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Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng Department of Hepatobiliary-pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Sidney Kimmel Comprehensive Cancer Center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic ***-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and ***-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been ***,the precise functions of these subtypes need to be studied and *** of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic *** clinical trials,including phase III trials targeting CAFs,have been performed ***,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be *** review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving ***,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： Cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

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Comparison of outcomes with stapler versus hand-sewn closure of the pancreatic stump following minimally invasive distal pancreatectomy: a retrospective cohort study

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胰腺病学杂志(英文) 2024年第2期7卷 106-110页

作者： Qian Tao Huang Kaiquan Chen Wen Bai Xueli Gao Shunliang Shen Yan Zhang Min Wu Jian Yu Jun Ma Tao Liang Tingbo Department of Hepatobiliary and pancreatic Surgery the First Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China Innovation Center for the Study of pancreatic Diseases of Zhejiang Province Hangzhou China Zhejiang Clinical research Center of Hepatobiliary and pancreatic Diseases Hangzhou China Zhejiang Provincial Key Laboratory of pancreatic Disease Hangzhou China Cancer Center Zhejiang University Hangzhou China

Background: pancreatic fistula after distal pancreatectomy is a common and potentially lethal complication. The optimal closure method for the pancreatic remnant during minimally invasive distal pancreatectomy (MDP) remains ***: Data of consecutive patients who underwent MDP in our institution between July 2018 and June 2021 were collected. The outcomes of MDP with stapler and hand-sewn closure were compared. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF) per the International Study group of pancreatic Surgery ***: Of the 384 patients (stapler closure, 339; hand-sewn closure, 45) enrolled, 249 developed CR-POPF (grades B and C: 242 and 7 patients, respectively). The rates of grade B and grade C POPF in the stapler group were similar to the corresponding rates in the hand-sewn group (64.6% and 1.5% vs 51.1% and 4.4%,P = .078 andP = .223, respectively). No differences between the stapler and hand-sewn groups were observed regarding the median operation time (207 vs 222 minutes,P = .139), incidence of major complications (16.5% vs 20.0%,P = .559), and mortality (0.2% vs 0%,P = 1.000). The independent risk factors of CR-POPF were abdominal abscess, prolonged operation time, and transection site (P = .004, .006, and .001, respectively).Conclusion: The incidence and severity of CR-POPF by stapler closure of the pancreatic stump were comparable to those associated with hand-sewn closure in MDP in this retrospective cohort. Randomized controlled trials are needed to verify this finding.

关键词： Distal pancreatectomy Minimally invasive surgery Outcome Postoperative pancreatic fistula Stapler closure

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Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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Cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan Man Song Gao Jihui Hao Department of pancreatic Cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China Department of Gastrointestinal pancreatic Surgery Shanxi Provincial People’s HospitalTaiyuan 030012China

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell ***-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine ***,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains ***:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were *** of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was ***:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and *** GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic *** tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and ***:Ki-67 is a valuable prognostic indicator for *** of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： pancreatic ductal adenocarcinoma prognosis Ki-67 differentiation TNM stage

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Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2380-2393页

作者： Qi-Feng Wang Zong-Wei Li Hai-Feng Zhou Kun-Zhong Zhu Ya-Jing Wang Ya-Qin Wang Yue-Wei Zhang Department of Hepatobiliary pancreatic Center Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua UniversityBeijing 102218China Department of Hepatobiliary and pancreatic Surgery Qinghai University Affiliated HospitalXining 810000Qinghai ProvinceChina

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy *** review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical *** of October 25,2023,51 articles have been retrieved based on keyword predictions and *** eligible articles were selected for inclusion in this *** literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging *** above indicators and their combined forms showed excellent predictive effects in retrospective *** review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.

关键词： Hepatocellular carcinoma Hepatic artery infusion chemotherapy Prediction Prognosis Imaging Biomarkers Genomics

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Design and verification of an FPGA programmable logic element based on Sense-Switch pFLASH

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Frontiers of Information Technology & Electronic Engineering 2024年第4期25卷 485-499页

作者： Zhengzhou CAO Guozhu LIU Yanfei ZHANG Yueer SHAN Yuting XU No.58 research Institute China Electronics Technology Group CorporationWuxi 214035China

This paper proposes a kind of programmable logic element(PLE)based on Sense-Switch pFLASH *** programming Sense-Switch pFLASH,all three-bit look-up table(LUT3)functions,partial four-bit look-up table(LUT4)functions,latch functions,and d flip flop(DFF)with enable and reset functions can be *** PLE uses a choice of operational logic(COOL)approach for the operation of logic functions,it allows any logic circuit to be implemented at any ratio of combinatorial logic to *** intrinsic property makes it close to the basic application specific integrated circuit(ASIC)cell in terms of fine granularity,thus allowing ASIC-like cell-based mappers to apply all their optimization *** measuring Sense-Switch pFLASH and PLE circuits,the results show that the“on”state driving current of the Sense-Switch pFLASH is about 245.52μA,and that the“off”state leakage current is about 0.1 *** programmable function of PLE works *** delay of the typical combinatorial logic operation AND3 is 0.69 ns,and the delay of the sequential logic operation DFF is 0.65 ns,both of which meet the requirements of the design technical index.

关键词： Field programmable gate array(FPGA) Programmable logic element(PLE) Boolean logic operation Look-up table Sense-Switch pFLASH Threshold voltage

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Towards an integrated risk analysis security framework according to a systematic analysis of existing proposals

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Frontiers of Computer Science 2024年第3期18卷 199-216页

作者： Antonio SANTOS-OLMO Luis Enrique SÁNCHEZ David G.ROSADO Manuel A.SERRANO Carlos BLANCO Haralambos MOURATIDIS Eduardo FERNÁNDEZ-MEDINA GSyA research group University of Castilla-La ManchaCiudad Real 13071Spain Institute for Analytics and Data Science University of EssexColchester CO43SQUK Alarcos research group University of Castilla-La ManchaCiudad Real 13071Spain ISTR research group Department of Computer Science and ElectronicsUniversity of CantabriaSantander 39005Spain

The information society depends increasingly on risk assessment and management systems as means to adequately protect its key information *** availability of these systems is now vital for the protection and evolution of ***,several factors have led to an increasing need for more accurate risk analysis *** are:the speed at which technologies evolve,their global impact and the growing requirement for companies to *** analysis processes must consequently adapt to these new circumstances and new technological *** objective of this paper is,therefore,to present the results of an exhaustive analysis of the techniques and methods offered by the scientific community with the aim of identifying their main weaknesses and providing a new risk assessment and management *** analysis was carried out using the systematic review protocol and found that these proposals do not fully meet these new *** paper also presents a summary of MARISMA,the risk analysis and management framework designed by our research *** basis of our framework is the main existing risk standards and proposals,and it seeks to address the weaknesses found in these *** is in a process of continuous improvement,as is being applied by customers in several European and American *** consists of a risk data management module,a methodology for its systematic application and a tool that automates the process.

关键词： information security management security system security risk assessment and management

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Evolution of biomass particles during pelletization process

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Particuology 2024年第3期86卷 182-187页

作者： Hamid Rezaei Maryam Tajilrou Jun Sian Lee Kanages Singaraveloo Anthony Lau Shahab Sokhansanj Biomass and Bioenergy research group Department of Chemical and Biological EngineeringUniversity of British ColumbiaVancouverCanada

Pulverizing is an essential unit operation in co-firing biomass with *** are only compatible with pellet forms of fibrous biomass materials and crush them down to their original forming particle *** is why the data on the size distribution of the particles forming a biomass pellet is crucial to achieving optimum combustion *** current study determines the internal particle size distribution of pellets after wet disintegration,following Iso 17830 standard,and aims to suggest improvements to the mentioned standard based on new measured *** were carried out on white wood pellets(no bark)and brown wood pellets containing bark at four water temperatures:20,40,60,and 95℃,with or without *** particle size distribution of the pre-pelletizer wood particles was also measured and compared with particles in the formed *** water temperature of 20℃ was found to be adequate for the complete disintegration of pellets,and no mechanical stirring was *** 30% of particles in the disintegrated pellets were 0.5-1.0 *** changes the particle size distribution to smaller *** disintegrated bark pellets contained more fines than white pellets.

关键词： Wood pellets Particle sizes distribution Wet disintegration Stirring Water temperature

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Incense smoke(IS)inhalation exposure system:Physicochemical characterization,IS particle deposition and clearance in human airway using MPPD model

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Particuology 2024年第4期87卷 271-285页

作者： Vyas Kumar Hafsa Hashmi Anshita Nasreen Ghazi Ansari Jyotsna Singh Inhalation Toxicology Facility Regulatory Toxicology GroupCSR-Indian Institute of Toxicology ResearchLucknow22001UPIndi Academy of Scientific and Innovative research(AcsSIR) Ghaziabad201002UPIndia Analytical Chemistry Regulatory Toxicology GroupCSIR-Indian Institute of Toxicology ResearchLucknow226001UPIndia

Incense smoke(IS)is source of indoor air pollution and key risk for diverse human *** in-formation is available regarding controlled IS rodent inhalation exposure system and IS particulate matter(PM)deposition in human *** aimed to demonstrate stable ISPM physicochemical parameters of 10 incense products inside the customized whole body inhalation exposure chamber(without animal)connected to smoke generation unit via aerosol mixing *** analyzed for size segregated PM emission,ISPM in vitro aerodynamics(MMAD and GSD determination),fine and ultrafine particle's SEM,SEM-EDX and PAH *** real life exposure scenario by utilizing MMAD,GSD and PM concentration after Tier 1 exposure assessment as key input parameters,ISPM dosimetry in infant(3 months)and adult(21 years male and female)human airways was calculated using multiple-path particle dosimetry(MPPD 3.04)*** median aerodynamic diameter(MMAD)and geo-metric standard deviation(GSD)ranged between 0.55 and 2.10μm and 1.22 to 1.77(polydisperse)***1.0 and PM0.1 showed multiple morphology and presence of heavy and trace *** like acenaphthylene,anthracene,fluorene,naphthalene and phenanthrene were detected(0.84-143.17μg/g).MPPD results showed higher ISPM deposition in pulmonary region and lowest in trachea bronchial *** deposition in tissue was higher in lower,peripheral lung as compared to upper and central lung *** body inhalation exposure system showed stable IS atmosphere(physi-cochemical parameters)indicating the device suitability in future inhalation *** ISPM deposition fraction and clearance data showed deep lung penetrating and retention behavior with higher risk in infant followed by female and then *** modeled particle deposition and clearance data may be useful in risk assessment analysis of IS.

关键词： Inhalation Incense smoke Multiple-path particle dosimetry(MPPD) Particle deposition Particulate matter(PM) Mass median aerodynamic diameter (MMAD) Human airway

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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of Hepatobiliary and pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Diagnosis&Treatment League for Hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Innovative research group for Hepatobiliary&pancreatic Surgery and Digestive Organ Transplantation Zhengzhou 450052China Henan Organ Transplantation Quality Control Centre Zhengzhou 450052China Henan Engineering Technology research Center for Organ Transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis Institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

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Achieving laparoscopic anatomic resection for hepatocellular carcinoma by fluorescence guided positive staining of hepatic cone unit

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Hepatobiliary & pancreatic Diseases International 2024年第4期23卷 406-411页

作者： Jun-Fang Deng Chuan-Hui Peng Yu Zhang Xiao-Feng Xu Rong-Liang Tong Zheng-Long Zhai Di-Yu Chen Cheng Zhang Li-Ming Wu Jian Wu Division of Hepatobiliary pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine green(ICG)-fluorescence imaging has been introduced as an effective tool for real-time intraoperative guidance[2].Liver anatomy is ***,liver is composed of 9 segments,each is composed of two to three subsegments,and each subsegment contains several hepatic cone units.A hepatic cone unit is dominated by a tertiary or quaternary hepatic pedicles[3].

关键词： hepatic resection anatomy

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