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The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles.Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency.After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three-cycle IC regimen was correlated with better OS and PFS than the two-cycle regimen for N2-3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0-1 patients. The incidences of acute toxicities were higher in the IC = 3 group.Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three-cycle IC regimen seemed to be preferable for N2-3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0-1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.

Nomograms specifically used to predict the prognosis of ascending type nasopharyngeal carcinoma (NPC) have not been constructed.Data of ascending type (T3-4N0-1M0) NPC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were extracted.Altogether 862 patients with ascending type NPC were enrolled, including 603 in training cohort and 259 in validation cohort. Age, marital status, pathology, grade, tumor size, T classification, and chemotherapy were the independent prognostic factors for overall survival (OS). Age, marital status, pathology, grade, and chemotherapy were the independent prognostic factors for cancer-specific survival (CSS). In training cohort, the concordance index of the OS and CSS nomograms were 0.694 (95% confidence interval [CI], 0.677-0.711) and 0.678 (95%CI, 0.659-0.697), respectively, while those in validation cohort were 0.740 (95%CI, 0.715-0.765) and 0.708 (95%CI, 0.679-0.737), separately.The as-constructed nomograms for ascending type NPC could provide accurate prognostic predictions of OS and CSS.

Background The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients.

De-Song Shen,1 Chang Yan,1 Yu Liang,1 Kai-Hua Chen,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaCorrespondence: Xiao-Dong Zhu Tel +86 771 533 1466Email zhuxdonggxmu@126.comPurpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy.Patients and Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test.Results: NPC patients with high levels of CD19+ B cells (> 9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly.Conclusion: NPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body’s immune function in NPC patients.Keywords: nasopharyngeal carcinoma, lymphocyte subsets, prognosis, chemoradiotherapy, immune function

Postoperative pulmonary complications (PPCs) most commonly occur after thoracic surgery. Not only prolonged hospital stay and increased financial expenses but also morbidity and even mortality may be troublesome for those with PPCs. Herein, we aimed to conduct a comprehensive systematic review and meta-analysis of available data to examine the effectiveness of incentive spirometry (IS) to reduce PPCs and shorten hospital stay. This systematic review and meta-analysis included 5 randomized controlled trials (RCT) and 3 retrospective cohort study (10,322 patients in total) in PubMed, Embase and Cochrane Library until September 31, 2021. We assessed the clinical efficacy of IS using length of hospital stay, PPCs, postoperative pneumonia, and postoperative atelectasis with meta-analysis, meta-regression and trial sequential analysis (TSA). With this meta-analysis, the length of hospital stay in patients undergoing IS was significantly shorter (1.8 days) than that in patients not receiving IS (MD = -1.80, 95% CI = -2.95 to -0.65). Patients undergoing IS also had reduced risk of PPCs (32%) and postoperative pneumonia (17.9%) with statistical significance than patients not undergoing IS (PPC: OR = 0.68, 95% CI = 0.51-0.90) (Pneumonia: OR = 0.821, 95% CI = 0.677-0.995).In meta-regression, the benefits of undergoing IS in patients with preoperative predicted FEV

Ru-Rong Peng,1 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Song Qu,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Oncology, Affiliated Wu-Ming Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 He-di Road, Nanning, 530021, People’s Republic of ChinaTel +86 15778028340Email zhuxdonggxmu@126.comPurpose: The prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC.Patients and Methods: This was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan–Meier methods.Results: Multivariate Cox analysis resulted that age, plasma Epstein–Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706– 0.738) and 0.747 (95% CI: 0.717– 0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680– 0.713) and 0.690 (95% CI: 0.660– 0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations.Conclusion: LAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.Keywords: intensity-modulated radiotherapy, nasopharyngeal carcinoma, lactate dehydrogenase to albumin ratio, platelet-to-lymphocyte ratio, tumor–node–metastasis staging system

Yu-Ting Jiang,1 Kai-Hua Chen,1 Zhong-Guo Liang,1 Jie Yang,1 Song Qu,1,2 Ling Li,1,2 Xiao-Dong Zhu1– 3 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Guangxi, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High‐Incidence‐ Tumor, Guangxi Medical University, Ministry of Education, Guangxi, People’s Republic of China; 3Department of Oncology, Affiliated Wuming Hospital of Guangxi Medical University, Guangxi, People’s Republic of ChinaCorrespondence: Xiao-Dong Zhu, Tel/Fax +86-771-5331466, Email zhuxiaodong@gxmu.edu.cnPurpose: We aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in advanced N-stage nasopharyngeal carcinoma (NPC).Patients and Methods: A total of 624 NPC patients with N2-3 stage received CCRT with or without IC were retrospectively reviewed. We constructed a nomogram for predicting overall survival (OS) based on the result of the multivariate analysis in the training cohort (n = 468) and then tested it on the validation cohort (n = 156). Harrell’s concordance indices (C-index) and time-independent receiver operating characteristic (tdROC) analysis were applied to evaluate the discriminatory ability of the nomogram and compare it with TNM staging. IC plus CCRT was compared with CCRT in the whole cohort and two risk groups based on the nomogram with balanced baseline characteristics. In addition, acute toxicities were compared between different treatment groups.Results: The nomogram showed good prognostic accuracy with a C-index of 0.716 (95% CI 0.669– 0.763) in the validation cohort. The 5-year OS of low and high-risk groups stratified by the nomogram were significantly different. IC+CCRT was significantly associated with superior OS as compared with CCRT (75.4 vs 52.6%, p = 0.009) in the high-risk group. However, no significant difference between IC plus CCRT and CCRT was observed (p = 0.843) in the low-risk group. IC plus CCRT was associated with more grade 1– 4 acute toxicities.Conclusion: Our study can help clinicians select NPC patients with advanced N stage who benefit from IC.Keywords: nasopharyngeal carcinoma, advanced N-stage, induction chemotherapy, survival, nomogram

To investigate the efficacy of chemotherapy among intermediate-risk (stage II/T3N0) nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT).We identified stage II/T3N0 NPC patients who received radiotherapy with or without chemotherapy from the Surveillance, Epidemiology and End Results database (2004-2019). Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method with log-rank test and Cox proportional hazards models to evaluate the efficacy of chemotherapy. Subgroup analysis was also conducted based on the baseline characteristics. Propensity score matching (PSM) was performed to balance the intergroup covariates.A total of 1623 patients were enrolled in the study, 1444 received chemoradiotherapy (CRT) and 179 received RT alone. CRT, compared to RT alone, was independently associated with a better OS (HR 0.57, 95% CI 0.45-0.71) and CSS (HR 0.55, 95% CI 0.39-0.79). After PSM, similar results were obtained, and CRT was superior to RT alone in terms of OS (HR 0.60, 95% CI 0.39-0.92) and CSS (HR 0.60, 95% CI 0.40-0.91). Subgroup analysis revealed that OS benefits from CRT were mainly observed in T0-2N1(HR 0.51, 95% CI 0.38-0.70) and T3N0 (HR 0.64, 95% CI 0.42-0.98) rather than T2N0 (HR 1.00, 95% CI 0.51-1.94). Interestingly, after PSM, OS benefits were still seen in T0-2N1 (HR 0.44, 95% CI 0.24-0.82), while not seen in T2N0 (HR 1.83, 95% CI 0.56-5.97) and T3N0 (HR 0.56, 95% CI 0.28-1.12).For T0-2N1 NPC patients, CRT was superior to RT alone with better survival, whereas, for T2-3N0 patients, CRT was comparable to RT alone. Prospective large studies should be encouraged to verify the results.

