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Potential value of detection of minimal residual disease in colorectal cancer following radical resection

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Chinese Journal of Cancer research 2024年第4期36卷 442-454页

作者： Wenji Pu Fang Chen Yuan Tang Yanling Qu Yunzhu Han Jiandong Zha Jing Jin Fengming Kong Medical Department of Shenzhen University/General Hospital of Shenzhen University/Academy of clinical medicine of Shenzhen University Shenzhen 518055China Department of clinical Oncology the University of Hong Kong-Shenzhen HospitalShenzhen 518053China Department of Radiotherapy National Cancer Center/National Cancer Clinical Medical Research Center/Shenzhen HospitalCancer Hospital of Peking Union Medical CollegeChinese Academy of Medical SciencesShenzhen 518116China

Although there has been significant advancement in the identification and management of colorectal cancer(CRC)in recent years,there is still room for improvement in the current standard treatment *** area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored *** to its dynamic,effective,and non-invasive benefits over tissue biopsy,the detection of minimal or molecular residual lesions(MRD)based on circulating tumor DNA(ctDNA)is beneficial to the clinical development of drugs for patients with CRC after radical treatment,as well as for continuous monitoring of tumor recurrence and malignancy molecular gene *** detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions(upgrade or downgrade treatment)in CRC,stratify the risk of clinical recurrence more precisely,and predict the risk of recurrence in advance of imaging examination,according to a large number of observational or prospective clinical *** increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA,which also improves the accuracy of clinical recurrence risk assessment for ***,it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized,stratified precision therapy;however,additional confirmation will require subsequent high-quality,prospective,large-scale randomized controlled *** article will provide an overview of the definition and clinical significance of MRD,the primary indications and technological challenges for MRD detection,along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.

关键词： Colorectal cancer minimal residual disease circulating tumor DNA prognosis recurrence biomarkers

clinical characteristics and outcomes of hospitalized kidney transplant recipients with COVID-19 infection in China during the Omicron wave:a single-center cohort study

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 529-540页

作者： Duo LV Xishao XIE Qinyun YANG Zhimin CHEN Guangjun LIU Wenhan PENG Rending WANG Hongfeng HUANG Jianghua CHEN Jianyong WU Department of clinical Pharmacy the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Zhejiang Provincial Key Laboratory for Drug Evaluation and clinical research Hangzhou 310003China Kidney Disease center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Laboratory of Kidney Disease prevention and Control Technology Zhejiang ProvinceHangzhou 310003China Institute of Nephrology Zhejiang UniversityHangzhou 310003China Zhejiang clinical research center of Kidney and Urinary System Disease Hangzhou 310003China The Third Grade Laboratory under the National State Administration of Traditional Chinese MedicineHangzhou 310003China Information center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are ***:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,*** patients were followed up until Mar.31,***:A total of 324 KTRs with COVID-19 were *** median age was 49 *** median time between the onset of symptoms and admission was 13 ***,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,***-nine(9.0%)patients were treated with more than one antiviral ***-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib *** acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care *** infections were observed in 55(17.0%)***(15.4%)patients lost their *** 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of *** Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized ***:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of *** administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

关键词： Coronavirus disease 2019(COVID-19) Kidney transplant Hospitalization Mortality

Novel de novo TRPV4 mutation identified in a Chinese family with metatropic dysplasia inhibits chondrogenic differentiation

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Genes & Diseases 2024年第3期11卷 83-86页

作者： Ping Wei Weizhe Shi Tianying Nong Caixia Xian Xia Li Zhaohui Li Xin Li Jianping Wu Liyuan Shang Fulong Xu Yibo Xu Hongwen Xu Mingwei Zhu Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China Department of Pediatric Orthopedics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China

Metatropicdysplasia(MD,MIM156530)is a rare congenital bone dysplasia primarily characterized by severe platyspondyly with long and wide vertebral bodies and dumbbell deformity of the tubular *** can be caused by heterozygous mutations in the gene encoding transient receptor potential vanilloid family member 4(TRPV4).We identifieda novel de novo mutation,c.2353T>C,in the TRPV4 gene,in a Chinese family with mild MD.

关键词： TRPV4 dysplasia congenital

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

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Neural Regeneration research 2024年第4期19卷 754-768页

作者： Wei You Yue Li Kaixi Liu Xinning Mi Yitong Li Xiangyang Guo Zhengqian Li Department of Anesthesiology Peking University Third Hospital Peking University Third clinical Medical College Beijing center of Quality Control and Improvement on clinical Anesthesia Anesthesia and Perioperative medicine Branch of China International Exchange and Promotive Association for Medical and Health Care(CPAM)

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial *** the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive *** review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

关键词： cognitive disorders mitochondrial dysfunction mitochondrial energy metabolism mitochondrial dynamics mitochondrial transport mitophagy mitochondrial biogenesis oxidative stress calcium homeostasis

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan Lu Jingwei Zheng Shuhao Mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu Department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina clinical research center for Neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina Key Laboratory of precise Treatment and clinical Translational research of Neurological Diseases HangzhouZhejiang ProvinceChina

preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral *** E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and ***,the effect of Spi1 on intracerebral hemorrhage remains *** this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage *** showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained ***,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and *** conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral *** new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

Optogenetics in oral and craniofacial research

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 656-671页

作者： Qinmeng ZHANG Luyao SONG Mengdie FU Jin HE Guoli YANG Zhiwei JIANG Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310000China Zhejiang University School of medicine Hangzhou 310058China

Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high *** modified photosensory sensors are engineered into proteins to modulate conformational changes with light ***,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral ***,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial *** addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational *** the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental *** future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.

关键词： Lasers Cell differentiation Bacterial virulence Nervous system Neurophysiology Behavioral science

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF:not just ICSI failure

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Asian Journal of Andrology 2024年第2期26卷 175-182页

作者： Jian-Fang Che Hui-Xia Wu Si-Cong Zeng Yue-Ren Wu Jing Dai De-Hua Cheng Fei Gong Guang-Xiu Lu Ge Lin Can Dai School of medicine Hunan Normal UniversityChangsha 410013China Reproductive and Genetic Hospital of CITIC-Xiangya Changsha 410008China clinical research center for Reproduction and Genetics in Hunan Province Changsha 410078China National Engineering and research center of Human Stem Cell Changsha 410205China

Phospholipase C zeta(PLC)is a key sperm-borne oocyte-activating factor that triggers Ca^(2+)oscillations and the subsequent block to polyspermy following gamete *** in PLCZ1,the gene encoding PLCζ,cause male infertility and intracytoplasmic sperm injection(ICSI)fertilization failure;and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate(FR).However,in conventional in vitro fertilization(cIVF),whether and how sperm PLCζ affects fertilization remain ***,we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei(PN)*** staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca^(2+) *** with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live ***,we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CiTiC-Xiangya(Changsha,China)between February 2019 and January *** found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total *** optimal cutoff value below which males were likely to experience low FR(total FR≤30%)after clVF was 56.7%for the proportion of spermatozoa expressing *** study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the widermale population and not onlymen with IcsI failure.

关键词： conventional IVF gene variants PLCζ polyspermy

Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of Laboratory medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Laboratory of clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of Laboratory medicine Zhejiang UniversityHangzhou 310000China Department of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response