[Proteomics of serum exosomes in children in the acute stage of Kawasaki disease: a prospective study]. / æ€¥æ€§æœŸå·å´Žç— æ‚£å„¿è¡€æ¸ å¤–æ³Œä½“è›‹ç™½è´¨ç»„å­¦çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD. METHODS: In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics. RESULTS: A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins. CONCLUSIONS: The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.

Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia.

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.

Cardiovascular disease outcomes in metabolically healthy obesity in communities of Beijing cohort study.

OBJECTIVE: The objective of this study was to investigate the association between metabolically healthy obese (MHO) phenotype and the risk of cardiovascular disease (CVD). METHODS: A total of 9393 subjects aged ≥40 years were enrolled in the cohort study (2011-2015). The participants were stratified by body mass index category and metabolic risk at baseline, and incidence of CVD was ascertained at follow-up. RESULTS: The MHO accounted for 6.7%. Compared with the metabolically healthy normal weight (MHNW) group, MHO subjects demonstrated increased risk of CVD events (HR = 1.91; 95% CI, 1.13-3.24). In people with obesity, there was no significant difference on increasing risk of incidence of CVD in the metabolically unhealthy individuals compared with metabolically healthy individuals (HR = 1.19; 95% CI, 0.74-1.91). Female (OR = 1.97; 95% CI, 1.06-3.64), smoking (OR = 2.09; 95% CI, 1.06-4.10), a larger waist circumference (OR = 1.07; 95% CI, 1.03-1.10) and higher LDL cholesterol levels (OR = 1.55; 95% CI, 1.20-2.00) were independent risk factors of the development of the MHO to the metabolically unhealthy obese (MUO) phenotype. CONCLUSIONS: The risk of CVD events of MHO phenotypes is similar to MUO phenotypes; both are higher than the MHNW phenotypes.

Correlation between brachial artery flow-mediated dilation and endothelial microparticle levels for identifying endothelial dysfunction in children with Kawasaki disease.

BACKGROUND: We investigated vascular endothelial dysfunction by sonographic features of flow-mediated dilation (FMD) and circulating endothelial microparticles (EMPs) in Kawasaki disease (KD). METHODS: Twenty-eight patients with KD were prospectively grouped according to stage of disease: acute, subacute, and convalescent. In addition, 28 healthy children and 28 febrile children were selected as controls. And cases in the convalescent phase were divided into two subgroups: coronary artery lesion (CAL) and no coronary lesion (NCAL). CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs were measured by flow cytometry; FMD was obtained by sonography. RESULTS: There were significant differences in FMD among the five groups. When compared with healthy controls, there were significantly greater numbers of CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs and a higher proportion of CD62E(+) EMPs in KD patients. The proportions and numbers of CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs in KD patients were not statistically different than in febrile controls. There were no significant differences in FMD and EMPs between the CAL and NCAL subgroups. There were significantly negative correlations between the values of FMD and EMPs in the three phases of KD. CONCLUSION: The increased levels of EMPs have significant correlation with decreased values of FMD, both of which may reflect endothelial dysfunction in child KD.

Evaluation of left ventricular systolic strain in children with Kawasaki disease.

The current study aimed to assess left ventricular (LV) longitudinal systolic strains in children with KD using two-dimensional speckle-tracking imaging and to analyze the relationship of LV myocardial deformation to coronary lesions and laboratory markers. The study enrolled 101 children with acute KD. An additional 50 age- and gender-matched normal children were enrolled as control subjects. During different phases of KD, echocardiograms were recorded for 61 children. Two-dimensional strain analysis software was used to track myocardial movement and obtain the strain from each LV segment. The LV longitudinal systolic strain decreased significantly in children with acute KD but increased immediately after intravenous immunoglobulin therapy. At 6-8 weeks after the onset of KD, all LV strains had recovered to normal. The LV systolic strain was not associated with coronary dilation in either acute or convalescent KD. In acute KD, aspartate transaminase, alanine transaminase, erythrocyte sedimentation rate, C-reactive protein (CRP), and hemoglobin (Hb) were found to be associated with coronary dilation, whereas LV systolic strains were found to be correlated with elevated CRP and decreased Hb. Speckle-tracking imaging of LV systolic strain was simple and accurate in evaluating LV function during different phases of KD. No association between LV dysfunction and coronary dilation was observed, but a relationship with CRP and Hb was found. Further studies are recommended to validate the current study results and explore further how these findings can improve clinical practice.

