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Background The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients.

Ru-Rong Peng,1 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Song Qu,1 Xiao-Dong Zhu1,2 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Oncology, Affiliated Wu-Ming Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 He-di Road, Nanning, 530021, People’s Republic of ChinaTel +86 15778028340Email zhuxdonggxmu@126.comPurpose: The prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC.Patients and Methods: This was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan–Meier methods.Results: Multivariate Cox analysis resulted that age, plasma Epstein–Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706– 0.738) and 0.747 (95% CI: 0.717– 0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680– 0.713) and 0.690 (95% CI: 0.660– 0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations.Conclusion: LAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.Keywords: intensity-modulated radiotherapy, nasopharyngeal carcinoma, lactate dehydrogenase to albumin ratio, platelet-to-lymphocyte ratio, tumor–node–metastasis staging system

AIMS This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

Purpose: Bevacizumab is considered a promising therapy for brain necrosis after radiotherapy, while some patients fail to derive benefit or even worsen. Hence, we developed and validated a radiomics model for predicting the response to bevacizumab in patients with brain necrosis after radiotherapy. Experimental Design: A total of 149 patients (with 194 brain lesions; 101, 51, and 42 in the training, internal, and external validation sets, respectively) receiving bevacizumab were enrolled. In total, 1,301 radiomic features were extracted from the pretreatment MRI images of each lesion. In the training set, a radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm. Multivariable logistic regression analysis was then used to develop a radiomics model incorporated in the radiomics signature and independent clinical predictors. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness with internal and external validation. Results: The radiomics signature consisted of 18 selected features and showed good discrimination performance. The model, which integrates the radiomics signature, the interval between radiotherapy and diagnosis of brain necrosis, and the interval between diagnosis of brain necrosis and treatment with bevacizumab, showed favorable calibration and discrimination in the training set (AUC 0.916). These findings were confirmed in the validation sets (AUC 0.912 and 0.827, respectively). Decision curve analysis confirmed the clinical utility of the model. Conclusions: The presented radiomics model, available as an online calculator, can serve as a user-friendly tool for individualized prediction of the response to bevacizumab in patients with brain necrosis after radiotherapy.

Purpose Improved antitumor responses have been observed in patients after combination radiation therapy (RT) and immune checkpoint blockade (ICB). Whether these clinical responses are linked to the host systemic immune system has not been elucidated. Methods and Materials In this single-institution prospective observational study, peripheral blood was longitudinally collected from 10 patients with metastatic disease who had responded to anti-PD-1/anti-PD-L1 ICB and received RT (8-50 Gy in 1-5 fractions) upon disease progression at the following timepoints: baseline (pre-RT), 1 to 2 weeks post-RT, and post-ICB (cycle 1) on reintroduction post-RT. To thoroughly characterize the interaction between combined RT-ICB and the host immune system, we performed high-dimensional, mass cytometry–based immunophenotyping of circulating lymphocytes using a 40-marker panel addressing lineage, differentiation, activation, trafficking, cytotoxicity, and costimulatory and inhibitory functions. Phenotypic expression of circulating lymphocytes was compared across patients and time points and correlated with post-RT tumor responses. Results Foremost, we demonstrated excellent posttreatment clinical responses, including 4 local responses with >50% reduction in radiated tumor size, 1 out-of-field response, and 4 patients who resumed ICB for >1 year. Baseline and post-RT immune states were highly heterogeneous among patients. Despite this interindividual heterogeneity in baseline immune states, we observed a systemic immune reaction to RT-ICB common across patients, histology, and radiation sites; a subset of pre-existing Ki-67+ CD8+ T cells were increased post-RT and further expanded upon reintroduction of ICB post-RT (2.3-fold increase, P = .02). Importantly, RT did not alter the phenotypic profile of these Ki-67+ CD8+ T cells, which was characterized by a distinct activated and differentiated effector phenotype. Conclusions Collectively, these findings point toward a sustained reinvigoration of host antitumor immunity after RT-ICB and suggest an expansion in activated Ki-67+ CD8+ T cells as a possible demonstration of this synergy, thereby providing new insights that may support the development of optimal sequencing strategies.

Surgical site infection (SSI) in colorectal cancer (CRC) has been a serious health care problem due to the delay of postoperative recovery. Our present study aimed to explore the risk factors for SSI in CRC patients. We have systematically searched these databases: PubMed, Cochrane Library, and EMBASE as of March 2020 for studies on risk factors associated with SSI. Two investigators independently conducted the quality assessment and data extraction. Related risk factors in the studies were recorded, and a meta-analysis was performed. The search initially provided 2262 hits, 1913 studies were screened by two independent investigators. Finally, 15 studies were identified to be relevant for this meta-analysis. In total, 25 risk factors were eligible. Our meta-analysis indicated that eight factors (obesity, male sex, diabetes mellitus, ASA score ≥ 3, stoma creation, intraoperative complications, perioperative blood transfusion, and operation time ≥ 180 min) were significant risk factors for SSI, and one factor (laparoscopic procedure) was protective for SSI. Effective interventions targeting the above factors may reduce the risk of developing postoperative SSI in CRC patients and improve the clinical outcome of patients. Further prospective studies are needed to confirm these findings.

Background Biliary hamartomas (BH) are a rare benign disease caused by malformation of the intrahepatic bile ducts. BH are occasionally diagnosed, but often lack obvious clinical symptoms. They are usually diagnosed by biopsy and imaging tests in clinical practice. Few studies have reported the association of BH with portal hypertension. Case summary A 40-year-old man was repeatedly admitted to our hospital due to hematochezia. The source of bleeding was considered to be gastroesophageal varices and portal hypertensive gastropathy by endoscopy. He had no history of hepatitis virus infection, alcohol abuse, drug-induced liver injury, or autoimmune liver disease. He underwent magnetic resonance imaging, which showed rounded, irregular, low-signal-T1 and high-signal-T2 lesions diffusely distributed on the liver, that were not communicated with the biliary system on magnetic resonance cholangiopancreatography. According to the imaging examination, the patient was considered to have a diagnosis of BH with portal hypertension. Conclusion Based on the present case report, BH may be a potential etiology of portal hypertension.

