Interaction of Ibuprofen with Partially Unfolded Bovine Serum Albumin in the Presence of Ionic Micelles and Oligosaccharides at Different λex and pH: A Spectroscopic Analysis.

The interaction between the plasma protein bovine serum albumin (BSA) and the drug ibuprofen (IBU) has been investigated at three different pH values (7.4, 6.5, and 8.0) in the presence of oligosaccharides and surfactants. The interaction analysis of BSA with oligosaccharides and surfactants has also been studied in the absence of the drug ibuprofen. The results obtained give convenient and efficient access to understand the mechanism of binding of ibuprofen to BSA, and the major forces involved are found to be hydrophobic forces, hydrogen bonding and ionic interactions. In addition to that, the formation of inclusion complexes of ibuprofen with oligosaccharides (ß-CD and 2-HP-ß-CD) has been observed, which has depicted that due to the hydrophobic nature of ibuprofen, it becomes more soluble in the presence of oligosaccharides, but due to the larger size of the inclusion complexes, these could not be able to access the hydrophobic pocket of BSA where tryptophan-212 (Trp-212) resides. The binding interaction between BSA and ibuprofen is observed in the presence of surfactants (SDS and CTAB), which partially unfold the protein. Non-radiative fluorescence resonance energy transfer (FRET) from Trp and Tyr residues of BSA in the presence of an anionic surfactant SDS to ibuprofen has depicted that there is a possibility of drug binding even in the partially unfolded state of BSA protein. Furthermore, the distance between the protein and the drug has been calculated from the FRET efficiency, which gives a comprehensive overview of ibuprofen binding to BSA even in its partially denatured state. The hydrophobic drug binding to the partially unfolded serum albumin protein (BSA) supports the "necklace and bead structures" model and opens up a new direction of drug loading and delivery system, which will have critical therapeutic applications in the efficient delivery of pharmacologically prominent drugs.

Radioprotective effect of vitamin E on salivary glands after radioiodine therapy for differentiated thyroid cancer: a randomized-controlled trial.

OBJECTIVES: This study aimed to examine the radioprotective effect of vitamin E on salivary glands after radioactive iodine (I) therapy in patients with differentiated thyroid cancer. PATIENTS AND METHODS: Eighty-two patients with differentiated thyroid cancer were enrolled in this study. They were divided randomly into four groups (control group: 22 cases, group A: 23 cases, group B: 22 cases, and group C: 15 cases) before postsurgical ablation therapy with 100 mCi I. The patients in groups A, B, and C received vitamin E 100, 200, and 300 mg/day orally, respectively, for a duration of 1 week before to 4 weeks after I therapy. Salivary gland function was assessed using salivary gland scintigraphy immediately before and 6 months after I therapy. Uptake fraction (UF), uptake index (UI), excretion fraction (EF), and excretion ratio (ER) of each salivary gland were measured and compared. RESULTS: On comparison between before and after I therapy in the control group, there was a significant decrease in UF of both right and left parotid glands (all P<0.01). In group A, a significant increase in EF of the right parotid gland (P<0.01) and UI of the right submandibular gland (P<0.05) was found. In group B, there was a significant increase in UI of the right parotid gland and both submandibular glands (all P<0.01). In group C, there was a significant increase in UF of the left parotid gland (P<0.05) and the right submandibular gland (P<0.01). Also, there was a statistical increase in UI in both submandibular glands (all P<0.01). However, on comparing the changes in the post-I therapy salivary scintigraphy parameters among the four groups, there was a significant difference in ΔUI of the right parotid gland (P<0.05) and both submandibular glands (all P<0.01), as well as ΔER of the left parotid gland (P<0.05) and ΔUF of the left submandibular gland (P<0.05). CONCLUSION: Vitamin E exerts significant protective effects on the parotid and submandibular glands after I therapy.

Effects of first radioiodine ablation on functions of salivary glands in patients with differentiated thyroid cancer.

