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Therapeutic cancer vaccines:advancements,challenges,and prospects

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Signal Transduction and Targeted Therapy 2024年第1期9卷 150-172页

作者： Ting fan Mingna Zhang Jingxian Yang Zhounan zhu Wanlu Cao Chunyan Dong Department of Oncology East Hospital Affiliated to Tongji UniversityTongji University School of MedicineShanghaiChina Postgraduate Training Base Shanghai East HospitalJinzhou Medical UniversityShanghai 200120China

With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies,cancer immunotherapy has undergone a profound transformation over the past decades.Recently,therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens,including tumor-associated antigens and tumor-specific antigens.The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells.However,the complete realization of these capabilities remains an ongoing pursuit.Therefore,we provide an overview of the current landscape of cancer vaccines in this review.The range of antigen selection,antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design.Furthermore,this review addresses the current status of clinical trials and discusses their strategies,focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment.However,current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges,including tumor immune microenvironment suppression,optimal candidate identification,immune response evaluation,and vaccine manufacturing acceleration.Therefore,the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

关键词： breakthrough approval overcome

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

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Neural Regeneration Research 2024年第3期19卷 598-605页

作者： Yaowei Lv Xiangyun Yao xiao Li Yuanming Ouyang Cunyi fan Yun Qian Department of Orthopedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration ShanghaiChina Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine ShanghaiChina College of Fisheries and Life Science Shanghai Ocean UniversityShanghaiChina

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

关键词： cell metabolism diabetic peripheral neuropathy peripheral nerve injury protein kinase C pathway reactive oxygen species.

Association of complement components with risk of colorectal cancer:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2168-2180页

作者： xiao-Lin zhu Lu Zhang Su-Xia Qi Department of Gastroenterology Qingdao Municipal HospitalQingdao 266071Shandong ProvinceChina Department of Medical Administration Qingdao Municipal HospitalQingdao 266071Shandong ProvinceChina

BACKGROUND Complement components could contribute to the tumor microenvironment and the systemic immune response.Nevertheless,their role in colorectal cancer(CRC)remains a contentious subject.AIM To elucidate the relationship between complement components and CRC risk and clinical characteristics.METHODS Searches were conducted in PubMed,the Cochrane Library,and the China National Knowledge Infrastructure database until June 1,2023.We included cohort studies encompassing participants aged≥18 years,investigating the association between complement components and CRC.The studies were of moderate quality or above,as determined by the Agency for Healthcare Research and Quality.The meta-analysis employed fixed-effects or random-effects models based on the I^(2)test,utilizing risk ratio(RR)and their corresponding 95%confidence interval(CI)for outcomes.Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity.RESULTS Data from 15 studies,comprising 1631 participants that met the inclusion criteria,were included in the meta-analysis.Our findings indicated that protein levels of cluster of differentiation 46(CD46)(RR=3.66,95%CI:1.75-7.64,P<0.001),CD59(RR=2.86,95%CI:1.36-6.01,P=0.005),and component 1(C1)(RR=5.88,95%CI:1.75-19.73,P=0.004)and serum levels of C3(standardized mean difference=1.82,95%CI:0.06-3.58,P=0.040)were significantly elevated in patients with CRC compared to healthy controls.Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis,whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression(P<0.05 for all).Although specific pooled results demonstrated notable heterogeneity,subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies.CONCLUSION Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC,emphasi

关键词： Complement components Colorectal cancer Lymph node metastasis Systematic review Meta-analysis

Research on blade tip clearance cavitation and turbulent kinetic energy characteristics of axial flow pump based on the partially-averaged Navier-Stokes model

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Journal of Hydrodynamics 2024年第1期36卷 184-201页

作者： xiao-qi Jia Shuai-kang Zhang Zu-chao zhu Key Laboratory of Fluid Transmission Technology of Zhejiang Province Zhejiang Sci-Tech UniversityHangzhou310018China

To reveal the cavitation forms of tip leakage vortex(TLV)of the axial flow pump and the flow mechanism of the flow field,this research adopts the partially-averaged Navier-Stokes(PANS)model to simulate the cavitation values of an axial flow pump,followed by experimental validation.The experimental result shows that compared with the shear stress transport(SST)k-ωmodel,the PANS model significantly reduces the eddy viscosity of the flow field to make the vortex structure clearer and allow the turbulence scale to be more robustly analyzed.The cavitation area within the axial flow pump mainly comprises of TLV cavitation,clearance cavitation and tip leakage flows combined effect of triangular cloud cavitation formed.The formation and development of cavitation are accompanied by the formation and evolution of vortex,and variations in vortex structure also generate and promote the development of cavitation.In addition,an in-depth analysis of the relationship between the turbulent kinetic energy(TKE)transport equation and cavitation patterns was also conducted,finding that the regions with relatively high TKE are mainly distributed around gas/liquid boundaries with serious cavitation and evident gas-liquid change.This phenomenon is mainly attributed to the combined effect of the pressure action term,stress diffusion term and TKE production term.

关键词： Cavitation axial flow pump tip leakage vortex(TLV) partially-averaged Navier-Stokes(PANS)model turbulent kinetic energy(TKE)

Predictive value of NLR, Fib4, and APRI in the occurrence of liver failure after hepatectomy in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 155-165页

作者： Tian-Zuo Kuang Meng xiao Yong-fan Liu Department of Hepatobiliary Surgery Ji’an Central People’s HospitalJi’an 343000Jiangxi ProvinceChina

BACKGROUND Neutrophil-lymphocyte ratio(NLR),fibrosis index based on four factors(Fib4),aspartate aminotransferase-to-platelet ratio index(APRI)can be used for prognostic evaluation of hepatocellular carcinoma.However,no study has established an individualized prediction model for the prognosis of hepatocellular carcinoma based on these factors.AIM To screen the factors that affect the prognosis of hepatocellular carcinoma and establish a nomogram model that predicts postoperative liver failure after hepatic resection in patients with hepatocellular carcinoma.METHODS In total,220 patients with hepatocellular carcinoma treated in our hospital from January 2022 to January 2023 were selected.They were divided into 154 participants in the modeling cohort,and 66 in the validation cohort.Comparative analysis of the changes in NLR,Fib4,and APRI levels in 154 patients with hepatocellular carcinoma before liver resection and at 3 mo,6 mo,and 12 mo postoperatively was conducted.Binary logistic regression to analyze the influencing factors on the occurrence of liver failure in hepatocellular carcinoma patients,roadmap prediction modeling,and validation,patient work characteristic curves(ROCs)to evaluate the predictive efficacy of the model,calibration curves to assess the consistency,and decision curve analysis(DCA)to evaluate the model’s validity were also conducted.RESULTS Binary logistic regression showed that Child-Pugh grading,Surgical site,NLR,Fib4,and APRI were all risk factors for liver failure after hepatic resection in patients with hepatocellular carcinoma.The modeling cohort built a column-line graph model,and the area under the ROC curve was 0.986[95%confidence in terval(CI):0.963-1.000].The patients in the validation cohort utilized the column-line graph to predict the probability of survival in the validation cohort and plotted the ROC curve with an area under the curve of the model of 0.692(95%CI:0.548-0.837).The deviation of the actual outcome curves from the calibration curves of the column-line plots gener

关键词： Hepatocellular carcinoma Hepatic resection Liver failure Influencing factors Columnar graphs

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

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Acta Pharmaceutica Sinica B 2024年第1期14卷 207-222页

作者： Hongrui zhu Yamin Gao Liyun Liu Mengyu Tao xiao Lin Yijia Cheng Yaoyao Shen Haitao Xue Li Guan Huimin Zhao Li Liu Shuping Wang fan Yang Yongjun Zhou Hongze Liao fan Sun Houwen Lin Research Center for Marine Drugs Department of PharmacyRen Ji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Oncology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Institute of Marine Drugs Guangxi University of Chinese MedicineNanning 530200China State Key Laboratory of New Drug and Pharmaceutical Process Shanghai Professional and Technical Ser-vice Center for Biological Material Drug-ability EvaluationShanghai Institute of Pharmaceutical IndustryChina State Institute of Pharmaceutical IndustryShanghai 200437China Institute of Marine Biomedicine Shenzhen PolytechnicShenzhen 518055China

Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.Here,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin pathway.Importantly,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC models.Collectively,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

关键词： Colorectal cancer TNKSeUSP25 interaction Multi-drug resistance TNKS overexpression Wnt pathway Apoptosis Neoantimycin analog

Screening and identification of functional bacterial attachment genes in aerobic granular sludge

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Journal of Environmental Sciences 2024年第7期141卷 205-214页

作者： Kai Qiao Tingting Zhao LeiWang Wei Zhang WeiMeng fan Liu Xu Gao Jianrong zhu School of Environment Beijing Normal UniversityBeijing 100875China State Key Laboratory of Water Simulation Beijing 100875China R&D Centre of Aerobic Granule Technology Beijing 100875China

The screening and identification of attachment genes is important to exploring the formation mechanism of biofilms at the gene level.It is helpful to the development of key culture technologies for aerobic granular sludge(AGS).In this study,genome-wide sequencing and gene editing were employed for the first time to investigate the effects and functions of attachment genes in AGS.With the help of whole-genome analysis,ten attachment genes were screened from thirteen genes,and the efficiency of gene screening was greatly improved.Then,two attachment genes were selected as examples to further confirm the gene functions by constructing gene-knockout recombinant mutants of Stenotrophomonas maltophilia;when the two attachment genes were knocked out,the attachment potential was reduced by 50.67%and 43.93%,respectively.The results provide a new theoretical principle and efficient method for the development of AGS from the perspective of attachment genes.

关键词： Attachment gene Genome-wide sequence Gene-knockout Attachment potential Aerobic granular sludge biofilm

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

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World Journal of Gastroenterology 2024年第7期30卷 663-672页

作者： xiao-Fei Cheng Feng Zhao Dong Chen fan-Long Liu Department of Colorectal Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Radiation Oncology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment

关键词： Neoadjuvant therapy Colorectal cancer liver metastasis Multidisciplinary teams Chemotherapeutic regimens Resectability criteria

Methods,Mechanisms,and Application Prospects for Enhancing Extracellular Vesicle Uptake

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Current Medical Science 2024年第2期44卷 247-260页

作者： Ying-peng XU Tao JIANG xiao-fan YANG Zhen-bing CHEN Department of Hand Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Extracellular vesicles(EVs)are considered to be a new generation of bioinspired nanoscale drug delivery systems due to their low immunogenicity,natural functionality,and excellent biocompatibility.However,limitations such as low uptake efficiency,insufficient production,and inhomogeneous performance undermine their potential.To address these issues,numerous researchers have put forward various methods and applications for enhancing EV uptake in recent decades.In this review,we introduce various methods for the cellular uptake of EVs and summarize recent advances on the methods and mechanisms for enhancing EV uptake.In addition,we provide further understanding regarding enhancing EV uptake and put forward prospects and challenges for the development of EV-based therapy in the future.

关键词： extracellular vesicles exosomes extracellular vesicle uptake extracellular vesiclebased therapy