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Ultra-pure copper sputtering target is a key material widely used in large-scale integrated circuits with 90-28 nm feature size. The copper target for 300 mm integrated circuit requires a reliable diffusion bonding between the ultra-pure copper target and the copper alloy backplate. The bonding ratio and bonding strength of diffusion bonding should reach over 99% and 80 MPa respectively. In this paper, the ascendant structure of electron beam welding united diffusion bonding with high quality was designed. The ultra-pure copper target and the C18000 copper alloy backplate were machined to coordinating size, meanwhile the backplate underwent surface treatment of toothed/smooth, ion cleaning, magnetron sputtering coating, then the combination of target and the backplate was proceeded electron beam welding and diffusion bonding. Metallographic microscope, scanning electron microscope (SEM), mechanical tensile machine, C-scan flaw detector were used to analyze the bonding properties including interface microstructure, bonding strength and bonding ratio. The results show that the bonding ratio of copper target was above 99%, and the bonding strength was up to 80-160 MPa.

The causative gene family of Parkinson's disease, PARK, plays important roles in the regulation of skeletal myopathy and is also involved in multiple biological processes, such as the modification of motor neurons, the transmission of nerve signals at the nerve-muscle junction, the regulation of skeletal muscle energy metabolism and mitochondrial quality, and the expression of myogenesis factors. PARK gene family regulates skeletal muscle mass, functions through a multi-level regulatory system, and plays a key role in the occurrence and development of skeletal myopathy. In this review, we summarize the structural characteristics, functions, and research of the PARK gene family in skeletal myopathy, providing a theoretical foundation and future research direction for in-depth study of the molecular mechanism for skeletal myopathy and giving references to further study on the role of PARK family in the development, the pathology, clinical diagnosis, and treatment of skeletal myopathy.PARK作为帕金森病的致病基因家族,在帕金森病的发生发展中发挥了关键作用。近年来的研究表明,这一关键基因家族在骨骼肌肌病的发生发展中也发挥着重要作用,作为运动神经元修饰剂,保护神经元的完整性,参与骨骼肌神经-肌肉接头处神经信号的传递,骨骼肌能量代谢及线粒体质量控制、同时调控肌生成因子表达,促进肌肉再生,维持肌肉含量和功能。本文主要综述了PARK基因家族在骨骼肌肌病中的研究进展,总结了骨骼肌肌病发生的分子机制及研究方向,以期为进一步研究PARK家族在骨骼肌肌病发生发展中的作用提供参考,为理解骨骼肌肌病分子病理机制及临床诊断和治疗带来新的启示。.

OBJECTIVES/HYPOTHESIS The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. STUDY DESIGN The effectiveness evaluation of diagnostic methods. METHODS Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. RESULTS The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P

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.

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. 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. 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. 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 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

Background We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. Methods The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA Results A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. Conclusions In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

Objective: The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma (NPC). Methods: Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study. Clinicopathologic information for each patient was analyzed. Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model. Concordance index (C-index) and calibration curves were used to verify discrimination and calibration, respectively and the results validated using bootstrap resampling. Results: Microscopic positive lymph node > 2 [hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.30-3.68; P = 0.003], extranodal extension (HR, 2.75; 95% CI, 1.69-4.47; P < 0.001), and lower neck involvement (HR, 1.78; 95% CI, 1.04-3.04; P = 0.034) were identified from multivariate analysis as independent factors for overall survival (OS). A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival (PFS). The novel scoring model demonstrated enhanced discrimination (C-index = 0.69; 95% CI, 0.62-0.76) relative to the original recurrent tumor-node-metastasis (rTNM) staging system (C-index = 0.56; 95% CI, 0.50-0.62), and was internally validated with a bootstrap-adjusted C-index of 0.70. The calibration curve showed good agreement between predicted probabilities and actual observations. Conclusions: The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.

