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Jing-Jin Weng,* Jia-Zhang Wei,* Min Li, Shao-Jie Zhang, Yun-Zhong Wei, Han-Wei Wang, Dan-Xue Qin, Jin-Long Lu, He Jiang, Shen-Hong Qu Department of Otolaryngology & Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China*These authors contributed equally to this work.Correspondence: Shen-Hong QuDepartment of Otolaryngology & Head and Neck, The People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6 Taoyuan Road, Nanning 530021, People’s Republic of ChinaTel +86-771-2186580Fax +86-771-2186317Email qshdoctor@163.comObjective: The efficacy of surgery as the primary treatment modality for nasopharyngeal carcinoma (NPC) is yet to be clarified. Therefore, we aimed to explore the short- and long-term efficacy of surgery for early-stage NPC.Methods: We retrospectively evaluated 341 patients diagnosed with early-stage NPC between September 2010 and December 2015. Among them, 58 patients underwent endoscopic nasopharyngectomy combined with chemoradiotherapy, whereas 283 patients underwent conventional chemoradiotherapy. The patients who underwent concurrent chemoradiotherapy or radiotherapy alone were matched to patients who underwent surgery in a 1:2 ratio using propensity score matching to analyze the clinical efficacy of each therapeutic modality. The primary endpoint was survival, and the secondary endpoints were tumor regression rate and reduction in Epstein–Barr virus (EBV)-DNA levels.Results: After matching, 156 patients were enrolled (58 patients in the surgery group; 98 patients in the non-surgery group). The baseline data of the matched patients had good inter-group comparability (All P> 0.05). The surgery group had significantly higher 5-year overall survival (98.30% vs. 91.70%), disease-free survival (98.30% vs. 81.40%), and recurrence-free survival (100.00% vs. 90.10%) rates than did the non-surgery group (All P< 0.05). In total, 0 and 14 patients in the surgery and non-surgery groups, respectively, had residual cancer at the end of treatment (P=0.001). All patients in the surgery group tested negative for EBV-DNA, whereas two patients in the non-surgery group tested positive. The incidence of hematologic toxicity during treatment was similar between the two groups (All P> 0.05). Still, the incidence of severe oral mucositis was lower in the surgery group than in the non-surgery group (37.9% vs. 54.08%, P=0.051).Conclusion: Surgery can improve the clearance rate of EB virus and reduce tumor residue. Surgery may be a safe and effective treatment for early NPC.Keywords: nasopharyngeal carcinoma, endoscopic surgery, radiotherapy, prognosis

Jia Jun Weng,*,1 Li Hua Wang,*,1 Hao Zhu,2 Wen Rong Xu,1 Yu Mei Wei,1 Zhi Yang Wang,1 Wen Juan Yu,1 Hua Fang Li1,3–41Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University of Medicine, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 4Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workObjective: Some lines of evidence show that D2/D3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375–0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability.Methods: Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit.Results: SAS total scores decreased significantly during the study in patients with DIP (P

Study Design: Retrospective study., Objectives: This study aimed to develop an initial deep-learning (DL) model based on computerized tomography (CT) scans for diagnosing lumbar spinal stenosis., Summary of Background Data: Magnetic resonance imaging is commonly used for diagnosing lumbar spinal stenosis due to its high soft tissue resolution, but CT is more portable, cost-effective, and has wider regional coverage. Using DL models to improve the accuracy of CT diagnosis can effectively reduce missed diagnoses and misdiagnoses in clinical practice., Materials and Methods: Axial lumbar spine CT scans obtained between March 2022 and September 2023 were included. The data set was divided into a training set (62.3%), a validation set (22.9%), and a control set (14.8%). All data were labeled by two spine surgeons using the widely accepted grading system for lumbar spinal stenosis. The training and validation sets were used to annotate the regions of interest by the two spine surgeons. First, a region of interest detection model and a convolutional neural network classifier were trained using the training set. After training, the model was preliminarily evaluated using a validation set. Finally, the performance of the DL model was evaluated on the control set, and a comparison was made between the model and the classification performance of specialists with varying levels of experience., Results: The central stenosis grading accuracies of DL Model Version 1 and DL Model Version 2 were 88% and 83%, respectively. The lateral recess grading accuracies of DL Model Version 1 and DL Model Version 2 were 75% and 71%, respectively., Conclusions: Our preliminarily developed DL system for assessing the degree of lumbar spinal stenosis in CT, including the central canal and lateral recess, has shown similar accuracy to experienced specialist physicians. This holds great value for further development and clinical application., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aims to evaluate complications, clinical outcomes, and radiographic results following Coflex implantation., Methods: We retrospectively studied 66 patients who had decompressive surgery combined with Coflex implantation to treat lumbar spinal stenosis. All imaging data were collected and examined for imaging changes. Clinical outcomes, included Oswestry Disability Index (ODI), back and leg visual analog scale (VAS) scores, were evaluated before surgery, six months after surgery and at the last follow-up. The number of complications occurring after five years of follow-up was counted. All reoperation cases were meticulously recorded., Results: 66 patients were followed up for 5-14 years. The VAS and ODI scores were significantly improved compared with baseline. Heterotopic Ossification (HO) was detectable in 59 (89.4%). 26 (39.4%) patients had osteolysis at the contact site of Coflex with the spinous process. Coflex loosening was detected in 39 (60%) patients. Spinous process anastomosis was found in 34 (51.5%) patients. There was a statistically significant difference in the VAS score of back pain between patients with and without spinous process anastomosis. Nine cases of lumbar spinal restenosis were observed, and prosthesis fracture was observed in one case., Conclusion: Our study identified various imaging changes after Coflex implantation, and majority of them did not affect clinical outcomes. The majority of patients had HO, but osteolysis and Coflex loosening were relatively rare. The VAS score for back pain of these patients was higher if they have spinous process anastomosis. After five-year follow-up, we found lumbar spinal restenosis and prosthesis fracture cases., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Identification of candidate SNPs from transcription factors (TFs) is a novel concept, while systematic large-scale studies on these SNPs are scarce., Purpose: This study aimed to identify the SNPs of six TF binding sites (TFBSs) and examine the association between candidate SNPs and osteoporosis., Methods: We used the Taiwan BioBank database; University of California, Santa Cruz, reference genome; and a chromatin immunoprecipitation sequencing database to detect 14 SNPs at the potential binding sites of six TFs. Moreover, we performed a case-control study and genotyped 109 patients with osteoporosis (T-score ≤ -2.5 evaluated by dual-energy X-ray absorptiometry) and 262 healthy individuals (T-score ≥ -1) at Tri-Service General Hospital from 2015 to 2019. Furthermore, we used the expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression database to identify downstream gene expression as a criterion for the function of candidate SNPs., Results: Bioinformatic analysis identified 14 SNPs of TFBSs influencing osteoporosis. Of these SNPs, the rs130347 CC + TC genotype had 0.57 times higher risk than the TT genotype (OR = 0.57, p = 0.031). Validation of eQTL analysis revealed that rs130347 T allele influences mRNA expression of downstream A4GALT in whole blood (p = 0.0041) and skeletal tissues (p = 0.011)., Conclusions: We successfully identified the unique osteoporosis locus rs130347 in the Taiwanese and functionally validated this finding. In the future, this strategy can be expanded to other diseases to identify susceptible loci and achieve personalized precision medicine.

Background: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients., Methods: The clinical data of 284 NPC patients, who received intensity-modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed., Results: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease-free survival (DFS) (p = 0.002) and relapse-free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05)., Conclusions: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required., (© 2022 Wiley Periodicals LLC.)

Background: Contrast-enhanced ultrasound (CEUS) is considered an attractive imaging technique to evaluate tumor microcirculation. However, the validity of CEUS for assessing laryngeal carcinoma is unclear., Purpose: To compare the performance of CEUS with conventional US and contrast-enhanced computed tomography (CECT) in the diagnosis and preoperative T-staging of laryngeal carcinoma., Material and Methods: Forty-one consecutive patients with laryngeal carcinoma underwent conventional high-frequency US, CEUS, and CECT before surgery. The CEUS characteristics of laryngeal carcinoma were recorded. The imaging findings of CEUS and conventional US were compared with CECT findings and the postoperative pathological examination., Results: CEUS showed hyperenhancement in 38 cases and isoenhancement in three cases. Homogeneous distribution of contrast agent was found in 20 cases and heterogeneous distribution in 21 cases, of which 16 cases showed local perfusion defects. In the enhanced phase, rapid entry was observed in 37 cases, synchronous entry was observed in two cases, and slow entry was observed in two cases. Rapid exit was observed in 25 cases and slow exit was observed in 16 cases. The pretherapeutic T-staging accuracy was not significantly different between conventional US, CEUS, and CECT ( P  ≥ 0.500). A high sensitivity and specificity were achieved by CEUS in the evaluation of involvement of thyroid cartilage., Conclusion: Compared with conventional US and CECT, CEUS has a reliable initial T-staging accuracy and diagnostic properties for detecting laryngeal cartilage invasion.

The present study aimed to investigate the roles of cancer-associated fibroblasts (CAFs), matrix metalloproteinase-9 (MMP-9) and lymphatic vessel density (LVD) during the progression from adenocarcinoma in situ (AIS) to invasive lung adenocarcinoma (IAC). A total of 77 patients with stage 0-IA lung adenocarcinoma were enrolled. The expression levels of α-smooth muscle actin, MMP-9 and D2-40 were immunohistochemically analyzed. Survival analysis was performed using the Kaplan-Meier method. In the non-invasive component, the proportion of CAFs and the expression levels of MMP-9 increased from AIS to IAC; however, the LVD was not significantly different. CAFs were positively correlated with levels of MMP-9. The LVD had no significant correlation with CAFs and MMP-9. In the invasive component, CAFs, MMP-9 and LVD were significantly higher in IAC compared with in minimally invasive adenocarcinoma. CAFs, MMP-9 and LVD were all positively correlated with each other. The micropapillary subtype in IAC was associated with overall survival (OS). The LVD in IAC, but not MMP-9 and CAFs, was associated with OS. CAFs, MMP-9 and LVD were involved in the progression from AIS to IAC. CAFs exhibited a strong association with MMP-9 levels in the non-invasive and invasive components. The increase in the proportion of CAFs and the expression levels of MMP-9 may have been an early event before the adenocarcinoma became invasive. Once the adenocarcinoma was invasive, the LVD served an important role in tumor invasion and metastasis, and hence may be used as a prognostic marker of poor OS in stage IA IAC., (Copyright: © Chen et al.)

A temperature sensor was fabricated with a functional conductive poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) coating on a long-period fiber grating (LPFG). The LPFG was fabricated by laser-assisted wet-chemical etching for controlling the grating depth of the LPFG after the treated surface of an optical fiber was inscribed by laser light. The functional conductive polymer acts as a temperature sustained sensing layer and enhances the grating depth of the LPFG sensor as a strain buffer at various temperatures. The sensor was subjected to three cycles of temperature measurement to investigate the sensor's wavelength shift and energy loss when exposed to temperatures between 30 and 100 °C. Results showed that the sensor's average wavelength sensitivity and its linearity were 0.052 nm/°C and 99%, respectively; average transmission sensitivity and linearity were 0.048 (dB/°C) and 95%, respectively.

Purpose: To investigate the clinical characteristics of nasopharyngeal carcinoma (NPC) and a concomitant hepatitis B virus (HBV) infection, as well as the potential effects of HBV infection and antiviral therapy on prognosis., Methods: We conducted a retrospective chart review of all NPC patients from December 2010 to December 2014. After collecting medical records and conducting follow-ups on patients, a total of 876 eligible NPC patients were included. For each patient, medical records were reviewed. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis., Results: Among the 876 participants, 106 (12.1%) patients were HBV-infected patients. The hepatitis B surface antigen-positive [HBsAg(+)] group had a lower CD 4+ T cell count than the HBsAg(-) group (P = .048). Among patients with stage I/II NPC, 5-year overall survival (OS), disease-free survival (DFS), relapse-free survival, and distant metastasis-free survival (DMFS) of the HBsAg(+) group were 82.5%, 70.7%, 87.7%, and 76.6%, respectively, whereas those of the HBsAg(-) group were 91.4%, 86.0%, 93.8%, and 92.1%, respectively. Statistically significant differences in OS, DFS, and DMFS existed between both groups (P = .017, .018, and .004, respectively). The multivariate analysis indicated that HBsAg status and N stage are independent risk factors affecting OS, DFS, and DMFS of NPC patients. A statistically significant difference in 5-year DMFS existed between the antivirus (90.0%) and no-antivirus groups (70.0%) (P = .043)., Conclusions: Hepatitis B virus infection is an independent risk factor for early stage NPC, which may be associated with its reduced immune functions compared to the HBsAg(-) group. Anti-HBV treatment may improve the prognosis of HBV-infected NPC patients., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Some lines of evidence show that D 2 /D 3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375-0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability., Methods: Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit., Results: SAS total scores decreased significantly during the study in patients with DIP ( P <0.001), and mild AEs were detected. Treatments with pramipexole did not show an anti-akathisia effect during the study, while 2 subjects experienced deterioration of akathisia and mood symptoms. The psychiatric symptoms of schizophrenia showed a trend of improvement during the study, but there was no improvement in depressive mood., Conclusion: A low dose of pramipexole can significantly relieve antipsychotic-induced parkinsonism, but not akathisia. Improvements in psychiatric symptoms of schizophrenia were found, but the results of this study need to be validated in a larger sample. No improvement of mood disorder was detected., Competing Interests: The authors report no conflicts of interest in this work.

Objective: To investigate the feasibility of endoscopic surgery for treatment of rT1-rT2 recurrent nasopharyngeal carcinoma. Method: The clinical data and of 57 patients who had recurrence of the primary lesion after treatment of nasopharyngeal carcinoma from February 2011 to December 2015 were retrospectively analyzed. The patients were re-staged according to Union for International Cancer Control(UICC, 2010) staging system for nasopharyngeal carcinoma before surgery. Patients suitable for surgery underwent endoscopic surgery to remove nasopharyngeal lesions; those combined with cervical lymph node metastases underwent cervical lymph node dissection at the same time; patients with positive surgical margins of pharyngeal lesions and cervical lymph node extramembranous filtration were treated with radiotherapy combined with chemotherapy; patients unsuitable for surgery were treated with radiotherapy combined with chemotherapy directly. All patients were followed up regularly to observe clinical efficacy and survival. Result: Fifty-seven patients were re-staged according to UICC(2010) staging system for nasopharyngeal carcinoma: 19 cases in stage Ⅰ,30 cases in stage Ⅱ, 6 cases in stage Ⅲ and 2 cases in stage Ⅳ,including 27 cases in stage rT1, 30 cases in stage rT2, and 43 cases in stage rN0,6 cases in stage rN1,6 cases in stage rN2,2 cases in stage rN3. Forty-four cases of primary lesions were sected for endoscopic surgery. Patients combined with cervical lymph node metastases underwent cervical lymph node dissection at the same time, with 6 cases of positive surgical margins of pharyngeal lesions and 4 cases of cervical lymph node extramembranous infiltration, who were treated with radiotherapy combined with chemotherapy after surgery. Thirteen patients received radiotherapy combined with chemotherapy directly. At a median follow-up of 36 months, the 3-year overall survival rate of 57 patients was 61.4%. The 3-year overall survival rates of patients in stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 73.7%, 63.3%, 33.3%, 0.0% respectively. Kaplan-Meier survival curve analysis showed a significant difference in the overall survival rate of patients in different stages( P =0.002). The 3-year overall survival rates of rT1 and rT2 patients were 63.0%, 60.0% respectively, and KaplanMeier survival curve analysis showed no significant difference in the overall survival rate between rT1 and rT2 patients( P =0.707). The 3-year overall survival rates of patients in stages rN0, rN1, rN2, rN3 were 69.8%, 50.0%, 33.3%, 0.0% respectively, and Kaplan-Meier Survival curve analysis showed a significant difference in overall survival between patients in different rN stages( P =0.002). The 3-year overall survival rate was 68.2% in 44 surgical patients, and 38.5% in 13 non-surgical patients. Kaplan-Meier survival curve analysis showed significant difference in overall survival rate between surgical and non-surgical patients( P =0.014). Conclusion: Endoscopic surgery for recurrent nasopharyngeal carcinoma is a safe and effective treatment to improve survival., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: This study aims to explore the feasibility of narrow-band imaging (NBI) applied for the diagnostic screening of a high-risk population of nasopharyngeal carcinoma (NPC) and increase the accuracy rate of nasopharyngeal biopsy and the diagnosis rate of early-stage patients., Methods: The positive high-risk population of NPC to EB virus antibody was followed up. At the same time, serological screening and pharyngorhinoscopy were carried out. The specific methods were as follows: (1) all subjects received nasopharyngeal examinations through both the HD endoscopic white light mode (WL) and NBI mode, (2) nasopharyngeal biopsy was conducted on positive subjects with microscopic examination, and, finally, (3) a comparative analysis was conducted between the biopsy pathology results and microscopy results. In addition, the following comparative indicators were recorded under different modes: sensitivity, specificity, accuracy, positive likelihood ratio, and negative likelihood ratio. Then, the area under the ROC curve and the kappa coefficient were calculated., Results: A total of 115 subjects were detected to be positive by microscopic examination under the WL mode. Among these subjects, 19 subjects were diagnosed with NPC. In addition, 24 subjects were detected to be positive by microscopic examination under the NBI mode. Among these subjects, 23 subjects were diagnosed with NPC. Under the WL mode, the specific values of the comparative indicators were as follows: sensitivity, 82.61%; specificity, 0%; and area under the ROC curve, 0.413. Furthermore, the WL mode in the diagnosis on the high-risk population of NPC exhibited poor consistency with the biopsy pathology results (kappa coefficient = - 0.069). Under the NBI mode, the specific values of the comparative indicators were as follows: sensitivity, 100%; specificity, 98.96%; and area under the ROC curve, 0.995. Furthermore, the NBI mode in the diagnosis on the high-risk population of NPC exhibited relatively satisfactory consistency with the biopsy pathology results (kappa coefficient = 0.973). Therefore, the NBI mode is significantly superior to the WL mode., Conclusion: NBI endoscopic examinations should be conducted on a routine basis for high-risk populations of NPC. This can decrease the frequency of biopsies and enhance diagnostic effects.

Objective: To evaluate the diagnostic value and feasibility of narrow-band imaging in detection of recurrent nasopharyngeal carcinoma (NPC). Methods: One thousand three hundred and sixty-four NPC patients who had completed NPC treatment were enrolled. All patients were followed-up with imaging, serological examination of EB virus and nasopharyngeal endoscopy(WL and NBI mode), in which (1) both white light (WL) and NBI modes were done; (2) positive endoscopic patients were given nasopharyngeal biopsy; (3) using histologic finding as criterion standard, the sensitivity, specificity, accuracy and Yonden's index of two modes were compared. Kappa index was used to evaluate the consistency between the two modes and pathological results respectively; (4) the positive rates of WL and NBI in patients with early recurrent (stage Ⅰ+ Ⅱ) were compared. Results: A total of 265 cases were suspected as having recurrent lesions by endoscopy in WL mode and 68 cases of them were pathologically diagnosed as having NPC; and 82 cases were suspected as having recurrent lesions by endoscopy in NBI mode and 74 cases of them were pathologically diagnosed as having NPC. The sensitivity, specificity, accuracy and Yonden's index of WL mode were 91.89%, 0, 25.09% and -0.0811, respectively, with a kappa of -0.045; the sensitivity, specificity, accuracy and Yonden's index of NBI mode were 100.00%, 95.94%, 97.05% and 0.9594, respectively. Conclusion: NBI has higher sensitivity, specificity, early diagnosis rate and Yonden's index than WL.

With the aim to support the experimental tests in a circulating fluidized bed pilot plant, the pyrolysis processes of coal, corn, and coal-corn blend have been studied with an online pyrolysis photoionization time-of-flight mass spectrometry (Py-PI-TOFMS). The mass spectra at different temperatures (300-800°C) as well as time-evolved profiles of selected species were measured. The pyrolysis products such as alkanes, alkenes, phenols, aromatics, as well as nitrogen- and sulfur-containing species were detected. As temperature rises, the relative ion intensities of high molecular weight products tend to decrease, while those of aromatics increase significantly. During the co-pyrolysis, coal can promote the reaction temperature of cellulose in corn. Time-evolved profiles demonstrate that coal can affect pyrolysis rate of cellulose, hemicellulose, and lignin of corn in blend. This work shows that Py-PI-TOFMS is a powerful approach to permit a better understanding of the mechanisms underlying the co-pyrolysis of coal and biomass., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of this study is investigate the influence of endoscopic sinus surgery on the quality of life and prognosis of patients with early nasopharyngeal carcinoma. Patients initially diagnosed with early nasopharyngeal carcinoma and received surgical treatment were matched with nasopharyngeal carcinoma patients who received chemoradiotherapy at a ratio of 1:1, according to the following seven factors: gender, age, T staging, N staging, clinical staging, radiotherapy options, and chemotherapy options. Patients in the surgery group received endoscopic sinus surgery plus chemoradiotherapy, while subjects in the control group received chemoradiotherapy. The quality of life of patients before and after treatment was evaluated based on the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck) and QLQ-H&N35 (Head and Neck Cancer Specific Module) questionnaires. In addition, overall survival and disease-free survival were compared between these two groups. The results showed overall survival was superior in the surgery group compared with the control group ( p = 0.007). However, the difference in disease-free survival between these two groups was not statistically significant ( p = 0.128). Furthermore, subgroup analysis revealed that for N0 patients, the effect of surgery combined with chemoradiotherapy on overall survival was superior to that of chemoradiotherapy ( p = 0.048); while for N1 patients, the difference in overall survival between these two groups was not statistically significant ( p = 0.065). For early nasopharyngeal carcinoma patients without lymph node metastasis, overall survival and disease-free survival in T1 patients were superior to those in T2 patients (χ 2 = 4.403, p = 0.036; χ 2 = 4.542, p = 0.033). At the end of treatment, the pain score was found to be significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.027). At 3 months and 1 year after treatment, dry mouth scores were significantly lower in the surgery group than in the chemoradiotherapy group ( p = 0.002, p = 0.026). These results demonstrated that the curative effect of surgery combined with chemoradiotherapy in the treatment of nasopharyngeal carcinoma was satisfactory and was particularly suitable for N0 patients.

