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Lenalidomide regulates the CCL21/CCR7/ERK1/2 axis to inhibit migration and proliferation in diffuse large B-cell lymphoma

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Oncology Research 2025年第1期33卷 199-212页

作者： WEN YANG BIN TANG DAN XU WENXIU YANG Department of pathology Guizhou Medical UniversityThe Affiliated Hospital of Guizhou Medical UniversityGuiyang550004China

Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported ***,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully ***:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control *** data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of ***,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide ***:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in ***,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression ***,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 *** effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide *** vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.

关键词： CCR7 CCL21 ERK1/2 Lenalidomide Diffuse large B-cell lymphoma(DLBCL)

Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 199-206页

作者： Radu Cristian Poenaru Elena Milanesi Andrei Marian Niculae Anastasia-Maria Dobre Catalina Vladut Mihai Ciocîrlan Daniel Vasile Balaban Vlad Herlea Maria Dobre Mihail Eugen Hinescu Faculty of Medicine Carol Davila University of Medicine and PharmacyBucharest 050474Romania Department of Radiobiology Victor Babes National Institute of PathologyBucharest 050096Romania Department of pathology Victor Babes National Institute of PathologyBucharest 050096Romania Department of Gastroenterology Prof.Dr.Agrippa Ionescu Clinical Emergency HospitalBucharest 011356Romania Department of pathology Fundeni Clinical InstituteBucharest 022258Romania

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United *** for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and *** To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into *** A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical *** genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥*** We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph *** Despite the low number of patients analyzed,these preliminary results seem to be *** lipid metabolism through a broad strategy could be a beneficial way to treat this *** in vitro and in vivo s

关键词： Carcinoma Pancreatic ductal Fatty acid transport Gene expression Biomarkers

Strength through unity: Alkaline phosphatase-responsive AIEgen nanoprobe for aggregation-enhanced multi-mode imaging and photothermal therapy of metastatic prostate cancer

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Chinese Chemical Letters 2025年第2期36卷 289-296页

作者： Ze Wang Hao Liang Annan Liu Xingchen Li Lin Guan Lei Li Liang He Andrew K.Whittaker Bai Yang Quan Lin State Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Department of Endocrinology Lequn Branch the First Hospital of Jilin University Department of Urology the First Hospital of Jilin University Australian institute for Bioengineering and Nanotechnology the University of Queensland

Prostate cancer(PCa) is characterized by high incidence and propensity for easy metastasis, presenting significant challenges in clinical diagnosis and treatment. Tumor microenvironment(TME)-responsive nanomaterials provide a promising prospect for imaging-guided precision therapy. Considering that tumor-derived alkaline phosphatase(ALP) is over-expressed in metastatic PCa, it makes a great chance to develop a theranostics system with ALP responsive in the TME. Herein, an ALP-responsive aggregationinduced emission luminogens(AIEgens) nanoprobe AMNF self-assembly was designed for enhancing the diagnosis and treatment of metastatic PCa. The nanoprobe exhibited self-aggregation in the presence of ALP resulted in aggregation-induced fluorescence, and enhanced accumulation and prolonged retention period at the tumor site. In terms of detection, the fluorescence(FL)/computed tomography(CT)/magnetic resonance(MR) multi-mode imaging effect of nanoprobe was significantly improved post-aggregation, enabling precise diagnosis through the amalgamation of multiple imaging modes. Enhanced CT/MR imaging can achieve assist preoperative tumor diagnosis, and enhanced FL imaging technology can achieve “intraoperative visual navigation”, showing its potential application value in clinical tumor detection and surgical guidance. In terms of treatment, AMNF showed strong absorption in the near infrared region after aggregation, which improved the photothermal treatment effect. Overall, our work developed an effective aggregation-enhanced theranostic strategy for ALP-related cancers.

关键词： AIE ALP responsive Enhanced multi-mode imaging Enhanced photothermal therapy Prostate cancer

NIR driven catalytic enhanced acute lung injury therapy by using polydopamine@Co nanozyme via scavenging ROS

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Chinese Chemical Letters 2025年第2期36卷 337-343页

作者： Xiaoshuai Wu Bailei Wang Yichen Li Xiaoxuan Guan Mingjing Yin Wenquan Lv Yin Chen Fei Lu Tao Qin Huyang Gao Weiqian Jin Yifu Huang Cuiping Li Ming Gao Junyu Lu Intensive Care Unit The Second Affiliated Hospital of Guangxi Medical University Department of Critical Care Medicine The Ninth Affiliated Hospital of Guangxi Medical University Life Sciences institute Guangxi Medical University Department of Emergency The First Affiliated Hospital of Guangxi Medical University College & hospital of Stomatology Guangxi Medical University Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction Guangxi Medical University

