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Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary Surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of interventional radiology and Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise intervention of Digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor *** cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated *** the dysregulated nervous systems might represent a novel strategy for cancer ***,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely *** staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC ***93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC *** all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

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Intra-arterial tenecteplase during thrombectomy for acute stroke(BRETIS-TNK II):rationale and design

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Stroke & Vascular Neurology 2024年第1期9卷 59-65页

作者： Zi-Ai Zhao Jing Qiu Wei Li Thanh Nguyen Shouchun Wang Huaizhang Shi Ming Wei Feng Wang Di Li Hui-Sheng Chen department of Neurology General Hospital of Northern Theater CommandShenyangLiaoning ProvinceChina Neurology RadiologyBoston Medical CenterBostonMassachusettsUSA department of Neurology First Affiliated Hospital of Jilin UniversityChangchunJilinChina department of Neurosurgery First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina department of Neurosurgery Tianjin Huanhu HospitalTianjinTianjinChina department of interventional Therapy First Affiliated Hospital of Dalian Medical UniversityDalianChina Neurological intervention department Dalian Municipal Central HospitalDalianLiaoningChina

Background Our recent pilot study suggests intra-arterial tenecteplase(TNK)during the first pass of endovascular treatment(EVT)seems safe,may increase first-pass reperfusion and good outcome in acute ischaemic stroke(AIS)patients with large-vessel occlusion(LVO).Aims To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom *** size estimates A maximum of 380 patients are required to test the superiority hypothesis with 80%power according to a two-side 0.05 level of significance,stratified by age,gender,baseline systolic blood pressure,prestroke modified Rankin Scale(mRS),baseline National Institute of Health stroke scale,baseline ASPECTS,time from onset to groin puncture,intravenous thrombolysis before EVT,stroke territory and stroke *** Intra-arterial TNK during thrombectomy for acute stroke(BRETIS-TNK II)study is a prospective,randomised,adaptive enrichment,open-label,blinded end point,multicentre *** AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:*** experimental group will be treated with intra-arterial infusion of TNK during *** control group will be treated with standard *** The primary end point is a favourable outcome,defined as an mRS score of 0–2 at 90 *** primary safety end point is symptomatic intracranial haemorrhage within 48 hours,which is defined as an increase in the National Institutes of Health Stroke Scale score of≥4 points as a result of the intracranial *** The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

关键词： rational stratified TNK

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Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)genetransfected hepatic stellate cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 499-512页

作者： Hongyi LIU Yuanyuan ZHOU Peng GUO Xiongwei ZHENG Weibin CHEN Shichao ZHANG Yu FU Xu ZHOU Zheng WAN Bin ZHAO Yilin ZHAO department of Oncology and Vascular interventional radiology Zhongshan Hospital Affiliated to Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361004China School of Medicine Xiamen UniversityXiamen 361102China Xiamen Health and Medical Big Data Center Xiamen 361008China Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma(Zhongshan Hospital Affiliated to Xiamen University) Xiamen 361004China Xiamen Key Laboratory of Cellular intervention and interventional Medical Materials Xiamen 361004China

Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal ***,it has poor elasticity and compliance,leading to stenosis and *** ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial *** have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM ***,mechanical stimulation can encourage ECM secretion and remodeling of a fiber *** on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV ***,these HBX-HSCs were implanted into a polycaprolactonepolyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the *** obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after ***,the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula *** exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s *** study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.

关键词： Composite bilayer bionic blood vessel Extracellular matrix(ECM) Hepatic stellate cells(HSCs) Hepatitis B viral X(HBX)gene Mechanical force

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Surgical timing and long-term outcomes in patients with severe haemorrhagic spinal cord cavernous malformations

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Stroke & Vascular Neurology 2024年第4期9卷 439-445页

作者： An Tian Ziwei Cui Jian Ren Yeqing Ren Ming Ye Guilin Li Chuan He Xiaoyu Li Gao Zeng Peng Hu Yongjie Ma Jiaxing Yu Jingwei Li Lisong Bian Fan Yang Qianwen Li Feng Ling Tao Hong Liyong Sun Hongqi Zhang department of Neurosurgery Xuanwu Hospital Capital Medical UniversityBeijingChina department of Neurosurgery Beijing Haidian HospitalBeijingChina department of Neurosurgery United Family HealthcareBeijingChina department of radiology Xuanwu Hospital Capital Medical UniversityBeijingChina

Background Surgical resection of the lesions remains the main treatment method for most symptomatic spinal cord cavernous malformations(SCCMs)to eliminate the occupation and associated subsequent lifelong haemorrhagic ***,the timing of surgical intervention remains controversial,especially for patients in the acute stage after severe *** Patients diagnosed with SCCMs who were surgically treated between January 2002 and December 2021 were selected and retrospectively *** Modified McCormick Scale(MMS)was used to evaluate neurological and disability *** medical information was reviewed,and all patients were followed up for at least 6 *** A total of 279 patients were ultimately *** regard to long-term outcomes,110(39.4%)patients improved,159(57.0%)remained unchanged and 10(3.6%)*** patients with an MMS score of 2–5 on admission,in univariate and multivariate analyses,a≤6 weeks period between onset and surgery(adjusted OR 3.211,95%CI 1.504 to 6.856,p=0.003)was a significant predictor of improved *** 69 patients who first presented with severe haemorrhage,undergoing surgery within 6 weeks of the onset of severe haemorrhage(adjusted OR 4.901,95%CI 1.126 to 21.325,p=0.034)was significantly associated with improvement of MMS *** Surgical timing can influence the long-term outcome of *** patients with symptomatic SCCMs,especially those with severe haemorrhage,early surgical intervention within 6 weeks can provide more benefit.

关键词： patients Surgical haemorrhagic

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Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

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World Journal of Gastroenterology 2024年第9期30卷 1189-1212页

作者： Jin-Lian Jiang Yi-Yang Zhou Wei-Wei Zhong Lin-Yan Luo Si-Ying Liu Xiao-Yu Xie Mao-Yuan Mu Zhi-Gang Jiang Yuan Xue Jian Zhang Yi-Huai He department of Infectious Diseases Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of Infectious Diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina department of Respiratory Medicine Anshun People’s HospitalAnshun 561099Guizhou ProvinceChina department of General Practice Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of intervention radiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina School of Public Health Zunyi Medical UniversityZunyi 563099Guizhou ProvinceChina department of Liver Diseases Third People’s Hospital of ChangzhouChangzhou 213000Jiangsu ProvinceChina department of Digestion Dafang County People’s HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous ***,its contribution to the progression of liver damage remains *** To determine the role and mechanism of UGT1A1 in liver damage *** We investigated the relationship between UGT1A1 expression and liver injury through clinical ***,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model *** Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic *** suggests that low UGT1A1 levels may be associated with the progression of liver *** mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be *** mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ***1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid *** UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver ***1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders

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Polyphyllin Ⅰ enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth via downregulating the Wnt/β-catenin pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 251-259页

作者： CHANG Junli ZHAO Fulai SUN Xingyuan MA Xiaoping ZHAO Peng ZHOU Chujie SHI Binhao GU Wenchao WANG Yongjun YANG Yanping Spine Disease Institute Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China department of Diagnostic and interventional radiology University of TsukubaIbaraki 315-0114Japan

OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling ***:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry *** morphology of cancer cells was observed with inverted phase contrast *** migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell *** expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting ***:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma *** synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling ***:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.

关键词： osteosarcoma tumor necrosis factor-related apoptosis-inducing ligand Wnt signaling pathway beta-catenin polyphyllinⅠ

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Dendritic nanomedicine enhances chemoimmunotherapy by disturbing metabolism of cancer-associated fibroblasts for deep penetration and activating function of immune cells

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3680-3696页

作者： Yunkun Li Xiaoding Shen Haitao Ding Yuxin Zhang Dayi Pan Liping Su Yahui Wu Zaixiang Fang Jie Zhoua Qiyong Gong Kui Luo department of radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China department of radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune ***,we constructed a PEGylated dendritic epirubicin(Epi)prodrug(Epi-P4D)to regulate the metabolism of cancer-associated fibroblasts(CAFs),thus enhancing Epi penetration into both multicellular tumor spheroids(MTSs)and tumor tissues in mouse colon cancer(CT26),mouse breast cancer(4T1)and human breast cancer(MDA-MB-231)*** cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin,α-SMA,and collagen ***,thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell(DC)maturation and subsequent immune activation,including elevating the CD4^(+)T cell population,reducing CD4^(+)and CD8^(+)T cell hyperactivation and exhaustion,and amplifying the natural killer(NK)cell proportion and effectively activating *** a result,this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

关键词： Dendritic prodrug Enhanced penetration Metabolic intervention Cancer-associated fibroblasts Immunogenic cell death Chemotherapy Immunotherapy Immune microenvironment reconstitution

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Prevalence,patterns,risk factors and outcomes of peritoneal metastases after laparoscopic hepatectomy for hepatocellular carcinoma:a multicenter study from China

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 3-15,I0001-I0004页

作者： Yuan-Xiang Lu Jian-Ping Zhao Guan-Dou Yuan Ming-Gen Hu Chuan-Dong Sun Kun-Lun Chen Yao Chen Yong-Yi Zeng Zhi-Ying Yang Wan-Guang Zhang Hepatic Surgery Center Tongji Hospital of Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningChina Faculty of Hepato-Pancreato-Biliary Surgery Chinese PLA General HospitalBeijingChina department of Hepatobiliary and Pancreatic Surgery The Affiliated Hospital of Qingdao UniversityQingdaoChina department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina department of radiology intervention The Affiliated Tumor Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina department of Hepatobiliary Surgery Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouChina department of General Surgery China-Japan Friendship HospitalBeijingChina

