Serum Lipidomic Analysis Reveals Biomarkers and Metabolic Pathways of Thyroid Dysfunction.

Abnormal thyroid hormone secretion is the most important feature of hypothyroidism and plays an important role in lipid metabolism. However, their connection has not been clearly established. This study aimed to identify the serum biomarkers and metabolic pathways associated with hyperthyroidism and hypothyroidism. The study enrolled discovery and validation sets of 175 and 300 participants, respectively, to identify and validate the serum biomarkers of hyperthyroidism and hypothyroidism via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry lipidomics through univariate and multivariate analyses. Eight and six biomarkers were identified for hyperthyroidism and hypothyroidism, respectively. Spearman correlation analysis was used to assess the correlation between the biomarkers and thyroid dysfunction indicators; subsequently, metabolic pathway and network analyses were performed for these biomarkers. Most biomarkers exhibited significant correlation with thyroid dysfunction indicators, mainly being enriched in the glycerophospholipid (GPL) metabolism. The diagnostic accuracies of the biomarkers and biomarker panels were assessed via receiver operating characteristic curve analysis. All the biomarkers demonstrated good diagnostic performance, and the hyperthyroidism and hypothyroidism biomarker panels reached an area under the curve value of 1.000. The results were validated using the validation set. Therefore, our findings revealed that thyroid dysfunction primarily affects the human metabolism via the GPL metabolism, thus providing a theoretical basis for the clinical prevention and control of thyroid dysfunction.

Clinical diagnostic performance of a fully automated TSI immunoassay vs. that of an automated anti­TSHR immunoassay for Graves' disease: a Chinese multicenter study.

BACKGROUND: Both thyroid-stimulating immunoglobulins immunoassay (TSI IA) and thyrotrophin receptor antibody immunoassay (TRAb IA) are commonly used for the diagnosis of Graves' disease (GD). The aim of the present study was to compare the clinical diagnostic performance of these two methods. METHODS: Sera were obtained from 1103 subjects presenting a variety of clinical conditions from three centers: 100 subjects with untreated GD, 200 with treated GD, 62 with autoimmune thyroid disease(AIT), 216 with other thyroid diseases (OTHER-T), 214 with non-thyroid autoimmune diseases (NTAD), 191 with other diseases (OD), and 120 healthy subjects (HS). Both TSI and TRAb IAs were performed for all 1013 serum samples. Bioassay was performed for 86 samples whose TSI results were inconsistent the TRAb assay results. RESULTS: Comparing untreated GD patients with the control groups (AIT, NTAD, OTHER-T, OD, and HS) resulted in an area under the curve (AUC) of 0.992 for the TSI IA and 0.989 for the TRAb IA with no statistically significant difference observed between these AUC values (P = 0.2733). The best TSI CDP (clinical decision point) value was 0.42 IU/L. The differences in sensitivity (100% vs. 95%, P = 0.7991) and specificity (97.1% vs. 97.6%, P = 0.9426) between the TSI and TRAb IA were not statistically significant. TSI IA had a higher agreement with the TSI bioassay than TRAb IA. CONCLUSION: The clinical diagnostic performance of the TSI IA for diagnosing Graves' disease was very similar to that of the TRAb IA. TSI IA can be used to diagnose GD in the Chinese.

The protective effect of iodide intake adjustment and 1,25(OH)2D3 supplementation in rat offspring following excess iodide intake.

BACKGROUND: In this study, we aimed to investigate the effect of iodide intake adjustment, 1,25(OH)2D3 supplementation, or both, on the thyroid gland of rat offspring. METHODS: The offspring of female rats administered 100 times the normal dose of iodide (100 HI; 750 µg/d) during pregnancy and lactation were divided into four different treatment groups. They were either having their iodide intake adjusted from 100 HI to normal iodide intake (7.5 µg/day) or supplemented with 25-hydroxy vitamin D3 [1,25(OH)2D3; 5 µg·kg-1·day-1], or both, for 4 weeks. Thyroid sodium pertechnetate (Na99mTcO4) uptake percentages were measured using single-photon emission computed tomography, while serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and vitamin D3 (VD3) were monitored using enzyme-linked immunosorbent assay. The messenger ribonucleic acid expression of interleukin (IL)-17A, interferon gamma (IFN-γ), and IL-10 in the thyroid gland was measured using quantitative real-time polymerase chain reaction, while the protein expression of thyroid-hormone-receptor α1 (TRα1) and thyroid-hormone-receptor ß1 (TRß1) in the thyroid gland was detected using Western blotting. Haematoxylin and eosin (H & E) and immunofluorescence staining were also used to assess thyroid follicular structure and lymphocytic infiltration in the thyroid glands. RESULTS: The immunofluorescence staining showed CD4+ co-localized with TRß1 or the vitamin D receptor in thyroid gland cells of rats that were continuously treated with 100 HI. Following iodide adjustment, 1,25(OH)2D3 supplementation, or both, an increase in serum levels of FT3, free thyroxine, and VD3, protein expression of TRα1 and TRß1 in the thyroid gland cells, and Na99mTcO4 thyroid uptake percentages was observed. The mRNA expression levels of IL-17A and IFN-γ, decreased, while the mRNA expression levels of IL-10 increased in the thyroid cells of each treatment group, except the group with continuous 100 HI intake. CONCLUSION: Iodide adjustment, 1,25(OH)2D3 supplementation, or both may increase the serum levels of FT3, FT4, and VD3, as well as the protein expression levels of TRα1 and TRß1, in thyroid cells. In addition, iodide adjustment, 1,25(OH)2D3 supplementation, or both, may potentially reverse the imbalance in pro-inflammatory and anti-inflammatory cytokines (IL-17A, IFN-γ, and IL-10) caused by 100 HI, which may be beneficial in improving Na99mTcO4 thyroid uptake percentages.

