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Abstract Background Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80–90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified. Results Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups. Conclusions The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

Purpose: To establish a risk classification of de novo metastatic nasopharyngeal carcinoma (mNPC) patients based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET-CT) radiomics parameters to identify suitable candidates for locoregional radiotherapy (LRRT). Methods: In all, 586 de novo mNPC patients who underwent 18 F-FDG PET-CT prior to palliative chemotherapy (PCT) were involved. A Cox regression model was performed to identify prognostic factors for overall survival (OS). Candidate PET-CT parameters were incorporated into the PET-CT parameter score (PPS). Recursive partitioning analysis (RPA) was applied to construct a risk stratification system. Results: Multivariate Cox regression analyses revealed that total lesion glycolysis of locoregional lesions (LRL-TLG), the number of bone metastases (BMs), metabolic tumor volume of distant soft tissue metastases (DSTM-MTV), pretreatment Epstein–Barr virus DNA (EBV DNA), and liver involvement were independent prognosticators for OS. The number of BMs, LRL-TLG, and DSTM-MTV were incorporated as the PPS. Eligible patients were divided into three stages by the RPA-risk stratification model: M1a (low risk, PPS low + no liver involvement), M1b (intermediate risk, PPS low + liver involvement, PPS high + low EBV DNA), and M1c (high risk, PPS high + high EBV DNA). PCT followed by LRRT displayed favorable OS rates compared to PCT alone in M1a patients ( p 0.05). Conclusions: The PPS-based RPA stratification model could identify suitable candidates for LRRT. Patients with stage M1a disease could benefit from LRRT.

Background The combined use of immune checkpoint inhibitors (ICIs) with palliative chemotherapy (PCT) is a promising first-line treatment for de novo metastatic nasopharyngeal carcinoma (mNPC). However, the efficacy of ICIs with PCT vs PCT with definitive radiation therapy (DRT) remain unclear. Methods Patients with mNPC who received first-line immunochemotherapy (ICI + PCT) or PCT + DRT were included. Propensity score matching (PSM) was applied to balance potential confounders between patients who did and did not undergo DRT (at a ratio of 1:1). Progression free survival (PFS) and overall survival (OS) were compared between the 2 groups using a log-rank test and Cox proportional hazard model. Results Among all participants, 149 received ICI + PCT. After PSM, 149 patients were included in the PCT + DRT group. First-line immunochemotherapy was associated with significantly improved PFS (median 9.0 months vs 12.0 months, P < .001) and OS (median 12.5 months vs 19.9 months, P < .001). Subgroup analysis revealed that tumor response to immunochemotherapy, metastatic organs, and number of metastatic sites potentially affected the efficacy of DRT after first-line immunochemotherapy. Conclusion Compared with PCT + DRT, first-line immunochemotherapy was associated with improved PFS and OS in patients with mNPC but not in patients with unfavorable tumor response and metastasis involving the liver, distant nodes, or multiple sites.

In Pseudomonas aeruginosa, an important opportunistic pathogen that causes numerous acute and chronic infections, the hybrid two-component system (TCS) regulates the swarming ability and biofilm formation with a multistep phosphorelay, and consists of hybrid-sensor histidine kinase (HK), histidine-containing phosphotransfer protein (Hpt) and response regulator (RR). In this work, two crystal structures of HptB and the receiver domain of HK PA1611 (PA1611REC) of P. aeruginosa have been determined in order to elucidate their interactions for the transfer of the phosphoryl group. The structure of HptB folds into an elongated four-helix bundle – helices α2, α3, α4 and α5, covered by the short N-terminal helix α1. The imidazole side chain of the conserved active-site histidine residue His57, located near the middle of helix α3, protrudes from the bundle and is exposed to solvent. The structure of PA1611REC possesses a conventional (β/α)5 topology with five-stranded parallel β-sheets folded in the central region, surrounded by five α-helices. The divalent Mg2+ ion is located in the negatively charged active-site cleft and interacts with Asp522, Asp565 and Arg567. The HptB–PA1611REC complex is further modeled to analyze the binding surface and interactions between the two proteins. The model shows a shape complementarity between the convex surface of PA1611REC and the kidney-shaped HptB with fewer residues and a different network involved in interactions compared with other TCS complexes, such as SLN1-R1/YPD1 from Saccharomyces cerevisiae and AHK5RD/AHP1 from Arabidopsis thaliana. These structural results provide a better understanding of the TCS in P. aeruginosa and could potentially lead to the discovery of a new treatment for infection.

Porous carbon materials derived from plant biomass offer great promise towards developing sustainable and advanced renewable materials for energy applications. Lignin is as an abundant and renewable aromatic biopolymer with high carbon content and chemical functionality for crosslinking, which make lignin a promising alternative for environmentally-friendly carbon aerogel production. In this study, carbon aerogels were produced using an industrial softwood kraft lignin isolated from renewable forest resources. Crosslinked lignin gels were synthesized using an epoxy compound and converted into carbon aerogels with subsequent sol-gel processing, supercritical drying and pyrolysis steps. The effect of lignin-to-crosslinker ratio on the chemical, physical and structural properties of resulting carbon aerogels were investigated. The bulk density of carbon aerogels increased as the lignin content increased from 56 wt% to 87 wt% and ranged from 0.45 to 0.83 g/cm3, respectively. FTIR results showed that crosslinked network structure was promoted when the lignin-to-crosslinker ratio was higher, which impacted the porous texture of resulting carbon aerogels as evidenced by SEM analysis. XRD analysis was used to correlate degree of graphitization and lignin content, which impacted the electrical conductivity and ion-charge transfer in carbon electrodes. To evaluate the hierarchical porous structure and determine the BET surface area and pore volume, N2 and CO2 gas adsorption experiments were conducted. Carbon aerogels with 81 wt% and 87 wt% lignin had superior structural characteristics, which further improved with surface activation with KOH resulting in 1,609 m2/g for BET surface area, 0.98 cm3/g for total pore volume and 0.68 cm3/g for micropore volume. The electrochemical tests of electrodes assembled from 87 wt% lignin carbonized sample with a specific capacitance of 122 F/g at 1A/g had better performance compared to a commercial activated carbon (74 F/g with 845 m2/g BET) and resorcinol-formaldehyde based carbon aerogel (61 F/g with 1,071 m2/g BET area), while maintaining ∼90% of its capacitance after 5,000 charge-discharge cycles. Surface activation of lignin carbon aerogels further boosted the capacitance properties, an outstanding energy density of 3.2 Wh/kg at 209.1 W/kg power density were obtained for the supercapacitor electrodes built from the A-CA-L87 activated carbon aerogel.

Purpose: Our purpose was to investigate the prognostic role of plasma Epstein-Barr virus (EBV) DNA levels in the middle of intensity modulated radiation therapy (IMRT). Methods and Materials: In total, 1881 patients with stage III-IVa tumors were included. The overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method, and the differences were compared using the log-rank test. Receiver operating characteristic curve analysis was performed to analyze the diagnostic value of EBV DNA levels for tumor progression or death. Multivariate analyses using the Cox model were used to evaluate potential prognostic factors. Results: The positive predict value and negative predict value of plasma EBV DNA > 0 copies/mL in the middle of IMRT in predicting nasopharyngeal carcinoma progression was 37.4% and 85.5%, respectively. In patients with plasma EBV DNA level = 0 copies/mL, no significant differences in OS were observed between patients treated with 200 mg/m² cisplatin and those treated with >200 mg/m² cisplatin (5-year OS, 94.9% vs 94.4%; PFS, 81.5% vs 87.6%). However, those treated with >200 mg/m² cisplatin had higher PFS. In patients with plasma EBV DNA level > 0 copies/mL, patients treated with >200 mg/m² cisplatin displayed a favorable 5-year OS (84.6% vs 73.9%) and PFS (72.3% vs 54.8%) compared with those treated with 200 mg/m² cisplatin. Additionally, higher incidences of grade 3 and 4 adverse events were recorded in patients treated with >200 mg/m² cisplatin than in those treated with 200 mg/m² cisplatin. Conclusions: Plasma EBV DNA > 0 copies/mL in the middle of IMRT suggests that higher doses of chemotherapy should be used. For concurrent chemoradiation therapy, >200 mg/m² cisplatin is recommended for patients with plasma EBV DNA level > 0 copies/mL in the middle of IMRT but not for patients with plasma EBV DNA level = 0 copies/mL considering the similar OS rates.

Natural products, characterized by intriguing scaffold diversity and structural complexity, as well as significant agricultural and medicinal activities, have been a valuable source of agrochemicals/drugs development and have historically made a huge contribution to pharmacotherapy. Structurally, bisabolanes are a family of naturally occurring sesquiterpenoids that featured a hexatomic ring core incorporating with eight continuous carbons, which cause high structural variability along the alkyl side chain to form abundant functionalities. Moreover, apart from their interesting structures, bisabolanes have shown multitudinous bioactivities. Bisabolanes are distributed in a variety of marine invertebrates, terrestrial plant, and microbial sources. Interestingly, bisabolanes characterized from marine environment possess unique characteristics both structurally and biologically. A total of 296 newly-discovered bisabolanes were searched. Among them, 94 members were isolated from marine organisms. This review particularly focuses on the new bisabolanes characterized from marine organisms (covering from 2000 to 2021), including marine-derived fungi, algae, soft corals, and sponges, with emphasis on the diversity of their chemical structures as well as the novelty and differences between terrestrial and marine sources. Moreover, a wide range of bioactivities of marine-derived bisabolanes, including antimicrobial, anti-inflammatory, enzyme inhibitory, and cytotoxic properties, are presented herein, which is considered to be a promising resource for the discovery of new drug leads and agrochemicals.

