4-Octyl itaconate attenuates glycemic deterioration by regulating macrophage polarization in mouse models of type 1 diabetes.

BACKGROUND: Pancreatic beta cell dysfunction and activated macrophage infiltration are early features in type 1 diabetes pathogenesis. A tricarboxylic acid cycle metabolite that can strongly activate NF-E2-related factor 2 (Nrf2) in macrophages, itaconate is important in a series of inflammatory-associated diseases via anti-inflammatory and antioxidant properties. However, its role in type 1 diabetes is unclear. We used 4-octyl itaconate (OI), the cell-permeable itaconate derivate, to explore its preventative and therapeutic effects in mouse models of type 1 diabetes and the potential mechanism of macrophage phenotype reprogramming. METHODS: The mouse models of streptozotocin (STZ)-induced type 1 diabetes and spontaneous autoimmune diabetes were used to evaluate the preventative and therapeutic effects of OI, which were performed by measuring blood glucose, insulin level, pro- and anti-inflammatory cytokine secretion, histopathology examination, flow cytometry, and islet proteomics. The protective effect and mechanism of OI were examined via peritoneal macrophages isolated from STZ-induced diabetic mice and co-cultured MIN6 cells with OI-pre-treated inflammatory macrophages in vitro. Moreover, the inflammatory status of peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients was evaluated after OI treatment. RESULTS: OI ameliorated glycemic deterioration, increased systemic insulin level, and improved glucose metabolism in STZ-induced diabetic mice and non-obese diabetic (NOD) mice. OI intervention significantly restored the islet insulitis and beta cell function. OI did not alter the macrophage count but significantly downregulated the proportion of M1 macrophages. Additionally, OI significantly inhibited MAPK activation in macrophages to attenuate the macrophage inflammatory response, eventually improving beta cell dysfunction in vitro. Furthermore, we detected higher IL-1ß production upon lipopolysaccharide stimulation in the PBMCs from type 1 diabetes patients, which was attenuated by OI treatment. CONCLUSIONS: These results provided the first evidence to date that OI can prevent the progression of glycemic deterioration, excessive inflammation, and beta cell dysfunction predominantly mediated by restricting macrophage M1 polarization in mouse models of type 1 diabetes.

Echo time optimization for in-vivo measurement of unsaturated lipid resonances using J-difference-edited MRS.

PURPOSE: Measuring lipid composition provides more information than just total lipid content. Hence, the non-invasive measurement of unsaturated lipid protons with both high efficiency and precision is of pressing need. This study was to optimize echo time (TE) for the best resolving of J-difference editing of unsaturated lipid resonances. METHODS: The TE dependence of J-difference-edited (JDE) MRS was verified in the density-matrix simulation, soybean oil phantom, in-vivo experiments of white adipose tissue (WAT), and skeletal muscles using single-voxel MEGA-PRESS sequence at 3T. The peak SNRs and Cramér-Rao lower bounds (CRLBs) acquired at the proposed TE of 45 ms and previously published TE of 70 ms were compared (eight pairs) in WAT, extramyocelluar lipids (EMCLs), and intramyocellular lipids (IMCLs). The lipid composition in skeletal muscles was compared between healthy males (n = 7) and females (n = 7). RESULTS: The optimal TE was suggested as 45 ms. Compared to 70 ms, the mean signal gains at TE of 45 ms were 151% in WAT, 168% in EMCL, 204% in IMCL for allylic resonance, and 52% in EMCL for diallylic resonance. CRLBs were significantly reduced at TE of 45 ms in WAT, EMCL, IMCL for allylic resonance and in EMCL for diallylic resonance. With TE of 45 ms, significant gender differences were found in the lipid composition in EMCL pools, while no difference in IMCL pools. CONCLUSION: The JDE-MRS protocol with TE of 45 ms allows improved quantification of unsaturated lipid resonances in vivo and future lipid metabolism investigations.

Automated Measurement of Pancreatic Fat Deposition on Dixon MRI Using nnU-Net.

