Background
The optimal extent of therapeutic lateral neck dissection (ND) in papillary thyroid carcinoma (PTC) continues to be debated. We analyzed the frequency, patterns, and predictive factors of ...occult level Va and Vb metastasis in clinically lateral node-positive PTC patients.
Methods
We reviewed the data of PTC patients who underwent thyroidectomy and therapeutic lateral ND from level II to V between May 2008 and August 2020. In our study, 46 patients without clinically positive metastatic lymph nodes (LNs) at level V on the preoperative evaluation were included to analyze occult metastasis at level Va and Vb, respectively. Patient demographics, including age, sex, distribution of pathologic LNs, and characteristics of the primary tumors, were reviewed. In addition, clinicopathologic factors associated with occult level Va and Vb metastasis were analyzed.
Results
Of the 46 patients, 14 (30.4%) patients had occult metastases at level Vb. No occult metastases were found at level Va. Clinically positive level II metastasis (
p
= 0.015) and simultaneous level II, III, and IV metastases (
p
= 0.010) in the preoperative evaluation were significantly associated with occult level Vb metastasis. Patients without LN metastasis at level IV or with three or fewer metastatic LNs in the lateral neck never had occult LN metastases at level Vb.
Conclusions
Occult metastasis at level Va is rare in PTC with lateral LN metastasis. Occult metastasis at level Vb may occur in PTC patients with multilevel involvement, including level II and/or four or more lateral LN metastases.
Plasma medicine is an emerging novel therapeutic field. It has been reported that plasma can kill bacteria, promote wound healing and induce apoptosis of tumor cells. However, the effects of plasma ...on immune cells and immune related skin diseases have not been well studied. In this study, we demonstrated that non-thermal atmospheric plasma (NTP) treatment could inhibit psoriasis-like skin inflammation in mice. NTP treatment in imiquimod-induced psoriasis-like mouse skin inhibited increases in epithelial cell thickness and expression of pro-inflammatory molecules compared to ones without the NTP treatment. In addition, differentiation of Th17 cells, an important cell type for pathogenesis of psoriasis, was inhibited in the NTP-treated mouse lymph nodes. It was also demonstrated that liquid type plasma (LTP), which is also known as indirect plasma, inhibited Th17 cell differentiation in vitro. Other in vitro experiments showed that LTP inhibited bone marrow-derived dendritic cell activation. Interestingly, LTP enhanced PD-L1 expression in HaCaT cells, suggesting that NTP may inhibit unwanted over-activation of T cells through increased PD-L1 expression. Taken together, these results suggest that NTP may be used in treatment of CD4+ T cell-mediated autoimmune diseases such as psoriasis.
Abstract
The thyroid gland plays a critical role in the maintenance of whole-body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence ...of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing (RNA-seq) of 54 726 cells derived from pathologically normal thyroid tissues from 7 patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into 5 distinct subpopulations, and a subset of cells was found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and major histocompatibility complex class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq datasets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.
Despite recent advances in understanding the complex immunologic dysfunction in the tumor microenvironment (TME), fewer than 20% of patients with head and neck squamous cell carcinoma (HNSCC) respond ...to immune checkpoint blockade (ICB). Thus, it is important to understand how inhibitory IC receptors maintain the suppressed dysfunctional TME, and to develop more effective combination immunotherapy. This study evaluated the immune-modulating effects of Curcumin, which has well-established anti-cancer and chemopreventive properties, and its long-term safety as a phytochemical drug.
We carried out the western blot and small interfering RNA (siRNA) transfection assay to evaluate the effects of Curcumin on IC ligands and IC ligands function in HNSCC. Through T-cell cytotoxicity assay and measurements of cytokine secretion, we assessed the effects of combination of Curcumin with programmed death-ligand 1 (PD-L1) Ab on cancer cell killing. Flow cytometry were used to analyze the effects of Curcumin on the expression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain3 (TIM-3) on CD4, CD8 and Treg. Immunofluorescence, immunohistochemistry and western blot were used to detecte the cytokine (IFN-γ, Granzyme B), IC receptors (PD-1 and TIM-3) and its ligands (PD-L1, PD-L2, Galectin-9) in xenograft mouse model and 4-nitroquinoline-1-oxide (4-NQO) oral cancer model.
We found that Curcumin decreased the expression of IC ligands such as PD-L1, PD-L2, and Galectin-9 in HNSCC, leading to regulation of epithelial-to-mesenchymal transition-associated tumor invasion. Curcumin also effectively restored the ability of CD8+ cytotoxic T cells to lyse cancer cells. To evaluate the effect of Curcumin on the TME further, the 4-NQO oral cancer model was used. Curcumin increased T-cell proliferation, tumor-infiltrating lymphocytes (TILs), and effector cytokines, and decreased the expression of PD-1, TIM-3, suppressive IC receptors and their ligands (PD-L1, PD-L2, and Galectin-9) in the TME, implying reinvigoration of the exhausted CD8+ T cells. In addition, Curcumin inhibited expression of CD4+CD25+FoxP3+ Treg cells as well as PD-1 and TIM-3.
These results show that Curcumin reinvigorates defective T cells via multiple (PD-1 and TIM-3) and multi-level (IC receptors and its ligands) IC axis suppression, thus providing a rationale to combine Curcumin with conventional targeted therapy or ICB as a multi-faceted approach for treating patients with HNSCC.
