Is transoral endoscopic thyroidectomy safe for total thyroidectomy compared to open thyroidectomy? A propensity-score matched cohort study with papillary thyroid carcinoma.

BACKGROUND: Transoral endoscopic thyroidectomy via vestibular approach (TOETVA) has become increasingly popular in the treatment of papillary thyroid cancer (PTC). This study aimed to describe the safety and feasibility of total thyroidectomy between the TOETVA and open thyroidectomy (OT) approaches for the treatment of patients with PTC. METHODS: We retrospectively reviewed 780 consecutive patients suffering from PTC that had undergone total thyroidectomy using TOETVA (n = 107) and OT (n = 673) between April 2016 and December 2021 at our institute. Afterward, a total of 101 matched patients' surgical outcomes were compared using propensity score matching (PSM) analysis. RESULTS: Before PSM, the patients in the TOETVA group were younger (p < 0.001), had a lower body mass index (p < 0.001) and a greater female population (p < 0.001). After PSM, the TOETVA group was associated with significantly longer operative time (p < 0.001), greater blood loss (p < 0.001), total drainage amount (p < 0.001), higher C-reaction protein level (p < 0.001), better cosmetic satisfaction (p < 0.001) and quality of life (p < 0.001) and lower scar self-consciousness (p < 0.001). There was no statistical difference between the groups in the rate of parathyroid autotransplantation and bilateral lymph node dissection, the positivity of lymph node metastasis, number of dissected lymph nodes and positive lymph nodes, multifocality, postoperative level of blood calcium and parathyroid hormone (PTH), rate of PTH < 15 ng/mL, visual analog scale score, duration of hospital stay, complications, mean thyroid stimulating hormone (TSH)-stimulated Tg level before radioactive iodine, mean Tg level without TSH stimulation, and the proportion of serum Tg level of <1. CONCLUSION: TOETVA is a safe and feasible technique for better cosmetic effects and similar surgical outcomes compared to conventional open surgery for the studied patients that required total thyroidectomy.

Comparison of the endoscopic thyroidectomy via areola approach and open thyroidectomy: A propensity score matched cohort study of 302 patients in the treatment of papillary thyroid non-microcarcinoma.

Background: The endoscopic thyroidectomy via areola approach (ETAA) is widely used in patients with benign thyroid tumors and papillary thyroid microcarcinoma (PTMC). Its safety and complication rates are reported to be similar to open thyroidectomy (OT). This study aimed to evaluate the safety and feasibility of ETAA, compared with OT, in patients with papillary thyroid non-microcarcinoma (PTNMC). Methods: We retrospectively reviewed all patients with PTNMC who underwent ETAA or OT in our hospital from January 2017 to December 2021. A total of 302 patients were matched at a ratio of 1:1 by the propensity score matching (PSM) analysis and surgical outcomes. Safety and feasibility were analyzed between two groups. Results: Before PSM, patients in the ETAA group were younger (p < 0.001) and had a larger proportion of female patients (p < 0.001) with a lower BMI (p < 0.001) compared with the OT group. The ETAA group also had a higher proportion of unilateral thyroidectomy (p = 0.002). PSM was used to create a highly comparable control group. After PSM, the ETAA group had a longer operative time (p < 0.001), larger blood loss (p = 0.046) and total drainage amount (p = 0.035), with higher C-reactive protein (p = 0.023) and better cosmetic outcomes (p < 0.001). There were no significant differences in the following clinicopathologic characteristics: number of dissected positive lymph nodes, rate of recurrent laryngeal nerve signal weakened, parathyroid autotransplantation, postoperative pain, hospital stay, complications, and oncologic completeness. There was no patient converted to OT in the ETAA group and two patients suffered from persistence/recurrence in the follow-up. Conclusion: ETAA is a safe and feasible surgical approach for patients with PTNMC.

Diagnosis of cervical lymph node metastasis with thyroid carcinoma by deep learning application to CT images.