BACKGROUND: Pancreatic fat accumulation may cause or aggravate the process of acute pancreatitis, ß-cell dysfunction, T2DM disease, and even be associated with pancreatic tumors. The pathophysiology of fatty pancreas remains overlooked and lacks effective imaging diagnostics. PURPOSE: To automatically measure the distribution of pancreatic fat deposition on Dixon MRI in multicenter/population datasets using nnU-Net models. STUDY TYPE: Retrospective. POPULATION: A total of 176 obese/nonobese subjects (90 males, 86 females; mean age, 27.2 ± 19.7) were enrolled, including a training set (N = 132) and a testing set (N = 44). FIELD STRENGTH/SEQUENCE: A 3 T and 1.5 T/gradient echo T1 dual-echo Dixon. ASSESSMENT: The segmentation results of four types of nnU-Net models were compared using dice similarity coefficient (DSC), positive predicted value (PPV), and sensitivity. The ground truth was the manual delineation by two radiologists according to in-phase (IP) and opposed-phase (OP) images. STATISTICAL TESTS: The group difference of segmentation results of four models were assessed by the Kruskal-Wallis H test with Dunn-Bonferroni comparisons. The interobserver agreement of pancreatic fat fraction measurements across three observers and test-retest reliability of human and machine were assessed by intragroup correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: The three-dimensional (3D) dual-contrast model had significantly improved performance than 2D dual-contrast (DSC/sensitivity) and 3D one-contrast (IP) models (DSC/PPV/sensitivity) and had less errors than 3D one-contrast (OP) model according to higher DSC and PPV (not significant), with a mean DSC of 0.9158, PPV of 0.9105 and sensitivity of 0.9232 in the testing set. The test-retest ICC of this model was above 0.900 in all pancreatic regions, exceeded human. DATA CONCLUSION: 3D Dual-contrast nnU-Net aided segmentation of pancreas on Dixon images appears to be adaptable to multicenter/population datasets. It fully automates the assessment of pancreatic fat distribution and has high reliability. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

IGF2 deficiency causes mitochondrial defects in skeletal muscle.

Exercise training improves muscle fitness in many aspects, including induction of mitochondrial biogenesis and maintenance of mitochondrial dynamics. The insulin-like growth factors were recently proposed as key regulators of myogenic factors to regulate muscle development. The present study aimed to investigate the physical exercise impact on insulin-like growth factor 2 (IGF2) and analyzed its functions on skeletal muscle cells in vitro. Using online databases, we stated that IGF2 was relatively highly expressed in skeletal muscle cells and increased after exercise training. Then, IGF2 deficiency in myotubes from C2C12 and primary skeletal muscle cells (PMSCs) led to impaired mitochondrial function, reduced mitochondria-related protein content, and decreased mitochondrial biogenesis. Furthermore, we explored the possible regulatory pathway and found that mitochondrial regulation in skeletal muscle cells might occur through IGF2-Sirtuin 1 (SIRT1)-peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) signaling pathway. Therefore, the present study first demonstrated the relationship between IGF2 and mitochondria in skeletal muscle.

Association of vitamin D receptor polymorphisms with metabolic syndrome-related components: A cross-sectional study.

BACKGROUND: The association between vitamin D receptor (VDR) polymorphisms and metabolic syndrome (MS) has been demonstrated by epidemiological studies while their correlation remain controversial. The aim of this study is to investigate the association of VDR gene polymorphisms with MS and MS-related components in the two communities of Hangzhou. METHODS: A total of 394 subjects were enrolled in the cross-sectional study. Four VDR gene polymorphisms (ApaI, BsmI, FokI, and TaqI) were selected based on human genome sequence databases and genotyped using the MassARRAY Analyzer Compact. RESULTS: In lipid profile, the TT genotype of ApaI had a significantly lower risk of hypertriglyceridemia compared with the GG+GT genotypes (recessive model: OR = 0.141; 95% CI = 0.041-0.486; p < 0.01) and the GG genotype (codominant model: OR = 0.155; 95% CI = 0.044-0.545; p < 0.01). The levels of triglyceride (TG) in the TT genotype of ApaI were lower than the GG+GT genotypes (1.29 ± 0.63 vs. 1.78 ± 1.59 mmol/L, p < 0.01). Furthermore, the AA+GA carriers of BsmI had lower levels of high-density lipoprotein cholesterol (HDL-C) than the GG carriers (1.28 ± 0.29 vs. 1.42 ± 0.34 mmol/L, p < 0.05). The CC+TC carriers of TaqI also suffered from lower HDL-C compared with the TT carriers (1.27 ± 0.29 vs. 1.42 ± 0.34 mmol/L, p < 0.01). For arterial blood pressure, the CC carriers had lower systolic blood pressure (SBP) than the TT+TC carriers (p < 0.01) and the TT carriers of FokI (p < 0.05). However, the FokI polymorphisms were not associated with SBP and the mean blood pressure of both groups laid within the normal range. CONCLUSIONS: In our study, VDR polymorphisms show no association with the MS risk. The present results suggest that the VDR ApaI polymorphism is associated with hypertriglyceridemia and predisposed to developing MS, while the variants of BsmI and TaqI seem to affect HDL-C. Nevertheless, the effect of FokI variants with SBP is ambiguous.