Acute lung injury(ALI) was characterized by excessive reactive oxygen species(ROS) levels and inflammatory response in the lung. Scavenging ROS could inhibit the excessive inflammatory response, further treating ALI. Herein, we designed a novel nanozyme(P@Co) comprised of polydopamine(PDA) nanoparticles(NPs) loading with ultra-small Co, combining with near infrared(NIR) irradiation, which could efficiently scavenge intracellular ROS and suppress inflammatory responses against ALI. For lipopolysaccharide(LPS) induced macrophages, P@Co + NIR presented excellent antioxidant and anti-inflammatory capacities through lowering intracellular ROS levels, decreasing the expression levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α) as well as inducing macrophage M2 directional polarization. Significantly, it displayed the outstanding activities of lowering acute lung inflammation, relieving diffuse alveolar damage, and up-regulating heat shock protein 70(HSP70) expression, resulting in synergistic enhanced ALI therapy effect. It offers a novel strategy for the clinical treatment of ROS related diseases.

关键词： Acute lung injury M2 directional polarization Nanozyme NIR driven ROS scavenging

Machine learning-based models for advanced fibrosis in nonalcoholic steatohepatitis patients:A cohort study

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World Journal of Gastroenterology 2025年第9期31卷 30-42页

作者： Fei-Xiang Xiong Lei Sun Xue-Jie Zhang Jia-Liang Chen Yang Zhou Xiao-Min Ji Pei-Pei Meng Tong Wu Xian-Bo Wang Yi-Xin Hou Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of pathology Beijing Ditan HospitalBeijing 100015China

BACKGROUND The global prevalence of non-alcoholic steatohepatitis(NASH)and its associated risk of adverse outcomes,particularly in patients with advanced liver fibrosis,underscores the importance of early and accurate *** To develop a machine learning-based diagnostic model for advanced liver fibrosis in NASH *** A total of 749 patients who underwent liver biopsy at Beijing Ditan hospital,Capital Medical university,between January 2010 and January 2020 were *** were randomly divided into training(n=522)and validation(n=224)*** machine learning models were applied to predict advanced liver fibrosis,with feature selection based on Shapley Additive Explanations(SHAP).The diagnostic performance of these models was compared to traditional scores such as the aspartate aminotransferase to platelet ratio index(APRI)and fibrosis index based on the 4 factors(FIB-4),using metrics including the area under the receiver operating characteristic curve(AUROC),decision curve analysis(DCA),and calibration *** The Extreme Gradient Boosting(XGBoost)model outperformed all other machine learning models,achieving an AUROC of 0.934(95%CI:0.914-0.955)in the training cohort and 0.917(95%CI:0.880-0.953)in the validation cohort(P<0.001).Incorporating liver stiffness measurement into the model further improved its performance,with an AUROC of 0.977(95%CI:0.966-0.980)in the training cohort and 0.970(95%CI:0.950-0.990)in the validation cohort,significantly surpassing APRI and FIB-4 scores(P<0.001).The XGBoost model also demonstrated superior clinical utility,as evidenced by DCA and calibration curve analysis in both *** The XGBoost model provides a highly accurate,non-invasive diagnosis of advanced liver fibrosis in NASH patients,outperforming traditional *** online tool based on this model has been developed to assist clinicians in evaluating the risk of advanced liver fibrosis.

关键词： Machine learning Advanced fibrosis Non-alcoholic steatohepatitis Extreme Gradient Boosting Non-invasive

A supramolecular nanoprodrug for prevention of gallstone formation

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Chinese Chemical Letters 2025年第2期36卷 354-359页

作者： Xiangjun Zhang Xiaodi Yang Yan Wang Zhongping Xu Sisi Yi Tao Guo Yue Liao Xiyu Tang Jianxiang Zhang Ruibing Wang College of Pharmacy Chongqing Medical University Chongqing university Fuling hospital Department of Pharmaceutics College of PharmacyThird Military Medical University (Army Medical University) Yu-Yue pathology Scientific Research Center State Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University (Army Medical University) State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau

Cholelithiasis affects approximately 10%-20% of the adult population globally. And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones. Hydroxypropyl-β-cyclodextrin(HPCD) is a supramolecular host compound that can solubilize cholesterol, potentially serving as a preventative or therapeutic agent for cholelithiasis. However, we found that the administration of HPCD treatment did not impede the formation of gallstones in mice, mainly attributed to the pre-complexation of its cavity during the transition process. Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP), which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection. In the bile, the HPCD-NP degraded into free HPCD, bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization, leading to gallstones regression. Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies, HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.

