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Introduction: Insulin degludec (degludec), an ultra-long-acting basal insulin analogue, provides equivalent glycemic control to other basal insulin analogues, with lower risk of hypoglycemia and flexible dosing. Chinese TREsiba AudiT (CN-TREAT) investigated outcomes with degludec in people with type 2 diabetes (T2D) in routine clinical practice in China., Methods: This was a retrospective chart review study in adults with T2D initiating or switching to degludec at 50 sites in China between January 2020 and July 2021. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study (EOS; week 20). Secondary endpoints included change from baseline to EOS in fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), daily insulin dose, and rate of hypoglycemia., Results: Data from 936 participants were included (499 insulin-naïve; 437 insulin-experienced). Mean (95% confidence interval [CI]) HbA1c change from baseline to EOS was - 1.48%-points (- 1.57; - 1.38; P < 0.0001) overall: - 1.95%-points (- 2.08; - 1.81; P < 0.0001) in insulin-naïve participants and - 0.95%-points (- 1.08; - 0.82; P < 0.0001) in insulin-experienced participants. Mean (95% CI) changes in FPG and SMPG were - 2.27 mmol/L (- 2.69; - 1.85; P < 0.0001) and - 2.89 mmol/L (- 3.52; - 2.25; P < 0.0001), respectively, with similar reductions in insulin-naïve and insulin-experienced subgroups. Rate of hypoglycemia did not change statistically significantly from baseline to EOS overall, or in insulin-experienced participants, except when adjusted for baseline hypoglycemia. Basal insulin dose did not change statistically significantly in insulin-experienced participants., Conclusion: In routine clinical practice in China, initiation or switching to degludec was associated with improvements in glycemic control in people with T2D, with no increased risk of hypoglycemia., Trial Registration: ClinialTrials.gov, NCT04227431., (© 2024. The Author(s).)

Impaired insulin secretion due to pancreatic β-cell injury is an important cause of type 2 diabetes (T2D). Regulators of guanine nucleotide binding protein (G protein) signaling proteins played a key role in regulating insulin sensitivity in vivo . To explore the role of RGS7 on palmitic acid-induced pancreatic β-cell injury, pancreatic β-cells Beta-TC-6 and Min6 were treated with palmitic acid (PA) to similar type 2 diabetes (T2D) injury in vitro . The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry were used to analyze cell viability, proliferation, and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the changes of inflammation-related cytokines. The expression of gene and protein was measured by quantitative real-time PCR (qRT-PCR) and western blot. PA modeling induced apoptosis, increased levels of inflammation-related cytokines, and suppressed cell viability and proliferation of pancreatic β-cells. RGS7 silence markedly alleviated the cell injury induced by PA. RGS7 overexpression further aggravated apoptosis and inflammatory response in PA-induced pancreatic β-cells and inhibited cell viability and proliferation. It is worth noting that RGS7 activated the chemokine signaling pathway. Silence of the key gene of the chemokine signaling pathway could eliminate the negative effect of RGS7 on PA-induced pancreatic β-cells. RGS7 silence protects pancreatic β-cells from PA-induced injury by inactivating the chemokine signaling pathway.

