11β-Hydroxylase deficiency (11OHD) is a common form of congenital adrenal hyperplasia that has been shown to result from inactivating CYP11B1 mutations, and pathogenic CYP11B2/CYP11B1 chimeras contribute to a minority of cases. Heterozygote cases (chimeras combined with missense mutation) are very rare, and genetic analysis of these cases is difficult.
Adrenal corticomedullary mixed tumours are very rare. Its mechanism is rarely reported. Here we report the first case of a corticomedullary mixed tumour resembling a “small adrenal gland” with distinct arrangement of the cortical and medullary layers. We further hypothesize regarding the tumorigenic mechanism of this tumour.
Metformin is an anti-hyperglycemic agent used to treat diabetes, and recent evidence suggests it has antitumor efficacy. Because growth hormone-secreting pituitary adenoma (GH-PA) patients have a high incidence of diabetes frequently treated with metformin, we assessed the antitumor effect of metformin on GH-PA. We found that metformin effectively inhibited proliferation and induced apoptosis in the GH-PA cell line GH3. We detected a decrease in mitochondrial membrane potential (MMP), an increase in expression of pro-apoptotic proteins, and a decrease in expression of an anti-apoptotic protein in metformin-treated GH3 cells, which suggests involvement of the mitochondrial-mediated apoptosis pathway. Inhibition of AMPK, which is activated by metformin, failed to reverse the antiproliferative effect. ATF3 was upregulated by metformin, and its knockdown significantly reduced metformin-induced apoptosis. In addition, GH secretion was inhibited by metformin through suppression of STAT3 activity independently of AMPK. Metformin also significantly suppressed cellular proliferation and GH secretion in primary human GH-PA cells. Metformin also significantly inhibited GH3 cell proliferation and GH secretion in vivo. ATF3 upregulation and p-STAT3 downregulation were confirmed in xenografts. These findings suggest metformin is a potentially promising therapeutic agent for the treatment of GH-PA, particularly in patients with diabetes.
亚急性甲状腺炎(以下简称亚甲炎)是甲状腺炎中比较常见的一种,亦称肉芽肿性甲状腺炎或巨细胞性甲状腺炎,是一种具有自限性的甲状腺疾病,可在数周或数月内自然消退[1].其发病原因尚不十分清楚,目前多认为与病毒感染有关,是否有自身免疫异常尚无定论,因对其临床表现的多样性,常易误、漏诊[2].有学者报道由于亚急性甲状腺炎发病率低,临床医师认识不够充分,导致初诊误诊率超过50%[3].现将2008年1月-2011年1月我院初诊时误诊为急性咽喉炎、上呼吸道感染、甲亢、桥本甲状腺炎、心肌炎、甲状腺癌等疾病的25例亚甲炎患者报告如下,总结其发病特点,以期提高对该病的诊治准确性.
Objective To explore the therapeutic effect of microsurgery for intra-suprasellar craniopharyngioma via endonasal transsphenoidal approach.Methods Clinical data of 10 patients with intra-suprasellar craniopharyngioma were analyzed retrospectively,who consisted of 4 juveniles and 6 adults.Microsurgery by endonasal transsphenoidal approach was performed in all the patients.Then,clinical symptoms and hormone levels before and after operation were compared.Results Total tumor removal was achieved in 8 patients and subtotal removal in 2,of the latter two,one was treated by gamma knife and the other by endonasal transsphenoidal surgery again.Pituitary stalks were intact in all the patients.One patient died of electrolyte disturbances 1 month after operation,and another was lost to fo11ow-up 4 months after operation.The clinical symptoms were improved to different degrees in most patients after the operation.Endocrine hormones decreased in 8 patients,and all of them were given hydrocortisone and levothyroxine sodium,while there was no significant difference between predose and maintenance dose (P > 0.05).During the follow-up period of 1 year,no tumor recurred.Conclusions Microsurgery by endonasal transsphenoidal approach have advantages with less trauma,short operation time,high resection rate,fewer postoperative complications for intra-suprasellar craniopharyngioma,and can obviously improve clinical symptoms.Moreover,it should be emphasized that the standardized long-term follow-up and appropriate hormone replacement therapy are necessary,for improving the quality of life in postoperative patients.
