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CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1029-1045页

作者： wen-qian Ma Ming-Chang Miao Ping-An Ding Bi-Bo Tan wen-Bo Liu Shuo Guo Li-Mian Er Zhi-Dong Zhang Qun Zhao Department of Endoscopy The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer Shijiazhuang 050011Hebei ProvinceChina Department of Radiotherapy The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina The Third Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

BACKGROUND CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors,including gastric cancer(GC),and is associated with tumor progression and immune infiltration;however,the roles and mechanisms of CALD1 in epithe-lial-mesenchymal transition(EMT)in GC are *** To investigate the role and mechanism of CALD1 in GC progression,invasion,and *** In this study,the relationship between CALD1 and GC,as well as the possible network regulatory mechanisms of CALD1,was investigated by bioinformatics and validated by ***1-siRNA was synthesized and used to trans-fect GC *** activity was measured using the CCK-8 method,cell migration and invasive ability were measured using wound healing assay and Transwell assay,and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot.A GC cell xenograft model RESULTS Bioinformatics results showed that CALD1 was highly expressed in GC tissues,and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of *** prognosis of patients with high expression of CALD1 was worse than that of patients with low expression,and a prognostic model was constructed and *** experimental results were consistent with the results of the bioinformatics *** expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1,with the strongest expression found in AGS and MKN45 *** activity was significantly reduced after CALD1-siRNA trans-fection of AGS and MKN45 *** ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection,and the related mRNA and protein expression was *** to bioinfor-matics findings in GC samples,the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway,and was closely rel

关键词： Gastric tumor CALD1 Epithelial-mesenchymal transition Gene disruption Invasion Migration Bioinformatics

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Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

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Biomedical and Environmental Sciences 2024年第2期37卷 170-177页

作者： GU wen Fei SHI Xia MA Xin YU Jun Lei XU Jin Chuan qian Cheng Cheng HU Zhi Dong ZHANG Hui Shanghai Public Health Clinical Center Fudan UniversityShanghai 201508China School of Laboratory Medicine and Life Science Wenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of Laboratory Medicine Zhejiang Putuo HospitalZhoushan 316100ZhejiangChina Zhongshan Hospital Fudan UniversityShanghai 200032China

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological *** assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),*** on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),*** examination showed the highest sensitivity but lowest ***,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of *** with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower *** combination of histopathology with Xpert showed the best performance characteristics.

关键词： Extrapulmonary tuberculosis Diagnosis Biopsy Histopathological examination Puncture samples

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PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines

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Chinese Chemical Letters 2024年第5期35卷 314-319页

作者： wen Xiao Fazhan Wang Yangzhuo Gu Xi He Na Fan qian Zheng Shugang Qin Zhongshan He Yuquan Wei Xiangrong Song Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450000China

Dendritic cell(DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tumor *** targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mRNA delivery *** the PEG linker length influences the targeting delivery efficiency of mRNA nanocarrier in vivo remains ***,we designed and constructed DC-targeted mRNA delivery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP_(400)-LPX(the linker was PEG400)showed the optimal mRNA expression and antigen presentation owing to the highly efficient uptake by ***,MP_(400)-LPX could better inhibited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse ***,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mRNA *** findings provided a new platform for the rational design of targeted mRNA nanovaccines with shorter-length PEG.

关键词： Cancer immunotherapy mRNA vaccines DC-targeted delivery PEGylated liposomes Cellular uptake

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Drug delivery systems for colorectal cancer chemotherapy

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Chinese Chemical Letters 2024年第2期35卷 163-175页

作者： wen Chen Kun Shi Yan Yu Peipei Yang Zhongwu Bei Dong Mo Liping Yuan Meng Pan Yu Chen Zhiyong qian Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Colorectal cancer causes the third most common type of malignant tumors with high morbidity and *** is currently one of the most effective and common treatments for colorectal ***,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer ***,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good ***,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer *** not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus ***,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also *** provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.

关键词： Colorectal cancer Chemotherapy Drug delivery systems Solubility Targeted Local administration

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Functional dissection of parabrachial substrates in processing nociceptive information

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Zoological Research 2024年第3期45卷 633-647页

作者： Jin Ke Wei-Cheng Lu Hai-Yang Jing Shen qian Sun-Wook Moon Guang-Fu Cui Wei-Xin qian Xiao-Jing Che qian Zhang Shi-Shi Lai Ling Zhang Ying-Jie Zhu Jing-Dun Xie Tian-wen Huang Shenzhen Key Laboratory of Drug Addiction Shenzhen-Hong Kong Institute of Brain ScienceBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China CAS Key Laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of Sciences Beijing 100049China Department of Anesthesiology State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China University of Science and Technology of China HefeiAnhui 230027China Department of Anesthesiology Shenzhen University General Hospital and Shenzhen University Academy of Clinical Medical SciencesShenzhen UniversityShenzhenGuangdong 518055China School of Medicine Yunnan UniversityKunmingYunnan 650091China

Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of *** lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity ***,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain *** this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such ***,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external ***,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive *** results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

关键词： Lateral parabrachial nucleus Substance P receptor Pain affect Defensive reaction Somatosensory

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Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature

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World Journal of Clinical Cases 2024年第5期12卷 995-1003页

作者： wen-wen Wang Shu-Ping Zhou Xiang Wu Luo-Luo Wang Yi ruan Jun Lu Hai-Li Li Xu-Ling Ni Li-Li Qiu Xin-Hua Zhou Department of Hepatobiliary and Pancreatic Surgery The Affiliated Li Huili HospitalNingbo University School of MedicineNingbo 315000Zhejiang ProvinceChina Ningbo College of Health Sciences Ningbo College of Health SciencesNingbo 315000Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315000Zhejiang ProvinceChina Department of Hepatobiliary and Pancreatic Surgery The Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou310006Zhejiang ProvinceChina Department of Diagnosis Ningbo Diagnostic Pathology CenterNingbo 315000Zhejiang ProvinceChina

BACKGROUND A solitary fibrous tumor(SFT)is often located in the pleura,while SFT of the pancreas is extremely ***,we report a case of SFT of the pancreas and discuss imaging,histopathology,and immunohistochemistry for accurate diagnosis and *** SUMMARY A 54-year-old man presented to our hospital with pancreatic occupancy for over a *** were no previous complaints of *** blood pressure was *** glucose,tumor markers,and enhanced computed tomography(CT)suggested a malignant *** the CT appearance of pancreatic cancer varies,we could not confirm the diagnosis;therefore,we performed endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB).Pathology and immunohistochemistry were consistent with SFT of the *** posto-perative pathology and immunohistochemistry were consistent with the puncture *** patient presented for a follow-up examination one month after discharge with no adverse *** Other diseases must be excluded in patients with a pancreatic mass that cannot be *** and pathological histology have diagnostic value for pancreatic *** puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed *** is an effective treatment for SFT of the pancreas;however,long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

关键词： Pancreas Neoplasm fibrous tumor Endoscopic ultrasound-guided fine-needle biopsy Treatment Case report

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan Chen Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang wenhai Deng Ping Li wen Lei Aibin Liang wenbin qian Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of Hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of Hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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Amlodipine inhibits the proliferation and migration of esophageal carcinoma cells through the induction of endoplasmic reticulum stress

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World Journal of Gastroenterology 2024年第4期30卷 367-380页

作者： Yan-Min Chen wen-qian Yang Cheng-Wei Gu Ying-Ying Fan Yu-Zhen Liu Bao-Sheng Zhao Department of Thoracic Surgery The First Affiliated Hospital of Xinxiang Medical UniversityWeihui 453100Henan ProvinceChina Department of Oncology The Affiliated HospitalHenan Polytechnic UniversityJiaozuo 454000Henan ProvinceChina Life Science Research Center The First Affiliated Hospital of Xinxiang Medical UniversityWeihui 453100Henan ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Xinxiang Medical UniversityWeihui 453100Henan ProvinceChina

