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Facing cancer diagnosis, patients with cancer are prone to psychological stress and consequent psychological disorders. The association between psychological stress and cancer has long been a subject of high interest. To date, preclinical studies have gradually uncovered the promotive effects of psychological distress on tumor hallmarks. In contrast, eustress may exert suppressive effects on tumorigenesis and beneficial effects on tumor treatment, which brings a practicable means and psychosocial perspective to cancer treatment. However, the underlying mechanisms remain incompletely understood. Here, by focusing on the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, as well as stress-related crucial neurotransmitters and hormones, we highlight the effects of distress and eustress on tumorigenesis, the tumor microenvironment, and tumor treatment. We also discuss the findings of clinical studies on stress management in patients with cancer. Last, we summarize questions that remain to be addressed and provide suggestions for future research directions.

Background: The IMpower133 represented the current standard of care in the 1L setting for patients (pts) with ES-SCLC (extensive-stage small cell lung cancer). However, there are still unmet needs for ES-SCLC treatment. LDRT could play a key role in the priming effect of immune system by acting as an immune adjuvant and having sensitive cytotoxic activity to SCLC. The interim analysis of MATCH study after stage I showed promising benefit and tolerability of combination of Atezo + chemotherapy + LDRT in pts with ES-SCLC. Here we report the primary efficacy and safety results of this study. Methods: The MATCH study was a single-arm phase II trial conducted in 8 centers across China. Previously untreated ES-SCLC pts with measureable disease per RECIST v1.1 at baseline, age≥18, ECOG 0-1 were eligible. Atezo (1200 mg IV, D1) + Cisplatin (75 mg/m2 IV, D1)/Carboplatin (AUC = 5 IV, D1) +Etoposide (100 mg/m2 IV, D1-D3) were administrated on a 21-day cycle for four cycles. Concurrent LDRT (15 Gy/5f) were conducted from D1-D5 in the first cycle. Then pts received Atezo maintenance until loss of clinical benefit or unacceptable toxicity. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with a complete response or partial response on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. A Simon’s minimax 2-stage design was adopted. Results: As the cutoff date of 30th Nov. 2022, 56 pts have been enrolled. 49 (87.5%) were males; mean age was 58.9 years with 78.6% pts had ECOG PS of 1. 80.4% pts had smoking history. Most pts were staged T4 (n = 33, 58.9%), N3 (n = 37, 66.1%) and M1(n = 40, 71.4%). Median follow-up was 14.8 months (range: 11.6-17.8 m). The confirmed ORR was 87.5% (95% CI: 75.9%-94.8%), all partial response. DCR was 94.6% (95% CI: 85.1%-98.9%). Median PFS was 6.9 m (95% CI: 5.4-9.3 m). The 6-month and 12-month PFS rate were 56.5% and 27.7%. Median OS was not reached (NR, 95% CI: 13.3m, NR). The 12-month OS rate was 71.9%. The safety profile, analyzed in all 56 pts, was consistent with the previous reports. Neutrophil count decreased (60.7%), white blood cell count decreased (58.9%) and platelet count decreased (23.2%) were the most common grade (G) 3-4 adverse events (AE). G5 AE occurred in 1 pt (pneumonia and pulmonary embolism). 4 pts experienced AEs leading to treatment discontinuation. IrAEs were reported in 21 (37.5%) pts, most common irAEs were hyperthyroidism (5.4%) and rash (5.4%). Radiation pneumonitis (G1) was observed in 1 pt. Conclusions: Adding LDRT to Atezo + chemotherapy shows impressive antitumor activity, potential survival benefit and well tolerability in 1L treatment of ES-SCLC. Clinical registration: NCT04622228. Citation Format: Lin Zhou, Jianguo Sun, Conghua Xie, Youling Gong, Meijuan Huang, Zhiyong Yuan, Lin Wu, Hui Wang, Nan Bi, Yaping Xu, Jiang Zhu, Yongmei Liu, Yan Zhang, Min Fan, Bingwen Zou, Min Yu, Yanying Li, Feifei Na, Weigang Xiu, Yong Xu, Jin Wang, Xuanwei Zhang, Jianxin Xue, You Lu. Efficacy and safety of Low dose radiotherapy (LDRT) concurrent Atezolizumab (Atezo) plus chemotherapy as first line (1L) therapy for ES-SCLC: Primary analysis of Phase II MATCH study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT219.

