青少年起病的成人型糖尿病12型1例暨文献复习

青少年起病的成人型糖尿病(maturity-onset diabetes of the young, MODY)是一组由胰岛素分泌相关基因缺陷导致的常染色体显性遗传的单基因糖尿病。多数MODY患者由于缺乏特异性的临床表现, 临床上易被误诊为1型糖尿病或2型糖尿病, 因此需要基因检测来确诊[1]。目前已发现的MODY相关基因共14个[2], 分别对应MODY 1～14型。在这14种MODY类型中, 最常见的是MODY2, 占所有MODY患者的10%～60%[3]。MODY12是一种罕见的MODY类型, 占所有MODY类型的比例<1%[4]。该病最早于2012年由Bowman等[5]报道, 目前我国关于MODY12的报道很少[6,7,8,9,10,11], 治疗经验有限。本研究报道了一例曾误诊为1型糖尿病的MODY12病例, 旨在提高临床医生对该病的认识, 减少误诊及漏诊。     

一个新的葡萄糖激酶基因-E339K突变导致的中国人青少年发病的成年型糖尿病2型家系

目的 寻找一个典型的青少年发病的成年型糖尿病2型(MODY2)家系的责任基因.方法 抽提MODY家系成员基因组DNA,PCR扩增、直接测序候选基因葡萄糖激酶(GCK)基因5'端、3'端非翻译区及1～10号外显子,确认突变.结果 在MODY2家系中确认了一个新型的GCK-E339K突变,该突变与糖尿病或糖耐量异常共分离.结论 GCK-E339K突变可能与该MODY2家系相关,是该MODY2家系的责任基因.     

成年起病型青少年糖尿病的识别及其不同亚型的临床特征

成年起病型青少年糖尿病（maturity—onsetdiabetesoftheyoung,MODY）是最常见的单基因糖尿病,以胰岛8细胞功能障碍为特征,约占所有糖尿病的1％～2％,易被误诊为1型或2型糖尿病。由于MODY的明确诊断对患者的治疗、预后和遗传咨询有重要影响,故应积极进行鉴别诊断。本文将简要介绍MODY与1型和2型糖尿病的鉴别要点,以及不同亚型MODY的临床特征。     

青少年起病的成人型糖尿病筛查与诊治专家共识

青少年起病的成人型糖尿病（MODY）是一类特殊类型糖尿病,迄今已报道有14种MODY类型,约占糖尿病患者人数的1%~5%。MODY发病常常较为隐匿,临床上时常被漏诊。随着对MODY临床特点认识的深入以及分子生物学检测技术的迅速发展,越来越多的MODY患者被早期发现和诊断。本共识旨在帮助MODY患者早期发现、正确诊断和精...     

一个葡萄糖激酶基因Gly162Asp错义突变致青少年发病的成年型糖尿病2型家系报告

目的对一个高度怀疑青少年发病的成年型糖尿病2型(MODY2),即葡萄糖激酶(GCK)基因突变所致MODY家系寻找基因突变位点,并探讨其临床特点。方法对1例意外发现血糖升高、无酮症倾向、有糖尿病家族史的10岁女孩采用芯片捕获高通量测序方法进行致病基因检测,发现其携带GCK基因突变,对其家系进行调查,收集家系成员相关临床资料并取得家系成员的外周血基因组DNA,使用Sanger测序技术对家系成员进行筛查。结果该家系的5名成员检测到GCK基因(NM_000162)第5号外显子c.485GA(p.Gly162Asp)杂合错义突变,其中有4例为糖尿病患者,1例为IGR,该突变与糖尿病和IGR共分离,在白种人群中已有报道,在中国人群中为首次发现。结论 GCK基因突变c.485GA是该MODY2家系的主要致病基因。     

5个青少年起病的成人型糖尿病2型家系的临床及遗传学分析

目的探讨青少年起病的成人型糖尿病2型(MODY2)患者的临床及分子遗传学特征。方法收集西安市儿童医院内分泌遗传代谢科近2年诊断的5例MODY2患者及其家系成员的临床资料和实验室检查结果。对所有先证者行全外显子组基因检测, 筛选出的变异位点在各家系中行Sanger测序验证。结果 5个先证者中除先证者4有多饮多尿表现外, 其余患儿的高血糖均为意外发现。所有先证者尿常规、尿蛋白五项及血脂均无异常, HbA1C 5.96%～8.15%。不同于以往MODY2患者, 本研究发现先证者5同时存在胰岛素抵抗。基因检测证实5个家系均存在葡萄糖激酶(GCK)基因突变, 共包含4种突变类型:c.146C>T(p.T49I)、c.1237T>G(p.Y413D)、c.683C>T(p.T228M)及c.952G>T(p.G318W)。c.1237T>G(p.Y413D)及c.952G>T(p.G318W)为尚未报道的新突变。给予所有先证者生活方式干预, 血糖控制相对平稳。结论 MODY2可能合并胰岛素抵抗;该病治疗可仅给予生活方式干预, 效果良好;本研究发现的GCK基因2个...     

