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Abstract Background Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Methods Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. Results We uncovered that LC-BrMs exhibited a significantly greater intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic, and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry, and multiplexed immunofluorescence staining of patients’ paired tumor specimens. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids of LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Conclusions In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.

Abstract Addressing the problem that the object size in Unmanned Aerial Vehicles (UAVs) aerial images is too small and contains limited feature information, leading to existing detection algorithms having less than ideal performance in small object detection, we propose a UAV aerial object detection system named YOLv5_mamba based on bidirectional dense feedback network and adaptive gate feature fusion. This paper improves the You Only Look Once Version 5 (YOLOv5) algorithm by firstly introducing the Faster Implementation of CSP Bottleneck with 2 convolutions (C2f) module from YOLOv8 into the backbone network to enhance the feature extraction capability of the backbone network. Furthermore, the mamba module and C2f module are introduced to construct a bidirectional dense feedback network to enhance the transfer of contextual information in the neck part. Thirdly, an adaptive gate feature fusion network is proposed to improve the head part of YOLOv5 and enhance its final detection capability. Experimental results on the public UAV aerial dataset VisDrone2019 demonstrate that the proposed algorithm improves the detection accuracy by 9.3% compared to the original YOLOv5 baseline network, showing better detection performance for small objects. For the UCAS_AOD dataset, the proposed algorithm outperforms YOLOv5-s by 9%. In the case of the DIOR dataset, the proposed algorithm exceeds YOLOv5-s by 12%.

Abstract Introduction Early screening and identification are crucial for fall prevention, and developing a new method to predict fall risk in the elderly can address the current lack of objectivity in assessment tools. Methods A total of 132 elderly individuals over 80 years old residing in some nursing homes in Shanghai were selected using a convenient sampling method. Fall history information was collected, and gait data during a 10-meter walk were recorded. Logistic regression was employed to establish the prediction model, and a nomogram was used to assess the importance of the indicators. The Bootstrap method was utilized for internal validation of the model, while the verification set was used for external validation. The predictive performance of the model was evaluated using the area under the ROC curve, calibration curve, and decision curve analysis (DCA) to assess clinical benefits. Results The incidence of falls in the sample population was 36.4%. The Tinetti Gait and Balance Test (TGBT) score (OR = 0.832, 95% CI: 0.734,0.944), stride length (OR = 0.007, 95% CI: 0.000,0.104), difference in standing time (OR = 0.001, 95% CI: 0.000,0.742), and mean stride time (OR = 0.992, 95% CI:0.984,1.000) were identified as significant factors. The area under the ROC curve was 0.878 (95% CI: 0.805, 0.952), with a sensitivity of 0.935 and specificity of 0.726. The Brier score was 0.135, and the Hosmer-Lemeshow test (χ 2 = 10.650, P = 0.222) indicated a good fit and calibration of the model. Conclusion The TGBT score, stride length, difference in standing time, and stride time are all protective factors associated with fall risk among the elderly. The developed risk prediction model demonstrates good discrimination and calibration, providing valuable insights for early screening and intervention in fall risk among older adults.

Abstract Background For prostate electrosurgery, where real-time surveillance screens are relied upon for operations, manual identification of the prostate capsule remains the primary method. With the need for rapid and accurate detection becoming increasingly urgent, we set out to develop a deep learning approach for detecting the prostate capsule using endoscopic optical images. Methods Our method involves utilizing the Simple, Parameter-Free Attention Module(SimAM) residual attention fusion module to enhance the extraction of texture and detail information, enabling better feature extraction capabilities. This enhanced detail information is then hierarchically transferred from lower to higher levels to aid in the extraction of semantic information. By employing a forward feature-by-feature hierarchical fusion network based on the 3D residual attention mechanism, we have proposed an improved single-shot multibox detector model. Results Our proposed model achieves a detection precision of 83.12% and a speed of 0.014 ms on NVIDIA RTX 2060, demonstrating its effectiveness in rapid detection. Furthermore, when compared to various existing methods including Faster Region-based Convolutional Neural Network (Faster R-CNN), Single Shot Multibox Detector (SSD), EfficientDet and others, our method Attention based Feature Fusion Single Shot Multibox Detector (AFFSSD) stands out with the highest mean Average Precision (mAP) and faster speed, ranking only below You Only Look Once version 7 (YOLOv7). Conclusions This network excels in extracting regional features from images while retaining the spatial structure, facilitating the rapid detection of medical images.

Abstract Aims Whether sodium‐glucose co‐transporter 2 inhibitors are effective for heart failure caused by ATTR‐CA (transthyretin cardiac amyloidosis) remains uncertain. The aim of this study is to investigate the cardiovascular prognosis in ATTR‐CA mice model with dapagliflozin treatment. Methods and results Humanized RBP4/TTRVal50Met and RBP4/TTR mice models were constructed with clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR‐Cas9) techniques and multiple generations breeding. A total of 6 RBP4/TTR mice received placebo treatment, when 12 RBP4/TTRVal50Met received dapagliflozin (1 mg/kg/day, 6 mice) and placebo (6 mice) treatment. Fasting glucose, intraperitoneal glucose tolerance test, and plasma brain natriuretic peptide (BNP) concentration were measured at Day 0, Week 2, and Week 4. BNP, transforming growth factor‐beta (TGF‐β), collagen type I alpha 1 (COL1A1) protein levels, and Cola1, TGFβ1, TNFα, IL‐1β, BNP relative quantities in cardiac, along with cardiac pathology examination including right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter were measured at Week 4 after treatment procedure. All 18 mice completed the experiment. The baseline characteristics were balanced among three treatment groups. In placebo‐treated mice, the cardiac BNP relative quantity was significantly higher in RBP4/TTRVal50Met mice than RBP4/TTR mice (RBP4[KI/KI], TTR [KI/KI]: 0.72 ± 0.46, RBP4[KI/KI], TTRVal50Met[KI/KI]: 1.44 ± 0.60, P = 0.043), indicating more significant heart failure progression in ATTR‐CA mice than normal mice. In ATTR‐CA mice, the cardiovascular prognosis measurements including heart failure (plasma BNP concentration and relative quantities of BNP), cardiac inflammation (relative quantities of Cola1, TGFβ1, TNFα, and IL‐1β), and pathological changes (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were statistically comparable between those under dapagliflozin and placebo treatment. Conclusions Dapagliflozin did not improve cardiovascular prognosis including the progression of heart failure, cardiac inflammation, and pathological changes in ATTR‐CA mice compared with placebo. The results of this study were not in support of dapagliflozin's therapeutic effects for ATTR‐CA. More pre‐clinical and clinical researches to validate these findings and demonstrate the underlying mechanisms are still required.

