More accurate prediction of treatment response than mean apparent diffusion coefficient value in multiple myeloma using whole body MRI histogram analysis.

Aim: To assess baseline histogram parameters from apparent diffusion coefficient (ADC) images in predicting early treatment response in newly diagnosed multiple myeloma (NDMM) patients. Methods: The histogram parameters of lesions in 68 NDMM patients were obtained with the Firevoxel software. The presence of deep response after two cycles of induction was recorded. Results: Some parameters were significantly different between the two groups, for example, ADC 75% in lumbar spine (p = 0.026). No significant difference in mean ADC for any anatomic site was found (all p > 0.05). The combination of ADC 75, ADC 90 and ADC 95% in lumbar spine; ADC skewness and ADC kurtosis in rib achieved a sensitivity of 100% in predicting deep response. Conclusion: Histogram analysis of ADC images can describe NDMM heterogeneity and accurately predict treatment response.

A gold nanoflower based dual mode aptasensor for aflatoxin B1 detection using SERS and fluorescence effect simultaneously.

Aflatoxin B1 (AFB1) is usually the major aflatoxin produced by toxigenic strains and has been identified the most potent natural carcinogen. Here, a SERS/fluorescence dual-mode nanosensor has been designed while gold nanoflowers (AuNFs) was used as substrate for the detection of AFB1. AuNFs exhibited excellent SERS enhancement effect as well as the good fluorescence quenching effect which made the dual signal detection possible. First, the surface of AuNFs was modified with AFB1 aptamer via Au-SH group. Then, the complementary sequence functionalized with Cy5 (the signal molecule) was attached to AuNFs based on the base complementary pairing principle. On this case, Cy5 was close to AuNFs, the SERS intensity was greatly enhanced and the fluorescence intensity was quenched. After incubation with AFB1, the aptamer was preferentially combined to its target AFB1. Thus, the complementary sequence detached from AuNFs which caused the SERS intensity of Cy5 decreased while its fluorescence effect recovered. Then, the quantitative detection was realized with two optical properties. The LOD was calculated to be 0.03 ng/mL. It was a convenient and fast detection method which expanded the application of nanomaterials based multi-signal simultaneous detection.

An ultrasensitive electrochemical sensor for phospholipase C via signal amplification based on breathing ATRP and its application.

Phospholipase C (PLC) has important biological functions in specific cancer types, immune disorders and neurodegeneration. Here, an ultrasensitive electrochemical sensor for PLC was developed via signal amplification based on breathing atom transfer radical polymerization (ATRP). First, phosphatidylethanolamine (PE) was immobilized on the surface of a gold electrode by L-cysteine and cross-linker. Then, PE was specially hydrolyzed by PLC to obtain the phosphate groups and tethered with the ATRP initiator α-bromophenacetic acid (BPAA) by the coordination action of Zr4+. After the breathing ATRP, a large number of electroactive monomers (ferrocenylmethyl methacrylate, FcMMA) were successfully grafted from BPAA. The experimental results indicated that the detection signal of the obtained electrode (sensor) was proportional to the concentration of PLC. The sensor showed a low detection limit of 0.270 U L-1 and a wide linear range of 1-40 U L-1 (R2 = 0.997). Most importantly, the sensor was successfully applied to detect PLC in breast cancer cells (MCF-7, MDA-MB-231) and nontumor cells (MCF-10A). The value obtained by our electrochemical sensor had no obvious difference from that determined by the commercial ELISA kit. These results showed that the fabricated PLC sensor had acceptable potential in clinical applications.

Does the Risk of Embryo Abnormality Increase in PCOS Women? A Secondary Analysis of a Multicenter, Randomized Controlled Trial.

CONTEXT: Some studies have reported the early miscarriage rate is higher in polycystic ovary syndrome (PCOS) women. However, there is a lack of evidence as to whether the risk of embryo abnormalities increases in PCOS women. OBJECTIVE: This work aimed to evaluate the association between PCOS and embryo ploidy. METHODS: A secondary analysis of a multicenter, randomized controlled trial was conducted from July 2017 to June 2018. The original intent was to identify whether preimplantation genetic test for aneuploidy (PGT-A) improves the live birth rate as compared with in vitro fertilization (IVF). From 14 reproductive centers, 190 patients diagnosed with PCOS and 1:1 age-matched non-PCOS patients were chosen from a PGT-A group. A total of 380 patients with 1118 embryos were included in our study. Intervention included women diagnosed with PCOS, and the main outcome measures were embryonic aneuploidy and embryonic mosaic. RESULTS: After adjusting for potential confounders, the rate of embryonic aneuploidy and embryonic mosaic in the PCOS group were comparable with the control group (embryonic aneuploid rate PCOS group: 14.0% vs control group: 18.3%, adjusted OR [95% CI]: 0.78 [0.54, 1.12]; P = .19; embryonic mosaic rate 10.9% vs 10.1%, adjusted OR [95% CI]: 0.91 [0.59, 1.40]; P = .66). We further stratified PCOS women into 4 groups according to phenotype. The rate of aneuploid and mosaic embryos was comparable between each PCOS phenotype and control group. There was still no significant difference of embryonic aneuploid and embryo mosaic rates among the 4 phenotypes. CONCLUSION: The risk of aneuploid and mosaic embryos did not increase in PCOS women. Thus, we suggest that the miscarriage rate arising from abnormal embryonic chromosomes could be similar between PCOS and non-PCOS women.

Accumulation, transportation, and distribution of tetracycline and cadmium in rice.

Co-exposure to heavy metal and antibiotic pollution might result in complexation and synergistic interactions, affecting rice growth and further exacerbating pollutant enrichment. Therefore, our study sought to clarify the influence of different Tetracycline (TC) and Cadmium(Cd) concentration ratios (both alone and combined) on rice growth, pollutant accumulation, and transportation during the tillering stage in hydroponic system. Surprisingly, our findings indicated that the interaction between TC and Cd could alleviate the toxic effects of TC/Cd on aerial rice structures and decrease pollutant burdens during root elongation. In contrast, TC and Cd synergistically promoted the accumulation of TC/Cd in rice roots. However, their interaction increased the accumulation of TC in roots while decreasing the accumulation of Cd when the toxicant doses increased. The strong affinity of rice to Cd promoted its upward transport from the roots, whereas the toxic effects of TC reduced TC transport. Therefore, the combined toxicity of the two pollutants inhibited their upward transport. Additionally, a low concentration of TC promoted the accumulation of Cd in rice mainly in the root tip. Furthermore, a certain dose of TC promoted the upward migration of Cd from the root tip. Laser ablation-inductively coupled plasma mass spectrometry demonstrated that Cd mainly accumulated in the epidermis and stele of the root, whereas Fe mainly accumulated in the epidermis, which inhibited the absorption and accumulation of Cd by the rice roots through the generation of a Fe plaque. Our findings thus provide insights into the effects of TC and Cd co-exposure on rice growth.

Prediction of Early Treatment Response in Multiple Myeloma Using MY-RADS Total Burden Score, ADC, and Fat Fraction From Whole-Body MRI: Impact of Anemia on Predictive Performance.

BACKGROUND. The recently released Myeloma Response Assessment and Diagnosis System (MY-RADS) for multiple myeloma (MM) evaluation using whole-body MRI (WB-MRI) describes the total burden score. However, assessment is confounded by red bone marrow hyperplasia in anemia. OBJECTIVE. The purpose of this study is to assess the utility of the MY-RADS total burden score, ADC, and fat fraction (FF) from WB-MRI in predicting early treatment response in patients with newly diagnosed MM and to compare the utility of these measures between patients with and without anemia. METHODS. This retrospective study included 56 patients (40 men, 16 women; mean age, 57.4 ± 9.6 [SD] years) with newly diagnosed MM who underwent baseline WB-MRI including DWI and modified Dixon sequences. Two radiologists recorded total burden score using MY-RADS and measured the ADC and FF of diffuse and focal disease sites. Mean values across sites were derived. Interobserver agreement was evaluated, and the mean assessments of the readers were used for further analyses. Presence of deep response after four cycles of induction chemotherapy was recorded. Patients were classified as having anemia if their hemoglobin level was less than 100 g/L. The utility of WBMRI parameters in predicting deep response was assessed. RESULTS. A total of 24 of 56 patients showed deep response, and 25 of 56 patients had anemia. Interobserver agreement, which was expressed using intraclass correlation coefficients, ranged from 0.95 to 0.99. Among patients without anemia, those with deep response compared with those without deep response had a lower total burden score (9.0 vs 18.0), a lower ADC (0.79 × 10-3 mm2/s vs 1.08 × 10-3 mm2/s), and a higher FF (0.21 vs 0.10) (all p < .001). The combination of these three parameters (optimal cutoffs: ≤ 15 for total burden score, ≤ 0.84 × 10-3 mm2/s for ADC, and > 0.16 for FF) achieved sensitivity of 93.8%, specificity of 93.3%, and accuracy of 93.5% for predicting deep response. In patients with anemia, none of the three parameters were significantly different between patients with and without deep response (all p > .05), and the combination of parameters achieved sensitivity of 56.3%, specificity of 100.0%, and accuracy of 72.0%. CONCLUSION. Low total burden score, low ADC, and high FF from WB-MRI may predict deep response in patients with MM, although only among those without anemia. CLINICAL IMPACT. WB-MRI findings may help guide determination of prognosis and initial treatment selection in MM.