The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABA A receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABA A and NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.

Purpose: Intrahepatic cholangiocarcinoma is a fatal primary liver cancer resulting from diagnosis at an advanced stage. Understanding the mechanisms of drug resistance and metastasis of cholangiocarcinoma may improve the disease prognosis. Enhanced aldehyde dehydrogenase (ALDH) activity is suggested to be associated with increased drug resistance and the metastasis. This study aims to investigate the roles of the ALDH isoforms in cholangiocarcinoma., Experimental Design: Aldefluor assays, RT-PCR, and Western blot analysis were used to identify the major ALDH isoforms contributing to Aldefluor activity in human cholangiocarcinoma cell lines. We manipulated isoform expression in HuCCT1 cells to elucidate the role of ALDH1A3 in the malignant progression of these cells. Finally, we used immunohistochemical staining to evaluate the clinical significance of ALDH1A3 in 77 hepatectomized cholangiocarcinoma patients and an additional 31 patients with advanced cholangiocarcinoma who received gemcitabine-based therapy., Results: ALDH(high) cholangiocarcinoma cells not only migrated faster but were more resistant to gemcitabine. Among the 19 ALDH isoforms studied, ALDH1A3 was found to be the main contributor to Aldefluor activity. In addition, we also found that knockdown of ALDH1A3 expression in HuCCT1 cells markedly reduced not only their sensitivity to gemcitabine, which might be attributed to a decreased expression of ribonucleotide reductase M1, but also their migration. Most importantly, this enzyme was also identified as an independent poor prognostic factor for patients with intrahepatic cholangiocarcinoma, as well as a prognostic biomarker of gemcitabine-treated patients., Conclusions: ALDH1A3 plays an important role in enhancing malignant behavior of cholangiocarcinoma and serves as a new therapeutic target. Clin Cancer Res; 22(16); 4225-35. ©2016 AACR., (©2016 American Association for Cancer Research.)

Type A γ-aminobutyric acid receptors (GABAAR) and N-methyl-D-aspartate receptors (NMDAR) are the major inhibitory and excitatory receptors in the central nervous system, respectively. Co-expression of the receptors in the synapse may lead to functional influence between receptors, namely receptor interaction. The interactions between GABAAR and NMDAR can be either positive or negative. However, the mechanisms of interaction between the two receptors remain poorly understood, and potential mechanisms include (1) through a second messenger; (2) by receptors trafficking; (3) by direct interaction; (4) by a third receptor-mediation. Dopamine is the most abundant catecholamine neurotransmitter in the brain, and its receptors, dopamine receptors (DR) can activate multiple signaling pathways. Earlier studies on the interaction between DR and GABAAR/NMDAR have shown some underlying mechanisms, suggesting that DR could mediate the interaction between GABAAR and NMDAR. This paper summarized some recent progresses in the studies of the interaction between DR and NMDAR/GABAAR, providing a further understanding on the interaction between NMDAR and GABAAR mediated by DR.

MicroRNAs (miRs) are small non‑coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer development and progression. However, the function of miR‑185 in the development of human colon cancer has not yet been investigated. In this study, the association between miR‑185 expression and the clinicopathological characteristics of patients with colon cancer was analyzed using quantitative polymerase chain reaction (qPCR). Using a gain‑of‑function approach, the effects of miR‑185 overexpression on the expression of hypoxia‑inducible factor‑2α (HIF‑2α), proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase‑2 (MMP‑2) were investigated in SW620 colon cancer cells using qPCR and western blotting. Functional analysis of cellular proliferative activities, by MTT assay, and invasive potential, by Transwell assay, was conducted on SW620 cells expressing low levels of miR‑185. miR‑185 was found to be significantly downregulated in cancer tissues compared with adjacent non‑cancerous tissues, and was negatively correlated with lymph node metastasis of colon cancer (P<0.001). miR‑185 overexpression in vitro impeded cellular proliferation and invasive potential with reduced expression of HIF‑2α, PCNA and MMP‑2 in SW620 cells transfected with an miR‑185 mimic. In addition, the tumor volumes in SW620 subcutaneous nude mouse models treated with miR‑185 were significantly smaller than those of the control group. In conclusion, these findings indicate that miR‑185 as a tumor suppressor may affect the development of colon cancer cells via inhibition of HIF‑2α signaling, suggesting that miR‑185 may serve as a potential therapeutic target in cancer treatment.

The PI3K/Akt/mTOR pathway is overactivated and heat shock protein (HSP) 90 is overexpressed in common cancers. We hypothesized that targeting both pathways can kill intrahepatic cholangiocarcinoma (CCA) cells. HSP90 and PTEN protein expression was evaluated by immunohistochemical staining of samples from 78 patients with intrahepatic CCA. CCA cell lines and a thioacetamide (TAA)-induced CCA animal model were treated with NVP-AUY922 (an HSP90 inhibitor) and NVP-BEZ235 (a PI3K/mTOR inhibitor) alone or in combination. Both HSP90 overexpression and loss of PTEN were poor prognostic factors in patients with intrahepatic CCA. The combination of the HSP90 inhibitor NVP-AUY922 and the PI3K/mTOR inhibitor NVP-BEZ235 was synergistic in inducing cell death in CCA cells. A combination of NVP-AUY922 and NVP-BEZ235 caused tumor regression in CCA rat animal model. This combination not only inhibited the PI3K/Akt/mTOR pathway but also induced ROS, which may exacerbate the vicious cycle of ER stress. Our data suggest simultaneous targeting of the PI3K/mTOR and HSP pathways for CCA treatment.

The identification of the molecular mechanisms controlling the degradation of regulatory proteins in mesenchymal stromal cells (MSC) may provide clues to promote MSC osteogenic differentiation and bone regeneration. Ubiquitin ligase-dependent degradation of proteins is an important process governing cell fate. In this study, we investigated the role of the E3 ubiquitin ligase c-Cbl in MSC osteoblast differentiation and identified the mechanisms involved in this effect. Using distinct shRNA targeting c-Cbl, we showed that c-Cbl silencing promotes osteoblast differentiation in murine and human MSC, as demonstrated by increased alkaline phosphatase activity, expression of phenotypic osteoblast marker genes (RUNX2, ALP, type 1 collagen), and matrix mineralization in vitro. Coimmunoprecipitation analyses showed that c-Cbl interacts with the transcription factor STAT5, and that STAT5 forms a complex with RUNX2, a master transcription factor controlling osteoblastogenesis. Silencing c-Cbl decreased c-Cbl-mediated STAT5 ubiquitination, increased STAT5 protein level and phosphorylation, and enhanced STAT5 and RUNX2 transcriptional activity. The expression of insulin like growth factor-1 (IGF-1), a target gene of STAT5, was increased by c-Cbl silencing in MSC and in bone marrow stromal cells isolated from c-Cbl deficient mice, suggesting that IGF-1 contributes to osteoblast differentiation induced by c-Cbl silencing in MSC. Consistent with these findings, pharmacological inhibition of STAT5 activity, or neutralization of IGF-1 activity, abrogated the positive effect of c-Cbl knockdown on MSC osteogenic differentiation. Taken together, the data provide a novel functional mechanism by which the ubiquitin ligase c-Cbl regulates the osteoblastic differentiation program in mesenchymal cells by controlling Cbl-mediated STAT5 degradation and activity., (Copyright © 2013 AlphaMed Press.)

