A case report of moyamoya disease in a pedigree with glucocorticoid-remediable aldosteronism / 中华内分泌代谢杂志

We report a family of glucocorticoid-remediable aldosteronism (GRA). A 20-year-old man presented with early-onset hypertension accompanied by hypokalemia was admitted to our hospital. Clinical data and family history were collected. Following genetic analyses with PCR and Sanger sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located in 264-380 nucletide, which was considered as GRA. There were 4 cases of GRA in the family, the average age of onset was 28 years, and all had different degrees of hypertension. Among them, the proband′s uncle suffered from moyamoya disease and died 6 months later due to sudden cerebral hemorrhage. In order to improve the understanding of this rare disease, the pathogenesis, biochemical profiles, diagnosis and treatment of GRA were summarized and analyzed.

Pedigree analysis of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene / 中华内分泌代谢杂志

Objective:To investigate clinical phenotypes of type Ⅳ hereditary hemochromatosis caused by c. 430A>G heterozygous mutation of SLC40A1 gene and the correlation between genotype and phenotype, exploring ferritin cutoff value for screening.Methods:One case of type Ⅳ hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene and 5 generations of their family lineage with a total of 47 members who were seen at the First Affiliated Hospital of Nanjing Medical University in July 2020 were studied for systematic clinical investigation. Thirty-nine surviving individuals were tested for ferritin, liver function, fasting plasma glucose (FPG), and sex hormones, and Sanger sequencing was performed to verify the mutation loci and to map the family tree. Spearman correlation analysis was used to explore the relationship between ferritin and other indicators, and receiver operating characteristic curves were used to calculate the ferritin cutoff value for screening for this genotype of hemochromatosis.Results:Ten patients with c. 430A>G heterozygous mutation in the SLC40A1 gene were identified among 39 family members, and five of them were diagnosed with hemochromatosis, presenting incomplete penetrance. The differences in levels of ferritin, aspartate aminotransferase (AST; both P<0.01) and FPG, as well as incidences of hypogonadotropic hypogonadism and arthritis (all P<0.05) between group of mutation positive and group negative were statistically significant, while the difference in alanine aminotransferase (ALT) was not. Spearman correlation analysis showed that, ferritin levels were significantly associated with ALT ( r=0.903), AST ( r=0.879), FPG ( r=0.782), and the incidences of hypogonadotropic hypogonadism ( r=0.798) and arthritis ( r=0.798; all P<0.01) in those with the c. 430A>G heterozygous mutation in the SLC40A1 gene. The ferritin cutoff value for screening of hereditary hemochromatosis with c. 430A>G heterozygous mutation in the SLC40A1 gene was 1 036.7 μg/L, with a sensitivity and specificity of 100% and 94.3%, respectively. Conclusion:The SLC40A1 gene c. 430A>G heterozygous mutation is closely associated with elevated levels of AST and FPG, increased incidences of hypogonadotropic hypogonadism and arthritis, and the ferritin cutoff value is a useful screening parameter.

Analysis of extreme obesity in two pedigrees due to leptin receptor mutation / 中华内分泌代谢杂志

This study reported two women with extreme obesity who underwent metabolic surgery due to their mutations in leptin receptor (LEPR).Genomic DNA was extracted from the anticoagulant blood samples of the two patients and their parents.A panel of genes related to metabolic diseases or whole exon sequencing was screened and the results were confirmed by Sanger sequencing.This is the first time that these three mutations in LEPR were reported.Two patients complained insatiety and early-onset obesity since childhood at clinics.Patient 1 was a 39-year-old woman with height 150 cm,weight 130 kg,and BMI 57.8 kg/m2.Serum leptin level was 156.4 μg/L.A homozygous mutation of c.2317G＞T was found in exon 15 of LEPR gene in patient 1,which was descended from her father and mother respectively.Patient 2 was a 37-year-old woman with height 158 cm,weight 167 kg,and BMI 67 kg/m2.Serum leptin level was 193.4 μg/L.Genetic analysis showed compound heterozygous mutations of c.1482delT and c.1892C ＞ A.Her father showed heterozygous c.1482delT mutation,and her mother carried heterozygous c.1892C ＞ A mutation.Two patients all underwent metabolic surgery with body weight reduction of about 22 kg and 40 kg respectively after first six months.However,the follow-up studies showed that the body weight of patient 1 rebounded to pre-surgery level in two years and patient 2 did not further lose weight in the following six months.