Objective The purpose of this study was to initially investigate whether previous antiangiogenic therapy (bevacizumab and endostar) affect the efficacy of anlotinib in patients with lung cancer (LC). Methods We retrospectively collected the clinical data of LC patients treated with anlotinib. They were divided into two groups, namely group A (anlotinib after failure of previous antiangiogenic drugs and group B (no prior use of antiangiogenic drugs). Use propensity score matching (PSM) to control the confounding factors between the groups.Results A total of 160 patients were included in the analysis. The median OS in group A and group B was 11.8 months vs. 16.1 months (P=0.120), and the median PFS was 3.1 months, 4.7 months, respectively (P=0.009). The ORR of the two groups was 9.6% vs. 10.4% (P=0.874), and the DCR was 71.1 % vs. 80.5% (P=0.165).After PSM (n=46), baseline characteristics were equitably comparable between the two groups. It was found that the median OS of the two groups was 14.6 months vs. 16.2 months (P=0.320), and the median PFS was 3.5 months vs. 4.5 months (P=0.040). The ORR of the two groups were 13.0%, 10.9% (P=0.748), and the DCR were 78.3%, 82.6% (P=0.599), respectively. These results provided further evidence that although PFS of group A was relatively shorter than that of group B, it may not affect patients’ OS.Conclusions Previous antiangiogenesis treatments may affect the PFS of patients who receive anlotinib later, but it might not affect the patient’s ORR and OS.

This paper focuses on the advanced Forward Error Correction (FEC) based on Low-Density Parity-Check (LDPC) codes for remote control and data transmission of Aeronautic and Astronautic Vehicles (AAV). It shows that the nontransparent LDPC codes with odd row weights are able to resist phase inversion with a small computational overhead. To the best of our knowledge, it is the first time to use FEC to resist phase inversion. Then, a high hardware-efficient FEC design for AAV, which is capable of correcting random errors as well as phase inversion, is proposed based on circulant decomposition with circulant size of 2s. Such a (4096, 2048) LDPC code has been adopted in a data transmission system due to its excellent error performance and hardware efficiency. Keywords: Circulant decomposition, FEC, High efficiency, LDPC, Nontransparent

The therapeutic efficacy of CAR-T cells in solid tumors, unlike in hematologic tumor, is greatly limited by the insufficient infiltration and persistence of CAR-T cells as well as the immunosuppressive tumor microenvironment. The aim of this study was to overcome these obstacles by introducing an αPDL1/CD28 switch-receptor construct and by seeking combinatorial strategies for CAR-T cells in solid tumors. We found that in non-transduction T cells, the cytokine release and T cell proliferation were repressed in response to PD-L1 protein, while T cells that express αPDL1/CD28 switch-receptor showed enhanced functions, indicating that αPDL1/CD28 could revert PD-L1 inhibition into CD28 costimulation. CAR-T cells with αPDL1/CD28 switch-receptor showed better effector function than that of unitary CAR-T in vitro studies and significant responses in tumor-bearing mice, with more effector memory T cells infiltrated in the tumor. On this basis, PD-1 inhibitor can further enhance the efficacy and persistence of αPDL1/CD28 CAR-T cells, especially in PDL1+ tumor models. We found in vitro studies that radiotherapy increased the expression of T-cell recruiting chemokines and promoted CAR-T cell transmigration. In tumor-bearing mice, synergistic anti-tumor efficacy of mice treated with radiotherapy and αPDL1/CD28 CAR-T cells was further observed. Finally, triple therapy with radiotherapy and anti-PD1 plus αPDL1/CD28 CAR-T cells maximized antitumor responses and induced complete cures in the tumor-bearing mice. Our study suggests that αPDL1/CD28 augments the function of CAR-T cells, and the combinatorial regime of αPDL1/CD28 CAR-T cells, radiotherapy and anti-PD1 in solid tumors could be further investigated. Citation Format: Limei Yin, Wenbo Wang, Zhuoran Yao, Jianxin Xue, Ruizhan Tong, Hui Wang, Shuangsi Liao, Laduona Wang, Yue Zheng, Feifei Na, Min Yu, Xuanwei Zhang, Youling Gong, Meijuan Huang, Xianming Mo, Chong Chen, You Lu. CAR-T cells with αPDL1/CD28 switch-receptor synergize radiotherapy and anti-PD1 therapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5569.

