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In recent years, the prevalence and incidence of diabetes mellitus (DM) have increased sharply worldwide. In order to evaluate the effect of chromium supplementation on patients with type 2 diabetes, a meta-analysis was conducted by searching the relevant literature. Randomized controlled trials on the effects of chromium supplements on glucose metabolism or lipid profile in patients with type 2 diabetes were retrieved from multiple databases. Literature screening, quality evaluation, and data extraction were conducted according to the inclusion and exclusion criteria, and Review Manager 5.4.0 was used for data analysis. A total of 10 randomized controlled trials involving 509 patients were included, including 269 cases in the experimental group and 240 cases in the placebo control group. Statistical analysis was conducted on the glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) to evaluate the blood glucose and lipid levels. Meta-analysis results showed that the differences between the experimental group and the control group in only one indicator of HbA1c were statistically significant, while there were no statistically significant differences in other indicators. The use of chromium supplements can reduce the glycosylated hemoglobin of type 2 diabetic patients to a certain extent, but it cannot effectively improve the fasting blood glucose and blood lipid levels of type 2 diabetic patients.

Aim The aim of the study was to compare the therapeutic strategies and prognostic factors of patients with primary intestinal diffuse large B-cell lymphoma (PI-DLBCL). Methods A total of 50 PI-DLBCL patients who accepted standard first-line treatment at National Cancer Center in China were included in this retrospective study. Survival analysis was performed to evaluate the prognostic risk factors. Results The 3-year overall survival (OS) and 3-year progression-free survival (PFS) for the entire group were 76.0% and 65.9%, respectively. Univariate analysis showed that B symptom, advanced Lugano stage, elevated LDH status, poor ECOG PS and immunochemotherapy alone were significantly correlated with a poor PFS. Elevated LDH status, poor ECOG PS, advanced Lugano stage, high IPI score and immunochemotherapy alone were significantly correlated with a poor OS. Multivariate analysis revealed that ECOG PS (P= 0.035; HR = 0.233; 95% CI, 0.060-0.905), LDH level (P = 0.010; HR = 0.223; 95% CI, 0.072-0.693) and surgery (P = 0.002; HR = 5.584; 95% CI, 1.883-16.563) were independent prognostic factors for OS. LDH level (P = 0.035; HR = 0.210; 95% CI, 0.049-0.894) and surgery (P = 0.003; HR = 6.410; 95% CI, 1.903-21.593) were independent risk factors for PFS in PI-DLBCL. R-CHOP immunochemotherapy combined surgery treatment was also associated with a lower rate of refractory/relapsed (R/R) disease (P = 0.004). Furthermore, stratified analysis revealed that partial resection or radical resection combined with immunochemotherapy had no significantly difference which affect OS (P = 0.338) and PFS (P = 0.207). Conclusion R-CHOP immunochemotherapy plus surgery was associated with a superior prognosis compared with R-CHOP alone in Chinese PI-DLBCL population.

Doxorubicin (Dox) is a widely used antineoplastic agent that can cause heart failure. Dox cardiotoxicity is closely associated with mitochondrial damage. Mitochondrial fission and mitophagy are quality control mechanisms that normally help maintain a pool of healthy mitochondria. However, unchecked mitochondrial fission and mitophagy may compromise the viability of cardiomyocytes, predisposing them to cell death. Here, we tested this possibility by using Dox-treated H9c2 cardiac myoblast cells expressing either the mitochondria-targeted fluorescent protein MitoDsRed or the novel dual-fluorescent mitophagy reporter mt-Rosella. Dox induced mitochondrial fragmentation as shown by reduced form factor, aspect ratio, and mean mitochondrial size. This effect was abolished by short interference RNA-mediated knockdown of dynamin-related protein 1 (DRP1), a major regulator of fission. Importantly, DRP1 knockdown decreased cell death as indicated by the reduced number of propidium iodide-positive cells and the cleavage of caspase-3 and poly (ADP-ribose) polymerase. Moreover, DRP1-deficient mice were protected from Dox-induced cardiac damage, strongly supporting a role for DRP1-dependent mitochondrial fragmentation in Dox cardiotoxicity. In addition, Dox accelerated mitophagy flux, which was attenuated by DRP1 knockdown, as assessed by the mitophagy reporter mt-Rosella, suggesting the necessity of mitochondrial fragmentation in Dox-induced mitophagy. Knockdown of parkin, a positive regulator of mitophagy, dramatically diminished Dox-induced cell death, whereas overexpression of parkin had the opposite effect. Together, these results suggested that Dox cardiotoxicity was mediated, at least in part, by the increased mitochondrial fragmentation and accelerated mitochondrial degradation by the lysosome. Strategies that limit mitochondrial fission and mitophagy in the physiologic range may help reduce Dox cardiotoxicity.-Catanzaro, M. P., Weiner, A., Kaminaris, A., Li, C., Cai, F., Zhao, F., Kobayashi, S., Kobayashi, T., Huang, Y., Sesaki, H., Liang, Q. Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy.

