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Introduction: Whether supraclavicular lymph node (SCLN) metastasis in patients with oesophageal cancer belongs to regional disease is controversial, leading to heterogeneity in clinical treatment decisions. This study aimed to determine the optimal treatment for lower thoracic oesophageal cancer (LTOC) with SCLN metastasis. Methods: Patients with LTOC registered in the Surveillance, Epidemiology, and End Results database during 2010–2015 were identified. Selected patients were grouped according to disease spread as those with locoregional disease, with SCLN metastasis or with distant metastasis, as well as according to treatment modality (neoadjuvant chemoradiotherapy followed by surgery (nCRT+S group), upfront surgery ± adjuvant therapy (upfront S group) and definitive chemoradiotherapy (dCRT group)). The Cox regression analysis and inverse probability of treatment weighting (IPTW) were used to identify the optimal treatment modality for different groups. Results: Of 11,767 LTOC patients identified from the database, the 5‐year overall survival (OS) rates for patients with the locoregional disease (n = 7,541), SCLN metastasis (n = 120) and distant metastasis (n = 4,106) were 28.3%, 10.0% and 3.0%, respectively (P < 0.001). Among patients with SCLN metastasis, median OS in the nCRT+S, upfront S and dCRT groups were 25, 14 and 8 months, respectively (P < 0.001). After IPTW, the nCRT+S group was still associated with better median OS compared with other groups. The multivariate analysis identified treatment modality as an independent prognostic factor for OS. Conclusions: Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment modality for LTOC with SCLN metastasis. The findings of this study need to be validated in large prospective studies. [ABSTRACT FROM AUTHOR]

Background and objective The presence of epidermal growth factor receptor (EGFR) mutations is predictive of a better response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and initial chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC). The aim of this study is to analyze the association between the EGFR mutations and the outcome of combined chemoradiotherapy in stage III non-squamous NSCLC. Methods Patients with stage III non-squamous NSCLC whose EGFR mutation status had been identified were retrospectively analyzed. The response of 87 patients to combined chemoradiotherapy, the two-year survival rate, and the response of 128 patients to initial chemotherapy were evaluated. Results The response rate to combined chemoradiotherapy was 84.6% (33/39) in EGFR mutation-positive patients, significantly higher than the 56.3% (27/48) response rate in EGFR mutation- negative patients (P=0.004). Two-year survival rates were 53.8% and 50% in EGFR mutation-positive and mutation-negative patients, respectively. There was no significant difference in the overall survival for both patient groups. The overall response rate to initial chemotherapy was 34.5% (19/55) in EGFR mutation-positive patients, compared with the 21.9% (16/73) response rate in EGFR mutation-negative patients. Conclusion EGFR mutation-positive status can predict better response to combined chemoradiotherapy, but is not associated with overall survival in patients with stage III non-squamous NSCLC. [ABSTRACT FROM AUTHOR]

Background and objective The presence of epidermal growth factor receptor (EGFR) mutations is predictive of a better response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and initial chemotherapy in advanced non-squamous non-small cell lung cancer (NSCLC). The aim of this study is to analyze the association between the EGFR mutations and the outcome of combined chemoradiotherapy in stage III non-squamous NSCLC. Methods Patients with stage III non-squamous NSCLC whose EGFR mutation status had been identified were retrospectively analyzed. The response of 87 patients to combined chemoradiotherapy, the two-year survival rate, and the response of 128 patients to initial chemotherapy were evaluated. Results The response rate to combined chemoradiotherapy was 84.6% (33/39) in EGFR mutation-positive patients, significantly higher than the 56.3% (27/48) response rate in EGFR mutation- negative patients (P=0.004). Two-year survival rates were 53.8% and 50% in EGFR mutation-positive and mutation-negative patients, respectively. There was no significant difference in the overall survival for both patient groups. The overall response rate to initial chemotherapy was 34.5% (19/55) in EGFR mutation-positive patients, compared with the 21.9% (16/73) response rate in EGFR mutation-negative patients. Conclusion EGFR mutation-positive status can predict better response to combined chemoradiotherapy, but is not associated with overall survival in patients with stage III non-squamous NSCLC. [ABSTRACT FROM AUTHOR]

Background: For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC., Methods: This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18-70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0-42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003., Findings: From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58-68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33-56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2-62·0]) than in the 45 Gy group (39·5 months [27·5-51·4]; hazard ratio 0·55 [95% CI 0·37-0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3-4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit., Interpretation: Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18-70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option., Funding: Chinese Society of Clinical Oncology-Linghang Cancer Research, the Wu Jieping Medical Foundation, and Clinical Research Fund For Distinguished Young Scholars of Peking University Cancer Hospital and Beijing Municipal Administration of Hospitals Incubating Program., 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.)

