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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao department of Hepatobiliary surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China department of Cardiothoracic surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c department of Hepatobiliary surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Hepatobiliary surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune *** shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein ***:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using ***-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following *** blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular ***:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer *** HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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Surgical techniques to prevent delayed gastric emptying after pancreaticoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 449-457页

作者： Peng Duan Lu Sun Kai Kou Xin-Rui Li Ping Zhang department of Hepatobiliary and Pancreatic surgery General Surgery Centerthe First Hospital of Jilin UniversityChangchun 130021China department of Dental Implantology Hospital of StomatologyJilin UniversityChangchun 130021China

Background: Delayed gastric emptying(DGE) is one of the most common complications after pancreaticoduodenectomy(PD). DGE represents impaired gastric motility without significant mechanical obstruction and is associated with an increased length of hospital stay, increased healthcare costs, and a high readmission rate. We reviewed published studies on various technical modifications to reduce the incidence of DGE. Data sources: Studies were identified by searching Pub Med for relevant articles published up to December 2022. The following search terms were used: “pancreaticoduodenectomy”, “pancreaticojejunostomy”, “pancreaticogastrostomy”, “gastric emptying”, “gastroparesis” and “postoperative complications”. The search was limited to English publications. Additional articles were identified by a manual search of references from key articles. Results: In recent years, various surgical procedures and techniques have been explored to reduce the incidence of DGE. Pyloric resection, Billroth II reconstruction, Braun's enteroenterostomy, and antecolic reconstruction may be associated with a decreased incidence of DGE, but more high-powered studies are needed in the future. Neither laparoscopic nor robotic surgery has demonstrated superiority in preventing DGE, and the use of staplers is controversial regarding whether they can reduce the incidence of DGE. Conclusions: Despite many innovations in surgical techniques, there is no surgical procedure that is superior to others to reduce DGE. Further larger prospective randomized studies are needed.

关键词： Pancreaticoduodenectomy Delayed gastric emptying Postoperative complications Surgical techniques

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Engineered stem cells by emerging biomedical stratagems

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Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao department of Vascular surgery.Nanjing Drum Tower hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary surgery and Transplantation surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Shenzhen Research Institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable *** the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical *** the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are *** optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell *** review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future *** begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical ***,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

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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

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Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 514-526页

作者： Stylianos Fiflis Grigorios Christodoulidis Menelaos Papakonstantinou Alexandros Giakoustidis Stergos Koukias Paraskevi Roussos Marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Dimitrios Giakoustidis First department of surgery General Hospital PapageorgiouThessaloniki 56429Greece department of General surgery University Hospital of LarissaLarissa 41110Greece

BACKGROUND Gastric cancer is the third most common cause of cancer related death *** with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain *** indexes have been proposed in the past few years in order to estimate the survival of patients undergoing *** preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been *** aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative *** To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction *** A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI *** PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic *** review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic *** patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual *** 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included st

关键词： Prognostic nutritional index Gastric adenocarcinoma Gastroesophageal junction cancer Prognosis Overall survival

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Feeding the vasculature with cruciferous vegetables:a secret for organ protection

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Signal Transduction and Targeted Therapy 2024年第3期9卷 828-830页

作者： Priya Veluswamy Jens Wippermann Max Wacker Heart surgery Research Department of Cardiothoracic SurgeryOtto-von-Guericke University HospitalMagdeburgGermany

Two very recent back-to-back papers published in Nature1,2 decipher the holistic role of the aryl hydrocarbon receptor(AHR)/dietary-ligand axis,in enteric and pulmonary vasculature to emphasize tolerance induction and vessel integrity during homeostasis,sterile inflammation and *** studies spectacularly highlight the significance of endothelium in orchestrating tissue tolerance by demonstrating the multifaceted activities of endothelial-expressed AHR that protects the vasculature to maintain organ homeostasis.

关键词： maintain sterile homeostasis

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The diagnostic value of tenascin-C in acute aortic syndrome

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Journal of Geriatric Cardiology 2024年第3期21卷 359-368页

作者： Ming MA Wei CHEN Hai-Long CAO Jun PAN Qing ZHOU Xin-Long TANG Dong-Jin WANG department of Thoracic and Cardiovascular surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina department of Thoracic and Cardiovascular surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina department of Thoracic surgery Kunshan Hospital of Traditional Chinese MedicineJiangsuChina

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases ***-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular *** elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains *** We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back *** to discriminate AAS from acute coronary syndrome(ACS)were compared and *** From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of *** the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute *** area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for *** a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and *** The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and ***-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

关键词： acute cardiovascular elevated

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Paeoniflorin,the Main Monomer Component of Paeonia lactiflora,Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

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Chinese Journal of Integrative Medicine 2024年第5期30卷 433-442页

作者： CHEN Pu ZHOU Jun RUAN An-min MA Yu-feng WANG Qing-fu department of Orthopaedic surgery Beijing University of Chinese Medicine Third Affiliated HospitalBeijing 100029China department of Orthopaedic surgery Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China department of Orthopaedic surgery Beijing Longfu HospitalBeijing 100010China

Objective:To explore the mechanism of paeoniflorin(PF)on osteoarthritis(OA)synovial inflammation from network pharmacology to experimental ***:Targets of OA were constructed by detecting the database of network database platforms(Therapeutic Target database,Drug Bank and Gene Cards),and the targets of PF were constructed by Pub Chem and Herbal Ingredients'Targets *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of these co-targeted genes were conducted via Database for Annotation,Visualization,and Integrated Discovery(DAVID)database,and protein-protein interaction(PPI)networks were conducted via the search tool for the retrieval of interacting genes(STRING)*** counting kit-8(CCK-8)assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes(FLS),quantitative real-time polymerase chain reaction(q PCR),enzyme-linked immunosorbent assay(ELISA)and Western blot were used to verify the potential mechanism of PF in synovial ***:Twenty-six co-targeted genes were *** enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm,and the biological processes mainly involved'cellular response to hypoxia''lipopolysaccharide(LPS)-mediated signaling pathway'and'positive regulation of gene expression'.KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with'hypoxia-inducible factor-1(HIF-1)signaling pathway'and'tumornecrosis factor(TNF)signaling pathway'.The PPI network showed that the top 3 hub genes were TP53,TNF,and *** docking results showed that PF was well docking with ***-8 showed no potential toxicity of 10,20 and 50μmol/L PF on human OA *** PF significantly decreased the expression levels of interleukin-1β,interleukin-6,TNF-αmatrix metalloproteinase 13(MMP13),and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5)and TNF

关键词： paeoniflorin osteoarthritis synovial inflammation tumor necrosis factor-α network pharmacology Paeonia lactiflora

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Skeletal interoception in osteoarthritis

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Bone Research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu department of Joint surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China department of Orthopedic surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

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Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang department of Thoracic surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Thoracic surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina department of Thoracic surgery Changhai HospitalNaval Medical UniversityShanghaiChina department of Thoracic-Cardiovascular surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental Animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： surgery chemotherapy treatment

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