Percutaneous computed tomography-guided permanent 125I implantation as therapy for pulmonary metastasis.

PURPOSE: To evaluate intermediate-term outcomes after computed tomography (CT)-guided radioactive 125I seed implantation (CTRISI), and to determine prognostic variables associated with outcomes in patients with pulmonary metastases. MATERIAL AND METHODS: Thoracic surgeons evaluated and performed implantation of 125I radioactive seeds under CT guidance or combined with surgical resection. Patients were monitored in the thoracic surgery clinic for recurrence and survival. RESULTS: Fifty patients (31 men, 19 women; median age, 59 years; range, 16-85) underwent CTRISI. The primary cancer was colorectal in 10 (20%), malignant fibrous histiocytoma in 8 (16%), sarcoma in 5 (10%), renal in 4 (8%), and other in 22 (44%) patients. CTRISI was the sole treatment in 45 patients (90%) and was combined with surgical resection in 5 patients (10%). The actuarial D90 of implanted 125I seeds ranged from 90 to 160 Gy (median, 120 Gy). No procedurally related deaths occurred. At a median follow-up of 41.5 months (range, 7-74 months), 6 patients were alive. The median survival time was 42.1 months (95% confidence interval: 26.5-53.4), and the estimated 1-, 3-, and 5-year overall survival rates were 88.0%, 58.0%, and 26.7%, respectively. Lesion size was an important prognostic variable associated with overall and progression-free survival (p < 0.05). CONCLUSIONS: CTRISI is safe in this group of patients with pulmonary metastases and provides reasonable results. Surgical resection remains the standard for resectable cases, but CTRISI offers an alternative for selected patients or may be used as a feasible approach in combination with surgical resection for selected patients.

125I inhibited the NSCLC both in vivo and in vitro.

Lung cancer is the main reason of cancer-linked death all over the world. Non-small cell lung cancer (NSCLC) patients always have an extremely poor prognosis. It is urgent to find novel treating methods. It was previously showed that 125I brachytherapy had been applied to the lung cancer treatment. However, fundamental researches are limited. In the present study, we first explored the mechanism by which 125I radiation induced arrest or apoptosis of the cell cycle and relevant protein expression. Furthermore, we explored its effect on the invasion. We found that 125I significantly induced cell apoptosis through mitochondrial pathway, triggered S phase arrest via regulating cyclinA2, p21 and CDK6 expressions. Meanwhile, 125I could inhibit invasion of NSCLC cells by altering the expression level of vimentin, N-cadherin and MMP-9. Furthermore, we confirmed the effects of 125I on NSCLC cell growth in vivo. The results indicated that 125I obviously inhibited the tumor growth. Thus, we determined that 125I brachytherapy remarkably restrained NSCLC cellular growth and intrusion by inducing apoptosis, S phase arrest and corresponding protein expression.

The application of technetium-99m-red blood cell scintigraphy in the diagnosis of orbital cavernous hemangioma.

OBJECTIVE: The purpose of this study was to evaluate the clinical value of technetium-99m-red blood cell (Tc-RBC) scintigraphy in the diagnosis of orbital cavernous hemangioma (OCH). PATIENTS AND METHODS: Forty-one patients with pathologically confirmed orbital mass, of which 10 were OCH, underwent Tc-RBC scintigraphy in this study. The scanning procedure included an initial perfusion phase, followed by an early and a delayed blood pool phase. All patients underwent ultrasonography and computed tomography (CT), and 15 patients also underwent MRI. RESULTS: All 10 OCH patients had no abnormal findings on radionuclide angiographic images and early blood pool phase, but increased activity was found during delayed blood pool phase. All other non-OCH orbital tumours did not have this tracer pattern. The radioactivity ratios of tumour to nontumour were 2.96±0.05 and 1.14±0.25, respectively, which had a statistically significant difference (t=15.18, P<0.001). Although nine of 10 OCH patients were diagnosed correctly with one false-positive case using ultrasound, both CT and MRI could not provide a definitive diagnosis. CONCLUSION: Tc-RBC scintigraphy is a reliable and useful procedure for the diagnosis of OCH. It may be considered as one of the routine clinical screening tools for the diagnosis of OCH and as a complement investigation to ultrasonography and CT.