Epidemic and pandemic influenza A virus (IAV) poses a significant threat to human populations worldwide. Iridoid glycosides are principal bioactive components from the Gardenia jasminoides J. Ellis fruit that exhibit antiviral activity against several strains of IAV. In the present study, we evaluated the protective effect of Fructus Gardeniae iridoid glycoside extracts (IGEs) against IAV by cytopathogenic effect(CPE), MTT and a plaque formation assay in vitro and examined the reduction in the pulmonary index (PI), restoration of body weight, reduction in mortality and increases in survival time in vivo. As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2α in A549 cells were detected; the levels of IFNβ, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication in vitro, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.

Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.

International audience; Background: Early biomarkers allowing effective treatment stratification in adult T-cell acute lymphoblastic leukemia (T-ALL) patients remain elusive.Materials and methods: The mutation spectrum of 116T-ALL adult patients enrolled in the Shanghai Institute of Hematology (SIH)-based hospital network or Multicenter Hematology-Oncology Protocols Evaluation System (M-HOPES) in China were studied by using RNA-sequencing or targeted next generation sequencing. A comprehensive survival analysis based on clinical characteristics, immunophenotype and oncogenetic classifier was performed.Results: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has higher mutation rates of N/K-RAS and lower mutation rates of FBXW7 compared to non-ETP ALL, but the survival probability of ETP-ALL patients is similar to that of non-ETP ALL patients. T-ALLs with a NOTCH1/FBXW7 (N/F) mutation in the absence of RAS or PTEN abnormalities (NFRP class I) show a more favorable outcome compared to T-ALLs with no N/F mutation and/or with the presence of RAS/PTEN alterations (NFRP class II). A survival analysis of TALL , taking into account both the ETP-ALL/non-ETP TALL groups and the NFRP oncogenetic classifier, demonstrates that, within the non-ETP TALL subtype, NFRP class II identifies a group with poor prognosis and significant decreases of both OS (14.8% versus 50.9%, P = 0.019) and EFS (11.4% versus 42.4%, P = 0.001). In contrast, no survival difference is observed within ETP-ALL between the NFRP class I or class II (OS: 37.9% versus 33%, P = 0.876; EFS: 39.8% versus 33.7%, P = 0.969).Conclusion: In summary, the oncogenetic classifier based on the NFRP classes is particularly useful to improve the stratification of non-ETP ALL.

We aimed to evaluate patients suitable for definitive radiation therapy (DRT) and liver local therapy (LLT) in addition to palliative chemotherapy (PCT) among those with de novo liver metastatic nasopharyngeal carcinoma (lmNPC).The overall survival (OS) and progression-free survival (PFS) rates were calculated and compared in 610 patients with lmNPC.Both the PCT+DRT and PCT+DRT+LLT groups had better survival outcomes than the PCT group. Among patients with complete response/partial response (CR/PR) after PCT, no significant differences in survival rates were observed between those treated with PCT+DRT and PCT+DRT+LLT (2-year PFS: 27.0% vs. 32.9%, p = 0.263). Among patients with progressive disease/stable disease (PD/SD) after PCT, significantly better survival rates were observed in patients treated with PCT+DRT+LLT.DRT might benefit patients with lmNPC regardless of the tumor response after PCT. For patients with CR/PR, LLT might not be needed. For patients with PD/SD, LLT might improve survival outcomes.

