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Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond

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World Journal of Gastroenterology 2018年第25期24卷 2686-2697页

作者： Emily M Lin Jun Gong Samuel J Klempner joseph chao Department of Internal Medicine Harbor-UCLA Medical CenterTorranceCA 90509United States Department of Medical Oncology and Developmental Therapeutics City of Hope Comprehensive Cancer CenterDuarteCA 91010United States The Angeles Clinic and Research Institute Los AngelesCA 90404United States Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical CenterLos AngelesCA 90048United States

Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.

关键词： Immunotherapy programmed cell death 1 programmed death ligand 1 microsatellite instablility Gastric cancer

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Perioperative chemotherapy for resectable gastric cancer:MAGIC and beyond

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World Journal of Gastroenterology 2015年第24期21卷 7343-7348页

作者： Audrey H Choi joseph Kim joseph chao Department of Surgical Oncology City of Hope Duarte Department of Medical Oncology City of Hope Duarte

Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase Ⅲ studies showing the treatment benefits of neoadjuvant and adjuvantchemotherapy and chemoradiation protocols. The objective of this editorial is to review the current highlevel evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy(MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer(ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST Ⅱ, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient's tumors are addressed.

关键词： Gastric cancer Neoadjuvant therapy Adjuvant therapy Chemotherapy Chemoradiation

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Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

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World Journal of Gastrointestinal Oncology 2022年第2期14卷 511-524页

作者： Lauren Midthun Sungjin Kim Andrew Hendifar Arsen Osipov Samuel J Klempner joseph chao May Cho Michelle Guan Veronica R Placencio-Hickok Alexandra Gangi Miguel Burch De-Chen Lin Kevin Waters Katelyn Atkins Mitchell Kamrava Jun Gong Department of Medicine Division of Hematology and OncologyCedars-Sinai Medical CenterLos AngelesCA 90048United States Biostatistics and Bioinformatics Research Center Cedars Sinai Medical CenterLos AngelesCA 90048United States Samuel Oschin Cancer Center Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Beth Israel Deaconess Medical Center/Harvard Medical SchoolBrigham and Women's Hospital/Harvard Medical SchoolBostonMA 02114United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaIrvineCA 92697United States Department of Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Pathology and Laboratory Medicine Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal ***,not all patients with metastatic disease receive *** To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and *** We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without *** A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving *** median follow-up was 69.45 *** median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no *** of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving *** the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on ***,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic

关键词： Esophageal cancer Metastatic Chemotherapy Predictors Survival

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Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

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World Journal of Gastrointestinal Surgery 2020年第9期12卷 377-389页

作者： Sungjin Kim Timothy P DiPeri Michelle Guan Veronica R Placencio-Hickok Haesoo Kim Jar-Yee Liu Andrew Hendifar Samuel J Klempner Ryan Nipp Alexandra Gangi Miguel Burch Kevin Waters May Cho joseph chao Katelyn Atkins Mitchell Kamrava Richard Tuli Jun Gong Biostatistics and Bioinformatics Research Center Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Surgical Oncology Department of SurgerySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Division of Hematology and OncologySamuel Oschin Comprehensive Cancer InstituteCedars Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonMA 02114United States Department of Pathology and Laboratory Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor *** all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are *** To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving *** The National Cancer Database was used to identify patients between *** with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were *** with unknown chemotherapy,RT,or nonprimary surgery status were ***-Meier estimates of OS were *** proportional hazards regression models were employed to examine factors influencing *** Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete *** age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic *** majority(72.7%)did not receive other palliative *** both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased *** histologic grade and T-stage were also as

关键词： Esophageal cancer Metastatic Palliative Chemotherapy Radiotherapy Survival

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Clinical effects of phospholipase D2 in attenuating acute pancreatitis

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World Journal of Gastroenterology 2025年第2期31卷 52-60页

作者： Jin-Wei Niu Guo-chao Zhang Wu Ning Hai-Bin Liu Hua Yang chao-Feng Li Department of General Surgery China-Japan Friendship HospitalBeijing 100029China