Implantation of computed tomography-guided Iodine-125 seeds in combination with chemotherapy for the treatment of stage III non-small cell lung cancer.

PURPOSE: We investigated the role of computed tomography (CT)-guided Iodine-125 (125I) seed implantation in combination with chemotherapy for the treatment of stage III non-small cell lung carcinoma (NSCLC). MATERIAL AND METHODS: The data from 182 patients with stage III NSCLC who were treated with radioactive 125I seed implantation between June 2002 and June 2009, and who received sequential platinum-based combination chemotherapy using the most common combination of platinum and gemcitabine, were retrospectively reviewed. The 182 patients received a prescribed dose of 110.0 Gy, with a median radioactivity of 0.70 mCi (range, 0.64-0.78 mCi, 2.37-3.26 × 107 Bq). The median number of 125I seeds was 38 pellets (range, 6-105 pellets). The median post-operation dose covering 100% of the target volume (D100) was 94.5 Gy (range, 54.6-125.5 Gy). The median D90 was 143.0 Gy (range, 121.6-184.0). RESULTS: The 1-, 3-, and 5-year overall survival rates were 83.35%, 25.57%, and 11.34%, respectively; the median survival time was 24.76 months. At 1, 3, and 5 years, the local control rates were 92.01%, 86.51%, and 76.45%, respectively; the median local control time was 25.28 months. For patients with stage IIIA and IIIB NSCLC, the median survival times were 26.67 and 24.59 months, respectively (p = 0.2). Pre-treatment hemoglobin level, tumor volume, and postoperative D100 were significantly associated with survival. A total of 24 patients experienced pneumothorax (incidence rate, 13.20%), and 17 patients experienced hemothorax (incidence rate, 5.0%). CONCLUSIONS: CT-guided 125I seed implantation combined with chemotherapy is an effective, minimally invasive method for the treatment of stage III NSCLC. Furthermore, hemoglobin levels before treatment, D100, and the maximum diameter of the tumor may be prognostic factors in patients with NSCLC treated sequentially with radiotherapy and chemotherapy.

Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells.

PURPOSE: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. MATERIALS AND METHODS: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. RESULTS: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. CONCLUSIONS: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.

Deguelin inhibits the migration and invasion of lung cancer A549 and H460 cells via regulating actin cytoskeleton rearrangement.

Deguelin, the main components from Mundulea sericea, was reported to suppress the growth of various cancer cells. However, the effect of Deguelin on tumor cell invasion and metastasis and its mechanism still unclear so far. In this study, we investigated the effects of Deguelin on the cell invasion in human lung cancer A549 and H460 cells. Our results demonstrate that Deguelin can significantly inhibited cell proliferation, cell migration and cell invasion. Moreover, Deguelin could also affected reorganization of the actin cytoskeleton and decreased filopodia and lamellipodia formation. Furthermore, deguelin-treated tumors showed decreased the tumor metastasis related genes such as CD44, MMP2 and MMP9 at protein and mRNA levels and the content of CEA, SCC, NSE, CYFAR21-1. In addition, Deguelin down-regulated protein expression of Rac1 and Rock1, which are impotent in actin cytoskeleton rearrangements and cell motility. Together, our results suggest that Deguelin inhibit tumor growth and metastasis of lung cancer cells and might be a candidate compound for curing lung cancer.

[The application of noninvasive urodynamics in early detection of diabetic cystopathy].

OBJECTIVE: To evaluate the early detection of diabetic cystopathy (DCP) with the technology of noninvasive urodynamics. METHODS: 70 patients with type 2 diabetes mellitus (DM) and 30 normal control subjects were checked with the technology of noninvasive urodynamics. Based on their disease course of less or more than 5 years, the DM patients were divided into two groups. Maximal flow rate, average flow rate, the volume leading to first bladder sensation and residual urine volume were measured by using noninvasive urodynamic technology. RESULTS: Among the 70 DM patients, 34 were detected to have bladder residual urine, so the DCP detection rate was 48.6%. In the patients with DCP, the average residual urine volume was 7-139 ml (30.1 +/- 27.1) ml, while there was no residual urine in the normal control group. As compared with the normal control group, maximal flow rate and average flow rate were decreased in all the patients with DM and those with DCP (P < 0.01). After follow up of the disease, the patients with a course of more than five years of disease control had even lower maximal flow rate and average flow rate. CONCLUSION: Maximal flow rate decrease and bladder residual urine detected with the technology of noninvasive urodynamics may be widely used in early detection and early diagnosis of DCP.