Background The aim of this study was to develop a prognostic nomogram for early stage extranodal natural killer/T-cell lymphoma, nasal type (ENKL) treated with high-dose radiotherapy (RT). Patients and Methods A total of 81 patients at 2 cancer centers with stage I to IIE ENKL who received chemotherapy (CT) and high-dose RT were retrospectively analyzed. The development of the nomogram was on the basis of the Cox proportional hazards model. We implemented the concordance index (C-index) and performed a calibration curve to determine its predictive and discriminatory capacity and compared our nomogram with the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI). Results The nomogram included 4 important variables and used a multivariate analysis: lactate dehydrogenase, primary tumor invasion, tumor response, and CT regimen. The 5-year OS rate and progression-free survival were 64.7% and 57.5%, respectively for the entire group. The C-index of the nomogram for overall survival (OS) prediction was 0.87, and it was superior to the predictive power of the IPI and KPI. The calibration curve showed that the nomogram accurately predicted the 5-year OS. Conclusion The proposed nomogram could provide an individualized risk estimate of the OS for early stage ENKL treated with CT and high-dose RT.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged

Purpose To construct a prognostic index (PI) for overall survival (OS) to stratify nasopharyngeal carcinoma (NPC) into high-risk and low-risk groups. We also applied the model to investigate the role of the addition of adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) regimens for the treatment of NPC. Methods A prognostic model was established based on a retrospective study of 362 patients from January 2008 to June 2011. The discriminative and calibration abilities of the model were evaluated by Harrell's concordance index (C-index), and calibration curves. Bootstrapping was used to perform for internal validation. External validation was conducted using 324 patients diagnosed with NPC from July 2011 to December 2012 at the same institution. Survival analyses were performed between CCRT-AC and CCRT alone groups for the high-risk and low-risk groups. Results The primary PI comprised covariates that were associated with OS in the training cohort, including T stage, N stage, age, and plasma alkaline phosphatase (ALP). Internal and external validation showed that the discrimination of the PI for OS was significantly better than that of the 8th edition AJCC staging system. Discretization by using a fixed PI score cut-off of 407.96 determined from the training data set yielded high- and low-risk subgroups with distinct OS outcomes in the validation cohort. Adjuvant chemotherapy improved OS in high-risk patients (HR 0.620, 95% CI 0.408 to 0.941; P = 0.023) but increased the risk of distant metastasis (HR, 4.222, 95% CI, 0.959 to 18.585; P = 0.038) in low-risk patients. Conclusion The proposed prognostic model achieved good prediction and calibration of OS for patients with NPC. The addition of adjuvant chemotherapy might be a double-edged sword, bringing survival benefit to high-risk patients but greater risk of distant metastasis to low-risk patients.

ObjectiveThe present study aimed to evaluate the role of integrating the pretreatment neutrophil-to-lymphocyte ratio (NLR) into the eighth edition of the AJCC staging system for nasopharynx cancer in an endemic region.MethodsBetween May 2007 and December 2012, a total of 713 cases with NPC were retrospectively analyzed. The separation ability in terms of overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS) was evaluated. The discriminatory ability was assessed using Harrell’s concordance index (c-index). Recursive partitioning analysis (RPA) was conducted and incorporated with pretreatment NLR.ResultsWhen integrated with NLR, the separate and discriminatory abilities for N classifications were improved in terms of OS and DMFS, but not for T categories. By using Recursive partitioning analysis, five subgroups were generated. Compared with the overall stage, the integration of NLR could not enhance the separate and discriminatory abilities. However, patients in the RPA 4 group gained significant benefits in terms of OS (HR 0.390 (95%CI 0.212-0.716), P = 0.002) and FFS (HR 0.548 (95%CI 0.314-0.958), P = 0.032) from the additional adjuvant chemotherapy after concurrent chemoradiotherapy.ConclusionThe integration of NLR into the 8th edition of the AJCC staging system could enhance the separation and discriminatory abilities for N classifications, but not for T categories. In addition, patients in the RPA 4 group could benefit from the addition of adjuvant chemotherapy to concurrent chemoradiotherapy.

Chang Yan,1 De-Song Shen,1 Xiao-Bo Chen,2 Dan-Ke SU,3 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Xia Liang,1 Hai Liao,3 Xiao-Dong Zhu1,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2School of First Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 4Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530100, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning City, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 1466Email zhuxdonggxmu@126.comHai LiaoDepartment of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 4950Email 42442427@qq.comPurpose: We aimed to construct of a nomogram to predict progression-free survival (PFS) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with risk stratification using computed tomography (CT) radiomics features and clinical factors.Patients and Methods: A total of 311 patients diagnosed with LA-NPC (stage III–IVa) at our hospital between 2010 and 2014 were included. The region of interest (ROI) of the primary nasopharyngeal mass was manually outlined. Independent sample t-test and LASSO-logistic regression were used for selecting the most predictive radiomics features of PFS, and to generate a radiomics signature. A nomogram was built with clinical factors and radiomics features, and the risk stratification model was tested accordingly.Results: In total, 20 radiomics features most associated with prognosis were selected. The radiomics nomogram, which integrated the radiomics signature and significant clinical factors, showed excellent performance in predicting PFS, with C-index of 0.873 (95% CI: 0.803∼ 0.943), which was better than that of the clinical nomogram (C-index, 0.729, 95% CI: 0.620∼ 0.838) as well as of the TNM staging system (C-index, 0.689, 95% CI: 0.592– 0.787) in validation cohort. The calibration curves and the decision curve analysis (DCA) plot obtained suggested satisfying accuracy and clinical utility of the model. The risk stratification tool was able to predict differences in prognosis of patients in different risk categories (p< 0.001).Conclusion: CT-based radiomics features, an in particular, radiomics nomograms, have the potential to become an accurate and reliable tool for assisting with prognosis prediction of LA-NPC.Keywords: computed tomography, locoregionally advanced nasopharyngeal carcinoma, radiomics, nomogram