BACKGROUND L-type calcium channels are the only protein channels sensitive to calcium channel blockers,and are expressed in various cancer *** Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial ***,we hypothesized that amlodipine,a long-acting dihydropyridine L-type calcium channel blocker,may inhibit the occurrence and development of esophageal cancer(EC).AIM To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum(ER)*** Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were ***,the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell *** vivo experiments were performed using murine xenograft *** elucidate the underlying mechanisms,in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with *** The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous *** treatment decreased the viability of esophageal carcinoma cells in a dose-and time-dependent *** vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in ***,amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition(EMT).Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses ***,amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B *** combination of amlodipine with the ER stress inhibitor 4-p

关键词： L-type calcium channel Amlodipine Esophageal cancer Autophagy Endoplasmic reticulum stress

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Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide

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International Journal of Dermatology and Venereology 2024年第2期7卷 99-107页

作者： Li-Qing Shi Shi-Hang Zhou Ping-Lang ruan Bo Zhang Yue Xin Cheng Zhao Xu Yao Jing-Ru Tian qian-Jin Lu Hospital for Skin Diseases(Institute of Dermatology) Chinese Academy of Medical Sciences and Peking Union Medical CollegeNanjingJiangsu 210042China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases Chinese Academy of Medical SciencesNanjingJiangsu 210042China Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs NanjingJiangsu 210042China Department of Dermatology Hunan Key Laboratory of Medical Epigenomicsthe Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

Objective:Heterogeneity of participants in clinical trials distorts intervention ***,factors associated with participant heterogeneity in randomized clinical trials(RCTs)focusing on systemic sclerosis(SSc)are not *** conducted this systematic review to establish normative standards for future research and help develop management ***:Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different *** of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ***:In total,261 trials met our inclusion *** quality of SSc RCTs worldwide was relatively poor,with no trend of improvement in recent years,and only 12.2%were ranked as having a low risk of *** with a low risk of bias as well as single-center,single-country,or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center,multiple-country,or double-blind ***,trial registration and primary outcome definition contributed to high *** income was also relevant;participant adherence in high-income countries,but not in upper-and lower-middle-income countries,was significantly altered by different ***:Overall,the risk of bias,national income,and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the *** with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.

关键词： systemic sclerosis randomized clinical trials heterogeneity participant adherence national income risk of bias

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柔直换流阀用相变冷却工质击穿特性研究

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电工技术学报 2024年第3期39卷 875-886,913页

作者：温英科阮琳中国科学院电工研究所北京100190 中国科学院大学北京100049

相变冷却技术冷却效率高、安全可靠,有望攻克柔直换流阀散热瓶颈,实现其高压、大容量发展,在换流阀冷却领域具有良好的应用前景。为实现相变冷却换流阀绝缘系统可靠设计,该文设计研制了三相态相变冷却工质可调频绝缘特性测试专用平台,... 详细信息

相变冷却技术冷却效率高、安全可靠,有望攻克柔直换流阀散热瓶颈,实现其高压、大容量发展,在换流阀冷却领域具有良好的应用前景。为实现相变冷却换流阀绝缘系统可靠设计,该文设计研制了三相态相变冷却工质可调频绝缘特性测试专用平台,并以换流阀用相变冷却工质为研究对象,依据换流阀典型运行工况,利用专用测试平台开展了相变冷却工质三相态、50~300 Hz频率范围的绝缘击穿特性研究。得到了相变冷却工质击穿特性随工质相态及电压频率的变化规律,分析了相变冷却工质不同相态的击穿机理,揭示了工质相态和电压频率变化对冷却工质击穿特性的影响机制。研究工作不仅解决了高频下相变冷却工质的三相态耐压测试方法问题,且所得研究成果为相变冷却柔直换流阀的绝缘设计奠定了基础,同时可指导相变冷却技术在其他电力电子器件及装备上的应用。

关键词：换流阀柔性直流输电相变冷却击穿特性高频绝缘

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