Retrospective analysis of primary hyperparathyroidism combined with papillary thyroid carcinoma / 中国医师进修杂志

Objective To evaluate the differences of the malignant rate of thyroid nodules between primary hyperparathyroidism (PHPT) patients and health examination population, and analyze the clinical characteristics of PHPT combined with papillary thyroid carcinoma (PTC). Methods The clinical data of 158 PHPT patients who had underwent parathyroidectomy and 468 thyroid nodule patients who had underwent fine-needle aspiration (FNA) from 2009 to 2014 were retrospectively analyzed, and the detection rate of PTC in patients with thyroid nodule was recorded. Results Of the 158 patients with PHPT, 61 patients had thyroid nodules, the incidence of PHPT with thyroid nodule was 38.6% (61/158), and postoperative pathologically proved PTC was in 12 cases (19.7%). Of the 468 thyroid nodule patients who had underwent FNA, postoperative pathologically proved PTC was in 19 patients (4.1% ). The malignant rate of thyroid nodules in PHPT patients was significantly higher than that in health examination population (P＜0.01). The adjusted serum calcium in patients with PHPT combined with PCT was significantly lower than that in patients with PHPT combined with benign thyroid nodules and patients with PHPT without thyroid nodules: (2.63 ± 0.26) mmol/L vs. (2.92 ± 0.32) and (2.93 ± 0.47) mmol/L, and there was statistical difference (P＜0.05). Conclusions The malignant rate of thyroid nodules in PHPT patients is significantly higher than that in patients from health examination population, which suggests that PHPT might be a risk factor for the malignancy of thyroid nodules. A lower level of serum calcium may predict the existence of PCT in PHPT patients with thyroid nodules.

Cholesterol ester transfer protein regulates the hepatic SR-B1 mRNA expression in mice / 中华内分泌代谢杂志

The effect of cholesterol ester transfer protein(CETP) on SR-B1 mRNA expression in mouse liver was investigated.The results demonstrated that CETP transgenic mice showed lower serum total cholesterol and high density lipoprotein-cholesterol levels but higher total cholesterol and cholesterol ester content in liver when compared with wild type mice(P＜0.05).The expression of SR-B1 mRNA in liver of CETP transgenic mice was significantly lower as compared with the control group(P＜0.05).

Difference in proprotein convertase subtilisin/kexin type 9 levels between premenopausal and postmenopausal women / 中华内分泌代谢杂志

Objective To compare proprotein convertase subtilisin/kexin type 9 (PCSK9) levels between premenopausal and postmenopausal women,and to investigate the relationship between serum PCSK9 and metabolic factors.Methods Totally 515 women were enrolled from the study on diabetes of prediction,prevention,and intervention in Nanjing in 2009.Survey,physical examinations,and determination of related metabolic indexes were performed.Serum PCSK9 level was measured by sandwich ELISA.Results Serum PCSK9 level was positively correlated with low density lipoprotein-cholesterol (LDL-C),total cholesterol (TC),triglyceride,fasting plasma glucose,body mass index,waist-hip ratio,and age in women (all P＜0.01).PCSK9 level was significantly lower in premenopausal women than that in postmenopausal women [(58.18 ± 25.44 vs 80.91 ± 33.74) ng/ml,P ＜0.01].Conclusion Higher level of PCSK9 exists in postmenopausal women compared with premenopausal women.The level of PCSK9 is closely correlated with age,TC,and LDL-C.