Introduction: The incidence of thyroid diseases has increased in recent years, and cervical lymph node metastasis (LNM) is considered an important risk factor for locoregional recurrence. This study aims to develop a deep learning-based computer-aided diagnosis (CAD) method to diagnose cervical LNM with thyroid carcinoma on computed tomography (CT) images. Methods: A new deep learning framework guided by the analysis of CT data for automated detection and classification of LNs on CT images is proposed. The presented CAD system consists of two stages. First, an improved region-based detection network is designed to learn pyramidal features for detecting small nodes at different feature scales. The region proposals are constrained by the prior knowledge of the size and shape distributions of real nodes. Then, a residual network with an attention module is proposed to perform the classification of LNs. The attention module helps to classify LNs in the fine-grained domain, improving the whole classification network performance. Results: A total of 574 axial CT images (including 676 lymph nodes: 103 benign and 573 malignant lymph nodes) were retrieved from 196 patients who underwent CT for surgical planning. For detection, the data set was randomly subdivided into a training set (70%) and a testing set (30%), where each CT image was expanded to 20 images by rotation, mirror image, changing brightness, and Gaussian noise. The extended data set included 11,480 CT images. The proposed detection method outperformed three other detection architectures (average precision of 80.3%). For classification, ROI of lymph node metastasis labeled by radiologists were used to train the classification network. The 676 lymph nodes were randomly divided into 70% of the training set (73 benign and 401 malignant lymph nodes) and 30% of the test set (30 benign and 172 malignant lymph nodes). The classification method showed superior performance over other state-of-the-art methods with an accuracy of 96%, true positive and negative rates of 98.8 and 80%, respectively. It outperformed radiologists with an area under the curve of 0.894. Discussion: The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images. The future research can consider adding radiologists' experience and domain knowledge into the deep-learning based CAD method to make it more clinically significant. Conclusion: The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images.

Sulfonium-Driven Neoantigen-Released DNA Nanodevice as a Precise Vaccine for Tumor Immunotherapy and Prevention.

Peptide-based neoantigen vaccines hold tremendous potential for personalized tumor immunotherapy. However, effective delivery and controllable release of antigen peptides remain major challenges in stimulating robust and sustained immune responses. Programmable DNA nanodevices provide accurate fixed positions for antigens, which are convenient for the calculation of clinical dosage, and hold great potential as precise carriers. Here, a peptide-nucleic acid conjugate was prepared, which was driven by a propargyl sulfonium-based efficient and reversible bio-orthogonal reaction under weakly alkaline conditions, and folded into regular DNA nanodevice vaccines. The well-defined nanoplatform not only exhibits outstanding stability in serum, satisfactory safety, and effective internalization by antigen-presenting cells (RAW264.7 and BMDCs) but also obviously enhances cytokine (TNF-α, IL-6, and IL-12) secretion for further immune response. In vivo, the nanovaccine cooperating with OVA model antigens and CpG adjuvants stimulated an antigen-specific CD8+T cell response, significantly preventing the lung metastases of melanoma. In the B16-OVA tumor-bearing model, the growth inhibition rate of melanoma reached up to 50%. Similarly, the DNA nanodevice with neoantigen induced up to a maximum degree of complete MC-38 tumor regression in 80% of mice, possibly owing to antigen peptide reversible release driven by sulfonium and further cross-presentation. In brief, this study demonstrates that DNA nanodevices with sulfonium centers can provide a precise, biocompatible, and effective co-delivery vaccine platform for tumor immunotherapy and prevention.

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center.

In recent years, cyclic peptides have attracted increasing attention in the field of drug discovery due to their excellent biological activities, and, as a consequence, they are now used clinically. It is, therefore, critical to seek effective strategies for synthesizing cyclic peptides to promote their application in the field of drug discovery. This paper reports a detailed protocol for the efficient synthesis of cyclic peptides using on-resin or intramolecular (intermolecular) bisalkylation. Using this protocol, linear peptides were synthesized by taking advantage of solid-phase peptide synthesis with cysteine (Cys) and methionine (Met) coupled simultaneously on the resin. Further, cyclic peptides were synthesized via bisalkylation between Met and Cys using a tunable tether and an on-tether sulfonium center. The whole synthetic route can be divided into three major processes: the deprotection of Cys on the resin, the coupling of the linker, and the cyclization between Cys and Met in a trifluoroacetic acid (TFA) cleavage solution. Furthermore, inspired by the reactivity of the sulfonium center, a propargyl group was attached to the Met to trigger thiol-yne addition and form a cyclic peptide. After that, the crude peptides were dried and dissolved in acetonitrile, separated, and then purified by high-performance liquid chromatography (HPLC). The molecular weight of the cyclic peptide was confirmed by liquid chromatography-mass spectrometry (LC-MS), and the stability of the cyclic peptide combination with the reductant was further confirmed using HPLC. In addition, the chemical shift in the cyclic peptide was analyzed by 1H nuclear magnetic resonance (1H NMR) spectra. Overall, this protocol aimed to establish an effective strategy for synthesizing cyclic peptides.

Effects of Intraoperative Neural Tunnel in Protecting Recurrent Laryngeal Nerve: Experiences in Open, Trans Breast, and Transoral Endoscopic Thyroidectomy.

