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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.
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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.
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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.
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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.
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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.
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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.
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<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Animals , Mice , Angiotensin II Type 1 Receptor Blockers , Pharmacology , Diabetes Mellitus, Experimental , Gene Knockdown Techniques , Glucose , Glucose Transporter Type 2 , Metabolism , Insulin , Bodily Secretions , Islets of Langerhans , Metabolism , Protein Serine-Threonine Kinases , Metabolism , RNA, Small Interfering , PharmacologyABSTRACT
The hospital grade assessment is an effective approach to measure the comprehensive strength and the overall level of a hospital, and it is also an effective carrier which can promote the standardized management , improve the quality of connotation and accelerate the development of the hospital .This article aims to expound the effective and concrete methods for preparation in the hospi -tal grade assessment by introducing the practice and experience of Jinling Hospital in grade assessement .It also points out that:defi-ning the purpose of the assessment is the fundation , having a thorough grasp of the assessment criteria is the basis , having a compre-hensive knowledge of the hospital is the premise , establishing and implementing the plan strictly is the crux .All these might be helpful to promote the hospital grade assessment .
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So far, the major therapeutic drugs of diabetes are western medicine , but side effects of hypoglycemic western med-icine are large and not easy to take for a long time .In recent years , we found the side effects of some kind of hypoglycemic Chinese herbal medicine were small , much easier to be accepted by the patients .Thus, the clinical treatment of diabetes may have new meth-ods.According to the mechanisms of Traditional Chinese Medicine for protection of islet function , this review will discuss them from re-ducing oxidative stress , increasing the number of islet cells and promoting βcells to secrete, relieving insulin resistance , increasing in-sulin sensitivity and so on .All of these aspects reflect the unique role of Traditional Chinese Medicine in the treatment of diabetes and protection of islet function .
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Low-triiodothyronine syndrome is a condition characterized by decreased total serum T 3 and free T3 , along with in-creased serum reverse triiodothyronine but normal levels of thyroxine and thyrotropin .However , it is not caused by the thyroid gland diseases.The latest research progress of mechanisms , diagnosis and clinical significance , and therapy strategy of low T 3 syndrome is reviewed in this paper .
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The construction of harmonious doctor-patient relationship is an important project in social medicine .The influen-cing factors about doctor-patient relationship are analyzed from three aspects which are responsibility ethics , bottom-line ethics and clin-ic ethics.Based on the discussion , certain countermeasures are proposed to reconstruct harmonious doctor -patient relationship .
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<p><b>OBJECTIVE</b>The aim of the present study is to investigate the effect of rhein treatment on the first-phase insulin secretory function in db/db mice.</p><p><b>METHOD</b>Twenty 4-week-old male db/db mice were randomized to treatment with rhein (120 mg x kg(-1), n = 10) and placebo respectively (1% natrium cellulose solution, n = 10) by gavage for 8 weeks respectively. Ten age-matched non-diabetic male littermates db/m mice treated with placebo were studied as non-diabetic control. Body weight and fasting blood glucose level were measured before and after medication. The islets were isolated after 8 weeks' gavage. Islet perifusion system was set up, and all columns were perfused in parallel at a flow rate of 0.5 mL x min(-1) with KRB (2.8 mmol L(-1) glucose) at 37 degrees C. After 60-min static incubation with KRB (2.8 mmol x L(-1) glucose), the islets were stimulated in the continuous presence of a high concentration of 16.7 mmol x L(-1) glucose. Samples were collected every 20-second until 2-min, every 1-min until 5-min, thereafter every 5-min until 30-min. Samples were immediately stocked at -80 degrees C until further analysis.</p><p><b>RESULT</b>Compared with the db/db control group, the fasting glucose concentration was significantly decreased in the rhein treatment group. The first-phase insulin secretory function was impaired significantly in db/db mice, while the first-phase insulin secretory peak was obvious in the rhein treatment mice.</p><p><b>CONCLUSION</b>Rhein treatment significantly improved glucose tolerance, restored the first-phase insulin secretion and protected the islets function.</p>
Subject(s)
Animals , Male , Mice , Anthraquinones , Therapeutic Uses , Blood Glucose , Body Weight , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , In Situ Nick-End Labeling , Insulin , Bodily Secretions , Mice, Inbred C57BLABSTRACT
Dioxin,one of the persistent organic pollutants,persistently exists in the environment and does serious harm to the ecological environment as well as to the human body because of its reproductive toxicity,carcinogenicity,immune toxicity,skin toxicity and toxicity to other systems and organs.This paper reviewed the toxicities of dioxins to the human body,especially to the endocrine and immune systems.
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Objectives: To explore the epidemiological distribution of body mass index(BMI),waist to hip ratio(WHR) and abdominal circumference in population of Nanjing,Jiangsu Province. Methods: BMI, WHR and abdominal circumference were measured on 3 445 healthy cases aged 18～90 of Nanjing. Epidemiological distribution of BMI,WHR and abdominal circumference were analyzed according to sex and age. Results:The total mean BMI was( 23.28 ?3.49)kg/m 2, and the BMI in male was higher〔(23.80?3.36)kg/m 2〕 than that in female 〔(22.25? 3.49)kg/m 2〕( t =12.75, P
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Objective To assess the association of obesity, serum lipid levels and insulin resistance with leptin in Nanjing population. Methods One hundred and eighty eight subjects aged 22～81 years in Nanjing were divided into three groups according to BMI and dignosis criteria of diabetes: normal group, obese group and diabetes group. Their weight, height, waist, abdomen and hip circumferences were measured. Total cholesterol, triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apoA, apoB, fasting plasma glucose (FPG), true insulin (TI), immunoreactive insulin (IRI) and leptin were also measured. ISI 1=1/(FPG?TI) and ISI 2=1/(FPG?IRI) as insulin sensitivity indexes were used to analyse the relation between leptin and insulin resistance. Results Fasting serum leptin level was associated with sex (four fold as high in women as that in men). BMI was the second strongest determinant of leptin. Leptin was positively correlated with TI (r=0.32, P