in men and women using a two-sample Mendelian randomization(MR) approach. Methods Genetic variation in testosterone(total testosterone, bioavailable testosterone) and sex hormone-binding globulin(SHBG) in females and males was used as an instrumental variable using the genome-wide association study(GWAS) pooled data, and the inverse variance weighting method was applied. Inverse variance weighted(IVW) was used as the main analytical method, along with six univariate MR methods based on other modeling assumptions to assess the causal relationship between testosterone(total testosterone, bioavailable testosterone) as well as SHBG and NAFLD in women and men. In addition, NAFLD data from Finnish Biobank(FinnGen) were applied to validate the results of the exploratory analysis. Further, sensitivity analyses were performed to assess the level of heterogeneity, genetic pleiotropy, and stability of the instrumental variables using Cochran′s Q test, MR-Egger regression, and leave-one-out methods. Results The results of exploratory analysis of IVW model showed that bioavailable testosterone and SHBG were causally associated with NAFLD in women, for each unit increase in bioavailable testosterone levels, the risk of developing non-alcoholic fatty liver disease(NAFLD) rose by 24%(OR=1.24, 95%CI 1.07-1.43, P=0.004) and with each unit decrease in women′s SHBG, the NAFLD risk increased by 31%(OR=0.69, 95%CI 0.57-0.83, P<0.001). However, testosterone(total testosterone, bioavailable testosterone) as well as SHBG in men and female total testosterone did not show a causal relationship with NAFLD. The results of the other six MR methods were generally consistent with the IVW method. The results of the external validation data provided further evidence of a causal relationship between female bioavailable testosterone and SHBG and NAFLD. Conclusion Elevated levels of bioavailable testosterone along lower levels of SHBG may increase the risk of developing NAFLD in women.

    总睾酮生物有效性睾酮性激素结合球蛋白孟德尔随机化因果推论非酒精性脂肪肝病

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    40岁及以上女性人群血清TSH水平与寿命及10年死亡的相关性研究

    徐萍彭年春张淼胡颖...
    132-138页
    查看更多>>摘要：目的 探讨40岁及以上女性促甲状腺素(TSH)水平与10年死亡及寿命的关系。 方法 对2011年参加"中国2型糖尿病患者肿瘤发生风险的流行病学(REACTION)研究"的贵阳市城区40岁及以上居民进行随访，最终5 614人入组，收集基线一般情况，进行体格检查及TSH检测，平均随访(9.77±1.55)年，记录受试者甲状腺相关疾病治疗及死亡情况，采用Cox比例风险模型分析中老年女性TSH水平与10年死亡的关系，并绘制生存时间曲线(K-M曲线)研究<65岁受试者中TSH升高与寿命的关系。 结果 多因素Cox比例风险模型表明，多变量校正后，TSH升高组与正常组相比，死亡风险降低(HR＝0.644, 95%CI 0.478～0.868, P<0.05)；将TSH升高组分层后，轻度升高组与正常组相比，死亡风险降低(HR＝0.566, 95%CI 0.405～0.791, P<0.001)；进一步将TSH升高组按年龄分组，<65岁组中，轻度升高组与正常组相比，死亡风险降低(HR＝0.429, 95%CI 0.245～0.751, P＝0.003)，≥65岁组中，轻度升高组、重度升高组与正常组相比，差异均无统计学意义(P>0.05)；<65岁组中，K-M曲线表明TSH轻度升高组的生存率明显高于正常组(χ2＝11.931, P＝0.003)，差异有统计学意义。 结论 40～65岁女性TSH水平轻度升高与未来10年全因死亡风险降低及寿命较长相关。 Objective To investigate the relationship between thyroid-stimulating hormone(TSH) levels and 10-year mortality in women aged 40 years and older. Methods Residents aged 40 and over in urban areas of Guiyang City who participated in the " Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)" were followed up in 2011. Finally, 5 614 people were enrolled, and the baseline general information, physical examination and TSH detection were carried out. The average follow-up was(9.77±1.55) years, and the treatment and death of thyroid-related diseases were recorded. The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women, and plotting survival time curves(Kaplan-Meier curves) to study the association between elevated TSH levels and lifespan in subjects under 65 years old. Results The multivariate Cox proportional hazards model showed that compared with the normal group, after multivariate adjustment, the risk of death in the TSH increased group was decreased(HR=0.644, 95%CI 0.478-0.868, P<0.05) after stratifying the elevated TSH group, the risk of death was decreased in the slightly elevated TSH group(HR=0.566, 95%CI 0.405-0.791, P<0.001) the elevated TSH group was further stratified by age. In the group under 65 years old, compared to the normal group, the mildly elevated group showed a reduced risk of mortality(HR=0.429, 95%CI 0.245-0.751, P=0.003). In the group aged 65 and above, there were no statistically significant differences in mortality risk between the mildly elevated group, severely elevated group, and the normal group(P>0.05). In the group under 65 years old, the K-M curve indicated that the survival rate of the mildly elevated TSH group was significantly higher than that of the normal group(χ2=11.931, P=0.003), the difference was statistically significant. Conclusion Mildly elevated TSH levels in women aged 40-65 years are associated with a reduced risk of all-cause death and longer lifespan.

