BACKGROUND:Tumor-initiating cells (TICs) play a pivotal role in the unfavorable outcomes of laryngeal tumor proliferation, recurrence, and resistance to chemoradiotherapy. This study aims to explore the expression of CD271 (p75 neurotrophin receptor (p75NTR) in human laryngocarcinoma Hep2 cells and unravel its potential biological functions as a marker of laryngeal TICs. MATERIALS AND METHODS:Immunomagnetic cell sorting was utilized to separate subsets of Hep-2 cells based on high and low expression levels of CD271. Various aspects such as proliferation activity, colony formation ability, cell cycle distribution, and the expression of cancer-related proteins in each subpopulation were evaluated using immunofluorescence, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, soft agar gel assay, flow cytometry, and western blot assay. Furthermore, the tumor-forming potential of the subsets displaying high and low CD271 expression was examined through an in vivo experiment involving nude mice. The proteins associated with the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/Octamer-binding transcription factor 4 (OCT4) pathway were detected via western blot assay. RESULTS:The expression of CD133 was the highest in the CD271 high-expression group, and the expression of CD133 was the lowest in the CD271 low-expression group. Hep2 cells with high CD271 expression exhibited enhanced proliferation capacity, in contrast to those with low CD271 expression which showed reduced proliferation (p < 0.05). The CD271 high-expression group of Hep2 cells demonstrated superior clonogenic ability, a higher proportion in the S and G2/M phases of the cell cycle, and an increased sphere-forming capacity. Moreover, Hep2 cells with high CD271 expression displayed enhanced tumor formation capability in nude mice (p < 0.001). Western blot analysis indicated significantly elevated levels of specific proteins such as OCT4, Nanog Homeobox (NANOG) and p-STAT3/STAT3 in the CD271 high-expression group were significantly higher than those in the control group (p < 0.01), and the protein levels of low-expression group were significantly lower than those in the control group (p < 0.01). CONCLUSIONS:CD271 serves as a marker for TICs in Hep-2 cells, presenting a novel target for further investigation.

Cancer-associated fibroblasts (CAFs) play pivotal roles in facilitating tumor growth, recurrence, and metastasis. Nevertheless, studies examining the clinicopathological significance of CAFs and microvessel density (MVD) in hypopharyngeal squamous cell carcinoma (HPSCC), as well as their implications for prognosis, are scarce. Tissue samples from 96 HPSCC patients were subjected to immunohistochemistry (IHC) for CAF markers (including FAP and α-SMA) and MVD (characterized by the CD31 marker). Bioinformatics analysis was conducted to elucidate the potential mechanisms through which CAFs exert their functions. Compared with normal hypopharyngeal tissues, HPSCC tissues exhibited a greater number of CAFs and greater MVD. The high-MVD group demonstrated increased levels of FAP and α-SMA expression, increased CAF density, and an elevated rate of lymph node metastasis. Both CAF enrichment and high MVD were significantly associated with adverse clinicopathological features in patients, thereby leading to reduced overall survival. Additionally, both MVD and lymph node metastasis were identified as being independent prognostic factors that markedly increase patient mortality risk. Bioinformatics analyses revealed that CAFs may affect tumor progression, angiogenesis, and metastasis by the PI3K-Akt, KRAS, and Hedgehog signaling pathways, as well as through mechanisms such as epithelial-mesenchymal transition and ECM remodeling. CD19 may act as a potential marker for how CAFs affect the prognosis of head and neck squamous cell carcinomas. In summary, our findings indicate that CAFs and the MVD may significantly influence the prognosis of HPSCC patients. Angiogenesis and immunosuppression may represent the central mechanism through which CAFs affect prognosis, as CAFs facilitate angiogenesis and immunosuppression, thereby driving tumor progression and metastasis.

The present study aimed to investigate the regulatory effects and mechanisms of human placental extracts (HPE) on rats and cell models of ovalbumin (OVA)‑induced allergic rhinitis (AR). IFN‑y and LPS induced AR in vitro. A total of 32 male Sprague‑Dawley (SD) rats were randomly divided into the following four groups: Sham group, model group, model + HPE group and model + HPE + AMPK inhibitor group (n=8 rats/group). With the exception of the sham group, the remaining three groups were sensitized with OVA to establish an AR model, followed by various treatments. Hematoxylin and eosin staining was utilized to observe morphological changes in the nasal mucosa, ELISA was employed to measure serum levels of IL‑1β, interferon (IFN)β, immunoglobulin (Ig)E, IgG1 and IgG2a, and western blotting was conducted to assess protein expression across the groups. The sham group exhibited intact tissue structure with no notable pathological alterations. The model group demonstrated pronounced pathological features, including extensive infiltration of inflammatory cells, tissue shedding and edema. The model + HPE group revealed a gradual restoration of tissue architecture, characterized by reduced edema and inflammatory infiltration, whereas the model + HPE + AMPK inhibitor group again exhibited significant inflammatory cell infiltration and other pathological manifestations. Compared with the sham operation group, the levels of IL‑1β, IFNβ, IgE, IgG1 and IgG2a in the serum of the model group were elevated. The levels of IL‑1β, IFNβ, IgE, IgG1 and IgG2a in the model + HPE group were lower than those in the model group. In addition, the levels of IL‑1β, IFNβ, IgE, IgG1 and IgG2a in the model + HPE + AMPK inhibitor group were higher than those in the model + HPE group. Relative to the sham group, the expression levels of phosphorylated (p)‑AMPK/total (t)‑AMPK, p‑Src homology 2‑containing phosphatase (SHP)1/t‑SHP1 and p‑SHP2/t‑SHP2 were diminished, whereas the expression levels of p‑STING/t‑STING and p‑TBK1/t‑TBK1 were heightened in the model group. In comparison to the model group, the expression levels of p‑AMPK/t‑AMPK, p‑SHP1/t‑SHP1 and p‑SHP2/t‑SHP2 were enhanced, whereas the expression levels of p‑STING/t‑STING and p‑TBK1/t‑TBK1 were reduced in the model + HPE group. Conversely, when compared with the model + HPE group, the expression levels of p‑AMPK/t‑AMPK, p‑SHP1/t‑SHP1 and p‑SHP2/t‑SHP2 were decreased, whereas those of p‑STING/t‑STING and p‑TBK1/t‑TBK1 were increased in the model + HPE + AMPK inhibitor group. In conclusion, HPE may inhibit AR by modulating the AMPK/SHP1/SHP2/STING signaling pathway.

RATIONALE:Hungry bone syndrome (HBS) is a forgotten and underdiagnosed cause. Postoperative HBS refers to patients with high bone turnover before surgery, but after surgery, the inhibition of osteoclast resorption by intact parathyroid hormone suddenly decreases, resulting in a sudden increase in the amount of calcium resorbed by the bone, and a rapid, severe and persistent hypocalcemia, which may be accompanied by hypophosphatemia and hypomagnesemia. We present a case with information about HBS and related complications after parathyroidectomy (PTX). PATIENT CONCERNS:The patient was a 57-year-old woman who presented to the hospital with "pain in both ankles for more than 3 years and in both knees for more than 2 years." DIAGNOSES:A parathyroid mass was found preoperative. Unilateral resection of the lesion was performed under general anesthesia. On gross examination, the mass was reddish brown in color, about 2.9 × 2.5 × 2.3 cm, with abundant blood supply. Postoperative pathology diagnosed parathyroid adenoma. INTERVENTIONS:The patient was diagnosed with HBS on day 3 post-PTX, which lasted for 9 days. OUTCOMES:After active calcium supplementation and other pharmacological interventions, her test parameters gradually returned to normal and she was discharged on the 13th day after surgery. LESSONS:Using the case of a patient with primary hyperparathyroidism with HBS lasting 9 days after PTX for diagnosis and management, we aimed to summarize possible predictors and perioperative management strategies to reduce the incidence, severity, and duration of postoperative HBS.

Objective: Laryngeal cancer (LC) is one of the most common squamous cell carcinomas of the head and neck in clinical practice, and its incidence has been increasing in recent years, but the prognosis of the patients is not favorable. Hence, it is critical to re-understand and deeply study the causes and mechanisms of LC and explore new effective treatment methods and strategies. In this study, we analyzed the effect of Dihydroartemisinin (DHA) on the pathological progression of LC through the periostin (POSTN)/Yes-associated protein (YAP)/interleukin (IL)-6 pathway, which can provide new clinical references and guidelines. Methods: POSTN, YAP, and IL-6 levels in 18 pairs of fresh LC tissues and adjacent counterparts in our hospital were detected. Additionally, LC TU686 cell line was purchased for DHA treatment of various concentrations to detect changes in cell biological behavior. Finally, we built a tumorbearing mouse model with C57BL/6 mice and intragastrically administrated DHA to the animals to observe the growth of living tumors and to measure POSTN, YAP, and IL-6 expression in tumor tissues. Results: As indicated by PCR, Western blotting, and immunohistochemistry, POSTN, YAP, and IL-6 presented higher expression in LC tissues than in adjacent counterparts. In cell experiments, the cloning rate of LC cells decreased and the apoptosis rate increased after DHA intervention, with 160 mu mol/L DHA contributing to the most significant effect on LC activity inhibition. Furthermore, DHA-intervened cells exhibited markedly reduced POSTN, YAP, and IL-6 levels. Finally, the tumorigenesis experiment in nude mice showed inhibited tumor growth after DHA administration. And consistently, the expressions of POSTN, YAP, and IL-6 in living tumors decreased. Conclusions: DHA can inhibit POSTN/YAP/IL-6 transduction, accelerate LC cell apoptosis, and alleviate the malignant progression of LC.

Objective Laryngeal cancer (LC) is one of the most common squamous cell carcinomas of the head and neck in clinical practice, and its incidence has been increasing in recent years, but the prognosis of the patients is not favorable. Hence, it is critical to re-understand and deeply study the causes and mechanisms of LC and explore new effective treatment methods and strategies. In this study, we analyzed the effect of Dihydroartemisinin (DHA) on the pathological progression of LC through the periostin (POSTN)/Yes-associated protein (YAP)/interleukin (IL)-6 pathway, which can provide new clinical references and guidelines. Methods POSTN, YAP, and IL-6 levels in 18 pairs of fresh LC tissues and adjacent counterparts in our hospital were detected. Additionally, LC TU686 cell line was purchased for DHA treatment of various concentrations to detect changes in cell biological behavior. Finally, we built a tumor-bearing mouse model with C57BL/6 mice and intragastrically administrated DHA to the animals to observe the growth of living tumors and to measure POSTN, YAP, and IL-6 expression in tumor tissues. Results As indicated by PCR, Western blotting, and immunohistochemistry, POSTN, YAP, and IL-6 presented higher expression in LC tissues than in adjacent counterparts. In cell experiments, the cloning rate of LC cells decreased and the apoptosis rate increased after DHA intervention, with 160 μmol/L DHA contributing to the most significant effect on LC activity inhibition. Furthermore, DHA-intervened cells exhibited markedly reduced POSTN, YAP, and IL-6 levels. Finally, the tumorigenesis experiment in nude mice showed inhibited tumor growth after DHA administration. And consistently, the expressions of POSTN, YAP, and IL-6 in living tumors decreased. Conclusions DHA can inhibit POSTN/YAP/IL-6 transduction, accelerate LC cell apoptosis, and alleviate the malignant progression of LC.

Objective The specific roles of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and β-Catenin in laryngeal squamous cell carcinoma (LSCC) remain unclear. Methods In this study, the correlations between p-STAT3, β-Catenin, and clinicopathological characteristics were investigated using tissues and clinical data from 124 LSCC cases. Immunohistochemistry and immunofluorescence assays were used to examine p-STAT3 and β-Catenin expression and localization in these samples. Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognostic significance of these proteins. LSCC cell lines were treated with a STAT3 inhibitor (dihydroartemisinin) or activator (interleukin-6) to explore the mechanism of p-STAT3 and β-Catenin. Results There was an inverse correlation between p-STAT3 and β-Catenin expression in the LSCC samples. Patients with high p-STAT3 and low β-Catenin expression levels had significantly worse overall survival. Multivariate Cox regression analysis revealed that lymph node metastasis and β-Catenin expression were both independently correlated with unfavorable overall survival. Cell treatment with the p-STAT3 inhibitor inhibited the nuclear accumulation of β-Catenin, while p-STAT3 activator treatment could promote β-Catenin translocation to the nucleus. Conclusion Overall, our data indicate that p-STAT3 expression is associated with LSCC by promoting β-Catenin degradation. Keywords β-Catenin , epithelial-mesenchymal transition , laryngeal squamous cell carcinoma , STAT3 , prognostic indicator , biomarker

Emerging evidence has revealed the significant roles of nicotinamide n-methyltransferase (NNMT) in cancer initiation, development, and progression; however, a pan-cancer analysis of NNMT has not been conducted. In this study, we first thoroughly investigated the expression and prognostic significance of NNMT and the relationship between NNMT and the tumor microenvironment using bioinformatic analysis. NNMT was significantly increased and associated with poor prognosis in many common cancers. NNMT expression correlated with the infiltration levels of cancer-associated fibroblasts and macrophages in pan-cancer. Function enrichment analysis discovered that NNMT related to cancer-promoting and immune pathways in various common cancers, such as colon adenocarcinoma, head and neck squamous cell carcinoma, ovarian serous cystadenocarcinoma, and stomach adenocarcinoma. NNMT expression was positively correlated with tumor-associated macrophages (TAMs), especially M2-like TAMs. The results suggest that NNMT might be a new biomarker for immune infiltration and poor prognosis in cancers, providing new direction on therapeutics of cancers.

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

e18035 Background: Guanine nucleotide-binding protein alpha subunit 13 (GNA13) is closely related to tumor development, but the effect of GNA13 on the biological behavior of head and neck tumors is unknown. The aim of this study was to investigate whether GNA13 can influence the alteration of tumor microenvironment components through exosomes, which in turn promotes the development of head and neck squamous carcinoma (HNSCC). Methods: Using the Gene Expression Omnibus database, the differentially expressed gene GNA13 was screened. Immunohistochemistry and western blotting were used to detect the expression of GNA13 in HNSCC tissues and control tissues. GNA13 expression was down-regulated in tumor cell lines using transfection techniques. The effect of GNA13 downregulation on tumor cell growth was examined by in vitro experiments. RT-PCR and dual luciferase reporter gene assays were used to validate GNA13-regulated miRNAs and their target genes. Clonogenesis assays were used to examine the effect of target gene expression on fibroblasts, and the HNSCC xenograft mouse model was used to verify the role of GNA13 in tumor growth in vivo. The peripheral blood from patients with different stages of HNSCC was collected to determine the expression level of GNA13 in serum exosomes and to analyze its relationship with metastasis and postoperative recurrence. Results: GNA13 expression was elevated in HNSCC tissues and cells. The growth capacity of HNSCC cells was significantly reduced after downregulation of GNA13, which induced fibroblast conversion to MAF via exosomes and promoted their proliferation and migration. Meanwhile, GNA13 was able to regulate miR-26a-5p/STRADB expression in fibroblasts via exosomes. The overexpression of STRADB promoted the proliferation and migration of fibroblasts and induced their conversion to MAF. More importantly, in the conditioned medium of STRADB overexpressing fibroblasts, the proliferation and migration of HNSCC cells were promoted. Furthermore, knockdown of GNA13 expression inhibited the tumor growth in nude mice. It appeared that high expression of GNA13 in serum exosomes of patients with HNSCC was associated with poor prognosis. Conclusions: GNA13 regulates the miR-26a-5p/STRADB axis in fibroblasts via exosomes to create a metastasis-friendly microenvironment for tumor cells, ultimately promoting the progression of HNSCC. Meanwhile, the expression of GNA13 was positively correlated with the pathological grade and clinical stage of HNSCC, which seems to be a reliable indicator of tumor recurrence. Targeting this signaling pathway would be a promising therapeutic strategy for HNSCC.

Objective The specific roles of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and β-Catenin in laryngeal squamous cell carcinoma (LSCC) remain unclear. Methods In this study, the correlations between p-STAT3, β-Catenin, and clinicopathological characteristics were investigated using tissues and clinical data from 124 LSCC cases. Immunohistochemistry and immunofluorescence assays were used to examine p-STAT3 and β-Catenin expression and localization in these samples. Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognostic significance of these proteins. LSCC cell lines were treated with a STAT3 inhibitor (dihydroartemisinin) or activator (interleukin-6) to explore the mechanism of p-STAT3 and β-Catenin. Results There was an inverse correlation between p-STAT3 and β-Catenin expression in the LSCC samples. Patients with high p-STAT3 and low β-Catenin expression levels had significantly worse overall survival. Multivariate Cox regression analysis revealed that lymph node metastasis and β-Catenin expression were both independently correlated with unfavorable overall survival. Cell treatment with the p-STAT3 inhibitor inhibited the nuclear accumulation of β-Catenin, while p-STAT3 activator treatment could promote β-Catenin translocation to the nucleus. Conclusion Overall, our data indicate that p-STAT3 expression is associated with LSCC by promoting β-Catenin degradation.

气管侵犯作为影响中晚期分化型甲状腺癌（DTC）预后的独立危险因素，临床上对于侵犯气管的处理仍有待进一步规范化。根治晚期DTC的同时保留和重建患者气管的解剖结构和呼吸功能，以及有效保留患者喉的发音和呼吸功能，提高患者生存时间和生存质量，是中晚期DTC气管侵犯手术治疗的最高目标。本文对于中晚期DTC气管侵犯的过程以及对预后的不同影响，如何根据患者的术前评估实施不同的手术方式以及如何避免术后并发症作了详细阐述。

为了进一步提高头颈肿瘤治疗的效果和实际水平，从实施头颈肿瘤精准治疗的必要性和紧迫性、头颈肿瘤精准治疗的概念和范畴、头颈肿瘤治疗中的精准评估、头颈肿瘤外科精准治疗的相关问题、头颈肿瘤非手术精准治疗的相关问题以及头颈肿瘤精准治疗的发展方向等多角度、多层次和多侧面论述实施头颈肿瘤精准治疗的重要性，强调多学科协作的必要性，通过对相关问题的深入剖析，提出贯彻实施头颈肿瘤精准治疗的理念和策略势在必行，对头颈肿瘤精准治疗提出指导意见和发展方向。

Objective:To explore the methods for the accurate resection of malignant tumors of the external nose, and the accurate evaluation and repair of tissue defects.Methods:We collected 48 cases with nasal malignant tumors treated in 980 Hospital, Joint Support Force of the People's Liberation Army from January 2010 to June 2020, including 28 males and 20 females, aged 36-86 years. The pathological types of tumors included basal cell carcinomas ( n=29), squamous cell carcinomas ( n=11), trichilemmal carcinomas( n=6), denoid cystic carcinoma ( n=1) and non-Hodgkin lymphoma ( n=1). Tumor resection was mainly based on the traditional extended resection determined by the safety margin, and Mohs surgery was used to minimize the scope of resection, for the margin that significantly affected the repairing results, such as the lesion adjacent to the nasal alar margin, nasal columella or deep easy-penetrating margin. All cases obtained tumor resection and primary/secondary defect reconstruction. Results:According to the pathological type and tumor size, the safe resection margin was mainly 4-10 mm, and Mohs surgery was used in 24 cases. Limited-size defects in 38 cases were repaired with double-leaf flaps, kite flaps, nasal dorsum brow flaps, nasolabial flaps or free tissues. Among 10 cases with compound defects, 8 cases were repaired with frontal flaps, including 4 cases with single frontal flaps, 2 cases with additional titanium mesh stent reconstruction and 2 cases with over and out frontal flaps. During follow-up of 1 to 10 years, all the flaps survived without flap necrosis, and the postoperative nasal contour and ventilation were satisfactory. One patient had tumor recurrence 18 months after operation, 2 patients died of cardiovascular and cerebrovascular diseases, and other patients survived without tumors.Conclusions:Mohs surgery can basically meet the requirements for precise resection of external nasal malignant tumors. Individualized application of adjacent tissue flaps and various frontal flaps is a reasonable choice to achieve the satisfactory outcome of external nasal repair and to take into account the complexity of operation.

In the diagnosis and treatment of throat disease, the application and development of combining voice analysis or endoscopic technology with artificial intelligence has developed rapidly. This paper reviews the history and principles of the combination of voice analysis or endoscopic technology with artificial intelligence, summarizes its status of application and development, and sums up its advantages that lie in the strong learning and interpretation ability, amazing speed and tolerance, and stable replication and expansion. The key to restrict its development is the uncertainty in the process of machine learning, the error caused by small samples, and the ethical philosophical thinking. Future development direction should be that the surgeons in otolaryngology head and neck department on the basis of excellent professional knowledge, learn related knowledge of epidemiology, classic statistics, strengthen the exchanges and cooperation with machine learning developers. Eventually, advanced science and technology can be truly used in clinical practice to maximize the benefit of the majority of patients.

头颈部鳞状细胞癌（鳞癌）作为一种免疫抑制性肿瘤，免疫逃逸及T细胞信号的破坏是其发生发展的重要机制，免疫治疗以此为靶点通过其独特的作用机制在头颈部鳞癌的治疗中成为了又一重要的治疗手段。在临床治疗中，若想达到理想的治疗效果，需要采取多学科联合治疗。其中，免疫治疗可与其他治疗手段联合或者不同的免疫治疗相结合，从而达到更好的治疗效果。本文就肿瘤免疫微环境的改变及当前头颈部鳞癌免疫治疗研究进展作一系统综述，以期更好地指导临床治疗。

Objectives The purpose of this study was to evaluate the potential predictor of tumor size on rates of overall and disease‐free survival (OS and DFS) as determined by postoperative pathologic examination in patients with glottic carcinoma. Study Design Retrospective cohort study. Setting Tertiary care university hospital. Subjects and Methods In this study, 1337 consecutive patients with glottic carcinoma who underwent surgical treatment from 2005 to 2010 were retrospectively reviewed. The influence of tumor size that was evaluated by tumor area (tumor length × tumor width) on OS and DFS outcomes was assessed by Cox regression analyses. Results In all, 1303 (97.5%) patients were male, and 34 (2.5%) were female, with a mean ± SD age of 60.4 ± 10 years. The 10‐year OS and DFS rates were 72.9% and 69.9%, respectively. The tumor area cutoff values that best discriminated OS and DFS rates were both 1.80 cm 2 . Patients with glottic carcinoma with a larger tumor area had inferior OS and DFS rates. Based on the results of multivariate analyses, tumor area was an independent prognostic factor for rates of OS (hazard ratio, 1.87; 95% CI, 1.37‐2.56; P <. 001) and DFS (hazard ratio, 1.79; 95% CI, 1.34‐2.38; P <. 001) in patients with glottic carcinoma. Conclusions The results of this study indicate that patients with glottic carcinoma with a tumor area >1.8 cm 2 have inferior survival outcomes, and this factor independently predicts survival outcomes in these patients.

