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MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer

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Journal of Pharmaceutical Analysis 2024年第6期14卷 863-877页

作者： Haowei Zhang Qixin Li Xiaolong Guo Hong Wu Chenhao Hu Gaixia Liu Tianyu Yu Xiake Hu Quanpeng Qiu Gang Guo Junjun She Yinnan Chen department of general surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Center for Gut Microbiome Research Med-X InstituteThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China department of High Talent The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA *** the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential *** this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in ***,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP ***,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of ***,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy *** transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant *** summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

关键词： Colorectal cancer MGMT Chemotherapy resistance Slow-cycling cells Nonhomologous end joining Wnt pathway

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Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer

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Cancer Communications 2024年第8期44卷 855-878页

作者： Jian Xiao Shuqing Cao Jiawei Wang Pengyu Li Quan Cheng Xinyi Zhou Jiacheng Dong Yuan Li Xinyu Zhao Zekuan Xu Li Yang department of general surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China

Background:Lymph node metastasis(LNM)is the primary mode of metastasis in gastric cancer(GC).However,the precise mechanisms underlying this process remain *** cells necessitate lipid metabolic reprogramming to facilitate metastasis,yet the role of lipoprotein lipase(LPL),a pivotal enzyme involved in exogenous lipid uptake,remains uncertain in tumor ***,the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this ***:Intracellular lipid levels were quantified using oil red O staining,BODIPY 493/503 staining,and flow *** analysis was employed to identify alterations in intracellular lipid composition following LPL *** expression levels were assessed through immunohistochemistry,Western blotting,and enzyme-linked immunosorbent *** mouse popliteal LNM model was utilized to investigate differences in *** and mass spectrometry were employed to examine protein *** vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4(ANGPTL4)***:We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive(N+)GC and further demonstrated that a high-fat diet can expedite *** was found to be significantly overexpressed in N+GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC ***,an obesity-related hormone,intercepted the effect exerted by ANGPTL4/Furin on LPL *** leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1(IRE1)kinase,leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with ***,our research revealed that LPL disrupted lipid homeostasis by elevating intrace

关键词： angiopoietin-like protein 4 leptin lipoprotein lipase lymph node metastasis prostaglandin E2

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Predictors of complications after prophylactic ileostomy reversal for rectal cancer:A retrospective study

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World Journal of Gastrointestinal surgery 2024年第5期16卷 1354-1362页

作者： Quan Lv Xin-Peng Shu Dong Peng Si-Qi Li Zheng Xiang department of Gastrointestinal surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key Laboratory of department of general surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Previous studies have analyzed the risk factors for complications after ileostomy reversal for rectal cancer(RC),but there were significant differences in the reported risk factors for complications after stoma *** studies have analyzed the risk factors for stoma-related complications and overall postoperative com-plications *** To analyze the risk factors for overall complications and stoma-related complications after ileostomy reversal for patients with *** This was a retrospective study of 439 patients who underwent ileostomy reversal at a clinical center and were followed up between September 2012 and September *** variables are expressed as the mean±SD and were analyzed with independent-sample t tests,while frequency variables are expressed as n(%),and theχ2 test or Fisher’s exact test was *** and multivariate logistic regression analyses were used to identify predictors of overall complications and stoma-related *** The overall complication rate after ileostomy reversal was 11.4%.Patients with lower preoperative albumin concentration(Psurgery to ileostomy reversal(Psurgery to ileostomy reversal(P<0.01,OR=1.140,95%CI:1.038-1.252)were independent risk factors for stoma-related compl

关键词： Ileostomy Reversal Risk factors Complications Rectal cancer

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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Breast surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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Developing risk models and subtypes of autophagy-associated LncRNAs for enhanced prognostic prediction and precision in therapeutic approaches for liver cancer patients

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Oncology Research 2024年第4期32卷 703-716页

作者： LU ZHANG JINGUO CHU YUSHAN YU department of general Practice The First Affiliated Hospital of Ningbo UniversityNingboChina

Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,identifying expression networks of ARLncRNAs using autophagy-related *** for prognostically relevant ARLncRNAs involved univariate Cox regression,Lasso regression,and multivariate Cox regression.A Nomogram was further employed to assess the reliability of Riskscore,calculated from the signatures of screened ARLncRNAs,in predicting ***,we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis,using consensus clustering to identify subgroups related to ***:The screening process identified 27 ARLncRNAs,with 13 being associated with HCC ***,a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for *** in the high-risk group showed very poor prognoses in most clinical *** Riskscore was closely related to immune cell scores,such as macrophages,and the DEGs between different groups were implicated in metabolism,cell cycle,and mitotic ***,high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel,suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for *** further identified C2 as the Paclitaxel subtype,where patients exhibited higher Riskscores,reduced survival rates,and more severe clinical ***:The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in *** drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs *** the identification of ARLncRNAsrelated isoforms,these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential av

关键词： Autophagy Hepatocellular carcinoma(HCC) Prognosis Precision medicine Paclitaxel

