Search

Head and neck squamous cell carcinoma (HNSCC), which occurs frequently worldwide, is characterized by high risk of metastasis. MicroRNAs (miRNAs) play crucial roles in tumorigenesis and cancer development. In this study, miR-29c-5p was identified using three high throughput microarrays. We measure miR-29c-5p expression in HNSCC tissues and cell lines. To determine the function of miR-29c-5p in HNSCC, we evaluated its effects in vitro on cell proliferation, the cell cycle, apoptosis, and cell migration. We employed a mouse tumor xenograft model to determine the effects of miR-29c-5p on tumors generated by HNSCC cell lines. The miR-29c-5p expression was lower in HNSCC tissues than in normal tissues. Upregulated miR-29c-5p expression in HNSCC cells inhibited migration and arrested cells in the G2/M phase of the cell cycle. Further, upregulated miR-29c-5p expression inhibited the proliferation of HNSCC cells in vivo and in vitro. In addition, transmembrane protein 98 (TMEM98) was identified as a direct target of miR-29c-5p by using a luciferase reporter assay. These findings provide new insights that link the regulation of miR-29c-5p expression to the malignant phenotype of HNSCC and suggest that employing miR-29c-5p may serve as a therapeutic strategy for managing patients with HNSCC.

OBJECTIVES/HYPOTHESIS To evaluate the application and advantages of coblation tonsillectomy with inferior pole capsule preservation in pediatric patients with tonsillar hypertrophy and recurrent tonsillitis. STUDY DESIGN Retrospective chart review. METHODS A total of 726 children who were diagnosed with either tonsillar hypertrophy or recurrent tonsillitis were included. Children were divided into two groups according to the surgical technique: conventional coblation tonsillectomy and coblation tonsillectomy with inferior pole capsule preservation. The duration of surgery, intraoperative hemorrhage volume, and postoperative pain, as well as postoperative hemorrhage data in the format of time, location, and degree were compared between the two groups. RESULTS Of the 726 children included, conventional coblation tonsillectomy was performed in 320 children, coblation tonsillectomy with inferior pole capsule preservation was performed in 406 children. There were no significant differences in duration of surgery or intraoperative hemorrhage volume between the two groups. Children who underwent coblation tonsillectomy with inferior pole capsule preservation showed a remarkable improvement in postoperative pain on days 3 and 5 postoperatively. Additionally, the coblation tonsillectomy with inferior pole capsule preservation group exhibited a significantly lower total postoperative hemorrhage rate, secondary hemorrhage rate, and hemorrhage rate in the inferior pole compared with that in the conventional coblation tonsillectomy group. During the 1-year follow-up period, no cases of tonsillar re-hypertrophy or recurrent tonsillitis were observed in either group. CONCLUSION For pediatric tonsillar hypertrophy and recurrent tonsillitis, coblation tonsillectomy with inferior pole capsule preservation is a safe and effective technique, capable of reducing postoperative pain and hemorrhage, especially secondary hemorrhage at the inferior pole. LEVEL OF EVIDENCE 3b Laryngoscope, 131:1157-1162, 2021.

Laryngeal carcinoma (LCC) is a common malignant tumor with low radiosensitivity and generally poor response rates. The ubiquitin protein ligase E3 component n-recognin 5 (UBR5) has prognostic implications in several neoplasms; however, its role in LCC and radiotherapy sensitivity remains unknown. Immunohistochemistry and bioinformatics analyses were performed to measure UBR5 protein and mRNA expression in LCC and adjacent non-tumor tissues. The gene and protein expression of UBR5 in LCC and HuLa-PC cell lines were measured using quantitative PCR and western blot analyses. Following transfection with small interfering RNA or UBR5 overexpression plasmid in LCC cells, the proliferation, cell cycle distribution, invasion, migration and radiosensitivity of LCC cells were analyzed. UBR5-related lncRNA, targeted miRNA and protein-protein interaction networks were analyzed using bioinformatics. Finally, the expression of the p38/mitogen-activated protein kinase (MAPK) pathway was evaluated following UBR5 silencing in M2E cells treated with radiation. Increased UBR5 expression was observed in LCC tissues compared with adjacent non-tumor tissues, and it was correlated with poor overall survival of LCC patients. After overexpression or silencing of UBR5 in M2E and M4E LCC cells, cell proliferation and radiosensitivity were significantly increased or decreased, respectively, compared with the control groups. The percentage of S phase cells decreased in the UBR5 si-RNA group compared with that in the control group, while overexpression of UBR5 exerted no effect on the cell cycle. In addition, the expression of Bcl-2 and p38 was decreased in the si-UBR5 combined with radiation groups. The level of phosphorylated p38 expression was increased after combination of si-UBR5 with radiation. The small molecule inhibitor of p38/MAPK signaling, SB203580, decreased the viability of UBR5-overexpressing cells and the survival fraction when cells were exposed to radiation. These findings demonstrated that UBR5 may be involved in regulating cell proliferation and sensitivity to radiotherapy in LCC via the p38/MAPK pathway, thereby highlighting its possible value for the development of new therapeutic strategies and targets for the treatment of this disease.

