Mitochondrial diabetes mellitus (MDM) is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) or nuclear DNA mutations, characterized by multi-system involvement and diverse clinical phenotypes. We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus. Systematic evaluation revealed concurrent bilateral sensorineural hearing loss, bilateral basal ganglia calcification, and electroencephalographic abnormalities. A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion. Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084. This case report is complemented by a literature review focusing on the pathogenesis, genetic characteristics, and therapeutic approaches of mitochondrial diabetes, with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations. Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

Objective To evaluate the efficacy and adverse reactions of BRAF inhibitor vermorafenib on the treat-ment of refractory craniopharyngioma carrying BRAF-V600E mutation.Methods Clinical data of two patients with refractory craniopharyngiomas(CP)were recorded and reviewed.The patients were followed up for 3-5 years.Lit-erature on CPs receiving BRAF or BRAF/MEK therapy was reviewed.Results 1)Papillary CP progressed after multiple operations and radiotherapy in two patients.Further treatments were very difficult.2)The presence of BRAF-V600E mutation in the tumor was confirmed,and vermorafenib was administered for 6.5-7.5 months.Tumor volumes remarkably shrank by 95%-99%.No tumor relapse was observed during the follow-up of 3-5 years after discontinuation of vemurafenib.3)The main adverse reaction was rash,which was dose dependent.4)Litera-ture review showed the volume shrank by 50%-100%in 33/34 tumors during BRAF or BRAF/MEK inhibitor therapy.Conclusions BRAF inhibitor vemurafenib is effective in treating refractory craniopharyngioma carrying BRAF-V600E mutation with endurable side effects,which may bring some changes to the management of CP in future.

OBJECTIVE: To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD). METHODS: Clinical data of 12 male DSD children with a mean age of 14.6±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients were treated with letrozole (1.25-2.5 mg, once a day) for 3 months or longer, and followed up for 0.5-2.5 years. Clinical manifestation and laboratory test findings were documented, and the efficacy and safety were evaluated. RESULTS: After half-year treatment, the blood luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels of patients increased (all < 0.05), and estrogen levels decreased from baseline ( < 0.05). After 1 year of treatment, the blood testosterone level was significantly higher ( < 0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease, but there was no significant statistical difference ( >0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant changes in biochemical results after treatment, and no significant adverse event was observed during the treatment. CONCLUSIONS Letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.
Adolescent ; Child ; Disorders of Sex Development ; drug therapy ; Follicle Stimulating Hormone ; Humans ; Letrozole ; therapeutic use ; Luteinizing Hormone ; Male ; Retrospective Studies ; Testosterone

Mammalian reproduction is closely related to their metabolic status. The hypothalamus-pituitary-gonad axis ( HPG axis) is regulated by various metabolic factors. Glucagon-like peptide-1 ( GLP-1) is one of various metabolic factors that not only affect glycemic and metabolic control, but also with many other effects, including affecting HPA axis. The function of GLP-1 is related to the location of glucagon-like peptide-1 receptor ( GLP-1R) distribution. It has been confirmed that GLP-1R is widely distributed in HPG axis. The effects of GLP-1 and GLP-1R agonists on the HPG axis have also attracted much attention. The positive effects of GLP-1 and GLP-1R agonists on the HPG axis indicated it could be the new target for the new treatment for gonadal diseases. The role of GLP-1 and GLP-1R agonists in the central nervous system is reviewed.

A retrospective study was conducted on one patient with postmenopausal hyperandrogenism. The postmenopausal female patient was found with significant hyperandrogenism ( total testosterone 6. 4 nmol/ L) and hirsutism, with normal adrenal androgen ( dehydroepiandrosterone-sulfate ) level. Computed tomography and ultrasound did not detect any ovarian and adrenal mass. Positron emission tomography revealed without high metabolic region, either. Ovarian and adrenal vein catheterization did not reveal any positive result. Obviously, ovary-derived hyperandrogenism was highly suspected, but the patient still refused any surgical exploration. After a trial of a single dose of gonadotropin releasing hormone analogue(GnRHa) triptorelin, increased testosterone level returned to normal along with decreasing level of gonadotropin. Multiple doses were needed for maintenance of testosterone at normal level with the intervals of 2 ～ 12 months. This response to the treatment was consistent with that of gonadotropin dependent hyperandrogenism.

[Summary] Cytochrome P450 oxidoreductase deficiency ( PORD) is a rare disease, which is a subtype of congenital adrenal hyperplasia. The predominant signs include no puberty development, infantile reproductive organs, ear deformities, and bone synostosis in skull or limbs. Here, we analyzed the clinical features of a case with PORD confirmed by gene sequencing. The pathology, genetic features, clinical manifestations, diagnosis and treatment for PORD were reviewed.

Objective To explore the relationship between SNPs in microRNA binding sites of ABCG5/8 and the glucolipid level during pregnancy.Methods 1 925 pregnant women were recruited at Peking Union Medical College hospital from 2006 to 2011.The clinical data were collected and the total genomic DNA was extracted from whole blood samples.ABCG5/8, which was reported to be related with the glucose and lipid metabolism closely, were selected as the candidate gene and the SNPs in its microRNA binding sites with minor allele frequency >5% in Han Chinese in Beijing were chosen.Then the genotyping was performed and analyzed.Results There was only one SNP matching the criteria, rs2278356, and it is significantly associated with LDL-C and TC level during pregnancy (LDL-C: b=0.104 mmol/L, 95% CI 0.023-0.185 mmol/L, P<0.05;TC: b=0.105 mmol/L, 95% CI 0.080-0.203 mmol/L, P<0.05).Conclusions The association of rs2278356 in 3′UTR of ABCG5/8 with LDL-C and TC level in pregnant Chinese Han women is found, which may provide an individualized treatment strategy for pregnant women with high cholesterol.

Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.

Objective To detect the expressions of microRNA-126 (miR-126) and microRNA-7 (miR-7) in esophageal squamous cell carcinoma (ESCC) and to analyze their correlations with clinicopathologic features and prognosis of ESCC.Methods The expressions of miR-126 and miR-7 in 116 ESCC samples and matched normal tissue samples were detected by real-time PCR.Statistical analysis was used to find the relationships among the expressions of miR-126 and miR-7,pathological characteristics and prognosis.Results Low expression,normal expression and high expression of miR-126 were found in 73 (62.9％),35 (30.2％) and 8 (6.9％) carcinoma samples respectively.Low expression,normal expression and high expression of miR-7 were found in 52 (44.8％),35 (30.2％) and 29 (25.0％) carcinoma samples respectively.The disease-free survival in patients with low expression of miR-126 and miR-7 was shorter than that in patients with non-low expression (x2 =4.268,P ＜0.05 ; x2 =4.993,P ＜0.05).The low expression of miR-126 was correlated with tumor location,family history and drinking (x2 =14.564,P ＜ 0.05 ; x2 =5.691,P ＜ 0.05 ; x2 =4.971,P ＜ 0.05),but was uncorrelated with gender,age,diferentiation,infiltration,lymphatic metastasis and smoking (all P ＞ 0.05).The low expression of miR-7 was uncorrelated with pathological characteristics of ESCC (all P ＞ 0.05).Conclusion The low expressions of miR-126 and miR-7 may be related to the prognosis of patients with ESCC,and have a certain clinical detection significance.