Diagnostic efficiency of postprandial plasma glucose and oral glucose tolerance test in patients with metabolic disorders / 中华全科医师杂志

A total of 1342 individuals underwent physical examinations according to the criteria of metabolic syndrome of International Diabetes Federation (IDF) in 2005.And 314 patients with metabolic disorders were screened for diabetes by standard meal and methods oral glucose tolerance test (OGTT).Newly diagnosed diabetics was 12 (4.1％ ) vs.17 (5.8％) respectively.No significant difference existed between two methods (P =0.332).Kendall's (τ)b =0.313,Kendall's (τ)c =0.208 and Gamma coefficient =0.580 (P =0.000).The mixed meal method was correlated with OGTT,Kappa =0.258 (P =0.000) and two methods were consistent.Diabetic screening should be stressed in the subjects with metabolic abnormalities.And the detecting efficiency of postprandial plasma glucose is similar to OGTT.

Clinical significance of α-galactosidase A activity assay in the screening and diagnosis of Febry disease / 中华内分泌代谢杂志

α-Galactosidase A (α-Gal A ) activities in plasma and peripheral blood granulocytes of 100healthy subjects and one patient with Fabry disease was determined by means of fluorogenic substrate.The results showed that the enzymatic activities of peripheral blood granulocytes and plasma in 100 subjects were (51.97 ± 15.24)and(148.08±26.30) nmol · h-1 · ml-1 respectively.The α-Gal A activities in plasma and granulocytes were positively correlated( r=0.533,P＜0.01 ).The enzymatic activities in peripheral blood granulocytes and plasma of the patients with Fabry disease were 1.05 and 10.06 nmol · h-1 · ml-1 respectively,both much lower than those of 100healthy subjects.These results suggest that α-Gal A activity in plasma and peripheral blood granulocytes can be used for diagnosis and screening of Fabry disease.

Prevalence of the metabolic syndrome in middle-aged and elderly individuals / 中华全科医师杂志

Totally 1136 individuals aged over 40 underwent health check up in March to May 2009. Fasting blood glucose, 2-h post-challenge blood glucose, glycated hemoglobin A1c ( HbA1c), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and serum uric acid were measured. The diagnosis of metabolic syndrome was based on the International Diabetes Federation Criteria. The results shows that total body fat, region body fat indices, blood pressure, blood glucose and serum uric acid levels increased with the age ( P < 0.01) . The prevalence rate of metabolic syndrome in this group of individuals were 15. 1% (171/1136) , and increased with age (P<0.01). The most common combination of metabolic syndrome was central obesity-hypertension-dyslipidemia (40. 9% , 70/171). Unconditional logistic regression revealed that waist-hip-ratio, body mass index and uric acid were the risk factors for metabolic syndrome.

Gene mutation and enzymatic activity analysis of α-galactosidase A in a patient with Fabry disease / 中华内分泌代谢杂志

Objective To analyse the clinical characteristics,gene mutation and enzymatic activity of αgalactosidase A(α-GalA)in a 15-year-old male patient with typical Fabry disease,whose mother was without any clinical manifestations.Methods Clinical features and laboratory data were collected from the patient and his mother.Genomie DNA was extracted from peripheral blood of the patient.his mother,and a healthy control subject.Seven exons of the GLA gene were amplified by PCR.PCR products were purified.cloned into T vector,and then sequenced.The enzymatic activity of α-GalA Was measured by fluorimetrie substrate assay. Results DNA sequencing results showed that a missense mutation of 10036-10038delAAG in exon 7 WaS identified in the patient,resulting in the replacement of 374 lysine and 375 glyeine by arginine,which Was not previously reported.The patient Was a hemizygote with gene mutation,his mother WaS a heterozygote carrying gene mutation,and the healthy control without mutation.α-GalA enzymatic activity assay showed that the enzymatic activity of the patient with GLA gene mutation was only 50%of the healthy control subject,while the enzymatic activity of the patient's mother Was about 70%of the heahhy control SObject.Conclusiolls Detecting GLA gene mutation and α-GalA enzymatic activity in patients with Fabry disease who have been clinically diagnosed seelns to be helpful in finding other patients in the family and in further understanding the molecular pathogenesis of that disease.