Objective Patients with chronic hepatitis C virus (HCV) infection are at high risk of developing hepatocellular carcinoma (HCC). Previous studies suggested that menopause may increase the risk of HCC. We investigated the association between bilateral oophorectomy (BO) and the risk of HCC in women with HCV infection. Study design We used data from the National Health Insurance Research Database of Taiwan and conducted a matched cohort study. Main outcome measures The main outcome was HCC. We used a competing risk model to adjust for potential confounding factors. Results From 1997–2013, we identified 2176 patients with BO and 8704 controls. A total of 107 HCC cases (4.9 %, 107/2176) were identified in the BO group compared with 465 HCC cases (5.3 %, 465/8704) in the control group. The incidence rates were 506.3 and 538.9 cases per 100,000 person-years among the HCV-infected patients with and without BO, respectively. The competing risk model showed that BO did not increase the risk of developing HCC. Furthermore, a sub-analysis of only women under 50 years of age similarly showed that BO did not increase the risk of developing HCC after adjusting for additional covariates. The log-rank test revealed that whether or not the patients had received HRT, patients with BO did not have an increased risk of developing HCC (non-BO vs BO with HRT, p = 0.10; non-BO vs BO without HRT, p = 0.09). The use of HRT after BO did not influence the risk of developing HCC. Conclusions This study examined a large dataset with a long follow-up period to test the relationship between BO and the risk of HCC in HCV-infected women. Our findings suggest that BO did not increase the risk of HCC, regardless of HRT usage, in these women.

Background: According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. Methods. Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients’ clinical and pathological characteristics were analyzed. Results. Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). Conclusions. MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.

Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens for T3-4N1M0 nasopharyngeal carcinoma (NPC) patients. Therefore, we established a nomogram to predict clinical prognosis and guide individualized IC in T3-4N1M0 NPC. Overall, 699 T3-4N1M0 NPC patients treated with CCRT with or without IC between January 2010 and December 2018 were examined. Overall survival (OS) was the main endpoint. A nomogram was developed that included prognostic variables selected by multivariable analysis. The risk score, which was calculated according to the nomogram, was used for risk stratification. The survival difference of patients undergoing CCRT with or without IC was then compared in risk-stratified subgroups. The nomogram yielded C-indexes of 0.708 (95% confidence interval [CI]: 0.682-0.734) in the training cohort and 0.670 (95% CI: 0.625-0.715) in the validation cohort. Calibration curves for 1-, 3- and 5-year OS suggested a good association between the nomogram predicted and observed probabilities. High-risk patients stratified by nomogram benefited from IC (IC + CCRT vs CCRT: 5-year OS: 77.8% vs 58.8%; P = 0.040; 5-year disease-free survival: 75.0% vs 58.2%; P = 0.017), whereas in the low-risk group, the application of IC was associated with worse locoregional recurrence-free survival and distant metastasis-free survival. This nomogram can serve as a reliable model for prognostic prediction and can be used to guide individualized treatment of T3-4N1M0 NPC. High-risk patients are candidates for IC before CCRT, while the use of IC for low-risk patients should be considered carefully.

Objective: The chest tube drainage system (CTDS) of choice for the pleural cavity after pulmonary resection remains controversial. This systematic review and network meta-analysis (NMA) aimed to assess the length of hospital stay, chest tube placement duration, and prolonged air leak among different types of CTDS. Methods: This systemic review and NMA included 21 randomized controlled trials (3399 patients) in PubMed and Embase until 1 June 2021. We performed a frequentist random effect in our NMA, and a P-score was adopted to determine the best treatment. We assessed the clinical efficacy of different CTDSs (digital/suction/non-suction) using the length of hospital stay, chest tube placement duration, and presence of prolonged air leak. Results: Based on the NMA, digital CTDS was the most beneficial intervention for the length of hospital stay, being 1.4 days less than that of suction CTDS (mean difference (MD): −1.40; 95% confidence interval (CI): −2.20 to −0.60). Digital CTDS also had significantly reduced chest tube placement duration, being 0.68 days less than that of suction CTDSs (MD: −0.68; 95% CI: −1.32 to −0.04). Neither digital nor non-suction CTDS significantly reduced the risk of prolonged air leak. Conclusions: Digital CTDS is associated with better outcomes than suction and non-suction CTDS for patients undergoing pulmonary resections, specifically 0.68 days shorter chest tube duration and 1.4 days shorter hospital stay than suction CTDS.