目的:比较低血糖指数(GI)全营养素与高蛋白营养素2种不同营养配方预进餐对2型糖尿病患者血糖控制效果的影响.方法:回顾性分析115例2型糖尿病患营养治疗记录,其中高蛋白营养素治疗组31例为高蛋白组、低GI全营养素治疗组39例为低GI组、无肠内营养治疗干预组45例为对照组,每组都进行糖尿病饮食指导、教育并编制糖尿病膳食食谱.观察比较3组患者营养干预前,营养干预后第1d、第3d、第7d的空腹、餐后2h血糖控制情况.结果:与对照组相比,高蛋白组与低GI组空腹血糖在干预前后均没有明显差异,无统计学意义(P>0.05);餐后2h血糖在干预前、第1d没有差异,无统计学意义(P>0.05),而在第3d、第7d血糖明显下降,有统计学意义(P<0.05).与低GI组相比,高蛋白组空腹血糖和餐后2h血糖干预前后均没有明显差异,无统计学意义(P>0.05).结论:不同营养配方预进餐有利于2型糖尿病患者血糖控制,尤其是餐后2h血糖控制,2种营养配方控制血糖效果相似.
目的:探讨健康教育在高血压护理中的应用效果。方法:选取2012年6月~2013年6月来我院接受治疗护理的100例高血压患者,随机将其分为观察组和对照组各50例,给予对照组患者采用常规护理,给予观察组患者在常规护理基础上加以健康教育,比较两组患者的护理效果。结果:经过对100例患者的健康教育评分,观察组患者总有效率为98%,对照组患者总有效率为86%,观察组患者的健康教育评分明显要高于对照组患者,P<0.05。结论:加强健康教育在高血压患者护理中发挥了重要的作用,通过有计划有目的地进行教育,能够保证患者在自身生活行为上规范自己,养成良好的生活习惯,达到治疗和护理高血压疾病的效果。
CONTEXTTransplantation with stem cells has been reported as a potential treatment for diabetes. However, there are few reports examining transplantation with umbilical cord blood (UCB) in type 2 diabetes (T2DM).OBJECTIVEThe aim of the study was to evaluate the efficacy of intrapancreatic UCB transplantation in patients with T2DM.DESIGN AND SETTINGThree patients were enrolled in the study, which was performed in a hospital setting from 2010 to 2012, and the duration of follow-up was approximately 6 months.PATIENTS AND INTERVENTIONSUCB cells were infused by microcatheter into the dorsal pancreatic artery in 3 T2DM patients with different diabetic histories.MAIN OUTCOME MEASURESBlood glucose (including 72-h continuous blood glucose), C-peptide, hemoglobin A1c, the requirement for insulin, and transplant complications were monitored before and after transplantation.RESULTSAfter the transplantation, C-peptide levels had increased in all of the patients. In addition, the 72-hour continuous blood glucose monitoring results obtained after transplantation revealed that levels were more stable than before transplantation for all of the patients (P < .05). In addition, the requirements of insulin were reduced in all patients after transplantation.CONCLUSIONUCB transplantation may be an approach that could somewhat improve C-peptide levels in patients with T2DM.
<正>1临床资料患者,女性,68岁,因"发现血糖高10年,控制不佳加重1月"入院。10年前,患者偶然查血糖16.2 mmol/L,无明显"三多一少"症状,于某三甲医院检查确诊为"2型糖尿病",予"二甲双胍"等口服降糖药治疗,患者反复于餐前及夜间发生低血
目的观察硫辛酸在早期糖尿病肾病(diabetic nephropathy,DN)中的疗效。方法筛选2009年1月至2011年12月该院确诊为早期DN患者131例,其中男性66例,女性65例,年龄(53±10)岁,随机分为硫辛酸组(n=45,注射用硫辛酸0.45 g+0.9%生理盐水250 ml静脉滴注1次)、厄贝沙坦组(对照组,n=40,厄贝沙坦0.15 g口服1次/d)、联合组(n=46,注射用硫辛酸0.45 g+0.9%生理盐水250 ml静脉滴注1次,厄贝沙坦0.15 g口服1次/d)。监测、对比3组患者治疗前后血糖、24 h尿微量白蛋白、糖化血红蛋白、血尿素氮、血清肌酐等指标。结果 3组病例治疗前后血糖、糖化血红蛋白、尿素氮、血清肌酐各项指标之间无明显统计学差异(P>0.05)。3组中尿白蛋白排泄率均显著降低(P<0.05),厄贝沙坦组与联合组间有统计学差异(P<0.05)。结论硫辛酸在糖尿病早期肾病中能降低蛋白尿。
Objective In order to detect the effects of rectal cancer caused by gene polymorphisms and environmental factors.Methods The risk factors of rectal cancer are analyzed by chi-square test,univariate and multivariate non-conditional logistic regression model,and we compare the degree of influence of factors.Results The results show that gene XRCC194 locus for the heterozygote(A/a-type)populations,gene XRCC7 locus for the homozygote(A/A-type)populations and the smoking habits populations have relatively higher risk for rectal cancer.The study also finds the relationship between gene locus XRCC194,XRCC7 single nucleotide polymorphism and rectal cancers diseases is not affected by age,gender and smoking and other factors,the result reveals gene locus XRCC194,XRCC7 are independent risk factors.Conclusion Smoking habits and genetic factors are relative to rectal cancers diseases.