Purpose To analyze the clinical outcomes of patients with regional persistent/recurrent nasopharyngeal carcinoma (NPC) who received neck dissection, and to evaluate the clinical benefit of postoperative adjuvant therapy (PAT) based on patients’ positive lymph node counts (PLNs), extracapsular spread (ECS) and preoperative plasma EBV DNA levels. Methods From 2003 to 2017, 342 patients with regional persistent/recurrent NPC were included in this study. All patients were treated with neck dissection and 76 patients received PAT. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were compared between groups using propensity score matching (PSM). Results 152 patients without PAT treatment and 76 patients with PAT treatment were selected by the PSM. There was no significant difference in 2-year PFS (52.4% vs. 61.3%, P = 0.371), 2-year OS (91.9% vs. 90.5%, P = 0.097) or 2-year LRFS (66.3% vs. 67.9%, P = 0.872) between the two groups. However, the application of PAT brought survival benefits to patients in terms of 2-year DMFS (76.5% vs. 84.7%, P = 0.020). PLN, ECS and preoperative EBV DNA level remained independent risk factors for poorer PFS. Accordingly, patients were divided into low-risk and high-risk groups using receiver operating characteristic (ROC) curve; the 2-year PFS rates for two risk groups were 73.4% and 59.1% (P P = 0.023). Conclusions PLNs, ECS and preoperative EBV DNA level are associated with the prognosis of patients with regional persistent/recurrent NPC. High-risk patients identified by PLNs, ECS and preoperative EBV DNA level may benefit from the addition of PAT after neck dissection.

Salvage radiotherapy (RT) is a potentially curative approach for advanced locally recurrent nasopharyngeal carcinoma (NPC), but it is associated with severe toxicities. We aimed to develop a model to predict which patients would benefit from salvage RT.A total of 809 patients who were diagnosed with advanced locally recurrent NPC and treated with salvage RT or palliative chemotherapy (CT) at a high-volume cancer center were included. Patients were randomly split into a training and validation set and matched using inverse probability of treatment weighting. The primary outcome was overall survival (OS). Candidate variables associated with heterogeneous treatment effects were identified with interaction terms in Cox model and incorporated into Salvage Radiotherapy Outcome Score (SARTOS).The final model included five interaction terms indicating that female sex, presence of prior RT-induced grade ≥ 3 late toxicities and suboptimal performance status were associated with less benefit from salvage RT. SARTOS from the model significantly predicted treatment effects of salvage RT in matched training (PWe found that the SARTOS model could identify a subgroup of patients who benefit from salvage RT versus palliative CT, which helps personalize treatment recommendations for patients with recurrent NPC.

Background To evaluate whether patients with post-treatment metastasis are suitable for GP first-line palliative chemotherapy (PCT) after undergoing GP IC. Methods Seven hundred and forty-six patients with post-treatment metastasis after undergoing GP IC were eligible. Survival outcomes were compared. Results Significant differences in survival rates were observed between patients treated with GP and non-GP chemotherapy (2-year progression-free survival [PFS]: 0.7% vs. 9.7%). We investigated survival outcomes of patients treated with GP PCT within 2 years after undergoing GP IC, treated with GP PCT 2 years after undergoing GP IC, and those of non-GP PCT patients (2-year PFS: 0.0%, 2.3%, 9.7%). However, there was no difference in the 2-year PFS between the patients that received GP PCT 2 years after undergoing GP IC and the non-GP PCT treated patients. Conclusions GP is not recommended for patients that have received GP IC within 2 years. Two years after undergoing GP IC, GP can be considered.

To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure.A total of 1124 eligible patients with Stage II-IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated.Patients with high ΔALC% were correlated with poorer 5-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2-3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low-risk group [with1 risk factor], intermediate risk group [with 1-3 risk factors], and high-risk group [with 4 risk factors]) that correlated with disparate risks of death (p 0.001), disease progression (p 0.001), and distant metastasis (p 0.001).High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk-adapted therapeutic strategies for NPC.

