Three cases of congenital adrenal hypoplasia with hypogonadotropic hypogonadism due to novel NR0B1 mutation / 中华内分泌代谢杂志

Objective:To advance the understanding of X-linked adrenal hypoplasia congenita(XL-AHC)through genetic analysis.Methods:Genomic DNA was extracted from peripheral blood of three patients with XL-AHC and their family members as well. Pathogenic genes were screened with whole exome sequencing followed by Sanger sequencing and pedigree verification.Results:All three probands were diagnosed as primary adrenal insufficiency at early age and developed hypogonadotropic hypogonadism in adolescence. The proband 1 was hemizygous for c. 420delG(p.R141Gfs*123)mutation in exon 1 of NR0B1 gene. His mother was a heterozygous mutation carrier while his brother did not carry the mutation, which was consistent with the X-linked recessive inheritance. A hemizygous mutation c. 212_213delAA(p.K71Rfs*41)of NR0B1 gene was detected in both proband 2 and proband 3. These two novel mutations were not reported in HGMD database.Conclusions:In this study, two novel NR0B1 mutations, c. 420delG and c. 212_213delAA were identified in 3 patients with XL-AHC. For men with early onset of adrenocortical hypofunction, XL-AHC should be considered. Early genetic screening of NR0B1 gene is helpful for early diagnosis.

Study on genetic etiology of three cases of Kallmann syndrome using whole-exome sequencing / 中华内分泌代谢杂志

Objective:Kallmann syndrome(KS) is a complex genetic disease characterized by congenital hypogonadotropic hypogonadism and anosmia. More than 20 genes have been reported to be associated with KS. Herein, we explore potential genetic aberration in 3 KS patients using the whole-exome sequencing. The potentially pathogenic variants filtered were validated by Sanger sequencing.Methods:Genomic DNA was extracted from the peripheral blood of 3 patients with KS and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants identified using whole-exome sequencing. The function of the mutation sites were analyzed with bioinformatics software.Results:The proband 1 was a 25 years old male, characterized by lower gonadotropin gonad hypofunction, early grey hair and bilateral sensorineural hearing loss. A heterozygous mutation c. 475C>T(p.R159W) of SOX10 gene was detected in the proband 1. His mother, sister and cousin who had KS phenotype were also found carrying this mutation, showing an autosomal dominant inheritance. The proband 2 was a 15-year-old male with hypogonadotropic hypogonadism and unilateral renal agenesis. The proband was hemizygous for c. 844delC(p.R282Vfs*28) of ANOS1 gene, his mother was heterozygous for the mutation, which was consistent with the X-linked recessive inheritance. The proband 3 was a 21 years old female, characterized by hypogonadotropic hypogonadism and anosmia. A heterozygous missense mutation c. 149G>A(p.R50Q) was detected in FGF17 gene. The mutation p. R50Q was predicted to be pathogenic by the SIFT and PolyPhen2 programs, and has not been reported in HGDM database yet, which considered to be a novel mutation.Conclusion:KS is a clinically and genetically heterogeneous disease. In this study, ANOS1 c. 844delC, SOX10 c. 475C>T and FGF17 c. 149G>A mutations were found in 3 patients with KS by whole exome sequencing, which would expand the genotypic and phenotype spectrum of KS.

Study on genetic etiology of two patients with mucopolysaccharidosis using whole-exome sequencing / 中华内分泌代谢杂志

Objective:To explore the underlying genetic cause in two patients with mucopolysaccharidosis(MPS)using the whole-exome sequencing.Methods:Genomic DNA was extracted from the peripheral blood of two patients with MPS and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants filtered by whole-exome sequencing. The function of the mutation sites was analyzed by bioinformatics software. The effect of the splice mutation on mRNA was further determined by reverse transcription-PCR(RT-PCR).Results:The proband 1 was a 25-year-old male, who carried compound heterozygous mutations of α-L-iduronidas(IDUA) gene: p. T179R and p. S633L, and was diagnosed as MPSⅠ. His mother and sister carried heterozygous p. T179R, while his father carried heterozygous p. S633L, consistent with the autosomal recessive inheritance pattern. The proband 2 was a 3-year-old male, who was hemizygous for IVS 6-8A>G of iduronate-2-sulfatase(IDS) gene. His mother and grandmother were heterozygous for this mutation, consistent with the X-linked recessive inheritance. The proband 2 was diagnosed as MPSⅡ. Sequencing of RT-PCR products showed that the IVS 6-8A>G mutation activated an upstream cryptic splice-site in intron 6, leading to 7 nucleotide insertion in exon 7, frameshift, and shorter peptide chain.Conclusion:In this study, IDUA p. T179R and p. S633L, and IDS IVS 6-8A>G mutations were found in two patients with MPS by whole exome sequencing, which further expanded the genotypic and phenotype spectrum of MPS.

Human leukocyte antigen analysis in a case of autoimmune polyendocrine syndrome type Ⅲ and complicated with myasthenia gravis / 中华内分泌代谢杂志

Type 1 diabetes mellitus and autoimmune thyroid disorders are the most common combination of autoimmune polyendocrine syndrome type Ⅲ(APS Ⅲ). However, APS Ⅲ combined with myasthenia gravis is rare. We described a male patient with myasthenia gravis, type 1 diabetes mellitus, and Hashimoto thyroiditis, who was diagnosed as APS Ⅲ. The human leukocyte antigen (HLA)type was analyzed in this patient. We subsequently reviewed 11 cases of APS Ⅲ combined with myasthenia gravis. This review revealed that HLA-DR9/DQ9 might be a specific HLA subtype associated with APS Ⅲ and complicated with myasthenia gravis .

Analysis of serum hepcidin levels and related factors in patients with diabetic lower extremity vascular disease and foot ulcer / 中国医师杂志

Objective:To investigate the serum hepcidin level and risk factors associated with peripheral arterial disease (PAD) and foot ulcer in type 2 diabetic patients.Methods:From January 2019 to June 2019, 70 patients with type 2 diabetes in Department of Endocrinology of Xiangya Third Hospital were selected, including 21 newly diagnosed patients with type 2 diabetes (DM group), 23 patients with lower extremity vascular disease (PAD group) and 26 patients with foot ulcer (DF group). Serum hepcidin was determined by enzyme linked immunosorbent assay (ELISA). The serum levels of hepcidin in different groups were compared, and the correlation between diabetic lower extremity vascular disease and foot ulcer was analyzed.Results:⑴ The hemoglobin, albumin, triglycerides and total cholesterol were significantly lower in DF group compared with PAD and DM groups ( P<0.05), while the DF group patients were with higher white blood cell (WBC) count and high sensitivity C reactive protein (hs-CRP) than patients in PAD and DM groups ( P<0.05). DF group also showed significantly higher WBC, hs-CRP and neutrophil ratio level (NEUT%) than DM group ( P<0.05). The inflammatory indicators of WBC, hs-CRP and NEUT% showed no significant difference between DM group and PAD group ( P>0.05). ⑵ The levels of hepcidin in DF and PAD groups were higher than those in DM group, while that in DF group were higher than those in PAD group ( P<0.05); Hepcidin was positively correlated with systolic blood pressure, WBC count, NEUT% and ferritin ( P<0.05), and negatively correlated with hemoglobin, glycosylated hemoglobin, albumin and 25-hydroxyvitamin D ( P<0.05). ⑶ Binary multivariate logistic regression analysis showed that elevated hepcidin level was an independent risk factor for diabetic foot ulcer [ OR=1.755, 95% CI: 1.063-2.897, P=0.028]. Conclusions:The fluctuation of serum hepcidin level in diabetic patients is related to the stimulation of inflammation, the degree of anemia and the nutritional status, which means it might be an early indicator of inflammation in diabetic patients with peripheral arterial disease. Moreover, the increase of hepcidin is an independent risk factor for diabetic foot ulcers in our study.

Diagnosis of one case of Williams-Beuren syndrome presenting with hypothyroidism by low-coverage massively parallel CNV sequencing / 中华内分泌代谢杂志

Objective@#To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism.@*Methods@#Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs).@*Results@#The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs.@*Conclusion@#A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease.

Role of UHRF1 in methylation regulation and angiogenesis / 中华医学遗传学杂志

Many recent studies have proved that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important nuclear protein associated with tumorigenesis, which plays a significant role in epigenetic regulation, especially in DNA methylation and histone methylation. For its particular domains, UHRF1 plays a critical role in biological behaviors including cell proliferation, cell cycle, and apoptosis. Overexpression of UHRF1 in various tumors is closely associated with the angiogenesis in tumors. This paper will provide a review of the regulation of UHRF1 in DNA methylation and histone methylation, and discuss the potential epigenetic role of UHRF1 in angiogenesis.

Multiple endocrine neoplasia-IIb with RET gene mutation p.M918T： A case report / 中南大学学报(医学版)

Multiple endocrine neoplasia-IIb (MEN-IIb) is a rare hereditary autosomal dominant syndrome caused by mutations in the RET proto-oncogene. It's characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), mucosal neuromas, and Marfanoid habitus. Because of the rarity of MEN-IIb and finiteness of clinical cognition, the majority of the patients suffer a delayed diagnosis. A MEN-IIb patient with the lingual mucosal neuromas since childhood was admitted in the Third Xiangya Hospital of Central South University in November, 2018. He had surgical history of mitral valve prolapse and spinal deformity. He was diagnosed with MTC and PHEO at the age of 22 and 28, respectively, and received surgical treatments. Sequencing of RET gene revealed a de novo heterozygous p.M918T mutation in the patient. Being aware of the unique clinical phenotype and screening of RET gene mutation may lead to the early diagnosis and better long-term outcome for MEN-IIb.

Efficacy and safety of Changsulin ? compared with Lantus ? in type 2 diabetes: a phase Ⅲ multicenter, randomized, open-label, parallel, controlled clinical trial / 中华内科杂志

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Diagnosis of one case of Williams-Beuren syndrome presenting with hypothyroidism by low-coverage massively parallel CNV sequencing / 中华内分泌代谢杂志

Objective:To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism.Methods:Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs).Results:The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs. Conclusion:A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease.

Two cases of autoimmune polyendocrine syndrome type Ⅰ caused by AIRE gene mutation / 中华内分泌代谢杂志

Objective@#Autoimmune polyendocrine syndrome type Ⅰ(APS-Ⅰ) is caused by mutations in the autoimmune regulator gene (AIRE) gene. In this study, phenotype and AIRE gene analysis were performed in two patients with APS-Ⅰ.@*Methods@#Peripheral blood samples were collected from two patients with APS-Ⅰ and their families. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. The silico analysis was performed to predict the possible impact of the mutations on the function of the AIRE protein. At the same time, 100 healthy controls were selected to confirm the mutation.@*Results@#Case 1 was a 31-year-old female who exhibited chronic mucocutaneous candidiasis, hypoparathyroidism, Addison′s disease, Hashimoto′s thyroiditis, and premature ovarian failure. A homozygous c. 483_484insC mutation in exon 4 of AIRE gene was identified in this patient. Her parents, siblings and son were heterozygous for this mutation, which is consistent with the autosomal recessive inheritance pattern. Case 2 was a 34-year-old male who had mucocutaneous candidiasis, Addison′s disease, primary hypoparathyroidism, and Hashimoto′s thyroiditis. A compound heterozygous AIRE mutation (c.179A>G/C.463+ 2T>C) were identified in this patient. His father was heterozygous for c. 179A>G mutation, and his mother was heterozygous for C. 463+ 2T>C, which is consistent with autosomal recessive inheritance mode. The c. 483_484insC and c. 463+ 2T>C have been reported to be pathogenic. The c. 179A>G mutation was predicted pathogenic by SIFT and PolyPhen2 software, which was not detected in 100 healthy controls. It has not been reported in the HGDM database and is a novel mutation.@*Conclusion@#We identified a novel AIRE gene mutation (c.179A>G), which contributed to further understanding of the pathogenesis of APS-Ⅰ. The clinical variation and rarity of APS-Ⅰ makes the syndrome hard to recognize. Early recognition of symptoms and screening for AIRE mutation in patients with APS-Ⅰ has important clinical implications for the diagnosis and treatment.

Two cases of autoimmune polyendocrine syndrome typeⅠcaused by AIRE gene mutation / 中华内分泌代谢杂志

Objective Autoimmune polyendocrine syndrome typeⅠ( APS-Ⅰ) is caused by mutations in the autoimmune regulator gene ( AIRE) gene. In this study, phenotype and AIRE gene analysis were performed in two patients with APS-Ⅰ. Methods Peripheral blood samples were collected from two patients with APS-Ⅰand their families. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. The silico analysis was performed to predict the possible impact of the mutations on the function of the AIRE protein. At the same time, 100 healthy controls were selected to confirm the mutation. Results Case 1 was a 31-year-old female who exhibited chronic mucocutaneous candidiasis, hypoparathyroidism, Addison' s disease, Hashimoto's thyroiditis, and premature ovarian failure. A homozygous c.483484insC mutation in exon 4 of AIRE gene was identified in this patient. Her parents, siblings and son were heterozygous for this mutation, which is consistent with the autosomal recessive inheritance pattern. Case 2 was a 34-year-old male who had mucocutaneous candidiasis, Addison' s disease, primary hypoparathyroidism, and Hashimoto' s thyroiditis. A compound heterozygous AIRE mutation (c.179A>G/C.463+2T>C) were identified in this patient. His father was heterozygous for c.179A>G mutation, and his mother was heterozygous for C.463+2T>C, which is consistent with autosomal recessive inheritance mode. The c.483484insC and c. 463+2T>C have been reported to be pathogenic. The c. 179A>G mutation was predicted pathogenic by SIFT and PolyPhen2 software, which was not detected in 100 healthy controls. It has not been reported in the HGDM database and is a novel mutation. Conclusion We identified a novel AIRE gene mutation ( c.179A>G) , which contributed to further understanding of the pathogenesis of APS-Ⅰ. The clinical variation and rarity of APS-Ⅰmakes the syndrome hard to recognize. Early recognition of symptoms and screening for AIRE mutation in patients with APS-Ⅰhas important clinical implications for the diagnosis and treatment.

Nivolumab-induced hypothyroidism: A case report / 中南大学学报(医学版)

Nivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody, which is a new drug for tumor immunotherapy. A 73-year-old female patient with colorectal cancer 3 years after surgery was treated in the Endocrinology Department of Third Xiangya Hospital, Central South University, who developed severe hypothyroidism resulting from treatment with nivolumab. After 4 months treatment of nivolumab, this patient presented with symptoms such as fatigue, dizziness, jaundice and palpebral edema, with decreased levels of FT3 and FT4 and elevated levels of TSH. Subsequently, nivolumab treatment was terminated. This patient's symptoms were relieved and thyroid function returned to normal after thyroxine replacement therapy. The clinical diagnosis was considered to be nivolumab-induced autoimmune thyroid damage, which was an immune-related adverse reaction in the treatment.