Chinese construction industry is gradually transforming to industrialization, which promotes the development of prefabricated buildings. As an efficient lateral force resisting system, prefabricated steel-plate concrete composite shear wall structure has become a research hotspot in the field of architecture at home and abroad. Based on the mechanical characteristics of the shear wall, this paper proposes a end steel plate connection prefabricated composite shear wall structure. Through numerical simulation and analysis of the prefabricated composite shear wall with different connection areas and the cast-in-place composite shear wall, which verified the feasibility and reliability of end steel plate connection. Based on the above verification, the influence of different parameters on the seismic performance of the prefabricated composite shear wall with end steel plate connection has been further studied, and the theoretical calculation of bearing capacity is carried out. The results show that the length of the connector should be controlled within a reasonable range. The tie bars in the node connection area can improve the strength and ductility of the prefabricated composite shear wall. The aspect ratio and axial pressure ratio have obvious influence on the seismic performance of the wall, which should be reasonably selected in design.

Background/Objectives: Metabolic-associated fatty liver disease (MAFLD) is one of the most common liver disorders associated with obesity and metabolic syndrome, and poses a significant global health burden with limited effective treatments. The aim of this study was to assess the protective effects of mulberry twig alkaloids (SZ-A) on MAFLD and to further investigate the underlying mechanisms including the specific targets or pathways. Methods: Diet-induced obesity (DIO) and normal mouse models were established by feeding C57Bl/6J mice with a high-fat diet (HFD) or common diet for 12 weeks. SZ-A, dapagliflozin, and placebo were administered to corresponding mouse groups for 8 weeks. Data of fasting blood glucose, glucose tolerance, insulin tolerance, and the body weight of mice were collected at the baseline and termination of the experiment. Serum liver enzymes and lipids were measured by ELISA. Western blotting, qPCR, and pathological section staining were implemented to evaluate the degrees of liver steatosis, fibrosis, and oxidative stress in mice. Results: In DIO mouse models, high-dose SZ-A (800 mg/kg/d) treatment significantly inhibited HFD-induced weight gain, improved insulin tolerance, and reduced serum alanine aminotransferase, total cholesterol, and triglyceride levels compared with placebo. In DIO mice, SZ-A could alleviate the pathological changes of hepatic steatosis and fibrosis compared with placebo. Lipid catabolism and antioxidant stress-related proteins were significantly increased in the livers of the high-dose SZ-A group (p < 0.05). Inhibition of PGC1α could inhibit the function of SZ-A to enhance lipid metabolism in hepatocytes. PGC1α might interact with NRF2 to exert MAFLD-remedying effects. Conclusions: By regulating the expression of PGC1α and its interacting KEAP1/NRF2 pathway in mouse liver cells, SZ-A played important roles in regulating lipid metabolism, inhibiting oxidative stress, and postponing liver fibrosis in mice with MAFLD.

(1) Background: Small objects in Unmanned Aerial Vehicle (UAV) images are often scattered throughout various regions of the image, such as the corners, and may be blocked by larger objects, as well as susceptible to image noise. Moreover, due to their small size, these objects occupy a limited area in the image, resulting in a scarcity of effective features for detection. (2) Methods: To address the detection of small objects in UAV imagery, we introduce a novel algorithm called High-Resolution Feature Pyramid Network Mamba-Based YOLO (HRMamba-YOLO). This algorithm leverages the strengths of a High-Resolution Network (HRNet), EfficientVMamba, and YOLOv8, integrating a Double Spatial Pyramid Pooling (Double SPP) module, an Efficient Mamba Module (EMM), and a Fusion Mamba Module (FMM) to enhance feature extraction and capture contextual information. Additionally, a new Multi-Scale Feature Fusion Network, High-Resolution Feature Pyramid Network (HRFPN), and FMM improved feature interactions and enhanced the performance of small object detection. (3) Results: For the VisDroneDET dataset, the proposed algorithm achieved a 4.4% higher Mean Average Precision (mAP) compared to YOLOv8-m. The experimental results showed that HRMamba achieved a mAP of 37.1%, surpassing YOLOv8-m by 3.8% (Dota1.5 dataset). For the UCAS_AOD dataset and the DIOR dataset, our model had a mAP 1.5% and 0.3% higher than the YOLOv8-m model, respectively. To be fair, all the models were trained without a pre-trained model. (4) Conclusions: This study not only highlights the exceptional performance and efficiency of HRMamba-YOLO in small object detection tasks but also provides innovative solutions and valuable insights for future research.

Abstract Inability to meet nutrition needs resulting from multiple diseases‐related, and individual factors contribute significantly to malnutrition and poor disease outcome among cancer patients. Strategies capable of delivering metabolically efficient nutrients with less digestive and metabolic stress without adding bulk to the diet of patients may be suitable for dealing with cancer‐related malnutrition and quality of life (QoL). We sought to test the hypothesis that peptide supplementation could attenuate weight loss and improve QoL among brain cancer patients compared to conventionally treated controls. In a non‐blind pilot study, brain cancer patients received 9 g soybean peptide supplementation twice per day (peptide group, n = 9) and compared with conventional treatment (control group, n = 10) over two chemotherapy cycles of 42 days. Compared to the controls, soypeptide supplementation attenuated weight loss with 5.4% increase in weight. Moreover, QoL, assessed using the European Organization for Research and Treatment of Cancer QLQ‐C30, revealed that physical (8.1 ± 15.6, p