This study constructed the recombinant plasmid of a TonB-dependent receptor from V. parahaemolyticus and evaluated the immunogenicity of the recombinant protein in mice. The TonB-dependent receptor gene (GI: 28901321) was obtained by PCR amplification and cloned into plasmid pET-32a (+). The recombinant plasmids were transformed into Escherichia coli BL21, and the protein expression was induced by isopropyl-β-d-thiogalactopyranoside (IPTG). The 6 × His-tagged TonB-dependent receptor inclusion bodies were purified by Ni-NTA Agarose column and renatured by gradient urea dialysis. The soluble and inclusion bodies of the TonB-dependent receptor were emulsified with Freund's adjuvant and subcutaneously injected into BALB/c mice. The serum titers with seven V. parahaemolyticus strains, eight Vibrio species, and nine other bacteria were studied by enzyme-linked immunosorbent assay and immunoblotting. The results showed that the serum homogenously bound the target protein in the V. parahaemolyticus cell lysates. The titers against the immunized protein were above 89K, while the titer against whole cells of seven V. parahaemolyticus strains ranged from 4.12K to 12.5K. However, the titers were higher for the soluble TonB-dependent receptor. The serums reacted with E. coli strains but did not cross-react with eight Vibrio species and Photobacterium damselae. These results showed that the TonB-dependent receptor proteins in this study were immunogenic, and the serums showed adequate specificity for V. parahaemolyticus. However, the availability of the TonB-dependent receptor on V. parahaemolyticus cells is probably limited.

To compare the prognosis and adverse effects of induction or adjuvant chemotherapy (IC or AC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in paediatric nasopharyngeal carcinoma (NPC) patients in the intensity-modulated radiotherapy (IMRT) era.549 patients diagnosed from 2005 to 2021 were enrolled. Our primary endpoint was progression-free survival (PFS). The recursive partitioning analysis (RPA) was applied to derive a risk stratification system. Kaplan-Meier survival curves were used to assess the cumulative survival rates, and cox analysis was applied to evaluate the relationship between variables and endpoints.The RPA-based risk stratification identified three different risk groups. In the intermediate-risk (stage IVa and EBV4000 copies/ml) group, patients who received IC followed by CCRT achieved a significantly better 3-year PFS rate than those treated with CCRT alone (87.35% versus 75.89%; P = 0.04). But survival benefit was not obtained from the additional IC or AC in the low-risk (stage II-III and EBV4000 copies/ml) or high-risk (stage II-IVa and EBV≥4000 copies/ml) group. The most common grade 3 or 4 adverse events in patients treated with CCRT, IC + CCRT, and CCRT + AC were neutropenia (8.1%, 33.0% versus 36.9%, respectively) and leukopenia (14.1%, 26.8% versus 32.3%, respectively) with statistically significant difference.Paediatric NPC patients in the intermediate-risk group treated with IC followed by CCRT had significantly better PFS compared with patients treated with CCRT alone. And the overall incidence of acute adverse events in patients treated with IC or AC plus CCRT was higher than in patients treated with CCRT alone.

To develop botanical pesticides and repellents against stored-product insects, the chemical composition and insecticide properties of the essential oil from Citrus medica L. var. sarcodactylis Swin...

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

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

BACKGROUND Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.

Objective: This study aimed to establish a nomogram to predict the risk of post-radiation necrosis in nasopharyngeal carcinoma (NPC) patients. Background: This study was performed to identify influencing factors for developing post-radiation necrosis, and to establish an effective nomogram model to predict individual risks in NPC patients. Methods: 7144 NPC patients receiving radical radiotherapy from 2007 to 2012 were involved in the study, and 207 of them developed nasopharyngeal necrosis (NPN). The clinical characteristics and baseline laboratory results were collected and analyzed. Independent predictive factors were selected using the Cox proportional model and incorporated into the nomogram. The receiver operating characteristic curve and the calibration curve were used to verify discrimination and calibration. Results: The experience of re-irradiation contributed most to the occurrence of NPN (HR, 15.56, 95% CI 10.84-22.35, p