To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 Gy RBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70Gy RBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The D mean of the total lung was 7.65 ± 2.47 Gy RBE , 14.78 ± 2.75 Gy RBE , and 21.64 ± 4.07 Gy RBE for VMAT and 3.69 ± 1.04 Gy RBE (p < 0.001), 7.13 ± 1.41 Gy RBE (p < 0.001), and 10.69 ± 1.81 Gy RBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT., Competing Interests: Conflict of Interest X.D. received industry research funding from IBA and Elekta outside the work presented here. X.D. received honoraria from IBA and Elekta speaker bureau outside the work presented here. X.D. holds a patent on particle arc therapy, and it has been licensed to IBA. All authors contributed to the article and approved the submitted version. The authors declared no potential conflicts of interest with respect to the research, author- ship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China., Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date., Results: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full., Conclusions: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Background: Phlegm-dampness constitution is a traditional Chinese medicine constitution typically associated with essential hypertension. Previous studies have demonstrated that auricular acupuncture effectively decreases blood pressure and adjusts the constitution. However, the mechanism underlying auricular acupuncture's effect is poorly understood., Methods: A non-blinded, randomized controlled trial will be undertaken between September 2022 and May 2023. Eighty essential hypertensive patients with a phlegm-dampness constitution will be randomly allocated to one of two groups. The intervention group will receive eight weeks of auricular acupuncture and regular use of antihypertensive drugs, while the control group will only receive antihypertensive drugs. The primary outcome will be any mean differences in office systolic blood pressure. The secondary outcomes investigations will include proteins of the renin-angiotensin system, office blood pressure of different genotypes, and phlegm-dampness constitution scores., Discussion: By demonstrating how auricular acupuncture affects the renin-angiotensin system, this research will offer significant new information on the mechanism underlying the action of auricular acupuncture in hypertension. Moreover, the results will provide crucial clinical information on the associations between renin-angiotensin system gene polymorphisms and the antihypertensive effects of auricular acupuncture., Trial Registration: Registered at the chictr.org., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Most of the currently available knowledge about protein structure and function has been obtained from laboratory experiments. As a complement to this classical knowledge discovery activity, bioinformatics-assisted sequence analysis, which relies primarily on biological data manipulation, is becoming an indispensable option for the modern discovery of new knowledge, especially when large amounts of protein-encoding sequences can be easily identified from the annotation of highthroughput genomic data. Here, we review the advances in bioinformatics-assisted protein sequence analysis to highlight how bioinformatics analysis will aid in understanding protein structure and function. We first discuss the analyses with individual protein sequences as input, from which some basic parameters of proteins (e.g., amino acid composition, MW and PTM) can be predicted. In addition to these basic parameters that can be directly predicted by analyzing a protein sequence alone, many predictions are based on principles drawn from knowledge of many well-studied proteins, with multiple sequence comparisons as input. Identification of conserved sites by comparing multiple homologous sequences, prediction of the folding, structure or function of uncharacterized proteins, construction of phylogenies of related sequences, analysis of the contribution of conserved related sites to protein function by SCA or DCA, elucidation of the significance of codon usage, and extraction of functional units from protein sequences and coding spaces belong to this category. We then discuss the revolutionary invention of the "QTY code" that can be applied to convert membrane proteins into water- soluble proteins but at the cost of marginal introduced structural and functional changes. As machine learning has been done in other scientific fields, machine learning has profoundly impacted protein sequence analysis. In summary, we have highlighted the relevance of the bioinformatics-assisted analysis for protein research as a valuable guide for laboratory experiments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is radiotherapy concurrent with chemotherapy, but the survival was not satisfied. With the development of intensity modulated radiotherapy, simultaneous integrated boost technique (SIB) becomes the research direction of locally advanced NSCLC. The aim of this study is to investigate the efficacy and safety of SIB intensity modulated radiotherapy technique for locally advanced NSCLC., Methods: We retrospectively reviewed the clinical data of locally advanced NSCLC who were treated with radiotherapy by SIB technique in Peking University Cancer Hospital from June 2015 to December 2018. Kaplan-Meier method was used for analysis., Results: Ninty-three patients were included in the analysis. After a median follow-up of 34.23 months, 3-year overall survival (OS), progression-free survival (PFS), local-recurrence free survival (LRFS) and metastasis free survival (MFS) rates were 53.0%, 37.0%, 50.5% and 50.5%, respectively. The incidence of grade ≥3 esophagitis was 5.4%. There were 2 (2.2%) patients experiencing grade ≥3 radiation-related pneumonia., Conclusions: Radiation with SIB intensity modulated radiotherapy technique is effective and safe for patients with locally advanced NSCLC.

Advances in the field of genome engineering demand the development of efficient non-viral transfection agents capable of delivering multiple distinct nucleic acids efficiently to cells (co-transfection). However, current delivery methods result in lower co-transfection efficiency than single plasmid transfections, and the efficiency decreases further with increasing numbers of plasmids. The development of a high-throughput methodology is required for the validation of co-transfection platforms to facilitate independent tracking of not only the multiple DNA plasmids during transfection but also the localisation of transfection agents. This is pivotal to determine the bottlenecks in achieving high transfection efficiencies at various stages of the cell internalisation and plasmid expression process. Herein we demonstrate that this can be achieved using a facile methodology in which quantum dots (QDs) are used to label two different plasmid DNA assemblies that are delivered to cells simultaneously using a dendronised polymer system. Multispectral confocal imaging can be used to separate signals from each polyplex as well as the expressed fluorescent reporter proteins to determine whether co-transfection difficulties result from poor internalisation or the inability of DNA to escape from polyplexes. The results demonstrate the utility of this facile approach to label polyplexes without interfering with gene expression, and enable high-throughput screening of transfection reagents for achieving optimal co-transfection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Association between the epithelial growth factor receptor (EGFR) mutation and the expression of breast cancer 1 (BRCA1) and receptor-associated protein 80 (RAP80) in non-small cell lung cancer (NSCLC) was studied. From September 2014 to September 2016, 51 patients with NSCLC who were hospitalized in Department of Thoracic Surgery in The Affiliated Jiangyin Hospital of Southeast University Medical College and underwent biopsy or operation were selected. The pathological changes of lung tissue were detected by hematoxylin and eosin histopathological staining. The fluorescent expression of BRCA1 and RAP80 protein in the two groups was determined by immunofluorescence staining. Reverse transcriptase polymerase chain reaction method and western blot analysis were used to detect BRCA1 and RAP80 mRNA and protein expression. Then the EGFR gene mutation was detected and analyzed. The results show that non-small cell lung cancer has an association with smoking. Compared with the control, the lung tissue structure of the NSCLC group was damaged. The protein fluorescence expression of BRCA1 and RAP80 in non-small cell lung cancer group was significantly increased. The expression of BRCA1 and RAP80 mRNA and protein in NSCLC group was significantly increased. The difference in expression of BRCA1 and RAP80 in the control and the non-small cell lung cancer group was statistically significant (P<0.05). EGFR gene mutations detected 14 of the 51 patients with genetic mutations. Non-small cell lung cancer and smoking have certain relevance, and BRCA1 and RAP80 expression in the development and progression of NSCLC has a close relationship. EGFR mutation in non-small cell lung cancer significantly related to the mutation of EGFR and BRCA1 and RAP80 gene expression plays an important role in the diagnosis and treatment of NSCLC.

Coriolus versicolor (CV) contains high levels of bioactive compounds, including the glucan (1→6)-α-D-glucopyranosyl. However, there is a lack of data regarding the potential effect of this CV glucan (CVG) on the stimulation of cytokine production. The present study evaluated the effect of CVG on the stimulation of cytokine production in sarcoma-180-bearing mice. Mice were treated with three doses of CVG (40, 100 or 200 mg/kg body weight) for nine days, after which serum levels of cytokines, namely interleukin (IL)-2, -4, -6, -10, -17A and interferon (IFN)-α and -γ, were investigated by ELISA. CVG significantly promoted the secretion of IL-2, -4, -6, -10, -17A and IFN-α and -γ at the doses of 100 (P<0.05) and 200 (P<0.01) mg/kg, but not at 40 mg/kg (P>0.05), when compared with cyclophosphamide treatment, as a positive control. Additionally, cytokine production associated with T helper (Th)2 and Th17 cells was enhanced compared with that of Th1 cytokines, and the immunomodulatory function of CVG appeared to be IL-10-dependent. These results demonstrate that CVG may stimulate the production of cytokines and serve as a Th2/IL-10-dependent immunomodulator, and thus has promise in supporting cancer therapies.

Background: Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. The study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer., Methods: Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by "classical" 3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV) was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. The planning target volume (PTV) received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. The primary endpoints were acute toxicities. The secondary endpoints included overall survival (OS), progression-free survival (PFS) and loco-regional failure-free survival (LRFFS) at 1-year of follow-up., Results: Twenty men and six women were included. The median age was 52 (30-68) months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months), 1-year OS, PFS and LRFFS were 89.0%, 51.0% and 85.0%, respectively., Conclusions: Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique.

Background: Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. This study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer., Methods: Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. The patients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). The primary endpoints were hematologic toxicities during treatment. The secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity., Results: From January 2013 to August 2016, 20 patients were enrolled in this study. The median age was 49.5 (30-68). After the first 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neutropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. The MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had ≥Grade 3 neutropenia and 1 patients had ≥Grade 3 acute esophagitis in Arm 1. 10 patients had ≥Grade 3 neutropenia and no patient had ≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91% and 61%, respectively., Conclusions: The MTD of RT with concurrent chemotherapy of EP regimen for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1).
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