青少年的成人起病型糖尿病2型和3型混合家系一例临床分析并文献复习

目的探究葡萄糖激酶基因(GCK)及肝细胞核因子1α基因(HNF-1α)同时突变致青少年的成人起病型糖尿病(MODY)的临床和遗传学特点。方法对北京协和医院2017年9月诊断的一例MODY患者及其家系的临床特征、实验室资料进行分析;对家系成员进行MODY相关致病基因检测。结果该家系的5名成员检测到GCK基因(NM_000162)c.686C>T(p.Thr229Met)杂合突变。其中3名成员同时检测到HNF-1α基因(NM_001306179)c.1531C>G(p.Gln511Glu)杂合突变。结论MODY混合家系GCK及HNF-1α基因突变导致同一家系出现不同的MODY类型。诊断时需考虑混合家系的可能性,以准确诊断。     

中国人MODY/NIDDM家系葡萄糖激酶和肝细胞核因子1α基因缺陷的分子筛查

目的 探索包含青少年起病的成人型糖尿病(maturity-onset diabetes of the young,MODY)患者的2型糖尿病家族中可能存在的MODY基因的致病突变。方法 选择MODY基因中突变率最高的葡萄糖激酶(GCK，MODY2)和肝细胞核因子1α(HNF—1α，MODY3)基因的微卫星多态遗传标志在2个包含临床MODY患者的中国人2型糖尿病家系中进行连锁分析，对HNF—1α基因进行全基因外显子的突变筛查--DNA序列直接测定以明确具体的核苷酸突变和所编码的氨基酸的改变。结果 HNF—1α基因标志物在家系50001中MODY3的最大LOD值达到2．38(θ＝0．00)，家系50002中，MODY3最大LOD值达到3．59(θ＝0．00)；两家系均末发现与MODY2连锁的依据。DNA直接测序发现在家系50001中所有家族成员外显子7中存在一个杂合多态SeR487 Asn(AGC／AAC)，该多态在正常人中也可见到；家系50002中NIDDM／MODY个体MODY3基因外显子5编码区存在一个杂合错义突变Tyr322 Asn(TAT→AAT)。结论 GCK基因内或附近的基因变异不是本家系糖尿病的主要致病原因；家系50001中，HNF—1α基因的启动子和所有外显子内没有发现明确的致病突变，但不能否定内含子或其他调节区域的变异可能的致病倾向；由于本家系遗传标志D12S86与糖尿病的连锁LoD最大值达到2．38(9＝0．00)，所以也不能排除HNF—1α基因附近其他未知疾病基因的致病可能。家系50002中HNF—1α基因外显子5中发现的杂合错义突变Tyr(TAT／AAT)Asn有可能是一个疾病关联突变，具体致病的机理有待蛋白质功能研究证实。     

MODY3的研究、认识现状及处理

<正>目前已明确"青少年的成人起病型糖尿病"(MODY)是一种异质性常染色显性遗传病,按1999年WHO对糖尿病公布的新的诊断标准和分型的建议,将MODY归属于第三类型中的特殊类型糖尿病中,在第三类型中,又细分为8个类型,其中之一即β细胞功能基因缺陷:提到了MODY3、     