Essential oils (EOs) extracted from leaves (EL) and fruit pericarp (EFP) of Zanthoxylum planispinum var. dintanensis were analyzed for their chemical composition by GC-MS technique and evaluated for their fumigant, contact toxicity and repellency against three stored-product insects, namely Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila adults. Results of GC-MS analysis manifested that EL and EFP of Z. planispinum var. dintanensis were mainly composed of oxygenated monoterpenes. Major components included linalool, sylvestrene and terpinen-4-ol. The obvious variation observed between two oil samples was that EL contained 2-dodecanone (11.52%) in addition to the above mentioned components, while this constituent was not detected in EFP. Bioassays of insecticidal and repellent activities were performed for EL, EFP as well as some of their individual compounds (linalool, terpinen-4-ol and 2-dodecanone). Testing results indicated that EL, EFP, linalool, terpinen-4-ol and 2-dodecanone exhibited potent insecticidal and repellent activities against the three target insects selected. Among the three individual compounds, 2-dodecanone was significantly toxic to T. castaneum (LD50 = 5.21 μg/adult), L. serricorne (LD50 = 2.54 μg/adult) and L. bostrychophila (LD50 = 23.41 μg/cm2) in contact assays and had beneficial repellent effects on L. serricorne at 2 and 4 h post-exposure. The anti-insect efficacy of Z. planispinum var. dintanensis EO suggests it has potential to be used as botanical insecticide or repellent to control pest damage in warehouses and grain stores.

The objective of this work was to analyze four essential oils (EOs) from Rhododendron species in China and evaluate their repellent activity against Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila adults. These four EOs from Rhododendron species, including R. capitatum, R. przewalskii, R. mucronulatum, and R. micranthum, were obtained by hydrodistillation. Major components of four EOs were identified as sesquiterpenoids by GC-MS. The relatively high components included cedrene (22.20%), borneol (36.64%), 4-(2,3,4,6-tetramethylphenyl)-3-buten-2-one (27.74%), and germacrene D (27.60%). Repellent activity of EOs from Rhododendron species was investigated against T. castaneum, L. serricorne, and L. bostrychophila adults for the first time. In this study, EOs had demonstrated their repellent activities against three stored-product insects in 2- and 4-h exposure. The above results can not only provide comprehensive utilization of plant resources of Rhododendron genus but also establish a very good perspective of novel application to control stored-product insects.

Background: The goal of this study was to explore the value of adding neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy (ACT) to concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC) with different risks of treatment failure. Patients and Methods: A total of 2,263 eligible patients with stage III–IVb NPC treated with CCRT ± NACT or ACT were included in this retrospective study. Distant metastasis–free survival (DMFS), overall survival, and progression-free survival were calculated using the Kaplan-Meier method and differences were compared using the log-rank test. Results: Patients in the low-risk group (stage N0–1 disease and Epstein-Barr virus [EBV] DNA P= .008). Multivariate analyses also demonstrated that additional NACT was the only independent prognostic factor for DMFS (hazard ratio, 0.42; 95% CI, 0.22–0.80; P=.009). In both the intermediate-risk group (stage N0–1 disease and EBV DNA ≥4,000 copies/mL and stage N2–3 disease and EBV DNA Conclusions: The addition of NACT to CCRT could reduce distant failure in patients with low risk of treatment failure.

Continuous use of synthetic insecticides increases environmental contamination and resistance in many species. Botanical insecticides, such as essential oil, were considered to be suitable alternatives due to multiple modes of action and low mammalian toxicity. Haplophyllum dauricum is a overlooked plant for the control of stored-product insects. Five essential oils (EOs) from Haplophyllum dauricum collected in October and November, rich in pinene, were extracted and evaluated on anti-insect activity against two stored-product insects, Tribolium castaneum (Coleoptera: Tenebrionidae) and Lasioderma serricorne (Coleoptera: Anobiidae). The lethal doses (LD50 and LD90), lethal concentrations (LC50 and LC90) and percentage repellency (PR) were evaluated. The GC-MS analysis showed that pinene (α-pinene and β-pinene) were major constituent of the EOs (54.61% and 57.33% in fruits, 46.80% in stems + leaves, and 30.57% in leaves), followed by β-phellandrene (14.49% and 21.34% in fruits and leaves), 3-carene (26.84% in leaves) and limonene (15.77%, 11.09%, 12.40%, 7.59%, and 6.24% in five EOs, respectively). Five EOs and selected major compounds provided promising fumigant, contact and repellent activity against T. castaneum and L. serricorne. The EO of stems + leaves collected in October showed the strongest contact toxicity on T. castaneum (LD50 = 20.21μg/adult), as well as fumigant and contact toxicity on L. serricorne (LC50 = 17.17 mg/L air, LD50 = 25.46 μg/adult). All the five EOs exhibited effective repellent activity (PR>80%) against T. castaneum. The results highlight that the EOs from H. dauricum have a promising potential as eco-friendly botanical insecticides.

The essential oil was extracted from the roots of Valeriana officinalis L. by hydrodistillation. The qualitative and quantitative analysis of its chemical constituents was conducted on GC-MS and GC-FID in this study. Seventeen compounds were detected and the major constituents included bornyl acetate (48.2%) and camphene (13.8%). The toxic and repellent effects of the essential oil and its two major constituents were evaluated on Liposcelis bostrychophila and Tribolium castaneum. The results of bioassays indicated that the essential oil showed the promising fumigant and contact toxicity against L. bostrychophila (LC50 = 2.8 mg/L air and LD50 = 50.9 μg/cm2, respectively) and the notable contact effect on T. castaneum (LD50 = 10.0 μg/adult). Meanwhile, the essential oil showed comparable repellent effect on T. castaneum at all testing concentrations. Bornyl acetate and camphene also exhibited strong fumigant and contact toxicity against both species of pests (LC50 = 1.1, 10.1 mg/L air and LD50 = 32.9, 701.3 μg/cm2 for L. bostrychophila; > 126.3, 4.1 mg/L air, and 66.0, 21.6 μg/adult for T. castaneum). Bornyl acetate and camphene showed moderate repellent effect on T. castaneum and conversely showed attractant effect on L. bostrychophila. This work highlights the insecticidal potential of V. officinalis, which has been noted as a traditional medicinal plant.

Five undescribed diterpenoid alkaloids tanguticulines A-E and two undescribed amide compounds 5-methoxy-N-Salicylanthranilic acid methyl ester and 3, 5-dimethoxy-4- hydroxycinnamamide-4-O-β-D-glucopyranoside, were isolated from the whole plant of Aconitum tanguticum (Maxim.) Stapf. Their structures were assigned by detailed analysis of MS and NMR spectroscopic data. Compounds 1 and 5 were evaluated for their antivirus activities against influenza a (H1N1) virus in vitro. Both of them showed obvious inhibitory effect on the cytopathic changes induced by H1N1, with IC50 values of 2.9 μg mL−1 and 2.4 μg mL−1, respectively.

The aim of this research was to determine the chemical constituents and toxicity of the oil derived from Alpinia katsumadai seeds against Tribolium castaneum, Liposcelis bostrychophila and Lasioder...

In this work, the essential oils (EO) were extracted from seven typical Chinese herbs, and their repellent and contact toxicities against Tribolium castaneum adults (red flour beetles) were evaluated. The experimental results showed that the above EOs presented the various levels of repellent and contact toxicities. The EOs extracted from A. lancea and A argyi of the Compositae (Asteraceae) family presented obvious repellent effects (Repellency Percentage > 90% at 3.15 nL/cm2 after 4 h exposure) and strong contact toxicity with LD50 values of 5.78 and 3.09 μg/adult respectively. Based on literature researches and screening results, the EO from A. lancea was analyzed by GC-MS and chosen for further identification of bioactive components. Altogether 59 chemical components were identified and 17 of them were recognized as sesquiterpene compounds, accounting for 57.8% of the total weight of the EO. From the identified sesquiterpenes, three individual compounds (β-eudesmol, hinesol, valencene) were selected for the laboratory bioassays of the toxicity against red flour beetles. It was found that all the three compounds expressed some repellent effects. Although β-eudesmol (31.2%) and hinesol (5.1%) were identified as main constituents and had been considered to be symbolic characteristics of high medicinal value, valencene (0.3%) showed strong repellent property which could be comparable to that of DEET (N, N‑diethyl‑3‑methylbenzamide), a powerful commercial pesticides, and it had best toxicity with LD50 values of 3.25 (μg/adult) in the contact test. This work may provide toxicity evidence of seven common herbs against red flour beetles, add the information for the development and comprehensive utilization of A. lancea, and will contribute to the application of grain preservation.