BACKGROUND The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2(PLD2)exerted a regulatory effect on neutrophil migra-tion,thereby alleviating the progression of acute *** To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration,thereby alleviating the progression of acute *** The study involved 90 patients diagnosed with acute pancreatitis,admitted to our hospital between March 2020 and November 2022.A retrospective analysis was conducted,categorizing patients based on Ranson score severity into mild(n=25),moderate(n=30),and severe(n=35)*** data was collected for each *** blot analysis assessed PLD2 protein expression in patient ***-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil *** levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent *** migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil *** Overall data analysis did not find significant differences between patient groups(P>0.05).The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups(P<0.05).The expression level of PLD2 in the moderate group was also lower than that in the mild group(P<0.05).The severity of acute pancreatitis is negatively correlated with PLD2 expression(r=-0.75,P=0.002).The mRNA levels of C-X-C chemokine receptor type 1,C-X-C chemokine receptor type 2,C-C chemokine receptor type 2,and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups(P<0.05),and the expression levels in the moderate group are also higher than those in the mild group(P<0.05).The levels of C-reactive protein,tumo

关键词： Phospholipase D2 Neutrophil migration Acute pancreatitis Retrospective analysis Inflammatory response

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Force and impulse multi-sensor based on flexible gate dielectric field effect transistor

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 214-220页

作者： chao Tan Junling Lü Chunchi Zhang Dong Liang Lei Yang Zegao Wang College of Materials Science and Engineering Sichuan UniversityChengdu 610065China The 54th Research Institute of China Electronics Technology Group Corporation Shijiazhuang 050081China

Nowadays,force sensors play an important role in industrial production,electronic information,medical health,and many other ***-dimensional material-based filed effect transistor(2D-FET)sensors are competitive with nano-level size,lower power consumption,and accurate ***,few of them has the capability of impulse detection which is a path function,expressing the cumulative effect of the force on the particle over a period of *** we fabricated the flexible polymethyl methacrylate(PMMA)gate dielectric MoS_(2)-FET for force and impulse sensor *** systematically investigated the responses of the sensor to constant force and varying forces,and achieved the conversion factors of the drain current signals(I_(ds))to the detected impulse(I).The applied force was detected and recorded by I_(ds)with a low power consumption of~30 *** sensitivity of the device can reach~8000%and the 4×1 sensor array is able to detect and locate the normal force applied on ***,there was almost no performance loss for the device as left in the air for two months.

关键词： flexible gate dielectric transistor force sensor impulse sensor force sensor array

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Engineered Cancer Nanovaccines:A New Frontier in Cancer Therapy

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Nano-Micro Letters 2025年第2期17卷 134-168页

作者： Yijie Wang Congrui Liu chao Fang Qiuxia Peng Wen Qin Xuebing Yan Kun Zhang Central Laboratory and Department of Medical Ultrasound Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo.32West Second SectionFirst Ring RoadChengdu 610072People’s Republic of China Department of Stomatology and Central Laboratory School of MedicineShanghai Tenth People’s HospitalTongji UniversityNO.301 Yan‑Chang‑Zhong RoadShanghai 200072People’s Republic of China Jiangsu Provincial Innovation and Practice Base for Postdoctors Suining People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityNo.2Bayi West RoadSuiningXu Zhou 221000Jiangsu ProvincePeople’s Republic of China

Vaccinations are essential for preventing and treating disease,especially cancer nanovaccines,which have gained considerable interest recently for their strong anti-tumor immune *** can prompt the immune system to generate antibodies and activate various immune cells,leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and *** enhance the flexibility and targeting of vaccines,nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level,enabling more controlled and precise drug delivery to enhance immune *** nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within *** small size of these nanomaterials allows for precise targeting of T cells,dendritic cells,or cancer cells,thereby eliciting a more potent anti-tumor *** this paper,we focus on the classification of carriers for cancer nanovaccines,the roles of different target cells,and clinically tested cancer nanovaccines,discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation,while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

关键词： Cancer nanovaccines Immunotherapy Nanobiotechnology Immune targets Signaling pathway

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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Neural Regeneration Research 2025年第3期20卷 821-835页

作者： Jing Wang Bing Zhang Lanfang Li Xiaomei Tang Jinyu Zeng Yige Song chao Xu Kai Zhao Guoqiang Liu Youming Lu Xinyan Li Kai Shu Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Neurosurgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Pathophysiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Institute for Brain Research Wuhan Center of Brain ScienceHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Graduate Student Chongqing Medical UniversityChongqingChina Department of Basic Medicine School of Medical ScienceHubei University for NationalitiesEnshiHubei ProvinceChina Department of Anatomy School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive ***,the mechanism underlying this neurogenesis impairment remains *** this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain *** results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and *** with repetitive traumatic brain injuryalso showed deficits in spatial memory ***,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was *** inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological *** findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