肝细胞核因子1β突变所致的以肾囊肿为突出表现的早发糖尿病临床特征及基因突变分析

目的对1例因肝细胞核因子1β(HNF1β)突变所致的以肾囊肿为突出表现的新发青少年起病的成人型糖尿病(MODY)5型患者的临床资料进行回顾性分析, 并对我国已发表MODY5患者的临床特征进行总结。方法选取1例于2021年7月就诊上海市公共卫生临床中心内分泌代谢科的MODY5型糖尿病患者作为研究对象, 对患者的临床资料、就诊及随访经过和基因检测结果进行详细描述, 并在美国国立医学图书馆数据库(PubMed)、中国期刊全文数据库(CNKI)和万方数据库自建库之日起至2022年8月15日检索所有关于中国MODY5患者的病例报告, 综合分析检索所得患者的相关临床数据。以基因突变类型将患者分为杂合突变体和缺失突变2类, 采用Mann‐WhitneyU检验对2类患者间相关指标进行比较。结果上海市公共卫生临床中心内分泌代谢科MODY5患者19岁糖尿病起病, 糖尿病自身免疫抗体均阴性, 合并肾囊肿、高尿酸、肾脏发育不良、胰腺萎缩, 携带HNF1β基因2号内含子c.544+3₅44+6del缺失突变, 该突变基因来自其母亲。文献检索共纳入32例MODY5患者, 包括上海市公共卫生临...     

On the behavior of a capillary surface in a wedge

Estimates above and below are obtained for the height of the equilibrium-free surface of a liquid when the liquid partially fills a cylindrical container whose cross section contains a corner with interior angle 2α. The surface is characterized by the condition that its mean curvature be proportional to its height above a reference plane (or, in the case of zero gravity, that the mean curvature be constant), and by the requirement that it meet the container wall with prescribed contact angle γ. It turns out that the qualitative behavior of such a surface near the vertex changes markedly, according as α + γ < ½π, or α + γ ≥ ½π. In the former case, the surface is either unbounded or fails to exist, while in the latter case every such surface is bounded. Some experimental comparisons are indicated, and an application to the problem of describing the mechanism of water rise in trees is discussed.

The above results describe a limiting case among corresponding properties that hold for surfaces defined over domains with smooth boundaries. This extension is indicated, as well as a formal extension to n-dimensional surfaces; here the interest centers on the fact that it is the mean curvature of an (n-1)-dimensional boundary element that controls the local behavior of the n-dimensional solution surface.

     

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

BackgroundA post‐operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality.MethodAn electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool.ResultsSix eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre‐operatively whereas 1 score included intra‐operative and two studies post‐operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50).ConclusionThese scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed.     

Assessing the impact of a fistula after a pancreaticoduodenectomy using the Post-operative Morbidity Index

Background

The Post-operative Morbidity Index (PMI) is a quantitative utility measure of a complication burden created by severity weighting. The Fistula Risk Score (FRS) is a validated model that predicts whether a patient will develop a post-operative pancreatic fistula (POPF). These novel tools might provide further discrimination of the ISGPF grading system.

Methods

From 2001 to 2012, 1021 pancreaticoduodenectomies were performed at four institutions. POPFs were categorized by ISGPF standards. PMI scores were calculated based on the Modified Accordion Severity Grading System. FRS scores were assigned according to the relative influence of four recognized factors for developing a clinically relevant POPF (CR-POPF).

Results

In total, 231 patients (22.6%) developed a POPF, of which 54.1% were CR-POPFs. The PMI differed significantly between the ISGPF grades and patients with no or non-fistulous complications (P < 0.001). 64.9% of POPFs and 84.0% of CR-POPFs contributed the highest Accordion grade to the PMI. Overall, the FRS correlated well with PMI (R² = 0.81, P < 0.001).

Conclusion

These data quantitatively reinforce the ISGPF grades that were developed qualitatively around the concept of clinical severity. CR-POPFs usually reflect the patient''s highest Accordion score whereas biochemical POPFs are often superseded. The correlation between FRS and PMI indicates that risk factors for a fistula contribute to overall pancreaticoduodenectomy morbidity.     

Evaluation of a program monitoring the quality of the services provided by a non-governmental organization

OBJECTIVE: To evaluate the effect of a quality-monitoring program on the occurrence of sentinel events and on attitudes and behaviors of personnel's responses in a Non-Governmental-Organization (NGO). MATERIAL AND METHODS: Between 1998 and 1999, a quasi-experimental design of the before-after type was conducted in 13 NGO clinics. Analysis of changes in attitudes and behaviors consisted in differences of means and analysis of variance between groups. RESULTS: The number of sentinel events decreased from 32 events detected before the quality-monitoring program to only 2 after it. Attitudes and behaviors improved, with differences of means of +1.1 and +1.2 (p < 0.05). CONCLUSIONS: The quality-monitoring program achieved the expected effects. It is noteworthy that attitudes and behaviors to prevent the occurrence of sentinel events were more prevalent after the intervention.