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Hypogonadotropic hypogonadism (HH) is a disease defined by dysfunction of the hypothalamic- pituitary-gonadal hormone axis, leading to low sex hormone levels and impaired fertility. HH with anosmia or hyposmia is known as Kallmann syndrome (KS). Waardenburg syndrome (WS) is a rare autosomal dominant genetic disorder characterized by sensorineural hearing loss and abnormal pigmentation. In this report, we collected the clinical data of a patient with hypogonadotropic hypogonadism and congenital hearing loss of unknown cause. The patient had no obvious secondary sexual characteristics development after puberty, and had a heterozygous deletion (at least 419 kb) in 22q13.1 region (Chr.22:38106433-38525560), which covered the SOX10 gene. The abnormalities were not found in gene sequencing analysis of both the parents and sister of the proband. By summarizing and analyzing the characteristics of this case, we further discussed the molecular biological etiological association between HH and WS type 2. This case also enriches the clinical data of subsequent genetic studies, and provides a reference for the diagnosis and treatment of such diseases.

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the adenosine 5'-triphosphate binding cassette subfamily D member 1 (ABCD1) gene encoding a peroxisomal transmembrane protein, which has various clinical manifestations and a rapid progression from initial symptoms to fatal inflammatory demyelination. Therefore, identification of early clinical symptoms and further early diagnosis as well as treatment can effectively prevent disease development. In this study, we reported the laboratory and radiographic features in a rare case of X-ALD with 3-year skin hyperpigmentation as the only manifestation. And the ABCD1 gene was sequenced for the patient and his parents by a high-throughput sequencing method. The results of laboratory examination showed adrenocortical hypofunction and increased serum concentrations of very long-chain fatty acids. Brain MRI showed no obvious abnormal signal shadow. A hemizygous mutation of c.521A>C was detected in the ABCD1 gene of the patient, and his mother has the same site heterozygous mutation. Therefore, this patient was diagnosed as "X-linked adrenoleukodystrophy". During the follow-up, adrenocortical hypothyroidism did not improve, and brain MRI showed few high-FLAIR signals in the white matter of the right radial corona and left parietal lobe, suggesting possible brain injury. X-ALD patients with only skin manifestations but no neurological abnormalities are easily neglected, but early diagnosis and early intervention are important ways to delay the progression of this disease. Therefore, genetic testing for early X-ALD is recommended in all male children patients with skin pigmentation as the sole clinical presentation and subsequent diagnosis of adrenal hypofunction.

Catch-up growth in adult, is increasingly recognized as an important causative factor for the extremely prevalent insulin resistance-related diseases especially in developing countries/territories. We aimed to investigate the alteration of bile acids level, phosphorylation and sumoylation of its interacting protein, bile acid receptor/farnesoid X receptor and their downstream signaling pathway, as well as insulin sensitivity and lipid profile in catch-up growth in adult rats. Male Sprague-Dawley rats were randomly allocated into four groups for two sampling points: caloric restriction group, catch-up growth in adult refed with normal chow and their normal chow controls for four or eight weeks (N4, N8 individually).We found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals; After refeeding, total serum bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as Cyp7a1, SREBP-1c mRNA levels were higher with significant decrease in small heterodimer partner expression, which is associated fat accumulation, and drastic insulin resistance in whole body and skeletal muscle. Our findings demonstrated that the fat accumulation and insulin resistance are associated with increases of bile acids, alteration of farnesoid X receptor phosphorylation, and sumoylation and its downstream signaling pathway. These changes of bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as their downstream signaling might be of importance in the etiology of fat accumulation and insulin resistance in catch-up growth in adult.

Vascular endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetes (T2DM). Circulating endothelial progenitor cell (EPC) is involved in the neovasculogenesis and maintenance of vascular homeostasis, whose impairment may have an important role in the pathogenesis of diabetic vasculopathy. This study was performed to investigate the relationship between vascular endothelial function and circulating EPC number in T2DM. A total of 46 newly diagnosed T2DM patients (DM group) and 51 healthy subjects (NG group) were recruited. Metformin was administered to all patients for 16 weeks. Endothelial function was assessed by flow-mediated brachial artery dilatation (FMD). EPC was defined by CD45( low)/CD34(+)/VEGFR2(+) and quantified by flow cytometry. The EPC number in the DM group was significantly lower than that in the NG group (p < 0.001), and improved markedly after treatment (p < 0.001). The results of FMD were consistent with EPC variations among the three groups (p < 0.001). In multivariate regression analysis, the EPC number was an independent risk factor for FMD at baseline (p < 0.05). The absolute changes of EPC number showed significant correlation with the changes of FMD before and after treatment (r = 0.63, p < 0.001). This study demonstrated that the circulating EPC number was related to endothelial function and could be considered as a surrogate biological marker of endothelial function for T2DM.