Aggregation-induced chirality amplification of optically active fluorescent polyurethane and a cyclic dimer in the ground and excited states.

Optically active linear polyurethane and a cyclic dimer were synthesized from 2,7-diisocyanatofluorene and 2,2'-dihydroxy-1,1'-binaphthyl. The circular dichroism (CD) spectral intensity of the polymer was amplified at a higher concentration through aggregate formation, while circularly polarized light (CPL) emission was not enhanced. The cyclic dimer's CPL emission was largely amplified (glum 1.1 × 10-2) due to intermolecular excimer formation through aggregation, while the CD intensity was not affected.

Photo racemization of 2,2'-dihydroxy-1,1'-binaphthyl derivatives.

Photo racemization of 2,2'-dihydroxy-1,1'-binaphthyl (BINOL) and its monomethyl ether, monobutyl ether, and dimethyl ether was studied by means of circularly dichroism spectra, chiral HPLC, and theoretical calculations of rotation energy barriers. Racemization was fastest for BINOL and about one seventh as fast for the monomethyl and monobutyl ethers while it was too slow to be detected for the dimethyl ether under the present conditions.

The prognostic role of the Transducin-like Enhancer of split protein family in lung adenocarcinoma.

BACKGROUND: Lung cancer claims more lives than any other cancer worldwide. Lung adenocarcinoma (LUAD) accounts for approximately 40% of all lung cancers. Members of the Transducin-like Enhancer of split (TLE) protein family repress transcription through multiple mechanisms; however, their prognostic value in LUAD is still unclear. METHODS: A dataset from The Cancer Genome Atlas was used to analyze the relationship between the expression of TLE family members and outcomes of LUAD. The expression of TLE family members in 59 normal and 513 tumor samples in the TCGA dataset was selected. For paired analysis, 57 normal and 57 tumor paired tissues were selected. Gene Ontology (GO) term and Reactome pathway enrichment analyses of the TLE family members were performed. Progression-free survival (PFS) and overall survival (OS) served as endpoints in this study. All statistical analyses were performed with R 3.6.0. RESULTS: The expression levels of TLE family proteins differed between 59 normal and 513 tumor samples. High TLE1 and low TLE2 levels were associated with poor progression-free and OS (all P<0.050). Multivariate analysis demonstrated that high TLE1 expression and low TLE2 expression were independent risk factors for a poor outcome in LUAD. Moreover, the combined expression of these two proteins was a good tool for prognostication. CONCLUSIONS: High TLE1 expression and low TLE2 are independent adverse prognostic factors in LUAD and can serve as prognostic biomarkers.

Optically active covalent organic frameworks and hyperbranched polymers with chirality induced by circularly polarized light.

Axial chirality was induced by circularly polarized light to covalent organic frameworks as well as hyperbranched polymers composed of bezene-1,3,5-triyl core units and oligo(benzene-1,4-diyl) as linker units where variation in induction efficiency was rationally interpreted in terms of internal rotation dynamics studied through CPMAS 13C NMR experiments including CODEX measurements.

A signature of estimate-stromal-immune score-based genes associated with the prognosis of lung adenocarcinoma.

