Objective: To investigate the relationship between gene mutation and clinical phenotype in patients with autosomal dominant osteopetrosis type 2 (ADO2) caused by single allele mutation of CLCN7. Methods: The two ADO2 cases were clinically described in detail, CLCN7 gene were screened by the next generation sequence assay, and validated by Sanger method. The hazard of mutations was evaluated on PolyPhen2 website. Literature review helped to browse and gather ADO2 cases with CLCN7 data, accordingly all found CLCN7 mutant loci were mapped on the peptide chain, and clinical presentations in each case were tentatively summarized corresponding gene mutation. Phenotype was classified as mild type, intermediate type and severe type according to the degree of clinical presentation. Mild type presents mainly with bone and/or joint pain and occasional bone fracture, intermediate type with additional multiple and recurrent bone fracture, sever type with hematopoietic dysfunction in addition to recurrent bone fractures. Results: The first case was a 30 year old man presenting as mild ADO2 with shorter stature than familial hereditary height, as well as back pain and knee joint pain for up-to nine years. The second case was a 13 year old boy who suffered from recurrent bone fractures since four years ago in addition to short stature and more severe bone pain, but had normal peripheral blood picture. His prominent bone change showed by X-Ray indicated a more typical and severe osteopetrosis than the former. Gene analysis indicated a mutation of c.2284C>T (E24), p.R762W in the first case and c.856C>T (E10), p.R286W in the second case. Literature review gathered 42 pathogenic mutations, mild, intermediate and severe clinical type account for 33.3%, 46.7% and 20.0%, respectively. Among family members of probands, 58.8% had unaffected mutation-carrier, and 44.7% had family history of the disease. Conclusions: In spite of single allele inactivation, CLCN7 related ADO2 may cause highly various clinical phenotype of osteopetrosis, covering normal unaffected, mild, intermediate and severe conditions. The relationship between genotype and phenotype remains obscure in the disease.

Familial Dysalbuminemic Hyperthyroxinemia (FDH) is thought of no clinical significance, but tends to to misdiagnosed and mistreated as Graves’ hyperthyroidism with long time. In a Chinese family to explore clinical characteristics, hereditary features and gene variation of FDH and its effect on pregnancy. Methods: Two propostitus (a father and his son) with hyperthyroidism were re-diagnosed as FDH due to the canonical profile of measured thyroid hormones. After screening thyroid function of the whole family, eight affected of FDH were identified among total thirteen lineal relatives. They were studied in terms of clinical history, biochemical and hormone examination, thyroid imaging and TSH secreting test by dexamethasone and bromocriptine. Three members accepted gene analysis with the next generation sequencing followed by Sanger method. Productive history was investigated in five spouse of the whole family. Results: In the two propostitus, FDH exhibited very high total thyroxine (T4) and mild high total triiodinethyronine (T3), and normal free T4 and T3 besides normal thyroid stimulating hormone (TSH). In addition, ultrasound discovered diffuse goiter and enhanced blood flow, and 99mTc uptake increased, while TSH receptor antibody and pituitary MRI scan remained normal. Other six family members had similar changes of the thyroid hormones and normal TSH which could be suppressed dramatically by dexamethasone and bromocriptine, then were suspected of FDH and thereafter confirmed with gene analysis. Among these eight FDH, four were misdiagnosed with hyperthyroidism and mistakenly received anti-thyroid medication at least one year. Gene analysis of three members revealed R218H variation of albumin gene. Conclusions: R218H associated FDH shows canonical changes of thyroid hormones with increased thyroid function, high penetrance and misdiagnose rate with hyperthyroidism, it exerts no effect on pregnancy.

围绝经期及绝经后女性是甲状旁腺功能亢进症(HPT)高发人群.绝经后女性维生素D缺乏发生率高,引起的低钙血症长期刺激甲状旁腺可导致继发性HPT(SHPT),甚至三发性HPT(THPT).雌激素水平下降引起骨丢失,促进骨钙向循环钙转移,代偿维生素D不足.此外,绝经还可通过影响钙敏感受体(CaSR)及成纤维细胞生长因子23-Klotho受体调控系统等参与HPT的发生.

Objective To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1 （MEN1） through analyzing the clinical diagnosis and treatment process,as well as outcomes in one case of this disorder.Methods The clinical manifestations,biochemical and hormone levels,imaging presentations,medical and surgical treatments,and post-operational

OBJECTIVE:To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations.METHODS:Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production.RESULTS:Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous.CONCLUSION:The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.

