The etiology of congenital heart disease (CHD) incluses genetic factors, environmental factors and maternal factors. The genetic etiology of CHD includes chromosomal abnormalities, single gene defects and multiple genetic defects. The genetic testing method of CHD has made great progress in karyotype analysis,fluorescence in situ hybridization, quantitative PCR, multiplex ligation dependent probe amplification, et al.

Objective To investigate the relationship between serum 25-OH vitamin D3 (25-OHD3)levels and carpal tunnel syndrome(CTS)in type 2 diabetes.Methods Data from 102 patients with type 2 diabetes were collected,and patients were divided into a CTS group(n=29)and a non-CTS group(n=73)according to clinical symptoms,signs,and electrophysiological testing.Fasting venous blood was collected to assay serum 25-OHD3 levels that were compared between the two groups.The correlation between 25-OHD3 and clinical parameters for type 2 diabetes was analyzed.Results The incidence of vitamin D3 deficiency was 65.5％ (n=19)in the CTS group and 46.6％(n=34)in the non CTS group,and the difference was statistically significant(x2 =16.85,P＜0.01).Levels of 25-OHD3 were lower in the CTS group(14.13±4.91) μg/L than in the non-CTS group(17.08±3.35)μg/L(t =4.067,P ＜ 0.01).Levels of 25 OHD3 were negatively correlated with those of glycosylated hemoglobin(HbA1c)(r =-0.176,P =0.041)and the duration of diabetes(r=-0.29,P=0.01) Conclusions Low 25-OHD3 is a risk factor for carpal tunnel syndrome in type 2 diabetes and is negatively associated with the duration of diabetes and HbA1c in patients with type 2 diabetes.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Objective:To investigate the clinical features and pathological classification of patients with nonfunctional pituitary adenomas(NFPAs)in single medical center according to 2017 World Health Organization.Methods:The clinical and pathological characteristics of 166 patients with NFPAs diagnosed by neurosurgery in Peking Union Medical College Hospital from April 2019 to January 2020 were analyzed retrospectively.Results:In 166 patients, the ratio of male to female was almost equal(1.05∶1). Their average operation age was(49.9±12.3) years, which was significantly higher than that of functional pituitary tumor patients in the same period. Headache, visual acuity decline, and visual field defect were the most common causes for the first visit. All the maximum diameter of tumors was more than 10 mm, and 15 cases(9.0%)were giant tumors. 18 patients(10.8%)were recurrent cases. According to the results of immunohistochemistry for anterior pituitary hormones and transcriptional factors, the most common pathological type was gonadotroph adenomas(50.6%), followed by corticotroph adenomas(24.7%), plurihormonal pituitary adenomas(11.4%), PIT-1-positive adenomas(6.6%), and null cell adenomas(6.6%). Gonadotroph adenomas were more common in men(male∶female ratio=4.1∶1), while corticotroph adenomas occurred mainly in women(male∶female ratio=1∶12.7). The average age of patients with gonadotroph adenomas was the highest, while those of patients with PIT1-positive adenomas and rare combining IHC plurihormonal pituitary adenoma were significantly lower than that of the former. There were no significant differences in the mean diameters of tumors, the proportion of giant adenomas, and recurrent cases among different pathological types of tumors. However, the mean Ki-67 index of PIT-1-positive adenomas was significantly higher than those of other groups( P=0.001). Conclusion:Although the clinical manifestations of NFPAs were similar, their pathological classifications were different. Gonadotroph adenomas occurs mainly in male patients while corticotroph adenomas is more common in women. The prognosis may be different among various pathological types of NFPAs.

