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Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 25-34页

作者： Hai-Li Bao Chuan-Zhi Chen Chang-Zhen Ren Ke-Yan Sun Hao Liu Shao-Hua Song Zhi-Ren Fu department of Organ Transplantation Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China department of surgical oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Cardiology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai 200003China department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various ***,little is known about its effect on hepatic ischemia-reperfusion(I/R)*** study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying ***:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R *** alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver *** severity related to the inflammatory response and reactive oxygen species(ROS)production was also ***,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in ***:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and *** oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin *** addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in *** blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling ***:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

关键词： Hepatic ischemia-reperfusion injury Polydatin Macrophage Polarization Inflammation

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Risk factors,prognostic factors,and nomograms for distant metastasis in patients with diagnosed duodenal cancer:A population-based study

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World Journal of Gastrointestinal oncology 2024年第4期16卷 1384-1420页

作者： Jia-Rong Shang Chen-Yi Xu Xiao-Xue Zhai Zhe Xu Jun Qian department of oncology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina department of Proctology Nanjing Hospital of Chinese MedicineNanjing 210000Jiangsu ProvinceChina department of digestive Cancer Surgery Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina

BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor *** nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal *** To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal *** Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results *** and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with *** novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of *** analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA *** results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal *** The two nomograms are expected as effective tools fo

关键词： Duodenal cancer Distant metastasis Nomogram Risk factors Prognostic factors

Should we perform decompressive laparotomy during severe acute pancreatitis with intra-abdominal hypertension below 25 mmHg:Only the gut knows

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1470-1473页

作者： Thibault Vieille Melissa Crotet Celia Turco Paul Monasterolo Hadrien Winiszewski Gael Piton Medical Intensive Care Unit Besancon University HospitalBesancon 25000France Intensive Care Unit Vesoul HospitalVesoul 70000France department of digestive surgical oncology-Liver Transplantation Unit Besancon University HospitalBesancon 25000France Inserm UMRS-938 Centre de Recherche Saint-Antoine(CRSA)Sorbonne UniversitéParis 10041NY212France Intensive Care Unit Nord Franche Comte HospitalTrevenans 90400France

We suggest that during severe acute pancreatitis(SAP)with intra-abdominal hypertension,practitioners should consider decompressive laparotomy,even with intra-abdominal pressure(IAP)below 25 ***,in this setting,non-occlusive mesenteric ischemia(NOMI)may occur even with IAP below this cutoff and lead to transmural necrosis if abdominal perfusion pressure is not promptly *** report our experience of 18 critically ill patients with SAP having undergone decompressive laparotomy of which one third had NOMI while IAP was mostly below 25 mmHg.

关键词： Acute pancreatitis Abdominal compartment syndrome Decompressive laparotomy Mesenteric ischemia Intra-abdominal pressure Abdominal perfusion pressure

Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1

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oncology Research 2024年第5期32卷 925-931页

作者： JINGJING TIAN XIBAO HU XINRONG ZHANG department of Gastroenterology Tianjin Nankai HospitalTianjin300100China department of digestive Medicine First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin300100China

To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,and FLOT1 were *** results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells,while miR-622 was lowly expressed(p0.05).Synthesizing the results of these experiments above,we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells,and its mechanism is related to miR-622 and FLOT1.

关键词： Circ_0003855 miR-622 FLOT1 Esophageal cancer Cell proliferation

Role of endoscopic-ultrasound-guided biliary drainage with electrocautery-enhanced lumen-apposing metal stent for palliation of malignant biliary obstruction

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 1981-1985页

作者： Smit S Deliwala Emad Qayed department of Medicine Division of Digestive DiseasesEmory University School of MedicineAtlantaGA 30303United States

In this editorial,we discuss the article by Peng et al in the recent issue of the World Journal of Gastrointestinal Surgery,focusing on the evolving role of endoscopicultrasound-guided biliary drainage(EUS-BD)with electrocautery lumen apposing metal stent(LAMS)for distal malignant biliary *** endoscopy has rapidly advanced in decompression techniques,with growing evidence of its safety and efficacy surpassing percutaneous and surgical *** endoscopic retrograde cholangiopancreatography(ERCP)has been the gold standard for biliary decompression,its failure rate approaches 10.0%,prompting the exploration of alternatives like *** random-effects meta-analysis demonstrated high technical and clinical success of over 90.0% and an adverse event rate of 17.5%,mainly in the form of stent *** based on stent size were not reported but the majority used 6 mm and 8 mm *** the body of literature continues to demonstrate the effectiveness of this technique,the challenges of stent dysfunction need to be addressed in future *** strategy that has shown promise is placement of double-pigtail stents,only 18% received the prophylactic intervention in this *** expect this to improve with time as the technique continues to be refined and *** results above establish EUS-BD with LAMS as a reliable alternative after failed ERCP and considering EUS to ERCP upfront in the same session is an effective *** the promising results,studies must explore the role of EUS-BD as first-line therapy for biliary decompression.