Abstract Background We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. Methods The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA

Abstract Background This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. Methods From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. Result Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. Conclusion In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.

Abstract Object To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II‐III nasopharyngeal carcinoma (NPC) patients with different Epstein‐Barr virus (EBV) DNA level in intensity‐modulated radiotherapy (IMRT) era. Methods A total of 2742 patients diagnosed with stage II‐III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut‐off value of pre‐DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level. Results In our cohort, the cut‐off value of pre EBV DNA was 1460 copies/mL (area under curve [AUC], 0.695‐0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse‐free survival (LRFS) and distant metastasis‐free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3‐year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high‐risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low‐risk patients (EBV DNA level ≤1460 copies/mL). Conclusion Pre‐EBV DNA could be a useful tool to guide individualized treatment for stage II‐III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre‐EBV DNA, while those with low pre‐EBV DNA could not.

Abstract Background Currently, the diagnosis and treatment of nasopharyngeal carcinoma (NPC) patients with residual cervical lymphadenopathy following radical radiotherapy with or without chemotherapy are challenging. We investigated the prognosis of NPC patients with residual cervical lymphadenopathy and assessed the diagnostic and prognostic values of Epstein-Barr virus (EBV) DNA in these patients. Methods This study included 82 NPC patients who were diagnosed with suspected residual cervical lymphadenopathy following completion of antitumor therapy. Their plasma EBV DNA levels were measured using quantitative polymerase chain reaction (qPCR) before the initiation of treatment and before neck dissection. Fine needle aspiration cytology (FNAC) was performed in 21 patients. All patients had undergone neck dissection and postoperative pathological examination to identify the nature of residual cervical lymphadenopathy. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analysis was used to estimate the effect of potential prognostic factors on survival. Results Following a median follow-up of 52.6 months, compared with patients with negative postoperative pathological findings for residual cervical lymphadenopathy, the patients with positive findings had a significantly lower 3-year PFS rate (49.9% vs. 83.3%, P = 0.008). Among NPC patients with residual cervical lymphadenopathy, the patients with preoperative plasma EBV DNA > 0 copy/mL had a lower 3-year PFS rate than did those with no detectable EBV DNA (43.7% vs. 61.1%, P = 0.031). In addition, combining FNAC with preoperative EBV DNA detection improved the diagnostic sensitivity. Multivariable analysis demonstrated that residual cervical lymphadenopathy with positive postoperative pathological result was an independent prognostic factor for PFS and that detectable preoperative plasma EBV DNA was an independent prognostic factor for OS. Conclusions Using FNAC combined with preoperative EBV DNA detection improves the sensitivity in diagnosing NPC with residual cervical lymphadenopathy. Compared with patients with undetectable EBV DNA, patients with detectable preoperative plasma EBV DNA have worse prognosis and may require a more aggressive treatment strategy.

Background: Despite the development of such multiple therapeutic approaches, approximately 20% patients experience recurrence. Identification of molecular markers for stratifying the different risks of tumour recurrence and progression is considered imperative.Methods: We used a RayBio Human Cytokine Antibody Array that simultaneously detected the levels of 297 proteins and profiled the conditioned medium of HONE1 cells and the radioresistant NPC cells HONE1-IR. We found Angiogenin(ANG) expression to be significantly increased in HONE1-IR and HONE1-IR cells exposed to 4-Gy X-ray radiation.Results: We investigated the expression of ANG in NPC tissues and explored its prognostic significance in patients with NPC. We found that ANG expression was increased in recurrent NPC tissues. Elevated expression of ANG induced radio-resistance in NPC cells, in addition to being significantly associated with shorter PFS, OS, and LRFS in patients with NPC. Multivariate analysis results revealed that ANG was an independent prognostic factor that predicted PFS, OS, and LRFS. Furthermore, a nomogram model was generated to predict OS in terms of ANG expression.Conclusion: Our results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.

