先天性高胰岛素血症家系ABCC8、KCNJ11、GLUD1基因突变分析

目的 通过对先天性高胰岛素血症患儿家系ABCC8、KCNJ11及GLUD1基因的突变分析,探讨先天性高胰岛素血症的遗传发病机制.方法 选取2008年11月至2012年2月北京儿童医院收治的11例临床诊断为先天性高胰岛素血症的患儿及其家系为研究对象,其中男7例,女4例.应用PCR DNA直接测序技术对11个患儿的家系ABCC8基因的39个外显子区、KCNJ11基因的非翻译区及外显子区以及GLUD1基因的第6、7、10、11、12外显子区进行测序分析.结果 11例患儿家系中,病例1及其父亲携带ABCC8基因P629PfsX17杂合突变;病例4及其父亲携带ABCC8基因W288X杂合突变;病例5携带ABCC8基因A640V和Q1196x杂合突变,而其父亲仅携带ABCC8基因Q1196x杂合突变;病例6及其父亲携带GLUD1基因R269H杂合突变;上述4例患儿母亲相应基因位点均正常.另7例患儿及其父母并未检测出上述3种基因突变.结论 ABCC8基因突变是导致中国儿童先天性高胰岛素血症发病的主要致病机制.在中国人中,ABCC8基因的P629PfsX17、W288X、A640V、Q1196x杂合突变,GLUD1基因的R269H杂合突变可以导致先天性高胰岛素血症的发生,其遗传方式可为父系遗传或新生突变.     

新生儿糖尿病48例临床特征及分子遗传学分析

目的 总结48例新生儿糖尿病（neonatal diabetes mellitus, NDM）的临床及分子遗传学特点,为精准治疗方案的确立提供依据。方法选取48例NDM患儿及其家系为研究对象,分析患儿的围生期情况、临床及实验室检查等资料,并先后应用PCR-DNA直接测序、甲基化特异性的多重连接依赖的探针扩增及二代测序技术进行分子遗传学分析。结果30例（62.5%）为永久性NDM,18例(37.5%)为暂时性NDM,与永久性NDM相比,暂时性NDM起病更早（P=0.015）,糖尿病酮症酸中毒发生率较低(P=0.03)。暂时性NDM缓解年龄2.5~10个月,其中4例4.5~8岁时复发。48例中有41例(85.42%) 明确了分子遗传学病因,分别有25例、3例、2例、3例、8例检出KCNJ11、ABCC8、INS、GCK基因突变及染色体异常。41例患儿中有28例(69%)成功转用格列本脲治疗,其中23例为KCNJ11基因突变,4例染色体异常,1例ABCC8基因突变。结论大部分NDM检测到分子遗传学异常,其中KCNJ11基因突变和染色体异常最为常见,其次为ABCC8基因突变。早期使用格列本脲治疗NDM是安全有效的。     

婴儿持续性高胰岛素血症性低血糖症9例临床和基因突变分析

目的分析婴儿持续性高胰岛素血症性低血糖症(PHHI)的临床表现、遗传学特点和基因突变特点。从基因水平了解PHHI的致病因素,以达到基因诊断和遗传咨询的目的。方法对9例PHHI患儿临床表现及检查结果进行分析。提取患儿外周血基因组DNA,利用聚合酶链式反应(PCR)先扩增外周血ABCC8和KCNJ11基因外显子所在片段,对扩增片段进行正向序列测定,以检测突变。结果 2例患儿KCNJ11基因突变,1例患儿KCNJ11外显子第101位点G→A纯合突变(R34H),1例患儿KCNJ11外显子第91位点C→T杂合突变(R31W);2例患儿ABCC8基因突变,1例患儿ABCC8外显子31第3832位点出现G→A杂合突变(G1255S),1例患儿AB-CC8外显子12第1861位点出现C→T杂合突变(R598X)。结论发现4例患儿的基因突变,并发现一个国内外尚未见报道的ABCC8新突变(G1255S),为临床治疗、遗传咨询及产前诊断提供依据。     

单基因突变导致的糖代谢异常的遗传学分类及临床提示

单基因突变导致的高血糖/低血糖是一种特殊类型糖代谢异常. KCNJ11、ABCC8、HNF1A、HNF4A、GCK、HNFIB、线粒体m.3243A等基因突变导致的糖尿病可以根据其临床表现不同,处理方法也不尽相同.     