Abstract Background Phosphoglycerate mutase 5 (PGAM5), a phosphatase involved in mitochondrial homeostasis, is reported to be closely related to the metabolic stress induced by high-fat diet (HFD) or cold. In this study, we aimed to investigate the effects of PGAM5 on hepatic steatosis, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Methods and results We generated PGAM5 global knockout (GKO) mice and their wildtype (WT) littermates using CRISPR/CAS9. The mice were fed with a high fat high fructose (HFHF) diet for 12 weeks or a methionine choline-deficient (MCD) diet (methionine choline supplemented (MCS) as control) for 6 weeks. Hepatic PGAM5 expression was up-regulated in humans with NASH and WT mice fed with HFHF and MCS, and reduced in WT mice fed with MCD diet. In HFHF-fed mice, GKO had reduced body weight, hepatic triglyceride (TG) content and serum transaminase along with decreased hepatic pro-inflammatory and pro-fibrotic responses compared with their WT control. GKO had increased expression of antioxidative gene glutathione peroxidase-6 (GPX6) and activation of mammalian target of rapamycin (mTOR). In mice fed with MCS diet, GKO significantly increased serum TNF-α and IL-6 and decreased hepatic GPX6 mRNA expression. There was no difference in hepatic steatosis, inflammation or fibrosis between GKO and WT mice fed with MCD diet. We investigated the role of PGAM5 deficiency in a variety of cell types. In differentiated THP-1 cells, PGAM5 silencing significantly increased pro-inflammatory cytokine secretion and decreased antioxidative proteins, including nuclear factor erythroid 2- related factors (NRF2), heme oxygenase-1 (HO-1) and GPX6 without affecting mTOR activity. In HepG2 cells with steatosis, PGAM5 knockdown reduced insulin sensitivity, increased mTOR phosphorylation and reduced the expression of NRF2, catalase (CAT), HO-1 and GPX6. Conversely, PGAM5 knockdown reduced TG accumulation, increased insulin sensitivity, and increased antioxidative genes in 3T3-L1 cells, despite the up-regulation in mTOR phosphorylation. Conclusions PGAM5-KO relieved hepatic steatosis and inflammation in HFHF model, promoted inflammation in MCS-fed mice and had no effects on the MCD-fed model. The distinct effects may be owing to the different effects of PGAM5-KO on anti-oxidative pathways in energy-dependent, possible involves mTOR, and/or cell type-dependent manner. Our findings suggest that PGAM5 can be a potential therapeutic target for NASH.

In the context of Industry 4.0, industrial production equipment needs to communicate through the industrial internet to improve the intelligence of industrial production. This requires the current communication network to have the ability of large-scale equipment access, multiple communication protocols/heterogeneous systems interoperability, and end-to-end deterministic low-latency transmission. Time-sensitive network (TSN), as a new generation of deterministic Ethernet communication technology, is the main development direction of time-critical communication technology applied in industrial environments, and Wi-Fi technology has become the main way of wireless access for users due to its advantages of high portability and mobility. Therefore, accessing WiFi in the TSN is a major development direction of the current industrial internet. In this paper, we model the scheduling problem of TSN and WiFi converged networks and propose a scheme based on a greedy strategy distributed estimation algorithm (GE) to solve the scheduling problem. Compared with the integer linear programming (ILP) algorithm and the Tabu algorithm, the algorithm implemented in this paper outperforms the other algorithms in being able to adapt to a variety of different scenarios and in scheduling optimization efficiency, especially when the amount of traffic to be deployed is large.

Abstract Background The high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups. Methods The study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables. Results After pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein–Barr virus (EBV)-DNA 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P

Abstract Objective To explore the histopathological characteristics of paired recurrent gliomas and their clinical significance. Methods Glioma patients who received both primary surgery and reoperation when recurrence at Sun Yat-sen University Cancer Center from June 2001 to June 2019 were enrolled. Clinical and pathological characteristics were analyzed retrospectively, and histopathology of reoperation specimens was divided into three categories according to tumor cell activity and the degree of necrosis: active group, low-activity group, and necrosis group. Results A total of 89 patients were included in this study. The 2016 WHO grade of the first operation pathology and IDH1 status were related to survival time after the first operation, but there was no significant association with survival time after reoperation. The time interval between primary and reoperation was shorter for primary high-grade glioma and/or IDH1 wild-type tumor patients than for low-grade glioma and/or IDH1 mutant tumor patients (P

Abstract Background Brain metastases (BM) from non-small-cell lung cancer (NSCLC) is the most common brain malignancy. Systemic inflammation biomarkers have recently been evaluated as prognosis indicators in several tumors. The combination of these markers has not been evaluated in NSCLC with BM yet. Here, we explored the predictive value of pretreatment inflammatory biomarkers and established a novel, clinically applicable prognostic index for NSCLC patients with BM. Methods A retrospective investigation of 951 NSCLC patients newly diagnosed with BM at Sun Yat-sen University Cancer Center was conducted. We randomly divided patients into a training cohort (n = 674) or validation cohort (n = 277). Receiver operating characteristic (ROC) curve analysis was carried out to obtain the optimal cut-off values of pretreatment systemic inflammatory indexes. The associations between serum biomarkers and overall survival (OS) were analyzed by Kaplan–Meier curves and Cox proportional models. The resulting prediction model has been externally verified through the validation cohort. Results The optimal cut-off value of the neutrophil–lymphocyte ratio (NLR) in predicting OS was 4.71, while the clinical standard of 40 mg/L was chosen as the optimal cut-off value of albumin. Univariate and multivariate analyses revealed that patients receiving local treatment, chemotherapy, a NLR

ObjectiveThe aim of this systematic review and meta-analysis was to systematically investigate the intervention effect of physical exercise on disordered social communication in patients with autism spectrum disorders.MethodsThis systematic review and meta-analysis used the PubMed, Web of Science, the Cochrane Library, and Embase electronic databases to conduct a systematic search of literature describing randomized controlled trials (RCTs) on the effect of physical exercise on disordered social communication in autistic patients from the first year of inclusion to 21 January 2023.ResultsA total of 14 RCTs including 460 autistic patients were analyzed. A meta-analysis showed that physical exercise had a positive effect on social communication disorder (SMD = 0.45, 95% CI: 0.15, 0.74, p

Deuterium-labelled compounds are useful for mechanistic studies and pharmaceutical science, but syntheses are not trivial. Here, the authors report deuteration of unactivated alkyl (pseudo)halides driven by electrochemical force, using deuterium oxide as the source of the isotope.