Serum γ-glutamyltransferase and uric acid levels are associated with impaired fasting glucose in adults from Inner Mongolia, China.

BACKGROUND: Serum γ-glutamyltransferase (GGT) and uric acid (UA) levels are elevated in patients with diabetes or cardiovascular disease. Prediabetes, characterized by impaired glucose tolerance, is an important risk factor for overt diabetes as well as cardiovascular disease. Therefore, the aim of this study was to explore the relationship between GGT, UA and prediabetes in a Chinese population, and provide a scientific basis for the early prevention and treatment of diabetes. METHODS: We performed a cross-sectional population-based study in a cohort of 2694 subjects (1211 men and 1483 women, aged 35-86 years). Questionnaires and physical examinations were performed using standardized procedures. Fasting blood was collected to measure glucose and other biochemical parameters. The subjects were divided into two groups with either normal fasting glucose (NFG) or impaired fasting glucose (IFG), according to international diagnostic criteria. Logistic regression analysis was performed to estimate odds ratios (OR) and 95% confidence intervals. RESULTS: Compared with the NFG group, the IFG group had significantly higher blood pressure but lower high-density lipoprotein-cholesterol in women. Body mass index, waist circumference, triglyceride, glucose, GGT, and UA levels were significantly higher in males and females in the IFG group than those in the NFG group. Logistic regression analysis revealed that the OR for prediabetes increased with increasing serum GGT quartiles and UA quartiles. GGT and UA were positively associated with prediabetes in men and women, independent of age, ethnicity, smoking, alcohol consumption, blood pressure, physical labor, and other confounders. CONCLUSIONS: We found that serum GGT and UA levels were positively associated with prediabetes in men and women living in areas inhabited by Chinese ethnic minorities. As elevated GGT and UA levels were associated with significantly increased risk of prediabetes, they may be used as sensitive biological markers of prediabetes.

A meta-analysis on the effect of corticosteroid therapy in Kawasaki disease.

UNLABELLED: The current recommended therapy for Kawasaki disease (KD) is the combination of intravenous immunoglobulin (IVIG) and aspirin. However, the role of corticosteroid therapy in KD remains controversial. Using meta-analysis, this study aimed to investigate the efficacy of corticosteroid therapy in KD by comparing it with standard IVIG and aspirin therapy. We included all related randomized and quasi-randomized controlled trials by searching Medline, the Cochrane Central Register of Controlled Trials, EMBASE, Pub Med, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the Japanese database (Japan Science and Technology) as well as hand searches of selected references. Data collection and meta-analysis were performed to evaluate the effect of corticosteroids. Our search yielded 11 studies; 7 of which evaluated the effect of corticosteroid for primary therapy in KD, and 4 investigated the effect of corticosteroid therapy in IVIG-resistant patients. Meta-analysis of these studies revealed a significant reduction in the rates of initial treatment failure among patients who received corticosteroid therapy in combination with IVIG compared to IVIG alone (odds ratio (OR) = 0.50; 95% CI, 0.32~0.79; p = 0.003). Furthermore, the use of corticosteroids reduced the duration of fever and the time required for C-reactive protein to return to normal. Our data did not show any significant increase in the incidence of coronary artery lesions or coronary aneurysms (OR = 0.67; 95% CI, 0.35~1.28; p = 0.23) in the corticosteroid group. CONCLUSION: Corticosteroid combined with IVIG in primary treatment or as treatment of IVIG-resistant patients improved clinical course without increasing coronary artery lesions in children with acute KD.

[Application of next-generation sequencing technology for genetic diagnosis of Duchenne muscular dystrophy].

OBJECTIVE: To detect genetic causes of Duchenne muscular dystrophy (DMD). METHODS: Next-generation sequencing was used to detect 6 DMD patients in whom no exonic deletions were detected by multiplex PCR. Sanger sequencing and multiplex ligation-dependent probe amplification were used to confirm the results. RESULTS: One case was found to have deletions of exons 10 and 11, 1 had exons 16 and 17 duplication, 4 cases have 8 point mutations including c.2776C>T, c.5475delA, c.6391_6392delCA, IVS64+1G>A, c.2645A>G, c.5244G>A, c.7728T>C, c.8729A>T, c.8734A>G and c.8810G>A. The former 4 mutations are suspicious pathogenicity, the other 6 mutations are polymorphisms in population. Three novel mutations (IVS64+1G>A, c.6391_6392delCA (p.Q2131NfsX3) and p.Q926X (CAG>TAG) were not reported before. CONCLUSION: Next-generation sequencing technology is a useful tool for the detection of deletion, duplication and point mutation, which is valuable for clinical application.

Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis.

Background: Hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CV-A6) has become prevalent in many parts of the world. It is commonly referred to as atypical HFMD which more likely to present as bullous lesions. Compared with traditional HFMD, its misdiagnosis rate is relatively high, which brings difficulties to clinical diagnosis. We retrospectively analyze the clinical characteristics of children with HFMD with bullous lesions caused by CV-A6. Methods: The study included 68 children with atypical HFMD caused by CV-A6 who were hospitalized from 2018 to 2020. Data of the children including age, sex, month of HFMD onset, the morphologies and distribution of rashes, the details of fever, the presence or absence of onychomadesis, and laboratory test results were analyzed and compared between an infant group (<1 year), a toddler group (1-<3 years), and a preschool group (3-<6 years). Results: Of the 68 children, 67 were younger than 5 years old, with a male to female ratio of 1.62:1. The disease peaked in the period from June to September. With 75.0% of the infant group had more than three kinds of rashes; 95.0% of the preschool group had rashes in more than five locations. These differences were statistically significant (P<0.05). All children had fever. The peak fever in the toddler group was lower (P=0.033). No critical cases were observed in any of the groups. Of the 61 children who were successfully followed up, 68.9% developed onychomadesis within 2-3 weeks. The proportion of cases with abnormal liver function was 83.3%, 41.7%, and 10.0% in the infant, toddler, and preschool groups (P<0.001). The proportion of cases with increased serum creatine kinase MB isoenzyme (CK-MB) were significantly higher in the toddler group (P<0.05). Conclusions: Atypical HFMD caused by CV-A6 infection usually occurred in children under 5 years old. The morphologies of the rashes in the infant group changed more, while the rashes in the preschool group was more widely distributed. The incidence of critical cases was low. More than half of the cases can develop onychomadesis in the recovery period. Organ damage was relatively mild in the preschool group.

Clinical data analysis of 22 cases with hypoparathyroidism misdiagnosed as epilepsy.

OBJECTIVE: Patients with hypoparathyroidism always present with recurrent tetany caused by hypocalcemia. These patients are usually misdiagnosed with epilepsy and incorrectly treated with anti-epileptic drugs. This research analyzed clinical data about 22 patients with hypoparathyroidism misdiagnosed as epilepsy and summarized the clinical experience for reducing misdiagnosis and incorrect therapy about hypoparathyroidism. METHOD: Totally 160 patients with hypoparathyroidism, administrated to the First Medical Center of Chinese PLA General Hospital from January 1st, 2008, to July 1st, 2021, were enrolled in this report. Clinical data about 22 patients initially misdiagnosed with epilepsy were analyzed. RESULTS: Of the 160 cases with hypoparathyroidism, 22 patients (12 males and 10 females) were misdiagnosed with epilepsy in local hospitals. The misdiagnosis rate was 13.75% and the median duration of misdiagnosis was 8.0 (2.0, 14.8) years. The clinical manifestations of the 22 patients misdiagnosed as epilepsy included tetany 81.8% (18/22), disturbance of consciousness 27.3% (6/22), limb numbness 13.6% (3/22), limb weakness 27.3% (6/22), mental and behavioral abnormality 9.1% (2/22), and memory impairment 13.6% (3/22), etc. Electroencephalogram (EEG) was performed in 9 cases, which presented as slow wave and spike-slow complex wave in 3 cases, slowing down of Î¸ and δ band background in 2 cases and normal EEG in 4 cases. Out of the 15 cases that underwent head computed tomography (CT) scan, in which 13 cases had intracranial calcification. Anti-epileptic drugs were used to treat 22 patients, of which 17 patients were treated with two kinds of drugs. With calcium and calcitriol supplement in all these 22 patients, the anti-epileptic drugs were gradually reduced and withdrawn in 17 cases. In the other 5 cases with secondary epilepsy, the type of anti-epileptic drugs was reduced to one and the clinical condition improved obviously. CONCLUSION: The clinical manifestations of hypoparathyroidism are complex and usually be misdiagnosed as primary epilepsy. Detection of serum calcium, phosphorus and parathyroid hormone is very important to avoid misdiagnosis and incorrect therapy about hypoparathyroidism.

High prevalence of coexisting prehypertension and prediabetes among healthy adults in northern and northeastern China.

BACKGROUND: Prehypertension and prediabetes are major risk factors of cardiovascular disease, and their combined presence may result in more serious cardiovascular outcomes than expected with either prehypertension or prediabetes alone. The aim of the present study was to evaluate the prevalence of coexisting prehypertension and prediabetes, and the associated risk profiles in a Chinese population. METHODS: A cross-sectional survey in a representative sample of 3,595 men and 4,593 women aged 18 years and older was performed between 2008 and 2010. Prehypertension and prediabetes were diagnosed using the guidelines from the Seventh Report of the Joint National Committee on prevention, detection, and treatment of high blood pressure and American Diabetes Association, respectively. Prehypertension was defined as a systolic blood pressure of 120-139 mmHg and/or diastolic blood pressure of 80-89 mmHg, and prediabetes was defined as a fasting blood glucose of 5.6-6.9 mmol/L. RESULTS: The prevalence of coexisting prehypertension and prediabetes was 11.0%. Men had a higher prevalence of coexisting prehypertension and prediabetes than women (14.2% vs. 8.4%; P < 0.0001). This prevalence increased with age and body mass index, and was the lowest among Mongolian-Chinese (5.1%). A multivariate analysis showed that γ-glutamyltransferase and uric acid were significantly and positively correlated with body mass index, waist circumference, blood pressure, triglycerides, and total cholesterol, and negatively correlated with high density lipoprotein cholesterol in subjects with prehypertension and prediabetes. CONCLUSIONS: There is a large proportion of Chinese adults with coexisting prehypertension and prediabetes. Thus, there is a need for more efforts that implement public health programs that target the earlier stages of hypertension and diabetes.

Insulinoma misdiagnosed as epilepsy in 44 Chinese patients.

OBJECTIVE: Insulinoma is a rare pancreatic neuroendocrine tumor that can spontaneously produce excess endogenous insulin, resulting in recurrent and serious hypoglycemia. Patients with insulinoma always have intermittent neuroglycopenia, which has been frequently reported as being misdiagnosed as epilepsy. In this report, we analyzed the clinical data of patients with confirmed insulinoma who had ever been misdiagnosed to have epilepsy. METHODS: The retrospective review was performed on 266 patients with confirmed insulinoma at the First Medical Center of Chinese PLA General Hospital between January 2000 and July 2020. RESULTS: 1. The diagnosis of insulinoma was confirmed in 266 patients. Forty-four patients [male/female=1/1.8, aged (41.25±12.30) years old] were misdiagnosed to have epilepsy, with a misdiagnosis rate of 16.5%. 2. Thirty-eight patients presented with consciousness disorder. Eleven patients presented with palpitation, sweating, and anxiety. Five patients presented with convulsion and 6 patients presented with abnormal behavior and delirium. 3. Twenty-two patients underwent EEG examination. EEG showed spike wave or spike-slow complex wave in 5 patients, decreased α wave and increased slow wave in θ and δ band in 7 patients, and was normal in 10 patients. 4. Thirty-five patients were incorrectly prescribed with AEDs and 22 patients were even misdiagnosed to have refractory epilepsy. 5. All these 44 patients underwent successful surgery, and hypoglycemia symptoms were relieved after insulinoma resection. CONCLUSION: Patients with insulinoma sometimes share common clinical characteristics with epilepsy. To patients with epilepsy or suspected epilepsy, especially with poor response to ADEs, hypoglycemia caused by insulinoma should be emphasized in the differential diagnosis.

[22q11 microdeletion test in patients with congenital heart defects by quantitative fluorescent PCR].

OBJECTIVE: To establish an assay for screening chromosome 22q11 microdeletion efficiently, and apply it for detecting del22q11 in patients with non-syndromic congenital heart defects (CHD). METHODS: Seventy nine patients with non-syndromic CHD and 84 normal controls were genotyped for 8 short tandem repeat (STR) markers located in 22q11 region, by using quantitative fluorescence polymerase chain reaction (QF-PCR). RESULTS: The average heterozygosity of the STR markers in patients and controls was 0.76 and 0.79, respectively. One patient with Tetralogy of Fallot (TOF) from the 79 CHD cases (1.3%) was found to have a deletion within chromosome 22q11.2, which was confirmed by multiplex ligation-dependent probe amplification (MLPA). CONCLUSION: The QF-PCR assay developed in this study was a reliable and an efficient alterative approach to screen for 22q11 microdeletion in clinical diagnosis and genetic counseling.

[Effects of candesartan on expressions of JAK2 and PTP-1B in adipose tissue of high-fat diet-fed rats].

OBJECTIVE: To observe the effects of candesartan on the expressions of JAK2 and protein tyrosine phosphatase-1B (PTP-1B) in adipose tissue of obese rats induced by high-fat diet. METHODS: A total of 45 male Wistar rats were randomly assigned into 3 groups of normal control (NC group), high fat diet (HF group) and high-fat diet with daily Candesartan treatment (FC group). The rats of FC group were treated with orally taken Candesartan at a dose of 8 mg/kg body weight per day. Blood chemistry and insulin were assayed at Week 16. Euglycemic-hyperinsulinemic clamp technique was performed to evaluate the peripheral insulin resistance. The expressions of JAK2 and PTP-1B in adipose tissue were confirmed by both reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: (1) The body weight and peri-renal fat weight of HF group were significantly higher than those of FC and NC groups (all P < 0.05). (2) total cholesterol (TC) and fasting insulin (FINS) of FC group were lower than those of HF group [TC, FC group: (1.37 ± 0.39) mmol/L vs HF group: (2.01 ± 0.26) mmol/L, P < 0.05; FINS, FC group: (3.03 ± 1.37) mU/L vs HF group: (4.76 ± 2.75) mU/L, P < 0.05] while insulin sensitive index (ISI) and angiotensin II (AngII) of FC group were much higher than those of HF group [ISI, FC group: (58 ± 12) × 10(-3) vs HF group: (29 ± 9) × 10(-3), P < 0.05; AngII, FC group: (61 ± 11) mmol/L vs HF group: (52 ± 10) mmol/L, P < 0.05]. (3) The steady-state glucose infusion rate (SSGIR) of FC group was significantly higher than that of HF group [FC group: (22 ± 5) mg×kg(-1)×min(-1) vs HF group:(14 ± 4) mg×kg(-1)min(-1), P < 0.05]. (4) Both the mRNA and protein expressions of JAK2 and PTP-1B in FC group were significantly lower than those in HF group respectively. CONCLUSION: There are insulin resistance and a high expression of JAK2 and PTP-1B in adipose tissue of obese rats induced by high-fat diet. And both are related with the elevated AngII level. Candesartan can reverse these effects.

Anxiety in Chinese pediatric medical staff during the outbreak of Coronavirus Disease 2019: a cross-sectional study.

BACKGROUND: Our study aimed to explore the anxiety levels and possible associated factors in the pediatric medical staff in Jiangsu province during an outbreak of Coronavirus Disease 2019 (COVID-19). METHODS: Pediatric medical staff (n=534) from nine hospitals in Jiangsu province were enrolled. Their anxiety levels and quality of sleep were assessed using the online SAS and PSQI questionnaires. RESULTS: The prevalence of anxiety was 14.0% among the medical staff. In children's hospital staff, anxiety levels in outpatient and emergency departments were significantly higher than those in inpatient departments, except for the intensive care unit. The SAS scores were significantly associated with educational background, professional title, lifestyle, and physical condition. Stepwise multiple linear regression showed that physical condition, lifestyle, attention to the epidemic, professional title, and educational background all had a linear relationship with the individual's anxiety levels. Pearson correlation analysis showed that sleep quality was moderately associated with anxiety levels. CONCLUSIONS: The prevalence of anxiety was 14.0% in pediatric medical staff in Jiangsu province during an outbreak of COVID-19. Department, professional title, and educational background were associated with anxiety levels in these workers. More attention should be paid to staff who are in poor health, and this anxiety can also be accompanied by poor sleep quality. Peer support can assist with anxiety relief.