Purpose: To calculate the dose distribution using Monte Carlo simulations for a novel high-dose-rate Yttrium-90 (Y-90) disc source recently developed for episcleral brachytherapy and provide a lookup table for treatment planning., Methods: Monte Carlo simulations were performed to calculate the in-water dose distribution of the Y-90 disc source using the "GATE", a software based on the "Geant4" Monte Carlo simulation toolkit developed by the international OpenGATE collaboration. The geometry of this novel beta source, its capsule, and the surrounding water medium were accurately modeled in the simulation input files. The standard Y-90 element beta spectrum from ICRU 72 was used, and the physics processes for beta and photon interactions with matters were all included. The dose distribution of this Y-90 disc source was measured in a separate study using Gafchromic EBT-3 films and the results were reported elsewhere. To match the setup of the experiment, a Gafchromic EBT-3 film was also included in the simulation geometry. The simulated dose profiles were exported from the 3D dose distribution results and compared with the measured dose profiles. Transverse dose profiles at different distances from the seed surface were also obtained to study the lateral coverage of the source., Results: The measured percent depth dose (PDD) curves along the central axis perpendicular to the surface of the Y-90 disc were constructed from the experimental and simulated data, and normalized to the reference point at 1 mm from the source capsule. Both PDD curves agreed well up to 4 mm from the source surface (maximum difference ± 10%) but deviated from each other beyond 4 mm. The deviation might be caused by the increased measurement uncertainty in the low-dose region. The dose rate at the reference point calculated from the Monte Carlo simulation was 1.09 cGy/mCi-s and agreed very well with the measured dose rate of 1.05 cGy/mCi-s. If the 80% isodose line is selected as the lateral coverage, the lateral dose coverage is maximal (∼4.5 mm) at the plane next to the source surface, and gradually decreases with the increasing distance, approaching 3.5 mm when the plane is 5 mm from the 6-mm diameter source surface., Conclusion: Monte Carlo simulations were successfully performed to confirm the measured PDD curve of the novel Y-90 disc source. This simulation work laid a solid foundation for characterizing the full dosimetry parameters of this source for episcleral brachytherapy applications., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Objective: Invariant natural killer T (iNKT) cells, which are depleted in obese individuals, play important roles in preventing diet-induced obesity and associated disorders. Probiotic supplementation can alter the gut microbiota and immunomodulation in obesity. However, it remains unclear whether probiotics can affect visceral adipose iNKT cells. The aim of this study was to analyze the effects of probiotics on adipose iNKT cells in mice with high-fat diet (HFD)-induced obesity and to assess the immunomodulatory function of probiotics and their role in obesity, glucose tolerance, lipid metabolism, insulin resistance, and adipose inflammation., Methods: Wildtype (WT) male C57BL/6 mice and CD1d knockout mice were fed an HFD or a normal-fat diet. Some mice received active or heat-sacrificed VSL#3 probiotics. Preventative VSL#3 therapy was also administered to HFD mice. Body weight, metabolic parameters, expression of genes encoding adipose inflammatory factors (interleukin [IL]-4, IL-10, tumor necrosis factor-α, interferon-γ, and IL-6), adipose iNKT cell frequency, and subphenotype were evaluated., Results: HFD induced more severe obesity in CD1dKO mice than in WT mice. VSL#3 intervention significantly improved HFD-induced weight gain, adipose iNKT cell depletion, and metabolic and adipose inflammatory profiles in WT mice, but not in CD1dKO mice. Preventative VSL#3 treatment improved HFD-induced obesity and metabolic parameters, and elevated total adipose iNKT and IL-4 + iNKT cell frequencies., Conclusions: Probiotic intervention alleviated weight gain, improved metabolic parameters, and reduced adipose inflammation in HFD-induced obesity. These effects seem to depend on the restoration of visceral adipose iNKT cells. These findings have potential implications for the management of obesity-related diseases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study was designed to investigate the correlation of vitamin D receptor (VDR) gene polymorphism with bronchial asthma in children. Seventy patients admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the first time from April 2015 to May 2017 were selected as observation group. Patients received routine treatment and intervention. Seventy healthy subjects admitted to hospital during the same period were enrolled as the control group. Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism assay; the levels of total serum immunoglobulin E (IgE) in the two groups were determined by electrochemiluminescence immunoassay; lung function levels in patients were measured using PowerCube (Germany) pulmonary function instrument before and after treatment, and the relationship between VDR gene polymorphism and lung function in children with bronchial asthma was analyzed. The difference in comparison of base frequency of rs1544410 locus of VDR gene had no statistical significance between the two groups (P>0.05). The locus CC frequency of rs7975232 of VDR gene in observation group was lower in the observation group than that in the control group (P<0.05); the locus AC and AA frequencies of rs7975232 of VDR gene were higher in the observation group than those in the control group (P<0.05). The level of vitamin D was lower in the observation group than that in the control group (P<0.05); the level of total serum IgE was higher in the observation group than that in the control group (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with bronchial asthma in the observation group were higher after treatment than those before treatment (P<0.05). The correlation research displayed that VDR gene polymorphism was negatively correlated with lung function levels in children with bronchial asthma (P<0.05). The results showed that children with bronchial asthma are often accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with the severity of asthma, so vitamin D should be strengthened to ameliorate the prognosis of children.