Objective:To summarize the clinical characteristics of 4 cases of mixed pituitary adenomas involving growth hormone(GH), prolactin(PRL), and thyroid stimulating hormone(TSH), and explore the standardized management approaches.Methods:The clinical data of four GH/PRL/TSH mixed pituitary adenoma patients diagnosed by Peking Union Medical College Hospital were retrospectively analyzed, including clinical manifestations, biochemical parameters, radiographic characteristics, as well as treatment and prognosis. Then literature review was conducted.Results:Among the 4 patients, 3 were male, with onset ages ranging from 15 to 38 years. All patients presented with coarse facial features as initial symptom. Three patients had visual impairment or visual field defects. All 4 patients had significantly elevated levels of GH and insulin-like growth factor-Ⅰ(IGF-Ⅰ). GH was not inhibited by oral glucose tolerance test. PRL concentration was over 100 ng/mL. Triiodothyronine(T 3)and thyroxine(T 4)were also elevated, while TSH was not inhibited. All pituitary adenomas in four cases were macroadenomas or giant adenomas, all of which were invasive growth, and one case developed pituitary stroke. Except for one patient who did not receive treatment in our hospital due to medical expenses, the remaining three patients underwent a combined treatment of medication and transnasal transsphenoidal pituitary adenoma resection. Among them, one patient had relief of central hyperthyroidism and hyperprolactinemia, but GH/IGF-Ⅰ did not meet the remission criteria. The other two patients had persistent non-resolution of at least 2 hormone axes. Conclusions:Patients with GH/PRL/TSH mixed pituitary adenoma were mainly characterized by coarse facial features, GH/PRL/TSH hyperfunction, large adenoma volume, low biochemical remission after surgery combined with drug treatment, and poor clinical prognosis.

Objective: To investigate the effect of Toll-like receptor 9 (TLR9) on high glucose-induced retinal ganglion cells-5 (RGC-5) apoptosis and the inhibitory effects of small interfering RNA-TLR9 (si-TLR9) on apoptosis. Methods: RGC-5 cells were divided into normal control group, high glucose group, high glucose+ negative control group and high glucose+ si-TLR9 group which cells were respectively dealt with normal culture medium, high glucose medium, transfection of non-specific siRNA under high glucose and transfection of siRNA-TLR9 under high glucose.The expression of TLR9 mRNA was detected by real time PCR; the survival rate of the cells was evaluated by MTT assay; the apoptotic rate of the cells was detected by flow cytometry; the caspase-3 activity in the cells was detected by related kit, and the expressions of TLR9, B cell lymphoma (bcl-2), bcl-2 associated X protein (bax), p38 mitogen-activated protein kinases (p38MAPK) and phosphorylated (p)-p38MAPK proteins were detected by Western blot. Results: The expressions of TLR9 mRNA and protein in the high glucose+ si-TLR9 group were significantly decreased in comparison with the high glucose+ negative control group (both at P<0.05). The cell survival rate of the high glucose group and high glucose+ negative control group was (78.36±5.13)% and (75.12±4.25)%, respectively, which was significantly lower than (95.48±7.25)% in the normal control group, and that in the high glucose+ si-TLR9 group was (86.58±5.32)%, which was significantly reduced in comparison with the high glucose+ negative control group (all at P<0.05). The apoptotic rate of the cells in the high glucose group and high glucose+ negative control group was (13.23±1.22)% and (12.52±1.38)%, respectively, which was significantly higher than (2.26±0.15)% of the normal control group, and apoptotic rate in the high glucose+ si-TLR9 group was (7.15±0.24)%, which was significantly lower than that in high glucose+ negative control group (all at P<0.05). The expression of bax in the cells of the high glucose+ si-TLR9 group was significantly decreased, and the expression of bcl-2 in the cells of the high glucose+ si-TLR9 group was significantly increased in comparison with the high glucose+ negative control group (both at P<0.05). Caspase-3 activity in the cells was significantly decreased in the high glucose+ si-TLR9 group compared with the high glucose+ negative control group (P<0.05). The relative expression of p-p38MAPK in the cells was significantly decreased in the high glucose+ si-TLR9 group compared with the high glucose+ negative control group (P<0.05). Conclusions Down-regulation of TLR9 expression in the RGC-5 cells can inhibit the apoptosis induced by high glucose probablely by suppressing p38MAPK signaling pathway.