e21174 Background: Low dose radiation (LDRT) can potentially enhance the synergistic anti-tumor effect in metastatic NSCLC when combining with immunotherapy and SBRT. We previously reported the safety and tolerability of this new combination strategy. Here we presented the updated safety and efficacy data. Methods: This phase I study included a dose escalation phase (aimed to determine the optimal LDRT dose) and a dose expansion phase. Eligible patients had histologically or cytologically confirmed NSCLC, stage IV, PD-L1 positive (TPS ≥ 1%), and at least 2 extra-cranial tumor lesions. Patients received SBRT (30Gy/3f) to a small lesion and LDRT to a large lesion concurrently, followed by sintilimab (200mg i.v., q3w) started within 7 days after radiation completion until disease progression, unacceptable toxicities or reached a maximum of 24 months. Primary endpoints were safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Between 4/2019 and 10/2021, 29 patients were enrolled and treated. No dose limiting toxicities were observed during the dose escalation phase and 4Gy/2f was chosen as recommended LDRT dose for expansion phase. Most patients were male (89.7%) with adenocarcinoma (58.6%). 34.4% patients had PD-L1 TPS ≥ 50%. Until data cutoff (1/8/2022), the median follow-up was 15.5 (range: 1.2-32.5) months. Treatment-related adverse events (TRAEs) occurred in 96.6% patients (28/29) and 20.7% (6/29) were grade 3-4. Permanent discontinuation due to TRAEs occurred in 6.9% (2/29) patients. Eight patients experienced pneumonitis, including 1 grade 1, 6 grade 2 and 1 grade 3. No grade 5 TRAE was observed. 51.7% (15/29) patients had potential immune-related AEs. Of the 28 patients who received at least one tumor assessment, the ORR was 60.7% (95%CI:40.6%-78.5%) and the confirmed ORR was 57.1% (95%CI:37.2%-75.5%). The median duration of response was 13.6 months (95%CI:7.9-19.3), and 4 patients maintained response after reaching the maximum treatment of 2 years. The disease control rate (DCR) was 78.6% (95%CI: 59.1%-91.7%). The median PFS was 8.6 months (95%CI: 5.7-11.5), the 12-month PFS rate was 39.6%, and the median OS was not reach. 17 patients were enrolled in the LDRT 4Gy/2f does group and 16 were evaluable. The ORR was 62.5%, the confirmed ORR was 56.3%, and the DCR was 81.25%. The median PFS was 9.0 months. Exploratory analysis revealed that patients with lower neutrophil to lymphocyte ratio (NLR) had longer PFS. Conclusions: This is the first prospective phase I study to evaluate a new combination with SBRT, LDRT and anti-PD-1 therapy. The result suggested it was tolerable and feasible, with encouraging ORR and PFS. The strategy of adding SBRT and LDRT to immuno-based systemic therapy in treatment naïve metastatic NSCLC warranted further exploration. Clinical trial information: NCT03812549.

e20608 Background: Immune checkpoint inhibitors (ICIs) provide a durable and long-term benefit but still unsatisfactory clinical efficacy for extensive-stage small cell lung cancer (ES-SCLC). An optimized dose and schedule of radiotherapy for ES-SCLC remain to be studied. We hypothesized that the addition of low-dose radiotherapy (LDRT) to ICI could improve the efficacy of ES-SCLC. Methods: In SCLC bearing mice, the tumor was irradiated with LDRT in dose-escalation starting at 3Gy×1 fractions (f) up to 3Gy×7f, and combined with PD-1 antibody injection (0.2mg/mouse, i.p, every 3 days). Mice were followed for tumor growth and survival. The tumor microenvironment was dynamically analyzed every 3 days till day 18 by flow cytometry and immunofluorescence. 15 patients (pts) with relapsed ES-SCLC who received the treatment with LDRT and PD-1 blockade were retrospectively reviewed. Results: LDRT with 3Gy×5f delivered over 5 days (LDRT15Gy/5f) was determined to be the optimized dose when combined with PD-1 blockade. Combined group exhibited obvious growth retardation and prolonged survival compared to either monotherapy.The most robust infiltration of T cells in combined group was observed on day 9 after start of treatment. Bulk and single-cell RNA-seq showed significant immune cells infiltration, predominately CD8+ T cells and M1 macrophage. The activation and degranulation of CD8+ T cells in combination group were enhanced. Intra-tumoral CD8+ T cells were mainly assigned to effector memory (Tem) cells, then exhausted precursor (Texp) cells and exhausted (Tex) cells. Pseudo-time analysis supported a state evolution model that CD8+ Tem cells differentiate into intra-tumoral CD8+ Tex cells through an intermediate CD8+ Texp state. Tumor cells were divided into clusters 0, 1, and 2. Cluster 0 nearly disappeared while the proportion of cluster 1 increased in combination therapy. Cluster 1 enriched inflammatory response pathways and higher expression of MHC class I versus clusters 0 and 2. Additionally, the density of intra-tumoral microvessel was decreased, while vascular perfusion and the number of pericyte-covered vessels increased in combined group. Correspondingly, 15 recurrent ES-SCLC pts who treated with up-front LDRT15Gy/5f plus PD-1 blockade showed an ORR of 80%. Median PFS and OS were 4.3 months and 10.9 months. PFS rates at 6, 12 and 24 months were 40%, 20% and 6.7%, and OS rates were 60%, 40% and 24%, respectively. No patient experienced above grade 4 radiation- and immunotherapy-related toxicity. Conclusions: Our study is the first report of the synergistic effect of LDRT15Gy/5f and PD-1 blockade in SCLC mice model and recurrent ES-SCLC pts. The LDRT15Gy/5f demonstrates both immunologic adjuvant and cytotoxic effect on SCLC, and is safe and feasible in clinical pts. Further translational research, Match trial (NCT04622228), is ongoing.

In present study, GO@SiO2 nanocomposites was prepared by coating nanoscale silica onto graphene oxide (GO). The nanocomposites were characterized with scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (IF-IR). Additionally, the demulsifying performance of the nanocomposites was investigated by the bottle test method. The results showed that GO@SiO2 nanocomposites had a good demulsifying performance both in oil-in-water (O/W) and water-in-oil (W/O) emulsions. When the concentration of GO@SiO2 was 200 ppm in O/W emulsion, the optimal light transmittance of aqueous phase (LTA) and corresponding oil removal rate (ORR) at room temperature could reach 86.9% and 99.48%, respectively. Also, GO@SiO2 had an excellent salt tolerance under acidic condition. Furthermore, GO@SiO2 nanocomposites also could demulsify the W/O emulsion, and the efficiency at 70℃ could reach 80.5% when the concentration was 400 ppm.