Background and aim Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China, Southeast Asia. Radiotherapy is the main treatment for NPC. Still, about 20% of patients with NPC have a recurrence. No effective serum biomarkers are available for recurrent nasopharyngeal carcinoma (rNPC) to date. This study aimed to explore whether amyloid beta (A4) precursor protein (APP) might serve as a valuable diagnostic and prognostic biomarker for patients with rNPC. Methods In a previous study, a tandem mass tag-based proteomic test was performed, which screened 59 differentially expressed proteins (DEPs) between nonrecurrent nasopharyngeal carcinoma (nrNPC) and rNPC. In this study, a protein-protein interaction was conducted to screen the key proteins among the 59 DEPs. APP was validated and evaluated by enzyme-linked immunosorbent assay in 70 serum samples [recurrence (n = 35) and no-recurrence (n = 35)]. Also, the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of APP. Results The area under the ROC curve was 0.666 (95% CI: 0.514-0.818, P = 0.044). The best cutoff point of the relative expression levels for APP was 1.23 (concentration = 16.95 ng/mL), at which the sensitivity was 55.2% and the specificity was 90.9%. Conclusion The findings indicated that APP might be a valuable diagnostic and prognostic biomarker for patients with rNPC.

Background Epidermal growth factor receptor (EGFR) overexpression is characteristic in head and neck cancers and is associated with tumour regrowth following photodynamic therapy (PDT). Purpose We investigated vandetanib, which selectively blocks EGFR and vascular endothelial growth factor receptor-2 (VEGFR-2), to enhance the efficacy of PDT. Methods We assessed the in vitro therapeutic efficacy of: 1) vandetanib; 2) PDT with the photosensitizer Chlorin e6 (Fotolon®); and 3) combined PDT + vadetanib treatment in CAL-27 oral squamous cell carcinoma (OSCC) cell line by cell viability, γH2AX foci immunostaining, cell cycle arrest and western blot. We also performed in vivo tumour regression study and immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) regressed and regrown tumour tissues. Results First, we observed significantly higher cytotoxicity and residual DNA damage in vandetanib + PDT-treated CAL-27 OSCC cells than tumour cells treated with PDT alone. This is due to impaired DNA DSB repair caused by downregulation of EGFR-mediated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activation. Next, combined vandetanib and PDT resulted in significant tumour growth delay in vivo that is linked to reduction of PDT-induced EGFR phosphorylation and cellular proliferation, along with loss of tumour vasculature. In particular, we observed significant revascularisation of the microenvironment that is associated with upregulated ERK1/2 phosphorylation in regrown tumours post-vandetanib + PDT, thereby corroborating the importance of microenvironmental modification for the observed drug-PDT synergistic interaction. Conclusion Taken together, our data suggests that vandetanib enhances the efficacy of PDT through both direct and indirect effects on the cellular DNA repair machinery and tumour microenvironment, respectively.

Cancer research has advanced throughout the years with respect to the personalization of the treatments and to targeting cancer-related molecular signatures on different organs. Still, the adverse events of the treatments such as radiotherapy are of high concern as they may increase the mortality rate due to their severity. With the improved efficiency of cancer treatments, patient survival has been increasing. Consequently, the number of patients with adverse effects from radiotherapy is also expected to increase in the forthcoming years. Therefore, approaches for personalized treatments include the elimination of adverse events and decreasing the toxicity in healthy tissues while increasing the efficiency of cancer cytotoxicity. In this context, this paper aims to discuss the recent advances in the field of thorax irradiation therapy and its related toxicities leading to radiation pneumonitis in cancer patients. Molecular mechanisms involved in the radiation-induced lung injury and approaches used to overcome this lung injury are discussed. The discourse covers approaches such as therapeutic administration of natural products, current and prospective radioprotective drugs, and applications of mesenchymal stem cells for radiation-induced lung injury.

Jin Zhao,1,* Zhong Guo,1,* Qiang Wang,2 Tianbin Si,3 Shuyan Pei,1 Hongmei Qu,1 Lina Shang,1 Yuqing Yang,1 Lili Wang11Department of Medical Function, Medical College of Northwest Minzu University, Lanzhou 730030, People’s Republic of China; 2Department of Pathology, No. 1 Hospital of Longnan City, Longnan 746000, People’s Republic of China; 3Department of Gynecology and Oncology, Gansu Provincial Cancer Hospital, Lanzhou 730050, People’s Republic of China*These authors contributed equally to this workObjectives: This study was to assess whether human papillomavirus (HPV) resulting in genetic instability is one reason for the high incidence and mortality of cervical cancer in Longnan.Methods: Between 2012 and 2016, a total of 346 samples from Longnan were collected and divided into four groups: cervicitis group (n=57), cervical intraepithelial neoplasia I group (CIN I, n=63), CIN II/III group (n=79) and invasive squamous cell carcinoma group (SCC, n=147). HPV E6/E7 mRNA was detected by Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA). The markers of DNA damage response (DDR) – ataxia telangiectasia mutated (ATM) pSer1981, H2AX pSer139 (γH2AX), Chk2 pThr68 and P53 – were analyzed by immunohistochemistry.Results: The activation of ATM, γH2AX, Chk2 and P53 was increased with increasing severity of cervical lesion. A significant difference of ATM expression in simple infection was also shown accompanied by the cervical lesion. The expression of γH2AX between HPV16+ and HPV16- specimens, γH2AX and P53 between HPV58+ and HPV58- groups had statistical significance. The expression and copy number of HPV E6/7 mRNA increases with the cervical lesion severity. A significant difference was shown for P53 expression between HPV E6/7 mRNA+ and mRNA- specimens. A close correlation with CHK2 expression for HPV E6/7 mRNA+ and HPV16 E6/7 mRNA+ specimens and γH2AX and CHK2 expression for SCC specimens was shown between low and high viral load groups.Conclusions: DDR, HPV genotypes and HPV E6/E7 oncogene expression correlated with the level of dysplasia of cervical lesions. HPV infection resulted in genetic instability may be one reason for the high incidence and mortality in Longnan.Keywords: human papillomaviruses, E6/E7 oncogenes, DNA damage response, cervical cancer

Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied. Methods We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed. Results Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P

Using a unique and hand-collected dataset, we investigate the impact of the risk factors disclosed in the prospectuses on the initial returns for ChiNext IPOs. After controlling for the market-, firm- and offer-specific characteristics, we identify several significant risk factors that include “policy changes on taxation or government subsidy”, “higher depreciation and/or amortization due to proposed capital expenditures”, “ongoing litigation or lawsuit”, and “piracy or trademark infringement”. Concerns for ongoing litigation risk seem to be most important as the risk affects both the opening and closing price returns positively and significantly, indicating risk compensation through deep underpricing. The other three risk factors only affect the closing price return. Similar to the impact from the ongoing litigation or lawsuit risk, the trademark infringement risk affects the closing price return positively. On the other hand, the risks associated with possible policy changes on taxation or government subsidy and higher depreciation and/or amortization due to proposed capital expenditures have negative impacts on the closing return. In line with our conjecture of a short-term equilibrium, none of the risk factors disclosed in the prospectuses are found significant for the 21st trading day (monthly) initial return.

Fang Su*, Kaihua Chen*, Zhongguo Liang, Song Qu, Ling Li, Long Chen, Yunli Yang, Chunhua Wu, Xia Liang, Xiaodong ZhuDepartment of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China*These authors contributed equally to this workObjective: Even in early-stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult tumor location. To compare the safety and efficacy of different fractions on the survival of patients with tumors smaller than 10 cm in size, hepatocellular carcinoma (HCC) patients ineligible for curative therapies were treated with three-dimensional conformal radiotherapy (3DCRT).Methods: A total of 198 HCC patients who had tumors smaller than 10 cm and were not eligible for surgical resection or local ablation therapy received 3DCRT. Participants were separated into two groups. The treatment for Group A (n=111) was a median total dose of 53Gy with a fraction of 2.5–4.9Gy given three times a week, while treatment for Group B (n=87) was a median total dose of 52Gy with a fraction of 5.0–7.0 Gy given three times a week. Propensity score matching (PSM) was conducted, and after the PSM, 81 pairs of patients arose. The Kaplan–Meier method was adopted to analyze overall survival; multivariate analysis was applied to identify the prognostic factors of survival.Results: The median follow-up time was 19.7months (ranging from 1 to 186months). The median survival for Group A patients versus Group B patients was 14.4 versus 24.8months (P=0.003), respectively. The overall survival rates at 1, 3, and 5years were 57.7%, 30.6%, and 18.9% for Group A patients and 73.6%, 43.7%, and 33.3% for Group B patients, respectively (P=0.009). In addition, the results in the PSM model appeared to be similar between the two groups. After PSM, the association between four independent prognostic factors and worse overall survival was discovered as follows: tumor size (>5 cm), Child–Pugh class B, portal vein tumor thrombosis, and fraction of 2.5−4.9Gy/fx. The two groups also shared similar toxicities.Conclusions: Higher fraction dose radiotherapy delivered by 3DCRT was effective, as it offered a survival benefit without aggravating the toxicities in patients with small- to medium-sized HCC tumors who were ineligible for curative therapies.Keywords: three-dimensional conformal radiotherapy, higher fraction dose, hepatocellular carcinoma, curative therapy, survival

Background: Primary cardiac tumors are rare, but few studies have examined the relationship between risk factors and the prognosis. The aim of this study was to provide a survival analysis and risk factors for mortality in patients with primary cardiac tumors. Methods: We retrospectively enrolled 71 patients diagnosed with primary cardiac tumors from June 2006 to November 2017 in our hospital. Patients’ population characteristics, treatment information, pathology, and follow-up data were obtained and analyzed. Results: Of the 71 patients, 60 cases were benign, and 11 cases were malignant. Sex, age, New York Heart Association classification, the percentage of peripheral embolism, and surgery had no significant difference between benign and malignant groups (P >.05), but the percentage of arrhythmia, leg edema, and mortality rate was higher in the malignant tumor group than in the benign tumor group (P

ObjectivesTo establish and validate an effective nomogram to predict clinical outcomes for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Materials and MethodsThe clinicopathological parameters and follow-up information of 402 locoregionally advanced NPC patients (training cohort, n = 302; validation cohort, n = 100) were retrospectively enrolled. The nomogram was built with the important prognostic variables identified by Cox regression analysis. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. The predictive power and clinical utility of the nomogram were assessed using the Harrell concordance index (C-index), calibration curve, and decision curve analysis. We compared the eighth staging system model with the nomogram to analyze whether the model could improve the accuracy of prognosisResultsEpstein–Barr virus (EBV) DNA load, the gross tumor volume (GTVnx), and cervical lymph node tumor volume (GTVnd) after induction chemotherapy were the independent predictors of OS and PFS. The calibration curves indicated superb agreement between the nomogram-predicted probabilities and observed actual probabilities of survival. The C-index and area under the receiver operator characteristic curve (AUC) of the nomogram integrating these significant factors and N stage, and TNM stage were higher than those of the eighth TNM system alone. In addition, the decision curve analyses demonstrated the clinical value and higher overall net benefit of the nomogram. High-risk groups identified by the nomogram had significantly poorer OS and PFS than the low-risk group (p < 0.05).ConclusionsThe multidimensional nomogram incorporating TNM stage, EBV DNA load, and tumor volume after induction chemotherapy led to a more precise prognostic prediction and could be helpful for stratifying risk and guiding treatment decisions in locoregionally advanced NPC patients who have undergone induction chemotherapy and concurrent chemoradiation.

This paper presents a novel architecture for model predictive control (MPC)-based indoor climate control of multi-zone buildings to provide energy efficiency. Unlike prior works, we do not assume the availability of a high-resolution multi-zone building model, which is challenging to obtain. Instead, the architecture uses a low-resolution model of the building that is divided into a small number of “meta-zones” that can be easily identified using existing data-driven modeling techniques. The proposed architecture is hierarchical. At the higher level, an MPC controller uses the low-resolution model to make decisions for the air handling unit (AHU) and the meta-zones. Since the meta-zones are fictitious, a lower level controller converts the high-level MPC decisions into commands for the individual zones by solving a projection problem that strikes a trade-off between two potentially conflicting goals: the AHU-level decisions made by the MPC are respected while the climate of the individual zones is maintained within the comfort bounds. The performance of the proposed controller is assessed via simulations in a high-fidelity simulation testbed and compared to that of a rule-based controller that is used in practice. Simulations in multiple weather conditions show the effectiveness of the proposed controller in terms of energy savings, climate control, and computational tractability.

We investigate how to distribute large quantity of sensors in such a way that workload is evenly shared by sensors. These techniques can also be used for regulating agile mobile sensors, such as UAVs, when the workload of sensors rather than the energy for mobility is the primarily concern. An algorithm is developed for partitioning sensing field such that different partitions have different sensor densities. The goal is to minimize unevenness of the workload to sensor density ratio. The output of the algorithm proved to be the global optimum for serving this purpose.

In various sensor network applications like monitoring and target localization, the occurrence of an event can only be effectively located if it falls within the sensing range of at least k ≥ 3 sensors. In this paper, we develop an algorithm to optimize to optimize the positions and orientations of heterogeneous sensors in order to maximize the probability of an event location being k-covered. Our proposed algorithms can handle rotatable mobile sensors with directional sensing regions. We show that our proposed algorithm converges to a local optimal solution, and present numerical results to verify its performance.

Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin–linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin–linezolid combination. The survival rates of colistin–linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin–linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P

This paper explored the impact of corporate social responsibility (CSR) and product market competition (PMC) on the financial performance of listed companies in China, using the panel data of 1,100 Chinese A-share companies listed on the Shanghai and Shenzhen Stock Exchanges over the period from 2009 to 2014. The results show that for listed companies in china: (1) CSR can significantly and positively impact the short-term and long-term financial performance of listed companies in China. (2) PMC can only enhance corporate short-term financial performance, but has a significantly negative impact on corporate long-term financial performance. (3) The synergy between CSR and PMC can significantly and negatively affect both corporate short-term and long-term financial performance.

Summary The study aimed to evaluate whether an intraoperative ilioinguinal neurectomy (IIN) would reduce the risk of postoperative pain without increasing other complications during tension-free mesh repair compared to those who accepting nerve preservation. We have searched the following databases: PubMed, Cochrane Library, and EMBASE from inception to January 2020 (the cut-off date was 1 January 2020). Two authors independently accomplished the study selection, data extraction, and quality assessment. Of 553 studies reviewed, 7 high-quality randomized-controlled trials (RCTs) were identified. We pooled the related effect values in each included study and conducted a meta-analysis. The pooled results showed that IIN could reduce postoperative pain rate (RR = 0.40, 95% CI: 0.17–0.95) and pain score (SMD = −0.26, 95%CI: −0.46 to −0.06) at 6 months. There are no statistical differences between postoperative numbness rate (RR = 1.48, 95%CI: 0.89–2.47), postoperative sensory disturbance (RD = 0.03, 95% CI: −0.03–0.1) and postoperative secondary complications rate (RR = 0.81, 95%CI: 0.53–1.24) at the same time point. In conclusion, we have found the routine IIN can reduce the incidence of postoperative pain without increasing complications. Therefore, the implementation of this simple intraoperative maneuver may be a major source of postoperative morbidity reduction. Further study on the evaluation of interventions targeted to the IIN is recommended.

Purpose: To investigate N-staging Assessment of pretreatment Shear wave elastrography (SWE) in small cervical lymph nodes (0. 5 cm ≤ maximum diameter < 1 cm, intact capsule, no central necrosis, sCLNs) in nasopharyngeal carcinoma (NPC) patients.Methods: Pathological biopsy proven 28 NPC patients with sCLNs shown in pretreatment magnetic resonance (MR) images and 40 target lymph nodes were enrolled. All target lymph nodes were divided into metastasis and benign lymph node groups according to pathology. SWE was used to exam the real time SWE imaging of each target lymph nodes before conducting ultrasonography guided fine needle biopsy. The minimum (Emin), maximum (Emax), and mean (Emean) elasticity indices (kPa) of target lymph nodes were recorded. The SWE examination was repeated three times for the same target lymph node and each elasticity indices for statistic was determined by average of three measurements. SPSS 21.0 statistics software is used for statistical analysis. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of elasticity indices of metastatic sCLNs. Statistical significance was assumed when the P < 0.05.Results: Nine lymph nodes were metastatic and 31 were benign. The Emin, Emax, and Emean of benign group were 8.15 ± 6.12, 25.05 ± 12.37, and 16.05 ± 8.29 kPa, respectively; Emin, Emax, and Emean of metastasis group were 11.5 ± 6.17, 41.38 ± 17.87, and 23.48 ± 6.50 kPa, respectively. The difference of the Emax and Emean between metastasis and benign group were statistically significant (P = 0.003 and 0.018). The area under the ROC curve of Emin, Emax, and Emean of metastasis lymph node were 0.685 (P = 0.095), 0.785 (P = 0.010), and 0.765 (P = 0.017), respectively. Emax of 27 kPa and Emean of 17 kPa were taken as the cutoff value of diagnosis for metastasis sCLNs: the sensitivity, specificity, and accuracy were 77.8 and 100%, 71.0 and 61.3%, 75.0 and 70.0%, respectively.Conclusions: Pretreatment SWE has high accuracy in evaluating the sCLNs in NPC patients and is helpful for accurate N-staging and survival prognosis. It can be used as a clinical supplementary examination.