To investigate insulin resistance of the fetal growth restriction (FGR) mice with catch-up growth (CUG) and the underlying mechanism, in this study, low protein diet was used during pregnancy to establish the FGR mice model, and high fat diet was applied to establish the CUG model of FGR mice. The insulin and Pifithrin-α stimulation was performed via intraperitoneal injection. The physical characters, biochemical parameters, expression of related molecules in each group were detected via ELISA, RT-PCR, WB, etc. The results showed FBG, FINS and HOAM-IR in CUG-FGR group were higher than those in high fat feeding control group (NC+HF), but the content of IGF-1 in blood was lower than that in NC + HF group. Meanwhile, RT-PCR and WB showed that the expression of IGF was negatively correlated with the expression of P53/IGFBP3. Moreover, the expression of P-IRS/p-PI3K/p-Akt decreased with the increasing of HOAM-IR in IGF signaling pathway. When the mice were injected with Pifithrin-α, the phosphorylation level of IGF signaling pathway and insulin resistance index in the CUG-FGR group were increased and decreased, respectively. In conclusion, insulin resistance in CUG-FGR mice is correlated with the IGFBP3/IGF-1/IRS-1/Akt signaling pathway and inhibited p53 could activate this signaling pathway and relieve insulin resistance.

目的 探讨分析沙格列汀联合阿卡波糖治疗初诊老年2型糖尿病的临床疗效.方法 选取我院2015年1月～2016年8月收治的老年2型糖尿病患70例,根据用药不同分为观察组和对照组各35例.对照组患者给予二甲双胍联合阿卡波糖治疗,观察组患者给予沙格列汀联合阿卡波糖治疗.比较两组患者治疗前后空腹血糖(FPG)、餐后2小时血糖(PBG)、空腹胰岛素(Fins)以及稳态模型胰岛素抵抗指数(HOMA-IR)的变化.结果 治疗前,两组FPG、PBG水平比较,差异均无统计学意义(P>0.05);治疗后,两组FPG、PBG水平较治疗前均明显的下降,差异具有统计学意义(P<0.05);两组治疗后FPG、PBG水平之间比较,差异无统计学意义(P>0.05).两组治疗前Fins、HOMA-IR比较,差异无统计学意义(P>0.05);治疗后两组Fins均明显的升高,HOMA-IR均明显的降低;与对照组治疗后比较,观察组治疗后Fins、HOMA-IR改善情况明显优越,差异均具有统计学意义(P<0.05).结论 沙格列汀联合阿卡波糖治疗初诊老年2型糖尿病患者,可以有效的控制患者的血糖水平,减轻胰岛素抵抗情况,具有较高临床应用价值.

Objective To improve the understanding of tumor induced osteomalacia (TIO) through analyzing the clinical features, diagnosis and treatment of three cases with this disease. Methods Clinical data about three patients with TIO in our hospital from 2011 to 2017 were respectively analyzed. The first case was a 17-year-old male presented with weakness in both legs and difficulties in walk for 2 years. The second case was a 60-year-old female with recurrent arthralgia in several joints for more than 2 years. The third one was a 63-year-old male complained of weakness in both legs and bone pain for 2 years. All three patients showed hypophosphatemia, hyperphosphaturia, increased level of alkaline phosphates and decreased level of tubular reabsorbtion of phosphorus (TRP). And the imaging results showed osteoporosis and pseudo-fracture in these patients. The tumor was found by PETCT in all the three cases, and was proved by the new 68Ga-DOTA-TATE-PET CT in the third case. Results All the patients were treated with surgery and pathologically confirmed as phosphaturic mesenchymal tumors. The serum phosphorus gradually returned to normal after tumor resection in the first and the third case. As for the second case, the serum phosphorus once returned to normal after surgery. Seven months later, the tumor recurred in situ proved by PET-CT, which cannot be resected by surgery. Conclusion For the patients with bone pain, weakness, and hypophosphatemia, hyperphosphaturia, increased levels of alkaline phosphates, decreased levels of TRP, TIO should be included in the differential diagnosis. Full physical examination and imaging tests are needed to find the tumor, and PET-CT imaging plays an important role in diagnosis.