Ebola virus (EBOV), one member of the family Filoviridae, can causes hemorrhagic fever and other severe diseases in humans with a high mortality rate (25-90%). Until recently, there were no approved drugs and very limited treatment method for Ebola virus disease. In this study, we discovered a series of potent Ebola entry inhibitors with the (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl)decahydroisoquinoline-3-carboxamide scaffold from high-throughput screening in reported pseudotyped virus system. Further optimization resulted a most potent compound 28 (IC

MicroRNAs (miRNAs) have been recently found in the mitochondria, and were named “mitomiRs”, but their function has remained elusive. Here, we aimed to assess the presence and function(s) of mitomiRs in tongue squamous cell carcinoma (TSCC). Methods: miRNA microarray was performed in paired TSCC cell lines, Cal27 and its chemoresistant counterpart, Cal27-re. Decreased expression of mitomiRs in chemoresistant cells was characterized. The functions of mitomiRs were investigated by a series of in vitro and in vivo experiments. Results: Differential microarray analysis identified downregulation of mitomiR-5787 in Cal27-re cells. We knocked down mitomiR-5787 in parental cells and upregulated its expression in cisplatin-resistant cells. The sensitivity of TSCC cells to cisplatin was regulated by miR-5787. The glucose metabolism assay suggested that reduced expression of miR-5787 changed the balance of glucose metabolism by shifting it from oxidative phosphorylation to aerobic glycolysis. Xenograft experiments in BALB/c-nu mice further verified the in vitro results. Reduced expression of miR-5787 contributes to chemoresistance in TSCC cells by inhibiting the translation of mitochondrial cytochrome c oxidase subunit 3 (MT-CO3). The prognostic analysis of 126 TSCC patients showed that the patients with low expression of miR-5787 and/or MT-CO3 had poor cisplatin sensitivity and prognosis. Conclusions: Mitochondrial miR-5787 could regulate cisplatin resistance of TSCC cells and affect oxidative phosphorylation and aerobic glycolysis. Downregulation of miR-5787 inhibited the translation of MT-CO3 to regulate cisplatin resistance of TSCC. Mitochondrial miR-5787 and MT-CO3 can be used as predictive biomarkers or therapeutic targets for cisplatin chemotherapy resistance.

Background Reconstruction of hemiglossectomy defects requires careful flap design to avoid adverse functional and aesthetic outcomes. Methods Hemitongue specimens were obtained from minipigs to study the three-dimensional anatomy and to define anatomic landmarks for precise measurements of flap requirement. The concept developed in animal models was then applied to hemiglossectomy reconstruction in clinical practice. Sixty-one patients were randomly enrolled into the following two groups: a "five-point eight-line segment" (FIPELS) flap design group (28 patients) and a conventional group (33 patients). Functional and aesthetic outcomes were compared between the two groups. Results All flaps designed with the FIPELS technique matched the hemiglossectomy defects without the need for flap trimming, thus reducing the operating time (P = .03). Swallowing functions, speech intelligibility, and aesthetic outcomes were superior in the FIPELS group than that in the conventional group (P Conclusions The FIPELS flap design for hemiglossectomy reconstruction yields improved functional and aesthetic outcomes compared to a conventional flap design.

Abnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial–mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3′-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.

Purpose: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. Experimental Design: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. Results: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. Conclusions: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.

Graphical abstract, The COVID-19 pandemic has drastically impacted global economies and public health. Although vaccine development has been successful, it was not sufficient against more infectious mutant strains including the Delta variant indicating a need for alternative treatment strategies such as small molecular compound development. In this work, a series of SARS-CoV-2 main protease (Mpro) inhibitors were designed and tested based on the active compound from high-throughput diverse compound library screens. The most efficacious compound (16b-3) displayed potent SARS-CoV-2 Mpro inhibition with an IC50 value of 116 nM and selectivity against SARS-CoV-2 Mpro when compared to PLpro and RdRp. This new class of compounds could be used as potential leads for further optimization in anti COVID-19 drug discovery.

Increasing evidence has shown that chemo-resistance is related to the process of epithelial-mesenchymal transition (EMT) and increased invasiveness by tongue squamous cell carcinoma (TSCC) cells. Long non-coding RNAs (lncRNAs) play pivotal roles in tumor metastasis and progression. However, the roles and mechanisms of lncRNAs in cisplatin-resistance-induced EMT and metastasis are not well understood. In this study, a chemotherapy-induced lncRNA 1 (CILA1) was discovered by using microarrays and was functionally identified as a regulator of chemo-sensitivity in TSCC cells. Upregulation of CILA1 promotes EMT, invasiveness, and chemo-resistance in TSCC cells, whereas the inhibition of CILA1 expression induces mesenchymal-epithelial transition (MET) and chemo-sensitivity, and inhibits the invasiveness of cisplatin-resistant cells both in vitro and in vivo. We also found that CILA1 exerts its functions via the activation of the Wnt/β-catenin signaling pathway. High CILA1 expression levels and low levels of phosphorylated β-catenin were closely associated with cisplatin resistance and advanced disease stage, and were predictors of poor prognosis in TSCC patients. These findings provided a new biomarker for the chemo-sensitivity of TSCC tumors and a therapeutic target for TSCC treatment.

