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Qian Feng,1 Liang-Jie Tang,2 Ding-Hai Luo,3 Ying Wang,1 Nan Wu,1 Hao Chen,1 Meng-Xia Chen,1 Lei Jiang,4 Rong Jin1,5 1Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Taizhou, 317000, People’s Republic of China; 4Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 5Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Rong JinDepartment of Gastroenterology, Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaEmail jinrongjrjr@163.comLei JiangCentral Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaTel +86-577-55579127Fax +86-577-55578999Email jiangleistone79@163.comPurpose: Hyperuricemia and metabolic syndrome (MetS) have been shown to correlate with prognosis in patients with malignant tumors. The present study evaluated the relationship between preoperative hyperuricemia and MetS in colorectal cancer (CRC) patients and analyzed the effect of this combination on prognosis within 5 years.Patients and Methods: The study enrolled patients who had undergone radical CRC resection at three independent medical centers from January 2014 to December 2016. Patients were preoperatively categorized into four groups, those with hyperuricemia alone (H), those with MetS alone (MS), those with MetS-related hyperuricemia (MSH), and those with neither condition (control [C] group). The disease-free survival (DFS) and overall survival (OS) rates of these four groups were compared.Results: The study population consisted of 1271 patients, with 114, 201, 101, and 855 patients categorized into the H, MS, MSH and C groups, respectively. Preoperative MetS was found to be significantly associated with hyperuricemia (P < 0.001). Multivariate Cox regression analysis showed that MetS-related hyperuricemia (hazard ratio [HR] = 2.728; P < 0.001) and MetS alone (HR = 1.631; P < 0.001) were independent predictors of death, whereas simple hyperuricemia was not (P > 0.1). Relative to the C group, the MSH group had the highest rate of tumor recurrence or metastasis (HR = 5.103, P < 0.001), followed by the MS (HR = 2.231, P < 0.001) group. In contrast, prognosis did not differ significantly in the H and C groups (P > 0.1). MetS was significantly associated with poor prognosis, with MetS-related hyperuricemia resulting in a significantly poorer prognosis. In contrast, hyperuricemia alone had no effect on the long-term prognosis of CRC patients.Conclusion: This study highlights the prognostic importance of MetS-related hyperuricemia on the survival of patients with CRC.Keywords: colorectal cancer, metabolic syndrome, hyperuricemia, prognosis

Background: Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein-Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant-adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma., Methods: This randomised, single-centre, double-blind, placebo-controlled, phase 2 trial was conducted at Sun Yat-sen University Cancer Centre in Guangzhou, China. Adult patients (aged 18-65 years) with newly diagnosed high-risk stage III-IVa locoregionally advanced nasopharyngeal carcinoma, with a pretreatment plasma EBV DNA concentration of at least 1500 copies per mL and an Eastern Cooperative Oncology Group performance score of 0-1, were eligible. Patients were randomly assigned (2:1) using an interactive web response system (block size of six), stratified by TNM stage (III vs IVa), to neoadjuvant toripalimab (240 mg intravenously) or placebo once every 2 weeks for two cycles, followed by concurrent cisplatin (100 mg/m 2 intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy and adjuvant toripalimab (240 mg intravenously) or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival in the intention-to-treat population. This study was registered with ClinicalTrials.gov, NCT03925090, and is closed to enrolment; follow-up is ongoing., Findings: Between Dec 6, 2019, and Dec 9, 2021, 150 patients were enrolled and randomly assigned to the toripalimab group (n=100) or placebo group (n=50). 115 (77%) patients were male and 35 (23%) were female. As of data cutoff (May 31, 2024), median follow-up for progression-free survival was 37·8 months (IQR 34·2-46·5) for the intention-to-treat population analyses. 2-year progression-free survival was higher in the toripalimab group (92·0% [95% CI 86·7-97·3]) than in the placebo group (74·0% [61·8-86·2]; stratified hazard ratio 0·40 [95% CI 0·18-0·89]; log-rank p=0·019). The most common grade 3 or worse acute adverse events (occurring within 1 year of randomisation) were leukopenia (40 [40%] of 99 patients in the toripalimab group vs 22 [44%] of 50 patients in the placebo group), mucositis (28 [28%] vs ten [20%]), neutropenia (17 [17%] vs nine [18%]), anaemia (16 [16%] vs five [10%]), and weight loss (12 [12%] vs six [12%]). The most common grade 3 or worse late adverse events (occurring >1 year after randomisation) was auditory or hearing loss (eight [8%] vs four [8%]). Immune-mediated adverse events of grade 3 or worse occurred in ten (10%) patients only in the toripalimab group. One (2%) of 50 patients in the placebo group died due to septic shock caused by bacteraemia considered not treatment related. There were no treatment-related deaths in the toripalimab group., Interpretation: Our findings suggested that a so-called sandwich approach involving toripalimab (in the neoadjuvant and adjuvant phases) combined with concurrent chemoradiotherapy could be a highly promising therapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Phase 3 non-inferiority trials are warranted comparing neoadjuvant and adjuvant toripalimab versus cisplatin plus gemcitabine neoadjuvant chemotherapy combined with concurrent chemoradiotherapy., Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Science and Technology Program of Guangzhou, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Postdoctoral Innovative Talent Support Program, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, and Fundamental Research Funds for the Central Universities., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Whether to perform local radiotherapy on metastatic bone for primary bone-only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment., Materials and Methods: We studied 308 primary bone-only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log-rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups., Results: The best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45-0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre-treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low-risk group while 153 were in high-risk group. Before and after IPTW, the high-risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42-0.67, p < 0.001; unadjusted HR = 0.59, 95% CI: 0.42-0.83, p = 0.007), while the low-risk group did not (adjusted HR = 0.79, 95% CI: 0.56-1.11, p = 0.345; unadjusted HR = 0.65, 95% CI: 0.37-1.14, p = 0.309)., Conclusion: Best outcomes of the whole cohort were seen with PCT + LRRT + bRT. Our study identified age, N stage, pre-treatment LDH levels, and EBV DNA levels as independent prognostic factors for OS. The high-risk group demonstrated a longer OS when treated with PCT + LRRT + bRT, whereas the low-risk group did not benefit from the combinatorial treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Kuey teow is one of the delicacies of Guangdong, China and is a gluten-free noodle dish made from rice. It has a short storage period and extending the shelf life by quick freezing induces quality deterioration due to temperature fluctuations. To improve its freeze-thaw frozen storage quality, this paper examined the effects of hydroxypropyl corn starch (HCS), guar gum (GG), and compound phosphates (CP) on the quality of quick-frozen kuey teow during freeze-thaw cycles. The mechanism was investigated by identifying changes in the moisture status, aging degree of the starch, and textural and cooking characteristics. The results showed that all three additions improved the toughness, chewiness and steaming characteristics of the kuey teow, with CP significantly enhancing chewiness. XRD and FTIR results revealed that GG more significantly inhibited the decrease of starch crystallinity, while HCS inhibited starch aging. GG, HCS and CP all improved the hydration characteristics and water holding capacity of rice starch. GG enhances the ability of starch to bind more tightly with water, resulting in a more uniform water distribution and a more continuous and tight structure of the kuey teow. This study will provide a theoretical basis for compounding and optimizing the quick-freezing of kuey teow., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: To evaluate the prognostic value of an integrated model consisting of tumour response to induction chemotherapy (IC) and gross tumour volume (GTV) after IC in nasopharyngeal carcinoma (NPC) and elucidate optimal cumulative cisplatin dose (CCD) in concurrent chemoradiotherapy (CCRT) for different subgroups., Design and Methods: This retrospective study enrolled 896 patients with NPC diagnosed from 2010 to 2017 receiving IC plus radiotherapy. The primary endpoint was disease-free survival (DFS). Cut-off points for GTV were combined with IC response to develop an integrated model. Propensity score matching (PSM) was used to adjust for potential confounders. Survival outcomes and acute toxicity were compared between the different CCD groups., Results: Unsatisfactory IC response and large GTV after IC were correlated with poor survival outcomes; the AUC increased to 0.668 when these factors were incorporated. The integrated model classified patients into three groups. After PSM, radiotherapy alone and CCRT demonstrated similar efficacy in the low-risk group (complete response (CR)/partial response (PR) and GTV <68 cm 3 after IC). In the intermediate-risk group (CR/PR but GTV ⩾68 cm 3 ), CCD of >200 mg/m 2 and 101-200 mg/m 2 increased the 5-year DFS rates (83.7% vs 81.1% vs 65.3%, p  = 0.042). In the high-risk group (stable disease/progressive disease and any GTV), the use of different CCDs did not result in significantly different survival outcomes ( p  = 0.793). Additionally, high CCD was significantly associated with increased incidence of grade 1-4 acute toxicity., Conclusion: The integrated model incorporating IC response and GTV after IC demonstrates satisfactory value in risk stratification and the potential to guide individualised decision-making in CCD selection. Balancing toxicity and efficacy, RT alone seems to be the optimal treatment for patients in low-risk groups and 200 mg/m 2 might be the optimal dose for intermediate-risk groups. Moreover, increasing CCD does not benefit patients in high-risk groups, and treatment options for these patients require further consideration., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: Fatigue stands out as a prevalent and debilitating symptom in both Multiple Sclerosis (MS) and the aging population. Traditional methods for measuring perceived fatigue may not adequately account for individual activity differences, leading to varied prevalence rates. Perceived fatigability anchors fatigue to specific activities with predetermined intensity and duration, thereby mitigating self-pacing bias. Despite its potential, perceived fatigability is poorly understood in older adults, particularly those with neurological conditions, including MS. This study thus aimed to (1) investigate whether, among older adults, MS was associated with worse perceived physical and mental fatigability; (2) evaluate whether, among older adults with MS (OAMS), greater patient-reported disease-related disability was associated with worse perceived physical and mental fatigability., Methods: Participants were 96 older adults with a physician-confirmed diagnosis of MS (mean age: 64.6 ± 4.2) and 110 healthy controls (mean age: 68.2 ± 7.2), all confirmed to be dementia-free through established case conference procedures. Physical and mental fatigability were measured using the Pittsburgh Fatigability Scale, a 10-item questionnaire (score range: 0 to 50) designed to assess fatigue levels that individuals expect to feel after engaging in a range of typical activities for older adults. MS disease-related disability was assessed with the Patient Determined Disease Steps scale, which ranges from 0 (normal) to 8 (bedridden), with scores ≥ 2 indicating worse MS-related disability after a median split. Separate linear regression models were performed to investigate associations between group status (MS vs. Control) as the predictor and perceived physical and mental fatigability scores as the outcome variables. Within the MS group, additional linear regression models were performed to explore the relationship between disease-related disability and fatigability levels. All models adjusted for age, sex, race, education, global health, general cognitive function, and depressive symptoms levels., Results: The fully adjusted models yielded the following key findings: OAMS reported significantly higher levels of perceived physical fatigability (M = 25.11 ± 9.67) compared to controls (M = 17.95 ± 8.35) (p = 0.003). Similarly, the perceived mental fatigability in OAMS (M = 16.82 ± 11.79) was significantly greater than that in controls (M = 9.15 ± 7.12) (p = 0.003). Within the MS group, individuals with greater disease-related disability reported significantly greater levels of both physical (M = 30.13 ± 7.71 vs. 18.67 ± 8.00, p < 0.001) and mental fatigability (M = 20.31 ± 12.18 vs. 12.33 ± 9.69, p = 0.009) compared to those with lower MS-related disability. Of note, the significance of these findings persisted in models that adjusted for depressive symptoms., Conclusion: Our study provides compelling evidence that OAMS exhibit significantly higher perceived physical and mental fatigability compared to healthy controls. Additionally, worse MS-related disability correlates with worse physical and mental fatigability. These results persist after adjusting for confounders including depressive symptoms. Our findings underscore the necessity of holistic management strategies that cater to both physical and psychological aspects of MS, laying a foundation for future studies to uncover the pathophysiological mechanisms of fatigability in older adults with and without MS., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To investigate the genetic and expression characteristics of transcription factor IIH (TFIIH) in pre-initiationcomplex in prostate cancer (PCa) and its relationship with prostate cancer progression. Methods: Analyzing the expression characteristics and clinical signification of TFIIH subunits about 495 cases of PCa and 52 cases of adjacent cancer in The Cancer Genome Atlas-Prostate adenocarcinoma (TCGA-PRAD) database. PCa microarray chip was used to verify the correlation between the key factor General Transcription Factor IIH Subunit 4 (GTF2H4) in TFIIH and clinical features. Results: The 495 patients with PCa were (61.01±6.82) years old.The mRNA expression of ERCC3、GTF2H4 and MNAT1 were high in PCa tissues with GS≥8( P <0.05). The expression of GTF2H4 and MNAT1 were relevant to the pathological stages( P <0.05). High expression of GTF2H4 has higher biochemical recurrence (BCR) rate in PCa patients( HR =2.47, 95% CI :1.62-3.77, P <0.001), which has better predictive effect of BCR in PCa patients(The 3rd, 5th, and 7th year AUC all>0.7) than other subunits, and it has been verified in four additional databases. Single-factor Cox regression analysis showed that GTF2H4 were risk factors for BCR ( HR =2.470, 95% CI :1.620-3.767, P <0.001) and GTF2H5 were protective factors( HR =0.506,95% CI : 0.336-0.762, P =0.001). The results of immunohistochemical staining showed that the protein expression of GTF2H4 was correlated with the clinical features of PCa patients.The differences of the above results were statistically significant. Conclusion: GTF2H4, the key factor of TFIIH, is highly expressed in PCa and indicates a poor prognosis.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Background and Purpose: Nab-paclitaxel is a promising albumin-bound paclitaxel with a therapeutic index superior to that of docetaxel, but the optimal dose of nab-paclitaxel combined with cisplatin and capecitabine as induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma remains unknown., Materials and Methods: This was an open-label, single-arm study investigating the safety and efficacy of nab-paclitaxel + cisplatin + capecitabin as IC for three cycles, followed by cisplatin CCRT, conducted by using the standard "3 + 3" design in LA-NPC. If more than one-third of the patients in a cohort experienced dose-limiting toxicity (DLT), the dose used in the previous cohort was designated the maximum tolerated dose (MTD). The recommended phase 2 dose (RP2D) was defined as one level below the MTD., Results: From 29 May 2021 to 17 March 2022, 19 patients with LA-NPC were enrolled, one patient withdrew informed consent. Two DLTs occurred in cohort 4 (grade 4 febrile neutropenia and grade 3 peripheral neuropathy), and an MTD was established as 225 mg/m 2 . The most frequent grade 3 or 4 adverse events were neutropenia (16.7 %), hypertriglyceridemia (16.7 %), leukopenia (5.6 %) and peripheral neuropathy (5.6 %) during IC., Conclusion: The RP2D is nab-paclitaxel 200 mg/m 2 on day 1, combined with cisplatin 75 mg/mg 2 on day 1 and capecitabin1000 mg/m 2 on days 1-14, twice a day, every 3 weeks, for three cycles as an IC regimen prior to CCRT., Trial Registration: ClinicalTrials.gov Identifier: NCT04850235., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC., Methods: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes., Results: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity., Conclusions: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC., (© 2023. The Author(s).)