Background/aims: Long non-coding RNAs (lncRNAs) have emerged as key players in several biological processes and complex diseases. The risk of type 2 diabetes (T2D) is determined by a combination of environmental factors and genetic susceptibility. The purpose of this study was to identify aberrant lncRNAs involved in T2D pathogenesis., Methods: Microarray analysis was performed using whole blood samples from patients newly diagnosed with T2D and healthy controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. Coding non-coding co-expression (CNC) analysis was performed to construct a co-expression network., Results: We found 55 lncRNAs and 202 mRNAs were differentially expressed in the T2D group compared to the healthy control group. Pathway and GO analyses demonstrated that dysregulated mRNAs were mainly associated with immune regulation, inflammation, and insulin resistance, whereas CNC analysis identified 10 pairs of co-expressed lncRNA-mRNAs in our patient cohort (R > 0.99). Furthermore, expression of the top three upregulated lncRNAs in the T2D group was correlated with measures of glycometabolism (P < 0.05)., Conclusion: This study identified aberrantly expressed lncRNAs and mRNAs in Han Chinese patients with T2D, and demonstrated that dysregulated lncRNAs may have roles in T2D pathogenesis through regulation of inflammation and insulin resistance., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background: Vitamin D status is related to obesity-related metabolic disorders. We investigated the risk of 25-hydroxyvitamin D [25(OH)D] deficiency among different metabolic phenotypes., Methods: This prospective cross-sectional study evaluated 1,292 individuals who were ≥40 years old. Participants were classified as metabolically healthy and normal weight (MHNW), metabolically obese but normal weight (MONW), metabolically healthy but obese (MHO) or metabolically unhealthy and obese (MUO). The demographic and clinical characteristics, as well as plasma 25(OH)D levels, were compared between the 4 groups., Results: The prevalences of MHNW, MONW, MHO and MUO were 32.1%, 19.3%, 17.9% and 30.7%, respectively. Approximately 58.5% participants had vitamin D deficiency, and vitamin D deficiency was more common in the MONW (68.7%) and MUO (73.6%) groups (MHNW, 42.7 and MHO, 50.2%). The MONW and MUO groups had lower 25(OH)D levels (versus the MHNW and the MHO groups). Among vitamin D-deficient participants, the MONW group exhibited increased risks of abdominal obesity (odds ratio [OR]: 3.28, P = 0.005), hypertension (OR: 3.08, P = 0.003) and elevated C-reactive protein (OR: 1.97, P = 0.03). In addition, the MUO group exhibited increased risks of hypertriglyceridemia (OR: 2.57, P = 0.001), insulin resistance (OR: 2.37, P = 0.001) and elevated C-reactive protein level (OR: 2.09, P = 0.003)., Conclusions: Individuals who were MONW and MUO had increased risks of vitamin D deficiency (versus MHNW and MHO), and individuals with vitamin D deficiency had worse metabolic status. Vitamin D supplementation may improve the metabolic status of individuals who are MONW or MUO., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

In this paper, we investigated the effects of Coptis chinensis polysaccharide (CCP) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. CCP was prepared by extraction from Coptis chinensis and oral given to the mice. C57BL/6J mice in each of the 5 groups (eight mice per group) were given either the normal diet (ND) (D12450B, 10% kcal% fat; Research diet, New Brunswick, NJ, USA), HFD (D12451, 45% kcal% fat; Research diet, New Brunswick, NJ, USA), or HFD with CCP of differing hardness (500, 1000, and 2000ppm) for 20 weeks. Mice given an HFD with CCP showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that CCP improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that CCP recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with CCP. CCP increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. CCP stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that CCP has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

In the present study, the expression levels and DNA methylation status of microRNA ( miRNA )-375 in patients with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were analyzed and the role of DNA methylation of miRNA-375 in the pathogenesis of T2DM was investigated. Compared with the miR-375 levels in patients with normal glucose tolerance (NGT; n=53), the samples from patients with IGT (n=44) exhibited downregulation of miR-375 , while those from patients with T2DM (n=54) exhibited upregulation of miR-375 in the plasma. Additionally, the samples from patients with IGT were observed to be hypermethylated compared with those from patients with T2DM and NGT (P=0.042). Analysis of three CpG units (CpG1.2, CpG20 and CpG25.26.27) from 17 CpG sites (between -990 and -1,258 bp, relative to the transcription start site) revealed higher methylation levels in patients with IGT compared with those in patients with NGT (P<0.05). The methylation of two CpG units (CpG1.2 and CpG25.26.27) was higher in patients with IGT than in the patients with T2DM (P<0.05). Thus, the present study demonstrated that the miR-375 promoter was hypermethylated and the levels of miR-375 in the plasma were downregulated in the patients with IGT. DNA hypomethylation may have an important role in the regulation of miR-375 expression and may contribute to the pathogenesis of T2DM.