BACKGROUND Harvesting an optimally thinned anterolateral thigh flaps is a challenge in overweight individuals and in the Western population. The authors describe a novel honeycomb technique to achieve a superthin anterolateral thigh flap in overweight patients. METHODS Forty patients with a body mass index greater than 25 kg/m(2) who required a thinned anterolateral thigh flap for reconstruction were assigned randomly to a honeycomb technique group or a microdissection technique group. The honeycomb technique group underwent flap thinning with the Cavitron Ultrasonic Surgical Aspirator, and flap thinning was performed with a conventional microdissection technique in the microdissection technique group. Perfusion of all flaps was measured by indocyanine green fluorescence angiography before and after thinning. Hypoperfusion was defined as 30 percent. RESULTS The mean body mass index was 28.6 ± 2.0 kg/m(2) and 27.3 ± 1.9 kg/m(2) in the honeycomb group and the microdissection group, respectively. Flap size, perforator, type of dissection, and initial perfusion were comparable between the two groups. However, significantly more patients (nine of 21) experienced final hypoperfusion in the microdissection group than in the honeycomb group (two of 19) (p = 0.034). In addition, blood loss and final flap thickness were significantly lower in the honeycomb group (p < 0.05), and the duration of thinning was comparable between the two groups. No flap necrosis was found in either group. CONCLUSION The honeycomb technique in combination with the Cavitron Ultrasonic Surgical Aspirator and indocyanine green angiography was able to remove adipose tissue but protect the integrity of the subcutaneous vascular plexus to reduce potential risk of jeopardizing flap perfusion while obtaining a superthin anterolateral thigh flap in an overweight population. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, II.

Made available in DSpace on 2018-12-11T17:13:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-08-01 Background Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the immune response after surgery. Methods A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery (T0) and at 2 (T1), 6 (T2), 24 (T3), and 72 h (T4) after surgery. Results A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p < 0.05), and cortisol levels were also lower in the endoscopic group (p < 0.05). Conclusions Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery. Department of Oral and Maxillofacial Surgery Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital Department of Otorhinolaryngology Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Department of Oral and Maxillofacial Surgery Dental School of Araçatuba Universidade Estadual Paulista (UNESP) Morphologic & Biochemical Lab of Pediatric Hematology Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University Department of Oral and Maxillofacial Surgery Dental School of Araçatuba Universidade Estadual Paulista (UNESP)

Objective The advantages and limitations of the endoscopy-assisted transoral approach (EATA) and external approaches (EAs) in resection of parapharyngeal space tumors (PSTs) remain unclear. In our study, we compared the use of the EATA and the EAs for the resection of large, benign PSTs. Study Design Forty-four patients with PSTs were divided into the EATA and EA groups. The perioperative and postoperative outcomes of the patients were evaluated. Results All of the tumors were completely removed. However, the procedure was converted to an open procedure for four patients in the EATA group and for six patients in the EA group who required endoscopic assistance. The intraoperative blood loss, amount and duration of drainage, postoperative pain, total hospital stay, and cosmetic outcomes were superior in the EATA group (P Conclusions Use of the EATA for resection of large, benign PSTs decreased the surgical invasiveness of the procedure and resulted in better aesthetic outcomes. However, use of the combined surgical approach allowed for improved access for the resection of PSTs.

Purpose: The overall biological roles and clinical significance of most long noncoding RNAs (lncRNA) in chemosensitivity are not fully understood. We investigated the biological function, mechanism, and clinical significance of lncRNA NR_034085, which we termed miRNA processing–related lncRNA (MPRL), in tongue squamous cell carcinoma (TSCC). Experimental Design: LncRNA expression in TSCC cell lines with cisplatin treatment was measured by lncRNA microarray and confirmed in TSCC tissues. The functional roles of MPRL were demonstrated by a series of in vitro and in vivo experiments. The miRNA profiles, RNA pull-down, RNA immunoprecipitation, serial deletion analysis, and luciferase analyses were used to investigate the potential mechanisms of MPRL. Results: We found that MPRL expression was significantly upregulated in TSCC cell lines treated with cisplatin and transactivated by E2F1. MPRL controlled mitochondrial fission and cisplatin sensitivity through miR–483-5p. In exploring the underlying interaction between MPRL and miR–483-5p, we identified that cytoplasmic MPRL directly binds to pre–miR–483 within the loop region and blocks pre–miR–483 recognition and cleavage by TRBP–DICER-complex, thereby inhibiting miR–483-5p generation and upregulating miR–483-5p downstream target-FIS1 expression. Furthermore, overexpression or knockdown MPRL altered tumor apoptosis and growth in mouse xenografts. Importantly, we found that high expression of MPRL and pre–miR–483, and low expression of miR–483-5p were significantly associated with neoadjuvant chemosensitivity and better TSCC patients’ prognosis. Conclusions: We propose a model in which lncRNAs impair microprocessor recognition and are efficient of pre-miRNA cropping. In addition, our study reveals a novel regulatory network for mitochondrial fission and chemosensitivity and new biomarkers for prediction of neoadjuvant chemosensitivity in TSCC. These findings uncover a novel mechanism by which lncRNA determines mitochondrial fission and cisplatin chemosensitivity by inhibition of pre-miRNA processing and provide for the first time the rationale for lncRNA and miRNA biogenesis for predicting chemosensitivity and patient clinical prognosis.