BACKGROUND: Immune and stromal component evaluation is necessary to establish accurate prognostic markers for the prediction of clinical outcomes in lung adenocarcinoma (LUAD). We aimed to develop a gene signature based on the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE)-stromal-immune score in LUAD. METHODS: The transcriptomic profiles of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA), and the immune and stromal scores were derived using the ESTIMATE algorithm. The prognostic signature genes were selected from the differentially expressed genes (DEGs) using the robust partial likelihood-based cox proportional hazards regression method. The negative log-likelihood and the Akaike Information Criterion (AIC) were used to identify the optimal gene signature. The validation was carried out in 2 independent datasets from the Gene Expression Omnibus (GSE68571 and GSE72094). RESULTS: Patients with high ESTIMATE, stromal, and immune scores had better overall survivals (P=0.0035, P=0.066, and P=0.0077). The expression of thirty-seven genes was related to ESTIMATE-stromal-immune score. A risk stratification model was developed based on a gene signature containing CD74, JCHAIN, and PTGDS. The ESTIMATE-stromal-immune risk score was revealed to be a prognostic factor (P=0.009) after multivariate analysis. Four groups were classified based on this risk stratification model, yielding increasing survival outcomes (log-rank test, P=0.0051). This risk stratification model and other clinicopathological factors were combined to generate a nomogram. The calibration curves showed perfect agreement between the nomogram-predicted outcomes and those actually observed. Similar observations were made in 2 independent cohorts. CONCLUSIONS: The gene signature based on the ESTIMATE-stromal-immune score could predict the prognosis of patients with LUAD.

Blue circularly polarized luminescent amorphous molecules with single-handed propeller chirality induced by circularly polarized light irradiation.

Preferred-handed propeller conformation was induced by circularly polarized light irradiation to three amorphous molecules with trigonal symmetry, and the molecules with induced chirality efficiently exhibited blue circularly polarized luminescence. In both chirality induction and luminescence, chirality appeared to be amplified due to intermolecular interactions through π-stacking.

Decreased miR-940 expression can predict a negative prognosis in early-stage nonsmoking female lung adenocarcinoma.

BACKGROUND: Early-stage female lung adenocarcinoma is the most common type of lung cancer encountered in thoracic surgery departments. Tumor-node-metastasis (TNM) staging does not adequately explain a significant stratification phenomenon in the prognosis of patients with stage I lung adenocarcinoma. We aimed to investigate the contributory role of miR-940 in the prognosis prediction. METHODS: We analyzed the microRNA (miRNA) expression level in tumor tissues (high-risk group vs. low-risk group) from 12 non-smoking female patients with stage I lung adenocarcinoma using miRNA array. Bioinformatic analyses of miR-940 were also carried out based on the public database. Then, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) tests of the tissue samples were further validated. And miR-940's function was analyzed and potential target genes were predicted. RESULTS: In all, 24 miRNAs were found to be significantly different between the high-risk group and low-risk group. The expression level of miR-940 was lower in tumor tissue (P=0.011), and the survival rate in the high miR-940 group was higher [hazard ratio (HR) =0.688; P=0.011]. Gene Ontology (GO) analysis showed that the assembly functions of targets regulated by miR-940 were mainly enriched in regulation of myeloid cell differentiation, G1/S transition of mitotic cell cycle, and cellular response to environmental stimulus. miR-940 is involved in transforming growth factor-beta (TGF-beta) signaling pathway; TNF signaling pathway; and estrogen signaling pathway. The number of lung adenocarcinoma cells (A549) was significantly decreased after miR-940 was transfected. Ten epithelial-to-mesenchymal-transition (EMT)-associated genes (MMP9, ZEB1, CDH1, KRT8, KRT18 KET19, TWIST1, VIM, SNAI1, and SNAI2) were found to be significantly related to miR-940. CONCLUSIONS: The present study showed that miR-940 might be a protective factor for positive prognosis in early stage nonsmoking female lung adenocarcinoma, with transforming growth factor-beta (TGF-beta) pathway, TNF pathway, and matrix metalloprotein (MMP9) being potential targets.

Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents.