In current work, GO@SiO2 nanocomposite was prepared by coating nanoscale silica onto graphene oxide (GO). GO@SiO2 was characterized with scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (IF-IR). Additionally, the demulsifying performance of GO@SiO2 was investigated by bottle test. The results showed that GO@SiO2 had a good demulsifying performance in both oil-in-water (O/W) and water-in-oil (W/O) emulsions. When the concentration of GO@SiO2 was 200 ppm in the O/W emulsion, the optimal light transmittance of aqueous phase (LTA) and corresponding oil removal rate (ORR) at room temperature could reach 86.9% and 99.48%, respectively. Also, GO@SiO2 had an excellent salt tolerance under acidic condition. Furthermore, GO@SiO2 also could demulsify the W/O emulsion, and the efficiency at 70 °C could reach 80.5% when the concentration was 400 ppm.

Background: Primary mediastinal yolk sac tumors is a kind of primary mediastinal non-seminomatous germ cell tumor . The current treatment strategies in primary mediastinal non-seminomatous germ cell tumor is neoadjuvant chemotherapy followed by residual mass surgical resection . We reviewed our institutional 5 years' experience with Primary mediastinal yolk sac tumors who treated with platinum-based neoadjuvant chemotherapy and extended resection.Methods： We experienced 10 cases of Primary mediastinal yolk sac tumors from October of 2014 to October of 2019. 7 patients received preoperative platinum-based chemotherapy followed by surgical resection of residual mediastinal mass. The other 3 patients were received initial surgical resection without preoperative chemotherapy.Results：R0 resection was achieved in 8 patients (80%), and R2 resection was in the other 2 patients (20%). All the 7 patients with neoadjuvant chemotherapy were R0 resections, however all of them had viable tumor in their surgical specimen. Morbidities after surgery occurred in 2 patients, including 2 pneumonias ,1 type I respiratory failure and 1 acute left heart failure, and They were died within 2 months after surgery. At the time of writing ,3 patients are alive without evidence of disease,7 patients died , of which 5 patients have died of tumor-related causes and 2 died of postoperative complications. 8 patients were included in the follow-up. Among them 7patients experienced progressed within one year. 8 patients were included in the follow-up,mPFS and mOS in 8 patients were 3.7 months (2.6-41.3m) and 23.15 months (8.6-41.3m) , respectively. The 7 patients with neoadjuvant chemotherapy followed by surgical resection of residual diseases, 2-year survival rate was 57.1%,The 3-year survival rate was 28.6%Conclusion: An aggressive, multidisciplinary treatment including neoadjuvant chemotherapy followed by residual mass surgical resection is the optimal treatment and can be associated with prolonged survival.

In the paper, we report the results for the NLPCC2021 shared-task of Few-shot Learning for Chinese NLP. This shared task is proposed in the context of pre-trained language models, where models only have access to limited human-labeled data. The goal of the task is to compare different learning schemes. The task includes nine sub-tasks and three task forms: single sentence classification, sentence pair classification, and machine reading comprehension. In order to accommodate the properties of few-shot learning, we sampled the examples using various sampling methods, some with 32 examples in total for one dataset, while others with 4 to 16 examples per class. Ninety teams registered for the shared task, employing a wide range of learning schemes, including data augmentation, utilizing multiple templates rather than a single template, using unlabeled data for pre-training or semi-supervised training. The best model achieved 65.3 in the mean accuracy, compared with the human score of 83.9. This result is 8 points higher than our baseline model (using the PET scheme). We believe our few-shot learning tasks and results demonstrate the potential of the recently introduced few-shot learning methods and provide guidance and important empirical evidence for future research.

Purpose Hypofractionated radiation therapy (HFRT) can induce antitumor T cell responses, particularly in combination with immune checkpoint inhibitors (ICI), but abscopal effects are often precluded by insufficient T cell infiltration of distant, nonirradiated tumors. Additional noncytotoxic, low-dose radiation therapy (LDRT) of distant tumors may enhance the abscopal response, but clinical evidence and preclinical studies for this scenario are lacking. Methods and Materials We investigated whether triple treatment consisting of HFRT, ICI, and LDRT could achieve better systemic antitumor response in bilateral mouse tumor models and in patients with stage IV non-small cell lung cancer. Results Our analyses of bilateral mouse tumor models show that HFRT treatment of the primary tumor combined with LDRT treatment of the abscopal tumor and anti-PD1 therapy enhances the abscopal response compared with HFRT/anti-PD1, HFRT/LDRT, or LDRT/anti-PD1 double treatments; complete cure was observed in more than half of the mice treated with triple therapy. The enhanced abscopal effect was associated with increased infiltration of CD8+ effector T cells and upregulated expression of T cell–attracting chemokines. Of 9 patients with metastatic non-small cell lung cancer who were treated with this triple therapy, 3 and 2 patients showed partial responses and stable disease, respectively. Among 9 relatively large (175.7 ± 42.3 cm3) LDRT lesions, 6 lesions decreased by 28% in size, on average. Conclusions Our study demonstrates preclinically that LDRT of established metastases significantly enhances the abscopal response to HFRT plus ICI. It also shows that additional LDRT was well tolerated by patients and that this treatment profile is effective and worth further study.

We present the results of shared-task 1 held in the 2020 Conference on Natural Language Processing and Chinese Computing (NLPCC): Light Pre-Trained Chinese Language Model for NLP tasks. This shared-task examines the performance of light language models on four common NLP tasks: Text Classification, Named Entity Recognition, Anaphora Resolution and Machine Reading Comprehension. To make sure that the models are light-weight, we put restrictions and requirements on the number of parameters and inference speed of the participating models. In total, 30 teams registered our tasks. Each submission was evaluated through our online benchmark system (https://www.cluebenchmarks.com/nlpcc2020.html), with the average score over the four tasks as the final score. Various ideas and frameworks were explored by the participants, including data enhancement, knowledge distillation and quantization. The best model achieved an average score of 75.949, which was very close to BERT-base (76.460). We believe this shared-task highlights the potential of light-weight models and calls for further research on the development and exploration of light-weight models.

The advent of natural language understanding (NLU) benchmarks for English, such as GLUE and SuperGLUE allows new NLU models to be evaluated across a diverse set of tasks. These comprehensive benchmarks have facilitated a broad range of research and applications in natural language processing (NLP). The problem, however, is that most such benchmarks are limited to English, which has made it difficult to replicate many of the successes in English NLU for other languages. To help remedy this issue, we introduce the first large-scale Chinese Language Understanding Evaluation (CLUE) benchmark. CLUE is an open-ended, community-driven project that brings together 9 tasks spanning several well-established single-sentence/sentence-pair classification tasks, as well as machine reading comprehension, all on original Chinese text. To establish results on these tasks, we report scores using an exhaustive set of current state-of-the-art pre-trained Chinese models (9 in total). We also introduce a number of supplementary datasets and additional tools to help facilitate further progress on Chinese NLU. Our benchmark is released at https://www.CLUEbenchmarks.com, Comment: Accepted by COLING2020; 10 pages, 4 figures

Incorporation of guest organic molecules into zeolites has attracted much more attention for its broad application prospect in the fields of sensing, detection, antibacterial and so on. In this study, indole and its derivatives were successfully incorporated into zeolite beta through in situ encapsulation approach for the first time, which can overcome the drawbacks brought by traditional impregnation method and ion-exchange method. Taking indole as an example, the structure of obtained zeolite beta encapsulation of indole (indole@beta) has been well characterized to confirm the location of indole at zeolite inner channels. Thanking to confinement effect of zeolite, the release of indole from indole@beta complexes showed much slower release rate than that of indole/beta complexes, and along with pH sensitivity and temperature dependence. Such release behavior can be described with ritger-peppas model to obey the Fick's Laws of diffusion. In comparison with indole/beta coating, indole@beta coating exhibited more sustainable and effective antibacterial activity for its controlled release properties.

An environmentally friendly LLP@SiO2 demulsifier was prepared by coating nano-SiO2 on the natural lotus leaf powder (LLP) via a simple hydrothermal method. Fourier-transform infrared spectroscope (FT-IR), field-emission scanning electron microscope (FE-SEM), energy dispersive X-ray spectroscope (EDS) and thermal gravimetric analyzer (TGA) were employed to characterize the demulsifier. The effect of the LLP@SiO2 dosage, temperature, settling time, pH value and salt concentration on the demulsifying process was studied in detail. The bottle test results showed that the demulsification efficiency (DE) reached 83.78% within 1 min when the dosage was 600 mg/L at 70 °C. The DE could increase to 91.91% if the settling time was prolonged to 60 min. The LLP@SiO2 demulsifier had excellent acid and salt tolerance, and the high salinity also could improve the demulsification performance. It showed that the DE could maintain at 91.91% even at strong acid condition of pH = 2 and it increased to 94.33% when the salinity was increased to 20,000 mg/L. In addition, the possible demulsification mechanism was systematically studied by the interfacial activity, interfacial tension (IFT), wettability and microexamination.

PTEN pseudogene (PTENP1) has a tumor suppressive role in multiple cancers. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains largely unknown. In this study, we set out to identify the role of PTENP1 in the development of ESCC. Gene Expression Omnibus database was employed to investigate the expression of PTENP1 in ESCC. sRNA target Database (StarBase v2.0) was used to query the downstream of PTENP1. Next, both in vitro and in vivo experiments were employed to explore the function. Cell proliferation was evaluated by CCK-8, soft agar, and colony formation assays. Expression of relative genes was assessed by quantitative real-time PCR (qRT-PCR) and Western blotting. 3'UTR luciferase assay was used to confirm the miRNA binding. The clinical significance of PTENP1 was further validated by immunohistochemistry (IHC) and correlation with clinicopathological indicators in additional samples (n = 93). We found expression of PTENP1 in ESCC was lower than that in the corresponding adjacent normal tissues (n = 17). Overexpression of PTENP1 in Eca109 and TE-1 cells resulted in inhibited proliferation and altered expression of SOCS6-p-STAT3-HIF-1α pathway both in vitro and in vivo. Subsequent IHC reported a similar trend in human ESCC samples. 3'UTR luciferase assay demonstrated that PTENP1 3'UTR decoyed miR-17-5p from binding to SOCS6. Moreover, PTENP1 expression was correlated with clinicopathological indicators to varying degrees, including histological grade, TNM stage, infiltration depth, lymph node metastasis, and overall survival. Taken together, these results suggested an anti-oncogenic role of PTENP1. Meanwhile, PTENP1 may also serve as a candidate of prognostic indicator for ESCC patients.