Background: Graves’ disease (GD) is an autoimmune disease that affects more women than men. In our previous study, a potent bioactive androgen, 5α-dihydrotestosterone (DHT) showed a protective effe...

The association between subclinical hypothyroidism (SCH) and metabolic syndrome (MetS) has been widely discussed. This study aimed to conduct an update and comprehensive meta-analysis to reveal the risk of MetS and its components in SCH. PubMed, Embase and ISI Web of Knowledge were searched to identify relevant studies through February 20th, 2020. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Both fixed-effects and random-effects models were used. In total, 18 articles (19 studies) incorporating 79,727 participants were included. The pooled OR for MetS comparing subjects with SCH with euthyroid subjects was 1.28 (95% CI: 1.19 to 1.39, p = 0.04, I2 = 40%). Subgroup analysis results showed significant associations of SCH and MetS in the adult subgroup (OR = 1.28, 95% CI: 1.18-1.40), Asian population subgroup (OR = 1.30, 95% CI: 1.19-1.42) and cross-sectional study design subgroup (OR = 1.31, 95% CI: 1.16-1.47). Significant associations of SCH and MetS also existed in all MetS definition criteria subgroups except the Chinese Diabetes Society (CDS) subgroup. SCH was correlated with MetS and was not affected by the subgroup analysis stratified by the proportion of females in the total population, the TSH cutoff value in SCH diagnostic criteria, or the adjustment for confounding factors. SCH was identified to be associated with an increased risk of obesity, hypertension, high triglyceride (TG) levels and low high-density lipoprotein cholesterol (HDL-C) levels. In conclusion, SCH is significantly associated with an increased risk of MetS and four out of five components of MetS.

Background Recently, the relationship between thyroid hormones (THs) across the euthyroid ranges and metabolic syndrome (MetS) has been widely discussed. This study aimed to present specific cutoff values of THs to assess the association between THs and MetS in a euthyroid cohort. Methods Data of 2694 subjects, aged 18–80 years, who attended health examination in Xi’an Electric Power Central Hospital from April 2011 to December 2015 were collected and analyzed. The first cohort enrolled 929 participants (followed up by 2221 person-years totally) to assess correlations between serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4) levels and MetS. The second cohort included 698 participants (followed up by 1709 person-years totally) to evaluate relationships between serum free triiodothyronine (FT3), free thyroxine (FT4) levels and MetS. MetS was defined according to the criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) scientific statements of 2009. Euthyroidism was defined as serum TSH, FT3 and FT4 levels within the reference ranges without taking any thyroid medication. Results The cutoff values for TSH, T3, T4, FT3 and FT4 were 2.0mIU/L, 1.9 nmol/L, 117 nmol/L, 4.3 pmol/L and 16 pmol/L, respectively. Participants were categorized into two groups according to cutoff values: the lower-THs group and the higher-THs group. There was no significant difference in the risk of MetS between two groups in TSH, T3, T4 and FT3. The incidence of MetS was significantly higher in lower-FT4 group than higher-FT4 group (1.00 vs 0.622 (0.458, 0.846), P = 0.002). The lower-FT4/higher-TSH group had the highest hazard ratios of MetS. (2.131vs 1.0 (1.380,3.291), P = 0.006). Conclusions Lower normal FT4 (FT4 ≤ 16.0 pmol/L) is an independent risk factor for MetS, and lower normal thyroid function (TSH > 2.0 mIU/L and FT4 ≤ 16.0 pmol/L) is associated with a higher risk of developing MetS.

To identify candidate neuroimaging and genetic biomarkers for Alzheimer's disease (AD) and other brain disorders, especially for little-investigated brain diseases, we advocate a data-driven approach which incorporates an adaptive classifier ensemble model acquired by integrating Convolutional Neural Network (CNN) and Ensemble Learning (EL) with Genetic Algorithm (GA), i.e., the CNN-EL-GA method, into Genome-Wide Association Studies (GWAS).Above all, a large number of CNN models as base classifiers were trained using coronal, sagittal, or transverse magnetic resonance imaging slices, respectively, and the CNN models with strong discriminability were then selected to build a single classifier ensemble with the GA for classifying AD, with the help of the CNN-EL-GA method. While the acquired classifier ensemble exhibited the highest generalization capability, the points of intersection were determined with the most discriminative coronal, sagittal, and transverse slices. Finally, we conducted GWAS on the genotype data and the phenotypes, i.e., the gray matter volumes of the top ten most discriminative brain regions, which contained the ten most points of intersection.Six genes of PCDH11X/Y, TPTE2, LOC107985902, MUC16 and LINC01621 as well as Single-Nucleotide Polymorphisms, e.g., rs36088804, rs34640393, rs2451078, rs10496214, rs17016520, rs2591597, rs9352767 and rs5941380, were identified.This approach overcomes the limitations associated with the impact of subjective factors and dependence on prior knowledge while adaptively achieving more robust and effective candidate biomarkers in a data-driven way.The approach is promising to facilitate discovering effective candidate genetic biomarkers for brain disorders, as well as to help improve the effectiveness of identified candidate neuroimaging biomarkers for brain diseases.