Objective To provide reference for fine management of blood donors by classifying and analyzing different types of blood donors from domestic blood stations. Methods The resident population of 15 regions in China from 2016 to 2019 were taken as the research object, among which the blood donors were divided into three categories: age-eligible citizens, registered donors and donated donors. The average value and proportion of the three categories were calculated and statistically analyzed. Results The resident population of the 15 regions varied greatly. The mean 95% CI of the proportion of age-eligible citizens to resident population from 2016 to 2019 was (60.16%, 67.84%); registered donors to age-eligible citizens and resident population was (2.21%, 2.86%) and (1.41%, 1.79%), respectively; donated donors to registered donors, age-eligible citizens and resident population was (84.63%, 91.68%), (1.93%, 2.55%) and(1.23%, 1.59%), respectively. Conclusion There were differences in the number and proportion of different types of blood donors in different regions. The fine management of blood donors can help blood stations carry out more effective recruitment and retention strategies.

Background and Aim: Postoperative radiotherapy with concomitant temozolomide (TMZ) followed by ≤ six cycles of adjuvant TMZ chemotherapy (Stupp regimen) is the standard treatment for newly diagnosed glioblastoma (GBM); however, its effectiveness is limited. Anlotinib inhibits both tumor angiogenesis and tumor cell proliferation by targeting multiple kinases, and showing promising results in preclinical GBM models. We designed a Phase II trial to assess the efficacy and safety of the Stupp regimen plus anlotinib. Methods/Design: This is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib (Stupp regimen + anlotinib) or placebo (Stupp regimen + placebo). Postoperative patient recruitment will begin in July 2021, the analysis of primary outcome measures will be completed in July 2023, and the study will finish in July 2024. Major eligibility criteria include histologically confirmed newly diagnosed GBM and an Eastern Cooperative Oncology Group performance score ≤2. Other criteria for inclusion include age ≥18 years and lack of significant comorbidity. In this study, the primary endpoint will be the median progression-free survival (PFS). Secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity. The protocol has received approval from Sun Yat-sen University Cancer Center Ethics Committee (Approval No. B2021-073-01; approved on April 19, 2021). Discussion: Updated treatment modalities are required for newly diagnosed GBM. Our proposed treatment modality of the Stupp regimen combined with anlotinib therapy are waiting conclusion. Trial Registration: This study was registered with ClinicalTrials.gov under identifier NCT04959500 on July 13, 2021.

Background and Aim: High-grade glioma is the most common malignant primary brain tumor in the central nervous system. Multiple strategies such as surgery, radiotherapy, and chemotherapy have been used, but the prognosis of patients with high-grade glioma remains poor. No standard treatment exists for recurrent gliomas; however, combination therapies of programmed cell death protein 1 blockades with antiangiogenic agents have demonstrated promising effects in different solid tumors. Therefore, since the end of 2020, a clinical trial designed to evaluate the safety and efficiency of neoadjuvant therapy using camrelizumab and apatinib in patients with recurrent high-grade gliomas has been carried out in our institution. Methods/Design: In this prospective, Phase II, single-arm study, patients with recurrent high-grade gliomas will receive single-dose intravenous injection of camrelizumab (200 mg) and daily oral administration of apatinib (250 mg/day for 7 days) 14 days before reoperation for tumor resection. Sequential therapy will begin 2 weeks after surgery with the biweekly injection of camrelizumab and 4 weeks after surgery with the daily administration of apatinib. Treatment of camrelizumab and apatinib will be continued until disease progression or unacceptable toxicity or death. The primary outcome measure will be the median overall survival rate. Secondary outcome measures will include progression-free survival rate at 6 months and at 12 months and other measures. The trial is planned to enroll 30 patients. This study was approved by the Ethics Committee of Sun Yat-sen University Cancer Center (Guangzhou, China; approval No. SL-B2020-149-01) on July 27, 2020. Results and Conclusions: Although an evaluation is still impossible to be conducted yet, 11 patients had been enrolled by the end of January 2022. Some patients have shown a promising outcome. These preliminary data suggest that this study would be worthwhile. We hope that this study will provide scientific evidence to better care of patients with recurrent high-grade glioma. Trial registration: This study was registered with ClinicalTrials.gov under identifier NCT04588987 on October 19, 2020.

Hypervelocity impact in the universe can be generated by a three-stage gas gun. Achieving the desirable planarity of the flyer enlarges the experimentally effective area of the flyer under the hypervelocity condition. The multidimensional graded density impactor (MDGDI) enhances the planarity of the flyer. In this investigation, a one-dimensional Lagrange elastoplastic hydrodynamic method and a Euler grid finite difference method were used to examine the relationship between the structure of graded density impactors (GDIs) and the planarity of flyers. MDGDIs lead to a deviation of the stress wave produced by the one-dimensional graded density impactor (1DGDI), which offsets the stress disturbance effect, changes the velocity at each particle, and enhances the planarity of flyers. The proportion of flat areas of the flyer increases from 52.70% to 95.71% by adopting MDGDIs. The proportion of flat areas is linear with the wave impedance of the high-impedance layer for 1DGDIs and the wave impedance near the barrel of the high-impedance layer for MDGDIs. This investigation guides the design of GDIs and expands the application of gas gun technology in the field of hypervelocity impact.