In this paper, we reported the synthesis of NiO/Ni bilayer nanotubes by electrodeposition and thermal oxidation using anodic aluminum oxide templates. The morphology, structure, chemical composition and magnetic properties, especially magnetic exchange bias induced by subsequent magnetic field cooling, in this one-dimensional antiferromagnetic/ferromagnetic hybrid system were investigated. It was found that the effect of the annealing temperature, which mainly dominated the thickness of the NiO layer, and the annealing time, which mainly dominated the grain size of the NiO, on the exchange bias field showed competitive relationship. The optimized exchange bias field was achieved by the combination of the shorter annealing time and higher annealing temperature.

To extrapolate the infiltration levels of immune cells in patients with lower-grade gliomas (LGGs) using magnetic resonance imaging (MRI)-based radiomic features. A retrospective dataset of 516 patients with LGGs from The Cancer Genome Atlas (TCGA) database was analysed for the infiltration levels of six types of immune cells using Tumor IMmune Estimation Resource (TIMER) based on RNA sequencing data. Radiomic features were extracted from 107 patients whose pre-operative MRI data are available in The Cancer Imaging Archive; 85 and 22 of these patients were assigned to the training and testing cohort, respectively. The least absolute shrinkage and selection operator (LASSO) was applied to select optimal radiomic features to build the radiomic signatures for extrapolating the infiltration levels of immune cells in the training cohort. The developed radiomic signatures were examined in the testing cohort using Pearson’s correlation. The infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils and dendritic cells negatively correlated with overall survival in the 516 patient cohort when using univariate Cox’s regression. Age, Karnofsky Performance Scale, WHO grade, isocitrate dehydrogenase mutant status and the infiltration of neutrophils correlated with survival using multivariate Cox’s regression analysis. The infiltration levels of the 6 cell types could be estimated by radiomic features in the training cohort, and their corresponding radiomic signatures were built. The infiltration levels of B cells, CD8+ T cells, neutrophils and macrophages estimated by radiomics correlated with those estimated by TIMER in the testing cohort. Combining clinical/genomic features with the radiomic signatures only slightly improved the prediction of immune cell infiltrations. We developed MRI-based radiomic models for extrapolating the infiltration levels of immune cells in LGGs. Our results may have implications for treatment planning.

Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 editing of immune checkpoint genes could improve the efficacy of T cell therapy, but the first necessary undertaking is to understand the safety and feasibility. Here, we report results from a first-in-human phase I clinical trial of CRISPR–Cas9 PD-1-edited T cells in patients with advanced non-small-cell lung cancer (ClinicalTrials.gov NCT02793856 ). Primary endpoints were safety and feasibility, and the secondary endpoint was efficacy. The exploratory objectives included tracking of edited T cells. All prespecified endpoints were met. PD-1-edited T cells were manufactured ex vivo by cotransfection using electroporation of Cas9 and single guide RNA plasmids. A total of 22 patients were enrolled; 17 had sufficient edited T cells for infusion, and 12 were able to receive treatment. All treatment-related adverse events were grade 1/2. Edited T cells were detectable in peripheral blood after infusion. The median progression-free survival was 7.7 weeks (95% confidence interval, 6.9 to 8.5 weeks) and median overall survival was 42.6 weeks (95% confidence interval, 10.3–74.9 weeks). The median mutation frequency of off-target events was 0.05% (range, 0–0.25%) at 18 candidate sites by next generation sequencing. We conclude that clinical application of CRISPR–Cas9 gene-edited T cells is generally safe and feasible. Future trials should use superior gene editing approaches to improve therapeutic efficacy. In a first-in-human phase I trial of patients with advanced lung cancer, infusions of autologous T cells edited to delete the PD-1 gene via CRISPR–Cas9 were well tolerated and did not lead to severe treatment-related adverse events.

// Ruxing Xi 1 , Shupei Pan 1 , Xin Chen 2 , Beina Hui 1 , Li Zhang 1 , Shenbo Fu 1 , Xiaolong Li 3 , Xuanwei Zhang 1 , Tuotuo Gong 1 , Jia Guo 1 , Xiaozhi Zhang 1 , Shaomin Che 1 1 Department of Radiotherapy, The First Hospital Affiliated of Xi’an Jiao Tong University, Xi’an, Shaan Xi, 710061, P.R.China 2 Department of Radiotherapy, People’s Hospital of Shaanxi Province, Xi’an, Shaan Xi, 710068, P.R.China 3 Department of Radiotherapy, The People’s Liberation Army 323 Hospital, Xi’an, Shaan Xi, 710054, P.R.China Correspondence to: Xiaozhi Zhang, email: zhang9149@sina.com Shaomin Che, email: chersm@126.com Keywords: esophageal squamous cell carcinoma, HPV16 E6-E7, CSCs, PI3K, p75NTR Received: October 22, 2015 Accepted: July 16, 2016 Published: July 30, 2016 ABSTRACT High-risk human papillomavirus (HPV), especially HPV16, correlates with cancerogenesis of human esophageal squamous cell carcinoma (ESCC) and we have reported that HPV16 related with a poor prognosis of ESCC patients in China. We aim to investigate the potential role and mechanism of HPV16 in ESCC development and progress. Our following researches demonstrated that ESCC cells which were stably transfected by HPV16 E6-E7 lentiviral vector showed a remarkable cancer stem-like cells (CSCs) phenotype, such as: migration, invasion, spherogenesis, high expression of CSCs marker in ESCC---p75NTR, chemoresistance, radioresistance, anti-apoptosis ability in vitro and cancerogenesis in vivo . HPV16 E6-E7 induced PI3K/Akt signaling pathway activation and this affect could be effectively inhibited by LY294002, a specific PI3K inhibitor. It was also indicated that the inhibition of PI3K/Akt signaling pathway by PI3K and Akt siRNA reverse the effect which induced by HPV16 E6-E7 in ESCC cells. Taken together, the present study demonstrates that HPV16 E6-E7 promotes CSCs phenotype in ESCC cells through the activation of PI3K/Akt signaling pathway. Targeting the PI3K/Akt signaling pathway in HPV16 positive tissues is an available therapeutic for ESCC patients.

Pulse wave contains human physiological and pathological information. Different people will exhibit different characteristics, and hence determining the characteristic points of the pulse wave of human physiological health makes sense. It is common that we extract the characteristic value of pulse wave signal with the method based on wavelet transform on a small scale, and then determine the locations of the characteristic points by modulus maxima and modulus minima. Before determining characteristic value by detecting modulus maxima and modulus minima, we need to determine every period of the pulse wave. This paper presents a new kind of adaptive threshold determination method which is more effective. It can accurately determine every period of the pulse wave, and then extract characteristic values by modulus maxima and modulus minima in every period of the pulse wave. The method presented in this paper promotes the research utilizing pulse wave on health life.

Radiation therapy is one of the most important treatments for unresectable and locally advanced esophageal squamous cell carcinoma (ESCC), however, the response to radiotherapy is sometimes limited by the development of radioresistance. Sinomenine hydrochloride (SH) has anticancer activity, but its effect on the radiosensitivity of ESCC is unclear. We determined the effect of SH on the radiosensitivity of ESCC cells and elucidated its potential radiosensitization mechanisms in vitro and in vivo. ESCC cells were subjected to SH and radiation, both separately and in combination. Untreated cells served as controls. The CCK-8 assay was used to evaluate cell proliferation, and the clonogenic assay to estimate radiosensitization. Flow cytometry was used to investigate cell cycle phases and cell apoptosis. Bcl-2, Bax, cyclin B1, CDK1, Ku86, Ku70, and Rad51 expression was evaluated using western blotting. In vivo, tumor xenografts were created using BALB/c nude mice. Tumor-growth inhibition was recorded, and Ki-67 and Bax expression in the tumor tissues was assessed using immunohistochemistry. SH inhibited ESCC cell growth and markedly increased their radiosensitivity by inducing G2/M phase arrest. SH combined with radiation therapy significantly increased ESCC cell apoptosis. The molecular mechanism by which SH enhanced radiosensitivity of ESCC cells was related to Bcl-2, cyclin B1, CDK1, Ku86, Ku70, and Rad51 downregulation and Bax protein expression upregulation. SH combined with radiation considerably delayed the growth of tumor xenografts in vivo. Immunohistochemical analysis showed that in the SH combined with radiation group, the expression of Bax was significantly higher while that of Ki-67 was lower than the expressions in the control groups. Taken together, our findings showed that SH could improve the sensitivity of radiation in ESCC cells by inducing G2/M phase arrest, promoting radiation-induced apoptosis and inhibiting DSB-repair pathways. SH appears to be a prospective radiosensitizer for improving the efficacy of radiotherapy for ESCC.

This study was intended to determine whether antidepressant outcome to SSRIs was associated with catecholamine gene polymorphisms and neuroendocrine factors in patients of Chinese Han ethnicity with MDD.A total of 290 MDD patients were recruited and received a 6-week randomized double-blinded treatment. Cortisol, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), 3'-triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4) levels were measured at the baseline. Allele, genotype, and haplotype frequencies of catecholamine genes were compared between responders and non-responders, remission and non-remission groups respectively.We found that genotype frequency of the rs1800544 polymorphism in the DRD4 gene was significantly different between responders and non-responders (P0.05). Also the frequency of the rs1800544 CG genotype was significantly higher (P0.05) in responders (51.4%) than that in non-responders (35.8%). No significant difference was found between responders and non-responders, remission and non-remission groups in the SNPs polymorphisms in the TPH, SLC6A2, SLC6A3, or DRD2 genes. The combination of all neuroendocrine factors, clinical characteristics and gene polymorphisms predicted 74.8% of the variation in SSRI response and 65.5% in SSRI remission.Polymorphisms of the DRD4 gene were associated with SSRI response in Chinese Han MDD patients. A combination of clinical characteristics, neuroendocrine factors, and gene polymorphisms might be able to predict the outcome to SSRIs.

Purpose Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell–mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment. Methods and Materials In mice bearing 2 B16-CD133 melanoma tumors, the primary tumor was irradiated with 3 × 9.18 Gy in 3 or 5 days or with 5 × 6.43 Gy in 10 days; an anti-PD1 antibody was given weekly. The mice were monitored for tumor growth and survival. T-cell responses were determined on days 8 and 15 of treatment. The role of regional lymph nodes was studied by administering FTY720, which blocks lymph node egress of activated T cells. Tumor growth measurements after combination treatment using short or extended hRT and control treatment were also performed in the wild-type B16 melanoma and 4T1 breast carcinoma models. Results In the B16-CD133 model, growth inhibition of irradiated primary and nonirradiated secondary tumors and overall survival were similar with all 3 hRT/anti-PD1 combinations, superior to hRT and anti-PD1 monotherapy, and was strongly dependent on CD8+ T cells. TIL infiltration and local and systemic tumor-specific CD8+ T-cell responses were also similar, regardless of whether short or extended hRT was used. Administration of FTY720 accelerated growth of both primary and secondary tumors, strongly reduced their TIL infiltration, and increased tumor-specific CD8+ T cells in the lymph nodes draining the irradiated tumor. In the 4T1 model, local and abscopal tumor control was also similar, regardless of whether short or extended hRT was used, although the synergy between hRT and anti-PD1 was weaker. No synergies were found in the B16 wild-type model lacking an exogenous antigen. Conclusions Our data suggest that combination therapy with hRT schedules extending into the period during which treatment-induced T cells infiltrate the irradiated tumor can provoke local and systemic antitumor effects similar to those with therapy using shorter schedules, if the regional lymph nodes supply sufficient tumor-specific T cells. This has implications for planning clinical RT/immune checkpoint blockade trials.

A new identification method of impact load is proposed based on the transient statistical energy analysis theory in the paper. Firstly, the location and input energy of impact load are identified according to the energy balance equation with a two-stage identification scheme from the averaged kinetic energy responses of subsystems. Secondly, the impact load amplitude spectrum is derived from the identified impact load input energy based on the Parseval theorem under the constant value assumption within each analysis frequency band. Lastly, a parametric fitting approach is developed to reconstruct further the time history of impact load for the given time domain waveform from the identified impact load amplitude spectrum. The impact load identification approach is qualified through the simulated and experimental studies for a two-plate coupling structural system and the simulated study for a three-plate coupling structure system. The results show that the location and input energy of impact load can be identified accurately using the presented method. The derived impact load amplitude spectrums have reasonable agreements with the real ones. As a result, the reconstructed impact load time histories by the fitting method agree well with the real impact load time histories. The present approach provides an effective and feasible way for impact load identification of engineering structures.

The paper proposes an identification method of high frequency loads based on statistical energy analysis theory. The load identification problems of structures subjected to multi excitations are classified into three cases according to the completeness of loads location information and subsystem response set, and the corresponding identification schemes are presented. The approaches for the derivation of load power spectrum from input power are described as well under the assumptions of constant value and linear variation on load power spectrum within each analytical frequency band. The simulated and experimental studies of load identification with the approach were conducted on a plate–shell assembled structural system. The results show that the input power of loads can be identified accurately in three cases using the presented identification method. Besides that, the computed load power spectrums under the constant value assumption have reasonable agreements with the measured load power spectrums.

An identification method is developed for nonlinear hysteretic systems by use of artificial neural network in the paper. Employing the Bouc–Wen differential model widely used for memory-type nonlinear hysteretic systems, the approach sets up a Bouc–Wen model-based neural network. The weights of the designed specifically network correspond to the Bouc–Wen model parameters and are thus physical ones. Taking advantage of powerful function approximation capability of neural network, the nonlinear hysteretic systems can be identified with the proposed approach by network training. The identification scheme is validated by a simulated case and thereafter applied to modeling of a wire cable vibration isolation experimental system. The results show that the presented identification method can identify the nonlinear hysteretic systems with high accuracy.

Since the industrial age, along with the promotion of economic development, problems of ecological destruction and environmental pollution are becoming more serious. To solve this problem, the implementation of environmental tax is an effective measure. Based on the analysis of the theoretical foundation of environmental taxes, international practice and experience in environmental tax system, in this paper, the authors describe the status quo of China’s environmental tax system, and frames the further step strategy in building China’s environmental tax system.