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Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 372-385页

作者： Jia-Li Chen Lu Guo Zhen-Ying Wu Kun He Han Li Chi Yang Yun-Wei Han Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Clinical Research institute The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Plastic Surgery Meguiar's Medical Beauty HospitalChengdu 610000Sichuan ProvinceChina

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the affiliated hospital of Southwest medical university,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

关键词： Circulating tumor cells Neutrophil–lymphocyte ratio Hepatocellular carcinoma Prognosis Survival Marker

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Knowledge-embedded spatio-temporal analysis for euploidy embryos identification in couples with chromosomal rearrangements

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Chinese medical Journal 2024年第6期137卷 694-703页

作者： Fangying Chen Xiang Xie Du Cai Pengxiang Yan Chenhui Ding Yangxing Wen Yanwen Xu Feng Gao Canquan Zhou Guanbin Li Qingyun Mai Reproductive Medicine Center The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory of Reproductive Medicine GuangzhouGuangdong 510080China School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong 510006China Department of General Surgery(Colorectal Surgery) The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655China Shanghai Artificial Intelligence Laboratory Shanghai 200232China

Background:The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy neonate.Some algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome,who subjected to preimplantation genetic testing for aneuploidy(PGT-A)treatment.However,it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal rearrangement.Methods:From February 2020 to May 2021,we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos,the clinical information of couples,and the comprehensive chromosome screening results of those blastocysts that had received PGT treatment.Initially,we developed a novel deep learning model called the Attentive Multi-Focus Selection Network(AMSNet)to analyze time-lapse videos in real time and predict blastocyst formation.Building upon AMSNet,we integrated additional clinically predictive variables and created a second deep learning model,the Attentive Multi-Focus Video and Clinical Information Fusion Network(AMCFNet),to assess the euploidy status of embryos.The efficacy of the AMCFNet was further tested in embryos with parental chromosomal rearrangements.The receiver operating characteristic curve(ROC)was used to evaluate the superiority of the model.Results:A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task,and 1422 qualified blastocysts received PGT-A(n=589)or PGT for chromosomal structural rearrangement(PGT-SR,n=833)were enrolled for the euploidy assessment task in this study.The AMSNet model using seven focal raw time-lapse videos has the best real-time accuracy.The real-time accuracy for AMSNet to predict blastocyst formation reached above 70%on the day 2 of embryo culture,and then increased to 80%on the day 4 of embryo culture.Combing with 4 clinical features of couples,the AUC of A

关键词： Euploidy status Embryo Time-lapse imaging Deep learning Spatio-temporal analysis Preimplantation genetic testing for chromosomal structural rearrangement

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Bronchoalveolar lavage fluid metagenomic next-generation sequencing assay for identifying pathogens in lung cancer patients

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BIOCELL 2024年第4期48卷 623-637页

作者： JIYU WANG HUIXIA LI DEYUAN ZHOU LIHONG BAI KEJING TANG Division of Pulmonary and Critical Care Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina institute of Pulmonary Diseases Sun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

Background:For patients with lung cancer,timely identiﬁcation of new lung lesions as infectious or non-infectious,and accurate identiﬁcation of pathogens is very important in improving OS of patients.As a new auxiliary examination,metagenomic next-generation sequencing(mNGS)is believed to be more accurate in diagnosing infectious diseases in patients without underlying diseases,compared with conventional microbial tests(CMTs).We designed this study toﬁnd out whether mNGS has better performance in distinguishing infectious and non-infectious diseases in lung cancer patients using bronchoalveolar lavageﬂuid(BALF).Materials and Methods:This study was a real-world retrospective review based on electronic medical records of lung cancer patients with bronchoalveolar lavage(BAL)and BALF commercial mNGS testing as part of clinical care from 1 April 2019 through 30 April 2022 at The First Afﬁliated hospital of Sun Yat-sen university.164 patients were included in this study.Patients were categorized into the pulmonary non-infectious disease(PNID)group(n=64)and the pulmonary infectious disease(PID)group(n=100)groups based onﬁnal diagnoses.Results:BALF mNGS increased the sensitivity rate by 60%compared to CMTs(81%vs.21%,p0.1).Among the patients with PID,bacteria were the most common cause of infection.Fungal infections occurred in 32%of patients,and Pneumocystis Yersini was most common.Patients with Tyrosine kinase inhibitors(TKIs)therapy possess longer overall survival(OS)than other anti-cancer agents,the difference between TKIs and immuno-checkpoint inhibitors(ICIs)was insigniﬁcant(median OS TKIs vs.ICIs vs.Anti-angiogenic vs.Chemo vs.Radiotherapy=76 vs.84 vs.61 vs.58 vs.60).Conclusions:our study indicates that BALF mNGS can add value by improving overall sensitivity in lung cancer patients with potential pulmonary infection,and was outstanding in identifying Pneumocystis infection.It could be able to help physicians adjust the follow-up treatmen

关键词： Lung cancer Bronchoalveolar lavage fluid Metagenomic next-generation sequencing Infectious diseases

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Prognostic significance and relationship of SMAD3 phosphoisoforms and VEGFR-1 in gastric cancer:A clinicopathological study

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 118-132页

作者： Shi-Lin Lv Pei Guo Jun-Rong Zou Ren-Sheng Chen Ling-Yu Luo De-Qiang Huang hospital of Gastroenterology Institute of Digestive DiseasesThe First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Pathology Shenzhen Hospital of Southern Medical UniversityShenzhen 518000Guangdong ProvinceChina institute of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Department of Pathology The First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of

关键词： Gastric cancer pSMAD3L(S204) pSMAD3C(S423/425) Survival Transforming growth factor-β1 VEGFR-1

