Adding Color to Mass Spectra of Biopolymers: Charge Determination Analysis (CHARDA) Assigns Charge State to Every Ion Peak.

Traditionally, mass spectrometry (MS) output is the ion abundance plotted versus the ionic mass-to-charge ratio m/z. While employing only commercially available equipment, Charge Determination Analysis (CHARDA) adds a third dimension to MS, estimating for individual peaks their charge states z starting from z = 1 and color coding z in m/z spectra. CHARDA combines the analysis of ion signal decay rates in the time-domain data (transients) in Fourier transform (FT) MS with the interrogation of mass defects (fractional mass) of biopolymers. Being applied to individual isotopic peaks in a complex protein tandem (MS/MS) data set, CHARDA aids peptide mass spectra interpretation by facilitating charge-state deconvolution of large ionic species in crowded regions, estimating z even in the absence of an isotopic distribution (e.g., for monoisotopic mass spectra). CHARDA is fast, robust, and consistent with conventional FTMS and FTMS/MS data acquisition procedures. An effective charge-state resolution Rz ≥ 6 is obtained with the potential for further improvements.

Prognostic factors for postoperative papillary thyroid cancer with unexplained elevated Tg: A retrospective study.

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients. Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled. The causal categorization for elevated Tg was analyzed 6 months post RAT and the long-term therapeutic responses were assessed at the end of follow-up. To identify risk factors influencing recurrence-free survival (RFS), both univariate and multivariate Cox regression analysis were employed. Kaplan-Meier method was utilized for plotting survival curves. Results: A cohort of 165 subjects was enrolled for the analyses. Based on the results of a six-month follow-up, the postoperative unexplained elevated Tg among 165 patients could be ultimately attributed to thyroid remnant in 13.94% (23/165), biochemical disease in 60.00% (99/165), and structural disease in 26.06% (43/165). With a median follow-up of 58 months, 51 (30.91%), 34 (20.60%), 21 (12.73%), and 59 (35.76%) of the 165 patients achieved ER, IDR, BIR and SIR, respectively. Univariate analysis showed that N stage, TNM stage and suppressed Tg 6 months post RAT may be prognostic factors affecting RFS. Multivariate analysis showed that N1b stage [HR:2.749, P = 0.003] and II/III stage [HR:2.910, P = 0.001] were independent risk factors for RFS. Conclusion: The proportion of 165 postoperative PTC patients with unexplained elevated Tg developing structural disease within nearly 5 years was over 30%. Patients with N1b stage and higher TNM stage were more likely to develop structural disease.

Ultralight Ultrafast Enzymes.

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it. Bacteria showed faster growth, with most proteins exhibiting higher thermal stability, while for recombinant enzymes expressed in depleted media, faster kinetics was discovered. At room temperature, luciferase, thioredoxin and dihydrofolate reductase and Pfu DNA polymerase showed up to a 250 % increase in activity compared to the native counterparts, with an additional ∼50 % increase at 10 °C. Diminished conformational and vibrational entropy is hypothesized to be the cause of the accelerated kinetics. Ultralight enzymes may find an application where extreme reaction rates are required.

Macrocyclic-Albumin Conjugates for Precise Delivery of Radionuclides and Anticancer Drugs to Tumors.

Precise delivery of radionuclides and anticancer drugs to tumor tissue is crucial to ensuring drug synergism and optimal therapeutic effects in radionuclide-based combination radio-chemotherapy. However, current codelivery vectors often rely on physical embedment/adsorption to load anticancer drugs, which lacks precise mechanisms for drug loading and release, resulting in unpredictable combination effects. Herein, a macrocyclic-albumin conjugate (MAC) that enables precise loading and controlled release of anticancer drugs is presented. By conjugating multiple macrocyclic hosts (sulfonate azocalix[4]arenes, SAC4A) to albumin molecules, the MAC facilitates the precise loading of anticancer drugs through host-guest interactions and site-specific labeling of radionuclides. Furthermore, the MAC degrades under hypoxic conditions, enabling the release of loaded drugs upon reaching tumor tissues. Through precise loading and targeted delivery of radionuclides and anticancer drugs, MAC achieves efficient cancer diagnosis and combined radio-chemotherapy in breast cancer cell (4T1)-bearing mice. Considering that SAC4A can load many anticancer drugs, MAC may provide a promising platform for effective combination radio-chemotherapy.

Tandem Mass Spectrometry de novo Sequencing of the Skin Defense Peptides of the Central Slovenian Agile Frog Rana dalmatina.

Peptides released on frogs' skin in a stress situation represent their only weapon against micro-organisms and predators. Every species and even population of frog possesses its own peptidome being appropriate for their habitat. Skin peptides are considered potential pharmaceuticals, while the whole peptidome may be treated as a taxonomic characteristic of each particular population. Continuing the studies on frog peptides, here we report the peptidome composition of the Central Slovenian agile frog Rana dalmatina population. The detection and top-down de novo sequencing of the corresponding peptides was conducted exclusively by tandem mass spectrometry without using any chemical derivatization procedures. Collision-induced dissociation (CID), higher energy collision-induced dissociation (HCD), electron transfer dissociation (ETD) and combined MS3 method EThcD with stepwise increase of HCD energy were used for that purpose. MS/MS revealed the whole sequence of the detected peptides including differentiation between isomeric Leu/Ile, and the sequence portion hidden in the disulfide cycle. The array of the discovered peptide families (brevinins 1 and 2, melittin-related peptides (MRPs), temporins and bradykinin-related peptides (BRPs)) is quite similar to that of R. temporaria. Since the genome of this frog remains unknown, the obtained results were compared with the recently published transcriptome of R. dalmatina.

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.

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.

EThcD Benefits for the Sequencing Inside Intramolecular Disulfide Cycles of Amphibian Intact Peptides.

Disulfide bonds formed by a pair of cysteine residues in the peptides' backbone represent a certain problem for their sequencing by means of mass spectrometry. As a rule, in proteomics, disulfide bonds should be cleaved before the analysis followed by some sort of chemical derivatization. That step is time-consuming and may lead to losses of minor peptides of the analyzed mixtures due to incomplete reaction, adsorption on the walls of the vials, etc. Certain problems in the de novo top-down sequencing of amphibian skin peptides are caused by the C-terminal disulfide loop, called the Rana box. Its reduction with or without subsequent derivatization was considered to be an unavoidable step before mass spectrometry. In the present study, EThcD demonstrated its efficiency in sequencing intact disulfide-containing peptides without any preliminary derivatization. Applied to the secretion of three frog species, EThcD provided the full sequence inside the intramolecular disulfide cycle for all S-S-containing peptides found in the samples, with the only exception being diarginine species. Proteolytic fragments, which are shorter than the original peptides, were helpful in some cases. HCD should be mentioned as a complementary tool to the EThcD tool, being useful as a confirmation method for some sequence details.

Establishment and validation of an AI-aid method in the diagnosis of myocardial perfusion imaging.

BACKGROUND: This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. METHODS: We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named "YOLO" to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). RESULTS: Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value < 0.05). CONCLUSION: The AI system of our study showed excellent predictive accuracy in the diagnosis of MPI protocols, and therefore might be potentially helpful to aid radiologists in clinical practice and develop more sophisticated models.

Hazard ratios of second primary malignancy after radioiodine for differentiated thyroid carcinoma: a large-cohort retrospective study.

INTRODUCTION: The objective of this study is to evaluate the benefits of radioactive iodine (RAI) treatment and the risk of second primary malignancy (SPM) in RAI-treated patients. MATERIAL AND METHODS: The cohort for this analysis consisted of individuals diagnosed with a first primary differentiated thyroid carcinoma (DTC), reported by the Surveillance, Epidemiology, and End Results (SEER) database in 1988-2016. Overall survival (OS) difference was estimated by Kaplan-Meier curves and log-rank test, and hazard ratios (HR) were obtained by Cox proportional-hazards model to evaluate the association between RAI and SPM. RESULTS: Among 130,902 patients, 61,210 received RAI and 69,692 did not, and a total of 8604 patients developed SPM. We found that OS was significantly higher in patients who received RAI than in those who did not (p < 0.001). DTC survivors treated with RAI had increased risk of SPM in females (p = 0.043), particularly for SPM occurring in the ovary (p = 0.039) and leukaemia (p < 0.0001). The risk of developing SPM was higher in the RAI group than in the non-RAI group and the general population, and the incidence increased with age. CONCLUSIONS: Increased risk of SPM occurs in female DTC survivors treated with RAI, which become more obvious with increasing age. Our research findings were beneficial to the formulation of RAI treatment strategies and the prediction of SPM for patients with thyroid cancer of different genders and different ages.

Establishment and analytical performance of light-initiated chemiluminescence assay method for detecting thyrotropin receptor antibody.

Aim: To evaluate double-antibody competitive light-initiated chemiluminescence assay method for detecting the thyrotropin receptor antibody. Materials & methods: The optimal working concentrations of competitive antibody and rTSHR were confirmed by checkerboard titration. Assay performance was assessed by precision, linearity, accuracy, limit of blank and clinical evaluation. Results: The coefficient of variation for repeatability and intermediate precision was 3.9-5.9 and 0.9-1.3%, respectively. The correlation coefficient was 0.999 by least squares linear fitting in linearity evaluation. The relative deviation ranged from -5.9 to 4.1%, and the limit of blank of the method was 0.13 IU/l. Compared with the Roche cobas system (Roche Diagnostics, Mannheim, Germany), the relationship between the two assays was shown to be significantly correlative. Conclusion: The light-initiated chemiluminescence assay method for detecting thyrotropin receptor antibody is a rapid, novel and accurate method for thyrotropin receptor antibody measurement.

Graves' disease is common in daily life. Patients often experience rapid heartbeat and weight loss. Blood tests (especially serum autoantibody levels) are meaningful in diagnosis and treatment. In this study, we used a new and useful approach to test blood markers. Compared with other methods, this new technique could perform better in terms of time and expense. Based on a full assessment, we believe that this new method will play an important role in clinical application.

Epidemiological and demographic drivers of lung cancer mortality from 1990 to 2019: results from the global burden of disease study 2019.

Background: Understanding the effects of demographic drivers on lung cancer mortality trends is critical for lung cancer control. We have examined the drivers of lung cancer mortality at the global, regional, and national levels. Methods: Data on lung cancer death and mortality were extracted from the Global Burden of Disease (GBD) 2019. Estimated annual percentage change (EAPC) in the age-standardized mortality rate (ASMR) for lung cancer and all-cause mortality were calculated to measure temporal trends in lung cancer from 1990 to 2019. Decomposition analysis was used to analyze the contributions of epidemiological and demographic drivers to lung cancer mortality. Results: Despite a non-significant decrease in ASMR [EAPC = -0.31, 95% confidence interval (CI): -1.1 to 0.49], the number of deaths from lung cancer increased by 91.8% [95% uncertainty interval (UI): 74.5-109.0%] between 1990 and 2019. This increase was due to the changes in the number of deaths attributable to population aging (59.6%), population growth (56.7%), and non-GBD risks (3.49%) compared with 1990 data. Conversely, the number of lung cancer deaths due to GBD risks decreased by 19.8%, mainly due to tobacco (-12.66%), occupational risks (-3.52%), and air pollution (-3.47%). More lung cancer deaths (1.83%) were observed in most regions, which were due to high fasting plasma glucose levels. The temporal trend of lung cancer ASMR and the patterns of demographic drivers varied by region and gender. Significant associations were observed between the contributions of population growth, GBD risks and non-GBD risks (negative), population aging (positive), and ASMR in 1990, the sociodemographic index (SDI), and the human development index (HDI) in 2019. Conclusion: Population aging and population growth increased global lung cancer deaths from 1990 to 2019, despite a decrease in age-specific lung cancer death rates due to GBD risks in most regions. A tailored strategy is needed to reduce the increasing burden of lung cancer due to outpacing demographic drivers of epidemiological change globally and in most regions, taking into account region- or gender-specific risk patterns.

Impacts of different reconstruction methods on the image quality of cadmium-zinc-telluride-based single photon emission computed tomography/computed tomography pulmonary perfusion imaging.

OBJECTIVE: The objective was to evaluate the impacts of different reconstruction methods [filtered back projection (FBP) and ordered subset expectation maximization (OSEM)] and different filters (Butterworth filter and Gaussian filter) on the image quality in cadmium-zinc-telluride (CZT)-based single photon emission computed tomography (SPECT)/computed tomography (CT) pulmonary perfusion imaging. METHODS: A combinations including FBP with Butterworth filter, OSEM with Butterworth filter (OSEM + Butterworth filter ), and OSEM with Gaussian filter (OSEM + Gaussian filter) were used during SPECT image reconstruction. Visual and quantitative parameters [root mean square (RMS) noise, contrast and contrast-to-noise ratio (CNR)] were used to evaluate image quality. RESULTS: The OSEM + Gaussian filter had better RMS noise and CNR than those of the FBP + Butterworth filter or OSEM + Butterworth filter, while the OSEM + Butterworth filter had the best contrast. The highest visual scores were obtained by OSEM + Gaussian filter ( P  < 0.0001). In the lesion size <2 cm group, the contrast ( P < 0.01) and visual scores ( P < 0.001) of OSEM + Butterworth filter were better than those of the other two groups. In the lesion size ≥2 cm group, the RMS noise and visual scores of OSEM + Gaussian filter were better than those of the other two groups. CONCLUSION: In CZT SPECT/CT pulmonary perfusion imaging, this study recommended the clinical use of the OSEM + Gaussian filter combination for reconstruction in both conventional and larger lesions, the OSEM + Butterworth filter image postprocessing method might be advantageous in small lesions.

Effect tracking of 131I treatment in Graves' hyperthyroidism patients within 1 year and analysis of the factors that may influence the cure.

OBJECTIVE: To observe the disease development and outcome of Graves' disease (GD) patients within 1 year after iodine-131 (131I) treatment, and analyze the factors affecting the treatment effect. SUBJECTS AND METHODS: Clinical data of 221 patients who received the first treatment with 131I in our department from June 2016 to October 2018 were retrospectively analyzed and they were followed up at 3 months, 6 months and 1 year after the treatment. According to the three follow-up records, the cure rate was calculated and the follow-up chart was drawn. The factors that may affect the clinical cure were analyzed according to the follow-up results after 1 year: Independent risk factors affecting the prognosis were screened out by Logistic regression analysis, and the effects of the above factors on the prognosis were further analyzed by Chi-square test, and the cure multiple relationship caused by the influencing factors was analyzed by Logistic regression analysis. RESULTS: The cure rate was 58.82% and the effective rate was 71.95%. At the 3-month follow-up, 11 patients (4.98%) presented complete response, 99 patients (44.80%) presented hypothyroidism, 93 patients (42.08%) presented partial response, and 18 patients (8.14%) presented no effect or recurrence. At 6 months, 18 cases (8.14%) had complete response, 90 cases (40.72%) had hypothyroidism, 59 cases (26.70%) had partial response, and 54 cases (24.43%) had no effect or recurrence. At 12 months, 36 cases (16.29%) had complete response, 94 cases (42.53%) had hypothyroidism, 29 cases (13.12%) had partial response, and 62 cases (28.05%) had no effect or recurrence. Thyroid weight and thyroid peroxidase antibody (TPOAb) were the influencing factors. Among all patients, patients with thyroid weight ≤28.70g were 4.25 times more likely to achieve clinical cure than patients with >28.70g [OR (95%CI):4.252 (2.383-7.588), P<0.01)], female patients with the thyroid weight ≤28.70g was 5.78 times than those with >28.70g [OR (95%CI): 5.776 (2.951-11.308), P<0.01]. In male, patients with TPOAb≤449.00IU/mL were 0.27 times more likely to achieve clinical cure than those with >449.00IU/mL [OR (95%CI): 0.274 (0.081-0.919), P<0.05]. CONCLUSION: Iodine-131 was an effective treatment to GD. Thyroid weight before treatment was the influencing factor for all patients and female patients, while TPOAb was the influencing factor for male patients.

Non-invasive diagnosis of acute kidney injury using Mn-doped carbon dots-based magnetic resonance imaging.

As Gd-based contrast agents suffer from the risk of causing nephrogenic systemic fibrosis, less toxic contrast agents are urgently needed in contrast-enhanced magnetic resonance imaging (CE-MRI) of kidney injury. Herein, we develop a non-invasive diagnosis method for acute kidney injury using CE-MRI based on manganese-doped carbon dots (Mn-CDs). The synthesized Mn-CDs possess an ultrasmall size of 5 nm, good biocompatibility, and a high T1 relaxation rate (10.8 mM-1 s-1), which can produce effective positive enhancement in the kidneys and clearly show the fine structures of the kidneys including the cortex, outer medulla, and inner medulla. In an acute kidney injury model, Mn-CDs-based CE-MRI can not only accurately and intuitively reveal the site of kidney injury consistent with the pathological analysis, but also reflect the functional changes in the injured kidney. Collectively, our study provides a new strategy for the non-invasive diagnosis of acute kidney injury using CE-MRI based on Mn-CDs.

Prognosis of thyroid carcinoma patients with osseous metastases: an SEER-based study with machine learning.

OBJECTIVE: Osseous metastasis (OM) is the second most common site of thyroid cancer distant metastasis and presents a poor prognosis. Accurate prognostic estimation for OM has clinical significance. Ascertain the risk factors for survival and develop an effective model to predict the 3-year, 5-year overall survival (OS) and cancer-specific survival (CSS) for thyroid cancer patients with OM. METHODS: We retrieved the information of patients with OMs between 2010 and 2016 from the Surveillance, Epidemiology, and End Result Program. The Chi-square test, and univariate and multivariate Cox regression analyses were performed. Four machine learning (ML) algorithms, which were most commonly used in this field, were applied. RESULT: A total of 579 patients having OMs were eligible. Advanced age, tumor size ≥ 40 mm, combined with other distant metastasis were associated with worse OS in DTC OMs patients. Radioactive iodine (RAI) significantly improved CSS in both males and females. Among four ML models [logistic regression, support vector machines, extreme gradient boosting, and random forest (RF)], RF had the best performance [area under the receiver-operating characteristic curve: 0.9378 for 3-year CSS, 0.9105 for 5-year CSS, 0.8787 for 3-year OS, 0.8909 for 5-year OS]. The accuracy and specificity of RF were also the best. CONCLUSIONS: RF model shall be used to establish an accurate prognostic model for thyroid cancer patients with OM, not only from the SEER cohort but also intended for all thyroid cancer patients in the general population, which may be applicable in clinical practice in the future.

Cancer-associated fibroblasts in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.

Effect of Lugol's solution on 131I therapy efficacy in Graves' disease.

PURPOSE: Lugol's solution could control thyroid function and suppress 131I uptake in hyperthyroidism. This study aimed to investigate the appropriate time to withdraw Lugol's solution before 131I therapy (RIT) in Graves' disease (GD) patients, and how this should influence 131I uptake and RIT outcome. METHODS: Two groups (125 cases and 1805 cases) of GD patients received RIT, who were pre-treated with and without Lugol's solution (RI-CI group and RI group). The RI-CI group was further divided into the following sub-groups depending on the duration span between Lugol's solution withdrawal and RIT: sub-group A, 4-7 d (n = 49); sub-group B, 8-14 d (n = 41); and sub-group C, 15-30 d (n = 35). The highest radioactive iodine uptake rate (RAIUmax), effective half-life (Teff), TRAb, and free triiodothyronine (FT3) and free thyroxine (FT4) levels were compared, and therapeutic outcome was evaluated. RESULTS: There were no significant differences in RAIUmax, TRAb, and Teff among the four sub-groups (P > 0.05). Both FT3 and FT4 levels in sub-groups A and B were lower than those in group RI and sub-group C (P < 0.05). The outcome of non-hyperthyroidism (euthyroidism + hypothyroidism) in groups RI-CI and RI was significantly different at post-RIT month 1 and 3 (P < 0.05). However, intergroup differences at 6 and 12 months were not significant (P > 0.05). CONCLUSIONS: Withdrawal of Lugol's solution 4-7 or 8-14 d before RIT does not influence 131I uptake and RIT efficacy in GD. Moreover, in order to avoid a rapid increase in thyroid hormone levels at the same time, Lugol's solution should be withdrawn 4-7 d before RIT.

The impact of low-dose CT on smoking behavior among non-smokers, former-smokers, and smokers: A population-based screening cohort in rural China.

BACKGROUND: Lung cancer screening may provide a "teachable moment" for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non-smokers has not been reported. METHODS: A baseline smoking behavior survey was conducted in 2000 participants who were screened by low-dose computed tomography (LDCT) from 2014 to 2018. All participants were re-surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non-smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression. RESULTS: From 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non-smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non-smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27-6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08-0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes. CONCLUSIONS: The overall decreased smoking prevalence indicated an overwhelming effect of "teachable moment" on "license to smoke." A tailored smoking cessation strategy should be integrated into lung cancer screening.

Testing the link between isoaspartate and Alzheimer's disease etiology.

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts protein structures, making them prone to aggregation. Here we strengthened the link between isoAsp and Alzheimer's disease (AD) by novel approaches to isoAsp analysis in human serum albumin (HSA), the most abundant blood protein and a major carrier of amyloid beta (Aß) and phosphorylated tau (p-tau) in blood. We discovered a reduced amount of anti-isoAsp antibodies (P < 0.0001), an elevated isoAsp level in HSA (P < 0.001), more HSA aggregates (P < 0.0001), and increased levels of free Aß (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with Aß and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of Aß and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.