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Pancreatic giant malignancy simulating a gastrointestinal stromal tumor

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 431-433页

作者： Ben-Jie Liu Chen-Hui Jin Yan-Lun Guo Zhi-Gang Ke Jun-Jun Huang Lin-Ping Cao department of Hepatobiliary surgery Department of General SurgeryPujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China department of Pathology Pujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China department of Hepatobiliary and Pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Pancreatic acinar cell carcinoma(PACC)is a rare malignant tumor of pancreatic epithelial cells,which produces pancreatic exocrine *** originates from acinar cells and terminal branches of the pancreatic ducts in the exocrine tissue of the *** accounts for 1%−2%of pancreatic exocrine tumors[1].Herein,we present an elderly woman with PACC who recovered after effective laparoscopic *** tumor was located on the left side of the abdomen;imaging suggested that it was a gastrointestinal stromal tumor of the gastric wall origin,infiltrating the tail of the pancreas and omentum,while postoperative pathology suggested PACC.

关键词： Pancreatic gastrointestinal pancreas

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Improving treatment plan and mental health in children with abdominal infection for broad-spectrum bacterial infections

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World Journal of Psychiatry 2024年第9期14卷 1319-1325页

作者： Gui-Bo Wang Xue-Feng Zhang Bing Liang Jie Lei Jun Xue department of Pediatric surgery the First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina department of general surgery the First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina

BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective *** surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment *** To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic *** A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were *** observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the *** White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(Phospital stay in the observation group was significantly shorter than that in the control *** hospitalization cost in the observation group was significantly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics,improving treatment outcomes and reducing medical costs to some extent.

关键词： Pediatric abdominal infection Nucleic acid detection of broad-spectrum bacterial infection Bacterial culture Drug sensitivity testing Treatment effect Cost Mental health

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Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells

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World Journal of Gastroenterology 2024年第5期30卷 485-498页

作者： Chu-Xuan Liu Ying Gao Xiu-Fang Xu Xin Jin Yun Zhang Qian Xu Huan-Xin Ding Bing-Jun Li Fang-Ke Du Lin-Chuan Li Ming-Wei Zhong Jian-Kang Zhu Guang-Yong Zhang department of general surgery Shandong Provincial Qianfoshan HospitalShandong UniversityJinan 250014Shandong ProvinceChina department of general surgery Linyi People's HospitalLinyi 276034Shandong ProvinceChina department of Nursing Huantai TCM HospitalZibo 256400Shandong ProvinceChina Center for Translational medical Research The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014Shandong ProvinceChina department of general surgery The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014Shandong ProvinceChina

BACKGROUND Gastric cancer(GC)is associated with high mortality *** acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains *** GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic *** confers additional cancer phenotypes,including ferroptosis *** is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant ***,it is not fully defined if BAs can influence GC progression by modulating *** To reveal the mechanism of BAs regulation in ferroptosis of GC *** In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to *** used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism *** Our data suggested that BAs could reverse erastin-induced ferroptosis in GC *** effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression ***,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and ***,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and ***,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis *** This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC *** work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

关键词： Gastric cancer Ferroptosis Bile acids Chenodeoxycholic acid Farnesoid X receptor Glutathione

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Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma

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Oncology Research 2024年第5期32卷 965-981页

作者： ZHEN LIU LIANGWANG YANG ZHENGXING XIE HUI YU TIANYI GU DAOMING SHI NING CAI SHENGHUA ZHUO department of Neurosurgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of Neurosurgery First Affiliated Hospital of Hainan Medical UniversityHaikou570100China department of Cardiothoracic surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of general surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China

Clinical data indicates that glioma patients have poor treatment outcomes and clinical *** role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully *** this study,we aimed to investigate the role and relationship between OSPRGs and *** and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha L,GNAL)was *** association of GNAL expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was *** was used to evaluate GNAL level in *** analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of *** was an independent prognostic factor,and patients with low GNAL expression have a poor *** of GNAL was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related *** infiltration analysis indicated that GNAL levels were negatively correlated with immune *** low-expression group showed efficacy with anti-PD-1 *** compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAL high and low-expression groups were ***,its expression was associated with several immune cells,immune-related genes,and *** expression of GNAL is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.

关键词： Glioma Olfaction GNAL Tumor immune microenvironment Immunotherapy/chemotherapy response

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Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang department of Neurology The First Affiliated Hospital of Ningbo UniversityNingboZhejiang ProvinceChina department of general surgery The First Affiliated Hospital of Ningbo UniversityNingboZhejiang ProvinceChina department of Neurosurgery The First Affiliated Hospital of Ningbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province NingboZhejiang ProvinceChina

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier *** microvascular endothelial cells are a major component of the blood-brain *** mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial *** this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial *** found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial ***,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial *** established an in vitro brain microvascular endothelial cell model of the blood-brain *** found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain *** a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic *** found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic *** findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

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