Adaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events.

Endogenous retroviruses (ERVs) are ancient retroviral remnants integrated in host genomes, and commonly deleted through unequal homologous recombination, leaving solitary long terminal repeats (solo-LTRs). This study, analysing the genomes of 362 bird species and their reptilian and mammalian outgroups, reveals an unusually higher level of solo-LTRs formation in birds, indicating evolutionary forces might have purged ERVs during evolution. Strikingly in the order Passeriformes, and especially the parvorder Passerida, endogenous retrovirus K (ERVK) solo-LTRs showed bursts of formation and recurrent accumulations coinciding with speciation events over past 22 million years. Moreover, our results indicate that the ongoing expansion of ERVK solo-LTRs in these bird species, marked by high transcriptional activity of ERVK retroviral genes in reproductive organs, caused variation of solo-LTRs between individual zebra finches. We experimentally demonstrated that cis-regulatory activity of recently evolved ERVK solo-LTRs may significantly increase the expression level of ITGA2 in the brain of zebra finches compared to chickens. These findings suggest that ERVK solo-LTRs expansion may introduce novel genomic sequences acting as cis-regulatory elements and contribute to adaptive evolution. Overall, our results underscore that the residual sequences of ancient retroviruses could influence the adaptive diversification of species by regulating host gene expression.

Stimulating thyroglobulin to TSH ratio predict long-term efficacy of 131I therapy in patients with differentiated thyroid cancer after total thyroidectomy: a retrospective study.

OBJECTIVE: This study utilized the stimulated thyroglobulin (sTg) to thyroid stimulating hormone (TSH) ratio to predict the long-term efficacy of 131I therapy in patients with moderate-to-high-risk differentiated thyroid cancer (DTC). METHODS: This study retrospectively analyzed 960 DTC patients with a median follow-up time of 30 months (6-92 months). The median age was 44 years. All patients underwent total thyroidectomy, lymph node dissection, and at least one 131I therapy. Patients were subjected to a final efficacy evaluation according to American Thyroid Association's 2015 guidelines. Patients were grouped according to their TSH levels before the initial 131I therapy and the final efficacy evaluation, and factors influencing TSH levels and final efficacy were analyzed. Construction of nomograms using independent risk factors affecting long-term outcomes. The cut-offs of sTg and sTg/TSH ratios were calculated for different long-term outcomes. Progression-free survival (PFS) of patients was analyzed by making Kaplan-Meier survival according to the cut-offs of sTg and sTg/TSH ratio. RESULTS: TSH (mU/L) levels were more concentrated at 60-90 in females (71.5%) and 30-60 in males (39.0%), while patients with younger age, more lymph node metastases, shorter time interval between surgery and the first 131I therapy, and lower dose of levothyroxine sodium taken prior to the first 131I therapy would have higher TSH levels (All P < 0.05).Patients who are male, have primary tumor involvement of the strap muscles, lymph node metastasis, distant metastasis, and higher sTg and sTg/TSH are more likely to have poor long-term outcomes (All P < 0.05).The cut-offs of sTg and sTg/TSH for long-term efficacy were 7.515 and 0.095. STg, sTg/TSH, tumor size, lymph node metastasis, and distant metastasis were shown to be independent risk factors for long-term efficacy. The mean PFSs were longer for patients who had sTg/TSH ≤ 0.095 and/or sTg≤7.515 ug/L. CONCLUSIONS: For patients with moderate-to-high-risk DTC, when sTg>7.515 ug/L and/or sTg/TSH > 0.095 before the first 131I therapy, patients are more likely to have a poor long-term efficacy after full 131I therapy. This means that this group of patients may require further surgical treatment or targeted drug therapy after 131I therapy.

LGCOAMix: Local and Global Context-and-Object-Part-Aware Superpixel-Based Data Augmentation for Deep Visual Recognition.

Cutmix-based data augmentation, which uses a cut-and-paste strategy, has shown remarkable generalization capabilities in deep learning. However, existing methods primarily consider global semantics with image-level constraints, which excessively reduces attention to the discriminative local context of the class and leads to a performance improvement bottleneck. Moreover, existing methods for generating augmented samples usually involve cutting and pasting rectangular or square regions, resulting in a loss of object part information. To mitigate the problem of inconsistency between the augmented image and the generated mixed label, existing methods usually require double forward propagation or rely on an external pre-trained network for object centering, which is inefficient. To overcome the above limitations, we propose LGCOAMix, an efficient context-aware and object-part-aware superpixel-based grid blending method for data augmentation. To the best of our knowledge, this is the first time that a label mixing strategy using a superpixel attention approach has been proposed for cutmix-based data augmentation. It is the first instance of learning local features from discriminative superpixel-wise regions and cross-image superpixel contrasts. Extensive experiments on various benchmark datasets show that LGCOAMix outperforms state-of-the-art cutmix-based data augmentation methods on classification tasks, and weakly supervised object location on CUB200-2011. We have demonstrated the effectiveness of LGCOAMix not only for CNN networks, but also for Transformer networks. Source codes are available at https://github.com/DanielaPlusPlus/LGCOAMix.

Experimental study on changes in metabolic mechanism of papillary thyroid carcinoma complicated with Hashimoto's thyroiditis.

Background: Whether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC. Methods: The ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background). Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least square (OPLS) discriminant analysis. HMDB was searched to identify potential differential metabolites and final metabolic pathway analysis was performed by MetaboAnalyst 5.0. We analyzed the differential metabolites diagnostic accuracy through receiver operating characteristic (ROC) curves analysis. Results: Seven different metabolites were screened from HT group and NC group, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil and taurine. Logistic regression model combined with ROC analysis of these 7 biomarkers had good discriminability for PTC (area under operating characteristic curve of HT group and NC group were 0.867 and 0.973, respectively). The HT group had specific metabolic pathways, including aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism. Conclusions: The metabolic profiles of the NC and HT groups had important similarities and differences in PTC. The correlation of PTC with HT may be related to aminoacyl-tRNA biosynthesis, serine and threonine metabolism.

Nanobody based immunoassay for alpha fetal protein detection using streptavidin-conjugated polymerized horseradish peroxidase for signal amplification.

The enzyme-linked immunosorbent assay (ELISA) offers several advantages, including simple operation, high throughput, and low cost, making it an ideal immunoassay method for efficient screening of disease-related biomarkers in clinical samples. However, the traditional colorimetric ELISA has relatively low sensitivity, which promotes the continuous emergence of various novel signal amplification technologies. In this work, we fused the AFP-specific nanobody (A1) with the streptavidin-binding peptide (SBP) to develop a fusion protein (A1-SBP) as biorecognition element in a colorimetric ELISA for detecting AFP. Besides, to further improve the sensitivity of the traditional colorimetric ELISA, the streptavidin-conjugated polymerized horseradish peroxidase (SA-PolyHRP) were selected as a detection probe for signal amplification. The proposed signal enhancement strategy demonstrated a limit of detection (LOD) of 0.597 ng/mL for the SA-polyHRP-based ELISA, which is 7.67-fold lower than that of the traditional SA-HRP-based ELISA without additional steps. Furthermore, the proposed SA-polyHRP-based ELISA showed a good correlation with the detection of clinical samples using the Roche E601 chemiluminescence immunoassay analyzer. Therefore, the proposed signal enhancement strategy is an attractive approach for improving the sensitivity of immunoassay without requiring additional steps.

Comprehensive Detection of PD-L1 Protein and mRNA in Tumor Cells and Extracellular Vesicles through a Real-Time qPCR Assay.

A growing number of studies have shown that tumor cells secrete extracellular vesicles (EVs) containing programmed death-ligand 1 (PD-L1) protein. These vesicles can travel to lymph nodes and remotely inactivate T cells, thereby evading immune system attack. Therefore, the simultaneous detection of PD-L1 protein expression in cells and EVs is of great significance in guiding immunotherapy. Herein, we developed a method based on qPCR for the simultaneous detection of PD-L1 protein and mRNA in EVs and their parental cells (PREC-qPCR assay). Lipid probes immobilized on magnetic beads were used to capture EVs directly from samples. For RNA assay, EVs were directly broken by heating and quantified with qPCR. As to protein assay, EVs were recognized and bound with specific probes (such as aptamers), which were used as templates in subsequent qPCR analysis. This method was used to analyze EVs of patient-derived tumor clusters (PTCs) and plasma samples from patients and healthy volunteers. The results revealed that the expression of exosomal PD-L1 in PTCs was correlated with tumor types and significantly higher in plasma-derived EVs from tumor patients than that of healthy individuals. When extended to cells and PD-L1 mRNAs, the results showed that the expression of PD-L1 protein was consistent with mRNA in cancer cell lines, while PTCs demonstrated significant heterogeneity. This comprehensive detection of PD-L1 at four levels (cell, EVs, protein, and mRNA) is believed to enhance our understanding of the relationship among PD-L1, tumors, and the immune system and to provide a promising tool for predicting the benefits of immunotherapy.

Extrathyroidal extension or tumor size of primary lesion influences thyroid cancer outcomes.

AIMS: Extrathyroidal extension (ETE) is a determined factor of T3 and T4 stage of differentiated thyroid cancer (DTC) in American Joint Committee on Cancer. We aimed to compare clinical outcomes between different extent of ETE according to tumor size. METHODS: Patients diagnosed with DTC were collected from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. They were categorized into two groups by presence of lymph node metastases (LNM) or distant metastases (DM): group A: no presence of LNM and DM, and group B: presence of LNM or DM. Each group was further divided into four groups according to tumor size: <1 cm, 1-2 cm, 2-4 cm, >4 cm. ETE was divided into three groups by the extent: no ETE, microscopic ETE, and macroscopic ETE. Kaplan-Meier method and log-rank test were used to analyze cancer-specific survival (CSS). RESULTS: 91,975 patients were included. In groups A and B, for tumor size 1 cm, there was no significant difference in CSS between no ETE and microscopic ETE, while a significant difference was observed between no ETE and macroscopic ETE. For tumor size >1 cm, there were significant differences in CSS (both no ETE vs. micro ETE and no ETE vs. macro ETE). CONCLUSION: We suggests that when tumor size is more than 1 cm, micro ETE is significantly associated with poorer outcome. T3 and T4 stages may take account into tumor size rather than merely based on the presence and extent of ETE. It may be prudent to revisit the omission of micro ETE in TNM staging.

Molecular characteristics of natural organic matter in the groundwater system with geogenic iodine contamination in the Datong Basin, Northern China.

Natural organic matter (NOM) plays an important role in the iodine mobilization in the groundwater system. In this study, the groundwater and sediments from iodine affected aquifers in the Datong Basin were collected to perform chemistry analysis and molecular characteristics of NOM by Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Total iodine concentrations in groundwater and sediments ranged from 1.97 to 926.1 µg/L and 0.001-2.86 µg/g, respectively. A positive correlation was observed between DOC/NOM and groundwater/sediment iodine. FT-ICR-MS results showed that the DOM in the high-iodine groundwater system is characterized by less aliphatic and more aromatic compounds with higher NOSC, indicating the features of more unsaturated larger molecule structures and more bioavailability. Aromatic compounds could be the main carriers of sediment iodine and were easily absorbed on amorphous iron oxides to form the NOM-Fe-I complex. More aliphatic compounds, especially those containing N/S, experienced a higher degree of biodegradation, which further mediated the reductive dissolution of amorphous iron oxides and the transformation of iodine species, thereby causing the release of iodine into groundwater. The findings of this study provide some new insights into the mechanisms of high-iodine groundwater.

Using eZIS of SPECT to evaluate the therapeutic effect of carotid endarterectomy.

OBJECTIVE: Stroke is an acute cerebrovascular disease with high morbidity and mortality. The main causes of ischemic stroke include carotid artery stenosis, and carotid endarterectomy (CEA) can be used to improve the blood flow of the lesion site. Regional cerebral blood flow (rCBF) can be decreased by using single photon emission computed tomography (SPECT). The Easy Z-Score imaging system (eZIS) can display the changes of rCBF as Z-Score. The purpose of this study was to determine whether eZIS of SPECT can be used to evaluate the therapeutic effect of CEA in the treatment of carotid artery stenosis. METHODS: In this study, subjects were divided into the surgery group and the control group. The surgery group included seven patients with unilateral or bilateral internal carotid artery stenosis who received CEA treatment, and the control group included 11 patients who only received conventional drug treatment but did not receive surgery. Cerebral perfusion imaging (CPI) was collected twice before and after the corresponding treatment (within 6 months). rCBF of the lesion site was measured and Z-score was calculated before and after treatment by the eZIS technique. RESULTS: The postoperative Z-score of the surgery group was 0.54 ± 2.71 compared with that of the preoperative -1.34 ± 2.68 ( P = 0.0034; t = 4.687; df = 6), while the z-score of the control group was -0.33 ± 2.58 compared with that of the pretreatment 1.84 ± 2.62 ( P = 0.0010; t = 4.618; df = 10). CONCLUSION: CEA can effectively improve the blood flow in the lesion area of patients with carotid artery stenosis. eZIS of SPECT can be used to evaluate the therapeutic effect of CEA on carotid artery stenosis visually.

Higher adjuvant radioactive iodine therapy dosage helps intermediate-risk papillary thyroid carcinoma patients achieve better therapeutic effect.

Objective: This retrospective study aims to evaluate the therapeutic effect of varying dosages of adjuvant radioactive iodine (RAI) therapy on intermediate-risk papillary thyroid carcinoma (PTC) patients. Methods: This retrospective study involved a total of 427 intermediate-risk PTC patients, out of which 202 received a 3.7GBq dosage of RAI, and 225 received a 5.55GBq dosage. The evaluation involved assessing the therapeutic outcomes, number of treatment cycles, and successful remnant ablation rates in both dose groups, six months post-adjuvant RAI therapy. Univariate and multivariate logistic regression analyses were employed to identify factors linked with excellent response (ER). Following this, prognostic nomograms were constructed to provide a visual representation of the prediction models. Calibration curves, the concordance index (C-index), and the receiver operating characteristic (ROC) curve were employed to evaluate the predictive performance of these nomograms. The Hosmer-Lemeshow test was applied to assess the models' goodness-of-fit. Additionally, the clinical utility of the prognostic nomograms was appraised through decision curve analysis (DCA). Results: The high-dose (HD) group exhibited significantly higher proportions of ER, single treatment cycles, and successful remnant ablation rates (p<0.05). Being male, receiving a 3.7GBq dose, having an N1b stage, an sTg level ≥10ng/ml, or an sTg/TSH ratio ≥0.11 were independent risk factors for Non-ER. Two prognostic nomograms, "sTg Nomogram" and "sTg/TSH Nomogram", were established. The ranking of factors contributing to ER, in descending order, included the sTg or sTg/TSH ratio, N stage, therapy dosage, sex, and soft tissue invasion. The "sTg/TSH Nomogram" demonstrated a higher C-index compared to the "sTg Nomogram". The calibration curves indicated excellent calibration for both nomograms. DCA demonstrated that the net benefit of the "sTg/TSH Nomogram" was higher than that of the "sTg Nomogram". Conclusion: Higher initial RAI therapy doses can improve therapeutic efficacy for intermediate-risk PTC patients. The developed nomograms, particularly the "sTg/TSH Nomogram", could assist clinicians in optimal therapeutic decision-making.

Effects of high-activity radioactive iodine treatment on renal function in patients with differentiated thyroid carcinoma - retrospective study.

INTRODUCTION: It is not clear whether high-activity radioactive iodine (¹³¹I) treatment will affect renal function. This study aimed to investigate the effects of high-activity ¹³¹I treatment on the clinical metrics of renal function in patients with differentiated thyroid carcinoma (DTC). MATERIAL AND METHODS: 262 DTC patients with abnormal baseline renal function (group A) and 262 DTC patients with normal baseline renal function (group B) who received 131I therapy were analysed. Each group was further divided into three subgroups based on the cumulative activity of 131I: subgroup 1 if the cumulative activity was less than 11.1 GBq; subgroup 2 if the cumulative activity was between 11.1 GBq and 18.5 GBq; and subgroup 3 if the cumulative activity was more than 18.5 GBq. The clinical metrics of renal function including serum creatinine (SCr), blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR) were measured and compared before initial 131I treatment and 5 years later. RESULT: There was no significant difference of the demographics between the two groups. In group A, SCr and BUN levels were elevated in 186 and 113 patients, respectively, and eGFR was decreased in 108 patients before the initial ¹³¹I therapy. SCr and BUN levels were found to be increased in all subgroups 5 years after the initial ¹³¹I therapy; furthermore, eGFR was found to be decreased in all subgroups after ¹³¹I therapy, and the difference was statistically significant (p < 0.05). A gender bias was not observed in the changing trends of SCr and BUN levels and eGFR. In group B, no significant difference in the mean levels of SCr, BUN, and eGFR was observed in the 3 subgroups (p > 0.05), regardless of gender, before the initial ¹³¹I therapy and 5 years later. A total of 5, 2, and 2 patients presented with abnormal renal function after ¹³¹I treatment in subgroups 1, 2, and 3, respectively. No statistically significant difference was observed in the incidence of renal dysfunction among the 3 subgroups (p = 0.423). CONCLUSION: Our findings suggest that the nephrotoxicity of high-activity ¹³¹I therapy, regardless of gender, is very low in patients with DTC with normal renal function; however, high-activity ¹³¹I therapy may exacerbate the loss of renal function in those with renal dysfunction.

Predictive factors for the efficacy of 131I therapy with formulated dosage calculation on Graves' disease.

OBJECTIVE: To analyse predictive factors to ensure the efficacy of iodine-131 (131I) therapy on Graves' disease (GD). SUBJECTS AND METHODS: Graves' disease patients from three tertiary medical centers were enrolled. Serological data, thyroid mass estimation, thyroid radioactive iodine uptake, thyroid texture and thyroid murmurs (bruits) were recorded. Iodine-131 treatment was performed by applying a formulated calculation method. After one year of follow-up, GD patients with euthyroidism and hypothyroidism were classified as the cured group, and the other thyroid function status refers to the uncured group. These analyses were performed by using SPSS17.0 software. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 970 GD patients, of which 540 patients (55.7%) belonged to the cured group, and 430 patients (44.3%) belonged to the uncured group, participated in the current analyses. Multivariate logistic regression analysis was performed. Moreover, estimated thyroid mass, thyroid murmurs (bruits), prescribed 131I dosage, FT3 and FT4 have independent prognostic value for 131I efficacy, and their odds ratios are 1.368, 2.283, 1.326, 1.467 and 1.419, respectively. CONCLUSION: Graves' disease patients who are undergoing 131I therapy using the formulated dosage calculation could be influenced by thyroid mass, thyroid murmurs, 131I dosage and thyroid function.

Analysis of correlation factors influencing the outcome of initial 131I remnant ablative therapy in intermediate- to high-risk patients with papillary thyroid microcarcinoma.

OBJECTIVE: To investigate the factors influencing the outcome of initial 131I remnant ablative therapy in intermediate- to high-risk patients with papillary thyroid microcarcinoma (PTMC). METHODS: We divided 99 patients with PTMC who underwent total thyroidectomy into two groups according to their response to initial 131I remnant ablative therapy: excellent response (ER) and non-ER groups. Clinical and laboratory characteristics were collected and retrospectively analyzed using univariate and multivariate binary logistic regression. Receiver operator characteristic (ROC) curves and diagnostic cutoff values were analyzed to evaluate the predictive value of significant quantitative influencing factors for 131I treatment outcomes. A prognostic nomogram model based on the above independent risk factors was established. RESULTS: Of the 99 eligible patients who accepted the initial 131I treatment following total thyroidectomy, 76 (76.7%) were classified into the ER group and 23 (23.3%) into the non-ER group. The univariate and multivariate analyses showed that extrathyroidal extension [ETE; odds ratio (OR) = 4.769; P = 0.041], preablative thyrotropin (TSH; OR = 0.972; P = 0.017), and stimulated thyroglobulin (sTg; OR = 1.614; P = 0.040) were independent predictors for the therapeutic effect of 131I treatment. Patients with higher sTg (>1.37 ng/ml) and lower TSH (<67.97 mU/l) and ETE tended to have a poor response to initial 131I treatment. The quantification of the therapeutic effect of initial 131I therapy in patients with PTMC using our newly constructed nomogram showed that ETE, preablative sTg, and TSH were contributors to non-ER. CONCLUSION: Intermediate- to high-risk patients with PTMC after total thyroidectomy who had low pretreatment sTg and high preablative TSH levels and negative ETE were more likely to achieve satisfactory response to initial 131I remnant ablative therapy. Our prognostic nomogram is a valuable tool to enable patients and clinical professionals to be better informed about patients' therapeutic response to initial 131I remnant ablative therapy.

Impact of reconstruction parameters on spatial resolution and its comparison between cadmium-zinc-telluride SPECT/CT and conventional SPECT/CT.

OBJECTIVE: To evaluate the impact of reconstruction parameters on the spatial resolution of the tomographic image in single photon emission computed tomography (SPECT)/computed tomography (CT), and compare spatial resolution between a new polyvalent whole-body Cadmium-Zinc-Telluride camera (CZT-SPECT/CT) and a conventional dual-head Anger camera (conventional SPECT/CT). METHODS: Spatial resolution was evaluated with four-line sources filled with 99mTc in tomographic images reconstructed by varying reconstruction parameters. Ordered-subset expectation maximization (OSEM) algorithm was performed with varying iterations (1-20), the number of subsets was fixed at 10. Butterworth filter, Gauss filter and no-filter were selected, respectively. Computed tomography-based attenuation correction (CTAC), scatter correction, resolution recovery and no correction (NC) were adopted for image correction. Filtered back projection (FBP) with Butterworth filter and CTAC was performed in image reconstruction. Spatial resolution was expressed by the full width at half-maximum (FWHM) value. RESULTS: The impact of reconstruction parameters on the spatial resolution was identical in both cameras: FWHM values decreased with the increase of iterations and converged uniformly when the number of iterations was over 4. FWHM values decreased with the increase of cutoff frequency of the Butterworth filter and increased with the increase of the Gauss filter. scatter correction and resolution recovery improved spatial resolution, whereas CTAC had a negligible effect on spatial resolution when reconstructed by OSEM. FWHM was generally lower with OSEM reconstruction than FBP reconstruction. On the whole, under the same reconstruction conditions, CZT-SPECT/CT had a lower FWHM value than conventional SPECT/CT. CONCLUSION: The spatial resolution was improved with the increase of iterations. Increasing the cutoff frequency of the Butterworth filter and decreasing the Gauss filter enhanced spatial resolution. The spatial resolution was better reconstructed by OSEM associated with attenuation correction, scatter correction and resolution recovery than FBP. CZT-SPECT/CT had better spatial resolution than conventional SPECT/CT.

Rapid enrichment and sensitive detection of extracellular vesicles through measuring the phospholipids and transmembrane protein in a microfluidic chip.

Extracellular vesicles (EVs) have attracted tremendous attention in recent years and quantification of EVs is a key issue in the evaluation of vesicle-based diagnostics and therapeutic development, but it's quite challenging to determine whether higher protein expression signals are due to larger vesicle amount or higher protein content within each vesicle. To solve this problem, herein, we proposed a strategy based on staining phospholipid bilayers of EVs with lipophilic dyes to evaluate their lipid amount, which was subsequently normalized as an internal standard for studying the expression of transmembrane protein (i.e., CD63) on EVs in different samples. In addition, a microfluidic platform based on electrophoresis technology was invented to effectively enrich and detect EVs. Small fluorescent labeling molecules (i.e., uncombined aptamers) were on-chip removed from EVs without pre-separation via ultracentrifugation or ultrafiltration which were indispensable in nanoparticle tracking analysis (NTA) and flow cytometry techniques and the performance of this assay is comparable to NTA. Finally, it was found obvious difference in the expression of CD63 on EVs before and after normalization based on lipid amount in plasma samples. This method is expected to provide more accurate information when comparing the expression levels of EVs biomarkers in different samples.

Prognostic value and dynamics of antithyroglobulin antibodies for differentiated thyroid carcinoma.

Background: The clinical value of antithyroglobulin antibodies (TgAb) as a tumor marker for differentiated thyroid cancer (DTC) is still controversial. Materials & methods: We studied 110 TgAb positive DTC patients who underwent total thyroidectomy and 131I therapies. Multivariate logistic regression was conducted to analyze the association between prognostic factors and disease outcomes. Results & conclusion: Pre-ablation TgAb levels and the changes of TgAb in 6-12 months after the first 131I therapy were risk factors for disease outcome in patients younger than 55, while extrathyroid extension was a risk factor in patients older than 55. The median TgAb half-life was 7.7 months and the median time for TgAb positivity to become negative was 15.8 months. The dynamics of TgAb within the first year after remnant ablation could predict disease outcome for DTC patients.

An innovative method for manganese (Mn2+) and ammonia nitrogen (NH4+-N) stabilization/solidification in electrolytic manganese residue by basic burning raw material.

High concentrations of manganese (Mn2+) and ammonia nitrogen (NH4+-N) in electrolytic manganese residue (EMR) have seriously hindered the sustainable development of electrolytic manganese industry. In this study, an innovative basic burning raw material (BRM) was used to stabilize/solidify Mn2+ and NH4+-N in EMR. The characteristics of EMR and BRM, stabilize mechanism of NH4+-N and Mn2+, and leaching test were investigated. The concentrations of NH4+-N and Mn2+ were 12.8 mg/L and 0.1 mg/L, respectively, when the solid liquid ratio was 1.5:1, and the mass ratio of EMR and BRM was 100:10, at the temperature of 20 °C reacting for 12 h Mn2+ was mostly solidified as bustamite ((Mn,Ca)Si2O6), groutite (MnOOH) and ramsdellite (MnO2). NH4+-N was mostly recycled by (NH4)2SO4 and (NH4)3H(SO4)2. Leaching test results indicated that the concentrations of heavy metals were within the permitted level for the integrated wastewater discharge standard (GB8978-1996). Economic evaluation revealed that the cost of EMR treatment was $ 10.15/t by BRM. This study provided a new research idea for EMR harmless disposal.

Anti-PD-1 Therapy plus Chemotherapy and/or Bevacizumab as Second Line or later Treatment for Patients with Advanced Non-Small Cell Lung Cancer.

Immune checkpoint inhibitor combination therapy exhibited outstanding efficacy in first line setting for advanced non-small cell lung cancer (aNSCLC) patients. However, whether PD-1 inhibitor combined treatment is effective in second line or later setting remains unknown. Therefore, we retrospectively evaluated the efficacy of combined therapy of PD-1 inhibitor with chemotherapy and/or bevacizumab compared to PD-1 inhibitor alone for aNSCLC patients in second line or later setting. Patients with aNSCLC who have received anti-PD-1 based therapy between 2015 and 2017 were screened, and 55 patients were ultimately included and divided into the monotherapy group (N=33) and the combination group (N=22). Patients treated with combination therapy exhibited superior PFS versus those treated with monotherapy (median PFS, 7.5 months vs 3.3 months; hazard ratio 0.28; 95% CI, 0.14-0.56; P<0.001). Objective response rate and disease control rate were 31.8% (7/22) and 95.5% (21/22) in the combination group and 10.0% (3/30) and 46.7% (14/30) in the monotherapy group, respectively (ORR, P=0.075; DCR, P<0.001). Five patients (22.7%) experienced grade 3-4 adverse events in the combination group and two patients (6.1%) in the monotherapy group. Taken together, our results indicated that for NSCLC patients who had failed on the first-line or later treatment, PD-1 inhibitor in combination with chemotherapy and/or bevacizumab might be a favorable treatment option. These findings warrant further validation in prospective studies.

Immune checkpoint inhibitors combined with chemotherapy for the treatment of advanced pancreatic cancer patients.

Immune checkpoint inhibitors (ICIs) represent a major breakthrough for cancer treatment. However, evidence regarding the use of ICIs in pancreatic cancer (PC) remained scarce. To assess the efficacy and safety of ICIs plus chemotherapy, patients with advanced PC were retrospectively recruited and were treated with either chemotherapy alone or chemotherapy plus ICIs. Patients previously treated with any agents targeting T-cell co-stimulation or checkpoint pathways were excluded. The primary outcome was overall survival (OS). The secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and safety. In total, 58 patients were included (combination, n = 22; chemotherapy, n = 36). The combination group showed a significantly longer OS than the chemotherapy group [median, 18.1 vs 6.1 months, hazard ratio (HR) 0.46 (0.23-0.90), P = 0.021]. The median PFSs were 3.2 months in the combination group and 2.0 months in the chemotherapy group [HR 0.57 (0.32-0.99), P = 0.041]. The combination group and the chemotherapy group had similar ORRs (18.2% vs 19.4%, P = 0.906). All patients who achieved a partial response received a doublet chemotherapy regimen regardless of co-treatment with ICIs. Grade 3 or higher adverse events occurred in 31.8% of the patients in the combination group and in 16.9% of those receiving chemotherapy. Although the incidence of serious treatment-related adverse events was higher in the combination group than in the chemotherapy group, the difference was not significant (P = 0.183). Our findings suggest that the combination of ICIs with chemotherapy is both effective and tolerable for advanced PC. ICIs combined with a doublet chemotherapy regimen might be a preferable choice.

Development of a nanobody tagged with streptavidin-binding peptide and its application in a Luminex fluoroimmunoassay for alpha fetal protein in serum.

Sensitive and accurate detection of disease-related biomarkers can promote the early screening and diagnosis of cancers for improving the prognosis and survival of patients. Herein alpha fetal protein (AFP) was selected as the model macromolecule antigen and we developed AFP-specific alpaca nanobodies (Nbs) from an immunized phage-displayed Nb library. Then Nbs tagged with streptavidin-binding peptide (Nb-SBP) were constructed and used to develop an Nb-SBP-mediated fluoroimmunoassay based on the Luminex-200 system (NS-LFIA). Based on the optimal experimental conditions, the NS-LFIA has a limit of detection of 0.237 ng mL-1 with a linear detection range of 0.49-125 ng mL-1. The average recovery rate and relative standard derivation were in the range of 98.2-110% and 2.8-13.8%, respectively. The NS-LFIA is highly selective for AFP and ignorable cross-reaction was observed with the other biomarkers. The content of AFP in clinical serum samples was determined by both the developed NS-LFIA and the Roche E601 automatic chemiluminescence immunoassay analyzer and a good correlation was obtained between the two methods (R 2 = 0.9894). Moreover, the Nb-SBP can significantly improve the homogeneity of the fluorescent signals tested by the Luminex-200 system compared with the biotinylated conventional monoclonal antibodies, which could reduce the magnetic microsphere consumption and test cost by decreasing the repetitions of each sample. Thus the results demonstrated that the Nb-SBP was a very promising immunological diagnostic reagent and indicated the applicability and reliability of the NS-LFIA for sensitive detection of AFP and other disease-related biomarkers.