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Pharmacotherapy of urethral stricture

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Asian Journal of Andrology 2024年第1期26卷 1-9页

作者： Hui Luo Ke-Cheng Lou Ling-Yu Xie Fei Zeng Jun-Rong Zou The First Clinical College Gannan Medical UniversityGanzhou 341000China Department of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China institute of Urology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China Jiangxi Engineering Technology Research Center of Calculi Prevention Ganzhou 341000China

Urethral stricture is characterized by the chronic formation of fibrous tissue,leading to the narrowing of the urethral lumen.Despite the availability of various endoscopic treatments,the recurrence of urethral strictures remains a common challenge.Postsurgery pharmacotherapy targeting tissue fibrosis is a promising option for reducing recurrence rates.Although drugs cannot replace surgery,they can be used as adjuvant therapies to improve outcomes.In this regard,many drugs have been proposed based on the mechanisms underlying the pathophysiology of urethral stricture.Ongoing studies have obtained substantial progress in treating urethral strictures,highlighting the potential for improved drug effectiveness through appropriate clinical delivery methods.Therefore,this review summarizes the latest researches on the mechanisms related to the pathophysiology of urethral stricture and the drugs to provide a theoretical basis and new insights for the effective use and future advancements in drug therapy for urethral stricture.

关键词： adjuvant therapy pathophysiology pharmacotherapy urethra urethral stricture

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Concept,breakthrough,and future of colonic transendoscopic enteral tubing

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Chinese medical Journal 2024年第6期137卷 633-635页

作者： Faming Zhang Gaochen Lu Xin Wang Lihao Wu Rui Li Yongzhan Nie Department of Microbiota Medicine The Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210011China Department of Gastroenterology Tangdu HospitalAir Force Medical UniversityXi’anShaanxi 710032China Department of Gastroenterology The First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510062China Department of Gastroenterology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215001China Xijing hospital of Digestive Diseases Xijing HospitalAir Force Medical UniversityXi’anShaanxi 710032China

Colonic transendoscopic enteral tubing(TET)is an interventional intestine therapeutic procedure.The colonic TET technique represents a novel drug delivery route,interventional diagnosis and therapy,and paradigm for concept validation,showing broad prospects in research and practice.Since its first meeting at the China Gut Conference in 2023,our panel of experts has held a series of discussions on TET’s concept,breakthroughs,and future.We strive to lay the groundwork for further establishing the TET Study Group for designing multicenter studies and developing relevant consensus or guidelines.

关键词： colonic intestine diagnosis

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Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First affiliated hospital of Guizhou university of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA institute of cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

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DNA damage chemotherapeutic drugs suppress basal-like breast cancer growth by down-regulating the transcription of the FOXO1-KLF5 axis

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Genes & Diseases 2024年第1期11卷 91-94页

作者： Qiuxia Cui Jian Sun Jingping Yuan Juanjuan Li Chuanyu Yang Guangshi Du Chengang Zhou Pu Qiu Jidong Gao Yuanqi Zhang Dewei Jiang Ceshi Chen affiliated hospital of Guangdong medical university Science&Technology of China ZhanjiangGuangdong 524000China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdong 518116China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Department of Pathology Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Department of Breast and Thyroid Surgery Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Translational Medicine Research Center of Guizhou medical university GuiyangGuizhou 550025China Department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Yunnan cancer hospital and the Third affiliated hospital of Kunming medical university and Yunnan cancer Center KunmingYunnan 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunmingYunnan 650500China

Most basal-like breast cancers(BLBCs)have a poor prognosis and high crossover with triple-negative breast cancers(TNBCs).However,approximately 50%of TNBC patients develop chemoresistance.^(1) Dexamethasone reportedly induces Krüppel-like factor 5(KLF5)and can cause docetaxel and cisplatin resistance in TNBC.A super-enhancer can maintain the transcription of KLF5.

关键词： FOXO1 drugs damage

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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-Yun Zhou Jie Sheng Lei Zhao Yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway inflammation.The envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this process.Pathogens could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)signaling.However,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be elucidated.Here,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial barrier.In addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial cells.This elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein.Overall,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Experimental models for cancer brain metastasis

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cancer Pathogenesis and Therapy 2024年第1期2卷 15-23页

作者： Zihao Liu Shanshan Dong Mengjie Liu Yuqiang Liu Zhiming Ye Jianhao Zeng Maojin Yao guangzhou institute of Respiratory Disease The First Affiliated Hospital of Guangzhou Medical UniversityChina State Key Laboratory of Respiratory DiseaseGuangzhouGuangdong 510182China Department of medical Genetics and Cell Biology GMU-GIBH Joint School of Life SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Microbiology Immunologyand Cancer BiologyUniversity of Virginia Health SystemCharlottesvilleVA 22908USA

Brain metastases are a leading cause of cancer-related mortality.However,progress in their treatment has been limited over the past decade,due to an incomplete understanding of the underlying biological mechanisms.Employing accurate in vitro and in vivo models to recapitulate the complexities of brain metastasis offers the most promising approach to unravel the intricate cellular and physiological processes involved.Here,we present a comprehensive review of the currently accessible models for studying brain metastasis.We introduce a diverse array of in vitro and in vivo models,including cultured cells using the Transwell system,organoids,microfluidic models,syngeneic models,xenograft models,and genetically engineered models.We have also provided a concise summary of the merits and limitations inherent to each model while identifying the optimal contexts for their effective utilization.This review serves as a comprehensive resource,aiding researchers in making well-informed decisions regarding model selection that align with specific research questions.

关键词： Brain metastases Blood-brain barrier Animal model In vitro model

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