miRNAs that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNAs (mitomiR). mitomiRs have been shown to modulate the translational activity of the mitochondrial genome, yet their role in mitochondrial DNA (mtDNA) transcription remains to be determined. Here we report that the mitomiR-2392 regulates chemoresistance in tongue squamous cell carcinoma (TSCC) cells by reprogramming metabolism via downregulation of oxidative phosphorylation and upregulation of glycolysis. These effects were mediated through partial inhibition of mtDNA transcription by mitomiR-2392 rather than through translational regulation. This repression required specific miRNA–mtDNA base pairing and Argonaute 2. mitomiR-2392 recognized target sequences in the H-strand and partially inhibited polycistronic mtDNA transcription in a cell-specific manner. A retrospective analysis of TSCC patient tumors revealed a significant association of miR-2392 and regulated mitochondrial gene expression with chemosensitivity and overall survival. The clinical relevance of targeted mitochondrial genes was consistently validated by The Cancer Genome Atlas RNA sequencing in multiple types of cancer. Our study revealed for the first time the role of mitomiR in mtDNA transcription and its contribution to the molecular basis of tumor cell metabolism and chemoresistance. Significance: These findings uncover a novel mechanism by which mitomiRNA regulates mitochondrial transcription and provide rationale for use of mitomiRNA and mtDNA-encoded genes to predict chemosensitivity and patient clinical prognosis.

A few modified approaches have been reported for performing endoscope-assisted dissections of benign parotid tumors, but none that use incisions totally hidden in a natural furrow. This study evaluated the feasibility of performing endoscope-assisted extracapsular dissections of benign parotid tumors using a single cephaloauricular furrow incision. Forty-six patients with benign parotid superficial lobe tumors were randomly divided into two groups: an endoscope-assisted (21 patients) group or a conventional (25 patients) surgery group. Perioperative and postoperative outcomes of the patients were evaluated, including the maximum diameter of the tumors, length of the incision, operating time, estimated blood loss during the operation, amount and duration of drainage, satisfaction scores based on the cosmetic results, perioperative complications, and follow-up information. The diameters of the tumors were comparable between the groups, and all operations were successfully performed as planned. The mean length of the incision in the endoscope-assisted group (3.6 ± 0.5 cm) was significantly shorter than that in the conventional group (9.1 ± 1.9). Meanwhile, the intraoperative blood loss, amount of drainage, perioperative complications, and cosmetic outcomes were all improved in the endoscope-assisted group. No tumor recurrence was found during 11–40 months of follow-up. Cephaloauricular furrow incisions were totally and naturally hidden in this procedure. Endoscope-assisted extracapsular dissections of benign parotid tumors via a small cephaloauricular furrow incision were found to be feasible and reliable, providing a minimally invasive approach and a satisfactory appearance.

Objectives A no-flap design based on actual tongue anatomy has been reported to achieve precise reconstruction, but large carcinologic tongue defects remain extremely challenging to treat. The aim of this pilot study was to explore an anatomy-based flap design for precision subtotal tongue reconstruction. Material and methods Thirty-five patients were randomly divided into two groups, a “five-points eight-line-segments” (FIPELS) technique flap design group (18 patients) and a conventional surgery group (17 patients), to undergo subtotal tongue reconstruction. All patients received an anterolateral thigh flap with nerve coaptation to the lingual or glossopharyngeal nerve. Swallowing function, speech intelligibility, and cosmetic results were assessed with a Likert scale, and epicritic and proprioceptive sensitivity and thermosensation of the neotongue were investigated. Outcomes were analyzed, and a p-value Results The FIPELS flaps were significantly larger than conventionally designed flaps. All flaps healed uneventfully, except in two patients who presented with partial necrosis. Relative to patients in the conventional group, patients in the FIPELS group showed significantly improved swallowing function (p = 0.043) and cosmetic results (p = 0.017) but not speech intelligibility (p = 0.154). Patients in the two groups recovered comparably in terms of epicritic and proprioceptive sensitivity and thermosensation. Conclusion The anatomy-based FIPELS technique is an innovative and effective solution for subtotal tongue reconstruction.

Neurotropic infiltrative growth and distant metastasis are the main causes of death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs (lncRNAs) are involved in many human neoplasms, however, their potential roles in SACC are unclear. In our study, we found that ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was significantly upregulated in SACC patients with metastasis and SACC-lung metastasis (LM) cells. Moreover, ADAMTS9-AS2 expression was closely associated with the prognosis and distant metastasis in SACC patients. Next, we found that c-myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore, ADAMTS9-AS2, which mainly expressed in the cytoplasm, shared microRNA (miRNA) response elements with Integrin α6 (ITGA6). Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and invasion in SACC by competing with miR-143-3p. This sheds a new insight into the regulation mechanism of ADAMTS9-AS2, and it provides a possible application for the SACC treatment.

Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity.

BACKGROUND: Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied. METHODS: Sanger sequencing, whole-genome sequencing, and bioinformatics and structural modeling analyses were performed. RESULTS: A family with patients with fibro-osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through whole-genome sequencing, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed. CONCLUSIONS: The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro-osseous lesions.

Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma.

Rapidly growing evidence has shown that long noncoding RNAs (lncRNAs) are playing more and more important roles in a variety of biological processes and have been involved in various types of cancer. How to better decode these noncoding transcripts and how to predict their potential roles in tumorigenesis particularly in nasopharyngeal carcinoma (NPC) are still open questions. In this study, we applied our custom-designed lncRNA+mRNA gene expression microarray, which contains probes against 38,141 lncRNA transcripts, to assaying the expression profiling of flash-frozen tumorous and non-tumorous tissue samples from nonkeratinizing carcinoma (NKC), which is the major histologic type of NPC. As a result, 481 differentially expressed (DE) lncRNAs (231 up-regulated and 250 down-regulated) were identified. Moreover, integrated bioinformatics analyses including gene ontology, lncRNA functional prediction based on coding-noncoding gene co-expression network, interactive miRNAs, and transcription factor binding motifs were all carried out to decode the potential functional roles of these newly identified DE-lncRNAs. This work hence offers new resource and insight into lncRNAs for further understanding the molecular mechanisms of tumorigenesis of NKC, and may also define new biomarkers or therapy targets for the translational studies of NKC.

To evaluate the effect of cervical esophagostomy for the treatment of patients with dysphagia induced by radiotherapy, in order to improve the therapeutic effects.A retrospective study was performed on 53 nasopharyngeal carcinoma (NPC) patients with dysphagia, who received cervical esophagostomy. The nutritional status of these patients was measured at five given time before and after operation. The occurrence of pneumonia and reflux esophagitis before and after operation was recorded, and the quality of life based on SF-36 quality of life (QOL) scale was studied.After operation, the nutritional status of these patients improved substantially, including the weight, levels of hemoglobin, total protein, albumin and transferring (P0.05). The pneumonia-infection decreased from 60.38% (32/53) before operation to 15.22% (7/46) after operation (χ(2)=21.04, P0.01). The incidences of reflux esophagitis decreased from 26.42% (14/53)without operation to 6.52% (3/46) after operation (χ(2)=5.00, P0.01). Meanwhile, the status of physical health, mental health as well as physical function and social function of these patients were improved significantly at 1 month, 6 months, 1 year and 2 years after operation (P0.05).Cervical esophagostomy can improve the life quality of patients with dysphagia induced by radiotherapy for nasopharyngeal carcinoma.

Backgroud IL-22 regulates various processes and has been linked to diverse effects. However, the importance of IL-22 in the pathogenesis of allergic rhinitis (AR) remains poorly understood. This study sought to evaluate the levels of IL-22 and IL-17A in AR patients and their association with clinical severity of AR. Methods Thirty-six AR patients and 22 normal controls were enrolled in this study. The frequencies of IL-22+, IL-17A+, and IL-9+ T helper (Th) cells in peripheral blood of AR patients and normal controls were examined by flow cytometry. Serum levels of IL-22 and IL-17A in AR patients and normal controls were determined by ELISA. The clinical relevance of the percentages of IL-22+ and IL-17A+ Th cells as well as serum IL-22 and IL-17A levels were evaluated. Results The frequencies of IL-22+ and IL-17A+ Th cells, but not IL-9+ Th cells, were significantly increased compared with those in normal controls (p < 0.05). Frequencies of IL-22+ and IL-17A+ Th cells in peripheral blood of AR patients significantly correlated with visual analog scale scores of nasal symptoms (nasal congestion and rhinorrhea; p < 0.05). Moreover, the serum levels of IL-22 and IL-1 were significantly increased compared with those in normal controls (p < 0.05) and significantly correlated with the levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae specific IgE in AR patients. Conclusion Our findings suggested that IL-22 as well as IL-17A may play an important role in the regulation of Th2-skewed inflammation in AR patients.

Schizophrenia is a debilitating mental disorder. The TP53 tumor suppressor gene, encoding a phosphoprotein, is a key element in maintaining genomic stability and cell apoptosis. Recently, reduced risk of cancer in patients of schizophrenia has been reported. Some evidence also suggests the possible implication of TP53 in neurodevelopment. In order to examine the role of the TP53 gene in the pathogenesis of schizophrenic disorders, we investigated the genetic association between a functional polymorphism rs1042522 and schizophrenia by sequencing the fragment covering 72Pro> Arg in 701 cases and 695 controls in this work. In addition, we studied two other SNPs rs2078486 and rs8064946 by allele-specific PCR in the same samples. Though rs1042522 and rs8064946 did not show positive association with schizophrenia, we did observe statistically significant differences on SNP rs2078486 ( P -value = 0.029; OR = 1.21; 95% CI 1.02–1.42) and on haplotype CAC ( P -value = 0.0068; OR = 1.36; 95% CI 1.09–1.70). These results demonstrated that TP53 might play a role in susceptibility to schizophrenia.