Abstract Introduction Circular RNAs (circRNAs) play critical roles in tumorigenesis, but their clinical efficacy in esophageal squamous cell carcinoma (ESCC) still retains controversial. This meta‐analysis aims at evaluating the associations between circRNA expressions and clinicopathologic features as well as the diagnostic and prognostic values of circRNAs in ESCC. Materials & Methods PubMed, EMBASE, and other online databases were systematically searched to collect studies on circRNAs and clinicopathological features, diagnostic, and/or prognostic assessments of ESCC. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) and Newcastle‐Ottawa Scale (NOS) scales. The included studies were quantitatively weighted and merged, and diagnostic indicators, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated. P values were merged by Fisher᾽s method. Sources of heterogeneity were traced using subgroup, sensitivity, and meta‐regression analyses. Results As a result, 12 studies were included, representing 769 ESCC patients. The meta‐analysis showed that abnormal expressions of circRNAs were associated to TNM stage as well as lymph node and distant metastases in ESCC cases. CircRNA was used to distinguish ESCC patients from healthy controls, and the merged sensitivity, specificity, and the area under the curve (AUC) of ESCC were 0.78 (95% CI: 0.74–0.81), 0.79 (95% CI: 0.75–0.83), and 0.86, respectively. The survival analysis showed that upregulated oncogenic circRNA levels in ESCC tissues was associated with the shorter overall survival (OS) of the patients (univariate analysis: HR = 2.25, 95% CI: 1.71–2.95, p = 0.000, I2 = 0.0%; multivariate analysis: HR = 2.50, 95% CI: 1.61–3.89, p = 0.000, I2 = 0.0%), while the OS of ESCC patients presenting overexpressions of tumor‐suppressive circRNAs was significantly ameliorated (HR = 0.29, 95% CI: 0.20–0.42, p = 0.000, I2 = 0.0%). The subgroup analyses based on circRNA biofunctions, sample size, and reference gene also revealed robust results. Conclusion CircRNAs can be used as promising molecular biomarkers for the early diagnosis and prognosis monitoring of ESCC.

Prediabetes is considered an important reversible checkpoint in T2DM development, which can be delayed and prevented by early interventions. Lonicerae Japonicae Flos (LJF), an edible-medicinal herb, is rich in chlorogenic acid (CGA, 5-O-caffeoylquinic acid) and exerts anti-diabetes effects, but its role in prediabetes remains unclear. The purpose of this study was to explore the effects of LJF extract and CGA on rat with prediabetes. Sprague-Dawley rats were given high-fat diet (HFD) to induce prediabetes, and glycolipid metabolism parameters and molecular mechanisms were evaluated. LJF (the LJF extract treatment group) and CGA (the pure CGA treatment group) significantly attenuated HFD-induced prediabetes with impaired glucose tolerance and dyslipidemia, but their mechanisms of action are not exactly the same. Specifically, LJF prioritizes increasing protective lipid species [such as increasing blood polyunsaturated fatty acids (PUFA)-containing diacylglycerol (DAG) species, high-density lipoprotein-cholesterol (HDL-C)], whereas CGA prioritizes reducing detrimental lipid species [such as saturated fatty acid-containing DAG species, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC)]. In addition, CGA significantly increased the content of blood very-long-chain fatty-acid (VLCFA)-containing ceramides species. This could be explained mechanically by a distinction between LJF and CGA’s effects on C1q/TNF-related proteins (CTRPs) which activate adiponectin receptors, triggering several downstream reactions. Because both LJF and CGA upregulated liver expression of adiponectin receptors (AdipoR1 and AdipoR2) and enhanced the activity of downstream AMPK. LJF also increased serum levels of CTRP3 and CTRP9, especially CTRP9, whereas CGA had higher serum CTRP3 and upregulated liver PPARa expression. Additionally, ELOVL6 expression in the liver was greater in CGA than LJF. This study demonstrates that LJF and CGA exert hypoglycemic and lipid modulation capacity to prevent prediabetes may through the CTRPs-AdipoRs-AMPK/PPARα axes and promoting ELOVL6 protein expression.

IntroductionImmune status was evaluated by means of lymphocyte subset counts and immune factors in cancer. This study analyzed the peripheral blood immune index and survival outcomes in intracranial germ cell tumor (iGCT) patients.MethodsPeripheral blood lymphocyte subset counts and levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), and interferon-γ (IFN) from 133 iGCT patients were collected and retrospectively analyzed. Their clinical information was extracted from the hospital database, and prognosis was confirmed by telephone visit. Patients (n=11) underwent prospective review and their samples of peripheral blood lymphocytes were verified.ResultsA total of 113 (84.2%) patients received comprehensive treatments, including 96 standard therapy (combination of full course chemotherapy and radiology with or without surgery) and 17 comprehensive but non-standard therapy (either without full course chemotherapy or with non-standard radiotherapy) and 98 (73.7%) reached complete or partial response. T lymphocytes (CD3+), cytotoxic T cells (CD3+CD8+ or Tc), and B lymphocytes (CD19+) decreased (p=0.047, p=0.004, and p

With the development of camel-derived food and pharmaceutical cosmetics, camel hoof, as a unique by-product of the camel industry, has gradually attracted the attention of scientific researchers in the fields of nutrition, health care, and biomaterial development. In this study, the protein composition and collagen type of Bactrian camel hoof collagen extract (CHC) were analyzed by LC-MS/MS, and the functional properties of CHC were further investigated, including its rheological characteristics, emulsification and emulsion stability, and hygroscopicity and humectancy. Proteomic identification confirmed that CHC had 13 collagen subunits, dominated by type I collagen (α1, α2), with molecular weights mainly in the 100–200 KDa range and a pI of 7.48. An amino acid study of CHC revealed that it carried the standard amino acid profile of type I collagen and was abundant in Gly, Pro, Glu, Ala, and Arg. Additionally, studies using circular dichroism spectroscopy and Fourier transform infrared spectroscopy revealed that CHC contains a collagen-like triple helix structure that is stable and intact. Different concentrations of CHC solutions showed shear-thinning flow behavior. Its tan δ did not differ much with increasing concentration. The CHC has good emulsifying ability and stability, humectancy, and hygroscopicity. This study provides a basis for utilizing and developing Bactrian camel hoof collagen as a functional ingredient.

Abstract The purpose of this study was to explore the effects of brisk walking on blood pressure (BP) in Chinese Han occupational populations to identify the appropriate volume of exercise needed for BP management. Eight‐hundred and two office staff with sedentary lifestyles were recruited to receive a prescription pedometer‐assisted brisk walking intervention for 3 months. To evaluate exercise intervention efficiency using statistical methods, the effective steps was divided as follows: 4000‐ 12 000 (Level 4) steps/day. The data of 688 participants who completed the study were analyzed. After intervention, Systolic BP (SBP) and Diastolic BP (DBP) at Levels 1–3 were significantly decreased (p

Abstract Background Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment. Methods Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months. Results In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

Abstract Background Differentiating glioma recurrence from treatment-related changes can be challenging on conventional imaging. We evaluated the efficacy of quantitative parameters measured by dual-energy spectral computed tomographic (CT) for this differentiation. Methods Twenty-eight patients were examined by dual-energy spectral CT. The effective and normalized atomic number (Zeff and Zeff-N, respectively); spectral Hounsfield unit curve (λHU) slope; and iodine and normalized iodine concentration (IC and ICN, respectively) in the post-treatment enhanced areas were calculated. Pathological results or clinicoradiologic follow-up of ≥2 months were used for final diagnosis. Nonparametric and t-tests were used to compare quantitative parameters between glioma recurrence and treatment-related changes. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and accuracy were calculated using receiver operating characteristic (ROC) curves. Predictive probabilities were used to generate ROC curves to determine the diagnostic value. Results Examination of pre-contrast λHU, Zeff, Zeff-N, IC, ICN, and venous phase ICN showed no significant differences in quantitative parameters (P > 0.05). Venous phase λHU, Zeff, Zeff-N, and IC in glioma recurrence were higher than in treatment-related changes (P

Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and European experts regarding subsequent treatment of Patient 2. Continuation of TMZ and bevacizumab was suggested until further deterioration. Whether tumor-treating field therapy should play a role in this patient could not be evaluated. However, some other molecular targeted agents (e.g. vascular endothelial growth factor receptor tyrosine kinase inhibitors such as regorafenib or apatinib) after bevacizumab failure, the effectiveness of these drugs remains unclear. Conclusion: In clinical practice, although we should follow established guidelines, the final treatment regimen requires informed consent from the patient. Thus, some real-world cases may deviate from the established guidelines. When patients reach end-stage disease with a marked decrease in their performance status and no standard treatment options, active antitumor treatment might be more likely to be attempted in China, while symptomatic treatment is more frequently performed in Europe. Although treatment philosophies for patients with glioma are slightly different between Eastern and Western medical experts, any treatment strategies should satisfy these patients.

Background: Anlotinib is a multi-target anti-angiogenic agent. This retrospective study aimed to evaluate the efficacy and safety of anlotinib alone or in combination with temozolomide for the treatment of recurrent high-grade glioma.Materials and Methods: The clinical data of patients with recurrent high-grade glioma treated with anlotinib alone or in combination with temozolomide in our cancer center were collected and analyzed. Treatment response was evaluated according to the response assessment for neuro-oncology criteria. Progression-free survival, progression-free survival at 6 months, overall survival, and overall survival at 12 months were evaluated by Kaplan–Meier method and compared by log-rank test.Results: Between August 2019 and December 2020, 31 patients with recurrent high-grade glioma (21 of grade 4 and 10 of grade 3) were enrolled in this study. Seventeen patients received anlotinib alone and 14 received anlotinib plus temozolomide. All patients were heavily treated, the median lines of previous treatments were 2, and the median Karnofsky score was 60. At the data cutoff date, the median progression-free survival was 4.5 months and the progression-free survival at 6 months was 43.5%. The median overall survival was 7.7 months, and the overall survival at 12 months was 26.7%. The progression-free survival at 6 months and the overall survival at 12 months for 21 patients with grade 4 glioma was 40.2 and 27.9%, respectively. The tumor objective response rate was 41.9% in all patients and 33.3% in patients with grade 4 glioma. No grade 3 or worse treatment-related adverse events were recorded during the treatment.Conclusion: Anlotinib alone or in combination with temozolomide showed encouraging efficacy and favorable tolerability in patients with recurrent high-grade glioma who had been heavily treated.

Network slicing in 5G is expected to essentially change the way in which network operators deploy and manage vertical services with different performance requirements. Efficient and secure slice provisioning algorithms are important since network slices share the limited resources of the physical network. In this article, we first analyze the security issues in network slicing and formulate an Integer Linear Programming (ILP) model for secure 5G core network slice provisioning. Then, we propose a heuristic 5G core network slice provisioning algorithm called VIKOR-CNSP based on VIKOR, which is a multi-criteria decision making (MCDM) method. In the slice node provisioning stage, the node importance is ranked with the VIKOR approach by considering the node resource and topology attributes. The slice nodes are then provisioned according to the ranking results. In the slice link provisioning stage, the k shortest path algorithm is implemented to obtain the candidate physical paths for the slice link, and a strategy for selecting a candidate physical path is proposed to increase the slice acceptance ratio. The strategy first calculates the path factor Pf which is the product of the maximum link bandwidth utilization of the candidate physical path and its hop-count, and then chooses the candidate physical path with the smallest Pf to host the slice link. Extensive simulations show that the proposed algorithm can achieve the highest slice acceptance ratio and the largest provisioning revenue-to-cost ratio, satisfying the security constraints of 5G core network slice requests.