A novel series of graveolinine derivatives were synthesized and evaluated as potential anti-Alzheimer agents. Compound 5f exhibited the best inhibitory activity for acetylcholinesterase (AChE) and had surprisingly potent inhibitory activity for butyrylcholinesterase (BuChE), with IC50 values of 0.72 µM and 0.16 µM, respectively. The results from Lineweaver-Burk plot and molecular modeling study indicated non-competitive inhibition of AChE by compound 5f. In addition, these derivatives showed potent self-induced ß-amyloid (Aß) aggregation inhibition. Moreover, 5f didn't show obvious toxicity against PC12 and HepG2 cells at 50 µM. Finally, in vivo studies confirmed that 5f significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, these graveolinine derivatives should be thoroughly and systematically studied for the treatment of Alzheimer's disease.

Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1α pathway in high-fat-diet-induced rats and insulin resistant cells.

Objective: Recent studies demonstrate circulating serum spexin levels are reduced in obesity or type 2 diabetes mellitus (T2DM) patients and may play a role in glucose metabolism. The mechanism underlying is not known. In this study, we explore whether spexin has a role in insulin resistance and hepatic glucose metabolism. Methods: The correlation between serum spexin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) was studied in newly diagnosed T2DM patients. After intraperitoneal injection of exogenous spexin for 8 weeks, the effect of spexin on exogenous glucose infusion rates (GIR), and hepatic glucose production (HGP) were assessed by extended hyperinsulinemic-euglycemic clamp in high-fat-diet (HFD)-induced rats. Glucose concentration with CRISPR/Cas9-mediated disruption of spexin expression in HepG2 cells culture was observed. Expression of transcription factors (Forkhead box O1, FoxO1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α) and key enzymes (G-6-Pase and PEPCK) of gluconeogenesis pathway were observed in vitro and in vivo. Results: The serum spexin level was significantly low in newly diagnosed T2DM patients as compared with healthy patients and significantly negatively correlated with the HOMA-IR values. Exogenous spexin treatment resulted in weight loss and decrease of HOMA-IR value in high-fat-diet (HFD)-induced rats. The exogenous glucose infusion rates (GIR) were higher in the HFD + spexin group than that in the HFD group (358 ± 32 vs. 285 ± 24 µmol/kg/min, P < 0.05). Steady-state hepatic glucose production (HGP) was also suppressed by ~50% in the HFD + spexin group as compared with that in the HFD group. Furthermore, spexin inhibited gluconeogenesis in dose-dependent and time-dependent manner in the insulin-resistant cell model. CRISPR/Cas9-mediated knockdown of spexin in HepG2 cells activated gluconeogenesis. Moreover, spexin was shown regulating gluconeogenesis by inhibiting FoxO1/PGC-1α pathway, and key gluconeogenic enzymes, (PEPCK and G-6-Pase) in both HFD-induced rats and insulin-resistant cells. Conclusions: Spexin plays an important role in insulin resistance in HFD-induced rats and insulin-resistant cells. Regulation of the effects of spexin on insulin resistance may hold therapeutic value for metabolic diseases.

EZH2 upregulation by ERα induces proliferation and migration of papillary thyroid carcinoma.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide in recent years. Therefore, novel potential therapeutic targets for PTC are urgently needed. Enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to PRC2, plays important roles in epigenetic silencing and cell cycle regulation. EZH2 overexpression has been found in several malignant tumor tissues, while its expression and function in PTC are largely unknown. METHODS: Sixty-five cases of PTC tissue confirmed by pathology and 30 cases of normal thyroid tissue adjacent to PTC tissue were collected from patients undergoing surgical treatment, between February 2003 and February 2006. We investigated the clinic pathologic significance of EZH2 expression using Realtime-PCR and IHC in 65 human PTC tissues and 30 normal thyroid tissue samples. The EZH2 expression in human PTC cell lines (K1 and W3) and the normal thyroid follicular epithelial cell line Nthy-ori 3-1 was analyzed by Western blotting and Realtime PCR. The expressions of ERα and ERß in cell lines were analyzed by Realtime PCR.The tumor cell biological behavior was evaluated by CCK8 assay, colony formation assay, transwell migration assay and xenograft tumors model. RESULTS: Higher rate of EZH2 expression was found in PTC tissues than in normal thyroid tissues, EZH2 expression is associated with lymph node metastasis and recurrent. Inhibition of EZH2 in PTC cell lines downregulates cellular proliferation and migration. PTC is a disease with high incidence of female and E2-ERα upregulates EZH2 expression. CONCLUSIONS: These results suggest a potential role of EZH2 for the PTC growth and metastasis. As a novel therapy, a pharmacological therapy targeting EZH2 has full potential in treatment of PTC.

Metal-dependent regioselective homocoupling of stannyl- and alkyl-substituted alkynes on group 4 elements. Formation of unsymmetrical titanacyclopentadienes and symmetrical zircona-cyclopentadienes.

Homocoupling of stannyl- and alkyl-substituted alkynes with Cp2TiBu2 gave unsymmetrical titanacyclopentadienes (αß isomers) with >95% regioselectivities, whereas the coupling with Cp2ZrBu2 provided symmetrical zirconacyclopentadienes (αα isomers) with >93% selectivities. This is the first example of metal-dependent regioselective homocoupling of unsymmetrical alkynes on group 4 elements.

Elevated serum neuregulin 4 levels in patients with hyperthyroidism.

OBJECTIVE: Recent studies have shown that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, plays an important role in the prevention of obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD). Considering that thyroid hormone (TH) has profound effects on whole-body energy metabolism, we speculate that circulating Nrg4 levels might be altered in patients with hyperthyroidism. DESIGN AND METHODS: A total of 129 hyperthyroid patients and 100 healthy subjects were recruited. Of them, 39 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum Nrg4 levels were determined using the ELISA method. To further confirm the relationship between TH and Nrg4, C57BL/6 mice were treated with T3 and quantitative real-time PCR was performed to detect Nrg4 gene expression. RESULTS: Serum Nrg4 levels were significantly elevated in hyperthyroid patients as compared with normal controls (3.84 ± 1.63 vs 2.21 ± 1.04 ng/mL, P < 0.001). After achieving euthyroidism by thionamide treatment, serum Nrg4 levels dropped markedly from 3.57 ± 1.26 to 1.94 ± 0.72 ng/ml (P < 0.001). After adjustment for potential confounders, serum Nrg4 levels were independently associated with hyperthyroidism. The upregulation of Nrg4 expression in the livers and white adipose tissues by T3 was further confirmed by animal and cell culture experiments. CONCLUSIONS: Serum Nrg4 levels were increased in patients with hyperthyroidism. The liver and white adipose tissue might be primary sources contributing to elevated serum Nrg4 concentrations.

Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

Triglycerides to high-density lipoprotein cholesterol ratio as a surrogate for nonalcoholic fatty liver disease: a cross-sectional study.

BACKGROUND: Triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been recommended as a surrogate marker for insulin resistance. In the present study, we aimed to investigate the relationship between TG/HDL-C and NAFLD in an apparently healthy population. METHODS: A total of 18,061 subjects who participated in a health checkup program were included. NAFLD was diagnosed by ultrasonography. RESULTS: The prevalence rate of NAFLD was 24.8% in the whole population, and progressively increased across the quartiles of TG/HDL-C (4.9, 14.1, 26.8 and 53.5%, respectively, P <  0.001). After adjustment for confounding factors, TG/HDL-C was independently associated with the risk of NAFLD. Compared with the first quartile of TG/HDL-C (Q1), the odds ratios (95% confidence intervals) for NAFLD in the increasing quartiles (Q2-Q4) were 2.1(1.8-2.6), 3.6 (3.0-4.3) and 9.2(7.6-11.1), respectively. In addition, the area under receiver operator characteristic curve (95% confidence interval) of TG/HDL-C for NAFLD was 0.85 (0.84-0.86) in women and 0.79 (0.78-0.80) in men, significantly higher than that of TG, TC, LDL-C, HDL-C, ALT and AST (P <  0.05). The optimal cutoff point of TG/HDL-C for detection of NAFLD was 0.9 in women (sensitivity = 78.8%, specificity = 77.3%) and 1.4 in men (sensitivity = 70.7%, specificity = 73.5%). CONCLUSIONS: TG/HDL-C is independently associated with NAFLD in apparently healthy individuals and may be used as a surrogate for NAFLD.