目的探讨沉默修复交叉互补基因1（excision repair cross complementary 1,ERCC1）表达对裸鼠人鳞状细胞癌移植瘤化疗增敏作用及其机制。方法 Balb/c纯系裸鼠背部皮下分别注入2×10~6个Hep-2细胞0.2 ml,制备裸鼠喉鳞状细胞癌移植瘤模型。实验随机分为空质粒对照组（A组）,顺铂化疗组（DDP组,B组）,顺铂化疗联合ERCC1 ShRNA组（DDP+ERCC1 ShRNA,C组）。测量并计算移植瘤体积,应用免疫组织化学方法检测喉癌Hep-2细胞移植瘤组织Ki67指数和ERCC1的表达,应用Western blot检测喉癌Hep-2细胞移植瘤组织ERCC1表达。结果移植瘤模型小鼠体积在C组于给药第15天和第20天明显减小,与B组相比差异有统计学意义（t值分别为13.103和17.022,P均＜0.01）。Ki67指数C组与B组相比明显降低,差异有统计学意义（t=3.794,P＜0.05）,ERCC1表达的免疫组织化学结果和Western blot结果均显示,B组与A组相比明显升高,两组相比差异有统计学意义（t值分别为4.919和6.345,P均＜0.01）;C组与B组相比明显降低,差异有统计学意义（t值分别为5.367和 6.463,P均＜0.01）。结论喉鳞状细胞癌裸鼠移植瘤体内实验证明抑制ERCC1表达对化疗有明显增敏作用。

Objective:The aim of this study was to evaluate the predicting role of tumor volume as evaluated by postoperative pathologic examination on overall survival（OS） and disease free survival（DFS） in patients with local advanced glottic carcinoma. Methods:In this study, the records of 406 consecutive patients with local advanced glottic carcinoma（T3-T4 stages） who underwent surgery ± chemoradiotherapy from January 2005 to December 2010 were retrospectively reviewed and followed up. The demographic characteristics, disease staging, and pathologic tumor volume were analyzed. The optimal cutoff values of tumor volume for OS and DFS were obtained by using receiver operating characteristic（ROC） curves. The association of tumor volume with T stages were assessed by using Logistic regression model, and the relationship between tumor volume and OS and DFS rates were evaluated by using Cox regression models. Results:The 5-and 10-year OS rates were 62.9% and 55.4%, respectively. The 5-and 10-year DFS rates were 55.5% and 50.8%, respectively. The mean tumor volume was（5.1±6.7） cm³, T4 stage patients had higher tumor volume than those of patients with T3 stage（P<0.001）. The factor of tumor volume was correlated with T stages by using Logistic regression analyses（OR=13.81, 95%CI: 6.03-31.59, P<0.001）. The optimal cutoff values of tumor volume that were both at 3 cm³ for OS and DFS rates were obtained by using ROC curve plots. The OS and DFS rates of glottic carcinoma patients with tumor volume ≤ 3 cm³ were better when compared with those of patients with tumor volume>3 cm³（P<0.001）. Upon multivariate analyses, tumor volume was strongly correlated with poorer OS and DFS rates and remained independent prognostic factors for both the OS and DFS of patients with glottic carcinoma（OS: HR=1.59, 95%CI: 1.09-2.32, P＝0.017; DFS: HR=1.54, 95%CI: 1.08-2.20, P=0.016）. Conclusion:This study demonstrates that tumor volume is correlated with T stages, and this factor is an independent predictive factor of survival outcomes in patients with local advanced glottic carcinoma.

Copy number alterations are crucial for gastric cancer (GC) development. In this study, Tocopherol alpha transfer protein-like (TTPAL) was identified to be highly amplified in our primary GC cohort (30/86). Multivariate analysis showed that high TTPAL expression was correlated with the poor prognosis of GC patients. Ectopic expression of TTPAL promoted GC cell proliferation, migration, and invasion in vitro and promoted murine xenograft tumor growth and lung metastasis in vivo. Conversely, silencing of TTPAL exerted significantly opposite effects in vitro. Moreover, RNA-sequencing and co-immunoprecipitation (Co-IP) followed by liquid chromatograph-mass spectrometry (LC-MS) identified that TTPAL exerted oncogenic functions via the interaction of Nicotinamide-N-methyl transferase (NNMT) and activated PI3K/AKT signaling pathway. Collectively, TTPAL plays a pivotal oncogenic role in gastric carcinogenesis through promoting PI3K/AKT pathway via cooperating with NNMT. TTPAL may serve as a prognostic biomarker of patients with GC.