ObjectivesTo investigate the optimal treatment pattern in patients with de novo metastatic nasopharyngeal carcinoma (NPC).MethodsWe assessed 502 consecutive and unselected de novo metastatic NPC patients in Sun Yat-sen University Cancer Center (SYSUCC) from November 2006 to October 2016 in our study. All patients were treated with palliative chemotherapy (PCT) and 308 patients received locoregional radiotherapy (LRRT) subsequently. Our primary study endpoint was overall survival (OS).ResultsThe patients treated with LRRT were associated with improved survival on univariate analysis (3-year OS rate 63.7% vs. 31.8%, P < 0.001) and multivariate analysis (HR 0.52, 95%CI 0.40–0.68, P < 0.001). The overall survival benefit of more than 4 PCT cycles was significant in female (HR 0.45, 95% CI 0.24–0.86, P = 0.016) and patients with multiple metastatic sites (HR 0.42, 95% CI 0.26–0.66, P < 0.001). The application of concurrent chemotherapy (CCT) was not associated with better survival among patients receiving LRRT (HR 1.31, 95% CI 0.92–1.86, P = 0.141).ConclusionLRRT prolonged survival in de novo metastatic NPC. For patients treated with multiple metastatic sites, more than 4 cycles of PCT is necessary. CCT does not improve survival in de novo metastatic NPC patients.

Objective: Our study aimed to compare the efficacy and toxicity of two chemotherapy regimens, gemcitabine plus cisplatin (GP) vs. docetaxel plus, fluorouracil plus cisplatin (TPF), in metastatic nasopharyngeal carcinoma (NPC) patients.Methods: We retrospectively enrolled metastatic NPC patients between July 2006 and December 2016 who were treated with TPF or GP palliative chemotherapy (PCT). The association between the PCT regimens and survival conditions was evaluated by log-rank tests and the Cox proportional hazards model. A cohort was created using propensity score matching with the ratio of 1:1 to clarify the results of the multivariable Cox regression analyses. Overall survival (OS) was the primary endpoint.Results: Of 266 eligible patients, 186 and 80 patients, respectively, received TPF and GP regimen. No significant difference was demonstrated in the survival rate between the GP and TPF groups (3-year OS: 52.6 vs. 50.3%; P = 0.929). However, multivariable analysis suggested receiving GP as an independent protective factor (hazard ratio, 0.864; 95% confidence interval, 0.753–0.992; P = 0.042). In the matched cohort, treatment with GP was also associated with a significantly higher OS (3-year OS: 52.6 vs. 35.6%, P = 0.042). Subgroup analysis indicated that the superiority of GP reflected in patients with secondary metastases rather than primary metastases. The incidence of grade 3 to 4 treatment-related toxicity was more common in the TPF group than in the GP group.Conclusion: Our study suggested that GP might be superior to TPF for metastatic NPC patients, especially those with secondary distant metastases. Further studies are necessary to validate our results.

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

Abstract Background To evaluate the clinical outcome in patients with de novo metastatic nasopharyngeal carcinoma (NPC) treated or not treated with locoregional radiotherapy (LRRT) based on plasma Epstein–Barr virus (EBV) DNA level and tumor response after palliative chemotherapy (PCT). Methods From 2007 to 2016, 502 patients with de novo metastatic NPC were included in this study. All patients were treated with PCT and 315 patients received LRRT. Our primary study endpoint was overall survival (OS). Results EBV DNA was detected in 461 patients (91.8%) before treatment but was undetectable in 249 patients (49.6%) after PCT. Three hundred and seventeen patients (63.1%) achieved satisfactory response (complete response or partial response) to PCT. Both the post-PCT EBV DNA level and tumor response were independent prognostic factors. Among low-risk patients (patients with undetectable EBV DNA and satisfactory tumor response after PCT), the 3-year OS rate was 80.4% in LRRT-treated patients and 45.3% in patients not treated with LRRT (P

Objective: To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC).Background: The current treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients.Methods: Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model.Results: Patients who received 60–75 Gy/30–35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37–0.78, P = 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46–0.84, P = 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67–0.95, P = 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10–0.75, P = 0.007), PFS (HR, 0.60, 95% CI, 0.42–0.87, P = 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29–1.03, P = 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS.Conclusions: Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor.

Abstract Background Despite increasing use, symptomatic venous thromboembolism (VTE) associated with peripherally inserted central catheter (PICC) is a common complication in nonmetastatic nasopharyngeal carcinoma (NPC) patients. Methods A total of 3012 nonmetastatic NPC patients were enrolled in this retrospective study, and we applied Cox regression and log-rank tests to assess the association between PICC-VTE and survival using the propensity score method (PSM) to adjust for gender, age, radiotherapy technique, tumor stage, node stage, UICC clinical stage and pre-treatment EBV DNA. Results 217 patients developed PICC-VTE, with an incidence of 7.20%. PSM identified 213 patients in the cohort with VTE and 852 in that without. Patients who developed PICC-VTE had a shorter 5-year PFS (77.5% vs 87.6%, p

Abstract Background We wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC). Methods A total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3–4 toxicities were compared between groups using propensity score matching (PSM). Results In total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3 years for OS (92.2% vs. 93.9%, P = 0.942), PFS (82.6% vs. 81.7%, P = 0.394), LRFS (94.7% vs. 93.3%, P = 0.981) or DMFS (84.6% vs. 87.4%, P = 0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein–Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3–4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P

AIM: To investigate the effect of Ghrelin on oxidative stress induced by high glucose in human retinal pigment epithelium(RPE)cells. METHODS: RPE cells were cultured and divided into the negative control group, high sugar group, Ghrelin low dose group(10-9 mol/L)and high dose group(10-6 mol/L). Cells survival rate were detected by CCK-8 colorimetry, cells oxidative damage were observed by oxygen sensitive fluorescence probe H2DCFDA staning, changes of intracellular reactive oxygen species(ROS)were detected by H2DCFDA staining, super oxide dismutase(SOD)activity and malondialdehyde(MDA)content were detected by spectrophotometer colorimetry. RESULTS: CCK-8 results showed that RPE cells survival rate increased to 54.79%±3.43% and 79.16%±3.29% after treated with 10-9 mol/L, 10-6 mol/L Ghrelin, the difference was statistically significant compared with high glucose group(41.65%±3.42%)(P2DCFDA fluorescent probe dying showed that Ghrelin reduced ROS generation in RPE cells and decreased oxidative damage cells. Spectrophotometer colorimetric method showed that according to the high sugar group, SOD activity increased and MDA content decreased in Ghrelin group. CONCLUSION: Ghrelin could inhibit high glucose-induced oxidative damage in human RPE cells, which has protective effect on the process of the occurrence and development of diabetic retinopathy.

Based on the analysis of the demands and challenges faced by the IoT, this paper proposed eight evaluating indicators for the IoT data storage solutions. From the perspective of the structure of the sensing network, the IoT storage mainly divided into inner-network mode and outer-network mode. Then it elaborated and evaluated the research progress of the IoT storage according to these two modes and the evaluating indicators. Furthermore, the IoT applications were classified as real-time, semi-real-time and historical three categories, and in accordance with the classification, it discussed the applicable scope of the storage modes respectively. Finally, it stated the focus of the future work of different IoT storage modes. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the prognostic significance of pretreatment quality of life for patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy. Methods We performed a prospective, longitudinal study on 554 newly diagnosed patients with NPC from April 2011 to January 2015. A total of 501 consecutive NPC patients were included. Patients were asked to complete the EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 questionnaires before treatment. Results Global health status among QLQ-C30 correlates with EBV DNA(P = 0.019). In addition, pretreatment appetite loss was significantly correlated with EBV DNA(P = 0.02). Pretreatment teeth, opening mouth, feeding tube was significantly correlated with EBV DNA, with P value of 0.003,

Abstract Background This study aimed to evaluate the long-term outcome and toxicities in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by concurrent chemoradiotherapy (CCRT) with/without adding cetuximab. Methods A total of 62 patients treated with CCRT plus cetuximab were matched with 124 patients treated with CCRT alone by age, sex, pathological type, T category, N category, disease stage, radiotherapy (RT) technique, Epstein-Barr virus (EBV) DNA levels, and Eastern Cooperative Oncology Group (ECOG). Overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method and log-rank test. Treatment toxicities were clarified and compared between two groups. Results A total of 186 well-balanced stage II to IV NPC patients were retrospectively analyzed (median follow-up, 76 months). Compared to CCRT alone, adding cetuximab resulted in more grade 3 to 4 radiation mucositis (51.6% vs. 23.4%; P

AIM: To explore the effect of different concentrations of salidroside on H2O2 induced oxidative stress damage in human lens epithelium cells(HLEC). METHODS: HLEC were cultured and divided into negative control group: cultured in normal cultivation; oxidative damage group: treated with 100μmol/L H2O2 for 12h; Salidroside low concentration group: 10μmol/L salidroside treated for 24h and H2O2 treated for 12h; Salidroside high concentration group: 100μmol/L salidroside treated for 24h and H2O2 treated for 12h. MTT method was applied to observe the effect of salidroside on HLEC survival rate. Morphological change of each group were observed and recorded under inverted microscope. DCFH-DA fluorescent probe was applied to detect intracellular ROS changes; content of malondialdehyde(MDA), superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in supernatants were detected by pectrophotometer. RESULTS: Salidroside obviously inhibited H2O2-induced HLEC vitality decline, inhibited ROS generation in cells, causing SOD, GSH-Px levels increased and MDA levels decreased. CONCLUSION: Salidroside inhibited H2O2 induced HLEC injury by decreasing the intracellular MDA content levels and increasing SOD, GSH-Px content levels, which conclude that salidroside may have a certain role in the treatment of HLEC damage.