The aim of this study was to evaluate the effects of the first radioactive iodine (I) therapy on functions of salivary glands in patients with differentiated thyroid carcinoma (DTC).There were 36 consented patients with DTC enrolled in this study, who received 3.7 GBq (100mCi) I for ablation after total thyroidectomy. Salivary gland function was assessed using salivary gland scintigraphy in two phases, one 4 hours before and the other 6 months after I therapy (both under thyrotropin stimulation condition). Quantitative parameters including uptake fraction (UF), uptake index (UI), excretion fraction (EF), and excretion ratio (ER) were measured and compared. Blood parameters were also compared. Associations between sex and outcome of the first I therapy as well as individual salivary gland function were measured. Wilcoxon Signed Rank Sum test and χ test were used for statistical analysis.When compared between pre-ablation and post-ablation, UF of bilateral parotid and submandibular glands were significantly increased (all P < .01). UI of both submandibular glands were significantly increased (P < .05). This seemingly increased uptake function after the first I therapy was actually compensatory mechanism of salivary gland, which indicated a possible intermediate state after radiation. But salivary glands' secretory function had not changed significantly except for left submandibular gland; we demonstrated that only left submandibular gland showed significantly decreased ER (P < .05). Thyroglobulin and thyroglobulin antibody significantly decreased after I therapy (P < .05). There were no sex differences on therapeutic outcome and salivary gland dysfunctions after the first I therapy. Salivary gland of both males and females could be affected by I therapy.The first I ablative therapy may impair the salivary uptake and secretory function of patients with DTC. There was no association between sex and salivary gland dysfunction.

Ultrasound-guided core needle biopsy for differential diagnosis of thyroid nodules: A systematic review and meta-analysis.

Ultrasound-guided core needle biopsy (US-CNB) of thyroid nodules is a relatively new technique used in surgical workup. However, no systematic review of this method has yet been performed. In the present meta-analysis, literature databases consisting of Cochrane Library, Medline, Embase, Scopus and Google Scholar were searched. Following eligibility assessments of the studies, quality appraisals were performed on the included studies using the Quality Assessment Tool for Diagnostic Accuracy Studies-2 method. The data were systematically analyzed by using Review Manager (version 5.3) and Meta-Disc (version 1.4). Eight investigations were included, and the study qualities were good. There were 1,621 nodules included in the final meta-analysis. The summary estimated that US-CNB had a sensitivity of 0.96 [95% confidence interval (CI)=0.94-0.97] and a specificity of 0.96 (95% CI=0.94-0.97). Positive and negative likelihood ratios, and the diagnostic odds ratio of US-CNB were 18.20 (95% CI=2.21-156.41), 0.08 (95% CI=0.02-0.27) and 250.60 (95% CI=19.11-3286.76), respectively. The area under the summary receiver operating characteristic curve was 0.979. Therefore, US-CNB may be considered as a reliable method in the assessment of thyroid nodules, and has an acceptable risk of complications.

Serum midkine as a surrogate biomarker for metastatic prediction in differentiated thyroid cancer patients with positive thyroglobulin antibody.

Serum thyroglobulin (Tg) is the main post-operative tumor biomarker for patients with differentiated thyroid cancer (DTC). However, the presence of thyroglobulin antibodies (TgAb) can interfere with Tg level and invalidate the test. In this study, we aimed to investigate the predicative value of midkine (MK) as a cancer biomarker for DTC patients with positive TgAb before the first 131I therapy. MK levels were measured by enzyme-linked immunosorbent assay in 151 recruited DTC patients after exercising strict inclusion and exclusion criteria. There were 28 TgAb positive DTC patients with metastases and 123 DTC patients without metastases. The value of pre-131I-ablative MK to predict metastasis was assessed by receiver operating characteristic (ROC) curves in these two groups of patients. MK levels in the TgAb positive DTC patients were significantly higher than the DTC patients without metastases. ROC showed good predictability of MK, with an area under the curve of 0.856 (P < 0.001), and a diagnostic accuracy of 83% at the optimal cut-off value of 550 pg/ml. In conclusion, we show that MK can potentially be used as a surrogate biomarker for predicting DTC metastases when Tg is not suitable due to TgAb positivity.

The associations between leukocyte, erythrocyte or platelet, and metabolic syndrome in different genders of Chinese.

Leukocyte, erythrocyte or platelet and metabolic syndrome (MS) are closely correlated, and there exist gender differences. We aimed to explore the associations between the hematological parameters and MS in different genders of Chinese. This cross-sectional study included 32,900 participants (20,733 males, 12,167 females) who were enrolled in a health examination. Clinical data including anthropometric measurements and serum parameters were collected. The associations between hematological parameters and MS of both genders were analyzed separately. Odds ratio (OR) of MS was calculated by binary logistic regression models. All hematological parameters were related to MS. With leukocyte and erythrocyte counts rising, the risks of developing MS increased in both genders, which was more obvious in women. For instance, in model 3, the ORs of MS in leukocyte quartiles in females were from 1.333 to 2.045 (P < 0.01), while in males, from 1.238 to 1.675 (P < 0.01). Platelet seemed as a protective factor in males. Model 1 and model 3 in quartile 2 demonstrated ORs of 0.922 (P < 0.05) and 0.912 (P < 0.05). However, platelet acted as risk factor in female. For instance, the ORs were 1.253 (P < 0.01), 1.461 (P < 0.01), and 1.322 (P < 0.01) in platelet quartile 4 of all 3 models in female. Gender has influences on the associations between leukocyte, erythrocyte or platelet, and MS. In both genders, higher levels of leukocyte and erythrocyte increased risks of MS. For men, platelet was a protective factor, but for women, platelet seemed as a risk factor.

