No abstract

Neoadjuvant chemoradiotherapy (nCRT) following surgery significantly improves the survival rate of patients with rectal cancer. However, nCRT is associated with significant adverse symptoms and high medical costs. Therefore, it is important to investigate potential biomarkers for the prediction of the response to nCRT in patients with rectal cancer. The present study identified candidate biomarkers for predicting a complete response (CR) to nCRT in patients with rectal cancer and investigated the associated mechanisms. Microarray data (accession no. GSE29298) was downloaded from the Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs/miR) were screened between the pathological CR (pCR) group and no pCR (incomplete response) group. miRNA target genes were predicted using the miRWalk 2.0 online tool and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, a miRNA co-regulatory network was constructed and disease-associated genes were predicted. The results demonstrated that a total of 36 upregulated and 5 downregulated miRNAs were identified between the two groups. Among these differentially expressed miRNAs, miR-548c-5p, miR-548d-5p and miR-663a were significantly associated with a CR to nCRT. The co-regulatory network and pathway analysis indicated that miR-548c-5p and miR-548d-5p may function together through stem cell pluripotency and ubiquitin-mediated proteolysis signaling pathways. Furthermore, the prediction of disease-associated genes demonstrated that miR-548c-5p/miR-548d-5p and miR-663a may regulate genes associated with rectal cancer, including mutated in colorectal cancers (MCC) and adenomatous polyposis coli (APC), and colorectal neoplasms, including interleukin-6 signal transducer (IL6ST), cell cycle checkpoint kinase 2 (CHEK2), marker of proliferation Ki-67 (MKI67), cadherin 7 (CDH7), calreticulin (CALR) and transforming growth factor β1 (TGFB1). Therefore, miR-548c-5p, miR-548d-5p and miR-663a are promising candidate biomarkers for predicting a CR to nCRT. miR-548c-5p/miR-548d-5p may be associated with a CR by regulating IL6ST, CHEK2, MKI67 and MCC. In addition, it may function through the pluripotency of stem cells and ubiquitin-mediated proteolysis signaling pathways. miR-663a may be associated with a CR to nCRT by targeting CDH7, CALR, APC and TGFβ1. Thus, the miRNA biomarkers investigated in the present study may represent novel therapeutic targets for the prediction and eventual improvement of the response to nCRT in patients with rectal cancer.

Background:The aim of this study is to compare microRNA expression patterns in different stages of colorectal cancer (CRC) and to discuss the significance of the application of microRNAs in the clinical treatment of CRC.Methods:The study used gene chip technology to analyze genetic sequences in CRC tissues and surrounding normal tissues at different cancer stages. The bioinformatics profiles of the target genes of the different microRNAs were analyzed to clarify the target gene-related pathways and their functions in the disease.Results:A total of 368 target genes with differential expression, including 275 upregulated and 93 downregulated genes, were screened from CRC patients in different stages of the disease. These microRNAs participated widely in the occurrence and development processes of CRC. The microRNA expression profiles obviously differed in tissues at different CRC stages.Conclusion:microRNA regulation of CRC samples can be used as a tool to control the occurrence and development of tumor cells.

Ultrasonography (US) is one of the most important methods for the management of thyroid nodules, which can be classified as solid, partially cystic, or cystic by composition. The various Thyroid Imaging Reporting and Data System classifications pay more attention to solid nodules and have reported pertinent US features associated with malignancy. However, the likelihood of malignancy of partially cystic thyroid nodules (PCTNs) is 3.3–17.6%, and few studies have systematically discussed the value of US in differentiating such entities. Therefore, we deemed it necessary to perform a systematic evaluation of US features in recognizing malignant PCTNs. Our systematic review and meta-analysis aimed to assess the value of US features in predicting malignant PCTNs. We searched the PubMed/MEDLINE, Web of Science, and Cochrane Library databases to find studies that researched US features of PCTNs and that were published before June 2020. Review Manager 5.3 was used to summarize suspicious US features and calculate the sensitivity, specificity, and likelihood ratios. MetaDiSc 1.4 was used to estimate receiver operating characteristic curves and calculate areas under the curves (AUCs). Our review included eight studies with a total of 2,004 PCTNs. Seven features were considered to be associated with malignancy. High specificity (>0.9) was found in nodules with a taller-than-wide shape, those that were spiculated/microlobulated or with an ill-defined margin, those with microcalcification, and a non-smooth rim. Among US features, eccentric configuration, microcalcification, and marked or mild hypoechogenicity were more reliable in predicting malignancy (AUC: 0.9592, 0.8504, and 0.8092, respectively). After meta-analysis, we recommend combining PCTN US features including an eccentric internal solid portion, marked or mild hypoechogenicity, and presence of microcalcification to better identify malignant nodules. More studies are needed to explore and improve the diagnostic value of US in PCTNs.

We aimed to evaluate the relevance of large-volume lateral lymph node metastases (LLNMs) at risk of recurrence/persistence in papillary thyroid carcinoma (PTC) with LLNMs (N1b). This retrospective study included 448 PTC patients, who had positive LLNMs confirmed by histology and suspected of LLNMs by preoperative ultrasound. According to the number of pathological LLNMs, patients were divided into large-volume LLNM (number of LLNMs >5) and low-volume LLNM (number of LLNMs ≤5). Risk factors of recurrence/persistence in PTC patients with N1b were analyzed. Preoperative ultrasound features of PTC with large-volume LLNM were analyzed. For the patients with a mean follow-up of 44.0 months, the risk of recurrence/persistence was 25.1% in PTC patients with N1b. The recurrence/persistence rate was significantly higher in patients with large-volume LLNM than in patients with low-volume LLNM by multivariate analysis (37.3% vs. 17.1%; HR = 2.451, 95% CI 1.41–4.261, p = 0.001). The 3-year and 5-year recurrence/persistence-free survival for those with large-volume LLNM were 93.2% and 47.2%, respectively. Moreover, we found that multilevel suspected LLNMs and loss of fatty hilum were independent preoperative indicative factors of large-volume LLNM (OR = 6.239, 95% CI 3.547–10.977, p < 0.001; OR = 5.149, 95% CI 1.859–14.261, p = 0.002). In conclusion, multilevel suspected LLNM and loss of fatty hilum on ultrasound tended to be more common in patients with large-volume LLNM. PTC patients with large-volume LLNM are at a higher recurrent/persistent risk than those with low-volume LLNM. Large-volume LLNM may be used to stratify the risk of recurrence/persistence in PTC.

Objective Parathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions. Methods and materials In this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young’s modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed. Results 36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young’s modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669–0.956 vs 0.720–0.983]; p <  0.001, p <  0.001; respectively). In contrast, the max SWV and Young’s modulus showed a better sensitivity of 0.75 and 0.81, respectively. The “colored lesion” and “stiff rim” patterns on the elastogram are more indicated in parathyroid carcinoma and atypical parathyroid tumor, whereas the negative elastogram prevails in parathyroid adenoma. The SWV and Young’s modulus of the parathyroid lesions were independent of the tumor size, but the max SWV and Young’s modulus slightly correlated with serum parathyroid hormone concentration (PTH) (r = 0.398, p = 0.016; r = 0.396, p = 0.017). Conclusions 2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy. The mean SWV and Young’s modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities, while the max SWV and Young’s modulus are more sensitive to distinguish the PC and APT compared with other parameters.

Pod size is one of the most important agronomic features of peanuts, which directly affects peanut yield. Studies on the regulation mechanism underpinning pod size in cultivated peanuts remain hitherto limited compared to model plant systems. To better understand the molecular elements that underpin peanut pod development, we conducted a comprehensive analysis of chronological transcriptomics during pod development in four peanut accessions with similar genetic backgrounds, but varying pod sizes. Several plant transcription factors, phytohormones, and the mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched among differentially expressed genes (DEGs) at five consecutive developmental stages, revealing an eclectic range of candidate genes, including PNC, YUC, and IAA that regulate auxin synthesis and metabolism, CYCD and CYCU that regulate cell differentiation and proliferation, and GASA that regulates seed size and pod elongation via gibberellin pathway. It is plausible that MPK3 promotes integument cell division and regulates mitotic activity through phosphorylation, and the interactions between these genes form a network of molecular pathways that affect peanut pod size. Furthermore, two variant sites, GCP4 and RPPL1, were identified which are stable at the QTL interval for seed size attributes and function in plant cell tissue microtubule nucleation. These findings may facilitate the identification of candidate genes that regulate pod size and impart yield improvement in cultivated peanuts.

Parathyroid carcinoma (PC) is a rare condition with propensity to relapse. The purpose of this study was to evaluate the sonographic findings of locoregional recurrences of parathyroid carcinoma, in order to facilitate diagnosis of this condition using ultrasound (US). This was a retrospective observational study including 21 patients confirmed with pathologically confirmed locoregional recurrence of parathyroid carcinoma. All patients had undergone preoperative US examination at a tertiary center. The imaging, clinical and laboratory data of each case were collected. Sonographic appearance of the largest lesion at each recurrence was evaluated by two experienced radiologists according to a pre-agreed protocol. Overall, 29 relapses occurred in 21 patients. The median age of the patients was 45 years (range 24-71 years). The median size of the largest recurrent lesion at each relapse was 1.8 cm (range 0.8-3.8 cm). Ultrasound images showed hypoechoic solid nodules in 28 relapses (96.6%), inhomogeneous echo-texture in 28 relapses (96.6%), intralesional echogenic septa-like structures in 21 relapses (72.4%), intralesional cystic change in two relapses (6.9%), infiltrative or blurred boundary in 20 relapses (69.0%), irregular shape in 22 relapses (75.9%), marked vascularization on color Doppler imaging in 19 relapses (65.5%), multiple lesions in 26 relapses (89.7%), contralateral recurrence in 3 relapses (10.3%), and subcutaneous recurrence in 10 relapses (34.5%). None of the recurrent lesions exhibited calcification. The total size of all the recurrent lesions at each relapse fairly correlated with the serum intact parathyroid hormone levels (r = 0.450; p = 0.014).