In this retrospective case-control study involving 424 pediatric patients diagnosed with Pediatric Acute Lymphoblastic Leukemia (ALL), the investigation focused on analyzing the clinical characteristics and prognosis associated with the Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) gene. Treatment and evaluation followed the South China Children's Leukemia Group-ALL-2016 protocol (SCCLG-ALL-2016). Among the cohort, 92 patients (21.7%) exhibited CDKN2A/2B gene deletions, with 11.1% homozygous and 10.6% heterozygous deletions. Notably, ALL patients that do have CDKN2A/2B gene deletions tended to present at an older age (P = 0.001), demonstrate hepatosplenomegaly on palpation (P

BACKGROUND:Hemoglobin (Hb) levels are regarded as an important determinant of outcome in a number of cancers treated with radiotherapy. However, for patients treated with intensity modulated radiotherapy (IMRT), information regarding the prognostic value of hemoglobin level is scarce. PATIENTS AND METHODS:A total of 650 patients with nasopharyngeal carcinoma (NPC), enrolled between May, 2005, and November, 2012, were included in this study. The prognostic significance of hemoglobin level (anemia or no-anemia) at three different time points was investigated, including before treatment, during treatment and at the last week of treatment. Univariate and multivariate analyses were conducted using the log-rank test and the Cox proportional hazards model, respectively. RESULTS:The 5-year OS (overall survival) rate of patients who were anemia and no-anemia before treatment were 89.1%, and 80.7% (P = 0.01), respectively. The 5-year DMFS (distant metastasis-free survival) rate of patients who were anemia and no-anemia before treatment were 88.9%, and 78.2% (P = 0.01), respectively. The 5-year OS rate of patients who were anemia and no-anemia during treatment were 91.7% and 83.3% (P = 0.004). According to multivariate analysis, the pre-treatment Hb level predicted a decreased DMFS (P = 0.007, HR = 2.555, 95% CI1.294-5.046). Besides, the mid-treatment Hb level predicted a decreased OS (P = 0.013, HR = 2.333, 95% CI1.199-4.541). CONCLUSIONS:Hemoglobin level is a useful prognostic factor in NPC patients receiving IMRT. It is important to control the level of hemoglobin both before and during chemoradiotherapy.

PURPOSE:To evaluate and compare the prognostic value of Epstein-Barr virus (EBV) DNA and maximal standard uptake values (SUVmax ) of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) in subgroups of nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence. PATIENTS AND METHODS:A total of 194 patients with recurrent NPC (locoregional recurrence: 107, distant recurrence: 87) were enrolled. Patients took evidence of recurrence performed with 18F-FDG-PET and an EBV DNA test before salvage treatment. Clinical parameters, the status of EBV DNA and the value of SUVmax were used for survival analysis using the Kaplan-Meier method and the Cox proportional hazards regression model. RESULTS:In the subgroup of patients with locoregional recurrence, patients with SUVmax

PURPOSE:This study aimed to clarify the prognostic utility of high-sensitivity C-reactive protein (hs-CRP) in nasopharyngeal carcinoma (NPC) patients in the Intensity-Modulated Radiotherapy (IMRT) era. PATIENTS AND METHODS:In this observational study, 1,589 non-metastatic NPC patients treated with IMRT were recruited. Blood samples were collected before treatment for examination of hs-CRP levels. We evaluated the association of pretreatment hs-CRP levels with overall survival rate (OS), progression free survival rate (PFS), locoregional relapse free survival rate (LRFS) and distant metastasis free survival rate (DMFS). RESULTS:Baseline hs-CRP levels were correlated with sex, clinical stage, body mass index, smoking status, and EBV DNA level. Multivariate analysis showed that hs-CRP had significant association with OS (HR:1.723; 95%CI:1.238-2.398; p = 0.001), PFS (HR:1.621; 95%CI:1.273-2.064; p

In order to explore the effect of co-fermentation with Monascus and Aspergillus oryzae on the quality of soybean paste, the volatile flavor components in soybean pastes produced using pure and mixed cultures of A. oryzae (Piniang M003) and Monascus (PM001) were determined by headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and comparatively analyzed by principal component analysis (PCA), and Illumina MiSeq sequencing technology was used to analyze the changes in the microbial community structure during the mixed culture fermentation process. Meanwhile, the correlation between the major microorganisms and the major flavor substances was analyzed. The results showed that the composition and content of flavor substances and the composition and relative abundance of microbial communities in the soybean paste produced by co-fermentation were significantly better than those in the soybean paste fermented with A. oryzae monoculture. The major flavor substances in soybean paste were significantly positively correlated with dominant genera such as Aspergillus, Bacillus, Monascus and Leuconostoc. The flavor quality of the soybean paste produced with a mixed culture of A. oryzae and Monascus in a ratio of 3:1 (m/m) was best. The results of the study showed that the mixed culture fermentation with Monascus and A. oryzae could significantly improve the flavor quality of soybean paste, which will be informative for the improvement of the flavor quality of soybean paste.

To select high-efficiency strains suitable for semi-dry black douchi fermentation, this study compared and analyzed the koji-making effects of six Aspergillus oryzae strains and one Lichtheimia corymbifera strain with large differences in enzyme-producing capacity. The results showed that A. oryzae HN3.042, DM1 and DM2 had a strong ability to metabolize amylase, and the fermented douchi had a lower L* value. A. oryzae 24M-1, 30M-1, and PNM003 had a strong ability to produce protease, aminopeptidase, and carboxypeptidase, resulting in greater utilization of protein substrates and higher contents of total acid and amino nitrogen in the fermented douchi. In terms of volatile flavor substances, the douchi fermented with stains HN3.042, DM1, and DM2 had a relatively higher content of 1-octen-3-ol, isovaleric acid, and 4-methylpentanoic acid. The douchi fermented with strains 24M-1, 30M-1, and PNM003 had a relatively higher content of trans-2-nonenal, 3-octanone, and isophorone, resulting in richer and better flavor quality. L. corymbifera QM3 had lower enzymatic activity when compared with A. oryzae, resulting in poorer physicochemical indicators, lower contents of free amino acids and volatile flavor substances and poorer quality in douchi. The study suggests that the quality of douchi is related to the enzyme-producing capacity of the koji mold. The predominance of amylase in the koji enzyme system is conducive to the formation of color and acidic flavor substances in douchi, while with the predominance of proteolytic enzymes is conducive to the formation of amino nitrogen and good flavor quality in douchi.

Listeria monocytogenes is a foodborne human pathogen responsible for severe listeriosis and poses a great threat to human health. Hence, controlling the growth of L. monocytogenes plays an important role in the prevention of food contamination. Listeria innocua is often studied experimentally as a substitute strain for L. monocytogenes. In order to better maintain the sensory properties and nutrients of foods and extend their shelf life, this study explored the antimicrobial effect and possible mechanism of high pressure processing (HPP) combined with lauroyl arginate ethyl ester hydrochloride (LAE) on L. innocua. The feasibility of applying the combined treatment as a preservative was also investigated in ham. The results showed that 12 mg/L LAE treatment for 60 minutes had a potent antimicrobial effect on L. innocua, achieving a bacterial reduction of 3.12 (lg (CFU/mL)). Under the combined action of HPP and LAE, the surface morphology of bacterial cells became more wrinkled and sunken, and intracellular contents leaked out, suggesting a severe change in cell membrane permeability. The combined treatment of HPP at 350 MPa for 5 min with 12 mg/L LAE reduced L. innocua count by 4.87 (lg (CFU/mL)), which was 3.25 and 3.54 (lg (CFU/mL)) higher than that achieved using HPP and LAE treatments alone, respectively, suggesting a synergistic antimicrobial effect. Such synergistic antimicrobial effect was also observed on ham inoculated with L. innocua. This study could provide a theoretical reference for controlling the contamination of foodborne pathogens in ready-to-eat meat products.

Large-scale marine equipment will overheat if it works for a long time and a cooling system is necessary to be established to ensure that the equipment works in a safe range of temperature. To meet the cooling requirements of a large-scale marine equipment, a model of seawater cooling system is established in FloMaster, and simulations under dynamic conditions are conducted. According to the temperature of the coolant (glycol solution) in the front or back of the room of the heat exchanger, the pump speed or valve opening is changed to realize automatic control of seawater flow. Three control schemes are proposed, and the control effects are evaluated by the response characteristics and operating characteristics of the system under variable working conditions using the FloMaster-Simulink co-simulation method. The results show that when the pump speed is controlled by both the open loop and closed loop, the best control effect and lower energy consumption can be achieved.

Aim: To investigate the associiations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma (HCC)., Methods: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio (OR) with 95% confidence interval (CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus (HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking., Results: The HCC risk was lower in patients with the MCM4 rs2305952 CC (OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT (OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2B rs17006625 GG (OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05)., Conclusion: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.