Gender impact on the correlation between thyroid function and serum lipids in patients with differentiated thyroid cancer.

The present study aimed to explore the association between thyroid stimulating hormone (TSH) and serum lipids in patients with differentiated thyroid cancer (DTC), with a focus on the risk of hyperlipidemia between different genders. The study included 352 DTC patients who were ready to receive I-131 therapy as well as 352 matched normal controls. In the DTC group, 157 patients were monitored for TSH and lipid parameters prior to and after 1 month of thyroxine therapy. Results were analyzed using t-tests, Pearson bivariate correlation and binary logistic regression analyses. All participants were divided into 3 subgroups according to TSH levels: Subgroup 1 (normal TSH level), subgroup 2 (TSH between 5 and 30 µIU/ml), and subgroup 3 (TSH >30 µIU/ml). Serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels were significantly higher in the DTC group than in the control group. The levels of these parameters decreased after thyroxine therapy and significant positive correlations were observed between TSH and TC, and TG and LDL-C in both genders. Binary logistic regression demonstrated that female DTC patients had higher risks of developing hyperlipidemia than male patients, and these risks increased when TSH increased. For example, the odds ratios (ORs) of high TC in subgroup 2 were 3.30 in males and 4.60 in females, respectively. However, in subgroup 3, the ORs were 9.40 in males and 13.12 in females, respectively. The results of the present study showed that after thyroidectomy, the risk of dyslipidemia markedly increased in DTC patients. More importantly, female patients had a higher risk than male patients.

Multiple-factor analysis of the first radioactive iodine therapy in post-operative patients with differentiated thyroid cancer for achieving a disease-free status.

131I treatment is an important management method for patients with differentiated thyroid cancer (DTC). Unsuccessful 131I ablation drastically affects the prognosis of the patients. This study aimed to analyze potential predictive factors influencing the achievement of a disease-free status following the first 131I therapy. This retrospective review included 315 DTC patients, and multiple factors were analyzed. Tumor size, pathological tumor stage, lymph node (LN) metastasis, distant metastasis, American Thyroid Association recommended risks, pre-ablation thyroglobulin (Tg), and thyroid stimulating hormone (TSH) displayed significant differences between unsuccessful and successful group. Cutoff values of Tg and TSH to predict a successful outcome were 3.525 ng/mL and 99.700 uIU/ml by receiver operating characteristic curves analysis. Binary logistic regression analysis showed that tumor stage T3 or T4, LN metastasis to N1b station, intermediate and high risks, pre-ablation Tg ≥ 3.525 ng/ml and TSH <99.700 µIU/mL were significantly associated with unsuccessful outcomes. Logistic regression equation for achieving a disease-free status could be rendered as: y (successful treatment) = -0.270-0.503 X1 (LN metastasis) -0.236 X2 (Tg) + 0.015 X3 (TSH). This study demonstrated LN metastasis, pre-ablation Tg and TSH were the most powerful predictors for achieving a disease-free status by the first 131I therapy.

Influence of the first radioactive iodine ablation on peripheral complete blood count in patients with differentiated thyroid cancer.