Background and Aim: Guidelines recommend adjuvant treatment for patients with high-grade gliomas and low-grade gliomas with high risk of progression. In clinical practice, however, treatments may not conform to these suggested guidelines. In this study, we reviewed the treatments and outcomes in patients with gliomas at Sun Yat-Sen University Cancer Center (SYSUCC), China. Materials and Methods: Medical records and radiologic images of 1215 glioma patients who underwent surgery at the center from 2000 to 2017 were retrospectively reviewed, and their clinicopathological characteristics, treatment method, and overall survival (OS) were analyzed. The study was approved by the Ethics Committee of SYSUCC on February 20, 2019 (approval No. GZR2019-219). Results: A total of 1001 patients diagnosed with glioma (initially World Health Organization 2007 criteria, then 2016 criteria) were enrolled, including 90 patients with Grade I, 307 Grade II, 239 Grade III, and 365 Grade IV gliomas. A total of 331 of 604 patients with high-grade glioma (54.8%) and 159 of 397 with low-grade glioma (40.1%) received postsurgical radiotherapy, and 285 patients with high-grade tumors (47.1%) and 80 with low-grade tumors (20.2%) received adjuvant chemotherapy. The median OS was 17.5 months for Grade IV and 43.1 months for Grade III gliomas. The median OS of patients with low-grade glioma was not reached. The 5-year survival rates of patients with Grades I, II, III, and IV gliomas were 94.7%, 73.7%, 45.7%, and 18.6%, respectively. Multivariate analysis identified onset age, preoperative seizure, tumor location, pathological subtype, resection extent, and postsurgical treatment as independent predictors of OS in patients with high-grade gliomas. Patients with high-grade glioma who received postsurgical treatment had better survival than those without adjuvant therapy (Grade III: 52.6 vs. 20.3 months, P = 0.012; Grade IV: 22.6 vs. 12.1 months, P < 0.001). Among patients with diffuse low-grade gliomas, age, performance status, preoperative seizure, Ki-67 index, tumor subtype, and resection extent were associated with clinical outcomes. Conclusion: Glioma patients are not always treated according to guidelines. Although standard care may lead to favorable prognoses, individualized treatments may be more acceptable and result in better outcomes and should thus be considered in routine clinical practice.

Background and Aim: Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) gene, which confers a limited response to standard-of-care treatment with temozolomide (TMZ), resulting in a lower survival. Dianhydrogalactitol (VAL-083) is a novel bi-functional DNA-targeting agent that induces interstrand cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated repair of the O6 guanine alkylator TMZ. A Phase 2 study has been initiated for VAL-083 in newly diagnosed MGMT unmethylated GBM. Subjects and Methods: The study has two parts: part 1 is a dose–escalation and induction format to enroll up to ten patients in which they received VAL-083 at 20, 30, or 40 mg/m2 per day for 3 days every 21 days concurrently with standard radiation treatment and VAL-083 for up to eight additional cycles. Part 2 comprises an expansion phase to enroll up to twenty additional patients. This study was performed with approval by the Institutional Review Board of Sun Yat-sen University Cancer Center (B2016-058-01) on January 13, 2017, and registered with the ClinicalTrials.gov (NCT03050736) on February 13, 2017. Results: After completion of dose escalation, VAL-083, 30 mg/m2 per day, in combination with radiation therapy, was generally safe and well tolerated. At the cutoff date, 23 patients had been enrolled, 14 of whom had been treated in the expansion phase. Consistent with prior studies, myelosuppression was the most common adverse event. Pharmacokinetic assessment indicated that the levels of VAL-083 were as high in the cerebrospinal fluid as in plasma, 2 h postinfusion. Of the 22 patients who had reached their four precycle magnetic resonance imaging assessments, 12 were assessed with disease progression, with a median progression-free survival of 9.9 (95% confidence interval 7.3–12.0) months for all the patients studied. Conclusion: These preliminary data support VAL-083 as a potentially valuable treatment option for newly diagnosed GBM.

BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

Background: Medulloblastoma (MB) is one of the most malignant neuroepithelial tumors in the central nervous system. This study aimed to establish an effective prognostic nomogram and risk grouping system for predicting overall survival (OS) of patients with MB.Materials and Methods: The nomogram was constructed based on data from the database of Surveillance, Epidemiology, and End Results (SEER). This database consisted of 2,824 patients with medulloblastoma and was used as the training cohort. The data of another additional 161 patients treated at the Sun Yat-sen University Cancer Center (SYSUCC) were used as the external validation cohort. Cox regression analysis was used to select independent prognostic factors. Concordance index (C-index) and calibration curve were used to predict the prognostic effect of the nomogram for overall survival.Results: In the training cohort, Cox regression analyses showed that the prognostic factors included histopathology, surgery, radiotherapy, chemotherapy, tumor size, dissemination, and age at diagnosis. The internal and external validated C-indexes were 0.681 and 0.644, respectively. Calibration curves showed that the nomogram was able to predict 1-, 3-, and 5-year OS for patients with MB precisely. Using the training cohort, a risk grouping system was built, which could perfectly classify patients into four risk nomogroups with a 5-year survival rate of 83.9%, 76.5%, 64.5%, and 46.8%, respectively.Conclusion: We built and validated a nomogram and risk grouping system that can provide individual prediction of OS and distinguish MB patients from different risk groups. This nomogram and risk grouping system could help clinicians making better treatment plan and prognostic assessment.

Purpose: Metastatic nasopharyngeal carcinoma (mNPC) remains incurable. This prospective study aimed to investigate whether adding cetuximab to cisplatin-based induction therapy could improve efficacy and survival for chemotherapy-naïve mNPC patients.Patients and Methods: Eligible chemotherapy-naïve mNPC patients were enrolled, including those initially diagnosed with mNPC (IM) and those with first-relapse metastases after radiotherapy (RM). Patients all received induction chemotherapy (IC) including docetaxel and cisplatin plus cetuximab. Those who obtained objective remission after IC would continue to receive radiotherapy concurrent with cetuximab and cisplatin, and further capecitabine as maintenance. Contemporaneous patients who received conventional therapy served as controls.Results: Forty-three patients were enrolled, including 17 IM and 26 RM patients. Thirty-nine (90.7%) patients had WHO III subtype. The overall response and complete response (CR) rates were, respectively, 79.1 and 34.9% after induction therapy and 76.7 and 46.5% after chemoradiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates reached 34.9 and 30%, respectively. Subgroup analysis showed that compared with RM patients, IM patients had a higher 5-year OS (58.8 vs. 19.2%) and PFS (52.9 vs. 19.2%). The IM group had a higher CR rate of induction treatment than the RM group (52.9 vs. 23.1%). No treatment-related death was observed. Twelve patients (27.9%) remained alive with disease-free survival times from 60+ to 135+ months. Control patients showed a substantially lower survival rate (5-year OS, 10.9%) and few long-term survivors.Conclusions: This regimen resulted in significantly improved efficacy and survival, which indicates a potentially curative role for chemotherapy-naïve mNPC, especially in newly diagnosed patients. A phase III clinical trial (NCT02633176) is ongoing for confirmation.