Two cases of primary hypertrophic osteoarthropathy with SLCO2A1 gene mutations / 中南大学学报(医学版)

Two patients with primary hypertrophic osteoarthropathy (PHO) and their available healthy family members were studied.All exons of the SLCO2A1 and HPGD gene and adjacent exonintron sequences were amplified by PCR and subsequently sequenced.To assess the damaging effects of missense mutations in silico,the online database,PolyPhen-2 and SIFT were used.We identified two homozygous mutations in SLCO2A1 gene:one was c.1106G＞A (p.G369D) in exon 9,the other was c.611C＞T (p.S204L) in exon 4.No HPGD mutation was found in the affected individuals.The two mutation were predicted in silico by the bioinformatic tools.Our study further supports the role of mutations in the SLCO2A1 gene in the pathogenesis of PHO.Identification of the genotype in PHO may not only help the clinical diagnosis of PHO but also help the interpretation of genetic information for prenatal diagnosis and genetic counseling.

A case of growth hormone deficiency combined with neurofibromatosis Type 1 and its gene analysis / 中南大学学报(医学版)

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by NF1 gene mutations. Café au lait spots, neurofibromatosis, Lisch nodules, axillary freckling, dermal neurofibromas and skeletal dysplasia are the most common manifestations for this disease. A 11-year-old boy visited Third Xiangya Hospital, Central South University due to growth-retardation. He was eventually diagnosed as NF1 with growth hormone deficiency. A novel heterozygous splicing mutation c.6579+2 T>C (IVS 34+2 T>C) of NF1 gene was identified in the patient and his mother. Considering NF1 may present with short stature due to growth hormone deficiency, all children with short stature combined with café au lait spots should be screened for NF1, which may assist the clinical diagnosis and the genetic counseling.

Van Wyk-Grumbach syndrome: A case report and literature review / 中南大学学报(医学版)

Van Wyk-Grumbach syndrome (VWGS) is a rare complication of prolonged untreated juvenile hypothyroidism characterized by precocious puberty and enlarged multicystic ovaries. A 13-year-old girl visited our outpatient clinic due to menstrual irregularities. She had precocious puberty, pituitary hyperplasia and multiple cystic ovaries in addition to clinical signs of severe congenital hypothyroidism. After the initiation of L-thyroxine therapy, the symptoms were alleviated in a short time. This rare syndrome is easy to be misdiagnosed as pituitary and ovarian tumor. High degree of suspicion and timely diagnosis can prevent unnecessary surgical procedures because the symptoms can be reversed with thyroid hormone supplementation.

Protective effect of silibinin on islet β cells in C57BL/6J mice fed a highfat diet / 中南大学学报(医学版)

OBJECTIVE@#To explore the eff ect of silibinin on β cells in C57BL/6J mice fed a high-fat diet and the possible mechanisms.@*METHODS@#A total of 18 male C57BL/6J mice at 3 weeks old were divided into a normal chow group (n=6), a high-fat diet group (n=6) and a high-fat diet plus silibinin group (n=6). Aft er intervention for 10 weeks, fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), alanine aminotransferase (ALT), creatinine (Cr) and blood urea nitrogen (BUN), lipid metabolism, antioxidant enzyme activities and apoptosis were evaluated. Pancreatic tissues were isolated to examine insulin-induced gene-1 (Insig-1), sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthetase (FAS) mRNA and protein expression.@*RESULTS@#Compared with the high-fat diet group, the function of insulin secretion was improved, and the level of blood glucose was decreased in the high-fat diet plus silibinin group (P0.05).@*CONCLUSION@#Silibinin can protect β cells of mice fed a high-fat diet, and this effect might be related to, at least partially, increase in its antioxidative ability through regulation of insig-1/SREBP-1c pathway. Moreover, silibinin is safe for long-term treatment.

