The timing of immunotherapy administration has been linked to variations in clinical outcome across multiple cancers, but its effect on clinical outcome in nasopharyngeal carcinoma (NPC) remains unstudied. In this single-center retrospective cohort study, patients with recurrent/metastatic (R/M) NPC who received first-line anti-PD-1-based immunochemotherapy (June 2019–December 2024) were included. The primary endpoint was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. Data regarding the time of day of administration (ToDA) during the initial four cycles were collected for each patient. Survival was estimated by the Kaplan–Meier method and compared with log-rank tests. Multivariable Cox models were adjusted for prespecified covariates. Propensity score matching (PSM) was performed between patients from different ToDA groups. The ToDA cutoff was derived from the data without a prespecified hypothesis, using a data-driven approach. Among the 334 screened patients, 312 met the eligibility criteria. The median follow-up was 24.9 months. The median PFS was 25.0 months, and the mOS was not reached. A data-driven optimal ToDA cutoff of 12:00 was identified. Patients who received immunotherapy after 12:00 had significantly longer PFS (31.2 vs. 18.3 months, p = 0.006) and OS (both not reached, p = 0.011). After PSM at a 1:2 ratio, PFS (36.1 vs. 18.3 months, p = 0.003) and OS (both not reached, p = 0.018) were still significantly improved in patients who received immunotherapy after 12:00. Multivariate analysis demonstrated that a ToDA after 12:00 was independently correlated with improved PFS (HR=0.63; 95

BACKGROUND:Reliable biomarkers for risk stratification and treatment monitoring in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) treated with first-line chemo-immunotherapy remain limited. This study evaluated the prognostic value of baseline computed tomography (CT)-derived body composition parameters and their early dynamic changes. METHODS:In this single-center retrospective cohort study, patients with R/M NPC receiving first-line chemo-immunotherapy were included. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Associations between body composition and outcomes were analyzed. RESULTS:A total of 199 patients were included, and 99 with post-treatment CT after two cycles were further analyzed for dynamic changes. Higher baseline skeletal muscle area (SMA) was independently associated with longer PFS (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006) and OS (HR = 0.46, 95% CI: 0.23-0.93, p = 0.03), and with higher ORR (82.8% vs 70.0%, p = 0.033) and DCR (98.0% vs 91.0%, p = 0.031). During early treatment, a ≤ 1.3% decrease or an increase in SMA was independently associated with longer PFS (HR = 0.53, p = 0.045) and OS (HR = 0.27, p = 0.018). A greater decline in visceral adipose tissue density (ΔVATD < -0.9%) was also associated with more favorable PFS and OS, whereas no significant difference in ORR was observed. CONCLUSION:Baseline SMA and early changes in SMA and VATD have prognostic value in R/M NPC treated with first-line chemo-immunotherapy. CT-based body composition assessment may serve as a practical imaging biomarker for risk re-stratification and individualized management. IMPLICATIONS FOR PRACTICE:CT-based body composition assessment may provide a practical approach for individualized management of patients with recurrent/metastatic nasopharyngeal carcinoma receiving chemo-immunotherapy. Incorporating body composition assessment into routine CT imaging analysis may further improve risk stratification and facilitate early identification of patients with poor prognosis. For patients with low skeletal muscle reserve or significant early muscle loss during treatment, timely nutritional assessment, exercise support, and closer clinical monitoring may be considered to optimize supportive care and treatment management.

BACKGROUND:Induction chemoimmunotherapy combined with definitive chemoradiotherapy (CRT) represents a promising approach for unresectable stage III non-small cell lung cancer (NSCLC). Nevertheless, the safety, efficacy, and prognostic markers for this treatment regimen remain to be established. METHODS:This single-center retrospective cohort included unresectable stage III NSCLC treated with definitive thoracic radiotherapy plus immune checkpoint inhibitors (ICIs) from January 2020 to October 2022. Patients receiving chemo-immunotherapy before radiotherapy were classified as induction ICIs (iICIs), and those receiving immunotherapy after thoracic CRT as consolidation ICIs (cICIs). The primary endpoint was progression-free survival (PFS). Propensity score matching (1:1) was performed. TNM restaging and CT-based tumor volume were assessed before radiotherapy in the iICIs group. RESULTS:Among 168 patients treated with definitive radiotherapy (iICIs, n = 111; cICIs, n = 57), with a median follow-up of 48.2 months, median PFS was longer with iICIs (35.6 vs 23.7 months; p = 0.035) and remained longer after matching (36.1 vs 22.9 months; p = 0.019), while overall survival was similar. Grade ≥ 3 pneumonitis occurred 3.6% and 5.2% in the iICIs and cICIs groups, respectively. In the iICIs group, downstaging after induction therapy was observed (T4: 56.3%→14.6%; stage IIIC: 22.2%→2.9%), with median gross tumor volume reduced from 101.3 to 32.3 cm3 (median relative reduction: 60.9%). Larger post-induction residual tumor volume independently predicted shorter PFS (HR = 2.12; p = 0.032), whereas greater tumor-volume reduction independently predicted longer PFS (HR = 0.38; p = 0.002) and OS (HR = 0.26; p = 0.001). CONCLUSIONS:iICIs was associated with longer PFS, substantial pre-radiotherapy downstaging and tumor-volume reduction. Post-induction volumetrics provided independent prognostic stratification and may inform individualized decisions within the iICIs strategy.