目的 通过1例糖尿病长期酗酒致低镁血症病例报道,提高临床对慢性酒精中毒引起的低镁血症加重神经病变的关注.方法 2017年10月本院收治1例53岁男性患者,酗酒多年,表现为血糖升高伴手足麻木7年,加重伴肌肉萎缩1年.神经电生理等检查提示外周神经损伤,心电图提示T波改变,颅脑磁共振提示脑萎缩等,多年的低镁血症未被重视.结果 此患者糖尿病诊断之初即表现为手足麻木,后逐渐进展为下肢乏力、肌肉萎缩,按照常规糖尿病神经病变治疗改善不明显;后结合患者长期酗酒多合并酒精中毒相关的维生素B1缺乏症,予补充B族维生素联合营养神经治疗,改善依然有限;后仔细分析其入院以来生化指标,复习文献,考虑该患者为长期酗酒导致的低镁血症,予补充镁剂(500 mg/d)联合营养神经治疗,下肢乏力、麻木明显改善.结论 对临床上长期酗酒的糖尿病患者,当出现手足麻木、乏力,甚至肌肉萎缩时,不仅应考虑到最常见的糖尿病外周神经病变,还应考虑酗酒引起的低镁血症.

目的 分析银离子敷料结合负压引流技术在糖尿病足溃疡中应用的安全性及疗效.方法 选择2014年12月~2016年12月期间于我院进行的患者共110例为研究对象,按照随机化原则将其分为观察组(55例)和对照组(55例),对照组采用常规清创术+凡士林纱布,观察组采用银离子敷料+负压引流技术,比较两组患者创面愈合情况、换药次数、住院时间、术后VAS疼痛评分及治疗效果.结果 观察组新鲜肉芽组织出现时间、创面愈合时间、换药次数及住院时间明显少于对照组[(6.74±1.86 vs 10.55±1.73)d、(33.04±5.82 vs 42.29±4.77)d、(8.87±2.85 vs 20.29±3.06)次、(15.38±5.51 vs 22.08±4.85)d],而创面缩小百分比明显高于对照组[(48.83±7.37 vs 34.49±6.94)%],差异有统计学意义(P<0.05).观察组、对照组患者治疗后VAS疼痛评分明显低于治疗前[(2.71±1.39 vs 5.44±1.58)分、(4.13±1.44 vs 5.51±1.49)分],差异有统计学意义(P<0.05);治疗后观察组的VAS疼痛评分明显低于对照组[(2.71±1.39 vs 4.13±1.44)分],差异有统计学意义(P<0.05).观察组治疗有效率明显高于对照组(90.91%vs 66.45%),差异有统计学意义(P<0.05).结论 银离子敷料结合负压引流技术可有效治愈糖尿病足溃疡,促进患者的康复.

OBJECTIVETo study the efficacy of metformin intervention on insulin resistance during catch-up growth in mice with fetal growth restriction (FGR).METHODSMouse models of FGR were established by low protein diet feeding of the pregnant mice. Both the newborn female mice with FGR and normal control (NC) mice were randomized for feeding with a standard diet (SF) or a high-fat diet (HF) after weaning and treatment with gavage of either metformin or normal saline. The mice were examined for vaginal opening time and the estrous cycle at the age of 8 weeks. At the age of 12 weeks, 6 mice in anestrus from each group were fasted for 12 h for measurement of body weight, height, poundera index (PI), fasting blood glucose (FBG), fasting insulin (Fins), follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), and the HOMA-IR was calculated. The reproductive capacity of female mice was assessed by mixing them with male mice at the ratio of 2:1. The 3 × 2 factorial analysis was conducted to determine the interactions between FGR, high-fat feeding and metformin.RESULTSFactorial analysis showed that FGR and high-fat feeding had significant effects on the PI index, Fins, HOMA-IR, vaginal opening time, and AMH (P<0.05). Metformin significantly affected the factors related to high-fat feeding including weight, PI, FPG, Fins, HOMA-IR and estrous cycle (P<0.05) and the factors related to FGR with the exception of height and FSH (P<0.05). FGR significantly affected the factors tested except for body weight (P<0.05); high-fat feeding affected all the factors but the FSH (P<0.05); metformin affected all the factors but the height and FSH (P<0.05). In the female mice treated with saline, the pregnancy rates differed significantly between FGR mice with high-fat feeding and control mice with standard feeding, and between FGR mice with standard feeding and high-fat feeding (P<0.05).CONCLUSIONFGR mice can present with delayed puberty with rare ovulation and adulthood insulin resistance, and high-fat feeding after birth can promote the catch-up growth of FGR mice. Metformin intervention is effective for improving insulin resistance and reproductive-endocrine disorders in FGR mice during catch-up growth.

肾性尿崩症包括获得性和遗传性(HNDI)两种,HNDI包括X连锁的肾性尿崩症(XLNDI)(占90%)和水通道蛋白2(AQP2)遗传缺陷.XLNDI则由X染色体上的编码加压素受体2型(AVPR2)的AVPR2基因突变所致[1],本文报道一个新的AVPR2突变位点所致的一个XLNDI家系3例早年起病、长期隐匿、且成年后才获确诊(至本研究时)患者的临床表现及基因分析结果.