To investigate the effect of operation on Benign thyroid nodules with hoarseness as primary symptom.Twelve patients were underwent the operation of subtotal thyroidectomy and exposing of recurrent laryngeal nerve. We evaluating the effect by fibrolaryngoscope and voice acoustic analysis before and after operation.All the 12 patients underwent surgery successfully. The hoarseness improved obviously and vocal cords were reactivate. Jitter, shimmer and dysphonia severity index showed significant difference pre and one month after surgery.Benign thyroid nodules could also cause vocal cord paralysis and hoarseness, the effect can be satisfying by subtotal thyroidectomy and exposing of recurrent laryngeal nerve if it can be early diagnosed.

Selective neck dissection (SND) in clinical N0 (cN0) cases of oral squamous cell carcinoma (SCC) has been performed by surgeons using a retroauricular or modified facelift approach with robotic or endoscopic assistance. However, these procedures provide cosmetic satisfaction at the cost of possible maximal invasiveness. In this prospective study, we introduced and evaluated the feasibility as well as surgical invasiveness and cosmetic outcome of endoscopically-assisted SND via a small submandibular approach.Forty-four patients with cT1-2N0 oral SCC (OSCC) were randomly divided into two groups of endoscopically-assisted SND and conventional SND. Perioperative and postoperative outcomes of patients were evaluated, including the length of the incision, operating time for neck dissection, estimated blood loss during the operation, amount and duration of drainage, total hospitalization period, total number of lymph nodes retrieved, satisfaction scores based on the cosmetic results, perioperative local complications, shoulder syndrome, and follow-up information.The mean operation time in the endoscopically-assisted group (126.04 ± 12.67 min) was longer than that in the conventional group (75.67 ± 16.67 min). However, the mean length of the incision was 4.33 ± 0.76 cm in the endoscopically-assisted SND group, and the amount and duration of drainage, total hospital stay, postoperative shoulder pain score, and cosmetic outcomes were superior in the endoscopically-assisted SND group. Additionally, the retrieved lymph nodes and complications were comparable.Endoscopically-assisted SND via a small submandibular approach had a longer operation time than the conventional approach. However, endoscopically-assisted SND was feasible and reliable while providing minimal invasiveness and satisfactory appearance.

The aim of the present study was to explore the effect of DJ-1-mediated PI3K/AKT/mTOR pathway on the proliferation, apoptosis, invasion, migration and other tumor biological characteristics of laryngeal squamous cell SNU-46, through stable transfection and overexpression of the DJ-1 gene. Retrovirus carrying DJ-1 gene was used to stabilize transfected human laryngeal squamous carcinoma SNU-46 cell line, and monoclonal cell line of stably overexpressed DJ-1 protein was screened out by G418. DJ-1 protein expression was determined by western blotting, and changes of p-AKT, p-mTOR and PTEN protein content were detected, followed by the detection of changes in proliferation, apoptosis, invasion, migration and other tumor biological characteristics of laryngeal squamous carcinoma cell line with stably transfected DJ-1 protein overexpression by flow cytometry, CCK-8 method and Transwell. We successfully constructed a laryngeal squamous carcinoma cell line of stably overexpressed DJ-1 protein and termed it SNU-46-DJ-1. After overexpression of DJ-1 protein, the levels of PTEN expression in laryngeal squamous cell SNU-46 decreased and p-AKT and p-mTOR protein expression levels increased. Compared to the untreated SNU-46 cells, the proliferation rate of SNU-46-DJ-1 cells increased (0.834±0.336 vs. 0.676±0.112; p

Objectives: The aim of this study was to evaluate the feasibility of an endoscope-assisted partial parotidectomy through a modified retroauricular incision. Patients and Methods: Thirty patients with benign parotid superficial lobe tumors with a diameter of 2.4 ± 0.5 cm, located in the anterior portion of the inferior auricular lobule, underwent an endoscope-assisted partial-superficial parotidectomy. A retrograde approach through a small skin incision was used. An additional 30 patients who underwent conventional surgeries were used as controls. The operation time, operative bleeding volume and subjective satisfaction with the incision scar were compared between the groups. Results: All operations were successfully performed. The endoscopic surgery duration (74.8 ± 15.7 min), bleeding volume (12.7 ± 3.9 ml) and incision length (4.8 ± 0.4 cm) differed between the groups (p = 0.001). The mean patient satisfaction score was 8.6 ± 1.2 in the endoscope-assisted surgery group and 5.4 ± 1.3 in the control group (p = 0.001). There were no tumor recurrences during the 9-36 months of follow-up. Conclusion: Endoscope-assisted partial-superficial parotidectomy via a modified retroauricular incision is a feasible method for the treatment of benign parotid superficial lobe tumors located in the anterior portion of the inferior auricular lobule. The main advantage of this procedure was that the small operative scars improved the cosmetic results.

