This article reports a patient with typical Cushing syndrome′s manifestations and extremely low plasma cortisol level, indicating glucocorticoid hypersensitivity syndrome. After treatment with the glucocorticoid receptor antagonist mifepristone, the patient′s Cushing symptoms were significantly relieved, and cortisol levels returned to normal. The aim of this report is to enhance clinical awareness among physicians regarding glucocorticoid hypersensitivity syndrome.

Background: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. Methods: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). Results: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. Conclusion These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

Objective:To evaluate the efficacy and safety of mycophenolate mofetil(MMF) in patients with active moderate to severe thyroid associated ophthalmopathy(TAO) refractory to multiple intravenous glucocorticoid(GC).Methods:Fifty-two patients with active moderate to severe TAO that was refractory to multiple intravenous GC were treated with MMF 0.5g orally, 2/d. To evaluate the overall response rate of TAO patients, the improvement of more than 3 items including clinical disease activity score(CAS), soft tissue involvement, proptosis, diplopia, decrease of eye movements, visual acuity and other improvements were defined as response.Results:After 12 weeks of MMF treatment, the overall response rate of TAO patients was 75.0%, and then increased to 88.5% significantly at the 24th weeks. At the 12th weeks, CAS decreased from(5.06±1.21) to(2.52±1.13), and then continued to decrease to(2.02±0.92) at the 24th week( P<0.05), the response rates were 82.7% and 90.4%, respectively. In addition, after 12 weeks of treatment, 58.1% of patients with diplopia improved significantly, and the response rate was 74.2% at the 24th weeks. Similarly, the degree of proptosis decreased significantly at the 12th and 24th weeks, and the response rates were 53.8% and 69.2%, respectively. No serious adverse events occurred during the treatment. Conclusion:The MMF therapy is efficient and safe for patients with active moderate to severe corticosteroid-resistant TAO.

This study was aimed to investigate the association between dyslipidemia and thyroid associated ophthalmopathy (TAO). We evaluated the relationship between dyslipidemia and TAO in 218 patients with Graves′ disease (GD) and found that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the GD subjects with TAO (n=110) were significantly increased [(5.32±1.39) mmol/L vs. (3.18±2.12) mmol/L, (2.98±0.75) mmol/L vs. (1.25±0.98) mmol/L] than those in the GD subjects without TAO (n=108). TC and LDL-C were positively correlated with the Clinical disease activity score (CAS) [TC (r=0.7, P=0.03),LDL-C (r=0.82, P=0.03)], and the levels of TC (OR=2.56, P=0.02) and LDL-C(OR=2.01, P=0.015) were positively associated with TAO. These suggested that high serum cholesterol level is a novel risk factor for TAO, and management of blood lipids should be included in the treatment of TAO.

Objective To explore the association between the different forms of in vivo ghrelin—Acyl ghrelin( AG) ,Des-acyl ghrelin( DAG) and AG/DAG with insulin resistance( IR) in patients with type 2 diabetes mellitus. Methods From June 2017 to November 2017,eighty-three patients with type 2 diabetes hospitalized in (group T2DM) and 40 healthy subjects (group NC) were hospitalized in Jinling Clinical Medicine were selected. Height body mass,blood pressure,blood lipid,glycated hemoglobin ( HbA1c) and fasting blood glucose (FPG),fasting insulin (FINS),and fasting C peptide (F-C-p) were measured,and all subjects were left with fasting serum,and the concentration of AG and DAG were measured by enzyme linked immunosorbent assay (ELISA). The body mass index (BMI),total gastric starvation (T-ghrelin) level,AG/DAG,insulin resistance index ( HOMA-IR) , insulin sensitivity index ( HOMA-IS ) and islet beta cell function ( HOMA- beta ) were calculated. The differences of the above indexes between the two groups were compared, and the relationship between AG,DAG,T-ghrelin,AG/DAG and FPG,HOMA-IR,HOMA-IS and HOMA- beta in T2DM patients were analyzed. Results ( 1) There were no significant difference in SBP、DBP、TC、LDL-C、AG between group NC and group T2DM(P>0. 05). Compared with NC group,the age、TG、BMI、HbA1c、FPG、FINS、HOMA-IR、HOMA-β、AG/DAG were significantly higher in T2DM group ( t=2. 690,-1. 990, 0. 873, 14. 257, 10. 528, Z=2. 885,-3. 483,-2. 284;P<0. 01,P<0. 05) . The HDL-C,F-C-p,HOMA-IS,HOMA-beta,DAG and T-ghrelin in group T2DM were lower than those of NC group( t or Z=0. 477,-3. 812,-3. 395,-4. 4,-2. 916,-2. 834;P<0. 05 or P<0. 01) . ( 2) The correlation analysis showed that there was a positive correlation between AG and FPG in T2DM group (r=0. 252,P<0. 05),DAG and T-ghrelin were negatively correlated with HOMA-IR (r=-0. 394,-0. 384,P<0. 05),and AG/DAG was positively correlated with HOMA-IR (r=0. 394,0. 384,P<0. 05),but is negatively correlated with HOMA-IS (r=-0. 292,P<0. 05). (3) multivariate linear regression analysis showed that FPG in T2DM patients were the influencing factors of AG ( t=2. 865,P<0. 05) ,while FINS and BMI were the influencing factors of DAG( t=-2. 808、-0. 330,P<0. 05) andT-ghrelin( t=-2. 725、-0. 330, P<0. 05) . HOMA-IR and BMI are the influencing factors of AG/DAG ( t=3. 718,3. 069,P<0. 05) . Conclusion The levels of DAG and T-ghrelin in group T2DM were significantly lower than those in the normal population, and was negatively correlated with the insulin resistance index,and the ratio of AG/DAG was closely related to insulin resistance,and the level of AG was mainly affected by fasting blood glucose.