Background: Energy-based devices (EBDs) increase the risks of thermal nerve injuries. This study aimed to introduce a surgical strategy of intraoperative neural tunnel protecting (INTP) for evaluating the effect in reducing the incidence of recurrent laryngeal nerve (RLN) damage in open, trans breast, and transoral endoscopic thyroidectomy. Methods: INTP strategy was introduced: a tunnel was established and protected by endoscopic gauze along the direction of the nerve. A total of 165, 94, and 200 patients with papillary thyroid carcinoma (PTC) were to use INTP in respectively open, trans breast, and transoral endoscopic thyroidectomy as the INTP group. Additionally, 150, 95, and 225 patients who received the same methods without INTP were enrolled in the control group. Ipsilateral thyroidectomy or total thyroidectomy, and central compartment dissection were performed on the enrolled patients. Results: Clinicopathologic characteristics, surgical outcomes, and surgical complications were similar between the INTP group and the control group in open, trans breast, and transoral endoscopic thyroidectomy. The incidences of electromyography (EMG) changes in the INTP group were lower as compared to the control group in trans breast endoscopic thyroidectomy (p < 0.05). The incidence of postoperative hoarse in the INTP group was lower as compared to the control group in open and transoral endoscopic thyroidectomy (p < 0.05). Postoperative calcium levels (p < 0.01) were significantly higher, and the white blood cells (p < 0.05) and C-reactive protein levels (p < 0.01) were significantly decreased in the INTP group compared with the control group in transoral endoscopic thyroidectomy. Conclusions: This was the first instance of the INTP strategy being introduced and was found to be an effective method for protecting the RLN in open, trans breast, and transoral endoscopic thyroidectomy. Additionally, INTP helped protect other important tissues such as the parathyroid glands in transoral endoscopic thyroidectomy as well as in reducing postoperative inflammatory responses.

Comparison of the transoral endoscopic thyroidectomy vestibular approach and open thyroidectomy: A propensity score-matched analysis of surgical outcomes and safety in the treatment of papillary thyroid carcinoma.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach has been demonstrated to have similar surgical outcomes as open thyroidectomy for selected papillary thyroid carcinomas. This study aimed to evaluate and compare the surgical outcomes and safety of the transoral endoscopic thyroidectomy vestibular approach with those of open thyroidectomy in the treatment of papillary thyroid carcinoma with a diameter between >1 cm and ≤3.5cm. METHODS: We retrospectively reviewed all patients who had papillary thyroid carcinoma that was between >1 cm and ≤3.5 cm in diameter and who had undergone the transoral endoscopic thyroidectomy vestibular approach (n = 96) or an open thyroidectomy (n = 425) from January 2017 to June 2020. We then performed 1:1 propensity score matching, yielding 78 matched pairs. Afterward, surgical outcomes and follow-up data were compared between the 2 matched groups. RESULTS: Compared with the matched open thyroidectomy group, the papillary thyroid carcinoma group had a significantly longer operative time (P < .001), more blood loss (P < .05), higher postoperative white blood cell count (P < .05), higher C-reactive protein (P < .001), more total drainage volume (P < .001), increased surgical cost (P < .05), better cosmetic satisfaction (P <.001), lower scar self-consciousness (P < .001), and better quality of life (P < .001). We observed no significant differences in the incidence of other outcomes, including the number of retrieved lymph nodes and metastatic central lymph nodes, the rate of intraoperative recurrent laryngeal nerve signal weakened and parathyroid autotransplantation, visual analog scale scores for pain, drainage duration, postoperative hospital stay, rate of complications, and oncologic completeness. We observed no conversion to open thyroidectomy and no intraoperative capsular disruption in the transoral endoscopic thyroidectomy vestibular approach group. There was 1 case of persistent nodal disease in the transoral endoscopic thyroidectomy vestibular approach group. No recurrence was observed in the 2 groups during the follow-up period. CONCLUSION: The transoral endoscopic thyroidectomy vestibular approach is feasible in selected patients with papillary thyroid carcinoma, not only because it is cosmetically advantageous but also because it is surgical and oncologically safe and may be an optional surgical method for treating papillary thyroid carcinomas having a diameter between >1 cm and ≤3.5 cm.

Memantine can improve chronic ethanol exposure-induced spatial memory impairment in male C57BL/6 mice by reducing hippocampal apoptosis.

