Tumor Supplying Artery Injection of Liposome@Sunitinib Could Effectively Inhibit the Progression of Kidney Tumor.

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system and is not sensitive to chemotherapy or radiotherapy in its advanced stages. Sunitinib is recommended as a first-line target drug for unresectable and metastatic RCC by targeting tyrosine kinase-related signaling pathways, but its therapeutic effect is unsatisfactory. Recently, nanomaterials have shown great prospects in the medical field because of their unique physicochemical properties. Particularly, liposomes are considered as ideal drug delivery systems due to their biodegradability, biocompatibility, and ideal drug-loading efficiency. Considering that tumor supplying artery injection can directly distribute drugs into tumor tissues, in this study, liposomes were employed to encapsulate water-insoluble sunitinib to construct the liposome@sunitinib (Lipo@Suni) complex, so that the drug could directly target and distribute into tumor tissue, and effectively trapped in tumor tissues after tumor supplying artery injection for the advantage of the physicochemical properties of liposomes, thereby achieving a better therapeutic effect on advanced RCC. Here, we found that compared with the peripheral intravenous administration, trans-renal arterial administration increases the content and prolongs the retention time of liposomes in tumor tissues; accordingly, more sunitinib is dispersed and retained in tumor tissues. Ultimately, trans-renal arterial administration of Lipo@Suni exerts a better suppressive effect on RCC progression than peripheral intravenous administration, even better than the conventional oral administration of sunitinib.

ESCO2's oncogenic role in human tumors: a pan-cancer analysis and experimental validation.

PURPOSE: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. METHODS: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro. RESULTS: In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration. CONCLUSIONS: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

Biodegradable nano black phosphorus based SDF1-α delivery system ameliorates Erectile Dysfunction in a cavernous nerve injury rat model by recruiting endogenous stem/progenitor cells.

Stem cell (SC) therapy has been shown high prospects in erectile dysfunction (ED) treatment. Without ethical issues and risks of immune rejection and tumorigenesis of exogenous SC therapy, endogenous stem/progenitor cells (S/PCs) have a better potential for ED management, and their homing and redistribution are controlled by SDF1-α/CXCR4 axis. Considering black phosphorus nanosheet (BPNS) has emerged as an efficient and safe drug vehicle due to its large surface area, biodegradability, and the ability to retain and slowly release its loaded drugs, BPNS is utilized to load SDF1-α, a chemokine for S/PCs, to construct the BP@SDF1-α complex to efficiently recruit stem cells (SCs) by injury-site injection and thus ameliorate ED within the bilateral cavernous nerve injury (BCNI) rat models. We find that BP@SDF1-α can efficiently recruit exogenous SCs and endogenous S/PCs to corpus cavernosum and main pelvic ganglion (MPG) by local administration. Of note, ascribing to endogenous S/PCs recruitment, it also successfully alleviates ED in BCNI rat models by enhancing the protein expression levels of α-SMA, CD31, and nNOs, and eliciting less collagen deposition in the penis after its combined injection at corpus cavernosum and MPG. Thus, this study provides a new insight into the treatment of ED with endogenous S/PCs. BIODEGRADABLE NANO BLACK PHOSPHORUS BASED SDF1-α DELIVERY SYSTEM AMELIORATES ERECTILE DYSFUNCTION IN A CAVERNOUS NERVE INJURY RAT MODEL BY RECRUITING ENDOGENOUS STEM/PROGENITOR CELLS.

A prognostic risk model for programmed cell death and revealing TRIB3 as a promising apoptosis suppressor in renal cell carcinoma.

Programmed cell death (PCD), a common modality of cell death, affects tumor development and acts as a target for tumor therapeutics. Many modalities of PCD regulate genesis, progression and metastasis of cancers, thus affecting the patients' prognosis, but the comprehensive molecular mechanisms of PCD in tumors are lacking, especially in renal cancer. Here, seventeen PRPCDGs were identified from 1257 genes associated with thirteen PCD modalities, which were highly differentially expressed and significantly affected patients' prognosis. Then, LASSO regression analysis of these PRPCDGs screened the 9-gene PRPCDGs risk signature in TCGA-KIRC database. The PRPCDGs risk signature was closely associated with the patients' prognosis and presented stable prediction efficacy for 5- and 7-year overall survival (OS) in three different cohorts of renal cancer. Immune cell infiltration, immune checkpoint expression and pathway enrichment (including GO, KEGG pathway, tumor-associated pathways and metabolism-associated pathways) were significantly different in the high- or low-PRPCDGs-risk group. Finally, we illustrated that TRIB3 might be a protumor factor responsible for the elevated proliferation and invasion capacities of renal cell carcinoma (RCC) cells. In summary, the PRPCDGs risk signature was developed and showed stable prediction efficacy for the prognosis of patients and that (such as TRIB3) could be a potential target for RCC management.

Regulating cathode surface hydroxyl chemistry enables superior potassium storage.

Potassium vanadium fluorophosphate (KVPO4F) is regarded as a promising cathode candidate for potassium-ion batteries due to its high working voltage and satisfactory theoretical capacity. However, the usage of electrochemically inactive binders and redundant current collectors typically results in inferior electrochemical performance and low energy density, thus implying the important role of rational electrode structure design. Herein, we have reported a scalable and cost-effective synthesis of a cellulose-derived KVPO4F self-supporting electrode, which features a special surface hydroxyl chemistry, three-dimensional porous and conductive framework, as well as super flexible and stable architecture. The cellulose not only serves as a flexible substrate, a pore-forming agent, and a versatile binder for KVPO4F/conductive carbon but also enhances the K-ion migration ability. Benefiting from the special hydroxyl chemistry-induced storage mechanism and electrode structural stability, the flexible freestanding KVPO4F cathode exhibits high-rate performance (53.0% capacity retention with current densities increased 50-fold, from 0.2 C to 10 C) and impressive cycling stability (capacity retention up to 74.9% can be achieved over 1,000 cycles at a rate of 5 C). Such electrode design and surface engineering strategies, along with a deeper understanding of potassium storage mechanisms, provide invaluable guidance for better electrode design to boost the performance of potassium-ion energy storage systems.

Low-dose graphene oxide promotes tumor cells proliferation by activating PI3K-AKT-mTOR signaling via cellular membrane protein integrin αV.

Along with the increasing production and application of graphene oxide (GO), its environmental health and safety (EHS) risks have become a global concern. Numerous studies have investigated the biosafety and toxicity mechanisms associated with GO, however, the majority of previous studies were based on its direct toxic dose, which could not reflect the realistic state of environmental exposure of GO with an indirect toxic dose (low dose). Meanwhile, the effects of low-dose GO on the progression of tumors are still unclearly. Herein, we found that GO can promote multiple types of tumor cell proliferation under its low-dose treatment. Moreover, the lateral size of GO has no obvious distinction on its promoting effect on tumor proliferation. The mechanistic investigation revealed that low-dose GO treatment increased the expression level of integrin αV protein, a cell membrane receptor, and further lead to the constitutively activated PI3K/AKT/mTOR signaling pathway and promoted mitotic progression. Collectively, these findings increased our understanding of the detrimental effects of GO in promoting tumor proliferation, as well as improved our biosafety assessment at its realistic exposure doses.

Pan-cancer analysis reveals the prognostic and immunotherapeutic value of cytoskeleton-associated protein 2-like.

Cytoskeleton-associated protein 2-like (CKAP2L), a cell cycle-related protein, is correlated to tumor progression in some tumors. But there were no pan-cancer studies on CKAP2L, and its role in cancer immunotherapy is also unclear. The expression levels, expression activity, genomic alterations, DNA methylation and functions of CKAP2L in various tumors, as well as the associations between CKAP2L expression and patient prognosis, chemotherapy sensitivity, and tumor immune microenvironment, were all analyzed in a comprehensive pan-cancer analysis of CKAP2L by various databases, analysis websites, and R software. The experiments were also conducted to verify the analysis results. In the majority of cancers, CKAP2L expression and activity were markedly elevated. Elevated CKAP2L expression led to poor prognostic outcomes in patients, and is an independent risk factor for most tumors. Elevated CKAP2L causes decreased sensitivity to chemotherapeutic agents. Knockdown of CKAP2L significantly inhibited the proliferation and metastasis capacity of the KIRC cell lines and resulted in cell cycle G2/M arrest. In addition, CKAP2L was closely related to immune subtypes, immune cell infiltration, immunomodulators and immunotherapy markers (TMB, MSI), patients with high CKAP2L expression were more sensitive to immunotherapy in the IMvigor210 cohort. The results indicate that CKAP2L is a pro-cancer gene that serves as a potential biomarker for predicting patient outcomes. By inducing cells to transition from the G2 phase to the M phase, CKAP2L may promote cell proliferation and metastasis. Furthermore, CKAP2L is closely related to the tumor immune microenvironment and can be used as a biomarker to predict tumor immunotherapy.

Long non-coding RNA MFSD4A-AS1 promotes lymphangiogenesis and lymphatic metastasis of papillary thyroid cancer.

Lymphatic metastasis is the leading cause responsible for recurrence and progression in papillary thyroid cancer (PTC), where dysregulation of long non-coding RNAs (lncRNAs) has been extensively demonstrated to be implicated. However, the specific lymphatic node metastatsis-related lncRNAs remain not identified in PTC yet. Lymphatic node metastatsis-related lncRNA, MFSD4A-AS1, was explored in the PTC dataset from The Cancer Genome Atlas and our clinical samples. The roles of MFSD4A-AS1 in lymphatic metastasis were investigated in vitro and in vivo. Bioinformatic analysis, luciferase assay and RNA immunoprecipitation assay were performed to identify the potential targets and the underlying pathway of MFSD4A-AS1 in lymphatic metastasis of PTC. MFSD4A-AS1 was specifically upregulated in PTC tissues with lymphatic metastasis. Upregulating MFSD4A-AS1 promoted mesh formation and migration of human umbilical vein endothelial cells and invasion and migration of PTC cells. Importantly and consistently, MFSD4A-AS1 promoted lymphatic metastasis of PTC cells in vivo by inducing the lymphangiogenic formation and enhancing the invasive capability of PTC cells. Mechanistic dissection further revealed that MFSD4A-AS1 functioned as competing endogenous RNA to sequester miR-30c-2-3p, miR-145-3p and miR-139-5p to disrupt the miRNA-mediated inhibition of vascular endothelial growth factors A and C, and further activated transforming growth factor (TGF)-ß signaling by sponging miR-30c-2-3p that targeted TGFBR2 and USP15, both of which synergistically promoted lymphangiogenesis and lymphatic metastasis of PTC. Our results unravel novel dual mechanisms by which MFSD4A-AS1 promotes lymphatic metastasis of PTC, which will facilitate the development of anti-lymphatic metastatic therapeutic strategy in PTC.

2D Titanium carbide printed flexible ultrawideband monopole antenna for wireless communications.

Flexible titanium carbide (Ti3C2) antenna offers a breakthrough in the penetration of information communications for the spread of Internet of Things (IoT) applications. Current configurations are constrained to multi-layer complicated designs due to the limited conformal integration of the dielectric substrate and additive-free Ti3C2 inks. Here, we report the flexible ultrawideband Ti3C2 monopole antenna by combining strategies of interfacial modification and advanced extrusion printing technology. The polydopamine, as molecular glue nano-binder, contributes the tight adhesion interactions between Ti3C2 film and commercial circuit boards for high spatial uniformity and mechanical flexibility. The bandwidth and center frequency of Ti3C2 antenna can be well maintained and the gain differences fluctuate within ±0.2 dBi at the low frequency range after the bent antenna returns to the flat state, which conquers the traditional inelastic Cu antenna. It also achieves the demo instance for the fluent and stable real-time wireless transmission in bending states.

Prediction of central lymph node metastasis in patients with papillary thyroid microcarcinoma by gradient-boosting decision tree model based on ultrasound radiomics and clinical features.

Background: In recent years, the study of radiomics in thyroid diseases has developed rapidly. This study aimed to establish a preoperative radiomics prediction model for central compartment lymph node metastases (CLNMs) in papillary thyroid microcarcinoma (PTMC) patients using gradient-boosting decision tree (GBDT) model and evaluate the performance of the model. Methods: A total of 274 patients with PTMC admitted for thyroid surgery at China-Japan Union Hospital of Jilin University from January 2020 to July 2022 were retrospectively analyzed. Patients were randomized into training and validation cohorts according to a ratio of 8:2. Radiomics features were extracted from the ultrasound (US) images of PTMC lesions. The open-source software Pyradiomics was used to extract radiomics features, and WEKA software was used to select CLNM-related radiomics features. Clinical risk factors for CLNM were screened by statistical methods. The GBDT model was constructed by combining radiomics features and clinical risk factors, and compared with the diagnostic efficacy of US-reported cervical lymph node status. Shapley Additive exPlanations (SHAP) was applied to visualize and analyze the GBDT model globally and locally. Results: A total of seven radiomics features were significantly correlated with central lymph node status in the training and validation cohorts. The predictors in the GBDT model included the radiomics features, sex, age, and body mass index (BMI). The area under the curve (AUC) values of the GBDT model in the training and validation cohorts were 0.946 [95% confidence interval (CI): 0.920-0.972] and 0.845 (95% CI: 0.714-0.976), respectively, compared with 0.583 (95% CI: 0.508-0.659) and 0.582 (95% CI: 0.430-0.736) for US-reported lymph node status alone. The Delong test showed a significant difference between AUS in the training and validation cohorts (P<0.001, respectively). SHAP visual analysis showed the effect of each parameter on the GBDT model globally and locally. Decision curve analysis demonstrated the clinical utility of the GBDT model. Conclusions: The prediction of CLNM by the GBDT model, based on US radiomics features and clinical factors, can be better than that by using US alone in patients with PTMC. Furthermore, the GBDT model may serve a guidance of clinical decision for patient's treatment strategy.

A novel risk stratification model based on tumor size and multifocality to predict recurrence in pediatric PTC: comparison with adult PTC.

Background: Pediatric papillary thyroid cancer presents with a more advanced stage of disease than adult PTC; and it is more likely to be aggresive and distant metastases, although the survival rate is high. Methods: A retrospective observational study was performed in children and adults with PTC. Fisher's exact, chi-square, and rank-sum tests were used to examine the differences. Univariate and multivariate Cox regression analyses were applied to determine the possible risk factors for prognosis. A Kaplan-Meier curve analysis was performed to investigate the relationship between the clinicopathological characteristics and recurrence rate. Results: The study involved 156 children and 1,244 adults with PTC. Compared to the group without recurrence, proportions of tumors measuring > 1 cm (48.3% vs. 90.9%) and multifocality (30.3% vs. 63.6%) were higher, N1b stage occurred more frequently (33.8% vs. 100%). However, among adult PTC patients, those with recurrence were older (76.1% vs. 59.4%) than those without recurrence. Risk factors for pediatric PTC recurrence included tumor size and multifocality. However, in adult PTC, the risk factor was LLNM. The newly constructed Stratification.N showed better performance, as illustrated by the fact that patients who were classified into Stratification.N 3 showed an obviously poorer prognosis (P=0.01 and P=0.00062), especially in those aged >14 years (P=0.0052). Conclusion: Compared with adult PTC, pediatric PTC showed unique characteristics in terms of clinical pathology and recurrence. Tumor size and multifocality were strong risk factors for pediatric PTC. Accordingly, the novel proposed risk stratification method could effectively predict the recurrence of pediatric PTC.

The feasibility of laryngeal nerve protection during thyroidectomy using sternocleidomastoid intermuscular approach with intraoperative neuromonitoring: a case series and step-by-step description of surgical procedure.

Background: Thyroid surgery is increasingly demanding in terms of cosmetic neck outcomes and protection of anterior neck function, so we have adopted an alternative sternocleidomastoid intermuscular approach (SMIA) for open/conventional thyroidectomy. The protection of recurrent laryngeal nerve (RLN) and external branch of superior laryngeal nerve (EBSLN) is the key and difficult point in thyroid surgery. The aim of this study was to testify the feasibility of RLN and EBSLN functional protection during SMIA thyroidectomy with the intraoperative neuromonitoring. Methods: A total of 39 patients and 39 RLN and EBSLNs who underwent monitored SMIA thyroidectomy were included. Thyroid gland is revealed and excised anterior to the cervical sheath between the sternal and clavicular heads of the sternocleidomastoid muscle. Standardized intraoperative neuromonitoring (IONM) procedures and postoperative laryngeal examination were performed to audit the SMIA. Following the four-step method, V1, R1, R2, and V2 were monitored and the signal values were recorded. Statistical analysis was used to evaluate the change of IONM amplitude of RLN, combined with the results of laryngoscopy before and after operation to determine the status of RLN. EBSLN injuries were identified from changes in cricothyroid muscle (CTM) twitch and EMG. SMIA video vignette is detailed. Results: All RLN and EBSLNs [17 on the left and 22 on the right] were monitored in 39 patients [5 men, 34 women; mean age 34.1±8.7 years; mean body mass index 22.5 (±3.0, 17.0-30.8) kg/m2] undergoing SMIA. For RLN of the affected side, we compared the V2 and V1 (1,236±672 vs. 1,240±428, P=0.973), R2 and R1 (1,676±778 vs. 1,656±765, P=0.849) signals separately, and the results were not statistically different (P>0.05). Comparing the V1 (1,240±428 vs. 1,309±395, P=0.601) signals of the bilateral recurrent laryngeal nerve, there was no statistical difference (P>0.05). CTM twitch and EMG were preserved. Conclusions: The SMIA technique appears feasible. RLN and EBSLN are easier to be exposed during thyroid surgery of SMIA, which is beneficial to the neuroprotection during the operation. At the same time, it can protect the anterior cervical function and improve the cosmetic effect after operation.

Biotransformation of graphene oxide within lung fluids could intensify its synergistic biotoxicity effect with cadmium by inhibiting cellular efflux of cadmium.

Graphene oxide (GO) has been widely studied and applied in numerous industrial fields and biomedical fields for its excellent physical and chemical properties. Along with the production and applications of GO persist increasing, the environmental health and safety risk (EHS) of GO has been widely studied. However, previous studies almost focused on the biotoxicity of pristine GO under a relatively high exposure dose, without considering its transformation process within environmental and biological mediums. Meanwhile, its secondary toxicity or synergistic effects have not been taken seriously. Here, two different kinds of artificial lung fluids were adopted to incubate pristine GO to mimic the biotransformation process of GO in the lung fluids. And, we explored that biotransformation within the artificial lung fluids could significantly change the physicochemical properties of GO and could enhance its biotoxicity. To reveal the synergistic effects of GO and toxic metal ions, we uncovered that GO could enhance the intracellular content of metal ions by inhibiting the efflux function of ATP binding cassette (ABC) transporters which are distributed on the cellular membrane, and artificial lung fluids incubation of GO could enhance this synergistic effect. Finally, toxic metal ions induced a series of toxic reactions through oxidative stress response and promoted cell death. Moreover, consistent with the results of in vitro experiments, the lungs of mice exposed to GOs combined with Cd exhibited significant inflammation and oxidative stress compared with Cd treatment alone, and it was more remarkable within the mice which were treated with bio-transformed GOs. In summary, this study explored the impact and mechanism of biotransformation of GO in the lung fluids on the synergistic and secondary effects between GO and metal ions.

Metastasis to lymph nodes at the contralateral entrance point to the recurrent laryngeal nerve in unilateral thyroid papillary carcinoma: a case report and literature review.

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. PTC is slow growing, and prognosis after surgery is excellent. However, PTC is associated with a high incidence of cervical lymph node metastasis, and usually metastasizes from the central lymph nodes to the ipsilateral cervical and mediastinal lymph nodes. Anatomic studies have shown that the thyroid gland and surrounding tissue have an abundant lymphatic network that facilitates tumor dissemination and lymph node metastasis, there may be many ways to connect lymph nodes on both sides of the neck of patients, which needs further research and discussion. Case Description: We report the case of a 45-year-old female who was diagnosed with thyroid cancer of the right lobe and right lateral lymph node metastasis by fine-needle aspiration (FNA). During surgery, 0.2 mL of carbon nanoparticle (CN) suspension was injected into the right lobe of the thyroid gland, which resulted in black staining of a lymph node at the contralateral entrance point to the recurrent laryngeal nerve (LN-epRLN). The black-stained lymph node was resected, and the pathology results revealed lymph node metastasis from thyroid cancer. The left lobe of the thyroid was benign. Conclusions: Retro-tracheal periesophageal lymph node metastasis may be a rare metastatic pathway in thyroid cancer.

Palladium Nanoplate-Based IL-6 Receptor Antagonists Ameliorate Cancer-Related Anemia and Simultaneously Inhibit Cancer Progression.

In recent years, targeted therapies and immunotherapeutics, along with conventional chemo- and radiotherapy, have greatly improved cancer treatments. Unfortunately, in cancer patients, anemia, either as a complication of cancer progression or as the result of cancer treatment, undermines the expected therapeutic efficacy. Here, we developed a smart nanosystem based on the palladium nanoplates (PdPLs) to deliver tocilizumab (TCZ, a widely used IL-6R antibody) to the liver for specific blockade of IL-6/IL-6R signaling to correct anemia. With chemical modifications, this nanosystem delivered a large mass of TCZ and enhanced liver delivery, inducing a marked suppression of hepcidin expression as a result of diminished IL-6 signaling. Through this mechanism, significant suppression of tumor progression was realized (at least in part) because of the corrected anemia after treatment.

Erratum: hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4.

[This corrects the article DOI: 10.1016/j.omtn.2021.02.023.].

Papillary thyroid carcinoma with rare lymph node metastasis between the non-ipsilateral sternocleidomastoid and striate muscles: two case reports and literature review.

Background: Differentiated thyroid cancer (DTC) has a high incidence but a generally good prognosis. However, lymph node metastasis is likely to occur. It usually metastasizes from the central group lymph nodes to the deep cervical lymph nodes and less frequently to the sternocleidomastoid-sternohyoid muscle. The lymph nodes between the sternocleidomastoid and sternohyoid muscles (LNSS) is easily overlook. Ignoring the preoperative assessment and dissection of level LNSS, especially in the contralateral neck level LNSS, may lead to incomplete surgery and thus require reoperation. The metastatic relevant factors and pathway for LNSS remains inconclusive require further investigation. There is a lack of reports of contralateral or bilateral cervical level LNSS metastasis in thyroid cancer. We hope to arouse attention to the level LNSS through our two case reports. Case Description: We report two cases of non-ipsilateral LNSS metastases. The patients were diagnosed with thyroid cancer by fine-needle aspiration (FNA), and ultrasound examination showed enlarged lymph nodes at the LNSS level. After surgical treatment and postoperative paraffin pathology, both patients were diagnosed with papillary thyroid carcinoma (PTC) and LNSS-level lymph node metastasis. Case 1 was a 63-year-old woman admitted to our hospital with a 15-day history of an untreated thyroid nodule and preoperative euthyroidism. This patient underwent total thyroidectomy, central and left neck LNSS dissection. Her prognosis was good, and there were no signs of recurrence at her 6-month follow-up appointment; Case 2 was a 24-year-old woman admitted to our hospital for a physical examination of an anterior cervical mass that had been present for 1 year and preoperative euthyroidism. This patient underwent total thyroidectomy, central and bilateral neck LNSS dissection. Her prognosis was good, and there were no signs of recurrence at her 12-month follow-up appointment. Conclusions: The occurrence of contralateral and bilateral simultaneous LNSS metastasis in thyroid cancer is relatively rare. However, in clinical practice, surgeons should focus on the evaluation and clearance of LNSS, especially in patients with cancer foci located in the lower pole, cancer foci invading the anterior cervical band muscle, extensive metastasis in the lateral cervical lymph nodes or stages T3/4 and to reduce postoperative recurrence.

Diagnostic performance of Midkine ratios in fine-needle aspirates for evaluation of Cytologically indeterminate thyroid nodules.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a basic diagnostic tool for thyroid nodules. However, 15-30% of nodules are cytologically indeterminate. Midkine (MK), a pleiotropic growth factor, is often upregulated in patients with cancers. This study aimed to evaluate the role of MK and its ratios in fine-needle aspirates (FNA) for predicting thyroid malignancy. METHODS: This retrospective study included patients with thyroid nodules who underwent preoperative FNA and/or thyroidectomy between April 2017 and September 2017. MK levels in FNA washout were measured by enzyme-linked immunosorbent assay, and thyroglobulin (TG) and free thyroxine (FT4) levels in FNA washout were measured by chemiluminescent immunometric assays. RESULTS: A total of 217 patients with 242 nodules were included in this study. The concentrations of TG, FT4, MK/TG, MK/FT4, and FT4/MK were significantly different between papillary thyroid carcinomas and benign thyroid nodules. Both MK/TG and MK/FT4 ratios were positively correlated with maximum tumor diameter, extrathyroidal extension, and T and N stages. The area under the curve for MK/TG was 0.719 with a cutoff value of 55.57 ng/mg, while the area under the curve for MK/FT4 was 0.677 with a cutoff value of 0.11 µg/pmol. FNAC in combination with MK/FT4 had a higher sensitivity (95% vs. 91%) and accuracy (96% vs. 92%) than FNAC alone for cytologically indeterminate specimens, those of unknown significance, or those suspected of malignancy. CONCLUSIONS: MK/FT4 and MK/TG may have diagnostic utility for evaluation of papillary thyroid carcinomas, particularly for cytologically indeterminate thyroid nodules.

Circ_0079558 promotes papillary thyroid cancer progression by binding to miR-26b-5p to activate MET/AKT signaling.

Circular RNAs (circRNAs) are a group of non-coding RNAs featured by covalently closed circular structure. CircRNA_0079558 (circ_0079558) is derived from RAPGEF5 gene, and it has been found to be significantly up-regulated in papillary thyroid carcinoma (PTC). However, the role and working mechanism of circ_0079558 in PTC progression have never been illustrated. The levels of circ_0079558 and MET proto-oncogene, receptor tyrosine kinase (MET) were up-regulated in PTC tissues and cell lines, as evidenced by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay. The silencing of circ_0079558 or MET restrained cell proliferation, migration and invasion whereas triggered cell apoptosis in PTC cells, as verified by Cell Counting Kit-8 (CCK8) assay, plate colony formation assay, transwell invasion assay, wound healing assay and flow cytometry. Through using MET specific inhibitor PHA665752, we found that circ_0079558 overexpression enhanced the malignant behaviors of PTC cells through activating MET/AKT pathway. Through dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay, microRNA-26b-5p (miR-26b-5p) was identified to be the intermediary molecular between circ_0079558 and MET, and circ_0079558 knockdown reduced the expression of MET partly through elevating miR-26b-5p in PTC cells. The miR-198/FGFR1 pathway was identified as another signal axis downstream of circ_0079558, and the co-overexpression of FGFR1 and MET largely rescued the proliferation ability of circ_0079558-silenced PTC cells. Through xenograft tumor model, we found that circ_0079558 silencing restrained xenograft tumor growth in vivo. In conclusion, circ_0079558 facilitated the proliferation and motility whereas inhibited the apoptosis of PTC cells largely through mediating miR-26b-5p/MET/AKT signaling.

hsa_circ_0001018 promotes papillary thyroid cancer by facilitating cell survival, invasion, G1/S cell cycle progression, and repressing cell apoptosis via crosstalk with miR-338-3p and SOX4.

We identified a novel interactome, circ_0001018/miR-338-3p/SOX4, in papillary thyroid cancer (PTC), and we intended to confirm the regulatory relationship between the three and to study the effects of the three in PTC. The bioinformatics method was used to screen out the circular RNA and mRNA of interest. A cellular fractionation assay and fluorescence in situ hybridization (FISH) assay were conducted to prove that circ_0001018 and CCT4 (the host gene of circ_0001018) mRNA primarily localized in the cytoplasm of PTC cell lines. By qRT-PCR analysis, the expression of circ_0001018 and SOX4 mRNA was found upregulated while the expression of miR-338-3p was found downregulated in PTC tissues and cells. circ_0001018 silence significantly inhibited the tumor growth in xenografted nude mice. A series of cytological experiments such as a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2'-deoxyuridine (EdU) assay, cell cycle profiling, wound healing, a transwell assay, and cell apoptosis were conducted and showed that circ_0001018 and SOX4 promoted cell proliferation, migration, and invasion, inhibited cell apoptosis, and reduced the cell cycle arrest at the G1 phase in PTC cells. Compared with circ_0001018 and SOX4, miR-338-3p held the opposite function. The regulatory relationship between circ_0001018 and miR-338-3p, and between miR-338-3p and SOX4 mRNA, was validated using a luciferase reporter gene assay and/or RNA immunoprecipitation (RIP assay). Our findings showed that circ_0001018 acted as the tumor promoter via sponging miR-338-3p to elevate SOX4 expression level in PTC. Importantly, this novel circ_0001018/miR-338-3p/SOX4 axis has the potential to be considered as a therapy target for PTC.