Objective: To observe the influence of heterogeneity on sleep-wake architecture in single-prolonged stress (SPS) animal model., Methods: SPS rats were subdivided into low responders (LR) and high responders (HR) based on their freezing responses to a novel environment. Sleeping time (ST), awakening numbers (AN), brief awakening numbers (bAN) and frequency distribution of sleep bouts were used as observing indicators, single factor variance analysis combined with Dunnett t test were used to compare the differences between control, exposure, LR and HR groups., Results: We found sleeping time was increased only in HR group. Moreover, awakening numbers and brief awakening number increased in exposure group and HR group during the light phase, but not in LR group. The number of sleep bouts for the ranges of 40-80s increased obviously in HR group, but not in exposure and LR group. In addition, there were significant correlation between sleep-related parameters and freezing in HR group, but not in LR group., Conclusions: Heterogeneity existed in SPS model in view of different sleep-wake architectures of SPS rats. Rats in HR group exactly mimicked the freezing response and sleep disorders of PTSD. So HR rats were more appropriate to be used as PTSD-like models, especially when studying sleep disorder in PTSD.

Wilson disease is an autosomal recessive disorder of copper metabolism that can cause fatal neurological and hepatic disease if not diagnosed and treated. The youngest child with normal liver function reported so far is an 8-mo-old Japanese boy with low ceruloplasmin levels, and the youngest child with elevated aminotransferase ever reported so far is a 9-mo-old Korean boy with confirmed by genetic testing. Here we report an 8-mo-old Chinese boy presented with elevated liver enzymes, and low serum ceruloplasmin level. Genetic analysis of ATP7B gene detected two heterozygous disease causing mutations (c.2621C>T/p.A874V and c.3809A>G/p.N1270S), and parental origins were determined. Persistent elevation of serum aminotransferase in this infant was normalized after zinc therapy. To our best knowledge, this is the youngest patient with elevated liver enzymes ever reported worldwide. We hope that this will raise awareness among pediatricians, leading to earlier diagnosis, timely treatment, and better clinical outcome.

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome (OMIM 208085) is an autosomal recessive disorder that is caused by mutations in 2 interacting genes VPS33B and VIPAS39. Mutations in VPS33B gene account for most cases of ARC. As low or normal gamma-glutamyl transpeptidase (GGT) activity has been described in all patients with ARC syndrome identified so far, ARC syndrome is a possible diagnosis for low GGT cholestasis. Here we describe a Chinese patient with neonatal cholestasis and a high GGT level in three consecutive tests. She had other typical manifestations of ARC syndrome, including arthrogryposis multiplex congenita, renal involvement and ichthyosis. Genetic study of the VPS33B gene further confirmed the diagnosis by identification of compound heterozygosity of two known disease-causing mutations, c.403+2T > A and c.1509-1510insG. The mechanism of high GGT in this patient is unclear. Nevertheless, this case indicates that ARC syndrome cannot be excluded from the differential diagnosis of neonatal cholestasis even if high GGT activity is found.

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare genetic disorder and has not been described in China. We present a female infant with neonatal intrahepatic cholestasis from a Chinese family with ARC syndrome. All 23 coding exons and flanking introns of the VPS33B gene were amplified and sequenced using peripheral lymphocyte genomic DNA of the patient and her parents. Genetic testing revealed two novel mutations (c.1033delA and c.1567C>T) in the VPS33B gene. The patient is a compound heterozygote and her parents were heterozygous for each of the mutations.

Memory is known as a series of behavioral changes caused by an experience, while learning is a process for acquiring memory. In the present study, we suggested a new method (hexagonal maze) to evaluate the learning and memory of rats. For preliminary validation, the authors used the maze to carry out two classical experiments. At first, the performance of rats of various ages was observed in the maze. Additionally, after establishing the rapid eye movement (REM) sleep deprivation model using the modified multiple platform method (MMPM), the authors also utilized a new experimental device to analyze learning and memory responses to REM sleep deprivation in rats. Behavior of the rats in the maze was recorded by a video recorder and was then quantified. According to the behavioral characteristics, rats of various ages showed differences in memory. Middle-aged male rats exhibited a higher level compared to the young (P<0.05) and the old group (P<0.01). The results also indicated that the ability of learning and memory showed a significant decrease (P<0.05) after REM sleep deprivation. These findings were consistent with those of several similar studies using one of the adopted procedures (Morris water maze, radial arm maze and the Y-maze). Based on the above-mentioned preliminary experiments, the introduction of a hexagonal maze may provide an applicable method for analyzing learning and memory of rat.