Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease

Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

Synergistic Impacts of Indian Ocean SST and Indo-China Peninsula Soil Moisture on the 2020 Record-breaking Mei-yu

The Yangtze River basin(YRB)experienced a record-breaking mei-yu season in June‒July 2020.This unique long-lasting extreme event and its origin have attracted considerable attention.Previous studies have suggested that the Indian Ocean(IO)SST forcing and soil moisture anomaly over the Indochina Peninsula(ICP)were responsible for this unexpected event.However,the relative contributions of IO SST and ICP soil moisture to the 2020 mei-yu rainfall event,especially their linkage with atmospheric circulation changes,remain unclear.By using observations and numerical simulations,this study examines the synergistic impacts of IO SST and ICP soil moisture on the extreme mei-yu in 2020.Results show that the prolonged dry soil moisture led to a warmer surface over the ICP in May under strong IO SST backgrounds.The intensification of the warm condition further magnified the land thermal effects,which in turn facilitated the westward extension of the western North Pacific subtropical high(WNPSH)in June‒July.The intensified WNPSH amplified the water vapor convergence and ascending motion over the YRB,thereby contributing to the 2020 mei-yu.In contrast,the land thermal anomalies diminish during normal IO SST backgrounds due to the limited persistence of soil moisture.The roles of IO SST and ICP soil moisture are verified and quantified using the Community Earth System Model.Their synergistic impacts yield a notable 32%increase in YRB precipitation.Our findings provide evidence for the combined influences of IO SST forcing and ICP soil moisture variability on the occurrence of the 2020 super mei-yu.

关节镜下有限与广泛清理术治疗膝骨性关节炎的效果比较

目的比较关节镜下有限与广泛清理术治疗膝骨性关节炎的效果。方法选取2019年1月~2020年1月广东省湛江中心人民医院收治的80例膝骨性关节炎患者作为研究对象,按照随机数字表法将其分为对照组与观察组,每组各40例。对照组患者实施关节镜下广泛清理术,观察组患者实施关节镜下有限清理术。比较两组患者的围术期相关指标、疼痛评分、膝关节功能评分、临床疗效及并发症发生情况。结果观察组患者的手术时间、住院时间短于对照组,差异有统计学意义(P<0.05)。术后3个月,观察组患者的视觉模拟量表(VAS)评分低于对照组,Lysholm评分、美国特种外科医院膝关节量表(HSS)评分高于对照组,差异有统计学意义(P<0.05)。两组患者的治疗优良率、并发症总发生率比较,差异无统计学意义(P>0.05)。结论在膝骨性关节炎患者的治疗中,关节镜下有限清理术、关节镜下广泛清理术的疗效相当,但关节镜下有限清理术具有手术时间短、疼痛轻、更利于术后恢复等优势。

后外侧入路小切口髋关节置换治疗股骨头坏死的临床效果及安全性

目的:探讨后外侧入路小切口髋关节置换治疗股骨头坏死的临床效果及安全性。方法:选取2018年1月-2020年1月在本院接受髋关节置换治疗的84例股骨头坏死患者,根据数字双盲法分为对照组与研究组,每组42例。对照组采用常规后外侧入路方式,研究组采用后外侧入路小切口。比较两组患者的疼痛评分、髋关节功能评分、手术及安全性指标。结果:手术前,两组患者疼痛评分、髋关节功能评分比较,差异均无统计学意义(P>0.05),手术后1、3周,研究组患者疼痛评分均低于对照组(P<0.05),手术后1、3个月,研究组髋关节功能评分均高于对照组,差异均有统计学意义(P<0.05)。研究组患者手术切口长度、手术时间、术中出血量、住院时间、并发症发生率均低于对照组,差异均有统计学意义(P<0.05)。结论:髋关节置换治疗过程中采用新型的后外侧小切口入路方式,缩小患者手术暴露性切口面积,降低并发症发生率,改善患者髋关节功能,有较高临床推广价值。

老年髋部骨折患者术后精神障碍影响因素分析及应对措施研究

目的:探究老年髋部骨折患者术后精神障碍的影响因素以及应对措施。方法:回顾分析2010年1月-2015年6月本院收治因髋部骨折行手术治疗的老年患者250例的临床资料,根据术后是否并发精神障碍分为精神障碍组(n=60)和非精神障碍组(n=190)。统计患者的基础资料及并发症情况,分析精神障碍发病的影响因素。结果:精神障碍组年龄、并发慢性阻塞性肺疾病和进行全身麻醉的比例均高于非精神障碍组,且血红蛋白浓度和血钠水平均低于非精神障碍组,比较差异均有统计学意义(P<0.05);Logistic回归分析显示,年龄、血钠含量、血红蛋白浓度、术后并发慢性阻塞性肺疾病以及全身麻醉均是影响患者术后发生精神障碍的危险因素(P<0.05)。结论:年龄、血钠含量、血红蛋白浓度、术后并发慢性阻塞性肺疾病以及全身麻醉均是老年髋部骨折患者术后发生精神障碍的危险因素,医护人员应在手术前后根据患者的实际情况制定合理的预防及治疗方案,防止术后出现精神障碍。