关键词： Endoscopic-ultrasound Malignant biliary obstruction Lumen apposing metal stent Choledochoduodenostomy Hepaticogastrostomy

Phase Ib study of anti-EGFR antibody(SCT200) in combination with anti-PD-1 antibody(SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer

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Cancer Biology & Medicine 2024年第7期21卷 636-650页

作者： Ming Bai Yao Lu Chunmei Shi Jianwei Yang Wei Li Xianli Yin Chenghui Huang Lin Shen Liangzhi Xie Yi Ba department of GI Medical oncology Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer Tianjin Key Laboratory of Digestive Cancer Fujian Medical University Union Hospital Fujian Provincial Cancer Hospital Cancer Center The First Hospital of Jilin University department of Medical oncology Gastroenterology and Urology Hunan Cancer Hospital Affiliated Cancer Hospital of Xiangya School of Medicine Central South University department of oncology The Third Xiangya Hospital Central South University department of Gastrointestinal oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing Engineering Research Center of Protein and Antibody Sinocelltech Ltd. department of Cancer Center Peking Union Medical College Hospital Chinese Academy of Medical Sciences

Objective: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR) antibody(SCT200) and an anti-programmed cell death 1(PD-1) antibody(SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF) wild-type(wt) metastatic colorectal cancer(mCRC).Methods: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate(ORR) and safety. The secondary endpoints included disease control rate(DCR), progression-free survival(PFS), and overall survival(OS).Results: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71%(18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events(TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination ***: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No. NCT04229537).

关键词： Colorectal cancer SCT-I10A SCT200 epidermal growth factor receptor programmed cell death 1

Chang’an decoction(肠安方) alleviates endoplasmic reticulum stress by regulating mitofusin 2 to improve colitis

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Journal of Traditional Chinese Medicine 2024年第3期44卷 427-436页

作者： CHEN Youlan DING Mingming HUANG Chaoyuan ZHENG Yiyuan LIU Fengbin Institute of Integrated Traditional Chinese and Western Medicine digestive Diseases Shuguang HospitalShanghai University of Traditional Chinese Medicine department of oncology Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai the First Clinical Medical School Guangzhou University of Chinese Medicine department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese Medicine Baiyun Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine

OBJECTIVE: To evaluate the protective effects of Chang'an decoction(肠安方, CAD) on colitis, and investigate the potential mechanisms underlying these effects from the perspectives of endoplasmic reticulum(ER) stress induced by mitofusin 2(MFN2). METHODS: The composition of CAD was identified by liquid chromatography-mass spectrometry technology. A mice model of dextran sulfate sodium(DSS) induced colitis was established and therapeutic effects of CAD were determined by detecting body weight, disease activity index, colon length and histopathological changes. Then, the expression levels of MFN2, ER stress markers and Nucleotide-binding domain and leucine-rich repeat protein3(NLRP3) relevant proteins were detected by polymerase chain reaction(PCR), Western blot, immunohistochemistry and immunofluorescence staining. Subsequently, knockdown and overexpression cell model were constructed to further investigate the underlying mechanism of MFN2 mediating ER stress and energy metabolism by PCR, Western blot, electron microscopy and reactive oxygen species(ROS) staining. Finally, inflammatory indicator and tight junction proteins were measured by PCR and immunofluorescence staining to evaluate the protective effects of CAD. RESULTS: Results showed that the indispensable regulatory role of MFN2 in mediating ER stress and mitochondrial damage was involved in the protective effects of CAD on colitis in mice fed with DSS. Network pharmacology analysis also revealed CAD may play a protective effect on colitis by affecting mitochondrial function. In addition, our data also suggested a causative role for MFN2 in the development of inflammatory responses and energy metabolic alterations by constructing a knockdown and overexpression cell model whereby alter proper ER-mitochondria interaction in Caco-2 cells. Furthermore, relative expression analyses of ER stress markers and NLRP3 inflammasome showed the onset of ER stress and activation of NLRP3 inflammasome, which is consistent with

关键词： Chang'an decoction colitis endoplasmic reticulum stress mitochondrial damage mitofusin 2

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Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina department of General Surgery Tianjin Medical University General HospitalTianjinChina department of Anorectal Tianjin People's HospitalTianjinChina department of Radiology Beijing Friendship Hospital Capital Medical UniversityBeijingChina department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina department of Thoracic Surgery/Institute of Thoracic oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong Leung Kwok Wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina department of Pediatrics The Chinese University of Hong KongHong KongChina department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease *** an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease *** research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue *** has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer *** transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc ***,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on *** also compile a summary of clinical trials involving zinc *** the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement