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Objective: At present, the true sagittal alignment of the cervical spine is uncertain, resulting in no standard reference for subaxial cervical surgery. So, we aimed to explore the age difference of normal cervical sagittal alignment and to further investigate the mid‐and long‐term changes of sagittal alignment after subaxial cervical spine surgery. Materials and Methods: This was a retrospective study and 1223 asymptomatic volunteers and 79 patients undergoing subaxial cervical spine surgery were retrospectively reviewed in total. Asymptomatic volunteers and patients were divided into six subgroups: 20–29, 30–39, 40–49, 50–59, 60–69 and ≥70 groups. The age difference and trend with age of cervical sagittal parameters of asymptomatic volunteers were assessed by cervical lateral radiography and analyzed by ANOVA test, and the regression equation of C2‐7 Cobb was established via multiple linear regression. Based on the C2‐7 Cobb regression equations of different ages, the theoretical value, deviation value, loss value of the C2‐7 Cobb, and JOA recovery rate of patients were calculated, and the correlation among the loss value, deviation value of the C2‐7 Cobb, and JOA recovery rate of the 79 patients was evaluated by Pearson correlation analysis. Results: For the asymptomatic volunteers, the C0‐2 Cobb decreased gradually with increasing age. The C2‐7 Cobb, C2‐7 SVA, T1S, NT, and TIA increased gradually with increasing age. The CBVA fluctuated with increasing age. T1S demonstrated a moderate correlation with C2‐7 Cobb (r = 0.60, p < 0.01); C0‐2 Cobb, C2‐7 SVA, CBVA, and TIA demonstrated a fair correlation with C2‐7 Cobb (r = −0.30, −0.33, 0.41, 0.40, p < 0.01); age demonstrated a poor correlation with C2‐7 Cobb (r = 0.19, p < 0.01). The regression equations of C2‐7 Cobb were established using C0‐2 Cobb, C2‐7 SVA, CBVA, and T1S. For the patients with subaxial cervical spine surgery, the loss of C2‐7 Cobb was moderately correlated with the deviation of C2‐7 Cobb (r = 0.33, p < 0.01). Conclusion: The age difference of cervical sagittal alignment was obvious, and the C2‐7 Cobb increased with age especially. The closer the postoperative C2‐7 Cobb was to the theoretical value of corresponding age, the smaller the loss of correction angle was, and the better the mid‐ and long‐term outcomes. The personalized sagittal reconstruction should be performed according to age difference for subaxial cervical spine surgery. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is one of the leading causes that severely limits the success of osteosarcoma treatment. Evaluating chemoresistance before chemotherapy poses a new challenge for researchers. We established an effective chemoresistance risk scoring model for prechemotherapy osteosarcoma using single-cell sequencing. Methods: We comprehensively analyzed osteosarcoma data from the bulk mRNA sequencing dataset TARGET-OS and the single-cell RNA sequencing (scRNA-seq) dataset GSE162454. Chemoresistant tumor clusters were identified using enrichment analysis and AUCell scoring. Its differentiated trajectory was achieved with inferCNV and pseudotime analysis. Ligand–receptor interactions were annotated with iTALK. Furthermore, we established a chemoresistance risk scoring model using LASSO regression based on scRNA-seq-based markers of chemoresistant tumor clusters. The TARGET-OS dataset was used as the training group, and the bulk mRNA array dataset GSE33382 was used as the validation group. Finally, the performance was verified for its discriminatory ability and calibration. Results: Using bulk RNA data, we found that osteogenic expression was upregulated in chemoresistant osteosarcoma as compared to chemosensitive osteosarcoma. Then, we transferred the bulk RNA findings to scRNA-seq and noticed osteosarcoma tumor clusters C14 and C25 showing osteogenic cancer stem cell expression patterns, which fit chemoresistant characteristics. C14 and C25 possessed bridge roles in interactions with other clusters. On the one hand, they received various growth factor stimulators and could potentially transform into a proliferative state. On the other hand, they promote local tumor angiogenesis, bone remodeling and immunosuppression. Next, we identified a ten-gene signature from the C14 and C25 markers and constructed a chemoresistant risk scoring model using LASSO regression model. Finally, we found that chemoresistant osteosarcoma had higher chemoresistance risk score and that the model showed good discriminatory ability and calibration in both the training and validation groups (AUCtrain = 0.82; AUCvalid = 0.84). Compared with that of the classic bulk RNA-based model, it showed more robust performance in validation environment (AUCvalid-scRNA = 0.84; AUCvalid-bulk DEGs = 0.54). Conclusions: Our work provides insights into understanding chemoresistant osteosarcoma tumor cells and using single-cell sequencing to establish a chemoresistance risk scoring model. The model showed good discriminatory ability and calibration and provided us with a feasible way to evaluate chemoresistance in prechemotherapy osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: This multicenter clinical trial was designed to evaluate the efficacy and safety of thalidomide (THD) in preventing oral mucositis (OM) in patients with nasopharyngeal carcinoma (NPC) undergoing concurrent chemoradiotherapy (CCRT). Methods: Patients with locally advanced NPC were randomly assigned to either a THD group or a control group. All 160 patients received radical intensity‐modulated radiotherapy plus cisplatin‐based concurrent chemotherapy and basic oral hygiene guidance. Patients in the THD group received additional THD at the beginning of CCRT. The primary end points were the latency period and the incidence of OM. The secondary end points were mouth and throat soreness (MTS), weight loss, short‐term efficacy, and adverse events. Results: The median latency period of OM was 30 and 14 days in the THD and control groups, respectively (hazard ratio, 0.32; 95% confidence interval, 0.23‐0.35; P <.0001). The incidence of OM and severe OM (World Health Organization grade 3 or higher) was significantly lower in the THD group than the control group (87.5% vs 97.5% [P =.016] and 27.5% vs 46.3% [P =.014], respectively). THD treatment also remarkably reduced the intensity of MTS and the degree of weight loss. In comparison with the control group, the incidence of nausea, vomiting, and insomnia was significantly decreased, whereas the incidence of dizziness and constipation was obviously increased in the THD group. The objective response rates 3 months after CCRT were similar between the groups. Conclusions: THD prolonged the latency period, reduced the incidence of OM, and did not affect the short‐term efficacy of CCRT in patients with NPC. Lay Summary: Oral mucositis is the most common complication of nasopharyngeal carcinoma during chemoradiotherapy; it decreases the patient's quality of life, and ideal mucosal protective agents are lacking.A few basic research and preclinical studies have shown that thalidomide may be an approach to ameliorating oral mucositis.The results of the current study confirm that thalidomide has a protective effect against oral mucositis in patients who have received chemoradiotherapy for nasopharyngeal carcinoma. Thalidomide could prolong the latency period and reduce the incidence of oral mucositis in patients who have received concurrent chemoradiotherapy for nasopharyngeal carcinoma. Thalidomide administration is well tolerated and safe. [ABSTRACT FROM AUTHOR]

Tongue squamous cell carcinoma (TSCC) is one of the deadliest cancers of the head and neck, but the role of the ferroptosis pathway in its development is still unknown. In this study we explored the pathogenetic mechanisms associated with ferroptosis in TSCC. We identified differentially expressed genes (DEGs) of TSCC patients and used gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) to annotate, visualize, and integrate these DEGs. Receiver operating characteristic curve (ROC) analysis was performed, and the STRING database was used to construct a protein–protein interaction network to evaluate the predictive value of ferroptosis‐related DEGs. A total of 219 DEGs were identified and GO, KEGG, and GSEA showed that extracellular matrix (ECM)‐receptor interaction and interleukin (IL)‐17 signaling pathways were substantially upregulated in TSCC. Univariate Cox analysis revealed that high expression of CA9, TNFAIP3, and NRAS were predictive of a worse outcome. We then constructed a prognostic model that predicted survival in the validation cohort at 1 year and 32 months. Finally, 60 cases of tongue carcinoma and normal tissues were collected, and immunohistochemistry was used to detect the expression of CA9. We found that CA9 was strongly expressed in tongue carcinoma tissues and absent in adjacent tissues. Overall, we found that ferroptosis‐related genes may affect TSCC prognosis through the ECM‐receptor interaction and IL‐17 signaling pathways. Additionally, immunohistochemistry confirmed that CA9 was highly expressed in tongue carcinoma tissues, and a model based on ferroptosis‐related genes showed a good ability to predict overall survival in TSCC. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the cervical lymph node metastasis of nasopharyngeal carcinoma (NPC) and to establish a novel N staging standard for NPC, based on intensity modulated radiation therapy (IMRT) via a prospective multicenter clinical trial. Between January 2006 and December 2009, a total of 492 patients with NPC without distant metastasis were included in the present study. All patients were treated with IMRT. According to Radiation Therapy Oncology Group division standards, the present study proposed a novel N staging system following the review of magnetic resonance images in comparison with the 7th edition of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system. Retropharyngeal lymph nodes, cervical lymph node level and cervical lymph node laterality were independent prognostic factors used in multivariate analyses. According to the results of the risk variety, the present study suggested that the novel N staging system included: N0 (no lymph node metastasis), N1 [retropharyngeal or/and unilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis], N2 [bilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis] and N3 (lymph node metastasis in IVa and Vb regions and their lower regions). The novel N staging system proposed in the present study performs better in risk difference and distribution balance. Furthermore, the differences of 5-year curves of distant metastasis-free survival and overall survival had greater statistically significant differences compared with the 7th edition of the UICC/AJCC staging system. The present study suggested a novel N staging system for cervical lymph node metastasis of NPC, which may predict the prognosis of patients with NPC in a more objective and accurate way. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the factors affecting postoperative quality of life in patients with ankylosing spondylitis (AS) and thoracolumbar kyphosis (TLK), and establish a personalized sagittal reconstruction strategy., Methods: Patients with AS and TLK who underwent pedicle subtraction osteotomy (PSO) from February 2009 to May 2019 were retrospectively included. Quality of life and spinal sagittal radiographic parameters were collected before surgery and at the last follow-up. Patients were divided into two groups based on the attainment of minimal clinically important difference (MCID) on the Bath Ankylosing Spondylitis Functional Index and Oswestry Disability Index. Comparisons of radiographic parameters and clinical outcomes were conducted between and within groups. Regression analysis was used to identify the risk factors within the missing MCID cohort. Sagittal reconstruction equations were established using the pelvic incidence (PI) and thoracic inlet angle (TIA) in the reached MCID cohort., Results: The study comprised 82 participants. Significant improvements were observed in most radiographic parameters and all quality-of-life indicators during the final follow-up compared with the preoperative measures (p < 0.05). Factors including cervical lordosis (CL) ≥ 18° (OR 9.75, 95% CI 2.26-58.01, p = 0.005), chin-brow vertical angle (CBVA) ≥ 25° (OR 14.7, 95% CI 3.29-91.21, p = 0.001), and pelvic tilt (PT) ≥ 33° (OR 21.77, 95% CI 5.92-103.44, p < 0.001) independently correlated with a failure to attain MCID (p < 0.05). Sagittal realignment targets were constructed as follows: sacral slope (SS) = 0.84 PI - 17.4° (R2 = 0.81, p < 0.001), thoracic kyphosis (TK) = 0.51 PI + 10.8° (R2 = 0.46, p = 0.002), neck tilt (NT) = 0.52 TIA - 5.8° (R2 = 0.49, p < 0.001), and T1 slope (T1S) = 0.48 TIA + 5.8° (R2 = 0.45, p = 0.002)., Conclusions: PSO proved efficacious in treating AS complicated by TLK, yielding favorable outcomes. CBVA ≥ 25°, CL ≥ 18°, and PT ≥ 33° were the primary factors affecting postoperative quality of life in patients with AS. The personalized sagittal reconstruction strategy in this study focused on the subjective sensations and daily needs of patients with AS, which were delineated by the equations SS = 0.84 PI - 17.4°, TK = 0.51 PI + 10.8°, NT = 0.52 TIA - 5.8°, and T1S = 0.48 TIA + 5.8°.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, with pathological characteristics of bone erosion, inflammation of attachment point, and bone ankylosis. Due to the ossified intervertebral disc and ligament, pedicle subtraction osteotomy (PSO) is one of the mainstream surgeries of AS-related thoracolumbar kyphosis, but the large amount of blood loss and high risk of instrumental instability limit its clinical application. The purpose of our study is to propose a new transpedicular vertebral body compression osteotomy (VBCO) in PSO to reduce blood loss and improve stability., Methods: A retrospective analysis was performed on patients with AS-related thoracolumbar kyphosis who underwent one-level PSO in our hospital from February 2009 to May 2019. A total of 31 patients were included in this study; 6 received VBCO and 25 received eggshell vertebral body osteotomy. We collected demographic data containing gender and age at diagnosis. Surgical data contained operation time, estimated blood loss (EBL), and complications. Radiographic data contained pre-operative and follow-up sagittal parameters including chin brow-vertical angle (CBVA), global kyphosis (GK), thoracic kyphosis (TK), and lumbar lordosis (LL). A typical case with L2-PSO was used to establish a finite element model. The mechanical characteristics of the internal fixation device, vertebral body, and osteotomy plane of the two osteotomy models were analyzed under different working conditions., Results: The VBCO could provide comparable restoring of CBVA, GK, TK, and LL in the eggshell osteotomy procedure (all p > 0.05). The VBCO significantly reduced EBL compared to those with eggshell osteotomy [800.0 ml (500.0-1,439.5 ml) vs . 1,455.5 ml (1,410.5-1,497.8 ml), p = 0.033]. Compared with the eggshell osteotomy, VBCO showed better mechanical property. For the intra-pedicular screw fixation, the VBCO group had a more average distributed and lower stress condition on both nails and connecting rod. VBCO had a flattened osteotomy plane than the pitted osteotomy plane of the eggshell group, showing a lower and more average distributed maximum stress and displacement of osteotomy plane., Conclusion: In our study, we introduced VBCO as an improved method in PSO, with advantages in reducing blood loss and providing greater stability. Further investigation should focus on clinical research and biomechanical analysis for the application of VBCO., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Zeng, Yan, Wu, Lv, Zhang, Zhang, Jiang, Zhang, Fu, Peng, Wang, Zhao, Li, Huang, Wang, Li, Hu, Wang and Gao.)

Purpose: This study aimed to establish a valid prognostic nomogram for osteocarcinoma after surgical management., Methods: Based on the SEER database, we retrieved the clinical variables of patients confirmed to have osteocarcinoma between 1975 and 2016. Then, we performed univariate and multivariate analyses and constructed a nomogram of overall survival., Results: Multivariate analysis of the primary cohort revealed that the independent factors for survival were age, grade, pathologic stage, T stage, and surgery performed. All these factors were showed by the nomogram. The correction curve of survival probability showed that the prediction results of nomogram well agreed with the actual observation results. The C index of the nomogram used to predict survival was 0.82; the AUC of 1-year, 3-year, and 5-year survival rates in the training cohort were 0.9, 0.819, and 0.80631, respectively, indicating that the model was accurate and reliable; whether the operation was performed or not; T stage; grade; and age were the main factors affecting the survival of patients. The AUC of the validation cohort for 1 year, 3 years, and 5 years were 0.8, 0.831, and 0.80023, respectively., Conclusion: The proposed nomogram can more accurately predict the prognosis of patients with osteocarcinoma after surgical management. This could be a potential method that services clinical work., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Qiuli Wu et al.)

Background: Osteoporosis often occurs with carotid atherosclerosis and causes contradictory calcification across tissue in the same patient, which is called the "calcification paradox". Circulating monocytes may be responsible for this unbalanced ectopic calcification. Here, we aimed to show how CD14 + monocytes contribute to the pathophysiology of coexisting postmenopausal osteoporosis and carotid atherosclerosis., Methods: We comprehensively analyzed osteoporosis data from the mRNA array dataset GSE56814 and the scRNA-seq dataset GSM4423510. Carotid atherosclerosis data were obtained from the GSE23746 mRNA dataset and GSM4705591 scRNA-seq dataset. First, osteoblast and vascular SMC lineages were annotated based on their functional expression using gene set enrichment analysis and AUCell scoring. Next, pseudotime analysis was applied to draw their differentiated trajectory and identify the key gene expression changes in crossroads. Then, ligand-receptor interactions between CD14 + monocytes and osteoblast and vascular smooth muscle cell (SMC) lineages were annotated with iTALK . Finally, we selected calcification paradox-related expression in circulating monocytes with LASSO analysis., Results: First, we found a large proportion of delayed premature osteoblasts in osteoporosis and osteogenic SMCs in atherosclerosis. Second, CD14 + monocytes interacted with the intermediate cells of the premature osteoblast and osteogenic SMC lineage by delivering TGFB1 and TNFSF10. This interaction served as a trigger activating the transcription factors (TF) SP1 and NFKB1 to upregulate the inflammatory response and cell senescence and led to a retarded premature state in the osteoblast lineage and osteogenic transition in the SMC lineage. Then, 76.49% of common monocyte markers were upregulated in the circulating monocytes between the two diseases, which were related to chemotaxis and inflammatory responses. Finally, we identified 7 calcification paradox-related genes on circulating monocytes, which were upregulated in aging cells and downregulated in DNA repair cells, indicating that the aging monocytes contributed to the development of the two diseases., Conclusions: Our work provides a perspective for understanding the triggering roles of CD14 + monocytes in the development of the calcification paradox in osteoporosis- and atherosclerosis-related cells based on combined scRNA and mRNA data. This study provided us with an elucidation of the mechanisms underlying the calcification paradox and could help in developing preventive and therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Guo, Wang, Yan, Lv, Zhao, Jiang, Zhang, Zhang, Yang, Li, Zhang, Wang, Huang, Li, Hu and Gao.)

Background: Thoracolumbar metastases is a difficult disease to deal with in spinal surgery. The aim of this study is to investigate the clinical efficacy of bone-filled mesh vertebroplasty combined with posterior spinal internal fixation in the treatment of thoracolumbar metastases., Methods: The clinical data of 68 patients with thoracolumbar vertebral metastases from January 2018 to April 2020 were retrospectively analyzed. A total of 37 cases underwent bone filling mesh pocket vertebroplasty combined with posterior spinal internal fixation as the observation group, and 31 cases underwent routine vertebroplasty combined with posterior spinal internal fixation as the control group. The visual analogue scale (VAS) scores, Oswestry disability index (ODI) scores, Karnofsky performance status (KPS) scores, and the heights of the anterior margin and middle of the diseased vertebra were compared between the 2 groups before and 1 week, 3 months, 6 months, and 1 year after surgery., Results: All cases successfully completed the operation, and there was no pulmonary embolism, paraplegia, or perioperative death in follow-up reported. Intraoperative bone cement leakage occurred in 4 cases with a total of 6 vertebrae in the observation group (leakage rate: 14.29%), and in 8 cases with a total of 11 vertebrae in control group (leakage rate: 31.43%). The differences in VAS scores, ODI scores, KPS scores, and the heights of the anterior margin and middle of the diseased vertebra between preoperative and postoperative periods at 1 week, 3 months, 6 months, and 1 year in both groups were statistically significant (P<0.05), while the differences between the 2 groups were not statistically significant (P<0.05)., Conclusions: The application of bone-filled mesh vertebroplasty combined with posterior internal pedicle screws fixation for the treatment of thoracolumbar metastases can not only reduce the injury of the operation, but also achieve the purpose of relieving pain, controlling local tumor growth to a certain extent, restoring neural function, and rebuilding the stability of the spine, which has important clinical value.

Background: This study aimed to identify the key genes related to male ankylosing spondylitis (AS) and to analyze the role of immune cell infiltration in the pathological process of this disease., Methods: The AS dataset was downloaded from the Gene Expression Omnibus (GEO) public database, and the data of male healthy controls (M&#95;HC) and male AS patients (M&#95;AS) were extracted. R software was used to identify differentially expressed genes (DEGs). Functional and pathway enrichment analysis of the DEGs was performed. A protein-protein interaction (PPI) network was constructed, and the hub genes were screened out. All expression profile data were analyzed by weighted correlation network analysis (WGCNA) to screen out the hub genes, which were then intersected with the hub genes from the PPI network to obtain the key genes. Finally, the difference in immune cell infiltration in the two sets of samples was evaluated with CIBERSORT, and the correlation between the key genes and infiltrating immune cells was analyzed., Results: A total of 689 DEGs were obtained, of which 395 genes were up-regulated and 294 genes were down-regulated. Functional and pathway enrichment analysis showed that DEGs were mainly enriched in pathways related to immune response. Based on the PPI analysis, five clusters with high scores were selected. Through WGCNA, 14 gene modules were obtained. The green module with the highest correlation was selected and intersected with the cluster previously obtained to obtain three key genes, RAB5C , SYNJ1 , and RNF19B . Immune infiltration analysis found that monocytes and gamma delta T cells may be involved in the process of AS. Also, RAB5C , SYNJ1 , and RNF19B are all related to increased levels of monocytes and macrophages., Conclusions: RAB5C , SYNJ1 , and RNF19B are key DEGs expressed in M&#95;AS and may play a role in the disease's occurrence and development through regulating immune cell functions., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-2721). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: To explore the feasibility and efficiency of posterior wedge osteotomy assisted by O-arm navigation treatment of ankylosing spondylitis (AS) patients with thoracolumbar fracture., Methods: This is a case series study. A total of 16 cases of AS accompanied by thoracolumbar fractures from January 2012 to July 2015 were retrospectively analyzed. All patients underwent "posterior wedge osteotomy assisted by O-arm navigation". The operation time, blood loss volume, preoperative and postoperative visual analogue scale (VAS), American Spinal Injury Association (ASIA) classification, and spinal imaging parameters [Cobb angle, C7 plumb line (C7PL), and jaw-brow angle] were collected and analyzed., Results: The operative time consumption was 120-350 mins and the intra-operative blood loss volume was 200-800 mL. No obvious postoperative complications occurred in any participants. The back pain of all participants was relieved, and the neurological functions of eight participants with spinal cord injury (SCI) were recovered in varying degrees except for one patient with severe SCI. The spinal deformities of the participants were corrected to varying degrees. The fracture sites of 16 participants were all healed, and there was no loosening or detachment of internal fixation during the 6-month follow-up period., Conclusions: Posterior wedge osteotomy assisted by O-arm navigation was shown to be a safe and effective method to treat AS accompanied by thoracolumbar fractures. This treatment strategy can accurately decompress and reduce the fracture and significantly correct the kyphosis, with good surgical effect.

Background: Overexpression of the membrane protein SEC61 translocon gamma subunit (SEC61G) has been observed in a variety of cancers; however, its role in head and neck squamous cell carcinomas (HNSCC) is unknown. This study aimed to elucidate the relationship between SEC61G and HNSCC based on data from The Cancer Genome Atlas (TCGA) database. Methods: Data for HNSCC patients were collected from TCGA and the expression level of SEC61G was compared between paired HNSCC and normal tissues using the Wilcoxon rank-sum test. The relationship between clinicopathologic features and SEC61G expression was also analyzed using the Wilcoxon rank-sum test and logistic regression. Receiver operating characteristic (ROC) curves were generated to evaluate the value of SEC61G as a binary classifier using the area under the curve (AUC value). The association of clinicopathologic characteristics with prognosis in HNSCC patients was assessed using Cox regression and the Kaplan-Meier methods. A nomogram, based on Cox multivariate analysis, was used to predict the impact of SEC61G on prognosis. Functional enrichment analysis was performed to determine the hallmark pathways associated with differentially expressed genes in HNSCC patients exhibiting high and low SEC61G expression. Results: The expression of SEC61G was significantly elevated in HNSCC tissues compared to normal tissues (P < 0.001). The high expression of SEC61G was significantly correlated with the T stage, M stage, clinical stage, TP53 mutation status, PIK3CA mutation status, primary therapy outcome, and cervical lymph node dissection (all P < 0.05). Meanwhile, ROC curves suggested the significant diagnostic ability of SEC61G for HNSCC (AUC = 0.923). Kaplan-Meier survival analysis showed that patients with HNSCC characterized by high SEC61G expression had a poorer prognosis than patients with low SEC61G expression (hazard ratio = 1.95, 95% confidence interval 1.48-2.56, P < 0.001). Univariate and multivariate analyses revealed that SEC61G was independently associated with overall survival (P = 0.027). Functional annotations indicated that SEC61G is involved in pathways related to translation and regulation of SLITs/ROBOs expression, SRP-dependent co-translational protein targeting to the membrane, nonsense-mediated decay, oxidative phosphorylation, and Parkinson's disease. Conclusion: SEC61G plays a vital role in HNSCC progression and prognosis; it may, therefore, serve as an effective biomarker for the prediction of patient survival., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: This study is to establish a new staging system for nasopharyngeal carcinoma (NPC) based on the magnetic resonance imaging (MRI) and intensity-modulated radiation therapy (IMRT)., Methods: Totally 492 patients with nasopharyngeal carcinoma were included in this study. These patients were diagnosed by pathological detection (without distant metastasis) and underwent the initial treatment of IMRT. These patients were subjected to the staging with the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system. Survival rates were calculated by the Kaplan-Meier method. Log-rank test was used to calculate the single factor prognosis, and the COX risk model was used to analyze the multivariate prognosis., Results: In these 492 patients, according to our recommended new T and N staging criteria, there were 290 cases of T1 and 202 cases of T2; there were 64 cases of N0, 159 cases of N1, 226 cases of N2, and 43 cases of N3. Univariate and multivariate analyses showed that the T and N staging combination parameters were independent prognostic factors, which affected the overall survival rates and tumor-free survival rates. According to risk difference and survival curve distribution, the following new clinical staging criteria were established: stage I (T1N0M0), stage II (T1N1M0 and T2N0M0), stage III (T1N2M0 and T2N1-2M0), stage IVa (T1-2N3M0), and stage IVb (TxNxM1)., Conclusion: A new staging system for NPC based on MRI and IMRT has been recommended, which provides valuable evidence for disease treatment and prognosis prediction., Competing Interests: CONFLICTS OF INTEREST All authors declare no financial competing interests. All authors declare no non-financial competing interests.

An accurate TNM staging system is crucial for treatment guidance and prognosis prediction in nasopharyngeal carcinoma (NPC) patients. In this retrospective study, we evaluated the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for NPC treated with intensity-modulated radiotherapy (IMRT). A total of 608 patients with biopsy-proven, non-metastatic NPC, treated with IMRT between January 2008 and March 2010, were enrolled. The 5-year overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 81.5%, 80.1%, 86.0%, and 81.1%, respectively. The LRFS rates of patients with stages T1 vs. T2, T2 vs. T3, and T1 vs. T3 did not differ between the 7th and 8th editions. By contrast, the DMFS rates of patients with N0 vs. N1, N1 vs. N2, and N2 vs. N3 differed between the 8th and the 7th editions, though no difference was observed between N3a and N3b, according to the 7th edition. The difference in OS between stages II and III, and between stages III and IVa, was larger according to the 8th edition than the 7th edition. There was no difference in the OS between stages I and II. These data indicate that in the IMRT era, the 8th edition staging system can predict the prognosis of NPC patients more accurately than the 7th edition., Competing Interests: CONFLICTS OF INTEREST The authors indicated no actual or potential conflicts of interest.

Purpose: This prospective multicentric study aimed to establish a new clinical T staging standard for nasopharyngeal carcinoma (NPC) based on intensity-modulated radiotherapy (IMRT)., Methods and Materials: Between January 2006 and December 2009, four hundred and ninety-two NPC patients undergoing IMRT were staged according to the seventh edition of the UICC/AJCC staging system. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to compare survival differences., Results: The 5-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and distant metastasis-free survival (DMSF) rates were 80.5%, 78.6%, 94.1%, and 84.3%, respectively. Univariate and multivariate analyses showed that the invasion of the nasal cavity, parapharyngeal space, oropharynx, skull base, internal pterygoid muscle, external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus, and intracalvarium were independent prognostic factors (P<0.05). According to the results of risk variety and survival curves, we suggest that the new T staging system for NPC based on magnetic resonance imaging and intensity modulated radiation therapy can be classified as T1 (nasopharynx, nasal cavity, parapharyngeal space, oropharynx, skull base and internal pterygoid muscle) and T2 (external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus and intracalvarium). Compared to the seventh edition of UICC/AJCC staging system, our new recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences between the substages of 5-year curves of LRFS, DMFS and OS were all statistically significant in our new recommended staging system., Conclusions: Our new recommended staging system is more adaptable to IMRT and can predict the prognosis of NPC patient in a more objective and accurate manner.

Purpose: To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial., Experiment Design: 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences., Results: According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2) , N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance . Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system., Conclusions: Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately.