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In recent years, various breakthroughs have been made in tumor immunotherapy that have contributed to prolonging the survival of tumor patients. However, only a subset of patients respond to immunotherapy, which limits its use. One reason for this is that the tumor microenvironment (TME) hinders the migration and infiltration of T cells and affects their continuous functioning, resulting in an exhausted phenotype. Therefore, clarifying the mechanism by which T cells become exhausted is of significance for improving the efficacy of immunotherapy. Several recent studies have shown that mitochondrial dynamics play an important role in the immune surveillance function of T cells. Dynamin-related protein 1 (Drp1) is a key protein that mediates mitochondrial fission and maintains the mitochondrial dynamic network. Drp1 regulates various activities of T cells in vivo by mediating the activation of a series of pathways. In addition, abnormal mitochondrial dynamics were observed in exhausted T cells in the TME. As a potential target for immunotherapy, in this review, we describe in detail how Drp1 regulates various physiological functions of T cells and induces changes in mitochondrial dynamics in the TME, providing a theoretical basis for further research.

Objectives The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte–macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment. Materials and methods Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8 Gy × 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research. Results Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n = 11), mediastinal lymph node (n = 5), liver (n = 1), abdominal lymph node (n = 1), pleural nodule (n = 1) and vertebra (n = 1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed. Conclusion Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants. Trial registration ClinicalTrials.gov, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC-Tabular View-ClinicalTrials.gov.

Lung cancer is the leading cause of cancer death worldwide as well as in China. For many years, conventional oncologic treatments such as surgery, chemotherapy, and radiotherapy (RT) have dominated the field of non-small cell lung cancer (NSCLC). The recent introduction of immunotherapy in clinical practice, led to a paradigm shift in lung cancer as in many other solid tumors. Recent pre-clinical and clinical data have shown RT may also modify antitumor immune responses through induction of immunogenic cell death and reprogramming of the tumor microenvironment. This has led many to reexamine RT as a partner therapy to immuno-oncology treatments and investigate their potential synergy in an exponentially growing number of clinical trials. Clinical trials combining radiotherapy and immunotherapy are attracting major attention, experts were invited to discuss frontier and controversial academic topics: (1) Recent developments of clinical synergy between radiation and immune checkpoint inhibitors (ICIs) in the treatment of NSCLC; (2) Will immunotherapy and radiotherapy increase the toxicity risk for cancer patients; (3) How to cope the mixed responses/disassociated responses phenomenon in checkpoint inhibition therapy to NSCLC with local ablative therapy; (4) Combining radiotherapy and immunotherapy in the treatment of NSCLC brain metastases.【中文题目：放疗联合免疫治疗非小细胞肺癌：前沿学术问题专家交流共识】 【中文摘要：肺癌是目前导致全球和中国癌症患者死亡的主要瘤种。多年来，常规的肿瘤治疗方法，如手术、化疗和放疗一直主导着非小细胞肺癌（non-small cell lung cancer, NSCLC）治疗领域。临床实践中引入免疫疗法使肺癌的治疗与其他实体瘤一样发生了根本性转变。最新临床前和临床数据表明，放疗可以通过诱导免疫原性细胞死亡和重新编程肿瘤微环境促进抗肿瘤免疫反应。研究者开始重新审视放疗作为免疫治疗的联合疗法，导致研究其潜在协同作用的临床试验数量呈指数级增长。放疗联合免疫治疗的临床试验引起了医疗界的广泛关注，会议邀请专家交流前沿及争议学术问题：①放疗联合免疫检查点抑制剂治疗NSCLC最新进展；②放疗联合免疫治疗是否显著增加毒性；③免疫检查点抑制剂治疗后出现的混合反应及局部治疗的干预价值；④放疗联合免疫治疗脑转移瘤的机制和进展。】 【中文关键词：免疫检查点抑制剂；肿瘤；放疗；免疫治疗；不良反应；毒性；混合反应；脑转移】.

BACKGROUND Before tyrosine kinase inhibitor (TKI) therapy can be administered in patients with advanced non-small cell lung cancer (NSCLC), EGFR mutation testing is required. However, few studies have evaluated the extent of EGFR testing in real-world practice in China. METHODS A multicenter, observational study of EGFR testing in NSCLC patients in North China was conducted. Treatment-naive patients or those with postoperative recurrent stage IIIB/IV NSCLC were enrolled. The primary objective was EGFR testing rate. Secondary objectives included EGFR mutation status, EGFR testing methods and specimens, factors associated with EGFR testing, and overall survival with or without EGFR testing. RESULTS Overall, 2809 patients with stage IIIB/IV NSCLC were enrolled; 90.78% had adenocarcinoma. The EGFR screening rate was 42.54%. EGFR testing rates were higher in tumor samples obtained by lymph node puncture, and in patients with urban medical insurance, adenocarcinoma, non-smokers, or those located in developed cities (all P < 0.001). The EGFR mutation rate was 46.44%. The most commonly used specimens for EGFR testing were biopsy tumor samples (67.53%). PCR-based methods (72.05%), Sanger sequencing (5.36%), and Luminex liquid chip (5.10%) were the most frequently used testing platforms. Similar positive EGFR mutation rates were achieved with different platforms. TKI therapy was the first-line treatment administered to most EGFR-positive patients (56.22%), and chemotherapy in EGFR-negative patients (84.88%). Overall survival was higher in EGFR-tested than in untested patients (27.50 vs. 19.73 months; P = 0.007). CONCLUSION Real-world EGFR testing rates for NSCLC in North China were relatively low because of clinical and social factors, including medical insurance coverage.

In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.近年来随着对肿瘤驱动基因的不断探索和分子检测技术的快速发展，在非小细胞肺癌（non-small cell lung cancer, NSCLC）领域，一系列的驱动基因如EGFR、KRAS、BRAF、PIK3CA、ALK和ROS-1等相继被发现，并逐渐研发出相应的针对特定驱动基因变异的靶向治疗药物，使NSCLC患者的生存得到极大改善。尽管如此，仍有部分NSCLC患者未能检测到任何已知驱动基因变异，称之为pan-negative型NSCLC。本文就pan-negative型NSCLC的概念、临床病理和流行病学特点以及治疗预后等作一综述。.

Self-assembled monolayers are the basis for molecular nanodevices, flexible surface functionalization, and dip-pen nanolithography. Yet self-assembled monolayers are typically created by a rather inefficient process involving thermally driven attachment reactions of precursor molecules to a metal surface, followed by a slow and defect-prone molecular reorganization. Here we demonstrate a nonthermal, electron-induced approach to the self-assembly of phenylacetylene molecules on gold that allows for a previously unachievable attachment of the molecules to the surface through the alkyne group. While thermal excitation can only desorb the parent molecule due to prohibitively high activation barriers for attachment reactions, localized injection of hot electrons or holes not only overcomes this barrier but also enables an unprecedented control over the size and shape of the self-assembly, defect structures, and the reverse process of molecular disassembly from a single molecule to a mesoscopic length scale. Electron-induced excitation may therefore enable new and highly controlled approaches to molecular self-assembly on a surface.

Supramolecular self-assembly on well-defined surfaces provides access to a multitude of nanoscale architectures, including clusters of distinct symmetry and size. The driving forces underlying supramolecular structures generally involve both graphoepitaxy and weak directional nonconvalent interactions. Here we show that functionalizing a benzene molecule with an ethyne group introduces attractive interactions in a 2D geometry, which would otherwise be dominated by intermolecular repulsion. Furthermore, the attractive interactions enable supramolecular self-assembly, wherein a subtle balance between very weak CH/π bonding and molecule-surface interactions produces a well-defined "magic" dimension and chirality of supramolecular clusters. The nature of the process is corroborated by extensive scanning tunneling microscopy/spectroscopy (STM/S) measurements and ab initio calculations, which emphasize the cooperative, multicenter characters of the CH/π interaction. This work points out new possibilities for chemical functionalization of π-conjugated hydrocarbon molecules that may allow for the rational design of supramolecular clusters with a desired shape and size.

OBJECTIVE To explore the relationship between mtDNA (mitochondrial DNA) and gastric cancer by comparing the difference of mtDNA copy number in gastric cancers and paracancerous tissues. METHODS The HVl (hypervariable region) and HV2 of the mitochondrial D-loop region from 20 cases of gastric cancer and 20 paracancerous tissues were amplified by PCR with [3-actin serving as a quantitative standard marker. The products were separated by polyacrylamide gel electrophoresis (PAGE) and silver stained in order to compare the difference in mtDNA copy number between gastric cancers and paracancerous tissues. The mtDNA copy number was determined for gastric cancers having various pathological characteristics and the results compared with previous immunohistochemical staining of the tumors. RESULTS There was a significantly quantitative difference in HV1, HV2 (standardized with 13-actin) between gastric cancers and paracancerous tissues ( P 0.05). CONCLUSION The occurrence of gastric cancer was closely associated with decreased mtDNA copy number, which may be a new tumor marker.

Epidermal growth factor receptor (EGFR) and KRAS status were particularly critical for the choice of first-line targeted therapy of non-small cell lung cancer (NSCLC), while the primary tumor and metastases might be different in the EGFR and KRAS gene status. The aim of this pooled analysis is to compare EGFR and KRAS status in matching primary NSCLC and metastases and further to guide clinical practice.Systematic computerized searches of the Pubmed and Medline databases (up to May 10, 2010) meeting specified search criteria were performed, followed by a further screening according to inclusive and exclusive criteria.Fourteen articles were selected into the final meta-analysis with paired primary and metastatic cases of 598. Expression level of EGFR protein and mutation frequency of KRAS gene in primary tumors were higher than that in metastases, relative risk (RR)=1.13 (95%CI: 0.98-1.31, P=0.09) and RR=1.39 (95%CI: 0.95-2.03, P=0.09), respectively. EGFR gene copy number in metastases was higher than that in primary tumor, RR=0.74 (95%CI: 0.53-1.02, P=0.06). There was no statistically significant difference of EGFR mutation frequency in primary tumors and metastases (P=0.31). The discordant rate in primary and metastases was 17.09% for EGFR mutation, 27.07% for EGFR amplification, 27.84% for EGFR protein expression and 25.91% for KRAS mutation.The systematic analysis showed that the EGFR mutation status in primary lung cancer and corresponding metastases was more stable than KRAS gene. KRAS mutation in primary lung cancerous foci seems to better reflect systemically cancerous genetic characteristics of KRAS gene. Determination of KRAS gene status based merely on metastatic foci might lead to more resistant selections of EGFR tyrosine kinase inhibitor (TKI) therapy. Combined detection of EGFR and KRAS mutation from primary NSCLC foci might serve as a better predictive biomarker for anti-EGFR targeted therapy.

2. The binary logistic regression analysis:  Pericardium V50 was positively associated with PCE; while the age, hypertension were negatively with the PCE. • The mean, maximum dose, and V5-V65 for heart were not significantly related to PCE. 3. The cox regression analysis:  Pericardium V55 was positively associated with survival; while the radiation tumor dose was negatively with the survival. • The mean, maximum dose, and V5-V65 for heart were not significantly related to survival.

(51 54%), and 40% (38 43%) with SBRT (P > 0.05). In view of acute toxicity, the most frequent complication of RFA is pneumothorax, which occurs in 32% (16 45%) patients, required chest tube insertion in 12% (7 39%) of patients. Conclusions: Local control rate for SBRT is significantly higher than that for RFA, though overall survival seems not significantly different between two treatment groups. However, caution is warranted due to the relatively limited number of RFA and short follow-up time. Author Disclosure: N. Bi: None. K. Shedden: None. X. Zheng: None. W. Wang: None. F. Kong: None.