关键词： complement C1 dendrite dentate gyrus hippocampus neural stem cell neurogenesis neuroinflammation neurological function neuron traumatic brain injury

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Flexible Graphene Field‑Effect Transistors and Their Application in Flexible Biomedical Sensing

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Nano-Micro Letters 2025年第2期17卷 252-313页

作者： Mingyuan Sun Shuai Wang Yanbo Liang chao Wang Yunhong Zhang Hong Liu Yu Zhang Lin Han Institute of Marine Science and Technology Shandong UniversityQingdao 266237ShandongPeople’s Republic of China State Key Laboratory of Crystal Materials Shandong UniversityJinan 250100ShandongPeople’s Republic of China School of Integrated Circuits Shandong UniversityJinan 250100ShandongPeople’s Republic of China Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application Jinan250100ShandongPeople’s Republic of China

Flexible electronics are transforming our lives by making daily activities more *** to this innovation are field-effect transistors(FETs),valued for their efficient signal processing,nanoscale fabrication,low-power consumption,fast response times,and ***,known for its exceptional mechanical properties,high electron mobility,and biocompatibility,is an ideal material for FET channels and *** combination of graphene and FETs has given rise to flexible graphene field-effect transistors(FGFETs),driving significant advances in flexible electronics and sparked a strong interest in flexible biomedical ***,we first provide a brief overview of the basic structure,operating mechanism,and evaluation parameters of FGFETs,and delve into their material selection and patterning *** ability of FGFETs to sense strains and biomolecular charges opens up diverse application *** specifically analyze the latest strategies for integrating FGFETs into wearable and implantable flexible biomedical sensors,focusing on the key aspects of constructing high-quality flexible biomedical ***,we discuss the current challenges and prospects of FGFETs and their applications in biomedical *** review will provide valuable insights and inspiration for ongoing research to improve the quality of FGFETs and broaden their application prospects in flexible biomedical sensing.

关键词： Flexible Graphene Field-effect transistor Wearable Implantable Biosensor

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Smart Cellulose‑Based Janus Fabrics with Switchable Liquid Transportation for Personal Moisture and Thermal Management

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Nano-Micro Letters 2025年第1期17卷 333-347页

作者： Jianfeng Xi Yanling Lou Liucheng Meng chao Deng Youlu Chu Zhaoyang Xu Huining Xiao Weibing Wu Jiangsu Co‑Innovation Center of Efficient Processing and Utilization of Forest Resources International Innovation Center for Forest Chemicals and MaterialsJiangsu Provincial Key Lab of Sustainable Pulp and Paper Technology and Biomass MaterialsNanjing Forestry UniversityNanjing 210037People’s Republic of China College of Materials Science and Engineering Nanjing Forestry UniversityNanjing 210037People’s Republic of China Department of Chemical Engineering University of New BrunswickFrederictonNB E3B 5A3Canada Macromolecular Chemistry and Bavarian Polymer Institute University of BayreuthBayreuth 95440Germany

The Janus fabrics designed for personal moisture/thermal regulation have garnered significant attention for their potential to enhance human ***,the development of smart and dynamic fabrics capable of managing personal moisture/thermal comfort in response to changing external environments remains a ***,a smart cellulose-based Janus fabric was designed to dynamically manage personal moisture/*** cotton fabric was grafted with N-isopropylacrylamide to construct a temperature-stimulated transport ***,hydrophobic ethyl cellulose and hydrophilic cellulose nanofiber were sprayed on the bottom and top sides of the fabric to obtain wettability *** fabric exhibits anti-gravity directional liquid transportation from hydrophobic side to hydrophilic side,and can dynamically and continuously control the transportation time in a wide range of 3–66 s as the temperature increases from 10 to 40℃.This smart fabric can quickly dissipate heat at high temperatures,while at low temperatures,it can slow down the heat dissipation rate and prevent the human from becoming too *** addition,the fabric has UV shielding and photodynamic antibacterial properties through depositing graphitic carbon nitride nanosheets on the hydrophilic *** smart fabric offers an innovative approach to maximizing personal comfort in environments with significant temperature variations.

关键词： Directional water transport Cotton fabric Anti-gravity directional liquid transportation Janus wettability

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