Background: A good understanding of the mechanism of gene regulation that is involved in bone mineralization is critical for the design of anabolic treatments for bone deficiency diseases. Alkaline phosphatase (ALP) expressed by osteoblasts plays an important role in promoting bone mineralization by hydrolyzing pyrophosphate. However, the mechanism by which the expression of ALP is regulated during osteoblast differentiation has not been thoroughly investigated., Methods: Chromatin immunoprecipitation. EMSA and mutagenesis were used to identify the Runx2 binding sites on ALP gene and to analyze the role of nuclear matrix-localization of Runx2 on the recognition and activation of ALP gene., Results: Using chromatin immunoprecipitation, we determined that both ectopic and endogenous Runx2 bound to ALP intron 1 in a region containing a cluster of five putative core-sites. The third one (11C3) among those fives was bound most strongly in vitro by Runx2 and acted as a Runx2-dependent transcriptional enhancer. Furthermore, a Runx2 mutant lacking the nuclear matrix-targeting sequence (Runx2deltaNMTS) bound to the ALP gene less efficiently than the wild-type protein and a Runx2 mutant that is deficient in its ability to bind to DNA (Runx2K120A) accumulated largely in the nuclear matrix., Conclusions: Nuclear matrix-localization of Runx2 influences its ALP gene recognition., General Significance: Our results showed for the first time that ALP is a direct target gene of Runx2 and illustrated that the recognition/binding and activation of the ALP by this transcription factor are dependent on its nuclear matrix-targeting.

Nucleophosmin (NPM/B23) is a nucleolar phosphoprotein involved in cellular response to many different stimuli. Herein, we studied the molecular mechanism of NPM/B23 induction by curcumin, a natural AP-1 inhibitor with antitumor properties. Exposure to 5-30 μM curcumin significantly and dose-dependently increased the level of NPM/B23 in non-transformed NIH 3T3 cells but not HeLa cells and F9 cells. Besides, the transformed F9 and HeLa cells are more sensitive to curcumin-induced cell death and growth inhibition than NIH 3T3 cells. Overexpression of c-Jun, but not c-Fos, decreased ∼40% of NPM/B23 and enhanced the sensitivity of NIH 3T3 cells to 30 μM curcumin. Furthermore, down-regulation of NPM/B23 by transfection with NPM/B23 antisense plasmid enhanced the sensitivity to curcumin-induced cell death and growth inhibition. These results indicated that NPM/B23 expression regulates cellular sensitivity to curcumin. Besides, NPM/B23 knockdown may facilitate as a novel strategy to promote the sensitivity of cancer cells to curcumin., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Ectopic over-expression of nucleophosmin/B23 caused a marked up-regulation in the amounts of Yin Yang 1 (YY1) and proliferating cellular nuclear antigen (PCNA) proteins. Transfection with nucleophosmin/B23-targeting siRNA induced a decrease in the intracellular amounts of nucleophosmin/B23, YY1, and PCNA. PCNA expression and its promoter activity were attenuated either by nucleophosmin/B23-siRNA or YY1-siRNA. The ChIP assay showed that positive regulation of PCNA is achieved by binding of YY1 to the initiation site of PCNA promoter. The binding of YY1 to the PCNA promoter and histone H4 acetylation was significantly decreased in nucleophosmin/B23-siRNA-treated cells as compared to control vector-transfected cells. Mutation in YY1 binding site resulted in the loss of PCNA promoter activity and the binding of YY1 to the promoter. The results have indicated that YY1 binds to the initiation site of the PCNA promoter along with histone H4 acetylation, leading to transcriptional activity. We have demonstrated that nucleophosmin/B23 plays an important role in the regulation of PCNA through YY1.

The Rev peptide that binds to nucleophosmin/B23 with the highest affinity exhibited the greatest cytotoxicity on Ras-3T3 cells and inhibited tumor growth most effectively in nude mice. The efficiency of colony formation in soft agar of Ras-3T3 cells was significantly inhibited by treatment with Rev peptide. In addition, Rev peptide could potentiate the doxorubicin-induced decrease of cellular viability in U1 bladder cancer cells and inhibition of tumor growth in nude mice. Treatment of Rev peptide increased protein expression and transcriptional activity of p53 and inhibited the nucleophosmin/B23-mediated PCNA promoter activation. Peptides having high affinity of binding to molecular targets such as nucleophosmin/B23 represent a potentially useful approach to anti-cancer biotherapeutics.