多项流行病学研究揭示了超重/肥胖与T2DM管理的严峻形势.T2DM患者多伴超重/肥胖,随着治疗的强化出现体重增加,对患者影响巨大.2016年ADA、2015年AACE及2013年CDS的指南均进一步强调了体重管理的重要性:建议对超重/肥胖的T2DM患者,通过生活方式、药物和手术等实现体重的有效控制;针对各种药物对体重的影响不同,应选择体重增加少的治疗策略,以预防因治疗带来的体重增加及不良结果;应用胰岛素治疗,需尽量避免或减少体重增加.

患者(先证者)女性,27岁,孕10周,因2周前产检意外发现低钾血症于2015年4月8日入院,平素无心悸、气促、手足麻痹、肌无力等症状；无妊娠剧吐症,无高血压病史；初胎妊娠；血压111/80 mmHg(1 mmHg=0.133 kPa),体重指数(BMI)19.15 kg/m2,发育正常,心肺腹及神经系统查体阴性。

胰岛素在机体外周和中枢都发挥着重要作用.胰岛素主要通过受体介导转运进入中枢神经系统,作用于下丘脑等位点,发挥调节能量代谢、摄食和体重作用.胰岛素治疗是控制血糖水平的常用手段.地特胰岛素作为新型基础胰岛素类似物,以其安全、有效的作用特点受到关注.与其他胰岛素及类似物相比,地特胰岛素能降低体重增加.本文将对胰岛素的中枢效应及减少体重机制方面的研究进行总结.

Objective: Endocrine dysfunction caused by pituitary abscess (PA) and its outcomes have not been fully studied. This study aims to investigate endocrine dysfunction and outcomes in patients with PA.Methods: Eight patients (3 males and 5 females) with PA were identified for collecting clinical, hormone, and therapeutic data before and after long-term follow-up lasting 12 to 116 months (median, 25 months) since the first hospitalization, which was regarded as the baseline time. All patients' pituitary and respective target gland functions were evaluated. Six patients had acute onset (less than 1 month), and the other 2 patients had chronic onset (more than 6 months). Five patients underwent surgical therapy, and the other 3 patients underwent conservative therapy. The factors associated with endocrine outcome were analyzed as well.Results: At baseline, the release of 91.7% (22 of 24 total) of pituitary tropic hormones was impaired, but 59.1% (13 of 22) had normalized by the last follow-up. Male gender, acute onset mode, and normal baseline prolactin level seemed to be the factors that favored tropic hormone normalization, whereas surgical operation was not. Two patients received provocative test suggesting decreased reserves of both somatotrophin and prolactin or only somatotrophin. Only 1 patient suffered from permanent diabetes insipidus.Conclusion: The production of almost all pituitary tropic hormones was impaired with PA in the present study, but production of nearly 60% percent of the hormones normalized during follow-up of > 1 year. A chronic abscess state may be the most important factor associated with permanent hormone deficiency.

[Summary] Sixty-one patients suffering from pituitary apoplexy( PA) were mainly diagnosed according to pathologic findings, and were collected from case record, pathology, and MRI databases. They were classified into 4 types according to the clinical condition: the insidious type was characterized with only positive pathological findings;the asymptomatic type had both positive pathologic and MRI findings; the subacute type had PA associated symptoms longer than 2 weeks; and the acute type had PA associated symptoms for 2 weeks or less. The latter 2 types had positive pathological and MRI findings additionally. The basic lesions, acute or chronic symptoms, endocrinopathies and MRI findings were compared among 4 types. Results showed as followed. In all patients, there were headache(60. 7% ), blurred vision(55. 7% ), vomiting(21. 3% ), and dizziness(14. 8% ). Apoplexy associated symptoms comprised severe headache (24. 6% ), rapid vision loss (29. 5% ), and blepharopotosis or diplopia (9. 83% ). Insidious, asymptomatic, subacute, and acute types were composed of 15 (24. 6% ), 9 (14. 8% ), 19 (31. 1% ), and 18 (29. 5% ) cases, respectively. Aging and intracranial space-occupying symptoms as first complaint showed increasing trend from mild to severe types(both P<0. 05), while in chronic course it showed decreasing trend(P<0. 05). Acute massive symptoms(P<0. 01), and non-functional tumor(P<0. 01) in the 2 clinical types were much more frequent than in the two mild types. Half or more pituitary-target glands showed impaired functions in each type, and the impairment showed increasing trend through mild to severe types(P<0. 01). The present study provided a brief typing system in order to expand PA concept to a wider span covering various conditions. Some differences in tumor composition and endocrinopathies existed among the four types.