In addition to the impaired insulin secretion,the dysregulation of hyperglycermic hormone glucagon also takes part in the development and progress of diabetes,exacerbating the diabetic metabolic outcome.Although there has been a significant breakthrough in the current research on the regulation of insulin secretion,relatively little research on the roleof glucagon has been carried out.Actually,except for the paracrine regulation on glucagon secretion,pancreatic α-cell has also been proposed to be regulated by intrinsic mechanism,juxtacrine-mediated and sodium-glucose cotransporter.Furthermore,some factors outside the islet also affect on the glucagon secretion.Thus,more research on the complex secretory regulation of glucagon will provide a theoretical basis for our further understanding of the development of diabetes.In this review,we will summary the progress in the regulation of glucagon secretion in intra islets.

Diabetic kidney disease is a common complication in patients with diabetes mellitus and so far,lacking effective therapy aiming at it.Glucagon like peptide-1 (GLP-1) receptor agonist is a novel hypoglycemic agent associated with incretin.Studies have shown that GLP-1 have additional renal protection independent of its hypoglycemic effect,mainly through the mechanisms such as antihypertension,reducing glomerular hyperfiltration,lowering proteinuria,anti-inflammatory,antioxidative stress and anti-RASS.In this review,we will summary their renal effects and mechanisms from the basic and clinical evidences.

OBJECTIVETo compare the safety and efficacy between three-field lymphadenectomy and normative Ivor-Lewis two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma METHODS: Clinical data of 375 patients with thoracic esophageal squamous cell carcinoma who underwent three-field lymphadenectomy(3FL) or Ivor-Lewis two-field lymphadenectomy(2FL, Ivor-Lewis) in Fudan University Shanghai Cancer Center during 2013 were retrieved and collected from electronic medical record system. Ninety-one patients received three-field lymphadenectomy (3FL group), including 16 cases of intra-cervical gastro-esophageal anastomosis and 75 cases of intra-thoracic gastro-esophageal anastomosis, while 284 patients received Ivor-Lewis two-field lymphadenectomy (2FL group) with all intra-thoracic gastro-esophageal anastomosis. Short-term outcomes were compared between two groups, including postoperative anastomotic leakage, pneumonia and respiratory failure, chylothorax, reoperation and 90-day death. Total harvested lymph nodes and positive lymph nodes in each group were also compared. A total of 338 patients were enrolled into survival analysis. Survival curve was presented by Kaplan-Meier method.

RESULTSAs compared to 2FL group, the 3FL group had significantly higher ratio of N3 patients [19.8% (18/91) vs. 5.3% (15/284), P=0.000], stageIII( patients [58.2%(53/91) vs. 43.0%(122/284), P=0.007], and upper thoracic cancer patients [12.1%(11/91) vs. 3.5%(10/284), P=0.027]; also the 3FL group had more harvested lymph nodes (40.1±14.6 vs. 25.3±9.4, P=0.000) and more positive lymph nodes (3.3±4.0 vs. 1.7±3.2, P=0.000). With respect to pneumonia and respiratory failure, chylothorax, reoperation and 90-day death, no significant differences were found between the group (P=0.447, P=0.751, P=0.678, P=0.685). The 3FL group had a significantly higher incidence of anastomotic leakage than 2FL group [7.7% (7/91) vs. 1.8% (5/284), P=0.011], while its incidence of intrathoracic anastomosis leakage was 4.0% (3/75), which was not significantly different with 1.8%(5/284) of 2FL group (P=0.372). Median follow-up was 33 months. Overall 1-, 2-, 3-year survival rates were 94%, 81% and 70%, while 1-, 2-, 3-year survival rates of 3FL group were 90%, 73% and 66%, of 2FL group were 95%, 84% and 72%, respectively, without significant differences between the two group(P=0.135). Further subgroup analysis showed that no significant differences of postoperative survival in stage I(, II( and III( patients were observed between the two groups (P=0.541, P=0.511, P=0.402), meanwhile no significant differences of postoperative survival in patients with metastasis and without metastasis were found between the two groups as well (P=0.985, P=0.233).