Emerging Microbes & Infections (2017) 6, e2; doi:10.1038/emi.2016.131; published online 4 January 2017

Acute hepatopancreatic necrosis disease (AHPND) is a severe shrimp disease originally shown to be caused by virulent strains of Vibrio parahaemolyticus (VPAHPND). Rare cases of AHPND caused by Vibrio species other than V. parahaemolyticus were reported. We compared an AHPND-causing V. campbellii (VCAHPND) and a VPAHPND isolate from the same AHPND-affected pond. Both strains are positive for the virulence genes pirABvp. Immersion challenge test with Litopenaeus vannamei indicated the two strains possessed similar pathogenicity. Complete genome comparison showed that the pirABvp-bearing plasmids in the two strains were highly homologous, and they both shared high homologies with plasmid pVA1, the reported pirABvp-bearing plasmid. Conjugation and DNA-uptake genes were found on the pVA1-type plasmids and the host chromosomes, respectively, which may facilitate the dissemination of pirABvp. Novel variations likely driven by ISVal1 in the genetic contexts of the pirABvp genes were found in the two strains. Moreover, the VCAHPND isolate additionally contains multiple antibiotic resistance genes, which may bring difficulties to control its future outbreak. The dissemination of the pirABvp in non-parahaemolyticus Vibrio also rises the concern of missing detection in industrial settings since the isolation method currently used mainly targeting V. parahaemolyticus. This study provides timely information for better understanding of the causes of AHPND and molecular epidemiology of pirABvp and also appeals for precautions to encounter the dissemination of the hazardous genes.

Efficient provisioning of 5G network slices is a major challenge for 5G network slicing technology. Previous slice provisioning methods have only considered network resource attributes and ignored network topology attributes. These methods may result in a decrease in the slice acceptance ratio and the slice provisioning revenue. To address these issues, we propose a two-stage heuristic slice provisioning algorithm, called RT-CSP, for the 5G core network by jointly considering network resource attributes and topology attributes in this paper. The first stage of our method is called the slice node provisioning stage, in which we propose an approach to scoring and ranking nodes using network resource attributes (i.e., CPU capacity and bandwidth) and topology attributes (i.e., degree centrality and closeness centrality). Slice nodes are then provisioned according to the node ranking results. In the second stage, called the slice link provisioning stage, the k-shortest path algorithm is implemented to provision slice links. To further improve the performance of RT-CSP, we propose RT-CSP+, which uses our designed strategy, called minMaxBWUtilHops, to select the best physical path to host the slice link. The strategy minimizes the product of the maximum link bandwidth utilization of the candidate physical path and the number of hops in it to avoid creating bottlenecks in the physical path and reduce the bandwidth cost. Using extensive simulations, we compared our results with those of the state-of-the-art algorithms. The experimental results show that our algorithms increase slice acceptance ratio and improve the provisioning revenue-to-cost ratio.

Polyamidoamine (PAMAM) dendrimers are efficient drug carriers. The presence of a physiological pathway for nasal brain transport provides a potential path for direct brain-targeted delivery of dendrimer nanocomposites. In this study, we synthesized PAMAM dendrimer composites with a nanoscale size; the particle size of PAE (Paeonol)/mPEG (the heterofunctional PEG polymer with a methoxy)-PAMAM G5.NHAc and mPEG-PAMAM G5.NH2-FITC were 72.41 ± 11.58 nm and 96.51 ± 7.77 nm, and the zeta potential of PAE/mPEG-PAMAM G5.NHAc and mPEG-PAMAM G5.NH2-FITC were + 0.57 ± 0.11 mv and + 9.60 ± 0.41 mv, respectively. The EE% and DL% of PAE in PAE/mPEG-PAMAM G5.NHAc were 53.77% and 13.92%, respectively. PAE/mPEG-PAMAM G5.NHAc/DGG ionic-sensitive in situ gel was prepared, the viscosity of solution and gel state were 112 ± 3.2 mPa and 1403 ± 38.5 mPa, respectively. The in vitro goat mucoadhesive strength of the gel was 4763.36 ± 85.39 dyne/cm2. In situ gel system was proven to be a non-Newtonian pseudo-plastic fluid with shear thinning, thixotropy and yield stress. The optimal model of PAE released from PAE/mPEG-PAMAM G5.NHAc and PAE/mPEG-PAMAM G5.NHAc/DGG were the Higuchi equation and the Korsmeyer-Peppas equation, respectively. The cytotoxicity of the nanocomposites showed a concentration-dependence, and the cell viabilities of PAE/mPEG-PAMAM G5.NHAc were both higher than 95% between 0.0001 μM and 10 μM. mPEG-PAMAM G5.NH2-FITC was efficiently taken up by cells and exhibited strong fluorescence in the cytoplasm and nucleus. Significant accumulation of nanocomposites was observed in the brain after administration of the in situ gel group, and maximum accumulation was reached at 12 h. A small amount of accumulation was observed in the nanocomposite solution group only at 2 h. Therefore, the direct nasal brain transport efficiency of PAMAM dendrimer nanocomposites can be significantly improved after combining with in situ gel. PAMAM dendrimer nanocomposite/DGG is a potential drug delivery system for nasal brain transport.

We recently showed that IGFBP2 is overexpressed in primary lung cancer tissues. This study aims to determine whether IGFBP2 is elevated in blood samples of lung cancer patients and whether its level is associated with clinical outcomes.Plasma IGFBP2 levels were determined blindly by enzyme-linked immunosorbent assay in 80 lung cancer patients and 80 case-matched healthy controls for comparison. We analyzed blood samples for IGFBP2 levels from an additional 84 patients with lung cancer and then tested for associations between blood IGFBP2 levels and clinical parameters in all 164 lung cancer patients. All statistical tests were two-sided and differences with p160.9 ng/ml is 15.1 months; whereas median survival time was 128.2 months for the patients whose blood IGFBP2 was ≤ 160.9 ng/ml (p =0.0002).Blood IGFBP2 is significantly increased in lung cancer patients. A high circulating level of IGFBP2 is significantly associated with poor survival, suggesting that blood IGFBP2 levels could be a prognostic biomarker for lung cancer.

Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues.We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA) assay. The results showed that 18 molecules were significantly different (p