Thyroid cancer is the most common endocrine cancer, of which the incidence has dramatically increased worldwide in the past few decades. The reasons for the observed rapid increase still are not fully understood, but evidence suggests that overdiagnosis, with the advancement in detection methods and screening policies, is not the sole driver of the substantial increase of the incidence. However, the effect of environmental/lifestyle factors remains speculative other than that of radiation exposure at a young age. This review tries to give a balanced view of debated factors leading to the thyroid cancer epidemic, to offer some alternatives in understanding the controversies, and to suggest potential directions in the search of modifiable risk factors to help reduce thyroid cancer.

Reasons behind the rapid increase of thyroid cancer (TC) in China are uncertain. We assessed the burden of TC and the role of access to screening and salt iodization. We analyzed two national databases in China: Hospital Quality Monitoring System (HQMS) and China Reinsurance Company (CRC) database. HQMS covered 1037 (44.3%) Class 3 hospitals and 76 263 617 Class 3 hospital inpatients in 2013 to 2017 and CRC covered 93 123 018 clients in 2000 to 2016. The proportion of TC inpatients among inpatients in HQMS and TC incidence in critical illness insurance buyers were used to evaluate the association with screening and iodine status. Between 2013 and 2017, the proportion of TC patients in HQMS with urban employee medical insurance and good access to screening increased sharply while there was little change among those with the other two forms of medical insurance. Across provinces, the proportion of TC inpatients in HQMS was positively correlated with per capita disposable income but not with median urinary iodine. Similar findings were observed in the CRC database. In 2017, approximately 1000 individuals were overdiagnosed with TC daily. We conservatively forecast that 5.1 million healthy individuals would become TC patients unnecessarily between 2019 and 2030. Our findings suggested the epidemic of TC in China was substantially underestimated. It was associated with screening but not with salt iodization.

Differentiation of benign and malignant thyroid nodules is crucial for clinical management. Here, we explored the efficacy of next-generation sequencing (NGS) in predicting the classification of benign and malignant thyroid nodules and lymph node metastasis status, and simultaneously compared the results with ultrasound (US). Thyroline was designed to detect 15 target gene mutations and 2 fusions in 98 formalin-fixed, paraffin-embedded (FFPE) tissues, including those from 82 thyroid cancer (TC) patients and 16 patients with benign nodules. BRAF mutations were found in 57.69% of the papillary thyroid cancer (PTC) cases, while RET mutations were detected among all the medullary thyroid cancer (MTC) cases. Multiple mutations were positive but none showed dominance in anaplastic thyroid cancer (ATC) and follicular thyroid cancer (FTC). The sensitivity and specificity of NGS prediction in differentiation of benign and malignant thyroid nodules were 79.27 and 93.75%, respectively, and the positive predictive value (PPV) and negative predictive value (NPV) were 98.48 and 46.88%, respectively. The sensitivity and specificity of US were 76.83 and 6.25%, respectively, and the PPV and NPV were 80.77 and 5.00%, respectively. The area under curve (AUC) of NGS and US were 0.865 and 0.415, respectively. A total of 27 patients had ≥1 metastases to lymph nodes, 19 of which carried mutations, including BRAF, RET, NRAS, PIK3CA, TP53, CTNNB1 and PTEN. However, there was no correlation between the variant allele frequency of specific gene mutations and the number of metastatic lymph nodes. In conclusion, the prediction value of NGS was higher than the US-based Thyroid Imaging Reporting and Data System (TI-RADS). NGS is valuable for the accurate differentiation of benign and malignant thyroid nodules, and pathological subtypes in FFPE samples. The findings of the present study may pave the way for the application of NGS in analyzing fine-needle aspiration (FNA) biopsy samples.

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A better understanding of the current features of type 2 diabetes mellitus (T2DM)related clinical trials is important for improving designs of clinical trials and identifying neglected areas of research. It was hypothesized that the trial registration policy promoted the designs of T2DM-related trials over the years. Therefore, this study aimed to present a comprehensive overview of T2DM-related clinical trials registered in the ClinicalTrials.gov database. Methods: T2DM-related clinical trials registered in the ClinicalTrials.gov database were searched and assessed the characteristics of the relevant trials. We searched PubMed and Google Scholar for the publication statuses of the primary completed trials. Results: Overall, 5117 T2DM-related trials were identified for analysis. Of the interventional trials, 71.5% had a primary treatment purpose while only 8.9% were prevention or health service. There were more interventional trials registered prior to patient recruitment between 2012 and 2019 than between 2004 and 2011 (44.6% vs 19.9%, P<0.001). The period between 2012 and 2019 also had more trials that enrolled <100 participants (59.2% vs 50.9%), were single-center studies (60.7% vs 50.6%), had non-randomized allocations (11.3% vs 6.3%), were open-label (49.2% vs 45.6%), and had smaller sample sizes than the period between 2004 and 2011 (all P<0.001). The five-year cumulative publication rates after primary completion of the trials were <40%. Conclusion: Although the ClinicalTrials.gov database did not include all clinical trials, the trials registered in the ClinicalTrials.gov database still accounted for most of the clinical studies. Encouragingly, more interventional trials were registered prior to patient recruitment over the years. The majority of T2DM-related clinical trials focused on drug-related treatment, and trials regarding prevention in T2DM should be promoted. More attention should be paid to improve the publication and dissemination of clinical trials results.