Chronic ethanol intake can induce neuronal apoptosis, leading to dementia. We investigated the protective effects of memantine on spatial memory impairment induced by chronic ethanol exposure in mice. Male C57BL/6 mice were administered 10% (m/V) or 20% (m/V) ethanol as the only choice of drinking water. Mice were treated for 60 d, 90 d, or 180 d. Mice were treated with memantine for the same duration (daily 10 mg/kg oral). The Morris water maze and radial arm maze test were used to measure spatial memory. Mice were sacrificed after the behavioral tests. Brains were removed to prepare for paraffin sections, and hippocampi were isolated for protein and RNA extraction. 4',6-diamidino-2-phenylindole (DAPI) staining and immunohistochemical staining of cleaved caspase-3 were performed. Western blot analysis was used to detect the expression of cleaved caspase-3 and calcium-related proteins, including N-methyl-d-aspartic acid receptor 1 (NR1), 1,4,5-trisphosphate receptor 1 (IP3R1), and sarco/endoplasmic reticulum calcium adenosine triphosphatase 1 (SERCA1). The changes of NR1, IP3R1 and SERCA1 mRNA were detected using quantitative polymerase chain reaction (qPCR). The results revealed that chronic ethanol exposure induced spatial memory impairment in mice, as well as increasing the expression of NR1, IP3R1 and SERCA1, the activation of caspase-3 and apoptosis in hippocampus. The effect was particularly prominent in the 20% ethanol group after 180 d exposure. Memantine decreased ethanol-induced spatial memory impairment, caspase-3 activation and apoptosis in the mouse hippocampus. These results suggest that disruption of intracellular calcium balance by ethanol can induce caspase-3 activation and apoptosis, which underlies subsequent spatial memory impairment in mice.

Preliminary application of multiple parameters spectral CT in the diagnosis of ovarian cancer.

The aim of the study was to evaluate the effectiveness of spectral CT in the diagnosis of ovarian cancer. We retrospectively analyzed the data of 22 patients with spectral CT enhanced scan. The patients were divided into 2 groups: ovarian cancer group (n = 11) and benign tumor group (n = 11), according to the pathologic results. CT values at 40 keV, iodine concentration (IC), water concentration (WC) and spectral curve slope (λHU) of arterial phase and venous phase in the tumors of 2 groups were measured with gemstone spectral imaging (GSI) post-processing software. The independent samples t test was used to compare these multiple parameters above between 2 groups. For the parameters which showed statistically different, the ROC curves were further generated to calculate their diagnostic effectiveness respectively. According to the results, CT values at 40 keV, IC and λHU measured in arterial and venous phases were higher in ovarian cancer group than those in benign tumor group. There were significant differences between these 2 groups (P < 0.05). While WC had no significant difference in these 2 groups (P > 0.05). CT values at 40 keV, IC and λHU had high effectiveness to the diagnosis of ovarian cancer according to ROC curves. The optimal parameter among them was IC in arterial phase with AUC of 0.90. Using 10.92 (100 ug/cm3) as a threshold value, the sensitivity and specificity for diagnosis were 88.9% and 94.7%. Thus, we concluded that spectral CT with multiple parameters was valuable in the diagnosis of ovarian cancer.

High-performance liquid chromatography with fluorescence detection for the determination of nitrofuran metabolites in pork muscle.

A simple and sensitive HPLC method with fluorescence detection (HPLC-FLD) is reported for the simultaneous determination of metabolites of four nitrofuran drugs (furazolidone, furaltadone, nitrofurantoin and nitrofurazone) in pork muscle. The method involves acid hydrolysis of the protein-bound drug metabolites and the conjugation of the released side-chains with a novel fluorescence agent 2-hydroxy-1-naphthaldehyde. After liquid-liquid extraction and effective separation of the derivatives on a YMC-Pack Polymer C18 column at 40°C under alkaline conditions, the high fluorescence intensity of these derivatives at emission wavelength λem = 463 nm enables their simultaneous determination in pork muscle at concentrations as low as 1 µg kg⁻¹. The method was validated using blank pork muscle fortified with all four metabolites at 0.5, 1.0 and 2.0 µg kg⁻¹. Recoveries were > 92.3% with RSDs < 8.5% for all four metabolites. The results obtained with HPLC-FLD and LC-MS/MS methods showed very good agreement for pork muscle samples.

Nonlinear optical response and biological applications of a series of pyrimidine-based molecules for copper(II) ion probe.

Biological metal detecting, small molecule probes bearing nonlinear optical (NLO) response provide powerful alternatives due to their favorable photophysical properties (e.g. excitation wavelength in the near-IR region), cell permeability (due to their size), and chemical structure flexibility. Here, we present a series of pyrimidine-based NLO biological metal probes, especially a novel copper specific one which taken into account of the small volume-scaled and low cost-scaled nonlinear optical response of TPP and TPP-Cu(2+) discussed in our present work. The photophysical properties of the probes were thoroughly investigated. (1)H NMR and theoretical computation prove the binding interaction between the probe and the copper ion, which supports the functions of the molecule as a fluorescence signaling unit showing strong fluorescence quenching upon copper metal ion binding. On the other hand, the two-photon absorption cross-section of the novel copper probe increased from 275 to 591 GM (λ(ex) = 830 nm) after interacting with copper ion. It was further demonstrated that the NLO response for the copper(ii) ion probe could be used for biological copper detection in live cells.