One new sesquiterpene (α-iso-cubebenol acetate, 8), together with 9 known compounds (1-7, 9, 10) were isolated from the stems of Schisandra chinensis (Turcz.) Baill. by repeated silica gel column c...

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

Objectives: To evaluate the prognostic significance of Adult Comorbidity Evaluation-27 (ACE-27) for elderly patients (age ≥70 years) with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with Intensity-Modulated Radiotherapy (IMRT), with or without chemotherapy. Methods: 206 elderly patients with locoregionally advanced NPC treated from December 2006 to December 2016 were involved into analysis as the training cohort. Besides, a separate cohort of 72 patients from the same cancer center collected between January 2003 and October 2006 served as the validation cohort. By using propensity score matching (PSM), we created a balanced cohort by matching patients who received chemoradiotherapy with patients who received IMRT alone. Treatment toxicities were calculated between CRT and RT groups using the χ2 test. The primary endpoint was cancer-specific survival (CSS). Multivariate analysis was performed to assess the relative risk for each factor by using a Cox's proportional hazards regression model. Results: The median follow-up was 39.0 months (range = 3-137 months). In the PSM cohort, patients in the CRT group achieved comparable survival compared with patients in the RT group. The 3-year CSS rate was 64.3% and 65.2%, respectively (P =0.764). In multivariate analysis, the addition of chemotherapy to IMRT was not an independent prognostic factor for CSS, whereas a high ACE-27 score was an independent risk factor. In subgroup analysis with ACE-27 score ≥ 2, the 3-year CSS rate was worse in patients from the CRT group (63.5% vs. 46.3%, P = 0.041). Conclusions: CRT is comparable to IMRT alone for elderly patients with locoregionally advanced NPC. The ACE-27 tool may help to identify high-risk subgroup for poor disease outcome and tailor individualized treatment.

The essential oil was obtained from the aerial parts of Pogostemon cablin by hydrodistillation. The chemical compounds of P. cablin essential oil were analyzed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. Eight compounds were totally identified and accounted for 92.4% of the oil. Patchoulol was the major component (51.1%), followed by phloroacetophenone (23.5%) and β-patchoulene (7.3%). The essential oil and its two major compounds patchoulol and phloroacetophenone were evaluated for their contact and repellent activities against Tribolium castaneum, Lasioderma serricorne, and Liposcelis bostrychophila. Results of bioassays indicated that the essential oil and patchoulol had great contact toxicity against three species of insects. Meanwhile, the essential oil and patchoulol showed great repellent activities against T. castaneum and L. bostrychophila but were mildly repellent to L. serricorne. Phloroacetophenone exhibited neither contact nor repellent activity against any of these target insects. This work emphasized the promising potential of P. cablin to control insect pests during storage.