对比观念、共同认知与政策制定——以土地托管政策过程为例

论文提出,如果为一个新观念确定一个既定政策观念作为其对比观念,那么就能推动这个新观念转化为政策,因为这样会使新观念更容易融入政策领域的共同认知。论文以土地托管政策过程为例,展示从观念阐释到政策制定的机制。已有理论强调的意义冲突、话语结构化、政策形象三类因素为研究奠定了理论基础,但它们对土地托管案例解释力不足,所以论文提出了新的理论框架。实证研究发现,土地托管政策制定发生的重要原因,是2013年开始由山东省供销社主导创造的新的观念阐释,它将土地托管阐释为土地流转政策的对比观念,即不流转土地也能发展农业规模经营。

不同剂量氨甲环酸静脉滴注对老年髋关节置换术患者围术期失血的影响

目的:探讨不同剂量氨甲环酸静脉滴注对老年髋关节置换术患者围术期失血的影响。方法:选取2014年1月至2018年8月湛江中心人民医院收治的拟行髋关节置换术的老年患者180例,采用随机数字表法分为A组(静脉滴注0.9%氯化钠注射液)、B组(静脉滴注氨甲环酸10 mg/kg)及C组(静脉滴注氨甲环酸15 mg/kg)。在术前,术后1、3和7 d检测三组患者的血红蛋白和红细胞比容水平,对比三组患者的引流量、失血量、最大血红蛋白丢失量、术中输血情况、并发症发生情况及术后凝血功能指标水平的差异。结果:术后1、3和7 d,三组患者血红蛋白水平逐渐升高,组间比较,差异均有极显著统计学意义(P<0.01);三组患者红细胞比容水平逐渐降低,组间比较,差异均有统计学意义(P<0.05)。B、C组患者的术中引流量、术后引流量、总引流量、隐性失血量、总失血量及最大血红蛋白丢失量明显低于A组,差异均有极显著统计学意义(P<0.01),且C组患者上述指标水平明显低于B组,差异均有统计学意义(P<0.05)。B、C组患者的输血率分别为41.67%(25/60)、18.33%(11/60),明显低于A组的78.33%(47/60),差异均有统计学意义(P<0.01),且C组患者的输血率明显低于B组,差异有统计学意义(P<0.05)。术后随访,三组患者均未发生深静脉血栓、感染及肾衰竭等并发症。术后,三组患者出血时间、血小板计数、凝血酶原时间及活化部分凝血酶时间的差异均无统计学意义(P>0.05)。结论:不同剂量氨甲环酸静脉滴注可有效减少老年髋关节置换术患者围术期的失血量,并降低患者的术中输血率,且15 mg/kg的氨甲环酸效果更佳。

骨不连原因及治疗研究进展

随着现代工农业和交通运输的发展,意外灾害事故增多,四肢骨折,包括粉碎及多段骨折,特别是开放骨折的发生率增高,治疗比较困难[1]。自1960年提出解剖复位、坚强内固定及早期无痛性和关节主动活动的治疗原则以来,骨折的治疗技术不断提高,90%~95%的骨折都能够愈合,但骨不连时有发生,已成为骨科医生面临的一个重大难题,给社会和家庭带来了沉重的经济负担[2]。我们复习国内外最新文献,总结关于骨不连方面的病因研究及治疗方法,来进一步阐述骨不连的研究进展。

关节镜下有限与广泛膝关节清理术治疗膝关节骨性关节炎的疗效对比

目的:对比用关节镜下有限膝关节清理术与广泛膝关节清理术治疗膝关节骨性关节炎(KOA)的临床疗效。方法:按照随机数表法将80例KOA患者均分为广泛组和有限组,用关节镜下有限膝关节清理术对有限组患者进行治疗,用关节镜下广泛膝关节清理术对广泛组患者进行治疗。术后,对比两组患者手术的效果、手术的耗时、住院的时间、术后关节疼痛的程度及膝关节的功能。结果:两组患者手术效果的优良率相比,P>0.05。与广泛组患者相比,有限组患者手术的耗时、住院的时间均较短,术后7 d其视觉模拟评分法(VAS)的评分较低,P<0.05。术前,两组患者吴海山综合评分体系的评分相比,P>0.05。术后12个月,两组患者吴海山综合评分体系的评分相比,P>0.05。结论:用关节镜下有限与广泛膝关节清理术治疗KOA均可提升患者膝关节的功能,但用关节镜下有限膝关节清理术治疗该病可显著缩短其手术的耗时,减轻其术后关节疼痛的程度,加快其术后康复的速度。

Diffusion tensor imaging assesses white matter injury in neonates with hypoxic-ischemic encephalopathy

With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy （14 moderate cases and 8 severe cases） underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.

嵌入性组织中的政策企业家如何推动政策创新?——基于农业生产托管政策变迁的历时观察

过往研究关注政府组织、企业和行业协会等组织形式中政策企业家对于推动政策创新的影响。然而,嵌入性组织中的政策企业家未被相关研究所涉及。论文基于2000—2016年间山东省农业生产托管政策的变迁,揭示具有中国特色的嵌入性组织(即农村供销合作社)中政策企业家推动政策创新的过程与机制。研究发现,在政策企业家推动政策创新的过程中,其所处的组织结构发挥着重要影响作用。政策企业家能够基于嵌入性组织多元、多层级的网络制度关系,凭借其充分信息和制度合法性形成广泛的子系统行动者网络,进而通过协同各方和各层级的行动者来推动理念的实践与论证,在经历信念形成、利益赋予、联盟扩张和创新涌现四个阶段后,推动政策创新的实现。具有中国特色的嵌入性组织,过去往往因混合了政府、企业等不同组织性质而受到诸多批判。论文发现了嵌入性组织新的优势领域,即嵌入性组织促进了超出自身的更大范围的政策创新的产生。我国应加强嵌入性组织的改革与建设,提升嵌入性组织在各类公共政策中的参与程度,从而基于其充分的信息与制度合法性的优势来推动高质量的政策创新。

Socioeconomics and attributable etiology of primary liver cancer,1990-2019

BACKGROUND Primary liver cancer(PLC)is a major contributor to cancer-related deaths.Data on global and country-specific levels and trends of PLC are essential for understanding the effects of this disease and helping policymakers to allocate resources.AIM To investigate the association between the burden of PLC and socioeconomic development status.METHODS Cancer mortality and incidence rates were obtained from the Global Burden of Disease(GBD)2019,and the data were stratified by country and territory,sex,and the Socio-demographic Index(SDI)level.The association between the attributable etiology of PLC and socioeconomic development status,represented using the SDI,was described.The attributable etiology of PLC included hepatitis B,hepatitis C,alcohol use,and nonalcoholic steatohepatitis.The association between the attributable etiology of PLC and SDI was further stratified by sex and geographical location.A confidence analysis was also performed based on bootstrap draw.RESULTS The age-standardized incidence rate of PLC was 6.5[95%confidence intervals(CI):5.9-7.2]per 100000 person-years,which decreased by-27.5%(-37.0 to-16.6)from 1990 to 2019.Several countries located in East Asia,South Asia,West Africa,and North Africa shouldered the heaviest burden of PLC in 2019.In terms of incidence rates,the first leading underlying cause of PLC identified was hepatitis B,followed by hepatitis C,alcohol use,and nonalcoholic steatohepatitis.Regarding stratification using the SDI,the incidence rate of PLC was the highest for high and middle SDI locations.Further,the leading attributable etiologies of PLC were hepatitis B for the middle and high middle SDI locations while hepatitis C and nonalcoholic steatohepatitis for the high SDI locations.CONCLUSION The pronounced association between socioeconomic development status and PLC burden indicates socioeconomic development status affects attributable etiologies for PLC.GBD 2019 data are valuable for policymakers implementing PLC cost-effective interventions.

基于体细胞突变数据库筛选免疫原性结直肠癌高频新抗原的方法

结直肠癌是世界高发和高致死率的恶性肿瘤。靶向新抗原的免疫治疗已被证实可以诱导癌症患者肿瘤持续消退,但这些特异性新抗原,仅适用于个体精准治疗。随着大量的高频肿瘤基因突变被发现,这些与突变相关的高频新抗原可覆盖更多人群,具有较强的临床意义。然而目前结直肠癌中是否也存在高频新抗原仍不清楚。本研究利用来源于321个结直肠癌患者的体细胞突变数据库,联合1种标准过滤和7种预测算法,筛选并获得了25个基于中国人高频分型HLA-A^*1101限制性的高频新抗原,它们均具有高亲和力(IC50<50 nmol/L)和高呈递分值(>0.90);其中,除了阳性对照多肽KRAS_G12V8-16外,11个高频新抗原能够在体外诱导细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)分泌γ干扰素(interferon gamma,IFN-γ),证实具有免疫原性。选取免疫原性最强的新抗原C1orf170_S418G413-421及阳性对照多肽KRAS_G12V8-16体外刺激T细胞,利用流式细胞分选及单细胞转录组测序技术,获得其特异性CTL的免疫组库信息,所构建的TCR-T(T-cell receptor engineered T cell)能够识别新抗原并分泌细胞因子。以上结果表明,本研究开发了一种利用体细胞数据库预测并体外筛选验证具有免疫原性高频新抗原的方法,为结直肠癌及其他癌种的多肽、DC(dendritic cells)疫苗、TCR-like抗体、TCR-T等免疫治疗提供了重要的多肽靶点和TCR信息,具有实际的临床应用价值。

Liver chemistries in severe or non-severe cases of COVID-19:A systematic review and meta-analysis

BACKGROUND Coronavirus disease(COVID-19)patients exhibit different patterns of liver impairment,according to growing evidence.AIM In this study,we sought to provide a comprehensive analysis of liver test parameters in patients with severe and non-severe COVID-19.METHODS We performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19.We searched PubMed,Google Scholar,Embase,Cochrane Library,medRxiv,bioRxiv,and three Chinese electronic databases through April 18,2020,in accordance with the Preferred Reporting Items for Meta-Analyses.We analyzed pooled data on liver chemistries stratified by COVID-19 severity using a fixed or random-effects model.RESULTS A meta-analysis of 56 studies,including 11052 patients,found that the pooled mean alanine aminotransferase(ALT)in severe COVID-19 cases was 35.9 IU/L whereas in non-severe COVID-19 cases was 27.3 IU/L.Average aspa-rtate aminotransferase(AST)levels were 44.3 IU/L in severe cases compared to 27.9 IU/L in non-severe cases.In addition,AST levels are often higher than ALT levels regardless of disease severity.The severe cases tended to have a higher gammaglutamyltransferase level but a lower albumin level than the non-severe cases.CONCLUSION Severe COVID-19 was more likely to be associated with abnormal liver test results.Monitoring liver chemistry closely can help detect disease progression early.

累犯非羁押强制措施适用的问题及其解决路径

法律、司法解释未对累犯适用非羁押强制措施作出禁止性规定,但实践中,累犯在非羁押措施上近乎零适用。有观点以累犯因符合径行逮捕条件且主观恶性、再犯可能性较之前科人员更大而直接推定有羁押必要解释之,这明显与宽严相济、少捕慎诉慎押刑事司法政策,与羁押必要性审查制度教育改造、保障人权之目的相背离。不同累犯社会危险性各不相同,侦查、司法机关应转变司法理念,坚持区分情形、区别对待,保留累犯适用羁押必要性审查之余地,并动态考察累犯社会危险性,对于没有继续羁押必要的,及时变更为非羁押措施,从而有效减少不必要羁押,推动降低诉前羁押率,进一步贯彻落实少捕慎诉慎押刑事司法政策。

Diversity and connectedness of brine shrimp viruses in global hypersaline ecosystems

Brine shrimp(Artemia)has existed on Earth for 400 million years and has major ecological importance in hypersaline ecosystems.As a crucial live food in aquaculture,brine shrimp cysts have become one of the most important aquatic products traded worldwide.However,our understanding of the biodiversity,prevalence and global connectedness of viruses in brine shrimp is still very limited.A total of 143 batches of brine shrimp(belonging to seven species)cysts were collected from six continents including 21 countries and more than 100 geographic locations worldwide during 1977–2019.In total,55 novel RNA viruses were identified,which could be assigned to 18 different viral families and related clades.Eleven viruses were dsRNA viruses,16 were+ssRNA viruses,and 28 were−ssRNA viruses.Phylogenetic analyses of the RNA-directed RNA polymerase(RdRp)showed that brine shrimp viruses were often grouped with viruses isolated from other invertebrates and fungi.Remarkably,most brine shrimp viruses were related to those from different hosts that might feed on brine shrimp or share the same ecological niche.A notable case was the novel brine shrimp noda-like virus 3,which shared 79.25%(RdRp)and 63.88%(capsid proteins)amino acid identity with covert mortality nodavirus(CMNV)that may cause losses in aquaculture.In addition,both virome composition and phylogenetic analyses revealed global connectedness in certain brine shrimp viruses,particularly among Asia and Northern America.This highlights the incredible species diversity of viruses in these ancient species and provides essential data for the prevalence of RNA viruses in the global aquaculture industry.More broadly,these findings provide novel insights into the previously unrecognized RNA virosphere in hypersaline ecosystems worldwide and demonstrate that human activity might have driven the global connectedness of brine shrimp viruses.

Impact of Antecedent Soil Moisture Anomalies over the Indo-China Peninsula on the Super Meiyu Event in 2020

In the summer of 2020,a super Meiyu event occurred in the Yangtze River basin(YRB),causing enormous economic losses and human casualties.Recent studies have investigated the possible causes of this super Meiyu event from the perspective of anomalous atmospheric circulation activities and sea surface temperature(SST)anomalies;however,the influence of land surface processes has not garnered considerable attention.This study investigates the possible contributions of land surface processes to this extreme event based on observational analysis and numerical simulations,and shows that antecedent soil moisture(SM)anomalies over the Indo-China Peninsula(ICP)may have had a vital influence on the super Meiyu in 2020.Negative SM anomalies in May over the ICP increased the surface temperature and sensible heat flux.The“memory”of soil allowed the anomalies to persist into the Meiyu period.The heating of the lower atmosphere by the surface strengthened the western Pacific subtropical high,which caused an anomalous anticyclone from the ICP to Northwest Pacific and thus enhanced the southwesterly winds and vertical motion over the YRB.Consequently,the water vapor flux and convergence were strengthened.Sensitivity experiments based on the Weather Research and Forecasting(WRF)model further confirmed the results of observational analysis and indicated that the warm air heated by the ICP surface significantly warmed the lower troposphere from the ICP to Northwest Pacific under the influence of the background wind,thus increasing the geopotential height and inducing an anticyclone.The results of the sensitivity experiments showed that the SM anomalies in May over the ICP increased the precipitation by 10.6%from June to July over the YRB.These findings can improve our understanding of the mechanism of the super Meiyu event in 2020 and facilitate the prediction of extreme Meiyu events.

Spatial transcriptome unveils a discontinuous inflammatory pattern in proficient mismatch repair colorectal adenocarcinoma

The preexistence of immune cells in the tumor microenvironment substantiates the efficacy of immunotherapy in cancer patients.Although the complex intratumoral immune heterogeneity has been extensively studied in single cell resolution,hi-res spatial investigations are limited.In this study,we performed a spatial transcriptome analysis of 4 colorectal adenocarcinoma specimens and 2 paired distant normal specimens to identify the molecular pattern involved in a discontinuous inflammatory response in pathologically annotated cancer regions.Based on the location of spatially varied gene expression,we unmasked the spatially-varied immune ecosystem and identified the locoregional“warmed-up”immune response in predefined“cold”tumor with substantial infiltration of immune components.This“warmed-up”immune profile was found to be associated with the in-situ copy number variance and the tissue remodeling process.Further,“warmed-up”signature genes indicated improved overall survival in CRC patients obtained from TCGA database.

药品管理秩序刑法保护的逻辑与限度

刑法增设妨害药品管理罪,意在适度扩张药品犯罪的犯罪圈,将药品管理秩序法益纳入刑法保护范畴。刑法对药品管理秩序并非独立保护,而是通过药品管理秩序与“足以严重危害人体健康”的规范关联,实现对秩序法益与公共健康法益的一体化保护。基于妨害药品管理罪作为混合犯的规范构造,应当确立二元的违法审查标准:在形式违法层面,应当坚持“先行政后司法”规则,以廓清本罪行政违法与刑事违法的递进关系,避免将行政违法行为刑事犯罪化。在实质违法层面,应当对“足以严重危害人体健康”要件进行实质限缩解释,以合理限定本罪的处罚范围。

LKB1-AMPK axis negatively regulates ferroptosis by inhibiting fatty acid synthesis

Dear Editor,Ferroptosis has emerged as a new programmed cell death modality highly relevant to disease.1 Ferroptosis was initially discovered as an iron-dependent non-apoptotic cell death induced by a serial of ferroptosis-inducing agents(FIN),such as erastin and RSL3.Erastin activates ferroptosis by inhibiting the activity of system Xc−,a cystine-glutamate antiporter,resulting in the depletion of cellular cysteine and glutathione(GSH),thus breaking cellular redox homeostasis.Inactivation of glutathione peroxidase 4(GPX4),an enzyme required to remove the toxic lipid hydroperoxides can induce ferroptosis without the depletion of cellular cysteine and GSH.