The aim of the study is to report the feasibility of endoscope-assisted second branchial cleft cyst resection via a small incision along the skin line on the lateral neck. In total, 41 patients from the Department of Otolaryngology, Foshan Hospital of Yat-sen University were randomly assigned to conventional (20 patients) or endoscope-assisted (21 patients) second branchial cleft cyst resection. The patient clinical characteristics, operation time, operative bleeding volume, postoperative complications, and subjective satisfaction with the incision scar (measured using a visual analog scale) were compared between the groups. All 41 s branchial cleft cyst resections were successfully performed, and the wounds healed uneventfully. The bleeding volume (6.3 ± 2.5 ml) and incision length (2.7 ± 0.3 cm) differed between the groups (P < 0.00). The mean patient satisfaction score was 8.0 ± 0.8 in the endoscope-assisted surgery group and 6.4 ± 0.9 in the control group (P < 0.00). All of the patients in the endoscope-assisted surgery group were satisfied with their cosmetic results. No marginal nerve palsy occurred. No complications such as bleeding, salivary fistula, or paresis of the marginal mandibular branch occurred. All of the patients were disease free through a follow-up period of 6-24 months (median: 14 months). Endoscope-assisted second branchial cleft cyst resection via a small incision along the dermatoglyph on the lateral neck is a feasible technique. This procedure may serve as an alternative approach, allowing a minimally invasive incision and better cosmetic results.

To evaluate the application of flaps or musculocutaneous flaps in repairing cervical postradiation ulcer (cpu) at nasopharyngeal carcinoma.Deltopectoral flaps and pectoralis major flaps were applied to repair cervical radiation ulceration with different size and depth in 19 cases.Twelve cases repaired with deltopectoral flaps and 7 cases repaired with pectoralis major flaps, impaired wound healing happened at distal end of one deltopectoral flap, and the wound was healing hy second intention after debridement and dressing change. All the other deltopectoral flaps and pectoralis major flaps stayed alive. Flaps stayed alive without the recurrence of ulcer after the long-term follow-up for one to ten years.The effectiveness of cervical radiation ulceration reconstruction by deltopectoral flaps and pectoralis major flaps was proved. The reconstruction could prevent the recurrence of ulcer. Refer to the poor prognosis of chronic radiation ulceration with expectant treatment, precautions do count.

Background: Epithelial–mesenchymal transition (EMT) is a crucial programme in cancer metastasis. Epidermal growth factor (EGF) is a key inducer of EMT, and Ezrin has an important role in this process. However, how Ezrin is activated and whether it mediates EGF-induced EMT in tongue squamous cell carcinomas (TSCCs) through activating NF-κB remains obscure. Methods: We used two TSCC cell lines as a cell model to study invasion and EMT in vitro, and used nude mice xenografts model to evaluate metastasis of TSCC cells. Finally, we evaluated the level of pEzrin Tyr353, nuclear p65 and EMT markers in TSCC clinical samples. Results: Ezrin Tyr353 was phosphorylated through Akt (but not ERK1/2, ROCK1) pathway, and lead to the activation of NF-κB in EGF-treated TSCC cells. Akt and NF-κB inhibitors blocked EGF-induced EMT, and suppressed invasion and migration of TSCC cells. In vivo, silencing Ezrin significantly suppressed EGF-enhanced metastasis of TSCC xenografts. Finally, high levels of expression of pEzrin Tyr353, nuclear p65, vimentin and low level of expression of E-cadherin were correlated with cancer metastasis and poor patient prognosis. Conclusion: Our data suggest that Akt/Ezrin Tyr353/NF-κB pathway regulates EGF-induced EMT and metastasis inTSCC, and Ezrin may serve as a therapeutic target to reverse EMT in tongue cancers and prevent TSCC progression.

To investigate the influence of obstructive sleep apnea hypopnea syndrome (OSAHS) on children's growth.Fifty-three children diagnosed as OSAHS were included in the treatment group and underwent tonsillectomy or adenoidectomy, and 51 normal children were employed as the control group. Main data monitored by PSG and growth hormone (GH) in children of the treatment group were recorded before and after surgery, in addition, growth hormone, height and weight of children in the treatment group and control group were respectively recorded and compared.Height and weight of children with OSAHS before treatment were lower than that of the normal children and the difference was significant (P0.05). Compared with the data before surgery, oxygen saturation of blood in children of treatment group recorded by PSG increased (P0.05), while value of other data decreased (P0.05). Growth hormone in children of the treatment group was lower than that of the control group and the difference between two group was significant (P0.05), while the content of growth hormone in children of the treatment group elevated after 3 months postoperatively and at this time no difference was found between the two groups.Children with OSAHS present the symptom of upper airway obstruction, which badly affects sleep quality and results in decreased secretion of growth hormone and finally the height and weight of children is got involved. Timely surgery is necessary to alleviate the symptom.