Impact of continuous veno-venous hemofiltration on endoplasmic reticulum stress and apoptosis of HUVEC cells induced by serum of patients with multiple organ dysfunction syndrome / 第三军医大学学报

Objective To investigate the effect and implying mechanism of continuous veno-venous hemofiltration(CVVH) on endoplasmic reticulum stress(ERS) and apoptosis of HUVEC cells which induced by serum of patients with multiple organ dysfunction syndrome(MODS).Methods Ten patients with MODS who received CVVH and 10 healthy volunteers were involved in this study.This experiment was divided into 4 groups: healthy control,group of pre-CVVH,group of 6-hour-CVVH and group of 20-hour-CVVH.Serum of healthy volunteers and the sera of patients with MODS at pre-CVVH,6-hour-CVVH and 20-hour-CVVH were used to induced HUVEC cells respectively in vitro for 24 h.The cell apoptosis was examined by TUNEL assay,the intracellular GRP78 protein was observed by immunocytochemistry,and the mRNA expressions of GRP78,CHOP,TNF-?,and IL-6 in the cells were measured by RT-PCR.The levels of serum SOD and MDA were detected by colorimetric method,and those of of TNF-? and IL-6 of by ELISA.Results Compared with healthy control,the group of pre-CVVH showed higher cellular apoptosis rate(P

The new hypoglycemic mechanism and other effects of metformin / 中国实用内科杂志

Metformin has been applied for 50 year.In recent years,new studies found that metformin could reduce glucose through activating inhibition of dipeptidyl peptidase Ⅳ(DPP Ⅳ) and enhancing the biological effect of glucagon-like peptide-1(GLP-1).In addition,metformin can reduce vascular disease risk of patients with type 2 diabetes by improving insulin resistance and the effect of reducing total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),blood coagulation factor Ⅶ,plasminogen activator inhibitor-1(PAI-1) and proteinuria.Merformin can't change blood pressure of patients with type 2 diabetes,however,it can significantly reduce the salt-sensitive blood pressure of patients with obesity.Metformin has also been applied to patients with polycystic ovary syndrome(PCOS).It can induce ovulation,decrease the rate of abortion and have effect on hypertrichosis and hyperandrogenism.Besides,metformin has been the focus of the treatment of non-alcoholic fatty liver disease.

Regulatory effects of insulin and glucose on aquaporin adipose expression in 3T3-L1 adipocytes / 中华内分泌代谢杂志

Aquaporin adipose (AQPap) is the physiological glycerol channel specific to adipocytes. By means of semiquantitive RT-PCR and Western blotting, this study showed that insulin was a negative regulator of AQPap expression, while high concentration of glucose could increase AQPap expression.

Preliminary study of insulin-like growth factor-Ⅰgene therapy for diabetic rats / 中华内分泌代谢杂志

Insulin like growth factor-Ⅰ (IGF-Ⅰ) gene was transferred to diabetic rats with intramuscle gene therapy pathway. It was showed that IGF-Ⅰ gene could express in the body and the blood glucose level was significantly decreased with increasing of serum IGF-Ⅰ.

The relationship between recurrent aphthae and immunologic reaction on Helicob acter pylori infection / 实用口腔医学杂志

Objetive:To investigate the relationship between recurre nt aphthae and immunologic reaction on Helicobacter pylori (H. pylori) i nfection. Methods: The dental plaque was collected and the blood serum were extracted from 107 patients with recurrent aphthae and 99 he althy individuals. H. pylori infection was detected by urease test, and the antibody to H. pylori was detected by ELISA assay. Results: In the dental plaque the detectable rate of H. pylori was 53.3% in t he patients and 32.3% in the controls (P0.05). The quantitative analysis showed that the level of anti-H . pylori antibody (?g/ml) in the controls,the patients with light recurrent a phthae and those with severe was 17.69?4.41,29.30?8.24 and 41.75? 9.73 res pectively (P