Recent studies have shown that DNA methylation in the promoter of microRNA-375 (miR-375) downregulates its expression during tumorigenesis. However, it is not known if CpG methylation of the miR-375 promoter also has a role in the pathogenesis of type 2 diabetes mellitus (T2DM). In this study, the expression level and CpG methylation status of miR-375 in patients with T2DM were analyzed. Plasma samples from 100 patients with T2DM and 100 healthy controls with normal glucose tolerance (NGT) were collected. The plasma levels of miR-375 were examined using quantitative polymerase chain reaction (qPCR) and the methylation status of 17 CpG sites in the promoter of the miR-375 were determined using MassARRAY spectrometry. The plasma levels of miR-375 were found to be upregulated in patients with T2DM compared with controls with NGT (P<0.05). Overall, the methylation levels of the miR-375 promoter in patients with T2DM were not significantly different compared with controls with NGT; however, further studies revealed that four of the eight analyzed individual CpG units within the amplicon were significantly hypomethylated in T2DM samples compared with the NGT samples. This study demonstrated for the first time, to the best of our knowledge, that miR-375 is overexpressed in plasma in patients with T2DM, and this may be used as a novel biomarker to distinguish between patients with T2DM and healthy individuals. It was also demonstrated in this study that the miR-375 promoter is hypomethylated, in patients with T2DM, which may regulate the expression of miR-375 and contribute to the pathogenesis of T2DM.

Han population is six times as likely as Kazak population to present with type 2 diabetes mellitus (T2DM) in China. We hypothesize that differential expression and CpG methylation of miR-375 may be an ethnic-related factor that influences the incidence of T2DM. The expression level of miR-375 was examined using real-time PCR on Kazak and Han T2DM plasma samples. Furthermore, the methylation levels of CpG sites of miR-375 promoter were determined by MassARRAY Spectrometry in these samples. The relative expression levels of plasma miR-375 in Kazak T2DM samples are 1, and the relative expression levels of plasma miR-375 in Han T2DM samples are 3. The mean level of miR-375 methylation, calculated from the methylation levels of the CpG sites, was 8.47% for the Kazak T2DM group and 10.38% for the Han T2DM group. Further, five CpG units showed a statistically significant difference between Kazak and Han T2DM samples, and, among them, four were hypomethylated and only one CpG unit showed hypermethylation in Kazak T2DM samples. These findings indicate that the expression levels of plasma miR-375 and its CpG methylation in the promoter region are ethnically different, which may contribute to the different incidence of diabetes observed in Kazak and Han populations.

Background: A number of studies evaluated the association of intracellular adhesion molecule-1 (ICAM-1) K469E (rs5498, A/G) gene polymorphism with diabetic microvascular complications (DMI) including diabetic nephropathy (DN) and diabetic retinopathy (DR) in different populations. However, the results of individual studies remain conflicting., Methods: A comprehensive search was conducted to identify all eligible studies of the above-mentioned associations. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using the fixed or random effect model., Results: Seven studies involving 3411 subjects were included. Overall, the meta-analysis showed a significant association of the A allele with increased risk of DMI susceptibility in a recessive model (OR = 1.37, 95% CI 1.04-1.80, P = 0.02). In the subgroup analysis stratified by ethnicity, significant association was found in Asians but not in Caucasians (OR = 1.78, 95% CI 1.13-2.81, P = 0.01; OR = 1.10, 95% CI 0.79-1.54, P = 0.58, respectively). Moreover, it showed a significant association between the A allele and risk of DN in a recessive model (OR = 1.25, 95% CI 1.02-1.55, P = 0.04)., Conclusions: This meta-analysis suggested that the K469E polymorphism in ICAM-1 gene might affect individual susceptibility to DMI and showed a discrepancy in different ethnicities. Further investigations are needed to validate the association.

The diamond amplifier (DA) is a new device for generating high-current, high-brightness electron beams. Our transmission-mode tests show that, with single-crystal, high-purity diamonds, the peak current density is greater than 400  mA/mm², while its average density can be more than 100  mA/mm². The gain of the primary electrons easily exceeds 200, and is independent of their density within the practical range of DA applications. We observed the electron emission. The maximum emission gain measured was 40, and the bunch charge was 50  pC/0.5  mm². There was a 35% probability of the emission of an electron from the hydrogenated surface in our tests. We identified a mechanism of slow charging of the diamond due to thermal ionization of surface states that cancels the applied field within it. We also demonstrated that a hydrogenated diamond is extremely robust.