Objective This study aimed to explore the effect of silencing hTERT on the CSC-like characteristics and radioresistance of CNE-2R cells. Results Silencing hTERT suppressed CNE-2R cell proliferation and increased the cell apoptosis rate and radiosensitivity in vitro. Moreover, it could also inhibit the growth of xenografts and increase the apoptosis index and radiosensitivity in vivo. Further study discovered that after silencing hTERT, telomerase activity in CNE-2R cells was markedly suppressed, along with remarkably down-regulated stem cell-related protein levels both in vitro and in vivo. Conclusion Silencing hTERT can suppress the CSC-like characteristics of CNE-2R cells to enhance their radiosensitivity, revealing that hTERT may become a potential target for treating radioresistant NPC. Methods An RNAi lentiviral vector specific to the hTERT gene was constructed to infect CNE-2R cells, the hTERT silencing effect was verified through qPCR and Western blot assays, and telomerase activity was detected by PCR-ELISA. Moreover, radiosensitivity in vitro was detected through colony formation assays, CCK-8 assays and flow cytometry. Tumor growth and radioresistance were also evaluated using xenograft models, while the apoptosis index in xenografts was measured through TUNEL assay. Levels of stem cell-related proteins were determined in vitro and in vivo.

Objective The present study aimed to investigate the predictive value of some inflammatory indexes, such as the ratio of C-reactive protein-to-albumin (CAR), high-sensitivity C-reactive protein-to-albumin (HCAR), C-reactive protein-to-lymphocyte (CLR), and high-sensitivity C-reactive protein-to-lymphocyte (HCLR) in the survival and toxicity of nasopharyngeal carcinoma and provide reference for the development of treatment. Methods A retrospective analysis was conducted on 162 patients from 2013 to 2018. The value of the indexes before the treatment was calculated. SPSS 25.0 software was used for the analysis, and the cutoff values of the indexes were determined by the receiver operating characteristic curve (ROC). The prognostic value of the indexes was evaluated according to the overall survival rate (OS), progression-free survival rate (PFS), and the incidence of toxic side effects. Results The index CLR was found to be the predictor of mortality of nasopharyngeal carcinoma but not the indicator for toxicity. Conclusion The index CLR can be used for risk-stratification. However, whether the risk-stratification treatment based on these indicators can improve the prognosis subsequently needs further prospective study.

Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. Accumulating data have indicated that VEGF is involved in tumour metastasis. However, the mechanism through which VEGF regulates nasopharyngeal carcinoma (NPC) metastasis is largely unknown. This study aimed to examine the biological function of VEGF in NPC metastasis and its underlying mechanism. Methods: We used western blotting and qPCR to examine the difference in VEGF expression between NPC cells and the immortalized nasopharyngeal epithelial cell line NP69. Wound healing assays, transwell assays and animal experiments were used to further verify the role of VEGF in the invasion and migration of NPC cells. The protein levels of the epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family were analysed by immunofluorescence (IF) and western blotting. Enzyme-linked immunosorbent assay (ELISA) and transwell assays were used to determine whether VEGF enhanced the invasion and migration of NPC cells in an autocrine manner. Western blotting was used to examine how autocrine VEGF-VEGFR2 signalling regulated EMT and MMPs. Results: We observed higher levels of VEGF in NPC cells than that in NP69 cells and identified an association between high VEGF levels and tumour invasion and migration. Mechanistically, the VEGF-mediated increase in EMT markers, MMP2 and MMP9 promoted NPC cell invasion and migration. Additionally, NPC cells secreted VEGF to promote cell invasion, migration and angiogenesis. Autocrine VEGF-VEGFR2 signalling increased ERK1/2 phosphorylation, promoted EMT process and MMPs at the indicated times. Conclusion: This study revealed that VEGF plays a role in controlling NPC cell metastasis by regulating EMT markers and MMPs in an autocrine manner.

Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. VEGF was reported to promote the occurrence of autophagy, which enhanced the radioresistance of tumors. The purpose of this study was to investigate the influence of VEGF silencing on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells and the underlying mechanisms. The radiosensitivity of NPC cells after VEGF silencing was detected by cell counting kit 8 (CCK-8) and clonogenic assay, while cell cycle and apoptosis were detected by flow cytometry. The processes of DNA damage, repair and autophagy were examined by immunofluorescence and western blotting. The interaction between VEGF and mTOR was confirmed by western blotting and co-immunoprecipitation studies. The effect of VEGF on radiosensitivity of NPC cells was investigated in vivo using a xenograft model. Furthermore, immunohistochemistry and TUNEL assays were used to verify the relationship between autophagy and radiosensitivity in NPC after VEGF depletion. Downregulation of VEGF significantly inhibited cell proliferation and induced apoptosis of NPC cells after radiotherapy in vitro and in vivo. In addition, VEGF knockdown not only decreased autophagy level, but also delayed the DNA damage repair in NPC cells after irradiation. Mechanistically, silencing VEGF suppressed autophagy through activation of the mTOR pathway. VEGF depletion increased radiosensitivity of NPC cells by suppressing autophagy via activation of the mTOR pathway.

We conducted a systematic review and meta-analysis to assess the efficacy of intragastric BTA injection in patients with obesity and morbid obesity. Five RCTs were identified. Intragastric BTA injection was no superior to saline in absolute weight loss or BMI change, but significantly lengthened the gastric emptying time (MD, 15.57; 95% CI, 8.75 to 22.38). In meta-regression analysis, the absolute weight loss was lower in the patients with high baseline BMI. In subgroup analysis, the use of BTA in absolute weight loss was significantly lower among the patients with baseline BMI more than 40 kg/m2 (MD, − 5.31; 95% CI, − 6.17 to − 4.45). The benefit of intragastric BTA injection in reduction of absolute weight was observed in patients with baseline BMI more than 40 kg/m2.

Background: Hyperglycemia in the acute phase after trauma is a stress response and a metabolic reflection in humans with injury, which could adversely affect outcome in trauma patients. In this study, we attempted to identify if hyperglycemia a reliable predictor for mortality in major trauma patients. Objectives: In order to identify if hyperglycemia a reliable predictor for mortality in major trauma, we designed and proformed a prospective observational study in a tertiary hospital. Method: We performed a prospective observational study to review the records of 601 patients with major trauma (injury severity scores >15) who visited our hospital’s emergency department from August 2012 to July 2015. Logistic regression was performed to assess the effect of hyperglycemia on mortality. Result: Major trauma patients in the hyperglycemia group had low systolic/diastolic blood pressure at triage, low initial Glasgow Coma Scale score, high incidence of hypotension episodes, coagulopathy, acidosis, and anemia. Hyperglycemia was significantly correlated with mortality in major trauma patients in this study (odds ratio: 1.97, 95% confidence interval: 1.04–3.74). Conclusion: In major trauma patients with injury severity scores >15, hyperglycemia has a positive correlation with mortality, which could be a predictor of mortality in clinical practice.

Background Malignant behavior and radioresistance, which severely limits the efficacy of radiation therapy (RT) in nasopharyngeal carcinoma (NPC), are associated with tumor progression and poor prognosis. Mesenchymal stem cells (MSCs) are used as a therapeutic tool in a variety of tumors. The aim of this study was to reveal the effect of tumor suppressor microRNA-34c-5p (miR-34c) on NPC development and radioresistance, as well as to confirm that exosomes derived from MSCs overexpressing miR-34c restore the sensitivity to radiotherapy in NPCs. Methods Potentially active microRNAs were screened by cell sequencing, Gene Expression Omnibus (GEO) database analysis, and analysis of clinical serum samples from 70 patients. The expression of genes and proteins was detected by Western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemistry (IHC). Proliferation, apoptosis, invasion, migration and radioresistance of NPC were detected. Luciferase reporter assays were used to verify the interactions of microRNAs with their downstream targets. MSCs exosomes were isolated by ultrafiltration and verified by electron microscopy and nanoparticle tracking technology. Results The expression of miR-34c was associated with the occurrence and radiation resistance of NPC. In vitro and in vivo experiments indicated that overexpression of miR-34c inhibit malignant behavior such as invasion, migration, proliferation and epithelial-mesenchymal transition (EMT) in NPCs by targeting β-Catenin. In addition, we found alleviated radioresistance upon miR-34c overexpression or β-catenin knockdown in NPCs. Exosomes derived from miR-34c-transfected MSCs attenuated NPC invasion, migration, proliferation and EMT. Moreover, miR-34c-overexpressing exosomes drastically increased radiation-induced apoptosis in NPC cells. Conclusion miR-34c is a tumor suppressor miR in NPC, which inhibits malignant behavior as well as radioresistance of tumor. Therefore, exogenous delivery of miR-34c to NPCs via MSC exosomes inhibits tumor progression and increases the efficiency of RT. Combination IR with miR-34c-overexpressing exosomes may be effective treatment for radioresistant NPCs.

Accumulating evidence has shown that Signal Transducer and Activator of Transcription 3 (STAT3) is thought to be a promising target for cancer therapy as STAT3 is frequently overexpressed in a wide range of cancer cells as well as clinical specimens, promoting tumor progression. It is widely accepted that STAT3 regulates a variety of cellular processes, such as tumor cell growth, survival, invasion, cancer stem cell-like characteristic, angiogenesis and drug-resistance. In this review, we focus on the role of STAT3 in tumorigenesis in ovarian cancer and discuss the existing inhibitors of STAT3 signaling that can be promisingly developed as the strategies for ovarian cancer therapy.

To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis.A total of 498 patients with stage III-IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122).Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein-Barr virus DNA, lymphocyte-to-monocyte ratio, and tumor response achieved an ideal C-index of 0.703 (95% CI 0.655-0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C-index, 0.670, 95% CI: 0.622-0.718). In addition, the nomogram could successfully classified patients into different risk groups.We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients.

The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT).From 2010 to 2018, 648 patients with LA-NPC treated with IC followed by CCRT were included.A total of 172 pairs of patients with LA-NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (75 days) had a significant lower 5-year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients.A prolonged wait time (75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA-NPC receiving IC plus CCRT, particularly those with IVa stage.

There is insufficient evidence to prove the effect of the Post-acute Care (PAC) program on post-stroke recovery. This study aimed to determine the effectiveness of the PAC versus traditional inpatient rehabilitation (non-PAC) for middle- and old-aged stroke survivors. This multicenter cohort study enrolled 334 stroke patients admitted for post-stroke rehabilitation. The outcome variables included the Barthel Index (BI), Functional Oral Intake Scale (FOIS), Mini Nutritional Assessment-Short Form (MNA-SF), EuroQoL-5D (EQ-5D), Lawton–Brody Instrumental Activities of Daily Living (ADL) Scale, and Mini-Mental State Examination (MMSE). The inverse-probability-of-treatment-weighting method was used to analyze the differences in outcomes between the PAC and non-PAC groups. The PAC group showed better improvements in BI, MNA-SF, EQ-5D, Instrumental ADL, and MMSE compared to the non-PAC group, with differences in effect sizes of 0.54 (95% confidence interval [CI] 0.38–0.71), 0.26 (95% CI 0.10–0.42), 0.50 (95% CI 0.33–0.66), 0.44 (95% CI 0.28–0.60) and 0.34 (95% CI 0.17–0.50), respectively. The PAC project showed more improvement in basic and instrumental ADL and status of swallowing, nutrition, and cognition than those of non-PAC, which had less length of stay restricted by the National Health Insurance. More studies are warranted to investigate the influence of hospital stay and duration from stroke onset on the PAC’s effectiveness.

Chang Yan,1 De-Song Shen,1 Xiao-Bo Chen,2 Dan-Ke SU,3 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Xia Liang,1 Hai Liao,3 Xiao-Dong Zhu1,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2School of First Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 4Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530100, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning City, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 1466Email zhuxdonggxmu@126.comHai LiaoDepartment of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 4950Email 42442427@qq.comPurpose: We aimed to construct of a nomogram to predict progression-free survival (PFS) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with risk stratification using computed tomography (CT) radiomics features and clinical factors.Patients and Methods: A total of 311 patients diagnosed with LA-NPC (stage III–IVa) at our hospital between 2010 and 2014 were included. The region of interest (ROI) of the primary nasopharyngeal mass was manually outlined. Independent sample t-test and LASSO-logistic regression were used for selecting the most predictive radiomics features of PFS, and to generate a radiomics signature. A nomogram was built with clinical factors and radiomics features, and the risk stratification model was tested accordingly.Results: In total, 20 radiomics features most associated with prognosis were selected. The radiomics nomogram, which integrated the radiomics signature and significant clinical factors, showed excellent performance in predicting PFS, with C-index of 0.873 (95% CI: 0.803∼ 0.943), which was better than that of the clinical nomogram (C-index, 0.729, 95% CI: 0.620∼ 0.838) as well as of the TNM staging system (C-index, 0.689, 95% CI: 0.592– 0.787) in validation cohort. The calibration curves and the decision curve analysis (DCA) plot obtained suggested satisfying accuracy and clinical utility of the model. The risk stratification tool was able to predict differences in prognosis of patients in different risk categories (p< 0.001).Conclusion: CT-based radiomics features, an in particular, radiomics nomograms, have the potential to become an accurate and reliable tool for assisting with prognosis prediction of LA-NPC.Keywords: computed tomography, locoregionally advanced nasopharyngeal carcinoma, radiomics, nomogram

Objective The purpose of this study was to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and the impact of chemoradiotherapy on lymphocyte subsets. Methods 934 patients with non-metastatic nasopharyngeal carcinoma were analyzed retrospectively. The percentage of circulating lymphocyte subsets was detected by flow cytometry and analyzed retrospectively. The correlation between lymphocyte subsets and prognosis was evaluated by the log-rank test and Cox proportional hazards model, and the differences of lymphocyte subsets before and after chemoradiotherapy was comparing by the paired t-test and Wilcoxon signed rank test. Results Univariate and multivariate analyses indicated that high CD19+ B lymphocytes (HR 0.705, 95%CI 0.519–0.958, P = 0.026) and CD4+ T lymphocytes (HR 0.560, 95%CI 0.331–0.946, P = 0.030) before treatment were independent favorable prognostic factors for overall survival (OS) and distant metastasis-free survival (DMFS) in NPC patients, respectively. After chemoradiotherapy, the percentage of CD3+ T lymphocytes, CD4+ T lymphocytes, CD4/CD8 ratio and CD19+ B lymphocytes decreased significantly, while the percentage of CD8+ T lymphocytes and NK lymphocytes increased significantly. Conclusion Patients with high CD19+B lymphocytes and CD4+T lymphocytes have a better prognosis, and perhaps the immune response can be improved to make the prognosis better by increasing the number of lymphocyte subsets. Chemoradiotherapy may reduce the immune function of patients with nasopharyngeal carcinoma.