Objective: To investigate the number and function of circulating endothelial progenitor cell (EPC) in different vascular complications of type 2 diabetes (T2DM) and its associations with vascular endothelial function., Methods: A total of 415 T2DM patients were recruited from the outpatients and inpatients of the Endocrinology Department at Union Hospital. Assessments of cardiovascular disease and cerebrovascular disease were based on each patient's medical records. Peripheral vascular disease was diagnosed by bilateral ultrasonography bilaterally. Non-mydriatic fundus camera screening was used as a tool to identify diabetic retinopathy. Urinary albumin exceeding 30 mg/24 h occurring twice over a period of six months was diagnosed as diabetic nephropathy. Circulating EPC was quantified by flow cytometry. Colony forming count (CFU) and migration assay were used for evaluating the function of circulating EPC. Vascular endothelial function was assessed by flow-mediated brachial artery dilatation (FMD)., Results: There were four groups in the study: T2DM without vascular disease (TC, n = 97), T2DM with macrovascular disease (TA, n = 106), T2DM with microvascular disease (TI, n = 100), T2DM with macro- and micro-vascular diseases (TAI, n = 112). The sequence of circulating EPC number and CFU in four groups was TA < TAI < TI < TC (532 +/- 90, 616 +/- 93, 768 +/- 97 and 1045 +/- 106 cell/ml; 21 +/- 4, 28 +/- 5, 43 +/- 7 and 70 +/- 9 unit/chamber) and there was a significant difference between any two groups (P < 0.05). The results of migration were consistent with circulating EPC number (125 +/- 12; 90 +/- 9 cell/HP field) except there were no significant differences in TA and TAI groups (24 +/- 6; 28 +/- 7 cell/HP field). Age, HbA1c, SBP, BMI and duration of T2DM were the independent risk factors of circulating EPC number in T2DM patients with macrovascular disease (P < 0.05). Age, HbA1c and duration of T2DM were the independent risk factors of circulating EPC number in T2DM patients with microvascular disease (P < 0.05). After the adjustment of traditional risk factors, the number of circulating EPC had a close correlation with FMD (standardized coefficient, t = 0.61, P = 0.01)., Conclusion: The number and function of circulating EPC decreased with different degrees in T2DM patients of different vascular diseases. Circulating EPC number was associated with endothelial function and can be considered as a surrogate biological marker of vascular endothelial function for T2DM.

Objective: To observe the effect of calorie restriction on the high fat diet rats mRNA expressions of liver forkhead box O1(FoxO1), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-P) and to explore the possible mechanisms., Methods: 24 normal 6-week-old male Wistar rats were randomly divided into three groups: normal chow group (NC, n = 7), high fat diet group (HF, n = 9) and calorie restriction group (CR, n = 8). They were fed for 12 weeks. At the end of the experiment, the rats were sacrificed and their fasting blood glucose (FBG), insulin (INS), triglycerides (TG), total cholesterol (TC) were measured. Their visceral fat (VF) and body weight (BW) were also measured and VF/BW was calculated. Gene expression was investigated by using semi-quantitative RT-PCR methods. Liver histology was studied with HE stained slides., Results: Compared with the NC group, HF group rats developed visceral obesity which was accompanied by higher FBG, plasma INS, TG, and TC. The levels of FoxO1, PEPCK, and G-6-P increased by 18.9%, 33.8%, and 24.6%, respectively (P less than 0.01). Liver steatosis was observed with microscopy. The BW, VF FBG, INS, TG and TC of the CR group rats were lower in comparison to those of the HF group. The levels of FoxO1, PEPCK and G-6-P were lower by 26.6%, 35.0%, 34.3% (P less than 0.01). Meanwhile, liver steatosis was also milder., Conclusion: Calorie restriction can inhibit the expressions of FoxO1, PEPCK and G-6-P, strengthen insulin signal conduction, suppress gluconeogenesis and thus regulate glycometabolism.

Objective: To observe the effect of Chinese herbs for supplementing Shen and strengthening bone (HB) on myelogenic osteoclasts formation, and gene expression of interleukin-6 (IL-6), IL-6 receptor (IL-6R) and gp130 in bone marrow., Methods: Seventy-two healthy female SD rats of 3 months, were randomly divided into three groups, 24 in the sham-operated group (A), 24 in the ovariectomized group (B) and 24 in the after ovariectomy HB treated group (C). Bone marrow cells of 6 rats from each group were respectively collected and cultured at four time points (2nd, 4th, 6th and 12th weeks after operation). After 6 days of culture, the bone marrow cells were differentiated by Wright-Giemsa stain and TRAP stain, and total RNA in them was extracted by TRIZOL., Results: Beginning from the 2nd week, the osteoclasts formation in Group B was higher than that in Group A (P < 0.05), and IL-6, IL-6R gene expression significantly increased in Group B (P < 0.05 or P < 0.01). These changes reached the peak in the 4th to 6th week, with the level maintained to the 12th week. As for comparison of Group B and C, the above-mentioned changes were significantly weakened in the latter (P < 0.05 or P < 0.01). No significant change of gp130 gene expression revealed in the whole course in either group., Conclusion: HB could inhibit the myelogenic osteoclasts formation in ovariectomized rats, this effect may be correlated with, partially at least, its inhibitory effect on the over-expressed IL-6 and IL-6R gene expression in myelocytes after ovariectomy.