Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23(FGF23)by tumor tissue.We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism.The patient's symptoms did not improve after removal of the tumor from the hyoid body,and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland.TIO derived from the tongue tumor is very rare,and also subsequent tertiary hyperparathyroidism is even rarer.This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Two patients with Gitelman syndrome were admitted to the Department of Endocrinology, Third Xiangya Hospital of Central South University. The genomic DNA from the patients' peripheral blood was extracted and the whole-exome sequencing was performed to detect the possible mutations. The function of the mutation sites was analyzed by bioinformatics software. Through whole-exome sequencing and Sanger sequencing, we have found that 2 patients with Gitelman syndrome carried compound heterozygous mutations of SLC12A3 gene, which were c.486_490delTACGGinsA, p.R943W, p.D486N, and p.R928C. Among them, c.486_490delTACGGinsA insertion deletion mutation causes frame shift and protein truncation. The p.R943W, p.D486N, and p.R928C of SLC12A3 gene were predicted to be pathogenic mutations by SIFT, PolyPhen2, and Mutation Taster. These 4 mutations were all reported, but p.R943W was first reported in Chinese population. Gitelman syndrome is rare in clinic and the rate of missed diagnosis is high. Early genetic analysis in patients with Gitelman syndrome is helpful to determine the etiology and guide the treatment.
Genetic Testing ; Gitelman Syndrome/genetics* ; Humans ; Mutation ; Pedigree ; Solute Carrier Family 12, Member 3/genetics* ; Whole Exome Sequencing

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

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.

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.

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.
Adrenal Gland Neoplasms ; Child ; Genes ; Humans ; Male ; Multiple Endocrine Neoplasia ; Multiple Endocrine Neoplasia Type 2a/genetics* ; Multiple Endocrine Neoplasia Type 2b/genetics* ; Mutation ; Proto-Oncogene Proteins c-ret/genetics* ; Thyroid Neoplasms/genetics*

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.

Objective To investigate if glucose-insulin-potassium (GIK)would relieve the liver injury induced by endotoxemia in rats.Methods Sixty SD male rats,weight 200-250g,were randomly divided into three groups (n = 20):control group (group C),lipopolysaccharide group (group LPS,LPS 8 mg/kg)and Glucose-insulin-potassium group(group GIK,8 mg/kg LPS+GIK 4 ml·kg-1 ·h-1 ).All the rats were injected with 20 mg/kg ketamine intraperitonealy before trial. Erythrocin was daubed on the wound to avoid infection.The rats of group LPS and group GIK were injected LPS 8 mg/kg intraperitoneal,then,rats in group LPS and group GIK received saline(4 ml·kg-1 ·h-1 )or GIK(Glucose 200 g/L,Insulin 60 IU/L,KCL 60 mmol/L)infusion continuously. Liver and serum samples were collected on before injection,3 days after injection and 5 days after in-jection.Serum concentrations of ALT and AST were measured.TNF-αlpha of liver homogenate was detected by ELISA.The severity of liver damage was assessed by an approprite histopathological sco-ring system and apoptosis of parenchymal cells were assessed by TUNEL immunofluorescence assay. Results Compared with group control,the level of serum ALT and AST in group LPS and group GIK were significantly higher at 3 days after injection.The level of hepatic TNF-α,the hepatic damage score and the index of hepatic apoptosis in group LPS and group GIK were significantly higher on 3 days after injection and 5 days after injection.(P<0.05).Compared with group LPS,the level of hepatic TNF-αand the hepatocyte apoptosis rates decreased significantly in group GIK on 3 days after injection.The level of serum ALT and AST,hepatic TNF-α,the hepatic damage score and the hepatocyte apoptosis rates decreased significantly in group GIK at 5 days after injection(P <0.05).Conclusion Intraperitoneal injection of endotoxin can cause liver injury in rats,resulting in the liver hepatdysfunction and hepatocyte damage.GIK has protective effects on LPS induced liver injury in rats.

Objective To evaluate the effect of glucose-insulin-potassium (GIK) on intestinal injury in endotoxemic rats.Methods Sixty male Sprague-Dawley rats, weighing 200-250 g, were equally and randonly divided into endotoxemia group (lipopolysaccharide [LPS] group) and GIK group.LPS 8 mg/kg was injected intraperitoneally once a day for 3 times in total to establish the model of endotoxemia-caused intestinal injury.Starting from 2 h after the initial injection of LPS, normal saline was continuously infused at 4 ml · kg 1 · h-t in group LPS, and GIK 4 ml · kg 1 · h 1was infused intravenously in group GIK.Before establishment of the model, and at 3 and 5 days after establishment of the model, 10 rats in each group were sacrificed, and blood samples were collected from the abdominal aorta for determination of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) and diamine oxidase (DAO) concentrations in plasma by enzyme-linked immunosorbent assay.TNF-α/IL-10 ratio was calculated.A segment of ileum of 2 cm in length, 20 cm from the ileocecal junction, was removed for microscopic examination.The degree of damage to the intestinal mucous membrane was scored according to Chiu.Results Compared with the values before establishment of the model, the plasma TNF-α/IL-10 ratio, DAO concentration, and Chiu's scores were significantly increased at 3 days after establishment of the model in the two groups, the plasma TNF-α/IL-10 ratio, DAO concentration, and Chiu's scores were increased at 5 days after establishment of the model in group LPS, and the plasma DAO concentration, and Chiu's scores were increased at 5 days after establishment of the model in group GIK (P＜0.05).Compared with the values at 3 days after establishment of the model, the TNF-α/IL-10 ratio and plasma DAO concentration were significantly increased in group LPS, and the TNF-α/IL-10 ratio and plasma DAO concentration were decreased in group GIK at 5 days after establishment of the model in group GIK (P＜0.05).Compared with group LPS, the TNF-α/IL-10 ratio, plasma DAO concentration, and Chiu's scores were significantly decreased at 3 and 5 days after establishment of the model in group G1K (P＜0.05).Conclusion GIK can reduce intestinal injury in endotoxemic rats.