Objective: To investigate the value of radiomics models based on magnetic resonance imaging (MRI) diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in distinguishing benign and malignant thyroid nodules. Methods: A cross-sectional study. Clinical data of 148 thyroid nodules (50 benign, 98 malignant) from 140 patients who underwent thyroid MRI examination in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences between January 2019 and December 2022 were retrospectively analyzed. The nodules were used as the study units, and a leave-one-out method was used to randomly divide the nodules into a training set and a test set at a 7∶3 ratio. Region of interest was segmented and radiomics features were extracted from the DWI and ADC images. In the training set, feature selection was performed using inter-observer agreement analysis, U -test, least absolute shrinkage and selection operator algorithm, and correlation analysis. Four classifiers, including support vector machine (SVM), random forest (RF), k-nearest neighbors (KNN) and logistic regression (LR) were used to build models with the selected features, including the DWI models, ADC models, and combined models. The models were independently tested in the test set. The performance of the radiomics models in distinguishing benign and malignant thyroid nodules was evaluated using the receiver operating characteristic (ROC) curve, with pathological results as the gold standard. Results: Of the 140 patients, there were 40 males and 100 females, with a mean age of (38.4±12.2) years. After feature selection, 11 DWI features and 11 ADC features were used to build the models. In the training set, the AUC values of the combined models were higher than those of the corresponding DWI and ADC models. In the test set, the SVM combined model showed the best predictive performance, with an AUC of 0.873 (95% CI :0.740-0.954), accuracy of 75.6%, sensitivity of 46.7%, specificity of 90.0%, positive predictive value (PPV) of 70.0% and negative predictive value (NPV) of 77.1%, while the RF combined model had an AUC of 0.836 (95% CI :0.695-0.929), accuracy of 77.8%, sensitivity of 40.0%, specificity of 96.7%, PPV of 85.7% and NPV of 76.3%, the KNN combined model had an AUC of 0.832 (95% CI :0.691-0.927), accuracy of 77.8%, sensitivity of 33.3%, specificity of 100%, PPV of 100% and NPV of 75.0%, the LR combined model had an AUC of 0.813 (95% CI :0.669-0.914), accuracy of 77.8%, sensitivity of 60.0%, specificity of 86.7%, PPV of 69.2% and NPV of 81.3%. Conclusions: Radiomics models based on DWI and ADC image features can effectively distinguish benign and malignant thyroid nodules. The SVM combined model had the best prediction performance.

Background: Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC)., Patients and Methods: We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov, number NCT03668730., Results: One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%-94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8-46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%-98.9%) with a median follow-up of 43.9 months (IQR 40.2-46.2). The most common late toxicity was grade 1-2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months., Conclusion: Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to compare the metastatic patterns of synchronous bone metastasis (SBM) and metachronous bone metastasis (MBM) in nasopharyngeal carcinoma (NPC)., Methods: This study included bone metastases in NPC patients from 2005 to 2016 in a Chinese hospital. Cohort 1 was collected from 2005 to 2010 for discovery, and Cohort 2 from 2011 to 2016 for validation. The chi-squared test, Wilcoxon rank sum test, and Kaplan-Meier technique were used to compare site, time, and survival between cohorts 1 and 2. Prognostic factors were analyzed using univariate or multivariate Cox regression., Results: Cohort 1 had 112 individuals with SBM and 394 with MBM, and cohort 2 had 328 with SBM and 307 with MBM. The thoracic vertebra was the most frequently affected site of metastasis. Patients with SBM more often had metastasis to the cervical vertebrae compared with patients with MBM (34.5% vs. 22.3%, p < 0.05). Patients with SBM had better overall survival (42.2 months, 95% CI: 33.9-50.7) than patients with MBM (24.9 months, 95% CI: 22.2-28.7). Age at bone metastasis detection, metastasis to other organs, and more bone metastasis locations were associated with worse prognosis. The majority of MBMs occurred at 7 to 18 months after NPC diagnosis., Conclusion: Radiotherapy does not modify the metastatic patterns of NPC bone metastases. Patients with SBM tend to have metastasis to the cervical vertebra, which is close to the nasopharynx. Paying more attention to bone metastases during follow-up in the first 2 years after an NPC diagnosis., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: The safety and objective clinical responses were observed in the phase I study using adjuvant autologous tumour-infiltrating lymphocytes (TILs) following concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients., Methods and Materials: One hundred fifty-six patients with stage III-IVb and pretreatment Epstein-Barr virus DNA levels of ≥4000 copies/ml were randomly assigned to receive CCRT combined with TIL infusion (n = 78) or CCRT alone (n = 78). All patients received CCRT and patients assigned to the TIL group received TIL infusion within 1 week after CCRT. The primary endpoint was investigator-assessed progression-free survival (PFS) at 3 years., Results: After a median follow-up of 62.3 months, no significant difference was observed in the 3-year PFS rate between the CCRT plus TIL infusion group and CCRT alone group (75.6% versus 74.4%, hazard ratios, 1.08; 95% confidence intervals, 0.62-1.89). TIL infusion was safe without grade 3 or 4 adverse events and all the high-grade adverse effects were associated with myelosuppression caused by CCRT. Exploratory analysis showed that a potential survival benefit was observed with TILs in patients with lower levels of circulating CD8+TIM3+ cells, serum IL-8 or PD-L1. The infused TIL products in patients with favourable outcomes were associated with increased transcription of interferon-γ and a series of inflammatory related genes and a lower exhausted score., Conclusion: The primary objective of prolonging PFS with CCRT plus TILs in high-risk NPC patients was not met. These findings may provide evidence for the design of future trials investigating the combination of TILs plus immune checkpoint inhibitors based on CCRT in high-risk NPC patients., Trial Registration Number: NCT02421640., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. The authenticity of this article will be validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn)., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation., Methods: We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT)., Findings: From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation., Interpretation: Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients., Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section., Competing Interests: All authors declared no potential conflicts of interest., (© 2023 The Author(s).)

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients., (© 2023. Springer Nature Limited.)

Background: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma., Methods: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m 2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m 2 intravenously on days 1 and 8) and cisplatin (80 mg/m 2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m 2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m 2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up., Findings: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths., Interpretation: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio., Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: This study focused on developing and validating a nomogram to predict the overall survival (OS) of patients with nasopharyngeal carcinoma (NPC) without distant metastasis based on their clinical characteristics, serum biomarkers, and presence of nasopharyngeal (NP) necrosis., Methods: This study included 9298 patients with NPC. Patients from January 2009 to December 2014 were randomly categorized into the training cohort and validation cohort A. Validation cohort B, whose data were collected from January 2015 to December 2017, was also included. OS was the primary endpoint of this study. Cox regression analysis was used to detect independent risk variables. Decision curve analysis, calibration curve, time-dependent receiver operating characteristic (ROC) curve, and concordance index (C-index) were used to evaluate the performance of the nomogram model., Results: A total of 267 patients developed NP necrosis after the first routine radiotherapy. After radiotherapy, patients with NP necrosis had significantly lower OS than other patients in all three cohorts (p < 0.001). Eleven factors, including NP necrosis, were involved in the nomogram, which had favorable discrimination and calibration with a C-index of 0.768 in the training cohort, 0.749 in validation cohort A, and 0.739 in validation cohort B. The nomogram exhibited a significantly larger area under the ROC curve for predicting OS than the TNM stage and Epstein-Barr virus (EBV) DNA (p < 0.001)., Conclusion: Compared with the TNM system and EBV DNA, we established a nomogram model with an accurate prognostic prediction for patients with NPC, which might help with patient management in NPC., Key Points: • This study included 9298 patients with NPC, and 11 factors were involved in the final model. • The nomogram had a significantly higher C-index and area under the ROC curve than the TNM stage and EBV DNA. • We established the first nomogram model for NPC involving the occurrence of NP necrosis, which was valuable for providing individual counseling and clinical assessments., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

To clarify the effects of non-rhizosphere/rhizosphere soil functional microbes (nitrifiers, denitrifiers, and phosphorus-solubilizing microorganisms) on lemon yield and quality, the lemon fruit and non-rhizosphere/rhizosphere soil were selected as subjects. To explore the correlation between non-rhizosphere/rhizosphere soil functional microbes and lemon yield and quality under a chemical fertilizer reduction substitute with organic fertilizer, traditional fruit quality determination and multiple molecular techniques were used. The results showed that:① 30% chemical fertilizer reduction substitute with organic fertilizer increased the nitrification intensity and phosphatase activity but effectively controlled the denitrifying enzyme activity. ② The chemical fertilizer reduction substitute with organic fertilizer significantly decreased the abundances of nitrifiers and nirS/nirK -harboring denitrifiers and significantly increased the abundances of nosZ -harboring denitrifier and phoD -harboring microorganisms. However, the diversities of functional microbial community structure did not have clear regularity under chemical fertilizer reduction substitute with organic fertilizer. ③ Compared with that under the application of chemical fertilizer and organic fertilizer alone, lemon yield and quality were the highest under the 30% reduction of chemical fertilizer substitute with organic fertilizer. ④ Nitrogen and its related microbes significantly affected lemon yield through internal and external quality. Phosphorus and its related microbes affected lemon yield mainly through internal quality. In addition, the influence factors of non-rhizosphere soil and rhizosphere soil on lemon intrinsic quality were obviously different. Altogether, these results showed that the 30% reduction of chemical fertilizer substitute with organic fertilizer significantly affected soil nitrogen and phosphorus functional microorganisms and further improved lemon yield and quality.

Aim: To assess the feasibility of applying field-of-view (FOV) optimised and constrained undistorted single-shot (FOCUS) diffusion-weighted imaging (DWI) in the thyroid gland by comparing its image quality with conventional DWI (C-DWI) qualitatively and quantitatively using a dedicated surface coil exclusively designed for the thyroid gland at 3 T magnetic resonance imaging (MRI)., Materials and Methods: In this prospective study, 32 healthy volunteers who had undergone 3 T the thyroid gland MRI with FOCUS-DWI and C-DWI were enrolled. Two independent reviewers assessed the overall image quality, artefacts, sharpness, and geometric distortion based on a five-point Likert scale. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) were quantified for both sequences. Interobserver agreement, qualitative scores, and quantitative parameters were compared between two sequences., Results: Agreement between the two readers was good for FOCUS-DWI (κ = 0.714-0.778) and moderate to good for C-DWI (κ = 0.525-0.672) in qualitative image quality assessment. Qualitatively, image quality (overall image quality, artefacts, sharpness, and geometric distortion) was significantly better in FOCUS-DWI than that in the C-DWI (all p<0.05); however, quantitatively, FOCUS-DWI had significantly lower SNRs (p<0.001) and CNRs (p=0.012) compared with C-DWI. The ADC value on FOCUS-DWI was significantly higher than that on C-DWI (p<0.001)., Conclusion: FOCUS-DWI depicted the thyroid gland with significantly better image quality qualitatively and less ghost artefacts, but had significantly lower SNR and CNR quantitatively, compared with C-DWI, suggesting that both DWI sequences have advantages and could be chosen for different purposes., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Importance: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear., Objective: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma., Design, Setting, and Participants: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1., Interventions: Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy., Main Outcomes and Measures: The primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety., Results: Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group., Conclusions and Relevance: This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile., Trial Registration: ClinicalTrials.gov Identifier: NCT02940925.

Background: To evaluate the cost-effectiveness of stage-based post-radiotherapy (PRT) nasopharyngeal carcinoma (NPC) surveillance strategies., Methods: Four post-radiotherapy surveillance strategies were established by a Markov model based on data from 1664 patients: 1) clinical follow-up (CFP) with biannual Epstein-Barr virus (EBV) DNA (EBV DNA strategy); 2) CFP with biannual EBV DNA, annual head and neck magnetic resonance imaging (HNMRI), chest X-ray, abdominal ultrasonography, bone scan (only for the first two years) for five years (MCWU strategy); 3) CFP with biannual EBV DNA, annual HNMRI, chest, abdomen, pelvic computerized tomography (CT) and bone scan for the first two years, followed by annual MCWU strategy (without bone scans) for the last three years (CT strategy); 4) CFP with biannual EBV DNA, annual whole-body positron emission/computerized tomography (PET/CT) for the first two years and biannual EBV DNA for the last three years (PET/CT strategy)., Results: Compared with the EBV DNA strategy, the MCWU, CT, and PET/CT strategies gained 0.017, 0.047, and 0.082 quality-adjusted life years (QALY) for stage I-II patients. For stage III and IVa patients, the PET/CT strategy had a favorable incremental effectiveness (ICERs) of 0.277 and 0.385 QALY, respectively. The ICERs for the MCWU, CT, and PET/CT strategies were $74,037, $34,882, and $34,696 for stage III and $62,364, $27,981, and $28,340 for stage IVa, respectively., Conclusion: EBV DNA strategy was cost-effective for the long-term surveillance of stage I-II NPC patients with CR. PET/CT strategy was recommeded for patients having IVa NPC. As for stage III NPC, PET/CT strategy was still acceptable with the development of economy in China., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to develop and validate a biochemical signature for predicting the prognosis of patients with nasopharyngeal carcinoma (NPC) and explore roles of the constructed signature for screening optimal candidates for induction chemotherapy (IC). The biochemical signature was constructed based on a retrospective cohort of 3742 patients from January 2008 to December 2010; 2078 patients from prospective studies from January 2011 to December 2012 and 2153 patients from January 2013 to December 2016 served as validation cohort A and validation cohort B. Overall survival (OS) was the primary endpoint. The least absolute shrinkage and selection operator coefficients on the Cox regression model were calculated to construct the prediction model with the data of 33 biochemical indicators. A total of six prognostic indicators, including sodium, alkaline phosphatase, lactate dehydrogenase, albumin, indirect bilirubin, and cystatin-C, were screened for constructing the biochemical signature. The patients were divided into low-risk and high-risk groups using an optimal cut-off value of 0.823. The patients in high-risk group had significantly lower OS and distant metastasis-free survival (DMFS) compared with patients in low-risk group in three cohorts (P < 0.05). Furthermore, among patients with high-risk scores in the combined cohort, the addition of IC to CCRT further improved their OS and DMFS, whereas patients with low-risk scores did not benefit from IC. Our study developed and validated a clinically useful biochemical signature that could predict the survival outcomes in NPC patients. This signature can help clinicians design personalized treatment strategies., Competing Interests: None., (AJCR Copyright © 2022.)

Purpose: Cumulative doses of 200 mg/m 2 for concurrent cisplatin (DDP) were indicated by retrospective studies as sufficient in conferring survival benefit for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We performed an open-label, phase II, randomized, controlled trial to test the noninferiority of a two-cycle 100 mg/m 2 concurrent DDP regimen over three-cycle in patients with low-risk LA-NPC with pretreatment Epstein-Barr virus DNA levels < 4,000 copies/mL., Patients and Methods: Eligible patients were randomly assigned 1:1 to receive two cycles or three cycles concurrent DDP-based chemoradiotherapy. The primary end point was 3-year progression-free survival (PFS). The secondary end points included overall survival, distant metastasis-free survival, locoregional relapse-free survival, etc., Results: Between September 2016 and October 2018, 332 patients were enrolled, with 166 in each arm. After a median follow-up of 37.7 months, the estimated 3-year PFS rates were 88.0% in the two-cycle group and 90.4% in the three-cycle group, with a difference of 2.4% (95% CI, -4.3 to 9.1, P noninferiority = .014). No differences were observed between groups in terms of PFS, overall survival, and the cumulative incidences of locoregional relapse and distant metastasis. Patients in the three-cycle group developed significantly more grade 3-4 mucositis (41 [24.8%] v 25 [15.1%]), hyponatremia (26 [15.8%] v 14 [8.4%]), and dermatitis (9 [5.5%] v 2 [1.2%]). The overall all-grade and grade 3-4 toxicity burdens were heavier in three-cycle group (T-scores, 12.33 v 10.57, P < .001 for all grades; 1.76 v 1.44, P = .05 for grade 3-4). Patients in the three-cycle group also showed more all-grade hearing impairment, dry mouth and skin fibrosis, and impaired long-term quality of life., Conclusion: Intensity-modulated radiotherapy plus two cycles of concurrent 100 mg/m 2 DDP could be an alternative treatment option for patients with low-risk LA-NPC.

Objective: In this study, we aimed to establish and validate an integrated prognostic model for locally recurrent nasopharyngeal carcinoma (lrNPC) patients, and evaluate the benefit of re-radiotherapy (re-RT) in patients with different risk levels., Materials and Methods: In total, 531 patients with lrNPC were retrospectively reviewed in this study, including 271 patients from 2006 to 2012 as the training cohort and 260 patients from 2013 to 2016 as the validation cohort. Overall survival (OS) was the primary endpoint. Multivariate analysis was performed to select the significant prognostic factors (P < 0.05). A prognostic model for OS was derived by recursive partitioning analysis (RPA) combining independent predictors using the algorithm of optimized binary partition., Results: Three independent prognostic factors (age, relapsed T [rT] stage, and Epstein-Barr virus [EBV] DNA) were identified from multivariate analysis. Five prognostic groups were derived from an RPA model that combined rT stage and EBV DNA. After further pair-wise comparisons of survival outcome in each group, three risk groups were generated. We investigated the role of re-RT in different risk groups, and found that re-RT could benefit patients in the low (P < 0.001) and intermediate-risk subgroups (P = 0.017), while no association between re-RT and survival benefit was found in the high-risk subgroup (P = 0.328). The results of risk stratification and re-RT efficacy were verified in the validation cohort., Conclusion: Age, rT stage and EBV DNA were identified as independent predictors for lrNPC. We established an integrated RPA-based prognostic model for OS incorporating rT stage and EBV DNA, which could guide individual treatment for lrNPC., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests. None of the authors has any financial and personal relationships with other people or organizations that could inappropriately influence (bias) of this work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Soil microorganisms have an important influence on the transformation of soil nutrients. As functional genes encoding phosphatase, phoC and phoD provide effective means for detecting the types, abundance, and community structure of microorganisms in the environment, and studying the changes in the diversity of phoC and phoD gene microbial communities in the rhizosphere and non-rhizosphere soil of the plant rhizosphere and non-rhizosphere soil under the treatment of chemical fertilizer and organic fertilizer combined with biochar can provide a scientific basis for the agricultural utilization of biochar. In this study, corn stalks and rice husk stalks were used as test materials, and the pot experiment method was used to set the following treatments:control (CK), traditional fertilization (F), chemical fertilizer+20 t·hm -2 rice husk biochar (FP), chemical fertilizer+10 t·hm -2 rice husk biochar+10 t·hm -2 corn biochar (FPM), organic fertilizer+20 t·hm -2 rice husk biochar (PP), and fresh organic fertilizer+20 t·hm -2 rice husk biochar (NPP). The community structure of phoC and phoD genes in rhizosphere and non-rhizosphere soil was analyzed by using T-RFLP and fluorescence quantitative PCR technology to clarify the response characteristics of phoC and phoD genes to the addition of biochar. The results showed that:① In rhizosphere soil and non-rhizosphere soil, the phoD gene community structure was more complicated than that of phoC , and the number of end restriction fragments of the phoC gene increased after chemical fertilizer and organic fertilizer were combined with biochar. ② The combined application of biochar with chemical fertilizer and organic fertilizer reduced the copy number of the phoC gene in non-rhizosphere soil compared with that in the CK. Compared with that in the CK, the copy number in the FP, FPM, PP, and NPP treatments decreased by 9.18%, 11.46%, 10.97%, and 13.76%, respectively. Organic fertilizer combined with biochar increased the copy number of the phoD gene in rhizosphere soil by 2.48% and 5.16% in the PP and NPP treatments, respectively, compared with that in the CK. ③ Total phosphorus in the soil was the main factor affecting the phoC gene microbial community structure in non-rhizosphere soil ( P <0.01), whereas the phoC gene microbial community structure in rhizosphere soil was regulated by a variety of environmental factors. pH was the most critical factor affecting the phoD gene copy number, and the copy number of phoD gene was significantly correlated with soil nitrate nitrogen and pH. The combined application of biochar with chemical fertilizers and organic fertilizers can promote the growth and reproduction of microorganisms that function in soil phosphorus conversion, which is of great significance for improving the utilization of phosphorus fertilizers.

To study changes in phosphatase activity, we examined the diversity of phoC and phoD gene microbial communities in the rhizosphere and non-rhizosphere soil of plants under the treatment of chemical fertilizer and organic fertilizer combined with biochar. These results can provide a certain theoretical guidance for the conversion of insoluble phosphorus in the soil phosphorus pool to the inorganic phosphate ion that can be absorbed by plant roots and also provide a certain experimental basis for the improvement of the availability of phosphorus in the soil and the agricultural utilization of biochar. In this study, corn stalks and rice husk stalks were used as test materials, and the pot experimental method was adopted using the following treatments:set control (CK), traditional fertilization (F), chemical fertilizer+20 t·hm -2 rice husk biochar (FP), chemical fertilizer+10 t·hm -2 rice husk biochar+10 t·hm -2 corn biochar (FPM), organic fertilizer+20 t·hm -2 rice husk biochar (PP), and fresh organic fertilizer+20 t·hm -2 rice husk biochar (NPP). We determined the rhizosphere and non-rhizosphere soil acid phosphatase (ACP) activity and alkaline phosphatase (ALP) activity and used T-RFLP technology to analyze the diversity of phoC and phoD genes in order to clarify the impact of biochar on the micro-ecosystem formed by the plants, soil, and microorganisms. The results showed that:① the ALP and ACP activities of each treatment in the non-rhizosphere soil were lower than that of CK. In the rhizosphere soil, the ALP activity was significantly increased after the combined application of chemical fertilizer and organic fertilizer with biochar, and the ACP activity in the rhizosphere soil was higher than that in the non-rhizosphere soil. ② The combined application of biochar with chemical fertilizers and organic fertilizers significantly increased the diversity of phoC and phoD genes communities in rhizosphere and non-rhizosphere soils ( P <0.05); the diversity and richness of microbial communities in rhizosphere soil were higher than that in non-rhizosphere soils. ③ ACP activity was negatively correlated with phoC gene microbial community, and most ALP activity was positively correlated with phoD microbial community.