To explore the effective treatment regimen for osteoradionecrosis of temporal bone.Twenty-seven patients with massive osteoradionecrosis in temporal bone were included and retrospectively analyzed, in which, 15 cases received surgery and the other 12 cases adopted non-surgical treatment.In the surgery group, three cases died one year postoperatively and died of massive hemorrhage due to internal carotid blowout. One case died four years after surgery without clear cause of death, and two cases were lost to follow up. Out of the nine survivors, the follow up period ranged from four months to eight years (one was followed up eight years, one was followed up over four years, four were followed up two-three years, one was followed up over one year, one was followed up nine months, and one was followed up four months, respectively). Patients classified as the type III received best outcome, and patients of type V and IV without invasion of the internal carotid artery received good surgical effects, while patients classified as the type IV with internal carotid artery invasion presented low survival rate. Two cases in the non-surgical group died of internal carotid rupture, and the other ten cases presented with repeated infection and expansion of the osteoradionecrosis lesion.The new classification criteria is helpful in diagnosis of location of lesions,and can serve as a guide for clinical therapy. Massive osteoradionecrosis in temporal bone responded unfavorably to conservative treatment, compared to that, surgery can effectively control the expansion of the lesion and markedly improve patient quality of life. Long-term follow up is necessary because of the slow development of osteoradionecrosis after surgery.

To compare the therapeutic effect between endoscopic thyroidectomy and open thyroidectomy.One hundred and nine patients were randomly divided into two groups. The first group with 52 patients were carried out endoscopic thyroidectomy; and the second group with 57 patients was carried out open thyroidectomy. Clinical features including operation time, operative blood loss, hospitalization and complications were compared between the two groups.The average operative time was (105.1 +/- 30.2) min in endoscopic group and (145.3 +/- 27.4) min in open group (P0.01); the mean operative blood loss was (7.5 +/- 4.2) ml in endoscopic group and (48.6 +/- 18.6) ml in open group (P0.01); the average hospitalization after operation was (4.1 +/- 1.4) days and (8.0 +/- 1.9) days (P0.01), the complication rate was 5.8% in endoscopic group and 8.8% in open group (P0.01).Compared to the traditional open surgery, endoscopic thyroidectomy is safe and effective,with advantages in terms of the aesthetic property,the amount of bleeding and the postoperative complications.

To investigate the cause of epistasis in patients irradiated for nasopharyngeal carcinoma.Seventy nasopharyngeal carcinoma cases with epistasis after radiotherapy were retrospectively analyzed.The causes of epistasis were local nasopharyngeal carcinoma recurrent 34.3% (24/70), pseudoaneurysm 14.3% (10/70) and nasopharyngeal crust 51.4% (36/70). Seven cases with local recurrent, 3 cases with pseudoaneurysm and 1 cases with nasopharyngeal crust and osteoradionecrosis died of intractable epistasis.Epistasis in patients irradiated for nasopharyngeal carcinoma is dangerous complication, especially in cases with local recurrent and pseudoaneurysm. Nasopharyngeal crust must be treated actively.

To analyze the EGG of laryngeal diseases and to evaluate the significance of Electroglottgrapihc waveform in the diagnosis of laryngeal diseases.The computer multimedia program of Dr. Speech science for Windows was used to obtain the EGG parameters in 120 cases of vocal polyp, 42 cases of vocal nodule, 21 cases of vocal cord paralysis, 42 cases of laryngeal cancer and 38 cases of Reinke's edema. The ECG parameters were analyzed.The special abnormal changes in the waves of EGG were related to the formation (type, position and size ) of laryngeal disease.The changes of Electroglottgraphic waveform perform a quantitative and objective index to the diagnosis of the laryngeal disease.

To evaluate surgical treatment methods for preserving laryngeal function and voice reconstruction for patients with hypopharyngeal and cervical esophageal carcinoma.16 patients with hypopharyngeal and cervical esophageal carcinoma were treated with preserving larynx in 8 cases, partial laryngectomy with laryngeal reconstruction in 3, voice reconstruction by blom-singer technique without laryngeal function preservation in 5. The types of hypopharyngeal and cervical esophageal reconstruction included gastric transpostion, pectoralis major myocutaneous flap, free forearm flap, delto-pectoral skin flap, sternocleidomastoid myocutaneous flap, platysma myocutaneous flap and laryngeal-tracheal flap following carcinoma resection.Deglutition restored in all patients except one who died of heat-break in 14th day after the operation. 13 patients rehabilitated speech, total laryngeal function restoration in 6 cases, partial laryngeal function restoration in 2 cases. The overall following-up was from 2 to 5 years. For the 5 cases with blom-singer voice reconstruction, all of them restored speech function.To improve life quality, laryngeal function preservation and voice reconstruction should be done for patients with hypopharyngeal and cervical esophageal carcinoma. Surgery methods should be carefully selected according to tumor's site, staging, patient's general condition and age.

Purpose: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action. Methods: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells. Results: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells. Conclusion: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.