The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.

Nasopharyngeal carcinoma (NPC) is the most common cancer originating in nasopharynx. Metabolic reprogramming plays a critical role in tumor progression. Exploring mechanisms underlying metabolic reprogramming contributes to deeper understanding of NPC pathogenesis. Here, we found downregulation of RORA and SPLUNC1 in NPC, and RORA downregulation indicates poor prognosis. RORA binds to SPLUNC1 promoter to induce its transcription, and RORA overexpression inhibits cell proliferation and glycolysis by directly upregulating SPLUNC1. UBR5 inhibits RORA via promoting RORA ubiquitination and degradation, and UBR5 silencing represses proliferation and glycolysis in NPC. Additionally, METTL14, which is highly expressed in NPC, facilitates UBR5 mRNA stability by promoting its m6A modification through IGF2BP2. UBR5/RORA/SPLUNC1 axis facilitates M2 polarization by activating the GPR132 signaling. UBR5 silencing inhibits tumor growth, glycolysis and M2 polarization through RORA/SPLUNC1 signaling in mice. In conclusion, UBR5 promotes proliferation, glycolysis and M2 polarization by metabolically reprograming NPC cells through suppression of the RORA/SPLUNC1 signaling.

研究了采用电沉积法从含铀废液中去除铀,考察了槽电压、沉积时间、溶液初始铀质量浓度、初始pH、搅拌作用对铀去除率的影响.结果表明:在槽电压30 V、沉积时间60～90 min、溶液中初始铀质量浓度0.1～3.0 g/L、初始pH为3～4、充分搅拌条件下,铀去除率最高可达96.27％;溶液中的UO2+2转化为铀氧化物或氢氧化物沉积在阴极上,去除效果较好.

The nano-Fe3O4 coated by polyvinyl pyrrolidone was systematically conducted this research as U(Ⅵ) adsorbent about the effect of pH value, initial U(Ⅵ) concentration, temperature, ion strength and adsorption time on U(Ⅵ) adsorption, meanwhile study the adsorption isotherm models, kinetics, thermodynamics and adsorption recycles. Results show that the adsorption equilibrium time is from 5 to 60 minutes when the pH value is 6.00 at 20-40 ℃, and the removal rate of U(Ⅵ) is more than 75%. The kinetic of U(Ⅵ) adsorption onto Fe3O4@PVP is nearly to pseudo-secondary adsorption kinetics and obeys Redlich-Peterson and Langmuir models. The adsorption rate constant of U(Ⅵ) adsorption onto Fe3O4@PVP is 0.000 646-0.012 500 g/(mg·min) at 20-40 ℃, and the corresponding maximum adsorption capacity of Langmuir isotherm models is 185.8-291.0 mg/g. Thermodynamic studies reveal that the adsorption process of U(Ⅵ) onto Fe3O4@PVP is endothermic and spontaneous（ΔH＞0, ΔG＜0）.

针对铀化工转化效率低的问题,课题组采用头脑风暴法、排列图、统计表等多种质量工具进行统计和分析,找到造成铀化工转化效率低的症结为系统积料率高.从人、机、料、法、环、测六个方面对系统积料率高的原因进行分析,得到7个末端原因,对末端原因逐一进行实验验证,确定水解柱进料口结构复杂和水解液输送管路过粗过长为两个主要原因.结合材料特性和积料特点,提出每批次水解后对水解柱进料口进行浸泡及每批次转移水解液后冲洗一遍水解液输送管路两个改进方法,改进后有效解决铀化工转化系统积料率高的症结,将铀化工转化效率从86.25％提高至97.00％.

Polyphosphate (poly-P) with linear phosphoanhydride (P-O-P) structure is increasingly being used as an alter-native phosphorus (P) fertilizer. Understanding the interfacial reactions of poly-P on minerals is essential for sustainable P management and water bodies protection. In this study, we investigated the selective adsorption and precipitation of two water-soluble ammonium polyphosphates (APP1 containing two P species and APP2 containing seven P species) by calcite via batch adsorption experiments and molecular dynamics (MD) simula-tions, mono-ammonium phosphate (MAP) as a comparison. Calcite presented the strongest fixation for APP1 at low P concentration and/or initial reaction time, followed by APP2 and MAP. However, calcite presented the strongest fixation for MAP at high P concentration, followed by APP1 and APP2. Calcite selectively fixed py-rophosphate (P2) in APP and formed Ca2P2O7 precipitate and/or ---Ca2P2O7 complex. The dissolution of Ca2P2O7 and/or ---Ca2P2O7 at high APP concentration contributed to the decline of the APP fixation by calcite. MD simulations showed that electrostatic interaction and hydrogen bonds played a key role in the water-phosphates -calcite systems. The results develop new insights regarding the selective adsorption and precipitation of various P species coexistence in calcite-rich environments.

本研究采用"5M1E"分析法对影响萃取法净化铀工程化中的各种因素进行全面分析,确认了"反萃取相比不佳""反萃取温度太低"与"反萃取槽部分相界面调节杆磨损"是要因所在;根据"5W1H"原则,制定了相应对策并逐一实施,最终将萃取净化工艺收率从73.3％～78.9％提高到 了 98.7％～99.6％,为萃取法净化铀工程化应用奠定了基础.

Background Treatment of nasopharyngeal carcinoma (NPC) is evolving toward Intensity-modulated radiotherapy (IMRT) era, which requires patient-specific reestimation of survival outcomes in modern health care. Methods A total of 488 detectable pre-treatment Epstein-Barr virus (EBV) DNA patients (stage II-IVa) treated with induction chemotherapy (IC) and IMRT were examined (training set, n = 325; validation set, n = 163). Results Concurrent chemotherapy (CC) was still an independent prognosticator for overall survival (OS) and progression-free survival (PFS). Both nomograms included age, T classification, N classification, post-IC EBV DNA, and CC. Predictions correlated well with observed 3-/5-year OS and PFS. The concordance index was 0.776 (95% confidence interval (CI) 0.69-0.86) for OS and 0.742 (95% CI 0.65-0.83) for PFS in the validation cohort. The nomograms can successfully classify patients into low- and high-risk groups. Conclusion The validated nomograms provided useful prediction of OS and PFS for detectable pre-treatment EBV DNA patients with NPC in IMRT era.

Background: Previous studies have shown that survivin has potential prognostic value in nasopharyngeal carcinoma. However, the results remained controversial until now. Thus, to investigate the influence of survivin expression on prognosis and clinical characteristics in nasopharyngeal carcinoma, we performed this meta-analysis. Methods: We searched PubMed, PMC, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure electronic databases from their establishment to 1 March 2021. The pooled hazard ratio (HR) and the pooled odds ratio (OR) were used to evaluate the prognostic and clinicopathological values of survivin in nasopharyngeal carcinoma. We used the I-2 statistic and the Q test to evaluate heterogeneity. Meta-regression, publication bias, and sensitivity analyses were also conducted. Results: A total of 26 eligible studies with 2278 patients were included in our meta-analysis. We found that the expression of survivin is connected with poor overall survival (HR=1.94; 95% confidence interval (CI)=1.52-2.48; P<0.001), lymph node metastasis (OR=3.01; 95% CI=2.31- 3.91; P<0.001), local recurrence (OR=2.40; 95% CI=1.60-3.61, P<0.001), distant metastasis (OR=2.58; 95% CI=1.74-3.84, P<0.001), and a higher clinical stage (OR=4.58; 95% CI=2.81-7.47, P<0.001). However, no significant correlations were found between survivin expression and radio-sensitivity (OR=1.33; 95% CI=0.25-7.17, P=0.737) or gender (OR=1.02; 95% CI=0.75-1.39, P=0.887). Conclusions: This meta-analysis indicates that survivin could be used as a biomarker for predicting prognosis in nasopharyngeal carcinoma.

BackgroundThe purpose of this retrospective analysis was to build and validate nomograms to predict the cancer-specific survival (CSS) and overall survival (OS) of head and neck neuroendocrine carcinoma (HNNEC) patients.MethodsA total of 493 HNNEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and 74 HNNEC patients were collected from the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital (HCH) between 2008 and 2020. Patients from SEER were randomly assigned into training (N=345) and internal validation (N=148) groups, and the independent data group (N=74) from HCH was used for external validation. Independent prognostic factors were collected using an input method in a Cox regression model, and they were then included in nomograms to predict 3‐, 5‐, and 10‐year CSS and OS rates of HNNEC patients. Finally, we evaluated the internal and external validity of the nomograms using the consistency index, while assessing their prediction accuracy using calibration curves. A receiver operating curve (ROC) was also used to measure the performance of the survival models.ResultsThe 3-, 5-, and 10-year nomograms of this analysis demonstrated that M classification had the largest influence on CSS and OS of HNNEC, followed by the AJCC stage, N stage, age at diagnosis, sex/gender, radiation therapy, and marital status. The training validation C-indexes for the CSS and OS models were 0.739 and 0.713, respectively. Those for the internal validation group were 0.726 and 0.703, respectively, and for the external validation group were 0.765 and 0.709, respectively. The area under the ROC curve (AUC) of 3-, 5-, and 10-year CSS and OS models were 0.81, 0.82, 0.82, and 0.78, 0.81, and 0.82, respectively. The C-indexes were all higher than 0.7, indicating the high accuracy ability of our model’s survival prediction.ConclusionsIn this study, prognosis nomograms in HNNEC patients were constructed to predict CSS and OS for the first time. Clinicians can identify patients’ survival risk better and help patients understand their survival prognosis for the next 3, 5, and 10 years more clearly by using these nomograms.

Background: Dry mouth sensation cannot be improved completely even though parotids are spared correctly. Our purpose is to develop a nomogram to predict the moderate-to-severe late radiation xerostomia for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) in intensity modulated radiation therapy (IMRT) / volumetric modulated arc radiotherapy (VMAT) era. Methods: A dataset of 311 patients was retrospectively collected between January 2010 and February 2013. The binary logistic regression was to estimate each factor's prognostic value for development of moderate-to severe patient-reported xerostomia at least 2 years (Xer2y) after completion of radiotherapy. Therefore, we can develop a nomogram according to binary logistic regression coefficients. This novel model was validated by bootstrapping analyses. Results: Contralateral Parotid mean dose (coMD<24.4Gy), VMAT (yes), and platinum-based concurrent chemoradiotherapy (no) were significantly related to patient-reported xerostomia at least 2 years (Xer2y) (all p < 0.001), and were included in the nomogram. Receiver operating characteristic (ROC) analysis revealed AUC (area under the ROC curve) with the value of 0.811 (0.710-0.912) of the nomogram, which was significantly higher than coMD 0.698 (0.560-0.840) from QUANTEC2010 (p<0.001). Calibration plots illustrated that the predicted Xer2y was close to the actual observation, and decision curve analyses (DCA) indicated valid positive net benefits. Conclusion: We developed a feasible nomogram to predict patient-rated Xer2y based on comprehensive individual data in patients with LA-NPC in the real world. The proposed model is able to facilitate the development of treatment plan and quality of life improvement.

BackgroundThe efficiency of concurrent chemotherapy (CC) remains controversial for stage II–IVa nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT). Therefore, we aimed to propose a nomogram to identify patients who would benefit from CC.MethodsA total of 434 NPC patients (stage II–IVa) treated with IC followed by IMRT between January 2010 and December 2015 were included. There were 808 dosimetric parameters extracted by the in-house script for each patient. A dosimetric signature was developed with the least absolute shrinkage and selection operator algorithm. A nomogram was built by incorporating clinical factors and dosimetric signature using Cox regression to predict recurrence-free survival (RFS). The C-index was used to evaluate the performance of the nomogram. The patients were stratified into low- and high-risk recurrence according to the optimal cutoff of risk score.ResultsThe nomogram incorporating age, TNM stage, and dosimetric signature yielded a C-index of 0.719 (95% confidence interval, 0.658–0.78). In the low-risk group, CC was associated with a 9.4% increase of 5-year locoregional RFS and an 8.8% increase of 5-year overall survival (OS), whereas it was not significantly associated with an improvement of locoregional RFS (LRFS) and OS in the high-risk group. However, in the high-risk group, patients could benefit from adjuvant chemotherapy (AC) by improving 33.6% of the 5-year LRFS.ConclusionsThe nomogram performed an individualized risk quantification of RFS in patients with stage II–IVa NPC treated with IC followed by IMRT. Patients with low risk could benefit from CC, whereas patients with high risk may require additional AC.

以主成分为焦磷酸铵的水溶性聚磷酸铵为实验原料,设置8.2、6.0、4.0、3.5、3.0、2.5、2.0等7组pH梯度,系统研究了酸度对焦磷酸铵水解的影响.结合一级反应动力学方程与阿累尼乌斯方程进行焦磷酸铵的水解动力学计算,结果表明:经过310 d(第二批260 d)的放置,pH从8.2降低到2.0时焦磷酸铵质量分数从初始态的92.6％依次减少为85.4％、51.2％、50.6％、50.2％、24.3％、12.9％和6.0％.焦磷酸铵在自然温度下的水解速率随着pH的降低而不同程度地加快,服从一级反应机理.pH从8.2降低到2.0时焦磷酸铵的水解速率常数从2.92×10-4～3.43×10-4增加至3.41×10-3～1.47×10-2,二者相差10～40余倍,对应半衰期为50～2000 d.秋冬与春夏两时段的水解速率差异很大,二者水解速率常数相差1.17～4.32倍,焦磷酸铵的水解活化能为7.5～68.5 kJ/mol.

Cytokeratin fraction 21-1 (CYFRA 21-1) has been widely studied as an important biomarker in non-small cell lung cancer for both diagnosis and prognosis. Many studies have also assessed the clinical applications of CYFRA 21-1 in head and neck cancer, but the diagnostic and prognostic values of CYFRA 21-1 are not yet fully established. This pooled analysis aims at evaluating the diagnostic accuracy and prognostic applications of CYFRA 21-1 in patients with head and neck cancer. A systematic retrieval of literatures was conducted without time or language restrictions by searching PubMed, EMBASE, Web of Science, Cochrane library and China National Knowledge Infrastructure. Twenty studies were eligible for systematic review, of which 14 conformed for diagnostic analysis and 7 for prognostic analysis. The pooled sensitivity and specificity of CYFRA 21-1 analysis were 0.53 (95% CI: 0.39-0.67) and 0.97 (95% CI: 0.93-0.99), respectively. A high level of CYFRA 21-1 was significantly correlated with shorter overall survival (HR 1.33, 95% CI: 1.13-1.56) and disease-free survival (HR 1.48; 95% CI: 1.10-1.97). Current evidence indicates that the level of CYFRA 21-1 in the serum could be used as an indicator for monitoring tumor status and evaluating its curative effects.

Objectives: To develop a multidimensional nomogram for predicting the progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) (stage III-IVa). Materials and methods: A total of 224 patients with locoregionally advanced NPC (training cohort, n = 149; validation cohort, n = 75) were retrospectively included. We extracted 260 radiomic features from the primary tumor and lymph nodes on the axial contrast-enhanced T1 weighted and T2 weighted MRI. Radiomic signatures of the gross tumor volume (RSnx) and lymph node (RSnd), Dose Volume Histogram (DVH) signature reflecting planning score (PS), and clinical characteristics were included as potential predictors of PFS. The least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and data dimension reduction. A nomogram was developed by incorporating the selected predictors. The C-index and calibration curve were used to assess discrimination and calibration power of the nomogram, respectively. Results: RSnd, PS, and tumor-node-metastasis (TNM) stage were the independent predictors for PFS (all p < 0.05). The nomogram integrating the three factors achieved a C-index of 0.811 (95% CI: 0.74-0.882) in the validation cohort for predicting PFS, which outperformed than that of the TNM stage alone (C-index, 0.613, 95% CI: 0.532-0.694). Subgroup analysis showed Epstein-Barr virus (EBV) DNA status improved the predictive accuracy of the nomogram (C-index, 0.86, 95% CI: 0.787-0.933). Conclusions: The multidimensional nomogram incorporating RSnd, PS, and TNM stage showed high performance for predicting PFS in patients with locoregionally advanced NPC.

聚磷酸铵作为一种富含氮、磷元素的新型缓溶性长效氮磷肥,对微量元素具有良好的螯合能力,可有效防止土壤中金属离子被固定,从而被植物更好地利用.采用滴定分析法测定了不同聚合度的水溶性聚磷酸铵(APP)对中量元素镁离子的螯合能力,探索了水溶性聚磷酸铵对镁离子的螯合规律,为聚磷酸铵-中微量元素螯合物的制备奠定基础.实验结果显示,水溶性聚磷酸铵聚合度越高,对镁离子的螯合能力越强,且螯合能力随着pH增大先减小后增大、随着温度升高逐渐降低,在pH=6.0、温度为5℃时高聚聚磷酸铵对镁离子的螯合量达到8.2 g(以100 g APP计),在pH=8.0、温度为5℃时低聚聚磷酸铵对镁离子的螯合量达到5.6 g(以100 g APP计).采用傅里叶变换红外光谱分析验证了螯合物的生成.