Radioactive iodine (RAI) is considered to be related with hematologic changes. This study aimed to evaluate influence of the first RAI ablation on peripheral complete blood count (CBC) in patients with differentiated thyroid cancer (DTC).Data of CBC at baseline and 6 months after RAI were obtained in 385 patients with DTC with approximately 3700 MBq I (ranging 2220-7585 MBq). Further comparison was done in 196 patients with 1-month postablation data available. Routine blood examinations were performed to determine impact of RAI on white blood cell (WBC), red blood cell (RBC), hemoglobin, platelet, neutrophil, lymphocyte, and monocyte in both sexes. Continuous variables were compared by paired t tests and independent samples t test, and categorical variables were compared by chi-square analysis. Data with repeated measurements were analyzed by analysis of variance.The first RAI after thyroidectomy was associated with mild, yet significant declines in WBC, platelet, and lymphocyte, which persisted for 6 months. One month after RAI, significant declines were found in all CBC, including RBC and hemoglobin (all P < 0.05). While CBC partly recovered 6 months after RAI, this follow-up CBC still demonstrated significant declines in WBC, platelet, and lymphocyte (all P < 0.05) without gender differences. Significant rises in RBC and hemoglobin in males and females were found. The decline of platelet in females was more obvious than in males at 3700 to 4440 MBq of RAI. On the contrary, the rises of RBC and hemoglobin in males were higher than in females. There were no significant complications during the follow-up.WBC and platelet decreased obviously 1 month after RAI. While they partly recovered 6 months after RAI, they were still lower than the baseline. However, RBC and hemoglobin transiently decreased at 1 month and then increased to levels even higher than baseline 6 months later. At 3700 to 4440 MBq of RAI, the decline of platelet in females was more obvious than in males. Yet, rises of RBC and hemoglobin in males were higher than in females. The risks associated with these changes are unlikely to outweigh the potential benefits of RAI in patients with DTC.

Harmonic versus LigaSure hemostasis technique in thyroid surgery: A meta-analysis.

Harmonic scalpel and LigaSure vessel sealing systems have been suggested as options for saving surgical time and reducing postoperative complications. The aim of the present meta-analysis was to compare surgical time, postoperative complications and other parameters between them in for the open thyroidectomy procedure. Studies were retrieved from MEDLINE, Cochrane Library, EMBASE and ISI Web of Science until December 2015. All the randomized controlled trials (RCTs) comparing Harmonic scalpel and LigaSure during open thyroidectomy were selected. Following data extraction, statistical analyses were performed. Among the 24 studies that were evaluated for eligibility, 7 RCTs with 981 patients were included. The Harmonic scalpel significantly reduced surgical time compared with LigaSure techniques (8.79 min; 95% confidence interval, -15.91 to -1.67; P=0.02). However, no significant difference was observed for the intraoperative blood loss, postoperative blood loss, duration of hospital stay, thyroid weight and serum calcium level postoperatively in either group. The present meta-analysis indicated superiority of Harmonic Scalpel only in terms of surgical time compared with LigaSure hemostasis techniques in open thyroid surgery.

Gender and Age Impacts on the Association Between Thyroid Function and Metabolic Syndrome in Chinese.

The relationship between thyroid dysfunction and metabolic syndrome (MS) is complex. We aimed to explore the impact of gender and age on their association in a large Chinese cohort. This cross-sectional study enrolled 13,855 participants (8532 male, 5323 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and serum metabolic parameters were collected. The associations between thyroid function and MS of both genders were analyzed separately after dividing thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and age into subgroups. MS risks were calculated by binary logistic regression models. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher prevalence than males. Females had higher incidence of thyroid dysfunction than males. By using TSH quartiles as the categorical variables and the lowest quartile as reference, significantly increased MS risk was demonstrated in quartile 4 for males, yet quartiles 3 and 4 for females. By using FT3 quartiles as the categorical variables, significantly increased MS risk was demonstrated in quartile 2 to 4 for females only. By using age subgroups as the categorical variables, significantly increased MS risk was shown in both genders, with females (4.408-58.455) higher than males (2.588-4.943). Gender and age had substantial influence on thyroid function and MS. Females with high TSH and high FT3 had higher MS risks than males. Aging was a risk for MS, especially for females. Urgent need is necessary to initiate interventional programs.

Retrospective imaging study on the diagnosis of pathological false positive iodine-131 scans in patients with thyroid cancer.

Iodine-131 (I-131) therapy and post-therapy I-131 scanning are essential in the management of differentiated thyroid cancer (DTC). However, pathological false positive I-131 scans can lead to misdiagnosis and inappropriate I-131 treatment. This retrospective study aimed to investigate the best imaging modality for the diagnosis of pathological false positive I-131 scans in a DTC patient cohort, and to determine its incidence. DTC patient data archived from January 2008 to January 2010 was retrieved. Post-therapeutic I-131 scans were conducted and interpreted. The imaging modalities of magnetic resonance imaging (MRI), computed tomography and ultrasonography were applied and compared to check all suspected lesions. Biopsy or needle aspiration was conducted for patients who consented to the acquisition of histopathological confirmation. Data for 156 DTC patients were retrieved. Only 6 cases of pathological false-positives were found among these (incidence, 3.85%), which included 3 cases of thymic hyperplasia in the mediastinum, 1 case of pleomorphic adenoma in the parapharyngeal space and 1 case of thyroglossal duct cyst in the neck. MRI was demonstrated as the best imaging modality for diagnosis due to its superior soft tissue resolution. However, no imaging modality was able to identify the abdominal false positive-lesions observed in 2 cases, one of whom also had thymic hyperplasia. In conclusion, pathological false positive I-131 scans occurred with an incidence of 3.85%. MRI was the best imaging modality for diagnosing these pathological false-positives.