A well-designed heteroleptic ruthenium(ii) polypyridyl complex demonstrated stable target-specific in vitro Golgi apparatus imaging abilities in HeLa cell lines. After utilizing photodynamic therapy via UV excitation, the Ru-SL complex could be triggered to generate singlet oxygen (1O2) and red fluorescence signals. 1O2 was highly cytotoxic and could induce DNA damage and the disappearance of the Golgi apparatus. The red fluorescence signals disappeared gradually, suggesting that the live or dead state of the cells can be estimated from the fluorescence signal intensity.

Context: Patients with diabetes are susceptible to heart failure. Defective mitochondria can cause cardiac damage. Mitochondrial autophagy or mitophagy is a quality control mechanism that eliminates dysfunctional mitochondria through lysosome degradation. Mitophagy is essential for maintaining a pool of healthy mitochondria for normal cardiac function. However, the effect of diabetes on the functional status of cardiac mitophagy remains unclear. Objective: To determine and compare cardiac mitophagy flux between diabetic and nondiabetic mice. Methods: Using a novel dual fluorescent mitophagy reporter termed mt-Rosella, we labeled and traced mitochondrial fragments that are sequestered by the autophagosome and delivered to and degraded in the lysosome. Results: Mitophagic activity was reduced in high-glucose–treated cardiomyocytes and in the heart tissue of type 1 diabetic mice. Conclusions: Mitophagy was impaired in the heart of diabetic mice, suggesting that restoring or accelerating mitophagy flux may be a useful strategy to reduce cardiac injury caused by diabetes.

Background: Programmed cell death protein 1 (PD1) inhibitors have revolutionized cancer therapy, yet many patients fail to respond. Thus, the identification of accurate predictive biomarkers of therapy response will improve the clinical benefit of anti-PD1 therapy. Method: We assessed the baseline serological autoantibody (AAb) profile against ~2300 proteins in 10 samples and ~4600 proteins in 35 samples with alveolar soft part sarcoma (ASPS), non-small-cell lung cancer (NSCLC) and lymphoma using Nucleic Acid Programmable Protein Arrays (NAPPA). 23 selected potential AAb biomarkers were verified using simple, affordable and rapid enzyme linked immune sorbent assay (ELISA) technology with baseline plasma samples from 12 ASPS, 16 NSCLC and 46 lymphoma patients. SIX2 and EIF4E2 AAbs were further validated in independent cohorts of 17 NSCLC and 43 lymphoma patients, respectively, using ELISA. The IgG subtypes in response to therapy were also investigated. Results: Distinct AAb profiles between ASPS, NSCLC and lymphoma were observed. In ASPS, the production of P53 and PD1 AAbs were significantly increased in non-responders (p=0.037). In NSCLC, the SIX2 AAb was predictive of response with area under the curve (AUC) of 0.87, 0.85 and 0.90 at 3 months, 4.5 months, 6 months evaluation time points, respectively. In the validation cohort, the SIX2 AAb was consistently up-regulated in non-responders (p=0.024). For lymphoma, the EIF4E2 AAb correlated with a favorable response with AUCs of 0.68, 0.70, and 0.70 at 3 months, 4.5 months, and 6 months, respectively. In the validation cohort, the AUCs were 0.74, 0.75 and 0.66 at 3 months, 4.5 months, and 6 months, respectively. The PD1 and PD-L1 IgG2 AAbs were highly produced in ~20% of lymphoma responders. Furthermore, bioinformatics analysis revealed antigen functions of these AAb biomarkers. Conclusion: This study provides the first evidence that AAb biomarkers selected using high-throughput protein microarrays can predict anti-PD1 therapeutic response and guide anti-PD1 therapy.

Autoimmune thyroid disease (AITD) is characterized by a loss of self-tolerance to thyroid antigen. Tregs, whose proportions are controversial among CD4+ T cell from AITD patients (AITDs), are crucial in immune tolerance. Considering that drugs might affect Treg levels, we assumed that the differences originated from different treatment statuses. Thus, we performed a meta-analysis to explore proportions of Tregs in untreated and treated AITDs. PubMed, Embase and ISI Web of Knowledge were searched for relevant studies. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Subgroup analysis based on different diseases and cell surface markers was performed. Egger linear regression analysis was used to assess publication bias. Approximately 1,100 AITDs and healthy controls (HCs) from fourteen studies were included. Proportions of Tregs among CD4+ T cells of untreated AITDs were significantly lower than those in HCs (p = 0.002), but were not in treated patients (p = 0.40). Subgroup analysis revealed lower proportions of Tregs in untreated Graves' disease patients (GDs) (p = 0.001) but did not show obvious differences in untreated Hashimoto's thyroiditis patients (HTs) (p = 0.62). Furthermore, proportions of circulating FoxP3+ Tregs were reduced in untreated GDs (p < 0.00001) and HTs (p = 0.04). No publication bias was found. In this first meta-analysis exploring proportions of circulating Tregs among CD4+ T cells of AITDs with different treatment statuses, we found that Tregs potentially contribute to the pathogenesis of AITD but function differently in GD and HT. Remarkably, FoxP3+ Tregs, which were decreased in both diseases, might be promising targets for novel therapies.

Hyperglycemia is an independent risk factor for diabetic heart failure. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Previous studies have shown an association between lysosomal dysfunction and diabetic heart injury. The present study examined if mimicking hyperglycemia in cultured cardiomyocytes could induce lysosomal membrane permeabilization (LMP), leading to the release of lysosome enzymes and subsequent cell death. High glucose (HG) reduced the number of lysosomes with acidic pH as shown by a fluorescent pH indicator. Also, HG induced lysosomal membrane injury as shown by an accumulation of Galectin3-RFP puncta, which was accompanied by the leakage of cathepsin D (CTSD), an aspartic protease that normally resides within the lysosomal lumen. Furthermore, CTSD expression was increased in HG-cultured cardiomyocytes and in the hearts of 2 mouse models of type 1 diabetes. Either CTSD knockdown with siRNA or inhibition of CTSD activity by pepstatin A markedly diminished HG-induced cardiomyocyte death, while CTSD overexpression exaggerated HG-induced cell death. Together, these results suggested that HG increased CTSD expression, induced LMP and triggered CTSD release from the lysosomes, which collectively contributed to HG-induced cardiomyocyte injury.

Purpose To investigate the importance of dietary selenium (Se) for hyperthyroidism. Methods We performed a more in-depth analysis of a large cross-sectional study of 6152 participants from two counties within the Shaanxi Province, China. These counties are characterized by different habitual Se intake. We investigated the effects of a different dietary Se supply (0.02, 0.18, 0.6, or 2.0 ppm Se) on disease development in a mouse model of Graves disease (GD). Results The cross-sectional study revealed a comparable prevalence of hyperthyroidism, irrespective of Se intake, in both counties. However, an unexpected sex-specific difference was noted, and Se deficiency might constitute a risk factor for hyperthyroidism, especially in males. In a mouse model, pathological thyroid morphology was affected, and greater Se intake exerted some protecting effects on the pathological distortion. Circulating thyroid hormone levels, malondialdehyde concentrations, total antioxidant capacity, and the titer of GD-causing TSH receptor autoantibodies were not affected by Se. Expression analysis of the transcripts in the spleen indicated regulatory effects on genes implicated in the immune response, erythropoiesis, and oxygen status. However, the humoral immune response, including the CD4/CD8 or T-helper 1/T-helper 2 cell ratio and the concentration of regulatory T cells, was similar between the experimental groups, despite the difference in Se intake. Conclusions Our data have highlighted a sexual dimorphism for the interaction of Se and thyroid disease risk in humans, with indications of a local protective effects of Se on thyroid gland integrity, which appears not to be reflected in the circulating biomarkers tested.

To review the relative researches about mechanical stimulation of stem cells differentiation in stem cells microenvironment in vitro.The recent related literature about stem cells differentiation in vitro was reviewed and summarized.The mechanical loads (including shear stress, mechanical strain, and stress), substrates stiffness, substrates nanotopography, and cell shape were the 4 important aspects of mechanical factors regulating stem cells differentiation. The mechanical stimulation can simulate the in vivo microenvironment, which can alter the size, shape, alignment, and differentiation state of stem cells, can change the expression of their differentiation markers, and can affect the lineage commitment of stem cells.Mechanical stimulation play an important role in regulating stem cells differentiation and cells morphology in addition to chemical and biological factors.