MiR-222-3p in Platelets Serves as a Distinguishing Marker for Early Recognition of Kawasaki Disease.

Kawasaki disease (KD) is an acute vasculitis, which leads to 20% of sufferers developing coronary artery aneurysm in children if not appropriately treated. Therefore, the early diagnosis of KD is essential for alleviating the risk of developing heart disease. MicroRNAs (miRNAs) are a large class of small non-coding RNAs which post-transcriptionally regulate gene expression and have been shown to play critical roles in numerous biological processes and diseases. In this study, we used high-throughput miRNA sequencing and found dozens of miRNAs are highly expressed in platelets. By comparing the miRNA expression profile of platelets of acute KD patients and other febrile patients, miR-222-3p is validated to be significantly upregulated in platelets of acute KD patients. Furthermore, KEGG pathway analysis shows that targets of miR-222-3p are enriched in immune-related signaling pathways. Our study uncovers the potential of miR-222-3p in platelets as biomarker for early diagnosis of Kawasaki disease.

[Candesartan improves insulin resistance induced by high-fat diet in rats].

OBJECTIVE: To investigate the effects of candesartan, an angiotension II type I receptor antagonist, in improvement of insulin resistance (IR) induced by high-fat diet and the possible mechanism thereof. METHODS: 45 male Wistar rats were randomly divided into 3 groups: normal chow group (NC, n = 15) fed with normal diet, high fat diet group (HF, n = 15) fed with high fat diet, and high-fat diet with daily candesartan treatment group (HF + C, n = 15) fed with high fat diet and given orally with candesartan 8 mg/kg per day. Body weight was measured regularly. Four weeks later, oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp technique were performed to estimate the insulin sensitivity. After 12 h fasting blood samples were collected from the abdominal aorta to test the contents of blood glucose, and serum triglyceride (TG), total cholesterol (TC), LDL, HDL, and free fatty acid (FFA). Radioimmunoassay was used to detect the serum insulin. Viscera were taken out. Immunohistochemistry was used to examine the expression of peroxisome proliferation activated receptor (PPAR)-gamma in hepatic and adipose tissues. RESULTS: The body weight 16 weeks later of the HF group was significantly higher than that of the HF + C group (P < 0.01). The liver weight and epididymal and peri-renal fat weights of the HF group were all significantly higher than those of the HF + C group and NC group (all P < 0.01). There was no significant difference in fasting blood sugar among these 3 groups (P > 0.05). The glucose levels 2 h after OGTT in the HF + C group was (6.3 +/- 0.5) mmol/L, significantly lower than that of the HF group [(7.3 +/- 1.2) mmol/L, P < 0.01]. The glucose infusion rate (GIR) of the HF + C group was (22 +/- 5) mmol/L, significantly higher than that of the HF group [(14 +/- 4) mmol/L, P < 0.01]. The PPARgamma expression levels in liver and adipose tissue of the HF + C group were up-regulated significantly compared with those of the HF group. CONCLUSION: Candesartan may improve insulin resistance through promoting the expression of PPARgamma in liver and adipose tissue.

Thyrotrophic status in patients with pituitary stalk interruption syndrome.

Pituitary stalk interruption syndrome (PSIS) is associated with simultaneous or subsequent pituitary hormone deficiencies (PHDs). Although the clinical features of multiple PHDs are well known, the status of the thyrotrophic axis in PSIS has not been thoroughly investigated.The clinical data of 89 PSIS patients and 34 Sheehan syndrome (SS) patients were retrospectively analyzed.The prevalence of central hypothyroidism in the PSIS patients and the SS patients was 79.8% and 70.6%, respectively. The thyroid-stimulating hormone (TSH) levels in the PSIS patients were significantly higher in comparison with the SS patients (5.13 ±â€Š3.40 vs 1.67 ±â€Š1.20 mU/L, P < .05). TSH elevation (8.79 ±â€Š3.17 mU/L) was noticed in 29 of 71 (40.85%) hypothyroid PSIS patients but not in the 24 hypothyroid SS patients. The TSH levels in the hypothyroid PSIS patients were significantly higher in comparison with the euthyroid PSIS patients (5.42 ±â€Š3.67 vs 3.66 ±â€Š1.50 mU/L). Thyroid hormone replacement significantly reduced the TSH levels in the PSIS patients with elevated TSH levels from 7.24 ±â€Š0.98 to 1.67 ±â€Š1.51 mU/L (P < .05). The logistic regression analysis suggested that TSH level was not significantly associated with pituitary stalk status and height of the anterior pituitary gland.PSIS is a newly recognized cause of central hypothyroidism. The proportion and amplitude of TSH elevations are higher in PSIS than in other causes of central hypothyroidism.