Serum microRNAs (miRNAs) have been reported as novel biomarkers for various diseases. But circulating biomarkers for predicting the radiosensitivity of nasopharyngeal carcinoma (NPC) have not been used in clinical practice. To screen out of differently expressed serum miRNAs from NPC patients with different radiosensitivity may be helpful for its individual therapy. NPC patients with different radiosensitivity were enrolled according to the inclusion and exclusion criteria. RNA was isolated from serum of these NPC patients before treatment. We investigated the differential miRNA expression profiles using microarray test (GSE139164), and the candidate miRNAs were validated by reverse transcription-quantitative real time polymerase chain reaction (RT-qPCR) experiments. Receiver operating characteristic (ROC) analysis has been applied to estimate the diagnostic value. In this study, 37 serum-specific miRNAs were screened out from 12 NPC patients with different radiosensitivity by microarray test. Furthermore, RT-qPCR analysis confirmed that hsa-miR-1281 and hsa-miR-6732-3p were significantly downregulated in the serum of radioresistant NPC patients (P

Objective This study aimed to evaluate the safety and efficacy of three‐dimensional conformal radiotherapy (3D‐CRT) and hepatic resection for patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT). Methods We retrospectively analyzed 323 HCC patients involving PVTT. Among them, 134 patients underwent 3D‐CRT, while 189 controls treated with hepatic resection (HR). Survival rate and prognostic analysis were performed using Kaplan‐Meier method and Cox regression analyses. Results The 1‐, 2‐, and 3‐year overall survival (OS) of RT group and HR group was 54% vs 62%, 33% vs 47%, and 18% vs 43%, respectively (P = 0.003). In the subgroup of PVTT type analysis, the 1‐, 2‐, and 3‐year OS in RT group was 65%, 39%, and 19%, respectively, while that in HR group was 83%, 53%, and 42%, respectively, in type I PVTT (P

Background We undertook a meta-analysis to evaluate the clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the detection of distant metastases in patients with non-small cell lung cancer (NSCLC) at initial staging. Materials and methods All topic-related studies were comprehensively searched in the MEDLINE and Embase databases. We obtained the summary estimates and constructed the summary receiver operating characteristic curve for 18F-FDG PET/CT using the bivariate regression model. Results Across 10 studies (1333 patients), the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for 18F-FDG PET/CT were 0.81 (95% confidence interval [CI] = 0.63-0.92), 0.96 (95% CI = 0.94-0.98), 22.9 (95% CI = 13.3-39.5), and 0.20 (95% CI = 0.09-0.42), respectively. Overall weighted area under the curve was 0.97 (95% CI = 0.96-0.98). Conclusion 18F-FDG PET/CT has a good diagnostic performance for distant metastasis staging in patients with NSCLC at initial staging.

Background Recent clinical studies have suggested that programmed death ligand 1 (PD-L1) expression in a tumour could be a potential biomarker for PD-L1/PD-1 blockade therapies. Methods To better characterise PD-L1 expression in hepatocellular carcinoma (HCC), we analysed its expression patterns in 453 HCC patients by double staining for CD68 and PD-L1 using the Tyramide Signal Amplification Systems combined with immunohistochemistry. We also investigated its correlation with clinical features, prognosis and immune status. Results The results showed that PD-L1 expression on tumour cells (TCs) was negatively associated with patients’ overall survival (OS; P = 0.001) and relapse-free survival (RFS; P = 0.006); however, PD-L1 expression on macrophages (Mφs) was positively correlated with OS (P = 0.017). Multivariate analysis revealed that PD-L1 expression on TCs and Mφs were both independent prognostic factors for OS (hazard ratio (HR) = 1.168, P = 0.004 for TC-PD-L1; HR = 0.708, P = 0.003 for Mφ-PD-L1). Further studies showed that Mφ-PD-L1+ tumours exhibited an activated immune microenvironment, with high levels of CD8+ T-cell infiltration and immune-related gene expression. Conclusion Our study provided a novel methodology to evaluate PD-L1 expression in the tumour microenvironment, which might help to select patients who would benefit from anti-PD-1/PD-L1 immunotherapies.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

In this paper, we introduce the swarm intelligence methods into the evolutionary dynamics, and have studied the impact of swarm intelligent algorithm on the evolution of cooperation among selfish individuals in the continuous version of spatial public goods games (PGG). We update an individual’s strategy according to the memory which records the most successful individual strategy in the past (referred to as its personal best strategy) as well as the knowledge of the best current strategy found by its nearest neighbors (referred to as the neighborhood best strategy). Through extensive simulations, we find that the introduction of swarm intelligence into PGG can promote cooperation strongly. Other pertinent quantities such as the time evolution of cooperator density, the spatial distribution of strategies and the updated velocities are also investigated.

We examine ChiNext IPOs' performance before and after the 2013 stock market reform. Majority of firm-level characteristics differ significantly over the two sub-periods. The initial return looks normal before the reform. It exhibits a uniform distribution truncated at the maximum 44% initial cap imposed by the reform thereafter and the cumulative return, based on listing day closing price keeps rising at a steady pace over the 1st month. The 2013 reform pushes the ChiNext IPO market off its track of becoming more efficient. Instead, it widens income gap in China. Our findings and recommendations support the 2020 new regulatory changes.

Dear Editor,We read with interest Dr. Liu and his colleagues’ [1] recent article published in Renal Failure: ‘Risk factors for calciphylaxis in Chinese hemodialysis patients: a matched case-control...

An artificial Ca2+-regulated PQQ glucose dehydrogenase (PQQ-GDH) enzyme was electrically connected to conducting electrodes and semiconductor interfaces. Direct electron transfer from the enzyme to the conducting electrode support was stimulated by the addition of Ca2+ cations resulting in reversible enzyme activation. A signal-switchable biofuel cell and biomolecular release have been realized using the Ca2+-activated enzyme immobilized on conducting electrodes. Interfacing the signal-switchable enzyme with a semiconductor chip allowed electronic read out of the enzyme ON-OFF states. The developed approach based on the signal-regulated PQQ-GDH enables numerous bioelectrochemical/bioelectronic applications of the developed systems in signal-activated biosensors and biofuel cells, as well as in biomolecular computing/logic systems.

The aim of this study was to determine the relationship between glucose fluctuation and global registry of acute coronary events (GRACE) risk score in patients with acute coronary syndrome (ACS) and abnormal glucose metabolism using continuous glucose monitoring system (CGMS). A total of 76 patients with ACS admitted into coronary care unit (CCU) were divided into two groups based on their blood glucose level and were further divided into subgroups based on GRACE risk score. A CGMS was used to real-time monitor blood glucose for 72 h in all patients after admitted into CCU. Twenty-four-hour mean blood glucose (24-h MBG) and 24-h mean amplitude of glycemic excursion (24-h MAGE) were calculated. Among the 76 patients, 52 patients had abnormal glucose metabolism. Among the 52 patients, there were 8 patients in low-risk group, 19 patients in moderate-risk group, and 25 in high-risk group. Among the 24 patients with normal glucose metabolism, there were 6 patients in the low-risk group, 6 patients in the moderate-risk group, and 12 in the high-risk group based on GRACE score. For patients with abnormal glucose metabolism, the 24-h MBG and 24-h MAGE of moderate- and high-risk groups were significantly higher than that of the low-risk group, which were not found in patients with ACS and normal glucose metabolism. High prevalence of abnormal glucose metabolism was found in ACS patients admitted into CCU and larger blood glucose fluctuation is associated with moderate and high GRACE risk scores in patients with ACS and abnormal glucose metabolism.

Statins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP), and the addition of ezetimibe to statins further reduces LDL-C and hsCRP. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a potentially important pathogenic factor participating in the progression of atherosclerosis. The aim of current study was to investigate how the addition of ezetimibe to rosuvastatin treatment affects reductions in LDL-C, hsCRP and Lp-PLA2 in patients with acute myocardial infarction (AMI). A total of 135 patients were enrolled in the study within 24 h of AMI, and were randomized to receive 10 mg rosuvastatin or 10 mg rosuvastatin plus 10 mg ezetimibe daily. HsCRP, Lp-PLA2, total cholesterol (TC), triglycerides (TG), LDL-C and high-density lipoprotein cholesterol (HDL-C) were determined at baseline and after 1, 3, 6 and 12 months of treatment. The addition of ezetimibe to rosuvastatin led to greater reduction of LDL-C compared with rosuvastatin monotherapy (from 3.00 to 1.19 mmol/l vs. 2.93 to 1.49 mmol/l, respectively; P

Crack fault diagnostics plays a critical role for rotating machinery in the traditional and Industry 4.0 factory. In this paper, an experiment is set up to study the dynamic response of a rotor with a breathing crack as it passes through its 1/2, 1/3, 1/4 and 1/5 subcritical speeds. A cracked shaft is made by applying fatigue loads through a three-point bending apparatus and then placed in a rotor testbed. The vibration signals of the testbed during the coasting-up process are collected. Whirl orbit evolution at these subcritical speed zones is analyzed. The Fourier spectra obtained by FFT are used to investigate the internal frequencies corresponding to the typical orbit characteristics. The results show that the appearance of the inner loops and orientation change of whirl orbits in the experiment are agreed well with the theoretical results obtained previously. The presence of higher frequencies 2X, 3X, 4X and 5X in Fourier spectra reveals the causes of subharmonic resonances at these subcritical speed zones. The experimental investigation is more systematic and thorough than previously reported in the literature. The unique dynamic behavior of the orbits and frequency spectra are feasible features for practical crack diagnosis. This paper provides a critical technology support for the self-aware health management of rotating machinery in the Industry 4.0 factory.

OBJECTIVE Acute gastric or intestinal spasm-like pain is common in clinical setting. Hyoscine butylbromide (HBB), an anti-cholinergic agent, relieves pain in stomach and bowel cramps by inhibiting smooth muscle contractility. In this study, we aimed to compare the efficacy and safety of parenteral HBB and anisodamine for treating acute gastric or intestinal pain. METHODS In this randomized, controlled, double-blind, parallel-group, multicenter non-inferiority trial, 299 Chinese patients were randomly assigned to HBB or anisodamine in a ratio of 1:1. They were administrated a single dose of either HBB 20 mg or anisodamine 10 mg, and a second dose was given when needed. The primary end-point was the difference in pain intensity (PID) from the pre-dose baseline at 20 min after the first injection. RESULTS Altogether 295 patients completed the protocol (153 in the HBB and 142 in the anisodamine group). For the primary end-point, the PID was -4.09 (95% confidence interval [CI]: -4.41, -3.76) for the HBB group and -3.66 (95% CI: -4.02, -3.31) for the anisodamine group (P < 0.0001 for non-inferiority). The percentage of patients with at least one adverse event was lower in the HBB group than in the anisodamine group (13.1% vs 17.6%), but there was no statistical significance (P = 0.279). The most frequent adverse events were thirst (7.8%) and dry mouth (2.6%) in the HBB group, and thirst (7.0%), dry mouth (3.5%) and nodal arrhythmia (2.1%) in the anisodamine group. CONCLUSIONS HBB 20 mg was not inferior to anisodamine 10 mg in pain relief of patients with acute gastric or intestinal spasm-like pain. Both drugs were safe and well tolerated.