    促甲状腺素全因死亡率女性中老年寿命

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    单侧原发性醛固酮增多症的病理类型分析及其临床特征

    李佳渝杨溢马林强李俊龙...
    139-144页
    查看更多>>摘要：目的 明确单侧原发性醛固酮增多症(原醛症)的病理类型分布，并探讨不同病理分型的单侧原醛症患者的临床特征及预后。 方法 连续纳入经肾上腺手术的单侧原醛症患者241例，搜集其临床及术后随访资料，并对其术后组织切片进行HE染色和醛固酮合酶染色。根据染色结果，对241例患者进行分型，比较不同病理分型的单侧原醛症患者的临床特征及手术预后。 结果 根据国际单侧原醛症病理共识，241例单侧原醛症患者中，有223例为经典型(92.5%)，17例为非经典型(7.1%)，另有1例为醛固酮癌(0.4%)。在经典型中，189例为醛固酮瘤，34例为醛固酮结节；非经典型中，8例为多发性醛固酮结节，9例为多发性醛固酮微结节。与经典型组相比，非经典型组中的高血压病程较长(9.0对5.0年，P＝0.062)，基线血浆醛固酮浓度较低(273对305 pg/mL，P＝0.147)，但差异不具有显著性。两组之间，术后获得完全生化缓解的患者比例无显著差异(98%对92.3%，P＝0.281)，但非经典组中获得完全临床缓解的患者比例显著更低(23.1%对52.9%，P＝0.046)。 结论 单侧原醛症的病理分型以经典型为主，其中醛固酮瘤最多见。经典型和非经典型患者的临床特征及术后生化缓解率无显著差别，但后者临床预后劣于经典组。 Objective To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types. Methods A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared. Results According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.

    单侧原发性醛固酮增多症醛固酮合酶病理分型预后

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    Vaspin通过调控脂肪组织巨噬细胞极化改善2型糖尿病大鼠的胰岛素敏感性

    庞少博刘师伟段瑞雪赵宇翔...
    145-157页
    查看更多>>摘要：目的 探讨脂肪组织丝氨酸蛋白酶抑制剂(visceral adipose tissue-derived serpin, Vaspin)对脂肪组织巨噬细胞极化的影响，为Vaspin改善糖代谢提供新的理论依据。 方法 选取8周龄SD雄性大鼠50只，随机分为正常组(NC组)、2型糖尿病组(T2DM组)、不同浓度Vaspin干预组(V1：480 ng/kg、V2：960 ng/kg、V3：1 440 ng/kg)。Vaspin腹腔注射干预大鼠8周，干预结束后采集外周血分析糖脂代谢相关指标，通过腹腔注射葡萄糖耐量试验(intraperitoneal glucose tolerance test, IPGTT)、腹腔注射胰岛素耐量试验(intraperitoneal insulin tolerance test, IPITT)、高胰岛素-正葡萄糖钳夹技术评估各组大鼠糖耐量和胰岛素抵抗。通过免疫荧光技术(immunofluorescence, IF)测定附睾白色脂肪组织(epididymal white adipose tissue, eWAT)中CD11c、CD206、PPARγ荧光表达；实时荧光定量PCR(real-time polymerase chain reaction，RT-PCR)测定eWAT CD11c和CD206及肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β及IL-10的mRNA表达水平；酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测血清中TNF-α、IL-1β及IL-10的浓度；免疫印迹法(Western blotting，WB)检测eWAT中iNOS、Arg-1、p-Akt、Akt和PPARγ的蛋白表达。 结果 干预8周后，各组的体重及血脂水平差异无统计学意义，IPGTT、IPITT及高胰岛素-正葡萄糖钳夹实验显示Vapsin干预组血糖及胰岛素敏感性改善，且呈剂量依赖性(P<0.05)；IF及RT-PCR显示Vaspin可下调eWAT中CD11c、IL-1β、TNF-α的表达，上调CD206、IL-10、PPARγ的表达，且与Vaspin干预浓度相关(P<0.05)；ELISA显示Vaspin干预可下调血清中IL-1β、TNF-α的浓度，上调IL-10的浓度(P<0.05)；WB显示Vaspin可下调iNOS蛋白的表达，上调Arg1、p-Akt及PPARγ的表达，且呈剂量依赖性(P<0.05)。 结论 Vaspin通过上调巨噬细胞PPARγ通路，使脂肪组织巨噬细胞向M2型极化，改善脂肪组织炎症因子谱，从受体后水平改善胰岛素抵抗，从而改善T2DM大鼠的糖耐量。 Objective This study aimed to explore the effect of Vaspin on adipose tissue macrophage polarization and its underlying mechanism. Methods Fifty male SD rats, aged 8 weeks, were chosen and randomly allocated into three groups: the normal control(NC), the type 2 diabetes(T2DM), and various concentrations of Vaspin intervention(V1: 480 ng/kg, V2: 960 ng/kg, V3: 1 440 ng/kg). Vaspin was administered via intraperitoneal injection for 8 weeks. Glucose tolerance and insulin sensitivity were evaluated via intraperitoneal glucose tolerance test(IPGTT), intraperitoneal insulin tolerance test(IPITT) and hyperinsulinemic-euglycemic clamp. Adipose tissue inflammation and macrophage polarization were assessed using immunofluorescence, RT-PCR and western blotting. Results After 8 weeks of intervention, there were no statistically significant differences in body weight and blood lipid levels among groups. IPGTT, IPITT, and hyperinsulinemic-euglycemic clamp experiments demonstrated that Vaspin intervention improved blood glucose and insulin sensitivity, exhibiting a dose-dependent manner(P<0.05). IF and RT-PCR showed that Vaspin downregulated the expression of CD11c, IL-1β, and TNF-α in eWAT, while upregulating the expression of CD206, IL-10, and PPARγ, which correlated with Vaspin concentration(P<0.05). ELISA revealed that Vaspin intervention reduced the concentrations of IL-1β and TNF-α in serum, while increasing the concentration of IL-10(P<0.05). Western blotting demonstrated that Vaspin downregulated iNOS protein expression, while upregulating Arg1, p-Akt, and PPARγ expression in a dose-dependent manner(P<0.05). Conclusion Vaspin promotes M2 polarization of adipose tissue macrophages via PPARγ pathway, leading to reduced inflammation and improved insulin sensitivity in T2DM rats.

    糖尿病,2型脂肪组织丝氨酸蛋白酶抑制剂胰岛素抵抗脂肪组织炎症巨噬细胞极化

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    miR-182-5p调控初级纤毛的缺失增加甲状腺乳头状癌细胞系TPC-1的迁移

    马承旭马小妮马丽华傅松波...
    158-163页
    查看更多>>摘要：目的 探讨miR-182-5p调控初级纤毛的缺失对甲状腺乳头状癌(PTC)细胞系TPC-1迁移的影响。 方法 收集10例兰州大学第一医院PTC组织和癌旁组织，qPCR检测癌旁组织、PTC组织和TPC-1细胞中miR-182-5p的表达量，免疫荧光检测初级纤毛的形成；过表达miR-182-5p，qPCR和Western blot检测TPC-1细胞中PI3K的表达量，Transwell实验检测TPC-1细胞迁移数量，免疫荧光检测初级纤毛的形成；siRNA-IFT88干扰TPC-1细胞，Transwell实验检测TPC-1细胞迁移数量，免疫荧光检测初级纤毛的形成，吉姆萨染色检测形态学变化，Western blot检测E-cadherin和N-cadherin的蛋白表达量。 结果 与癌旁组织相比，PTC组织中初级纤形成受损；miR-182-5p表达量显著上调。与Nthy-ori3-1相比，TPC-1细胞中初级纤毛的频率减少；miR-182-5p表达量显著上调(P＝0.001)；miR-182-5p mimic治疗后的TPC-1细胞中PI3K的表达量降低，迁移数量增加(P＝0.001)，初级纤毛频率降低为27%(P＝0.002)；siRNA-IFT88治疗后的TPC-1细胞表面初级纤毛变短变细，频率减少(P＝0.001)，迁移数量增加(P<0.001)。 结论 miR-182-5p通过PI3K通路调控初级纤毛的缺失有助于TPC-1细胞的迁移，初级纤毛的丢失对PTC预后具有不利的影响。 Objective To investigate the role of miR-182-5p regulated primary cilia loss on migration of TPC-1 in papillary thyroid cancers(PTC). Methods Ten cases of PTC and adjacent tissues were collected from the First Hospital of Lanzhou University, The expression of miR-182-5p in PTC tissue and TPC-1 cells was detected by qPCR, and the frequency of primary cilia was detected by immunofluorescence Overexpressing miR-182-5p, the migrated number of TPC-1 was detected by Transwell assay Interfering TPC-1 with siRNA-IFT88, the migrated number of TPC-1 and the frequency of primary cilia were detected, respectively. Results Compared with control, the expression of miR-182-5p was significantly upregulated in PTC and TPC-1, the frequency of primary cilia in PTC and TPC-1 was downregulated. Overexpressing miR-182-5p increased the migrated number of TPC-1 cell and reduced the number of TPC-1 cell migration(27%, P=0.002) After siRNA-IFT88 treatment, primary cilia in TPC-1 became shorter and thinner, with a decrease in frequency(P=0.001), the migrated number of TPC-1 cell increased, and TPC-1 cell showed smaller nuclei and fewer microvilli. Conclusion The regulation of primary cilia loss by miR-182-5p through the PI3K pathway contributes to the migration of TPC-1 cells. The loss of primary cilia has an adverse impact on the prognosis of PTC.

    甲状腺乳头状癌迁移初级纤毛miR-182-5pTPC-1

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