CONCLUSIONSThree-field lymphadenectomy can be performed with acceptable perioperative morbidity and mortality. The prognosis value of three field lymphadenectomy needs further investigation. Patients with thoracic esophageal squamous cell carcinoma may have favorable survival through normative Ivor-Lewis two-field lymphadenectomy.

Anastomotic Leak ; etiology ; Antineoplastic Protocols ; Carcinoma, Squamous Cell ; mortality ; surgery ; China ; Esophageal Neoplasms ; mortality ; surgery ; Esophagectomy ; adverse effects ; methods ; mortality ; Humans ; Incidence ; Lymph Node Excision ; adverse effects ; methods ; mortality ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Survival Rate ; Thoracic Neoplasms ; mortality ; surgery ; Treatment Outcome

OBJECTIVETo investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on the first-phase insulin secretion in isolated islets of db/db mice and explore the possible mechanisms.

METHODSIslets were isolated from db/db and db/m mice and the expression level of AT1R in the islets was assayed. A recombinant adenovirus containing siRNA targeting AT1R (Ad-siAT1R) and a recombinant adenovirus with nonspecific siRNA (Ad-siControl) were constructed to infect the isolated islets for 72 h. AT1R, GLUT-2, and GCK expressions in the islets were investigated and islet perifusion was performed to evaluate the kinetics of insulin release.

RESULTSThe expression level of AT1R in the isolated islets from db/db mice was twice that of islets from db/m mice. The islets treated with Ad-siAT1R showed significantly decreased AT1R mRNA and protein levels and significantly increased expression of GLUT-2 (by 190%) and GCK (by 121%) compared to those treated with Ad-siControl (P<0.05). In response to stimulation with 16.7 mmol/L glucose, the first-phase insulin secretion was impaired in both Ad-siControl group and mock infected group with the peak insulin levels only 1.8 times of the basal level; the first-phase insulin secretion was markedly improved in islets treated with Ad-siAT1R, with a peak insulin level reaching 2.8 times of the basal level.

CONCLUSIONSIn isolated islets of db/db mice, selective AT1R inhibition can restore the first phase insulin secretion by up-regulating GLUT-2 and GCK, which may be one of the potential mechanisms by which AT1R blockers improve insulin secretion function.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Diabetes Mellitus, Experimental ; Gene Knockdown Techniques ; Glucose ; Glucose Transporter Type 2 ; metabolism ; Insulin ; secretion ; Islets of Langerhans ; metabolism ; Mice ; Protein-Serine-Threonine Kinases ; metabolism ; RNA, Small Interfering ; pharmacology

Objective To investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on the first-phase insulin secretion in isolated islets of db/db mice and explore the possible mechanisms. Methods Islets were isolated from db/db and db/m mice and the expression level of AT1R in the islets was assayed. A recombinant adenovirus containing siRNA targeting AT1R (Ad-siAT1R) and a recombinant adenovirus with nonspecific siRNA (Ad-siControl) were constructed to infect the isolated islets for 72 h. AT1R, GLUT-2, and GCK expressions in the islets were investigated and islet perifusion was performed to evaluate the kinetics of insulin release. Results The expression level of AT1R in the isolated islets from db/db mice was twice that of islets from db/m mice. The islets treated with Ad-siAT1R showed significantly decreased AT1R mRNA and protein levels and significantly increased expression of GLUT-2 (by 190%) and GCK (by 121%) compared to those treated with Ad-siControl (P<0.05). In response to stimulation with 16.7 mmol/L glucose, the first-phase insulin secretion was impaired in both Ad-siControl group and mock infected group with the peak insulin levels only 1.8 times of the basal level; the first-phase insulin secretion was markedly improved in islets treated with Ad-siAT1R, with a peak insulin level reaching 2.8 times of the basal level. Conclusions In isolated islets of db/db mice, selective AT1R inhibition can restore the first phase insulin secretion by up-regulating GLUT-2 and GCK, which may be one of the potential mechanisms by which AT1R blockers improve insulin secretion function.