Circulating tumor cells (CTCs) are used for metastasis surveillance in cancer patients, but low detection rates limit their use in colorectal cancer (CRC). We investigated the distribution of CTCs in peripheral and portal blood of CRC patients, and analyzed the relationship between serum tumor CEA/CA19-9 markers and CTCs blood levels. CTC levels detected in first reflux/portal vein blood were higher than in peripheral blood, and liver reduced CTCs amount. CTCs-positive patients had increased serum CEA and CA 19-9 levels, and the CEA and CA 19-9 levels correlated with the CTCs levels. Even in non-metastatic CRC patients with barely detectable CTCs in peripheral blood, serum CA 19-9 levels correlated with the CTC levels in first reflux/portal vein blood. These results demonstrate that CTC detection in the first reflux vein/portal vein blood is more sensitive than in peripheral blood, suggesting that clinical diagnosis using the CellSearch System should be based on the CTC detection in first reflux vein blood due to the high detection rates. In addition, our results indicate that serum CA 19-9 levels may serve as a diagnostic marker for further evaluation of CTC levels in portal blood.

We compared treatment outcomes in patients with stage II nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT). Stage II (2010 UICC/AJCC staging system) NPC patients treated with IMRT (n = 178) or 2D-CRT (n = 73) between January 2007 and December 2014 were retrospectively analyzed. Patients were matched using the propensity score-matching method. The primary endpoint was overall survival (OS). Secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Acute and late toxicity reactions to IMRT and 2D-CRT were also compared. In an unmatched cohort of 251 patients, no significant survival differences were found between those receiving IMRT and those receiving 2D-CRT (5-year OS, 95.67% vs 94.44%, P = 0.0556; LRFS, 97.34% vs 98.59%, P = 0.6656; RRFS, 99.26% vs 100%, P = 0.6785; DMFS, 96.5% vs 98.63%, P = 0.7910; DFS, 92.2% vs 97.24%, P = 0.8719). In the propensity-matched cohort of 146 patients, 5-year OS (97.06% vs 94.44%, P = 0.1325), LRFS (96.75% vs 98.59%, P = 0.8869), RRFS (100% vs 100%, P = 1.0000), DMFS (98.63% vs 98.63%, P = 0.4225), and DFS (95.37% vs 97.24%, P = 0.5634) were similar between patients treated with IMRT or 2D-CRT. However, IMRT correlated with fewer acute and late toxicity reactions. Thus although IMRT provides no survival advantage, it has a lower incidence of toxicity than 2D-CRT in stage II NPC patients.

The present study aimed to identify whether CD166 can be used as a biomarker for predicting the response of nasopharyngeal carcinoma (NPC) to radiotherapy. The serum concentration of CD166 in patients with NPC were detected by enzyme-linked immunosorbent assay. The secreted level of CD166 with radioresistant NPC was significantly higher than that with radiosensitive NPC. In vitro, the CD166 positive rate in the CNE2 cell membrane was significantly lower than that in the CNE2R cell membrane. The magnetic-activated cell sorting technology was used to obtain CNE-2R-CD166(+) and CNE-2R-CD166(−) cell lines. Then radiosensitivity, cell proliferation, and apoptosis were assessed using colony formation assay, cell counting kit 8 assay (CCK-8), and flow cytometry, respectively. The radiation sensitivity ratio was 1.28, indicating that the CNE2R-CD166(−) cells had a stronger radiation sensitivity. The result of CCK-8 assay indicated that the survival fraction of CNE2R-CD166(+) cells was significantly higher than that of CNE2R-CD166(−) cells. The apoptotic rate of CNE2R-CD166(+) cells was significantly lower than that of CNE2R-CD166(−) cells. Our data demonstrate that the secreted protein CD166 may be can used as a biomarker for predicting the response of NPC to radiotherapy.

Flexible loads are a resource for the Balancing Authority (BA) of the future to aid in the balance of supply and demand in the power grid. Consequently, it is of interest for a BA to know how much flexibility a collection of loads has, so to successfully incorporate flexible loads into grid level resource allocation. Loads' flexibility is limited by all their Quality of Service (QoS) requirements. In this work we present a characterization of capacity for a collection of flexible loads. This characterization is in terms of the Power Spectral Density (PSD) of the reference signal. Two advantages of our characterization are: (i) it easily allows for a BA to use the characterization for resource allocation of flexible loads and (ii) it allows for precise definitions of the power and energy capacity for a collection of flexible loads., Comment: 9 pages, 11 figures

An aggregate model is a single-zone equivalent of a multi-zone building, and is useful for many purposes, including model based control of large heating, ventilation and air conditioning (HVAC) equipment. This paper deals with the problem of simultaneously identifying an aggregate thermal dynamic model and unknown disturbances from input-output data. The unknown disturbance is a key challenge since it is not measurable but non-negligible. We first present a principled method to aggregate a multi-zone building model into a single zone model, and show the aggregation is not as trivial as it has been assumed in the prior art. We then provide a method to identify the parameters of the model and the unknown disturbance for this aggregate (single-zone) model. Finally, we test our proposed identification algorithm to data collected from a multi-zone building testbed in Oak Ridge National Laboratory. A key insight provided by the aggregation method allows us to recognize under what conditions the estimation of the disturbance signal will be necessarily poor and uncertain, even in the case of a specially designed test in which the disturbances affecting each zone are known (as the case of our experimental testbed). This insight is used to provide a heuristic that can be used to assess when the identification results are likely to have high or low accuracy., Comment: 10 pages, 15 figures