Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

交互式数字叙事:加拿大Writing New Body Worlds阅读治疗新探索

文章基于相关研究文献与语料,对加拿大WNB阅读治疗实践进行梳理与归纳。WNB首次使用交互式数字叙事技术,构建面向公众的阅读治疗平台,以其交互式特征,融合了阅读和治疗引导两个过程,提供可访问的非临床方式,可面向大规模人群实现预防性健康干预。基于数据与计算的精准化阅读治疗是数字人文视角下的新变革,更具推广应用价值;以在线阅读平台建设为依托,推进实施平台化的阅读和治疗应成为未来发展方向之一;基于阅读形态与体验因技术赋能而改变的现状,图书馆应发挥引领作用,积极收集、创建或协助创建数字故事,推进阅读推广、服务与治疗的融合性发展,成为社区建设促进者、历史欣赏者和社区参与倡导者,也使阅读借助交互式数字叙事这一新载体,更好地发挥变革的力量,促进健康与幸福。

New Maikhanellid Shells and Siphogonuchitid Spicule Bundles from the Cambrian Fortunian Stage of South China

Maikhanellids are a distinct group of Cambrian Fortunian small shelly fossils by the capshaped profiles and scaly shell ornamentation.According to the individual shell shape and ornamentation feature types of 50 maikhanellids fossils which were collected from Xixiang botia,we confirmed the family Maikhanellidae content of six genera,which are Maikhanella,Ramenta,Purella,Ramentoides,Yunnannopleura and Mediata.Unlike the halkieriid animals whose shells and spicules are articulated on different body parts,maikhanellids were presumably yielded by siphogonuchitid spicules penetrating the intermediate matrix（the ＂spicule shell＂ hypothesis）,and this is the reason that some researchers treated maikhanellids and co-occurring siphogonuchitids as synonyms.The affinities of Maikhanellids and siphogonuchitids remain debatable.Here,we report three dimensionally phosphatized maikhanellid shells and siphogonuchitid spicule bundles from the Cambrian Fortunian small shell faunas of South China.They differ from all the previously reported maikhanellids and siphogonuchitids,and may represent new types.The intact and smooth surface underneath the partially preserved scales of the shells challenges the ＂spicule-shell＂ hypothesis.The present siphogonuchitid spicules differ from the maikhanellid scales in size,morphology,and.arrangement pattern,thus the spicules might not be derived from the shells.Whether the shells and spicule bundles were articulated on different body parts of the same animals remains unknown.

New Small Shelly Fossils(Acanthocassis and Xinlispina Gen.Nov.) from the Fortunian Stage(Early Cambrian) in Southern China

We describe new material of three-dimensionally phosphatized small shelly fossils Acanthocassis and Xinlispina gen.nov.from the Fortunian Stage（early Cambrian） of southern Shaanxi and northern Sichuan Provinces.The new materials allow description of the delicate morphology of these skeletons, and also their skeletogenesis.Acanthocassis and Xinlispina have comparable morphological features： a main branch and radially arranged sub-branches.They differ from each other in many details, e.g., the presence of a single central branch only in Xinlispina, and the presence of small nodes only in Acanthocassis.Acanthocassis cannot be a naked anthopolyp or hydropolyp because of the more-or-less stiffened cuticle and the absence of a mouth.Acanthocassisand Xinlispina differ from coeval sponge spicules and chancelloriid sclerites and rosettes of crossed pedicellariae of echinoderms, and might be cuticular ornaments of animals of unclear affinities.They occur in the first small shelly fossil assemblage zone, and could be adopted as auxiliary fossils for biostratigraphic correlation in southern China.

A New Species of Septuconularia(Hexangulaconulariidae,Cnidaria)from Cambrian Stage 2,South China

Hexangulaconulariids,an extinct family of medusozoan small shelly fossils(SSFs),were a conspicuous component of early Cambrian,shallow marine platform communities in South China.Described herein is Septuconularia crassiformis sp.nov.from Bed 5 of the Yanjiahe Formation(Cambrian Stage 2)in the Three Gorges area of Hubei Province.The new species differs from the type and only other known species,S.yanjiaheensis,in the shape of the abapical portion and in the degree of curvature of the adapertural margin.The anatomy of the apical portion of the new species is unknown.The diagnosis of the genus Septuconularia is emended and the spatio-temporal distribution of hexangulaconulariids in South China is summarized.Finally,S.yanjiaheensis,with its slit-like aperture and very narrow transverse cross-section,may have been better adapted to the shallow platform environment than the broader S.crassiformis,which appears to have been less common than the type species.

Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients

Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration:(1) the disease factor, related to the extension and localization of the disease as well as tumor biology;(2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and(3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel.

Proposal of a new T-stage classification system for ampullary carcinoma based on Surveillance,Epidemiology and End Result(SEER)database

Background:Tumor size is still considered a useful prognostic factor in currently available tumor-nodemetastasis(TNM)classification staging systems for most solid tumors,but the significance of tumor size on the prognosis of ampullary carcinoma remains controversial.The aim of the current study was to propose a new T-stage classification system for ampullary carcinoma to address the impact of tumor size on the prognostic outcome.Methods:Using the Surveillance,Epidemiology,and End Results(SEER)database,we identified 1080 patients with ampullary carcinoma who underwent radical surgical resection between 2004 and 2015.Based on the results obtained from analysis of various clinicopathologic factors,a new T-stage classification system was proposed.Results:Among the 1080 patients,618 were men and 462 were women,with a median tumor size of 2.3(range 0.1–12)cm.Using the 7 th edition of the American Joint Committee on Cancer(AJCC)staging manual,we noticed significant differences in overall survival(OS)between T2 vs.T3 tumors(P<0.001)and T3 vs.T4 tumors(P=0.002),but failed to observe significant differences between T1 vs.T2 tumors(P=0.498)in our pair-wise comparison.Using the newly developed T-stage classification system,we were able to differentiate significant differences in OS between T1 vs.T2 tumors(P=0.032),T2 vs.T3 tumors(P<0.001)and T3 vs.T4 tumor(P=0.003)in all pair-wise comparisons.The c-index of the new staging system was 0.653(95%CI:0.629–0.677),showing a better discriminatory power than the 0.636 of the 7 th AJCC staging system(95%CI:0.612–0.660).Conclusions:The new T-stage classification system described herein can better differentiate prognostic outcomes after radical resection in patients with ampullary carcinoma by incorporating tumor size and depth of tumor infiltration.

网络新媒体视阈下客家议题在日传播特征分析——基于日本Google News的考察

以日本Google News中的客家相关日文报道为语料,通过文本挖掘工具KH Coder进行文本数据挖掘,发现日本网络新闻媒体的客家议题日文报道具有分布零散性及以图片报道为主的特点。报道关注的客家区域主要涉及台湾地区、福建、香港地区、广东等地,其中,台湾地区的客家关注度最高。报道聚焦客家的观光旅游、产业振兴、客家书籍出版等相关内容,形成了客家传统建筑类、台湾地区客家文化交流类、客家文学作品推介类、客家观光旅游类等四大主要议题。本文提出要充分运用Google News等网络新媒体强大的技术功能和传播优势加大客家文化的传播力度。

A New Method of Embedded Fourth Order with Four Stages to Study Raster CNN Simulation

A new Runge-Kutta （PK） fourth order with four stages embedded method with error control is presentea m this paper for raster simulation in cellular neural network （CNN） environment. Through versatile algorithm, single layer/raster CNN array is implemented by incorporating the proposed technique. Simulation results have been obtained, and comparison has also been carried out to show the efficiency of the proposed numerical integration algorithm. The analytic expressions for local truncation error and global truncation error are derived. It is seen that the RK-embedded root mean square outperforms the RK-embedded Heronian mean and RK-embedded harmonic mean.

The Characteristics of the Stage of Ideology of Chinese Meteorological Film since the Founding of New China

Since the founding of the New China in 1949,with the gradual development of the history and the constant change of the realistic situation,China's national ideology has also undergone profound changes.As an important type of film,meteorological film plays an important role in the history of Chinese film.From the founding of New China to the end of 1970 s,Chinese meteorological films showed a strong atmosphere of class struggle and political propaganda style in ideology.From the beginning of 1980 s to the end of 1990 s,Chinese meteorological films showed new ideas in ideology and the characteristics of coexistence and spread of new viewpoints.Since the 21 stcentury,Chinese meteorological films have integrated into globalization ideologically and stuck nationalization.

Analysis of Cardiovascular Risk Factors in Newly Defined Stage 1 Hypertension among Chinese on the Basis of the 2017 ACC/AHA Hypertension Guidelines

In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood pressure levels greater than 130/80 mm Hg were defined as hypertension[1].Based on these modified guidelines,the morbidity of hypertension in US increased from 32%to 46%.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.

New Stage for Railway Reform and Development

1. Review of railway work in 1996 The year 1996 was an important year for China’s railways in facing a historic turning point—— committing itself to a programme of structural re-

Development Zones Enter New Stage

The economic and technological development zones (ETDZ) in China began their 11th year in 1995. Since 1984 the State Council has approved 32 ETDZs. In the past few years the ETDZs have gained remarkable achievements in improving the investment climate, raising the management and service level and attracting foreign funds. The economic benefits have had a simultaneous develonment in the first 14 ETDZs in

China Moving Closer to Global Center Stage in the New Era

Economic development has always been the main focus of the Chinese government, as the economy lays a foundation for the country＇s social progress.

New Drivers of China＇s Industrial Growth in Its Late-Stage Industrialization and ＂New Normal＂

According to our analysis of variations in Chinas＇ industrial growth rate. industrial demand, industrial structure, regional structure and the performance of industrial firms, China ＇s＇ industrial economv is moving towards＇ a ＂new normal＂ of slower growth and structural improvement. This process coincides with the late stage of China＇s industrialization, which international experience suggests is often frauht with twists and challenges. Among these challenges, great attention must be paid to overcapacity industrial restructuring and upgrades, and the ＂reindustrialization＂ of developed countries. As China enters the late stage of its industrialization, particularly during the 13th Five-Year Plan period from 2016 to 2020, the promotion of industrial development is of strategic significance for China to successfully complete industrialization and its economy to adapt to the ＂new normal ＂. In the face of these new challenges regarding industrial development, policymakers must strive to increase the dynamism of growth for industrial economy. In this new era, the momentum of industrial growth derives from the integration of the supply impetus of industrialization and the pull of demand caused by urbanization, while, the comprehensive deepening of refom provides the key source of momentum.

Boehmeria nivea var. strigosa (Urticaceae), a new variety from Southwest China

Boehmeria nivea var.strigosa Zeng Y.Wu&Y.Zhao,a new variety of B.nivea(Urticaceae)from Southwest China,is here described based on evidence from morphology and molecular phylogeny.This new variety is mainly characterized by its green abaxial leaf blade,partly connate stipules,and densely patent strigose hairs on stems and potioles.The phylogenetic analysis based on rbc L,nrDNA and rbc L+nrDNA datasets,revealed that all individuals of B.nivea var.strigosa formed a monophyletic group.The conservation status of B.nivea var.strigosa is assessed as“Near Threatened”(NT)according to IUCN evaluation criteria.The discovery of this new variety is not only crucial for the taxonomy of ramie,but also provides reference for the exploration and utilization of ramie.