[A novel mutation W257R in GCK gene discovered from a Chinese patient with maturity onset diabetes of the young].

Maturity onset diabetes of the young (MODY) is a monogenic autosomal dominant inherited disease. Its clinical manifestations are asymptomatic with slightly elevated fasting blood glucose and few complications. This paper reports a novel mutation W257R in glucokinase (GCK) gene from a Chinese patient with MODY. Heterozygous mutation c.769T>C (p.W257R) in exon 7 of GCK gene (Chr744187343) was found in the proband, her father and brother. This W257R mutation was first reported in Chinese population.

Recurrence of diet-treated gestational diabetes in primiparous women in northern Zhejiang, China: Epidemiology, risk factors and implications.

AIM: This study sought to determine the rate of recurrence of gestational diabetes mellitus (GDM) recurrence during the second pregnancies of women who were diagnosed with GDM during their first pregnancies, to identify risk factors associated with the probability of such recurrence and to evaluate the influence of GDM recurrence on pregnancy outcomes in north Zhejiang, China, after the recent adjustment to the nation's childbirth policy. METHODS: A retrospective longitudinal study was performed in north Zhejiang, China (at Jiaxing Maternal and Child Health Hospital). A total of 128 women who delivered two sequential live singleton infants and were diagnosed with diet-treated GDM during their first pregnancies were included. RESULTS: According to the 2013 World Health Organization diagnostic criteria for diabetes during pregnancy, the prevalence of gestational diabetes was 11.02% in northern Zhejiang. The recurrence rate of GDM in northern Zhejiang was 43.75% (56/128). The age at second pregnancy, weight gain during pregnancy, interpregnancy interval and macrosomia during the index pregnancy were risk factors for GDM recurrence. Among those women with recurrent GDM, GDM developed earlier and caesarean section was more frequently required during the second pregnancy; in addition, the second pregnancy was associated with more premature and low birthweight infants but less macrosomia. CONCLUSION: The recurrence rate of GDM is high in northern Zhejiang. Glucose monitoring and management are needed during subsequent pregnancies for patients who previously presented with GDM to improve maternal and fetal outcomes.

Autophagy protects against cholesterol-induced apoptosis in pancreatic ß-cells.

Autophagy is believed to play an important role in maintaining homeostasis in pancreatic ß-cells during insulin resistance. This study investigated the role of autophagy in ß-cell damage induced by cholesterol and its possible activation mechanism. Rat and mouse pancreatic ß-cell lines INS-1 and ßTC-6 were incubated with cholesterol alone or in combination with autophagy inhibitors E-64d/Pepstatin A or bafilomycin A1. DAPI staining, western blotting, transmission electron microscopy and immunofluorescence were conducted to assess the effects of autophagy inhibitors on cholesterol-induced apoptosis and autophagy activity. An increase in FITC-LC3 fluorescence dots, autophagic vacuoles and LC3-II protein indicated that autophagy was activated in cells treated with cholesterol. This was further confirmed by blocking the natural turnover processes in lysosomes and autolysosomes with autophagy inhibitors, suggesting enhanced autophagic activity rather than blockage of autophagy. Furthermore, inhibition of autophagy significantly augmented the activation of caspase 3 and the percentage of cholesterol-induced apoptotic nuclei. These results demonstrate that autophagy plays a protective role against cholesterol-induced apoptosis in pancreatic ß-cells.