Objective To study the efficacy and safety of autologous bone marrow stem cells(BMSCs)transplantation via dorsal pancreatic artery(DPA)for type 2 diabetes mellitus(T2DM).Methods Six T2DM patients aged 45.67±14.92 years(3 males and 3 females) admitted to our department from June 2009 to April 2011 were enrolled in this study.The patients underwent BMSCs transplantation.Their bone marrow was mobilized and collected.BMSCs were isolated and infused into the DPA.Changes in fasting and postprandial blood glucose level,glycosylated hemoglobin(HbA1c) value,function of pancreatic islets,area under curve for C-peptide(AUCC),and insulin dose were observed.Adverse reactions of BM-SC transplantation for T2DM were recorded during and after operation with its safety and efficacy assessed.Results The HbA1c value decreased from(10.33±2.78)% before operation to(7.05±0.90)% after operation,which was <7% in 2 patients.The fasting C-peptide(FC-P)level increased from(0.71±0.54) ng/ml before operation to(1.54±0.63) ng/ml after operation.The 2 h postprandial C-peptide(2 h C-P)level increased from(1.63±0.88) ng/ml before operation to(4.67±2.31) ng/ml after operation.The mean AUCC increased from(2.29±1.31) ng/ml before operation to(6.05±2.94) ng/ml after operation.The insulin dose decreased from(27.17±13.08) U/d before operation to(18.63±7.04) U/d after operation.Subcutaneous insulin injection was withdrawn in 2 patients who changed to have oral hypoglycemic drugs.No adverse reaction occurred during autologous BMSCs transplantation and follow-up.The tumor markers and amylase level were normal before and after BMSCs transplantation.Conclusion Autologous BMSCs transplantation can improve the function of pancreatic islets of T2DM patients and decrease their dependence on hypoglycemic drugs with rather good safety.
Although experimental animal and clinical trials have suggested that additional mechanisms other than protein kinase C (PKC)-β activation are involved in the vascular pathology of diabetic complications, current knowledge on the role of PKC-delta is incomplete and inconclusive. Human umbilical vein endothelial cells (HUVECs) were cultured in both high and normal glucose conditions and infected with recombinant adenovirus to overexpress PKC-delta. PKC-delta expression was also down-regulated using the PKC-delta inhibitor, rottlerin. Using flow cytometric analysis, we showed that PKC-delta is activated and translocates to the nucleus under high glucose conditions. Augmented cell apoptosis and cell cycle arrest were observed in a PKC-delta-dependent manner in the HUVECs. Furthermore, proteomic analyses identified 51 high glucose-induced and PKC-delta-associated proteins, and subsequent matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis uncovered a total of 37 unique proteins. The majority of identified proteins were previously unknown targets of PKC-delta signaling and were involved in the regulation of the cell cycle and apoptosis, tumor suppression, transcription, stress and signal transduction within the nucleus. Our data show that PKC-delta is an important mediator of cell apoptosis and cell cycle arrest in HUVECs under high glucose stress.
李女士是个演员.一天化妆时,她无意间从镜子里看到自己脖子左侧有个小包块,到医院一检查,竟是甲状腺囊肿.李女士顿时紧张起来,"医生,这个病需要动手术吗?会不会留下疤痕影响美观呀?"听到她的顾虑,医生给她推荐了无水酒精注射治疗法.经过2次治疗,李女士高兴地发现疤痕没有现身,脖子上的包块消失了.
Objective:To construct endothelial cell model with hPRKCD gene overexpression under high glucose stress,and to investigate the expression of PKCδ in human umbilical vein endothelial cell(HUVEC) transfected with Ad5-PRKCD.Method:Full length PRKCD cDNA was obtained from p rimary plasmid by PCR amplification.The PCR product and eukaryotic expression vector pDC316-lacZα were digested by restriction endonucleases AgeⅠ and NheⅠ and constructed the recombinant shuttle plasmid pDC316-PRKCD.Gene sequencing was performed to identify the recombinant shuttle plasmid.The adenovirus genomic plasmid pBHGlox△E1,3Cre co-transfected with shuttle plasmid into 293 cells to construct recombinant adenovirus Ad5-PRKCD.The virus titer was calculated by TCID50.Ad5-PRKCD was then used to transfect into HUVEC under high glucose stress(25mmol/L),and the expression of PKCδ was investigated by immunofluorescence assay.Result: The recombinant shuttle plasmid was successfully identified by gene sequencing as repoted in GenBank,the recombinant adenovirus Ad5-PRKCD was successfully constructed with high titer(1.0×1010IU/ml).under high glucose stress,the expression of PKCδ was increased by 1.5 fold compared with the normal control(P0.05),thus after transfected with Ad5-PKCδ,it is even more increased under high glucose stress,and the fluorescence of cytosol-to-nuclei is decreased by 35%(p0.05),indicating obvious nuclear translocation.Conclusion: The recombinant adenovirus vector Ad5-PRKCD was successfully constructed and effectively transfected into HUVEC,PKCδ translocated to nucleus under high glucose stress,It is a potential tool for screening HUVEC stably expressing PKCδ.And isolating protein complex.
1 临床资料 病例1:患者女性,48岁,因"头晕、乏力、全身肌肉疼痛5 d"到当地中心医院就诊.查心肌酶谱:门冬氨酸氨基转移酶(AST)204.4 IU/L、磷酸肌酸激酶(CK)8 136.5 IU/L、CKMB 293.6 IU/L、α-羟丁酸脱氢酶(HBDH)524.3 IU/L、乳酸脱氢酶(LDH)587 IU/L.血脂:胆固醇(TC)9.9 mmol/L、甘油三酯(TG) 1.8 mmol/L、低密度脂蛋白胆固醇(LDC-c)5.66 mmol/L、高密度脂蛋白胆固醇(HDL-c)2.99 mmol/L.
1 临床资料 患者,女性,39岁.因反复口干、多饮、多尿、多食10余年,于2009年5月26日入我科.患者于1996年妊娠5个月时出现口干、多饮、多尿、多食,尿糖(+ + + +)、空腹血糖23 mmol/L,诊断为"妊娠糖尿病",经胰岛素治疗后空腹血糖控制在7~8 mmol/L,产后患者口服"二甲双胍、格列本脲"治疗,但未监测血糖,1998年因口干、多饮、多尿、多食加重,查空腹血糖23 mmol/L,经相关检查后确诊为1型糖尿病,长期使用胰岛素泵控制血糖,基础量为26 U,三餐前各追加5 U,空腹血糖控制在7~8 mmol/L.
Objective: To observe the influencing factors for efficiency of liposome-mediated transfection into human umbilical vein endothelial cell(HUVEC). Methods: Transferring HUVECs by distinct conditions,such as ratios of liposome and plasmid,densities of per well and different times of incubation,and transfection rates were observed and calculated by fluorescent microscope and flow cytometry. Results:⑴ When density of per well exceeded 2×l04 and times exceeded 4 hours,liposome-mediated transfection efficiency of endothelial cells decreased. ⑵With adding plasmid quality, transfection rates increased;while plasmid quality exceeded 1.0 μg,in condition of 2×l04 per well and liposome volume 2 μl, transfection efficiency reached the peak level. ⑶With adding liposome volume, transfection rates increased;while liposome volume was 8 μl,in condition of 2×104 per well and plasmid quality 1 μg, transfection efficiency was depressed.When ratios of liposome and plasmid were 1:6~1:8,the optimal transfection efficiency was 18.62%. Conclusion: Using optimal transfection parameter,we obtained the optimal transfection efficiency .
Objective To construct the endothelial cell model with overexpressed human protein kinase C β_2(PKC β_2) after high glucose inducement in order to study the function of human PKCβ_2. Methods The PRKCB1 gene was amplified from pMD18-T-PRKCB1 plasmid and then directly cloned into shuttle plasmid pDC315 to construct shuttle plasmid. Then the recombinant shuttle plasmid and adenovirus genomic plasmid pBHGlox△E1 ,3Cre were co-transfected into 293 cells to construct recombinant adenovirus Ad-PRKCB1. The virus titer was calculated by TCID50. The Ad-PRKCBl was verified by immunocytochemistry and RT-PCR. Ad-PRKCB1 was transfected into human umbilical vein endothelial cells (HUVECs) followed by the treatment of high glucose (25 mmol/L) for 96 h, and then the cells were observed by laser scanning confocal microscopy ( LSCM). Results Restrictive endonuclease digestion and PCR result showed that the target gene was correctly cloned into shuttle plasmid. Cytopathic effect (CPE) was observed under inverted microscope through homologous recombination. The virus titer was 7.9 ×10~9IU/ml. Immunocytochemical staining and RT-PCR indicated the expression of human PKC β_2 the transfected HUVECs. The translocation was observed under LSCM. Conclusion A recombinant adenovirus vector with human PKC β_2 and the endothelial cell model with human PKC β_2 overexpression by high glucose are constructed successfully.