Background:We aim to investigate the prevalence,patterns,risk factors,and outcomes of peritoneal metastases(PM)after curative laparoscopic hepatectomy(LH)for hepatocellular carcinoma(HCC).Methods:A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively *** incidence of PM following LH was evaluated and compared with that in open hepatectomy(OH)after 1:1 propensity score matching(PSM).Results:PM prevalence was 5.1%(15/295)in the early period[2010-2013],2.6%(47/1,843)in the later period[2014-2016],and 2.9%(62/2,138)in all LH patients,which was similar to 4.0%(59/1,490)in the OH *** recurrence patterns,timing,and treatment did not significantly vary between the LH and OH patients(P>0.05).Multivariate logistic regression revealed that tumor diameter>5 cm,non-anatomical resection,presence of microvascular invasion,and lesions<2 cm from major blood vessels were independent risk factors of PM after *** the 62 cases with PM,26(41.9%)had PM only,34(54.9%)had intrahepatic recurrence(IHR)and PM,and 2(3.2%)had synchronous extraperitoneal metastases(EPM).Patients with resectable PM had a 5-year overall survival(OS)of 65.0%compared to 9.0%for unresectable PM(P=0.001).Conclusions:The prevalence,patterns and independent risk factors of PM were identified for HCC patients after *** was not associated with increased incidence of PM in HCC patients for experienced *** re-excision of PM was associated with prolonged survival.

关键词： Prevalence hepatocellular carcinoma(HCC) peritoneal metastases(PM) laparoscopic hepatectomy(LH) open hepatectomy(OH)

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Personalized and continuous care intervention affects rehabilitation,living quality,and negative emotions of patients with breast cancer

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World Journal of Psychiatry 2024年第6期14卷 876-883页

作者： Ling-Xia Kong Yan-Hong Zhao Zhi-Lin Feng Ting-Ting Liu department of Breast Surgery The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Operating room The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina

BACKGROUND Breast cancer is among the most common malignancies *** progress in treatment methods and levels,the overall survival period has been prolonged,and the demand for quality care has *** To investigate the effect of individualized and continuous care intervention in patients with breast *** Two hundred patients with breast cancer who received systemic therapy at The First Affiliated Hospital of Hebei North University(January 2021 to July 2023)were retrospectively selected as research *** them,134 received routine care intervention(routing group)and 66 received personalized and continuous care(intervention group).Self-rating anxiety scale(SAS),self-rating depression scale(SDS),and Functional Assessment of Cancer Therapy-Breast(FACT-B)scores,including limb shoulder joint activity,complication rate,and care satisfaction,were compared between both groups after *** SAS and SDS scores were lower in the intervention group than in the routing group at one and three months after *** total FACT-B scores and five dimensions in the intervention group were higher than those in the routing group at three months of *** range of motion of shoulder anteflexion,posterior extension,abduction,internal rotation,and external rotation in the intervention group was higher than that in the routing group one month after *** incidence of postoperative complications was 18.18%lower in the intervention group than in the routing group(34.33%;Pintervention group than in the routing group(78.36%;P<0.05).CONCLUSION Personalized and continuous care can alleviate negative emotions in patients with breast cancer,quicken rehabilitation of limb function,decrease the incidence of complications,and improve living quality and care satisfaction.

关键词： Breast cancer Personalized care Continuous care Negative emotions Living quality Rehabilitation effect

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Computerized tomography-guided therapeutic percutaneous puncture catheter drainage-combined with somatostatin for severe acute pancreatitis: An analysis of efficacy and safety

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 59-66页

作者： Xue-Lan Zheng Wan-Ling Li Yan-Ping Lin Ting-Long Huang department of Critical Care Medicine The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina CT room The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina

BACKGROUND Severe acute pancreatitis(SAP),a condition with rapid onset,critical condition and unsatisfactory prognosis,poses a certain threat to human health,warranting optimization of relevant treatment plans to improve treatment *** To evaluate the efficacy and safety of computerized tomography-guided the-rapeutic percutaneous puncture catheter drainage(CT-TPPCD)combined with somatostatin(SS)in the treatment of *** Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were *** the basis of routine treatment,20 patients received SS therapy(control group)and 22 patients were given CT-TPPCD plus SS intervention(research group).The efficacy,safety(pancreatic fistula,intra-abdominal hemorrhage,sepsis,and organ dysfunction syndrome),abdominal bloating and pain relief time,bowel recovery time,hospital stay,inflammatory indicators(C-reactive protein,interleukin-6,and pro-calcitonin),and Acute Physiology and Chronic Health Evaluation(APACHE)II score of both groups were evaluated for *** Compared with the control group,the research group had a markedly higher total effective rate,faster abdominal bloating and pain relief and bowel recovery,INTRODUCTION Pancreatitis,an inflammatory disease occurring in the pancreatic tissue,is classified as either acute or chronic and is associated with high morbidity and mortality,imposing a socioeconomic burden[1,2].The pathogenesis of this disease involves early protease activation,activation of nuclear factor kappa-B-related inflammatory reactions,and infiltration of immune cells[3].Severe acute pancreatitis(SAP)is a serious condition involving systemic injury and subsequent possible organ failure,accounting for 20%of all acute pancreatitis cases[4].SAP is also characterized by rapid onset,critical illness and unsatisfactory prognosis and is correlated with serious adverse events such as systemic inflammatory response syn-drome an

关键词： Computerized tomography guidance Therapeutic percutaneous puncture catheter drainage Somatostatin Severe acute pancreatitis Efficacy and safety

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