关键词： Gallstone Hepatobiliary transport Host-guest interaction Hydroxypropyl-β-cyclodextrin Solubilization

Anti-programmed death-1 immunotherapy-promising treatment for metastatic colorectal cancer:A case report

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 291-298页

作者： Tian-Hao Guo Sheng-Wei Hong Wen-Jian Zhu Yi-Fan Hui Wen-Li Qiu Yan Wu Xuan Li Fei Ke Liu Li Hai-Bo Cheng institute of Health and Regimen Jiangsu Open UniversityNanjing 210036Jiangsu ProvinceChina The First Clinical Medical College Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina Department of Radiology Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Oncology Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of pathology Jiangsu Provincial Hospital of Traditional Chinese Medicine(Affiliated Hospital of Nanjing University of Chinese Medicine)Nanjing 210029Jiangsu ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most prevalent form of cancer *** patients with CRC,colorectal liver metastasis(CRLM)is the foremost direct contributor to *** recent years,immunotherapy has swiftly risen to prominence as a vital approach for treating a range of solid tumors,including *** present a unique case of a patient suffering from CRLM,with the goal of offering an insightful example and relevant references for the treatment of *** SUMMARY We report a patient who experienced liver metastasis after undergoing successful surgical removal of CRC,with the postoperative pathological stage identified as *** patient has been receiving a combination treatment of Western and Traditional Chinese *** assessments of the patient’s condition have been conducted,encompassing evaluations of serum carcinoembryonic antigen levels,carbohydrate antigen 199,and observations of the tongue complexion and its *** patient achieved clinical remission after anti-programmed death-1 immunotherapy when various systemic therapies *** the diagnosis of CRLM,the patient has survived for more than 6 years,surpassing the expected survival time for those with advanced *** This case illustrates the considerable promise of anti-programmed death-1 immunotherapy in managing CRLM,especially in scenarios of drug resistance and disease progression.

关键词： Colorectal cancer Colorectal liver metastasis Drug resistance Immunotherapy Anti-programmed death-1 Case report

An ionic liquid functionalized sericin hydrogel for drug-resistant bacteria-infected diabetic wound healing

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Chinese Chemical Letters 2025年第2期36卷 307-313页

作者： Jiajia Wang XinXin Ge Yajing Xiang Xiaoliang Qi Ying Li Hangbin Xu Erya Cai Chaofan Zhang Yulong Lan Xiaojing Chen Yizuo Shi Zhangping Li Jianliang Shen National Engineering Research Center of Ophthalmology and Optometry Eye HospitalWenzhou Medical University School of Chemical Engineering Nanjing University of Science&Technology School&hospital of Stomatology Wenzhou Medical University Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of Sciences The Quzhou Affiliated hospital of Wenzhou Medical university Quzhou People's Hospital

Diabetic wound healing is often complicated due to bacterial infections that intensify inflammation. Employing hydrogel dressings with inherent antibacterial properties can significantly reduce reliance on antibiotics for treating infected wounds in diabetics. Traditional hydrogels typically rely on the infiltration of bacteria into their porous structure to manifest antibacterial effects. However, this infiltration process is not only prolonged but can also exacerbate inflammation, further delaying the healing of the ***, promptly capturing and eliminating bacteria is crucial for enhancing the antibacterial efficiency of the hydrogel. In this context, we present a multifunctional hydrogel dressing, termed SIP, designed to tackle drug-resistant bacterial infections in diabetic wounds. This dressing integrates ionic liquid functional groups into a sericin-based matrix: phenylboronic acid for the immobilization of bacteria and imidazole for their subsequent annihilation. Expectedly, the SIP system demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus, verified through in vitro and in vivo experiments. As a result, SIP emerges as a promising candidate in the realm of hydrogel dressings with innate antibacterial properties, showcasing considerable potential for addressing diabetic wounds plagued by drug-resistant bacterial infections.

关键词： Diabetic wound healing Hydrogels Ionic liquids Methicillin-resistant Staphylococcus aureus infection Sericin

Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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Oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN JIANG YICHUN TANG FENG MA YUCHUN NIU LEI SUN Department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China Department of pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China Department of Radiation Oncology The First People’s Hospital of FoshanFoshan528000China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China Department of Oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape