Novel suspension system for gasless transoral vestibular thyroidectomy.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is receiving increased attention, frequently due to growing requirements for cosmetic incisions. Here, we report our initial experience and discuss the safety and efficacy of the innovative surgical working space suspension system for gasless TOETVA. METHODS: We retrospectively analyzed 75 consecutive patients for whom gasless TOETVA with our novel working space suspension system was used. This suspension system included self-developed retractors, a sterile bandage, and an anesthesia stand. We also improved some main surgical instruments in gasless TOETVA. RESULTS: The study included 75 patients who successfully underwent thyroidectomy and central neck dissection via gasless TOETVA. The mean operating time was 143.27 ± 34.60 min. The mean number of retrieved lymph nodes was 8.00 ± 5.39. Conversion to open surgery did not occur, nor did patients exhibit serious postoperative complications. Postoperative complications included 4 cases of transient recurrent laryngeal nerve (RLN) palsy, 9 of transient hypoparathyroidism, and 3 of transient mental nerve injury. One patient with subcutaneous fluid after surgery recovered after aspiration. Another patient with submental minor perforation recovered well after suturing. There was no evidence of specific complications related to self-designed retractors. CONCLUSION: The innovative working space suspension system for gasless TOETVA provided enough and stable working space and optimized the clarity of the surgical field without CO2-related complications.

SAV4 is required for ethylene-induced root hair growth through stabilizing PIN2 auxin transporter in Arabidopsis.

Root hair development is regulated by hormonal and environmental cues, such as ethylene and low phosphate. Auxin efflux carrier PIN2 (PIN-FORMED 2) plays an important role in establishing a proper auxin gradient in root tips, which is required for root hair development. Ethylene promotes root hair development through increasing PIN2 abundance in root tips, which subsequently leads to enhanced expression of auxin reporter genes. However, how PIN2 is regulated remains obscure. Here, we report that Arabidopsis thaliana sav4 (shade avoidance 4) mutant exhibits defects in ethylene-induced root hair development and in establishing a proper auxin gradient in root tips. Ethylene treatment increased SAV4 abundance in root tips. SAV4 and PIN2 co-localize to the shootward plasma membrane (PM) of root tip epidermal cells. SAV4 directly interacts with the PIN2 hydrophilic region (PIN2HL) and regulates PIN2 abundance on the PM. Vacuolar degradation of PIN2 is suppressed by ethylene, which was weakened in sav4 mutant. Furthermore, SAV4 affects the formation of PIN2 clusters and its lateral diffusion on the PM. In summary, we identified SAV4 as a novel regulator of PIN2 that enhances PIN2 membrane clustering and stability through direct protein-protein interactions. Our study revealed a new layer of regulation on PIN2 dynamics.

CircPCNXL2 promotes papillary thyroid carcinoma progression by regulating fatty acid metabolism induced by anabolic enzyme ACC1.

Papillary thyroid cancer (PTC) is an endocrine malignant tumor with a rapidly increasing incidence in recent years. Although the disease prognosis is good in general, there are still some patients with local invasion, distant metastasis and recurrence, which make treatment difficult. This study aimed to investigate the effect of a novel circRNA, circPCNXL2, on the progression of PTC and to explore its underlying mechanism in PTC. In this study, we found that the expression of circPCNXL2 was upregulated in PTC, which was positively correlated with the proliferation of PTC, and knockdown of circPCNXL2 enhanced the cell cycle arrest of PTC and promoted cell apoptosis. Further research revealed that circPCNXL2 can interact with ACC1, a key enzyme of cellular lipid metabolism, and then promote cell growth by affecting the de novo synthesis of fatty acids. Mechanistically, circPCNXL2 enhances the protein activity of ACC1 by reducing ACC1 phosphorylation of ser 79, thereby promoting the formation of fatty acids such as free fatty acids and triglycerides in cells to meet the energy metabolism needs of cells and promote cell growth. In a nude mouse subcutaneous tumorigenesis model, knockdown of circPCNXL2 inhibited the growth of PTC tumors while high levels of circPCNXL2 expression promoted tumor proliferation. This study revealed that circPCNXL2 regulates PTC lipid metabolism by enhancing the protein activity of ACC1 and identified a novel signaling pathway, the circPCNXL2-ACC1 axis, that can be targeted for the treatment of PTC.

Gasless submental-transoral combined approach endoscopic thyroidectomy: a new surgical technique.

Background: The development of transoral endoscopic vestibular approach thyroidectomy (TOETVA) has been limited by inherent defects, such as mental nerve injury and carbon dioxide (CO2)-related complications. Herein, we proposed a new technique without CO2 called gasless submental-transoral combined approach endoscopic thyroidectomy (STET) to solve the problems in TOETVA. Methods: We reviewed 75 patients who successfully underwent gasless STET using novel instruments at our institution from November 2020 to November 2021. A main incision of approximately 2 cm was made in the natural submental crease line and then combined with two vestibule incisions to complete the procedure. Demographic data, surgical technique and perioperative outcomes were retrospectively recorded. Results: Thirteen male and sixty-two female patients with a mean age of 34.0 ± 8.1 years were enrolled in this study. Sixty-eight patients had papillary thyroid carcinomas and seven had benign nodules. We successfully performed all gasless STET without conversion to open surgery. The average postoperative hospital stay was 4.2 ± 1.8 days. One transient recurrent laryngeal nerve injury and two transient hypoparathyroidisms were observed. Three patients complained of slight lower lip numbness on the first postoperative day. One case of lymphatic fistula, subcutaneous effusion, and incision swelling occurred each, all of which were conservatively cured. One patient developed a recurrence six months after surgery. Conclusions: Gasless STET using our own designed suspension system is technically safe and feasible with reasonable operative and oncologic results.

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.

Comparison of iPTH and calcium levels between total thyroidectomy and lobectomy: a prospective study of 840 thyroid cancers with three years of follow-up.

BACKGROUND: Hypocalcemia is the most frequent complication after thyroidectomy and central neck dissection (CND). Early intact parathyroid hormone (iPTH) determination has been proposed as an early predictor parathyroid gland state. We aim to describe iPTH kinetics after central compartment lymph node dissection (CLND). METHODS: A large prospective observational study was conducted among 840 patients who underwent thyroid cancer surgery between July and December 2016 in China-Japan Union Hospital of Jilin University. Data were obtained from the patient's iPTH evaluation 15 min after CND and serum calcium records during three years of post-operative follow-up. Age, sex, BMI, preoperative PTH, operative and pathologic details were analyzed. Backward stepwise logistic regression analyses were performed to find potential risk factors for predicting iPTH <15 pg/mL. The odds ratio and 95% confidence interval are estimated using the logistic regression coefficients. The prediction model was assessed using the receiver operating characteristic curve. RESULTS: The incidence of permanent hypocalcemia was 0.12%, while, 44.52% of patients were central lymph node metastasis. Multivariate analyses found associations among iPTH <15 pg/mL and several risk factors, especially preop PTH and type of surgery. The risk of iPTH <15 pg/mL, after total thyroidectomy plus CND, is almost 17 times that of lobectomy plus CND (OR =17.648, 95% confidence interval: 10.011-31.110). A model was created using multivariate analysis, which involved surgical procedure, and preop PTH could separate thyroid operation with iPTH <15 pg/mL. The biological index showed an area under the ROC curve of 0.697 and 0.613 separately. Using values below the lowest or above the highest cut-off point, the presence or absence of iPTH <15 pg/mL could possibly be predicted before thyroidectomy and CND. CONCLUSIONS: A lobectomy procedure for papillary thyroid carcinoma patients with clinically uninvolved neck lymph nodes (cN0) who have primary tumors (T1 or T2) could accompany prophylactic CND (ipsilateral or bilateral) to provide clearance of disease compared to total thyroidectomy.

miR-424-5p Promotes Anoikis Resistance and Lung Metastasis by Inactivating Hippo Signaling in Thyroid Cancer.

miR-424-5p has been widely identified to function as an oncomiR in multiple human cancer types. However, the biological function of miR-424-5p in distant metastasis of thyroid cancer, as well as the underlying mechanism, remains not clarified yet. In the current study, miR-424-5p expression was elucidated in 10 paired fresh thyroid cancer tissues and the thyroid cancer dataset from The Cancer Genome Atlas (TCGA). Lung metastasis colonization models in vivo and functional assays in vitro were used to determine the role of miR-424-5p in thyroid cancer. Bioinformatics analysis, western blot, luciferase reporter, and immunofluorescence assays were applied to identify the potential targets and underlying mechanism involved in the functional role of miR-424-5p in lung metastasis of thyroid cancer. Here, we reported that miR-424-5p was upregulated in thyroid cancer, and overexpression of miR-424-5p significantly correlated with distant metastasis of thyroid cancer. Upregulating miR-424-5p promoted, whereas silencing miR-424-5p inhibited, anoikis resistance in vitro and lung metastasis in vivo. Mechanistic investigation further revealed that miR-424-5p promoted anoikis resistance and lung metastasis by inactivating Hippo signaling via simultaneously targeting WWC1, SAV1, and LAST2. Therefore, our results support the idea that miR-424-5p may serve as a potential therapeutic target in lung metastasis of thyroid cancer.

Expression, Purification and Characterization of Recombinant Canine FGF21 in Escherichia coli.

The canine metabolic diseases, such as obesity and diabetes, have become a worldwide problem. Fibroblast growth factor 21 (FGF21) is a potent regulator which has many biological functions relative to metabolism regulation. It suggests that FGF21 plays important roles in regulating canine metabolic diseases. To acquire the recombinant canine FGF21 (rcFGF21) in Escherichia coli, the recombinant bacteria were induced by 0.5 mM IPTG for 16 hours at 16 °C, and the rcFGF21 protein was purified by Ni-NTA. 8 mg rcFGF21 was acquired from one liter bacteria. The rcFGF21 protein has specific immunoblot reactivity against anti-FGF21 and anti-His antibody. The in vivo experimental result showed that rcFGF21 can significantly reduce plasma glucose of STZ-induced diabetic mice.