Association between Self-reported Snoring and Prediabetes among Adults Aged 40 Years and Older without Diabetes.

BACKGROUND: Several previous studies have shown that snoring is associated with glucose metabolism and the development of diabetes, but rare study has shown the association between snoring frequency and prediabetes, particularly in China. We hypothesized that individuals who snore might have a higher risk of prediabetes. This study aimed to investigate the association between self-reported snoring and prediabetes in a Chinese population. METHODS: A cross-sectional study was performed in three large communities of Beijing from December 2011 to August 2012 by recruiting individuals aged ≥40 years old. All participants were requested to complete a detailed questionnaire and undergo anthropometric measurements. A 75 g oral glucose tolerance test was performed in individuals without diabetes. Blood samples of all participants were collected; blood glucose and blood fat levels were measured. Multivariate logistic regression models were built to assess the association between snoring frequency and prediabetes. RESULTS: A total of 13,592 participants (female: 66.56%; mean age: 56.8 ± 7.9 years; mean body mass index: 25.5 ± 3.4 kg/m2) were included in the final analysis. Of these, 30.9% were diagnosed with prediabetes, while 41.3% and 25.4% had occasional and habitual snoring, respectively. Habitual snoring was associated with an increased risk of prediabetes (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1-1.4, P< 0.001), after adjusting for diabetes and sleep-related confounders in the multivariable models. Habitual snoring was also associated with isolated impaired fasting glucose (IFG; OR: 1.3, 95% CI: 1.0-1.6; P< 0.001) and isolated impaired glucose tolerance (IGT; OR: 1.3, 95% CI: 1.2-1.5; P< 0.001), but not IFG + IGT (OR: 1.1, 95% CI: 0.9-1.4; P = 0.281). When stratified by total cholesterol (TC) levels, this association between habitual snoring and prediabetes was observed only in individuals with TC <5.6 mmol/L (OR: 1.4, 95% CI: 1.2-1.6; P< 0.001). CONCLUSIONS: Habitual snoring is associated with prediabetes, but only in individuals with TC <5.6 mmol/L. Further prospective studies are needed to confirm this finding.

Candesartan cilexetil prevents diet-induced insulin resistance via peroxisome proliferator-activated receptor-γ activation in an obese rat model.

Angiotensin II type 1 receptor (AT1R) blockers (ARBs) have been shown to reduce the incidence of type 2 diabetes mellitus; however, the underlying molecular mechanism is unknown. Peroxisome proliferator-activated receptor γ (PPARγ) is the central regulator of insulin and glucose metabolism, which improves insulin sensitivity. Whether candesartan cilexetil, as a prodrug of the AT1R blocker candesartan, has PPARγ-activating properties remains to be elucidated. The aim of the present study was to investigate the effects of oral administration of candesartan cilexetil on glucose tolerance and the actions of PPARγ on liver and adipose tissue in the insulin-resistant obese rat induced by high-fat diet. Animals treated with candesartan cilexetil showed an improved glucose tolerance after oral glucose challenge. Whole-body insulin sensitivity was evaluated using the hyperinsulinemic-euglycemic clamp technique. During high-fat feeding in high-fat diet (HF) rats, the glucose infusion rate (GIR) was 52.3% lower than that in normal chow (NC) rats. However, the GIR was significantly enhanced following candesartan cilexetil treatment. Angiotensin II receptor antagonism also resulted in significant increases in PPARγ protein expression in adipose and liver tissue. These results indicate that PPARγ activation by candesartan cilexetil may provide novel therapeutic options in the treatment of patients with metabolic syndrome.