The mutation of Japanese encephalitis virus envelope protein residue 389 attenuates viral neuroinvasiveness.

The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.

A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo. IL-21 enhanced proliferation capacity, promoted memory differentiation, downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation. A novel engineered IL-21 receptor was established, and TCR-T armed with the novel engineered IL-21 receptors (IL-21R-TCR-T) showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand. IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo. IL-21R-TCR-T exhibited a less differentiated, exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation. The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization. The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

Citrus peel polyphenols alleviate intestinal inflammation in mice with dextran sulfate sodium-induced acute colitis.

Citrus peel polyphenols have possess the distinct anti-inflammatory activities. However, its underlying mechanism on ulcerative colitis have not been elucidated. The aim of this research was to investigate the anti-inflammatory effect and action mechanisms of citrus peel polyphenols. Total citrus peel polyphenols were concentrated using macroporous resins and separated into water-soluble citrus polyphenols and ester-soluble citrus peel polyphenols. These extracts were then gavaged to acute colitis mice induced by dextran sulfate sodium for 14 days using a dose of 300 mg/kg▪bw. High performance liquid chromatography results showed that the extracts contained flavanones, flavonoids, and phenolic acids. Compared to the dextran sulfate sodium group, total citrus peel polyphenols, water-soluble citrus polyphenols, and ester-soluble citrus peel polyphenols significantly ameliorated the severity of colitis symptoms. Additionally, citrus peel polyphenols reduced the activity of myeloperoxidase, lowered secretion of tumor necrosis factor-α and interleukin-6, and increased interleukin-10. Meanwhile, total citrus peel polyphenols, water-soluble citrus polyphenols, and ester-soluble citrus peel polyphenols effectively blocked the activation of the nuclear factor-kappa B. These results demonstrated that citrus peel polyphenols alleviated ulcerative colitis in mice by damping pro-inflammatory cytokine secretion and suppressing the nuclear factor-kappa B pathway activation.

Delayed Initial Radioiodine Adjuvant Therapy Does Affect Biochemical Response in Intermediate- to High-Risk Differentiated Thyroid Cancer.

Background: There are no definite recommendations on the optimal time of initiating radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC) patients in current relevant guidelines. This study aimed to investigate the relationship between the timing of initiating radioiodine adjuvant therapy (RAT) and the clinical outcomes based on dynamic follow-ups and assessments in intermediate- to high-risk DTC patients. Methods: A total of 206 patients with intermediate- to high-risk DTC receiving RAT of 150 mCi were retrospectively reviewed. According to the time interval (TI: between thyroidectomy and initial RAT), the patients were divided into 2 groups: Group 1: TI < 3 months (n=148), and Group 2: TI ≥ 3 months (n=58). The RAT therapy response was evaluated as excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), structural incomplete response (SIR). The univariate and multivariate analyses were conducted to screen out factors associated with incomplete response (IR= BIR+SIR). Finally, the prognostic nomogram was used to explain IR rates as a valuable tool in clinical practice. Results: Response to initial RAT was significantly different between 2 groups during dynamic follow-ups (all P<0.05). Group 2 had significantly lower ER rates (37.9 vs 63.5, 52.0 vs 73.9, 64.4 vs 80.3, all P<0.05, respectively) and higher IR rates (39.7 vs 14.9, 36.0 vs 9.7, 12.2 vs 3.9, all P<0.05, respectively) than group 1 during dynamic follow-ups. By univariate and multivariate analyses, prolonged TI (HR: 6.67, 95%CI: 2.241-19.857, P=0.001), soft tissue invasion (HR: 7.35, 95%CI: 1.624-33.296, P=0.010), higher sTg (HR: 7.21, 95%CI: 1.991-26.075, P=0.003) were manifested to be independent risk factors for IR. The nomogram showed that soft tissue invasion, sTg, and TI were the top 3 contributors to the IR. Conclusions: Early RAT is associated with greater biochemical response but has no impact on SIR. Delayed initial RAT (≥3 months after thyroidectomy) related to IR in intermediate- to high-risk DTC.

Nomogram Model to Predict the Probability of Ovarian Hyperstimulation Syndrome in the Treatment of Patients With Polycystic Ovary Syndrome.

Objective: The objective of this study was to explore the risk factors of ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and to establish a nomogram model evaluate the probability of OHSS in PCOS patients. Methods: We retrospectively analyzed clinical data from 4,351 patients with PCOS receiving IVF/ICSI in our reproductive medical center. The clinical cases were randomly divided into a modeling group (3,231 cases) and a verification group (1,120 cases) according to a ratio of about 3:1. The independent risk factors correlation with the occurrence of OHSS was identified by logistic regression analysis. Based on the selected independent risk factors and correlated regression coefficients, we established a nomogram model to predict the probability of OHSS in PCOS patients, and the predictive accuracy of the model was measured using the area under the receiver operating curve (AUC). Results: Univariate and multivariate logistic regression analyses showed that FSH (OR, 0.901; 95% CI, 0.847-0.958; P<0.001), AMH (OR, 1.259; 95% CI, 1.206-1.315; P<0.001), E2 value on the day of hCG injection (OR, 1.122; 95% CI, 1.021-1.253; P<0.001), total dosage of Gn used (OR, 1.010; 95% CI, 1.002-1.016; P=0.041), and follicle number on the day of hCG injection (OR, 0.134; 95% CI, 1.020-1.261; P=0.020) are the independent risk factors for OHSS in PCOS patients. The AUC of the modeling group is 0.827 (95% CI, 0.795-0.859), and the AUC of the verification group is 0.757 (95% CI, 0.733-0.782). Conclusion: The newly established nomogram model has proven to be a novel tool that can effectively, easily, and intuitively predict the probability of OHSS in the patients with PCOS, by which the clinician can set up a better clinical management strategies for conducting a precise personal therapy.

Predictive Value of Thyroglobulin Changes for the Curative Effect of Radioiodine Therapy in Patients With Metastatic Differentiated Thyroid Carcinoma.

Background: Serum thyroglobulin (Tg) serves as a sensitive and easily available tumor marker for patients with metastatic differentiated thyroid carcinoma (m-DTC). The aim of the present study was to evaluate the predictive value of suppressed Tg changes (Δsup-Tg) and/or stimulated Tg changes (Δsti-Tg) to evaluate the efficacy of radioiodine therapy (RT). Methods: We studied 117 patients with m-DTC who received RT. Δsup-Tg and Δsti-Tg were compared after the first RT in different therapeutic response groups and a receiver-operating characteristic (ROC) curve was used to determine the cut-off values to predict non-remission. Univariate and multivariate analyses were used to investigate the effects of 17 observed factors on the efficacy of RT. Results: A total of 218 RT events in 117 patients with m-DTC were analyzed. After the last RT, the remission rate was 70.94% (83/117), and the proportion of remission events accounted for 74.77% (163/218). ROC curve analysis showed that the cut-off values for Δsup-Tg and Δsti-Tg after the first RT to predict the non-remission of RT were 21.54% and 27.63%, respectively. Age, the size of the metastasis, the maximum count of target metastatic lesions and the average count of contralateral non-target tissue on tomographic imaging (Tmax/NTmean) of the first RT, and Δsup-Tg after the first RT were identified as independent factors associated with RT efficacy. Conclusions: Tg response was valuable to predict RT efficacy for patients with m-DTC. Age, the size of the metastasis, Tmax/NTmean, and Δsup-Tg after the first RT were verified as independent predictive factors of RT efficacy.

Predictive Value of a Thyroid-Absorbed Dose with a Shorter Effective Half-Life on Efficacy in Graves Disease Patients Receiving Iodine-131 Therapy.

BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.

Genotype profiles of Helicobacter pylori from gastric biopsies and strains with antimicrobial-induced resistance.

BACKGROUND AND AIMS: The genotypic method could significantly shorten the time needed to obtain antibiotic susceptibility data for Helicobacter pylori. The aim of this study was to explore the profile of H. pylori from gastric biopsies and strains with antibiotic-induced resistance. METHODS: A total of 124 gastric biopsies were used to perform gene sequencing and to perform bacterial culture and susceptibility testing. Seven susceptible strains were selected to develop resistance to clarithromycin, levofloxacin, and metronidazole. Four susceptible strains were selected to transfer candidate mutations. The genotype profiles of these groups were analyzed by sequencing analysis. The antibiotic susceptibility of these strains was detected using the E-test method. RESULTS: Phenotypic resistance to clarithromycin, levofloxacin, and metronidazole was observed in 35.5%, 40.0%, and 79.8% strains, respectively. Point mutations in 23 S rRNA, gyrA, and rdxA genes were observed in 39.5%, 38.7%, and 86.3% of gastric biopsies, respectively. The A2143G mutation in the 23S rRNA occurs in most clarithromycin-resistant samples. The A2142C point mutation showed a higher efficacy than A2142G and A2143G for inducing clarithromycin resistance. The D91N and N87K mutations in gyrA occurs in most levofloxacin-resistant samples, and double point mutations showed a higher efficacy than single mutations for inducing levofloxacin resistance. Phenotypic resistance and mutations in rdxA lacked consistency. CONCLUSION: Genotype-based gastric biopsy analysis was reliable for determining clarithromycin and levofloxacin resistance. A2143G in 23S rRNA and N87K/D91N in the gyrA gene occurred in most resistant strains. Mutations in the rdxA gene were not good indicators of metronidazole resistance.

The prognostic value of gender in gastric gastrointestinal stromal tumors: a propensity score matching analysis.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are the most common GISTs. The risk, incidence, and outcome of cancer are different between the sexes. Whether gender is related to the prognosis of gastric stromal tumors is unclear. Therefore, this study aims to explore the relationship between gender and gastric GIST prognosis. METHODS: Data from gastric GIST patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce confounding factors, and the clinicopathological features and prognosis of GIST patients were comprehensively evaluated. RESULTS: There were 512 male patients and 538 female patients with gastric GIST. The gender of gastric GIST patients was associated with marital status, surgical treatment, tumor size, and mitotic index (P < 0.05). The Kaplan-Meier analysis and log-rank test revealed that male patients had a higher mortality rate than female patients (P = 0.0024). After matching all the potential confounding factors, the survival of the female gastric GIST patients was better than that of the male gastric GIST patients (P = 0.042). Cox regression analysis revealed that gender was an independent risk factor for overall survival. The risk of death was higher for males than for females (HR 1.677, 95% CI 1.150-2.444, P = 0.007). CONCLUSION: Gender could be a prognostic factor for gastric GIST survival, and male patients had a higher risk of death.

ECM1 Prevents Activation of Transforming Growth Factor ß, Hepatic Stellate Cells, and Fibrogenesis in Mice.

BACKGROUND & AIMS: Activation of TGFB (transforming growth factor ß) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not clear. We investigated the role of ECM1 (extracellular matrix protein 1), which interacts with extracellular and structural proteins, in TGFB activation in mouse livers. METHODS: We performed studies with C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Δhep). ECM1 or soluble TGFBR2 (TGFB receptor 2) were expressed in livers of mice after injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl4) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy livers were analyzed by immunohistochemistry and in situ hybridization. RESULTS: ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with αv integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl4-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl4-induced liver fibrosis was accelerated in ECM1Δhep mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl4-induced fibrosis in mice. CONCLUSIONS: ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.

Multiple Antigen Stimulating Cellular Therapy (MASCT) For Hepatocellular Carcinoma After Curative Treatment: A Retrospective Study.

Background & Aims: The prognosis of hepatocellular carcinoma (HCC) remains poor and available treatment options are limited. This retrospective study evaluated the efficacy of Multiple Antigen Stimulating Cell Therapy (MASCT) as an adjuvant therapy for the treatment of HCC after curative treatment. Methods: Patients who underwent HCC curative treatments were classified into two groups: the MASCT group, in which patients received MASCT treatment after curative treatment (n = 47), and the control group, in which patients did not receive any treatment after curative treatment (n = 99). Patients who received ≥ 5 courses of MASCT treatment before recurrence or death (n = 26) were further stratified into a subgroup (multiple-course MASCT group) for analysis. The primary endpoint was overall survival (OS). The secondary endpoints were disease-free survival (DFS) and safety. Results: Kaplan-Meier analysis showed no statistically significant difference in OS between the MASCT group and the control group (P = 0.132), nor in DFS (P = 0.310) (median: 36.17 vs. 24.27 months). However, when comparing the multiple-course MASCT treated group to the control group, Kaplan-Meier analysis showed a significant difference in OS (P = 0.011), but not in DFS (P = 0.104) (median: 47.10 vs. 24.27 months). The overall incidences of treatment-related adverse events in the MASCT group and control group were 14.89% (7/47) and 19.19% (19/99), respectively. No MASCT treatment-related serious adverse events were reported. Conclusions: Although the MASCT group was not associated with significantly longer OS or DFS, the multiple-course MASCT group showed significantly improved overall survival after curative treatment, and the treatment procedures were well-tolerated. Multiple-course MASCT may therefore provide another choice for patients with HCC after curative treatment.

Analysis of radioiodine therapy and prognostic factors of differentiated thyroid cancer patients with pulmonary metastasis: An 8-year retrospective study.

To assess the efficacy of radioiodine therapy (RIT) and investigate the prognostic factors for patients with pulmonary metastasis secondary to differentiated thyroid carcinoma (DTC) through a retrospective study. A total of 80 patients with radioactive iodine-131 (I)-avid pulmonary metastasis from DTC treated with I from 2007 to 2014 at our institution entered the study. Treatment response was mainly measured by two parameters: serum thyroglobulin (Tg) levels and post-therapeutic I whole-body scan (WBS). Treatment variables were assessed for statistical significance using the univariate and multivariate analyses. A receiver-operating characteristic (ROC) curve was also plotted to verify the accuracy of predictors. Of these 80 patients, the overall effective rate was 72.5% (58/80), the rates for complete response (CR), partial response (PR), and no response (NR) were 20.0%, 52.5%, and 27.5%, respectively. Univariate analysis showed that gender, pulmonary nodule size, absence or presence of extrapulmonary distant metastases, age, and Tg level at diagnosis were significantly associated with I therapy efficacy. Binary logistic regression analysis revealed that older patients (odds ratio [OR]:1.481, 95% confidence interval [CI]: 1.457-2.091, P = .020), subjects with higher Tg levels at diagnosis (OR: 1.046, 95% CI: 1.016-1.119, P = .014), and those with extrapulmonary distant metastases (OR: 1.185, 95%CI: 1.025-1.463, P = .020) had a higher probability of poor prognosis. The optimal cutoffs for age and Tg level to predict I therapy efficacy for DTC with lung metastases were 46 years old and 55.50 ng/mL, respectively, based on ROC analysis. This study indicated that most DTC patients with pulmonary metastases can obtain partial or complete remission after RIT, while older patients with higher Tg levels at diagnosis and extrapulmonary distant metastases more likely show poor prognosis.

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.

Gender impact on the correlations between subclinical thyroid dysfunction and hyperuricemia in Chinese.

Overt hypothyroidism and hyperthyroidism can lead to hyperuricemia. However, few data are available regarding the association between subclinical thyroid dysfunction and hyperuricemia, especially from the perspective of gender impact. This study aimed to investigate the association between subclinical thyroid disorders and hyperuricemia with emphasized focuses on differences resulting from different gender. Eleven thousand four hundred forty-six healthy subjects (6870 male, 4576 female) were enrolled in this cross-sectional study, with exclusions of known thyroid, renal, hepatic, gastrointestinal, or oncological diseases. Clinical data including anthropometric measurements, thyroid function, uric acid, renal and liver function were collected. The associations between thyroid function and hyperuricemia of males and females were analyzed separately. Prevalence of hyperuricemia was substantially higher in male (23.17%) than that in female (9.11%). Serum uric acid was correlated well with various factors, especially with creatinine, whose coefficients were 0.283 and 0.386 for males and females. The significantly elevated risk for hyperuricemia was observed in mild hypothyroidism male participants with an odd ratio of 1.49 (1.10-2.02), whereas no statistical risk was found in female. No meaningful risk was found in mild hyperthyroidism participants. Estimated glomerular filtration rate was significantly depressed in both genders with mild hypothyroidism, while obviously increased in both genders with mild hyperthyroidism. For hyperuricemia, mild hypothyroidism is a risk factor in males while it is not in females. This difference could be caused by the protective effect of estrogen in females. Monitoring serum uric acid in subclinical hypothyroidism is more necessary in males.

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.

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.

The study of external dose rate and retained body activity of patients receiving 131I therapy for differentiated thyroid carcinoma.

Radiation safety is an integral part of targeted radionuclide therapy. The aim of this work was to study the external dose rate and retained body activity as functions of time in differentiated thyroid carcinoma patients receiving 131I therapy. Seventy patients were stratified into two groups: the ablation group (A) and the follow-up group (FU). The patients' external dose rate was measured, and simultaneously, their retained body radiation activity was monitored at various time points. The equations of the external dose rate and the retained body activity, described as a function of hours post administration, were fitted. Additionally, the release time for patients was calculated. The reduction in activity in the group receiving a second or subsequent treatment was more rapid than the group receiving only the initial treatment. Most important, an expeditious method was established to indirectly evaluate the retained body activity of patients by measuring the external dose rate with a portable radiation survey meter. By this method, the calculated external dose rate limits are 19.2, 8.85, 5.08 and 2.32 µSv·h-1 at 1, 1.5, 2 and 3 m, respectively, according to a patient's released threshold level of retained body activity <400 MBq. This study is beneficial for radiation safety decision-making.

Immunohistochemical evaluation of midkine and nuclear factor-kappa B as diagnostic biomarkers for papillary thyroid cancer and synchronous metastasis.

AIMS: Midkine (MK) is a multifunctional cytokine identified to be a promising cancer biomarker. Nuclear factor-kappa B (NF-κB) is an important transcription factor that plays a pivotal role in tumorigenesis. We aimed to investigate values of MK and NF-κB as markers for diagnosis and synchronous metastasis prediction in papillary thyroid cancer (PTC). MAIN METHODS: 76 cases of PTC and 70 cases of multi-nodular goiter (MNG) were retrieved. The PTC group was further divided into subgroup 1 (16 cases with synchronous metastases) and subgroup 2 (60 cases without metastases). A retrospective review of demographic and clinical information was performed. Immunohistochemistry of MK, NF-κB p65 and Ki-67 was performed on paraffin-embedded specimens and results were quantified. Diagnostic values of the parameters were conducted by receiver operating characteristic (ROC) curves. Protein levels of MK and NF-κB p65 were then confirmed by Western blot. KEY FINDINGS: Immunoreactivities of MK, NF-κB p65 and Ki-67 were significantly higher in the PTC group than in the MNG group with good differential diagnostic capabilities. Moreover, immunoreactivities of all three parameters were significantly higher in subgroup 1 than in subgroup 2 with good synchronous metastasis predictive efficacies. Western blot showed that MK and NF-κB p65 protein levels in lesions from subgroup 1 were significantly higher than those from subgroup 2, both of which were significantly higher than in MNG lesions. SIGNIFICANCE: We discovered that MK and NF-κB immunohistochemistries can potentially be used for differential diagnosis between PTC and MNG, and for prediction of synchronous metastases.