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Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

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Chinese Journal of Cancer research 2024年第4期36卷 410-420页

作者： Nan Chen Minghe Zhao Yunfeng Yao Lin Wang Yifan Peng Tingting Sun Tiancheng Zhan Jun Zhao Aiwen Wu Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer *** patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during *** pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major ***:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable *** fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

关键词： Neoadjuvant chemotherapy rectal cancer mesorectal fascia disease-free survival anal function

Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

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Cancer Biology & Medicine 2024年第6期21卷 473-483页

作者： Shuyi Chen Jing Gu Kaichun Wu Xiaodi Zhao Yuanyuan Lu State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research Center for Digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’an 710032China School of Basic Medical Sciences Fourth Military Medical UniversityXi’an 710032China

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

关键词： Genetic variation gene mutation gene amplification gene rearrangement targeted therapy

Reassessing the impact of post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy on mortality in patients with cirrhosis

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 540-543页

作者： Qiuju Ran Zhang Wen Shuyue Tuo Jinhai Wang Xinxing Tantai Department of Gastroenterology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Clinical research Center for gastrointestinal diseases of Shaanxi Province The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

Nardelli et al.(1)conducted a multi-center observational study to assess the mortality risk in patients with and without overt hepatic encephalopathy(HE)after transjugular intrahepatic portosystemic shunt(TIPS).In their paper,the authors disclosed that post-TIPS overt HE was not linked to an increased risk of mortality in patients with cirrhosis during a median follow-up of 30 months(1).However,many other studies have reported that post-TIPS HE is significantly associated with a higher risk of mortality based on long-term follow-up in patients with cirrhosis(2-6).Given this inconsistency,we conducted a meta-analysis to evaluate the association between post-TIPS HE and mortality,using both unadjusted and adjusted effect estimates in patients with cirrhosis.

关键词： mortality cirrhosis TIPS

Radiation injury and gut microbiota-based treatment

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Protein & Cell 2024年第2期15卷 83-97页

作者： Weihong Wang Bota Cui Yongzhan Nie Lijuan Sun Faming Zhang Department of Microbiota Medicine and Medical Center for Digestive diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China Department of Microbiotherapy Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers and National Clinical research Center for Digestive diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'an 710032China National Clinical research Center for Digestive diseases Xi'an 710032China Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineNorthwest UniversityXi'an 710069China

The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury(RI).RI is a common disease involving multiple human body parts and organs,yet effective treatments are currently *** evidence suggests gut microbiota are closely associated with the development and prevention of various *** article summarizes 10 common types of RI and their possible *** also highlights the changes and potential microbiota-based treatments for RI,including probiotics,metabolites,and microbiota ***,a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.

关键词： microbiome ionizing radiation radiation-induced injury short-chain fatty acids fecal microbiota transplant washed microbiota transplantation war nuclear microbiota medicine

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

Advances in MET tyrosine kinase inhibitors in gastric cancer

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Cancer Biology & Medicine 2024年第6期21卷 484-498页

作者： Yifan Zhang Lin Shen Zhi Peng Key Laboratory of Carcinogenesis and Translational research(Ministry of Education) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China

Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths *** gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment *** is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound ***,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient *** such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase *** review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and *** on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies.

关键词： Gastric cancer MET alterations MET tyrosine kinase inhibitors savolitinib MET testing

Association of DNA methylation/demethylation with the functional outcome of stroke in a hyperinflammatory state

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Neural Regeneration research 2024年第10期19卷 2229-2239页

作者： Yubo Wang Ling Zhang Tianjie Lyu Lu Cui Shunying Zhao Xuechun Wang Meng Wang Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research Center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina research unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research Center of Digital Healthcare for Neurological diseases BeijingChina

Inflammation is closely related to stroke prognosis, and high inflammation status leads to poor functional outcome in stroke. DNA methylation is involved in the pathogenesis and prognosis of stroke. However, the effect of DNA methylation on stroke at high levels of inflammation is unclear. In this study, we constructed a hyperinflammatory cerebral ischemia mouse model and investigated the effect of hypomethylation and hypermethylation on the functional outcome. We constructed a mouse model of transient middle cerebral artery occlusion and treated the mice with lipopolysaccharide to induce a hyperinflammatory state. To investigate the effect of DNA methylation on stroke, we used small molecule inhibitors to restrain the function of key DNA methylation and demethylation enzymes. 2,3,5-Triphenyltetrazolium chloride staining, neurological function scores, neurobehavioral tests, enzyme-linked immunosorbent assay, quantitative reverse transcription PCR and western blot assay were used to evaluate the effects after stroke in mice. We assessed changes in the global methylation status by measuring DNA 5-mc and DNA 5-hmc levels in peripheral blood after the use of the inhibitor. In the group treated with the DNA methylation inhibitor, brain tissue 2,3,5-triphenyltetrazolium chloride staining showed an increase in infarct volume, which was accompanied by a decrease in neurological scores and worsening of neurobehavioral performance. The levels of inflammatory factors interleukin 6 and interleukin-1 beta in ischemic brain tissue and plasma were elevated, indicating increased inflammation. Related inflammatory pathway exploration showed significant overactivation of nuclear factor kappa B. These results suggested that inhibiting DNA methylation led to poor functional outcome in mice with high inflammation following stroke. Further, the effects were reversed by inhibition of DNA demethylation. Our findings suggest that DNA methylation regulates the inflammatory response in stroke

关键词： DNA demethylation DNA methylation DNMT3A functional outcome hyperinflammatory state interleukin neuroinflammation stroke TET2

Genome Analysis of Plasmodium falciparum:A Preliminary Observation-Sierra Leone,2022-2023

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China CDC weekly 2024年第17期6卷 368-373页

作者： Tianyu Wang Haimo Shen Bin Xu Wanxuan Yang Shenbo Chen Junhu Chen National Institute of Parasitic diseases Chinese Center for Disease Control and Prevention(Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector BiologyWHO Collaborating Centre for Tropical DiseasesNational Centre for International Research on Tropical DiseasesShanghaiChina School of Basic Medical Sciences and Forensic Medicine Hangzhou Medical CollegeHangzhou CityZhejiang ProvinceChina School of Global Health Chinese Centre for Tropical Diseases ResearchShanghai Jiao Tong University School of MedicineShanghaiChina Hainan Tropical diseases research Center(Hainan Sub-Center Chinese Center for Tropical Diseases Research)Haikou CityHainan ProvinceChina.

What is already known about this topic?Sierra Leone,with a gross domestic product(GDP)per capita below$300 and significant poverty,ranks among the world’s least developed countries(LDCs).Despite its modest population of 8.6 million,the nation reports approximately 2.6 million malaria cases ***,there has been no reporting on the malaria genome data from this *** is added by this report?In this study,we present the first reported wholegenome sequence analysis of 19 high parasite-density Plasmodium falciparum isolates from Sierra Leone,providing insights into the genomic epidemiology of this high-prevalence *** found a high degree of relatedness among infections and substantial genetic diversity,consistent with the gradual reduction in overall case ***,our whole-genome analysis revealed that,beyond drug-resistance genes,gene families related to blood cell invasion,immune evasion,and others are undergoing directional *** suggests that the population in Sierra Leone has developed a relatively strong acquired *** are the implications for public health practice?The genomic data not only facilitate the creation of single nucleotide polymorphism barcodes for case tracking but also enable the analysis of evolving transmission dynamics and selection ***,the samples from Sierra Leone exhibited higher selective pressures on resistance genes compared to those from Asia,a trend not commonly observed in other African *** suggests that less stringent healthcare systems and inconsistent treatment strategies can subject parasites to increased drug pressure,thereby accelerating the development of resistant strains.

关键词： epidemiology invasion Observation

Lung microbiome:new insights into the pathogenesis of respiratory diseases

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Signal Transduction and Targeted Therapy 2024年第2期9卷 652-678页

作者： Ruomeng Li Jing Li Xikun Zhou Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Oral diseases National Clinical Research Center for Oral DiseasesChinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and ManagementWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China

The lungs were long thought to be sterile until technical advances uncovered the presence of the lung microbial *** microbiome of healthy lungs is mainly derived from the upper respiratory tract(URT)microbiome but also has its own characteristic *** selection mechanisms in the lung,including clearance by coughing,pulmonary macrophages,the oscillation of respiratory cilia,and bacterial inhibition by alveolar surfactant,keep the microbiome transient and mobile,which is different from the microbiome in other *** pulmonary bacteriome has been intensively studied recently,but relatively little research has focused on the mycobiome and *** up-to-date review retrospectively summarizes the lung microbiome’s history,composition,and *** focus on the interaction of the lung microbiome with the oropharynx and gut microbiome and emphasize the role it plays in the innate and adaptive immune *** importantly,we focus on multiple respiratory diseases,including asthma,chronic obstructive pulmonary disease(COPD),fibrosis,bronchiectasis,and *** impact of the lung microbiome on coronavirus disease 2019(COVID-19)and lung cancer has also been comprehensively ***,by summarizing the therapeutic potential of the lung microbiome in lung diseases and examining the shortcomings of the field,we propose an outlook of the direction of lung microbiome research.

关键词： respiratory diseases Lung