Visfatin level after laparoscopic Roux-en-Y gastric bypass surgery in patients with Type 2 diabetes / 中南大学学报(医学版)

OBJECTIVE@#To investigate the change in serum visfatin level after laparoscopic Roux-en-Y gastric bypass surgery in patients with Type 2 diabetes mellitus (T2DM) and to explore the relationship between visfatin insulin resistance and diabetes.@*METHODS@#Thirty-three patients with Type 2 diabetes were studied before and after the gastric bypass surgery. The level of fasting serum visfatin was measured by enzyme-linked immunosorbent assay. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting insulin (FINS) were measured before and after the gastric bypass surgery.@*RESULTS@#Compared with before the operation, the indicators of HbA1c, FINS, and insulin resistance index (HOMA-IR) were decreased after the laparoscopic Roux-en-Y gastric bypass surgery. The body mass index (BMI) [(24.53 ± 0.62) kg/m² vs (26.71 ± 0.69) kg/m2] was decreased, with significant difference (P<0.001). The serum visfatin level [(9.79 ± 0.64) ng/mL] was significantly lower than before the operation [(38.24 ± 5.32) ng/mL], with significant difference (P<0.001).@*CONCLUSION@#Serum level of visfatin is decreased in T2DM patients who undergo gastric bypass surgry, reflecting an improvement in insulin resistance and diabetes.

Effect of GLP-1 on high glucose-induced human umbilical vein endothelial cell apoptosis and mechanism / 中南大学学报(医学版)

Objective: To investigate the effects of glucagon-like peptide-1(GLP-1)on high glucose-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Methods: HUVECs were cultured under varying conditions for 48 h, and the cell viability was spectrophotometrically measured by MTT assay. Flow cytometry detected the ratio of cell apoptosis. Western blot detected the protein levels of p-Akt and p-eNOS, while NO assay kit detected the NO concentration. Results: Treatment of high glucose (33 mmol/L) for 48 h signiifcantly decreased the HUVECs viability and induced the apoptosis of HUVECs, concomitant with decreased Akt and eNOS phosphorylation leves and subsequent NO production. Treatment with GLP-1 (3 nmol/L) for 48 h in the high glucose group increased the HUVECs viability (P Conclusion: GLP-1 can ameliorate high glucose-induced HUVECs apoptosis, which is probably related to the up-regulation of PI3K/Akt/eNOS pathway.

A clinical trial of xenotransplantation of neonatal pig islets for diabetic patients / 中南大学学报(医学版)

ObjectiveTo ascertain the safety and function of the transplantation of neonatal pig islets (NPIs) for diabetic patients.MethodsNPIs were injected into the hepatic artery of 22 patients.After the transplantation,the patients were treated with a multiple drug immunosuppressive regimens.The first 14 patients were treated with cyclosporine (CsA),mycophenolate mofetil (MMF) and prednisolon,and porcine C-peptide was not monitored,the following 2 patients were given cyklosporin and MMF only,while the next 6 patients were given a quadruple drug regimen consisting of OKT3,takrolimus,sirolimus and prednisolon.The blood glucose levels,exogenous insulin requirement,HbA1c,porcine endogenous retrovirus (PERV) and liver function were assessed before and after NPI transplantation.The serum porcine C peptide were monitored in last 8 patients.ResultsThe first 14 patients required less insulin and the HbAlc dropped after the transplantation.In the 2 subsequent patients,the metabolic parameters remained unchanged and monitor of porcine C-peptide was negative.Insulin requirements were reduced in all 6 patients,and HbAlc was normalized 3 months after the transplantation.Significant levels of porcine C-peptide were detected in the patient serum.Two of the patients were given a second injection of NPIs,and one of them became insulin independent for 7 d.No serious adverse events were noted after the transplantation.There was no evidence of PERV transmission.Six out of the 22 patients were followed up for 4-6 years after the NPIs injection,immunosuppressive treatment was stopped 1 year after the transplantation.The patients started to take insulin at the time of follow up.Four patients restricted the intake of sugar,while the other 2 did not.One patient had ketoacidosis twice and slight diabetic retinopathy,and another patient had ketoacidosis induced by acute gastroenteritis.The remaining 4 patients did not have any complications.Assays for PERV were again negative.ConclusionXenogenic islets can survive and function in the human body.No serious adverse events are noted.