Background: Mild cognitive impairment (MCI), which is common in older adults, is a risk factor for dementia. Rapidly growing health care demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults., Objective: To overcome methodological drawbacks of previous studies (e.g., use of potentially imprecise screening tools that fail to include patients with MCI), this study investigated the feasibility of assessing multiple cognitive functions in older adults with and without MCI by using a social robot., Methods: This study included 33 older adults with or without MCI and 33 healthy young adults. We examined the utility of five robotic cognitive tests focused on language, episodic memory, prospective memory, and aspects of executive function to classify age-associated cognitive changes versus MCI. Standardized neuropsychological tests were collected to validate robotic test performance., Results: The assessment was well received by all participants. Robotic tests assessing delayed episodic memory, prospective memory, and aspects of executive function were optimal for differentiating between older adults with and without MCI, whereas the global cognitive test (i.e., Mini-Mental State Examination) failed to capture such subtle cognitive differences among older adults. Furthermore, robot-administered tests demonstrated sound ability to predict the results of standardized cognitive tests, even after adjustment for demographic variables and global cognitive status., Conclusion: Overall, our results suggest the human-robot interaction approach is feasible for MCI identification. Incorporating additional cognitive test measures might improve the stability and reliability of such robot-assisted MCI diagnoses.

Importance: Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear., Objective: To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC., Design, Settings, and Participants: This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021., Interventions: Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)- or cisplatin (100 mg/m2)-based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy., Main Outcomes and Measures: The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis-free survival, and locoregional relapse-free survival., Results: A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, -6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis-free survival (85.9% vs 90.4%, P = .17), and locoregional relapse-free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04)., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC., Trial Registration: ClinicalTrials.gov Identifier: NCT01540136.

Although lots of work has reported the structural variations of starch in microwave treatment, most of them are detected in the environment with non-constant microwave power and inhomogeneous heating, and the results are always in poor repeatability. In this study, the equipment with constant microwave power (CPM) and homogeneous heating was designed. And the phase transition of multi-scale structure of rice starch (30% moisture content) caused by CPM treatments with two heating modes, namely rapid microwave heating (RWH) and slow microwave heating (SWH) were investigated systematically. SEM results showed that the surface of starch granules after CPM treatment were rough and broken, and the damage caused by RWH was more distinct than that by SWH. SAXS, XRD and 13 C NMR results revealed that the CPM treatment decreased the degree of crystallinity and content of double helices of starch. Moreover, the influence of RWH on the variation of starch granules was greater than that of SWH, which can be attributed to the intensive friction and collision as well as the rapid evaporation of water in RWH treatment. Specifically, it exhibited greater destruction on the linkage of starch and the internal crystalline region in RWH treatment than SWH treatment, thereby resulting in more obvious damages on the lamellar and morphological structure of rice starch. In conclusion, CPM equipment has improved the problems of uneven heating and poor experimental repeatability. After CPM treated starch, the molecular structure of starch was destroyed, which provides a useful method to modify properties of starch., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients., Materials and Methods: Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS)., Results: Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis-free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05)., Conclusion: Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.

Purpose: Radiotherapy is the most important primary treatment for patients with nasopharyngeal carcinoma. Generally, the treatment duration of radiotherapy takes six or six and half weeks with 30 to 33 fractions. The current study was conducted to evaluate the association between prognosis and the duration of radiotherapy in nasopharyngeal carcinoma patients., Methods: Patients with primary nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy, with or without induction chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed., Results: In total, 1292 patients were included. At a median follow-up of 71.0 months (range 2.0-126.0 months), locoregional recurrence, distant failure and death were observed in 8.8%, 12.2% and 15.6% of all patients, respectively. Estimated 5-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival and overall survival in patients with radiation ≤ 7 weeks versus patients with radiation >7 weeks were: 93.2% versus 87.0% (P < 0.001), 89.4% versus 84.4% (P = 0.016), 79.8% versus 70.6% (P < 0.001) and 87.2% versus 78.4% (P < 0.001), respectively., Conclusions: Prolonged duration of radiotherapy with a significantly higher risk of distant metastasis and death in nasopharyngeal carcinoma patients. Understanding this point, healthcare providers should make efforts to avoid prolonged duration of radiotherapy to minimize the risk of treatment failure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hua, Ou-Yang, Zou, Xia, Luo and Chen.)

Background: We aimed to compare the survival outcomes of patients with nasopharyngeal carcinoma (NPC) who had different smoking behaviors and were treated with two- or three-dimensional radiotherapy (2D/3DRT) or intensity-modulated radiotherapy (IMRT) with a long-term follow up., Methods: From 1990 to 2016, 23,325 patients with NPC were included. The primary endpoint of this study was overall survival (OS). The log-rank test and Cox proportional hazards regression model were used to assess the patients' survival outcomes., Results: The 5-year OS rates in the entire cohort were 76.4%, 68.9%, and 79.8% in the former, current, and never smokers, respectively. In the IMRT cohort, the OS rates showed the same trend. Compared with the never smokers, the 5-year distant metastasis-free survival (DMFS) was lower in the former (P = 0.004) and current smokers (P < 0.001). In the multivariate analysis of the IMRT cohort, the risk of death (P = 0.003) and recurrence (P = 0.027) was higher in the current smokers, while the risk of metastasis was higher in the former and current smokers (P = 0.031 and P = 0.019, respectively) than the never smokers. A total of 53.9% of the effect of smoking status on OS was through sex, age, and Epstein-Barr virus DNA, which were significant mediators., Conclusion: In the IMRT era, being a former smoker or current smoker was an independent risk factor for DMFS. The difference in OS and locoregional relapse-free survival was significant only between the current smokers and never smokers., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests. None of the authors has any financial and personal relationships with other people or organizations that could inappropriately influence (bias) of this work., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to establish an effective prognostic nomogram to predict the risk of early metastasis (EM) in nasopharyngeal carcinoma (NPC) patients, as a guide for intensive treatment., Materials and Methods: A total of 9021 patients with biopsy-confirmed NPC at our institute were enrolled in this study between December 2006 to December 2016. We randomized these patients using a proportion of 2/3 and 1/3 and selected 6044 and 2977 patients as the training and validation cohorts, respectively. All patients received radiotherapy with or without chemotherapy. Univariate and multivariate logistical regressions were used to identify independent risk factors. The nomogram's predictive value was evaluated by concordance indexes (C-indexes), calibration curves, probability density functions (PDFs), and clinical utility curves (CUCs). ROC analysis using Delong test was used to compare efficiency between the nomogram and other risk factors., Results: In total, 174 (2.9%) and 81 (2.7%) patients in training and validation cohorts, respectively, had EM. Pretreatment plasma EBV DNA, N stage, LDH, ALP, BMI, and sex were independent predictive factors of EM. The C-indexes of nomogram were 0.756 (95% CI = 0.719-0.793) and 0.766 (95% CI = 0.720-0.813), in the training and validation cohorts, respectively. The C-index of the nomogram was significantly superior to any one of independent factors. According to the PDFs and CUCs and considering the balance of the true positive EM patients and true positive non-EM patients, we chose 5.0% as a threshold probability for clinical decision-making, which could distinguish about 85% and 48% of non-EM and EM patients, respectively., Conclusion: Our nomogram had good accuracy in predicting EM incidence, and a 5.0% threshold was appropriate for clinical decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Previous studies suggest that a cumulative cisplatin dose of 200 mg/m 2 might be adequate in the intensity-modulated radiation therapy (IMRT) era for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, two cycles of once-every-3-weeks cisplatin at 100 mg/m 2 has never been prospectively compared with standard once-a-week cisplatin regimen., Patients and Methods: This trial was conducted at three hospitals from 2011 to 2016. Patients who met the eligibility criteria were recruited (ChiCTR-TRC-12001979) and randomly assigned (1:1) via a computer-generated sequence to receive once-every-3-weeks cisplatin at 100 mg/m 2 for two cycles or once-a-week cisplatin at 40 mg/m 2 for six cycles concurrently with IMRT. Primary endpoint was failure-free survival and between-group absolute difference of 10% as the noninferiority margin., Results: A total of 510 patients were enrolled. Median follow-up time was 58.3 months with 85.4% of 3-year failure-free survival in the once-every-3-weeks group and 85.6% in the once-a-week group. An absolute difference of -0.2% (95% confidence interval, -6.3 to 5.9; P noninferiority = 0.0016). Acute toxicities of grade 3 or higher occurred in 55.8% in the once-every-3-weeks group and 66.3% in the once-a-week group ( P = 0.015). The most common acute toxicities were hematologic abnormalities, including leukopenia (16% vs. 27%; P = 0.0022) and thrombocytopenia (1% vs. 5%; P = 0.015). The late grade 3-4 auditory loss rate was significantly lower in the once-every-3-weeks group than the once-a-week group (6% vs. 13%; P = 0.0039)., Conclusions: Once-every-3-weeks cisplatin as concurrent chemoradiotherapy is noninferior to once-a-week cisplatin in the treatment efficacy in the LANPC. Although both regimens are well tolerated, severe acute toxicities and late-onset auditory loss are higher in the once-a-week group., (©2021 The Authors; Published by the American Association for Cancer Research.)

Objectives: The value of using PET/CT for staging of stage I-II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy., Methods: A total of 1003 patients with pathologically confirmed NPC of stages I-II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat., Results: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3-82.1] vs. 91.1% [84.8-97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8-100.0] vs. 76.4% [67.6-85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival., Conclusions: This study showed PET/CT is of little value for staging of stage I-II NPC patients at initial imaging., Key Points: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I-II NPC patients.

Purpose: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT., Methods: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed., Results: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76-0.83) and 0.779 (95% CI, 0.74-0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses., Conclusion: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.

Objective: To investigate the clinical value of magnetic resonance imaging (MRI) plain scan and diffusion weighted imaging (DWI) in the diagnosis of brain metastases. Methods: The MRI plain imaging findings of 105 cases with brain metastases and 103 cases without brain metastases confirmed by enhanced MRI examination and clinical diagnosis were retrospectively analyzed. The comparisons of plain MRI findings including T1 weighted image (T1WI), T2WI, T2/fluid attenuated inversion recovery (T2/FLAIR), DWI and apparent diffusion coefficient (ADC) values were made between brain metastases and non-brain metastases. Results: The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T1WI in the brain metastatic group were 54, 23, 9 and 19, respectively, while the numbers of hypo-intensity and iso-intensity in the non-brain metastatic group were 52 and 51, respectively, with statistically significant difference ( P <0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI in the brain metastatic group were 1, 9, 72 and 23, respectively, while the numbers of iso-intensity and hyper-intensity in the non-brain metastatic group were 11 and 92, respectively, with statistically significant difference ( P <0.001). The numbers of hypo-intensity, hyper-intensity and heterogeneous signal intensity of DWI in the brain metastatic group were 4, 31 and 65, respectively, while the number of hyper-intensity in the non-brain metastatic group was 4 and others were iso-intensity, respectively, with statistically significant difference ( P <0.001). The numbers of hypo-intensity, iso-intensity, hyper-intensity and heterogeneous signal intensity of T2WI/FLAIR in the brain metastatic group were 4, 5, 60 and 36, respectively, while all cases in the non-brain metastatic group were hyper-intensity, with statistically significant difference ( P <0.001). The number of lesion accompanied with peripheral edema in the brain metastatic group were 69 cases, significantly higher than 0 cases in the non-brain metastatic group ( P <0.001). The mean ADC value in the brain metastatic group were (0.919±0.019)×10(-3) mm(2)/s, significantly lower than (1.098±0.012)×10(-3) mm(2)/s of non-brain metastatic group ( P <0.05). Conclusions: For patients with a history of primary malignancy, the MRI plain scan signals of T1WI, T2WI, T2WI/FLAIR and DWI are significantly different between brain metastatic tumor and non-metastatic tumor. The mixed signal, peripheral edema and the restriction of DWI diffusion indicate brain metastases. The combined application of the above parameters can improve the diagnostic efficacy of predicting brain metastases, and contrast enhancement MRI examination should be performed for the confirmation of diagnosis.

Background: Studies have reported that apolipoprotein E epsilon 4 (APOE ɛ4) has adverse effects on executive functions (EFs) in late adulthood. However, the results have been inconsistent. Insufficient measurements of executive functioning, uncontrolled clinical and demographic confounders, and moderation effects from other environmental factors are suspected to account for the inconsistency., Objective: This study used aggregate measures to examine the effects of APOE ɛ4 on four components of EFs, namely switching, working memory, inhibition, and reasoning. We further investigated whether high educational attainment, a proxy measure for cognitive reserve, moderates the adverse effects of ɛ4 on EFs., Methods: Cognitively unimpaired older participants were divided into groups based on APOE genotype and into subgroups based on educational attainment level. The demographic and clinical variables were matched between the groups. Four core components of the EFs were measured using a relatively comprehensive battery., Results: The results revealed that although no main effect of the APOE genotype was observed across the four EF components, the potentially adverse effects of ɛ4 on inhibition were alleviated by high educational attainment. A main effect of education on the reasoning component was also observed. The moderation analysis revealed that for older adults with 12 years of education or fewer, the relationship between the APOE ɛ4 genotype and inhibition performance became increasingly negative., Conclusion: This study highlights the distinctive role of response inhibition in the gene-environment interaction and underlines the importance of considering factors of both nature and nurture to understand the complex process of cognitive aging.

Objective: This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [ 18 F]-fluorodeoxyglucose positron emission tomography., Patients and Materials: A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model., Results: Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values<0.05). The addition of IC to CCRT was associated with survival improvement in OS, PFS, and DMFS in high-risk patients, while no survival difference was found between CCRT and IC+CCRT in low-risk patients., Conclusions: Our study can help clinicians select stage II-IVa NPC patients who benefit from IC, which is important in guiding individual treatment., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To investigate the optimal treatment pattern in patients with de novo metastatic nasopharyngeal carcinoma (NPC)., Methods: We 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)., Results: The 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)., Conclusion: LRRT 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., (Copyright © 2020 Sun, Liang, Chen, Guo, Liu, Sun, Luo, Tang and Mai.)

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., (Copyright © 2020 Sun, Wang, Liu, Luo, Sun, Liu, Guo, Chen, Tang and Mai.)

Background: Vancomycin remains a mainstay of the treatment of Gram-positive bacterial infections. It is crucial to accurately determine vancomycin serum concentration for adequate dose adjustment., Objectives: To evaluate the precision and accuracy of commercial assay techniques for vancomycin concentration and to assess the comparability of vancomycin detection methods in Chinese laboratories., Methods: Human serum samples spiked with known concentrations of vancomycin were provided to laboratories participating in the external quality assessment scheme (EQAS). Assay methods included chemiluminescence, enzyme immunoassay (EIA) and so on. The dispersion of the measurements was analysed and the robust coefficient of variation (rCV), relative percentage difference (RPD) and satisfactory rate for method groups were calculated. Moreover, performance of the Chinese laboratories was assessed., Results: A total of 657 results from 75 laboratories were collected, including 84 samples from 10 Chinese laboratories. The median rCV, median RPD and satisfactory rates classified by methods ranged from 1.85% to 15.87%, -14.75% to 13.34% and 94.59% to 100.00%, respectively. Significant differences were seen in precision, between kinetic interaction of microparticles in solution (KIMS) and other methods, and in accuracy, between enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA) and other techniques. Vancomycin detection in China mainly depended on the chemiluminescence and EMIT methods, which tended to result in lower measurements., Conclusions: Although almost all assays in this study achieved an acceptable performance for vancomycin serum concentration monitoring, obvious inconsistencies between methods were still observed. Chinese laboratories were more likely to underestimate vancomycin concentrations. Thus, recognizing inconsistencies between methods and regular participation in vancomycin EQAS are essential., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Thus far, there is no final conclusion on the treatment of local recurrent nasopharyngeal carcinoma (lrNPC) patients. Herein, we developed a nomogram which combined prognostic biomarkers to predict clinical outcome and guide individual treatment., Materials and Methods: From 2006 to 2016, 303 patients with lrNPC were retrospectively reviewed. Overall survival (OS) was the primary endpoint. The nomogram was established with the significant prognostic factors (P < 0.05) selected by multivariate analysis using Cox regression model. Harrell Concordance Index (C-index), calibration curves, and decision curve analysis (DCA) were applied to evaluate this model., Results: Four independent prognostic factors (age, hypertension, relapsed T (rT) stage, and Epstein-Barr virus DNA) identified from multivariable analysis were included into the nomogram. The C-index of the nomogram was 0.687. The calibration curves for 1-, 3-, and 5-year OS rate showed satisfactory agreements between the predicted and actual values. The decision curve analysis also exhibited a preferable net benefit of this model. All patients were subdivided into three risk groups based on the nomogram. Local treatment was associated with higher OS than palliative chemotherapy alone in the low (P < 0.001) and intermediate-risk groups (P = 0.001). However, no significant difference was observed between different treatment methods in the high-risk group (P = 0.176)., Conclusion: We established the nomogram for patients with lrNPC to predict OS and guide individual treatment, which showed satisfactory performance in accuracy, discrimination capability, and clinical utility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To clarify the response of a nitrogen-related microbial community and function to different vegetation types in subtropical forest, soil samples were collected for analysis from the topsoil of five vegetation types in the Jinyun Mountain National Nature Reserve, i.e., coniferous forest, broadleaf forest, mixed broadleaf-coniferous forest, P. pubescen forest, and grassland. To analyze the microbial abundance, community, and function discrepancy between different vegetation soils, multiple molecular techniques, such as terminal restriction fragment length polymorphism (T-RFLP) and quantitative polymerase chain reaction (qPCR) analysis, and nitrogen-related microbial enzyme activity procedures were used. The results showed:① The denitrifying enzyme activity was much higher than nitrifying potential in Jinyun Mountain National Nature Reserve, and the two enzyme activities were much lower in coniferous forest soil than in the other vegetation soils ( P <0.05). In addition, dissolved organic carbon, soil water content, and total nitrogen were the key environmental factors controlling enzyme activity. ② The qPCR data showed that the abundance of nitrogen-related microbes was highest in P. pubescen forest, whereas it was lowest in coniferous forest. The abundances of the three nitrogen-related microbes were all significantly correlated with dissolved organic carbon, total nitrogen, available nitrogen, total potassium, and available potassium ( P <0.01). ③ Based on T-RFLP data, the α -diversity of nitrogen-related microbes was highest in broadleaf forest, whereas it was lowest in P. pubescen forest. Principal co-ordinates analysis (PCoA) showed that the community structure of ammonia-oxidizing archaea responded significantly to different vegetations, and the community structure of nitrogen-related microbes showed the most difference in coniferous forest. In addition, distance-based redundancy analysis (db-RDA) showed that the community structure of nitrogen-related microbes was mainly shaped by dissolved organic carbon ( P <0.001), available nitrogen ( P <0.002), and soil water content ( P <0.001). ④ Soil-denitrifying enzyme activity was mainly affected by the abundance of nirS -denitrifiers, ammonia-oxidizing archaea, and the community structure of nitrogen-related microbes, whereas nitrifying potential was only controlled by the abundance of ammonia-oxidizing archaea. Above all, subtropical forest vegetation significantly affects the abundance and community structure of soil nitrogen-related microbes, thereby changing their function of controlling the soil nitrogen cycle. This study can provide basic data for the coupling mechanism between soil microbes and N 2 O release in subtropical forests in China.

Background: The tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC)., Methods: Using multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients., Results: Eight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed., Conclusions: The immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to elucidate the optimal cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) according to the post-induction chemotherapy (IC) plasma Epstein-Barr virus (EBV) DNA level., Results: EBV DNA was detected and undetected in 179 and 370 patients, respectively. Of the entire cohort, 73/549 (13.3%) patients received a total CCD ≥ 160 mg/m 2 and 476/549 (86.7%) patients, <160 mg/m 2 . CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, higher 3-year PFS and locoregional relapse-free survival (LRFS) rates were observed in those who received a CCD ≥ 160 mg/m 2 . Multivariate analysis also showed CCD was an independent prognostic factor for PFS and LRFS in patients with post-IC detectable EBV DNA., Conclusions: CCD enhancement was not associated with a survival benefit in patients with undetected EBV DNA after IC. However, among patients with post-IC detectable EBV DNA, those receiving ≥160 mg/m 2 CCD showed significantly improved 3-year PFS and LRFS., Methods: NPC patients (549) treated with IC and CCRT were included. Prognosis was assessed using a multivariate Cox proportional hazards model. Furthermore, grade 1-4 toxicities were compared between different CCD groups.

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., (Copyright © 2020 Li, Jia, Sun, Guo, Liu, Liu, Yan, Luo, Sun, Guo, Mo, Tang, Chen and Mai.)

Phosphorus is an essential nutrient for crop growth, but the input of excess phosphorus is a significant cause of eutrophication. This study explored the relationship between fertilization methods and phosphorus loss in actual production, providing a theoretical basis for scientific fertilization and rational reduction of fertilizer application. In the experiment, a wild-type OD flow plot was used to monitor the occurrence of multiple rainfall runoff and sediment yield in purple soil sloping farmland in 2017-2018. Four different schemes of non-fertilizer treatment, conventional fertilization treatment, optimized fertilization treatment, and reduced fertilization combined with biochar were studied. The effects of soil flow, surface runoff, and sediment phosphorus loss on purple soil sloping farmland were analyzed. The results showed that:①The total yield of each treatment was optimized (20737.23 L) > conventional (18513.17 L) > CK (18134.58 L) > biochar (13594.85 L), and the total sediment yield of each treatment was CK (1998 kg·hm -2 ) > biochar (1884 kg·hm -2 ) > optimized (1681 kg·hm -2 ) > conventional (910 kg·hm -2 ). The middle stream of soil is the main type of runoff in the rainy season, accounting for 60.14%-87.34% of the total output flow. The total amount of sediment produced by each treatment was not significantly different from that of the conventional treatment ( P >0.05). ②The flux of total phosphorus loss in each treatment was characterized by sediment > surface runoff > soil middle flow. Phosphorus lost through the middle stream of soil is the least, accounting for only 2.63%-12.91% of the flux of total phosphorus loss, while the flux of sediment loss of phosphorus can reach 63.74%-78.74%, and thus is the main output route of soil phosphorus loss. ③The application of biochar can effectively reduce the abortion flow in the soil of purple soil sloping land, and the loss flux of orthophosphate in the middle stream, which are 49.94% and 56.45% lower than the conventional treatment, respectively. However, the interception effect on surface runoff is not good, and there is no significant influence on the flux loss of particulate phosphorus. At the same time, the flux of total phosphorus in surface runoff and sediment is significantly increased by 73.28% and 123.53%, respectively, compared with conventional treatment ( P <0.05). Therefore, to control the loss of phosphorus in purple soil sloping farmland in southwest China, we should focus on reducing the occurrence of soil sediment loss. Bio-carbon should be further optimized in the practical application of agricultural production with the phosphorus fertilizer input ratio.