Serum selenium level and gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The association between serum selenium level and gestational diabetes mellitus (GDM) is controversial. The aim of our study was to systematically review available literature linking selenium to GDM for a comprehensive understanding of the relationship between serum selenium level and GDM in human. METHODS: PubMed, The Cochrane Library and Medline were searched for studies published up to August 2016. Manual searches of references of the relevant original studies were carried out. Pooled estimates were measured using the fixed or random effect model. Overall effect was reported in a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0. RESULTS: Of 44 references reviewed, seven studies involving 569 patients met our inclusion criteria and contributed to meta-analysis. All the studies were used to evaluate the relationship between serum selenium level and GDM. Selenium level was significantly lower in women with GDM than those without GDM (SMD = -1.17; 95 % CI: -1.98 to -0.35, P = 0.005). Subgroup analysis showed that such trend was consistent within the non-Caucasian population (Asia: SMD = -2.82; 95 % CI: -5.21 to -0.43, P = 0.02; Africa: SMD = -0.56; 95 % CI: -1.07 to -0.05, P = 0.03) and in the third trimester (SMD = -1.78; 95 % CI: -3.04 to -0.52, P = 0.006), but not within the Caucasian population (Europe: SMD = -0.6; 95 % CI: -1.98 to 0.78, P = 0.39) or in the second trimester (SMD = -0.68; 95 % CI: -1.6 to 0.25, P = 0.15). CONCLUSIONS: The available evidences suggested that serum selenium level was lower in women with GDM than those with normal glucose tolerance, especially within the non-Caucasian population and in the third trimester. However, well-designed prospective studies are needed to understand dynamic associations between selenium status and GDM risk.

Alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigates isoflurane-induced cognitive impairment in aged rats.

BACKGROUND: Postoperative cognitive dysfunction is increasingly recognized as an important clinical syndrome. Inhalation anesthetics are commonly used during surgery, and it has been proposed that inhalation anesthetics impair cognitive function. However, there are few clinical interventions and treatments available to prevent this disorder. GTS-21, a selective agonist of alpha 7 nicotinic acetylcholine receptor, has been indicated to exert neuroprotective effects in the experimental animal models of neurodegenerative diseases. Therefore, we hypothesized that pretreatment with GTS-21 attenuates isoflurane-induced cognitive decline in aged rats. METHODS: In the present study, 20-mo-old rats were administered GTS-21 or an equal volume of saline by intraperitoneal injection 30 min before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Spatial learning and memory of the rats were assessed at 2 wk after isoflurane exposure. The expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in the hippocampus and cerebral cortex were determined by enzyme-linked immunosorbent assay. Simultaneously, neuronal apoptosis in the hippocampus was also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and Nissl staining. RESULTS: We found that exposure to isoflurane induces learning and memory deficits of old rats. IL-1ß in the hippocampus was increased at 4 h after isoflurane exposure. Isoflurane also increased neuroapoptosis in the hippocampus and decreased neuronal density in the CA1 region. And GTS-21 pretreatment effectively alleviated these changes. CONCLUSIONS: The study demonstrated that pretreatment with α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates isoflurane-induced learning and memory impairment in aged rats.

Clinical analysis of 65 cases of hyperemesis gravidarum with gestational transient thyrotoxicosis.

AIM: We investigated thyroid function and the impact of gestational transient thyrotoxicosis (GTT) on pregnancy outcome in patients with hyperemesis gravidarum (HG; n = 143) who were hospitalized for rehydration. METHODS: Serum thyroid-stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), thyroid globulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and hCG were measured after admission. RESULTS: The total prevalence of thyrotoxicosis in HG was 48.3%; GTT was the main form (45.5%). The total incidence of GTT increased significantly if serum hCG was more than 80,000 IU/L, subclinical GTT if serum hCG was 80,000-140,000 IU/L and clinical GTT if serum hCG was more than 180,000 IU/L. GTT did not require antithyroid therapy. The course of TSH, FT3 and FT4 were followed in 34 cases of GTT; thyroid function normalized by the second trimester. Of 65 patients with GTT, two underwent abortions due to unplanned pregnancies, two delivered prematurely and two infants had macrosomia. There were no other complications. All newborns (n = 63) of mothers with GTT had normal TSH levels. CONCLUSION: GTT is common in HG. The severity of GTT is related to serum hCG levels. In patients with HG and GTT, thyroid function normalized by the second trimester without antithyroid treatment. GTT did not affect pregnancy outcomes.

[The correlation between serum uric acid level and abdominal obesity or metabolic syndrome].

OBJECTIVE: To investigate the relationship between serum uric acid (UA) level and abdominal obesity or metabolic syndrome (MS). METHODS: A total of 875 subjects, with 350 males and 525 females, aged 40-65 years old, were enrolled in this study. The clinical and biochemical data were collected and MRI was used to assess the visceral and subcutaneous adipose tissues. The relationships between UA level and abdominal obesity or MS were analyzed, and the cut-off values of UA for abdominal obesity and MS were determined. RESULTS: Raised risks of abdominal obesity(OR = 4.35, 95%CI 1.91-9.90 in males; OR = 5.44, 95%CI 2.41-12.31 in females) and MS(OR = 4.47, 95%CI 2.08-9.62 in males; OR = 11.62, 95%CI 3.43-39.37 in females) were observed with the increase of UA level. The multiple logistic regression analysis showed that UA was an independent risk factor for hypertriglyceridemia(OR = 2.23, 95%CI 1.02-4.87 in males; OR = 3.04, 95%CI 1.49-6.23 in females) in all subjects and for abdominal obesity(OR = 3.23, 95%CI 1.32-7.91) and hypertension (OR = 2.35, 95%CI 1.37-4.05) in the females. Among the females, the regression line analyzed by simple correlation indicated that the UA level of 244.0 µmol/L was corresponded to the visceral adipose tissue area of 80 cm(2). The optimal cut-off point of UA for the diagnosis of MS was 258.8 µmol/L determined by the receiver operating characteristic curve. CONCLUSIONS: The level of UA is closely correlated with abdominal obesity and MS in the middle-aged Chinese. The elevated UA level is an independent risk factor for abdominal obesity and MS in the female.

Opposite luminescence thermal behavior of upconversion core/shell nanocrystals for anticounterfeiting.

Inorganic luminescent materials generally suffer from thermal quenching due to accelerated nonradiative transitions at high temperature, whereas Yb3+ sensitized core nanocrystals with small sizes (<30 nm) exhibit a temperature-dependent upconversion luminescence (UCL) enhancement. The related mechanism of the anomalous UCL thermal behavior is still under debate. In this work, we find that the UCL of NaGdF4:Yb/Tm@NaGdF4 inert-shell nanocrystals declines at elevated temperature, while that of NaGdF4:Yb/Ho@NaGdF4:Yb active-shell ones is enhanced. The thermally-induced UCL enhancement of active-shell nanocrystals is attributed to a gradually attenuated surface quenching effect. The initiators of the surface quenching are H2O molecules, which mainly attenuate Yb3+ excited states through an overtone energy transfer. The energy transfer is a coupling effect between ion dipoles of Yb3+ and atomic dipoles of H2O. Utilizing the opposite UCL temperature-dependence of active- and inert-shell nanocrystals, we designed their hybrids, which exhibit temperature-responsive multicolor emissions. The color-tunable hybrids are demonstrated to be excellent candidates for producing anticounterfeiting patterns with high security but simple recognition methods.

7-Ketocholesterol accelerates pancreatic ß-cell senescence by inhibiting the SIRT1/CDK4-Rb-E2F1 signaling pathway.

Pancreatic ß-cell dysfunction is a key factor in the development of type 2 diabetes. Pancreatic ß-cell senescence accelerates abnormal glucose metabolism, which decreases insulin secretion and cell regeneration ability, eventually leading to diabetes. A cholesterol oxidation product, 7-ketocholesterol (7-KC) can affect pancreatic ß-cell function. However, its role in pancreatic ß-cell senescence has not been reported. We investigated the role of 7-KC in pancreatic ß-cell senescence and its underlying molecular mechanism in MIN6 cells. MIN6 cells were treated with 25 µmol/L 7-KC for 24 h and the proportion of senescent cells was detected based on senescence-associated ß-galactosidase (SA-ß-gal) activity. The cell cycle, DNA damage, and the senescence-associate secretory phenotype (SASP) and protein expression were detected by flow cytometry, immunofluorescence, and western blotting, respectively. 7-KC can significantly increase SA-ß-gal activity, promoted G0/G1 arrest, DNA damage, and interleukin-1ß expression in MIN6 cells and significantly inhibited insulin synthesis. Further studies indicated that 7-KC induced ß-cell senescence by inhibiting the SIRT1/CDK4-Rb - E2F1 signaling pathway.

Sulfated fuco-manno-glucuronogalactan alleviates pancreatic beta cell senescence via PI3K/AKT/FoxO1 pathway.

Appearance of senescent beta cells in the pancreas leads to the onset of type 2 diabetes (T2D). The structural analysis of a sulfated fuco-manno-glucuronogalactan (SFGG) indicated SFGG had the backbones of interspersing 1, 3-linked ß-D-GlcpA residues, 1, 4-linked α-D-Galp residues, and alternating 1, 2-linked α-D-Manp residues and 1, 4-linked ß-D-GlcpA residues, sulfated at C6 of Man residues, C2/C3/C4 of Fuc residues and C3/C6 of Gal residues, and branched at C3 of Man residues. SFGG effectively alleviated senescence-related phenotypes in vitro and in vivo, including cell cycle, senescence-associated ß-galactosidase, DNA damage and senescence-associated secretory phenotype (SASP) -associated cytokines and hall markers of senescence. SFGG also alleviated beta cell dysfunction in insulin synthesis and glucose-stimulated insulin secretion. Mechanistically, SFGG attenuated senescence and improved beta cell function via PI3K/AKT/FoxO1 signaling pathway. Therefore, SFGG could be used for beta cell senescence treatment and alleviation of the progression of T2D.

Genomic Epidemiology and Antimicrobial Resistance Profiles of Clostridioides difficile from Multi-Hospitals in a City in Eastern China.

Background: Clostridioides difficile is an important pathogen causing approximately 20-30% of the cases-with antibiotic-associated diarrhea and 90% of those with Pseudomembranous enteritis. However, limited surveillance of C. difficile infections (CDI) in China is done at present, especially in terms of multi-hospital epidemiological reports. Methods: Between June 2020 and November 2020, we conducted a prospective study addressing antimicrobial susceptibility profiles and genomic epidemiology of C. difficile strains isolated from inpatients with diarrhea in seven tertiary hospitals in the same city. Results: In total, 177 strains of toxin-producing C. difficile were isolated, and the dominant toxin gene profiles were tcdA+tcdB+ (84.2%, 149/177) and tcdA-tcdB+ (15.8%, 28/177). Furthermore, 130 isolates were successfully analyzed for antimicrobial susceptibility phenotype in which the rates of resistance to clindamycin, erythromycin, levofloxacin, and moxifloxacin were higher than to other antibiotics. All strains were susceptible to metronidazole and vancomycin. Fluoroquinolone-associated mutations (such as gyrA) were the most frequently found ones in the analyzed genomes. Moreover, 24 different sequence types (STs) were identified in the 130 isolates, and the most prevalent types were ST3 (26.2%, 34/130) followed by ST54 (16.9%, 22/130) and ST2 (10%, 13/130). The so-called highly virulent strain ribotyping 027 (B1/NAP1/ST1) was not identified. In addition, we also compared single nucleotide polymorphisms (SNPs) among the isolates and carried out genomic epidemiological studies on the isolates. We found that ST3 and ST54 could cause transmission in both intra- and inter-hospital settings. Conclusion: Although it is the so-called hypervirulent epidemic strain, ribotyping 027 (ST1), was not detected. ST3 and ST54 can be transmitted through different hospitals. Therefore, it is necessary to conduct further molecular epidemiological monitoring of C. difficile and screening of patients admitted to key departments.

Association between MRI-based visceral adipose tissues and metabolic abnormality in a Chinese population: a cross-sectional study.

BACKGROUND: Previous studies have indicated that the deposition of abdominal adipose tissue was associated with the abnormalities of cardiometabolic components. The aim of this study was to examine the relationship of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and metabolic status and the different effects between males and females. METHODS: The 1388 eligible subjects were recruited in a baseline survey of metabolic syndrome in China, from two communities in Hangzhou and Chengdu. Areas of abdominal VAT and SAT were measured by magnetic resonance imaging (MRI). Serum total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) were measured by an automated biochemical analyzer. Metabolic abnormality (MA) was defined more than one abnormal metabolic components, which was based on the definition of metabolic syndrome (IDF 2005). Multiple logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95%CI). Predictive value was assessed by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI), respectively. RESULTS: Their mean age was 53.8 years (SD: 7.1 years), the mean body mass index (BMI) was 23.7 kg/m2, and 44.8% of the subjects were male. Both male and female with MA had higher VAT levels compared to subjects with normal metabolism (MN), and male had higher SAT levels than female (P < 0.05). Higher VAT was significantly associated with MA with ORs in the fourth quartile (Q4) of 6.537 (95% CI = 3.394-12.591) for male and 3.364 (95% CI = 1.898-5.962) for female (P for trend < 0.05). In female, VAT could increase the risk of metabolic abnormalities, but SAT could increase the risk of MA in the second and fourth quartiles (Q2 and Q4) only at BMI > 24 kg/m2. In male, VAT improved the predictive value of MA compared to BMI and waist circumference (WC), the AUC was 0.727 (95% CI = 0.687-0.767), the NRI was 0.139 (95% CI = 0.070-0.208) and 0.106 (95% CI = 0.038-0.173), and the IDI was 0.074 (95% CI = 0.053-0.095) and 0.046 (95% CI = 0.026-0.066). Similar results were found in female. CONCLUSIONS: In male, VAT and SAT could increase the risk of metabolic abnormalities both at BMI < 24 kg/m2 and at BMI ≥ 24 kg/m2. In female, VAT could increase the risk of metabolic abnormalities but SAT could increase the risk of MA in the second and fourth quartiles (Q2 and Q4) only at BMI > 24 kg/m2. Deposition of abdominal adipose tissue was associated with metabolic abnormalities. VAT improved the predictive power of MA.

Sulfated Fucogalactan From Laminaria Japonica Ameliorates ß-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1-PGC1-α Signaling Pathway Activation.

As mitochondrial metabolism is a major determinant of ß-cell insulin secretion, mitochondrial dysfunction underlies ß-cell failure and type 2 diabetes mellitus progression. An algal polysaccharide of Laminaria japonica, sulfated fucogalactan (SFG) displays various pharmacological effects in a variety of conditions, including metabolic disease. We investigated the protective effects of SFG against hydrogen peroxide (H2O2)-induced ß-cell failure in MIN6 cells and islets. SFG significantly promoted the H2O2-inhibited proliferation in the cells and ameliorated their senescence, and potentiated ß-cell function by regulating ß-cell identity and the insulin exocytosis-related genes and proteins in H2O2-induced ß-cells. SFG also attenuated mitochondrial dysfunction, including alterations in ATP content, mitochondrial respiratory chain genes and proteins expression, and reactive oxygen species and superoxide dismutase levels. Furthermore, SFG resulted in SIRT1-PGC1-α pathway activation and upregulated the downstream Nrf2 and Tfam. Taken together, the results show that SFG attenuates H2O2-induced ß-cell failure by improving mitochondrial function via SIRT1-PGC1-α signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic ß-cell failure.

Case Report: Recurrent Autoimmune Hypoglycemia Induced by Non-Hypoglycemic Medications.

We present a case of recurrent autoimmune hypoglycemia induced by non-hypoglycemic agents. We review reported cases of autoimmune hypoglycemia related to non-hypoglycemic agents, and discuss the effects of different detection methods for insulin autoantibodies on the results obtained. We aim to provide information for clinicians and a warning for medication usage. Considering the increasing number of clopidogrel-induced AIH cases and the hypoglycemia-induced increase in the risk of cardiovascular events, we recommend that cardiovascular disease patients being treated with clopidogrel be informed of this rare side effect and that clinicians be vigilant for the possibility of autoimmune hypoglycemia in this patient population.