The essential oil extracted from roots and rhizomes of Ligusticum jeholense Nakai et Kitagawa was investigated for its chemical composition by GC-MS analysis, and evaluated for its contact toxicity and repellency against Tribolium castaneum and Lasioderma serricorne, along with some of its individual components. The essential oil was rich in aromatics (65.34%) with low molecular weight. Major components included sedanolide (33.95%), 3-butylidenephthalide (18.76%), spathulenol (8.90%) and myristicin (6.76%). The results of bioassays indicated that the essential oil of L. jeholense and 3-butylidenephthalide possessed significant repellent activities against T. castaneum at 2 and 4 h post-exposure. Meanwhile, 3-butylidenephthalide had potent contact toxicity against L. serricorne (LD50 = 13.64 µg/adult). The minor component n-butylbenzene in the oil was highly toxic to T. castaneum (LD50 = 23.99 µg/adult) and L. serricorne (LD50 = 7.86 µg/adult) in contact assays, but failed to repel these beetles at all testing concentrations. Spathulenol and myristicin exerted good insecticidal and repellent effects on the two target insects. This work suggests that the essential oil of L. jeholense has promising potential for development as natural insecticide or repellent to control pest damage in warehouses.

6068 Background: Neoadjuvant treatment with gemcitabine plus cisplatin (GP) prior to concurrent chemoradiotherapy (CCRT) has favorable survival outcomes with acceptable toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC), 10% of whom achieved complete response (CR) after neoadjuvant treatment. Immune checkpoint blockade therapy plus GP regimen has been shown to improve the survival in recurrent or metastatic NPC. We investigated the efficacy and safety of neoadjuvant treatment with GP plus tislelizumab, an anti-PD-1 monoclonal antibody, in previously untreated LANPC. Methods: In this phase II, single-armed Simon two-stage study, eligible patients are of age 18-70, with adequate haematological, renal, and hepatic function, diagnosed with staged III-IVa（AJCC 8th） non-keratinizing LANPC. Enrolled patients received intravenous gemcitabine (1000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and tislelizumab (200mg) on day 1 every 3 weeks for 3 cycles followed by standard CCRT. The primary endpoint was CR rate after neoadjuvant treatment, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. The secondary endpoints included pathology complete response (pCR) rate, 2-year progress-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRRFS), distant metastasis-free survival (DMFS), and toxicity. This study is registered with ClinicalTrials.gov, NCT04833257, all enrolled patients have finished their treatment and the follow-up is ongoing. Results: From April 14th 2021 to August 5th, 2021, a total of 63 patients (median age 46y, 74.6% male) were enrolled at Sun Yat-sen University Cancer Center. As of January 31st, 2022, the median follow-up is 7.37 months, no patients had disease progression. The CR rate after neoadjuvant treatment was 41.3% (95% CI, 28.8% to 53.8%). The ORR and pCR rate were 88.9% (95% CI, 80.9% to 96.9%) and 75.8% (95% CI, 64.8% to 86.8%), respectively. The incidence of acute treatment-related AEs (trAEs) and immune-related adverse events (irAEs) of grade 3 or 4 was 69.8% and 3.2%, respectively. All of irAEs for grade 3 or 4 were hepatotoxicity and skin rash. Long-term efficacy is awaited. Conclusions: Neoadjuvant treatment with GP plus tislelizumab achieved impressive CR rate and pCR rate with manageable toxicities. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: NCT04833257.

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

BACKGROUND: Nutritional status is a key factor influencing the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) has been used to predict mortality risk and long-term outcomes. In this study, we aimed to evaluate the predictive value of pretreatment GNRI in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1,065 patients with biopsy-proven non-disseminated nasopharyngeal carcinoma were included. Based on a cutoff value of pretreatment GNRI, patients were divided into two groups (low ≤107.7 and high >107.7). Combining GNRI and baseline Epstein-Barr virus (EBV) DNA, all patients were further stratified into three risk groups, namely, high-risk (high EBV DNA and low GNRI), low-risk (low EBV DNA and high GNRI), and medium-risk (except the above) groups. Multivariate analyses were performed using the Cox proportional hazards model to assess the predictive value of the GNRI. RESULTS: Among the 1,065 patients, 527 (49.5%) and 538 (50.5%) were divided into low and high GNRI groups, respectively. Within a median follow-up of 83 months, patients with a high GNRI score exhibited significantly higher overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) compared to those with low GNRI scores (P