Sec-Auditor:A Blockchain-Based Data Auditing Solution for Ensuring Integrity and Semantic Correctness

Currently,there is a growing trend among users to store their data in the cloud.However,the cloud is vulnerable to persistent data corruption risks arising from equipment failures and hacker attacks.Additionally,when users perform file operations,the semantic integrity of the data can be compromised.Ensuring both data integrity and semantic correctness has become a critical issue that requires attention.We introduce a pioneering solution called Sec-Auditor,the first of its kind with the ability to verify data integrity and semantic correctness simultaneously,while maintaining a constant communication cost independent of the audited data volume.Sec-Auditor also supports public auditing,enabling anyone with access to public information to conduct data audits.This feature makes Sec-Auditor highly adaptable to open data environments,such as the cloud.In Sec-Auditor,users are assigned specific rules that are utilized to verify the accuracy of data semantic.Furthermore,users are given the flexibility to update their own rules as needed.We conduct in-depth analyses of the correctness and security of Sec-Auditor.We also compare several important security attributes with existing schemes,demonstrating the superior properties of Sec-Auditor.Evaluation results demonstrate that even for time-consuming file upload operations,our solution is more efficient than the comparison one.

Group Decision-Making Method with Incomplete Intuitionistic Fuzzy Preference Relations Based on a Generalized Multiplicative Consistent Concept

Based on the analyses of existing preference group decision-making(PGDM)methods with intuitionistic fuzzy preference relations(IFPRs),we present a new PGDM framework with incomplete IFPRs.A generalized multiplicative consistent for IFPRs is defined,and a mathematical programming model is constructed to supplement the missing values in incomplete IFPRs.Moreover,in this study,another mathematical programming model is constructed to improve the consistency level of unacceptably multiplicative consistent IFPRs.For group decisionmaking(GDM)with incomplete IFPRs,three reliable sources influencing the weights of experts are identified.Subsequently,a method for determining the weights of experts is developed by simultaneously considering three reliable sources.Furthermore,a targeted consensus process(CPR)is developed in this study with reference to the actual situation of the consensus level of each IFPR.Meanwhile,in response to the proposed multiplicative consistency definition,a novel method for determining the optimal priority weights of alternatives is redefined.Lastly,based on the above theory,a novel GDM method with incomplete IFPRs is developed,and the comparative and sensitivity analysis results demonstrate the utility and superiority of this work.

An Evolutionary Algorithm Based on a New Decomposition Scheme for Nonlinear Bilevel Programming Problems

In this paper, we focus on a class of nonlinear bilevel programming problems where the follower’s objective is a function of the linear expression of all variables, and the follower’s constraint functions are convex with respect to the follower’s variables. First, based on the features of the follower’s problem, we give a new decomposition scheme by which the follower’s optimal solution can be obtained easily. Then, to solve efficiently this class of problems by using evolutionary algorithm, novel evolutionary operators are designed by considering the best individuals and the diversity of individuals in the populations. Finally, based on these techniques, a new evolutionary algorithm is proposed. The numerical results on 20 test problems illustrate that the proposed algorithm is efficient and stable.

非小细胞肺癌围手术期免疫治疗相关不良反应管理的临床诊疗建议

背景与目的肺癌围手术期治疗(术前新辅助治疗及术后辅助治疗)作为手术的重要辅助手段,已成为非小细胞肺癌(non-small cell lung cancer,NSCLC)全程管理中越来越重要的环节。近年来,小规模临床研究发现免疫新辅助治疗主要病理缓解率明显提升,甚至达到完全病理缓解,有望成为NSCLC治疗的重要组成部分。然而,免疫新辅助治疗带来疗效和生存获益,同时,其相关严重不良反应(延误手术、丧失手术机会、死亡等)备受关注。本诊疗建议目的是针对免疫检查点抑制剂相关不良反应(immune-related adverse event,irAE)形成适合国内医疗现状的诊疗方案。方法本文由胸外科专家、肿瘤学专家、胸内科专家以及irAE相关科室专家(消化内科、呼吸内科、心血管内科、感染内科、血液内科、内分泌科、风湿免疫科、神经内科、皮肤科和急诊科)共同完成本诊疗意见的制定工作。专家充分参考irAE指南、胸外科公开发表的大型临床研究数据以及国内医生的临床实战经验和公开发表个案,多学科反复讨论,形成针对围手术期免疫治疗相关不良反应的诊疗建议。结果本诊疗意见涵盖irAE相关的预防、评估、检查、治疗和监测全过程,以便全面、有效的指导临床工作。结论围手术期irAE管理是肺癌免疫围手术期治疗的重要组成部分,随着免疫围手术期治疗的不断发展,未来需要更多的研究,以优化围手术irAE的诊疗。

Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer

Objective:The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics,as well as its impact on prognoses and responses to immunotherapy in East Asian patients with non-small cell lung cancer(NSCLC).Methods:We performed an integrated analysis using publicly available data to identify associations between anti-programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)immunotherapy efficacy and classic driver oncogene mutations in East Asian NSCLC patients.Four pooled and clinical cohort analyses were used to correlate driver oncogene mutation status and tumor microenvironment based on PD-L1 and CD8+tumor-infiltrating lymphocytes(TILs).Immune infiltrating patterns were also established for genomic NSCLC subgroups using the CIBERSORT algorithm.Results:Based on East Asian NSCLC patients,TIDE analyses revealed that for anti-PD-1/PD-L1 immunotherapy,epidermal growth factor receptor(EGFR)-mutant and anaplastic lymphoma kinase(ALK)-rearranged tumors yielded inferior responses;however,although Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors responded better,the difference was not statistically significant(EGFR:P=0.037;ALK:P<0.001;KRAS:P=0.701).Pooled and clinical cohort analyses demonstrated tumor immune microenvironment heterogeneities correlated with oncogenic patterns.The results showed remarkably higher PD-L1-and TIL-positive KRAS-mutant tumors,suggesting KRAS mutations may drive an inflammatory phenotype with adaptive immune resistance.However,the EGFR-mutant or ALK-rearranged groups showed a remarkably higher proportion of PD-L1-/TIL-tumors,suggesting an uninflamed phenotype with immunological ignorance.Notably,similar to triple wild-type NSCLC tumors,EGFR L858R-mutant tumors positively correlated with an inflammatory phenotype,suggesting responsiveness to anti-PD-1/PD-L1 immunotherapy(P<0.05).Furthermore,the CIBERSORT algorithm results revealed that EGFR-mutant and ALK-rearranged tumors were characterized by an enriched resting memory CD4+T cell population(P<0.001),as well as a lack of CD8+T cells(P<0.01),and activated memory CD4+T cells(P=0.001).Conclusions:Our study highlighted the complex relationships between immune heterogeneity and immunotherapeutic responses in East Asian NSCLC patients regarding oncogenic dependence.

Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials

Lung cancer is the leading cause of cancer-related death across the world.Unlike lung adenocarcinoma,patients with lung squamous cell carcinoma(LSCC)have not benefitted from targeted therapies.Although immunotherapy has significantly improved cancer patients’outcomes,the relatively low response rate and severe adverse events hinder the clinical application of this promising treatment in LSCC.Therefore,it is of vital importance to have a better understanding of the mechanisms underlying the pathogenesis of LSCC as well as the inner connection among different signaling pathways,which will surely provide opportunities for more effective therapeutic interventions for LSCC.In this review,new insights were given about classical signaling pathways which have been proved in other cancer types but not in LSCC,including PI3K signaling pathway,VEGF/VEGFR signaling,and CDK4/6 pathway.Other signaling pathways which may have therapeutic potentials in LSCC were also discussed,including the FGFR1 pathway,EGFR pathway,and KEAP1/NRF2 pathway.Next,chromosome 3q,which harbors two key squamous differentiation markers SOX2 and TP63 is discussed as well as its related potential therapeutic targets.We also provided some progress of LSCC in epigenetic therapies and immune checkpoints blockade(ICB)therapies.Subsequently,we outlined some combination strategies of ICB therapies and other targeted therapies.Finally,prospects and challenges were given related to the exploration and application of novel therapeutic strategies for LSCC.

Treatmentsforresectableesophageal cancer:from traditional systemic therapy to immunotherapy

Esophageal cancer(EC)has a high incidence and poor prognosis.The two major histological types,squamous cell carcinoma and adenocarcinoma,differ in their epidemiology and treatment options.Patients with locally advanced EC benefit from multimodal therapy concepts including neoadjuvant chemotherapy,neoadjuvant chemoradiotherapy,and perioperative chemotherapy.Currently,immunotherapy for the solid tumor is a hot spot.Treatment with adjuvant immune checkpoint inhibitors(ICIs)is the first immunotherapy for resectable EC listed in the latest National Comprehensive Cancer Network Guidelines for the Esophageal and Esophagogastric Junction Cancers.Recent clinical trials have established ICIs for three treatment models of resectable EC.Their short-term results demonstrated ideal efficacy and tolerable toxicity,though some concerns remain.This review summarizes the novel data on the ICIs for resectable EC and lists the registered related clinical trials.Hopefully,this review can provide a reference for ongoing research on the treatment options for resectable EC.