11例糖代谢异常患儿的遗传病因分析及诊治方案

目的：探讨遗传学病因分析在糖代谢异常患儿诊治中的作用。方法：回顾性分析2019年10月至2022年10月广西医科大学第二附属医院儿科收治的11例糖代谢异常患儿的临床表现、遗传病因及诊治方案。结果：11例糖代谢异常患儿中，5例高胰岛素血症（CHI）,6例糖尿病。5例CHI患儿中有3例检出基因变异，其中2例分别检出ABCC8基因c.3976G>A和FOXA2基因c.428A>G杂合变异，经治疗，血糖恢复至正常范围；1例检出KCNJ11基因c.560C>A杂合变异，需要长期二氮嗪维持治疗；5例CHI均对二氮嗪治疗敏感。6例糖尿病患儿中有2例分别检出HNF1A基因c.475C>T和KCNJ11基因c.601C>T杂合变异。所有患儿初诊后均应用胰岛素治疗，检出KCNJ11基因变异的患者改用格列本脲治疗，所有患儿血糖控制良好。结论：遗传因素是导致儿童糖代谢异常的重要原因之一。对糖代谢异常儿童行基因检测以鉴定遗传学病因，对疾病的分子分型、针对性治疗、全程管理及预后改善均有重要意义。     

南宁市1 027例新生儿耳聋基因筛查结果分析

目的:探讨GJB2、GJB3、SLC26A4和线粒体12SrRNA四个耳聋基因在南宁市新生儿耳聋基因检测中的应用价值。方法:随机选取2016年1月-2018年12月南宁市新生儿疾病筛查中心1 027例新生儿足跟血滤纸片,并提取DNA,应用测序法检测耳聋基因突变位点,包括GJB2(c.35del G、c.176-191del16、c.235delC、c.299-300del AT、c.109GA、c.11 GA)、GJB3(c.538CT)、SLC26A4(IVS 7-2AG、c.2168AG)和线粒体12SrRNA(1555AG、1494CT)共11个突变位点。结果:1 027例新生儿中检出耳聋基因的突变者183例,占17.82%,其中GJB2基因突变176例,占17.14%,其中纯合子突变23例(c.235del C 1例,c.109GA 22例),占2.24%;杂合子突变153例(c.235del C 10例,c.299-300del AT 1例,c.109GA 138例,c.11 GA 4例),占14.90%。GJB3(c.538CT)杂合子突变1例,占0.10%。SLC26A4(IVS 7-2AG)杂合子突变3例,占0.29%。线粒体12SrRNA(1555AG)均质突变3例,占0.29%。本地区的GJB2和SLC26A4突变率与济宁、东莞、珠海、绍兴的突变率比较,差异均有统计学意义(P0.05)。结论:南宁市新生儿耳聋GJB2基因突变率比较高,GJB3、SLC26A4和线粒体12SrRNA基因突变率较低。致病基因以GJB2 c.109GA为主,通过测序方法才能检测出基因突变位点比较多,有利于发现本区域的致病基因突变位点。     

先天性高胰岛素血症18例临床特征和遗传学分析

目的对先天性高胰岛素血症(CHI)的临床特征及致病基因携带情况进行总结及分析。方法选取2015年12月—2018年10月北京儿童医院内分泌遗传代谢科收治临床先天性高胰岛素血症患儿18例为研究对象,对患儿的临床特征、致病基因携带情况、诊疗经过和后期随访资料等进行回顾性分析。结果18例患儿中,男7例,女11例,起病年龄生后1 d~1岁2个月,中位起病年龄为45 d,出生体质量2.7~4.9(3.74±0.68)kg;足月胎龄儿10例,巨大儿8例。携带ABCC8基因或GULD1基因突变7例(38.9%),未发现已知CHI相关致病基因突变11例。3例患儿携带ABCC8基因突变:2例(1例为巨大儿,1例出生体质量正常,均于生后第1天起病,均对二氮嗪治疗无效)携带ABCC8基因复合杂合突变,突变均分别遗传自父亲或母亲;另1例患儿携带父系遗传ABCC8基因突变,患儿于生后第3天起病,出生体质量正常,对二氮嗪治疗无效。4例患儿携带GULD1基因新生杂合错义突变,起病年龄生后1 d~1岁2个月,对二氮嗪治疗均有效,经长期随访,其中2例患儿确诊为癫痫。结论中国CHI患儿中,ABCC8基因和GULD1基因突变可导致CHI的发生。携带ABCC8基因突变者通常起病较早,多对二氮嗪治疗无效。携带GLUD1基因突变的患儿起病相对较晚,均对二氮嗪治疗有效,有发生癫痫的倾向。     

杭州市5279例新生儿耳聋基因突变筛查及突变携带者随访结果分析

目的了解杭州市新生儿常见耳聋基因突变携带率和突变类型,探讨听力-耳聋基因联合筛查在先天性耳聋早期诊断与干预中的作用。方法采集2018年6月至2019年12月在杭州市妇产科医院出生的5279例新生儿足底血,提取DNA并应用微阵列芯片杂交法检测4个常见耳聋基因（GJB2、GJB3、SCL26A4、线粒体12SrRNA）15个突变位点,关联新生儿听力筛查结果比较相关性,对耳聋基因突变新生儿父母行耳聋基因筛查验证,评估遗传因素的作用,对GJB2和SLC26A4耳聋基因突变者行基因测序诊断以确定基因型,随访耳聋基因突变和听力筛查未通过新生儿听力诊断和干预措施。结果5279例耳聋基因突变筛查新生儿中,突变280例,突变率为5.30%。4个耳聋基因中,GJB2突变率最高,为3.05%,其中纯合和复合杂合突变3例,杂合突变158例;其余由高到低分别为SLC26A4杂合突变84例,突变率为1.59%;GJB3杂合突变18例,突变率为0.34%;线粒体12SrRNA均质突变14例,突变率为0.27%;双基因杂合突变3例,突变率为0.06%;GJB2基因突变中c.235delC位点突变最多,SLC26A4基因中c.919-2A＞G位点突变最多。在耳聋基因突变携带者中,150例新生儿父母进行耳聋基因突变筛查验证,有135例新生儿突变来源于无表型的父母一方,占90.0%。在新生儿听力筛查中,耳聋基因未突变者未通过率为0.50%（25/4999）;耳聋基因突变携带者未通过率为1.79%（5/280）,两组比较差异有统计学意义（P＜0.01）。随访耳聋基因筛查和诊断均为GJB2纯合/复合杂合突变3例,听力筛查未通过;其中GJB2基因c.235delC纯合突变2例,出生2个月确诊为重度耳聋,出生6个月准备安装人工耳蜗;GJB2基因c.235delC/c.299delAT复合杂合突变1例,出生2个月确诊为中度耳聋,准备配戴助听器。结论本研究显示杭州市新生儿常见耳聋基因突变携带率5.30%,开展听力-耳聋基因联合筛查,有利于聋儿的早期诊断及早期干预。     

儿童结节性硬化症TSC2基因突变2例报道

目的 分析2例儿童结节性硬化症（TSC）散发病例TSC1和TSC2基因突变情况。方法 采用高通量测序技术和多重连接探针扩增（MLPA）相结合的方式对两例TSC家系先证者外周血DNA行TSC相关基因（TSC1、TSC2）检测,确定基因突变位点,并针对突变位点设计扩增引物,采用聚合酶链反应和Sanger测序法对先证者及其父母外周血DNA行二代测序验证。结果 家系1先证者存在TSC2基因(chr16),c.1228(外显子12)_c.1229(外显子12)insG（p.L410RfsX11）杂合突变,该突变为新发移码突变;家系2先证者存在TSC2基因(chr16),c.4925G>A(外显子38)（p.G1642D）杂合突变,该突变为新发错义突变。结论 检测出2例TSC患者均出现TSC相关基因新发突变,但这2个新发突变与疾病的关系还需经突变蛋白功能细胞模型和动物模型的进一步验证。     

基因编码ATP敏感性钾通道亚单位Kir6.2的激活突变与持久性新生儿糖尿病

背景:持久性新生儿糖尿病通常出现在出生后前3 个月的时间里,需要胰岛素治疗。多数情况下,其病因尚不清楚。因为ATP敏感的钾通道(KATP)参与了胰腺β细胞葡萄糖刺激的胰岛素分泌,因此我们推测使这一通道(KCNJ11)基因编码的Kir6.2亚单位激活突变,就可以引起新生儿糖尿病。方法:我们对29例患有持久性新生儿糖尿病患者的KCNJ11基因进行测序,对该基因有     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Acupuncture Treatment of Vomiting

CASE HISTORY A female patient, 46 years old, head of the foreign affairs department of a certain university in Beijing, paid her first visit on October 9, 2006, with the chief complaint of vomiting for one month. She got vomiting after meals in early September. Before that, she had discomfortable sensation in the stomach due to angry with others, but she didn't pay much attention. Later, it developed into vomiting after eating. After the vomiting, the discomfort would be relieved, but with slight hypodynamia. She was once diagnosed as having 'neurogenic vomiting'. Having taken some western and Chinese drugs, the above symptoms were a little bit improved, but she would have nausea upon eating and with regurgitation. Because of the fear for vomiting, she did not dare to have food intake, with body weight reduction of 6 kilos in one month.     

Qiu Baoguo''''s Experience in Treating Consumptive Syndromes after Radio-Chemotherapies

Radiotherapy and chemotherapy are the important modern medical therapies for malignant tumors,yet they can also bring about serious local and systemic toxic side reactions so to decrease the patient;'s life quality,manifested by a series of consumptive symptoms.Having engaged in the combined work of Chinese and western medicine for nearly 50 years,the research fellow Qiu Baoguo in Henan Provincial Academy of TCM has developed his unique views on the TCM study of consumptive syndromes.The author of this essay had once the fortune tO follow Dr.Qiu in clinic,and specially would like to introduce in the following Dr.Qiu's experience in treating consumptive syndromes after radio-chemotherapies for patients with malignant tumor.     

Insomnia Due to Deficiency of Both the Heart and Spleen Treated by Acupuncture-Moxibustion and Chinese Tuina

OBJECTIVE: To observe therapeutic effects of the comprehensive therapy of acupuncture-moxibustion and Chinese Tuina for treatment of insomnia due to deficiency of both the heart and spleen. METHODS: 92 cases were divided randomly into the treatment group (treated by acupuncture-moxibustion and Chinese Tuina) and the control group (treated by acupuncture-moxibustion). RESULTS: The therapeutic effect of the treatment group was obviously superior to that of the control group (the CHI2 test showed P < 0.01). CONCLUSIONS: The comprehensive therapy of acupuncture-moxibustion and Chinese Tuina can give marked therapeutic effects for treatment of insomnia due to deficiency of both the heart and spleen.     

Analysis of CK-19,PDX-1,Nestin,Ngn3 in different donor islet purity in rats

Objective: To investigate if there are the CK-19, PDX-1, Nestin, Ngn3 positive cells in the donor islets of different purity in rats. Methods: Thirty male adult SD rats were randomly divided into 3 groups. Islets were isolated using digestion by ductal injection of collagenase. Group Ⅰ (n=10): Separating cell preparations were not purified, Group Ⅱ(n=10): Islet sediment was purified with 25% Ficoll400 ,Group Ⅲ (n=10): Islet sediment was purified with 25% and 11% Ficoll-400. The levels of protein of CK-19, PDX-1, Nestin and Ngn3 were detected by immunohistochemistry and the mRNA of CK-19, PDX-1, Nestin, Ngn3 was amplified by RT-PCR. Results: After two different purification methods applied, three islet preparations of different purities were obtained. The difference of islet purity was significant among various groups (P＜0.05). Compared with group Ⅱ and group Ⅲ,the protein and mRNA of CK-19, PDX-1, Nestin,Ngn3 were both higher in group Ⅰ; group Ⅲ was poorly expressed. Conclusions: The three different islet purity donor islet have different CK-19, PDX-1, Nestin, Ngn3 positive cells within them, indicating that there are some islet stem cells in the purified donor islet.     

Dr.Zhang Ren''''s Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

Luo Lingjie''''s Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.