Gender and Age Impact on the Association Between Thyroid-Stimulating Hormone and Serum Lipids.

The relationship between thyroid-stimulating hormone (TSH) and hyperlipidemia is still a topic of debate. We aimed to explore the impact of gender and age on the association between serum TSH and lipid profile in a large cohort of Chinese.This cross-sectional study enrolled 13,915 participants (8565 male, 5350 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and other serum parameters were collected. The associations between TSH and hyperlipidemia of males and females were analyzed separately after dividing TSH and age into subgroups. Odds ratio for hyperlipidemia was calculated by binary logistic regression models.Young males had significantly higher prevalence of hypercholesterolemia, hypertriglyceridemia, and high serum low-density lipoprotein-cholesterol than females, yet after menopause, females had higher prevalence than males. TSH was positively associated with hyperlipidemia independent of thyroid hormones. Males showed more reduced risks of hyperlipidemia in low TSH concentrations, while females demonstrated more enhanced risks of hyperlipidemia in high TSH concentrations. For instance, if TSH was lower than 0.3 µIU/mL, the risks of developing hypercholesterolemia and hypertriglyceridemia in males were only 0.198 (P < 0.01) and 0.425 (P < 0.05) of the reference TSH risks (between 2.0 and 3.0 µIU/mL), while in females the risks were 0.553 (P < 0.05) and 0.642 (P > 0.05), respectively. If TSH was higher than 4.0 µIU/mL, women displayed significantly higher risks of developing hypertriglyceridemia than the reference TSH risks (P < 0.05), yet, men did not demonstrate such significances.Our results showed thyroid hormone independent positive associations between serum TSH and lipids, which were substantially influenced by gender and age. Males demonstrated more protective effects of low TSH against hyperlipidemia, while females showed more detrimental effects of high TSH on hyperlipidemia.

Sleep Quality of Patients with Differentiated Thyroid Cancer.

OBJECTIVE: We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants. METHODS: Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then 131I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ2 test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after 131I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar's test. RESULTS: Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After 131I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%). CONCLUSION: DTC patients suffer from sleep disturbance, 131I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.

Evaluation of serum midkine as a biomarker in differentiated thyroid cancer.

AIMS: Midkine is a multifunctional cytokine identified to be a promising cancer biomarker. We aimed to prospectively investigate serum midkine as a diagnostic and prognostic biomarker in differentiated thyroid cancer (DTC). MAIN METHODS: 162 patients with thyroid nodules participated in the surgical cohort (post-surgical pathology proved 70 cases with DTC and 92 cases with benign thyroid nodules), 75 healthy subjects served as control. Diagnostic values of pre-surgical midkine and thyroglobulin for DTC were conducted by receiver operating characteristic (ROC) curves. 214 DTC patients participated in the (131)I treatment cohort. Prognostic values of pre-(131)I-ablative midkine and thyroglobulin to predict (131)I-avid metastases were performed by ROC curves. Metastasis-free survival was analyzed by the Kaplan-Meier method. KEY FINDINGS: Much better diagnostic capability of midkine than thyroglobulin was shown to differentiate DTC from benign thyroid nodules, with cut-off midkine value of 323.12pg/ml and diagnostic accuracy of 75.31%. Nearly similar diagnostic capabilities of midkine and thyroglobulin were shown to distinguish DTC from normal participants. Pre-(131)I-ablative thyroglobulin demonstrated perfect ability to predict metastases, with cut-off value and diagnostic accuracy of 19.50ng/ml and 96.73%. Midkine also performed well with a cut-off value and diagnostic accuracy of 504.71pg/ml and 89.25%. DTC patients with midkine or thyroglobulin levels higher than those of thresholds (500pg/ml or 20ng/ml) showed a significantly worse (131)I-avid metastasis-free survival by the Kaplan-Meier method (P<0.01). SIGNIFICANCE: Our results show that midkine is as good as or even better than thyroglobulin to screen patients with thyroid nodules for DTC before surgery, and to predict whether metastases exist before the first (131)I ablative therapy.