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Adequate and rapid mucosal regeneration is one of the most important factors in the healing process of nasal mucosa after surgery or trauma. In particular, delayed mucosal regeneration after surgery ...is an important cause of surgical failure. However, no effective treatment is available yet. Non-thermal plasma (NTP) has several medical effects, but the existing probe type is limited to local direct treatment. Therefore, we investigated the various effects using liquid type plasma to overcome this limitation. In addition, the therapeutic effects of non-thermal plasma treated solution (NTS) on nasal mucosa have yet to be determined. Experiments were carried out using BEAS-2B, a human bronchial epithelial cell line similar to nasal mucosa epithelium. NTS had no cytotoxicity to the BEAS-2B cells and enhanced cell proliferation. NTS also promoted migration of BEAS-2B cells. NTS increased cell proliferation and migration via epidermal growth factor receptor (EGFR) activities and epithelial-to-mesenchymal transition (EMT) signaling. Furthermore, NTS enhanced wound healing of nasal mucosa in an animal model. Accordingly, NTS promotes nasal mucosa wound healing by increasing cell proliferation and migration. These findings suggest the therapeutic potential of NTS in nasal mucosa wound healing.
Oral squamous cell carcinoma (OSCC) has high recurrence and mortality rates despite advances in diagnosis and treatment. Therefore, it is necessary to identify new biomarkers for early detection, ...efficient monitoring, and prognosis prediction. Since microRNA (miRNA) is stable and detectable in serum, it has been reported to inform the diagnosis and monitor disease progression through liquid biopsy. In this study, a circulating specific miRNA panel in OSCC patients was developed, and its usefulness as a dynamic monitor was validated. Small RNAs were extracted from the serum of OSCC patients (n = 4) and normal controls (n = 6) and profiled using next-generation sequencing. NGS identified 42 differentially expressed miRNAs (DEmiRNAs) in serum between patients with OSCC and healthy controls, with threefold differences (p < 0.05). Combining the 42 DEmiRNAs and The Cancer Genome Atlas (TCGA) databases OSCC cohort, 9 overlapping DEmiRNAs were screened out. Finally, 4 significantly up-regulated miRNAs (miR-92a-3p, miR-92b-3p, miR-320c and miR-629-5p) were identified from OSCC patients via validation in the Chungnam National University Hospital cohort. Application of the specific miRNA panel for distinguishing OSCC patients from healthy controls produced specificity and sensitivity of 97.8 and 74%, respectively. In addition, the serum levels of these 4 miRNAs significantly decreased after complete surgical resection and increased after recurrence. We suggest that circulating 4-miRNA panel might be promising non-invasive predictors for diagnosing and monitoring the progression of patients with OSCC.
It has been reported that neutrophil extracellular traps (NETs) impair wound healing in diabetes and that inhibiting NET generation (NETosis) improves wound healing in diabetic mice. ...Gonadotropin-releasing hormone (GnRH) agonists are associated with a greater risk of diabetes. However, the role of GnRH in diabetic wound healing is unclear. We determined whether GnRH-promoted NETosis and induced more severe and delayed diabetic wound healing. A mouse model of diabetes was established using five injections with streptozotocin. Mice with blood glucose levels >250 mg/dL were then used in the experiments. GnRH agonist treatment induced delayed wound healing and increased NETosis at the skin wounds of diabetic mice. In contrast, GnRH antagonist treatment inhibited GnRH agonist-induced delayed wound healing. The expression of NETosis markers PAD4 and citrullinated histone H3 were increased in the GnRH-treated diabetic skin wounds in diabetic mice and patients. In vitro experiments also showed that neutrophils expressed a GnRH receptor and that GnRH agonist treatment increased NETosis markers and promoted phorbol myristate acetate (PMA)-induced NETosis in mouse and human neutrophils. Furthermore, GnRH antagonist treatment suppressed the expression of NETosis markers and PMA-induced NETosis, which were increased by GnRH treatment. These results indicated that GnRH-promoted NETosis and that increased NETosis induced delayed wound healing in diabetic skin wounds. Thus, inhibition of GnRH might be a novel treatment of diabetic foot ulcers.
Vocal fold leukoplakia is clinically defined by the presence of white mucosal lesions. Benign and malignant lesions of vocal fold leukoplakia can be distinguished clinically based on pathological ...biopsy. This study compared the acoustic and aerodynamic parameters of vocal cord carcinoma and dysplasia (mild to severe).
From February 2014 to December 2018, 1,925 voice evaluation assessments were collected before laryngeal microsurgery (LMS). Of 147 patients clinically diagnosed with vocal cord leukoplakia before LMS, 112 male patients were selected for examination. The pathologic findings after LMS were divided into the carcinoma group (56 patients) and dysplasia group (56 patients). Only patients with carcinoma in situ and early glottis cancer were included in the carcinoma group. Analysis of covariance was used to calibrate the age between the two groups.
There was no difference in smoking duration between the two groups. F0 (P < 0.00), jitter (P < 0.00), and mean pitch (P = 0.010) were significantly higher, while the mean sound pressure level parameter (P = 0.024) was significantly lower, in the carcinoma group than in the noncarcinoma group.
In patients with early glottis cancer, differences in voice analysis parameters may be used to differentiate between early glottic carcinoma and noncarcinoma.
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