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Molecular Engineering of Aptamer to Solubilize Hydrophobic Near-Infrared Photosensitizer for Enhanced Cancer Photodynamic Therapy

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CCS Chemistry 2024年第5期6卷 1240-1254页

作者： Rongjun Zhang Ding-Kun ji Defan Yao Zeyu Xiao Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200240 department of Radiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092 department of Pharmacology and Chemical Biology School of MedicineShanghai Jiao Tong UniversityShanghai 200025 Zhejiang Cancer hospital Hangzhou Institute of Medicine(HIM)The Chinese Academy of SciencesHangzhouZhejiang 310022 Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangshaHunan 410082

Photodynamic therapy(PDT)is a clinically representative treatment strategy for ***,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting ***,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer *** pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click *** coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and ***,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering *** reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell *** growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo *** therapeutic effect is more than 20-fold higher than that of *** with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and *** DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.

关键词： aptamer aptamer-drug conjugates photosensitive drugs targeted photodynamic therapy cancer theranostics

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MAL2 DNA methylation serves as a biomarker for the diagnosis and prognosis of glioma

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Genes & Diseases 2024年第5期11卷 36-39页

作者： Hao Luo Xing Xiao Weiliang Hou jing Cai Ming Chen Qisheng Tang Yusheng tong Zengxin Qi Kaicheng Li Liang Chen department of Neurosurgery Huashan HospitalShanghai Medical CollegeState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain Science and Institutes of Brain ScienceFudan UniversityShanghai 200040China National Center for Neurological Disorders Shanghai 200040China shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration Shanghai 200040China Tianqiao and Chrissy Chen Institute Clinical Translational Research Center Shanghai 200040China shanghai QuietD Biotechnology Co. Ltd.Shanghai 201210China

Glioma is a common and malignant brain tumor,and molecular diagnostics for glioma have received increasing attention.1,2 Previous studies have suggested that the MAL2 gene may be involved in the transcytosis of various cancers.3 This study aimed to investigate the potential of MAL2 as a biomarker for *** candidate MAL2 CpG sites were validated by pyrosequencing and used to construct a diagnostic model for *** analysis was also conducted to determine the relationship between highly methylated MAL2-specific CpG sites and the prognosis of *** findings also showed that MAL2 was more highly methylated in glioma than in other *** constructed diagnostic model can distinguish glioma from other cancers with high sensitivity(93.3%)and specificity(86.5%).Additionally,a risk score model was built based on MAL2 methylation to assess the prognosis of glioma。

关键词： glioma diagnosis MAL

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Regulable toehold lock for the effective control of strand displacement reaction sequence and circuit leakage

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Chinese Chemical Letters 2024年第7期35卷 372-376页

作者： Kuangdi Luo Yang Qin Xuehao Zhang Hanxu ji Heao Zhang jiangtian Li Xianjin Xiao Xinyu Wang department of Breast Surgery Second Hospital of Jilin UniversityChangchun 130041China Institute of Reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China department of Pancreatic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Life Science and Technology Wuhan Polytechnic UniversityWuhan 430023China

Strand displacement reaction enables the construction of enzyme-free DNA reaction networks,thus has been widely applied to DNA circuit and *** has the characteristics of high efficiency,universality and ***,the existing regulation tools cannot enable effective control of the reaction sequence,which undoubtedly limits the construction of complex nucleic acid ***,we developed a regulation tool,toehold lock,and achieved strict control of reaction sequence without loss of the main reaction signal ***,we applied the tool to scenarios such as seesaw circuits,AND/OR logic gates,and entropy-driven circuits,and respectively demonstrated its significant superiority compared to the original *** believe that the proposed toehold lock has greatly optimized the efficiency of DNA strand displacement-based networks,and we anticipate that the tool will be widely used in multiple fields.

关键词： DNA circuit Toehold lock DNA strand displacement Reaction sequence Seesaw circuit

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Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-jin Wang Nan Shen Hao Li ji-Wen Wang department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

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Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

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Chinese Journal of Integrative Medicine 2024年第1期30卷 25-33页

作者： GAO Quan LI Lin ZHANG Qi-man SHENG Qin-song ZHANG ji-liang jiN Li-jun SHANG Rui-yan School of Pharmacy and department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China department of Colorectal Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Beijing tong Ren Tang Chinese Medicine Co. Ltd.Beijing(100000)China department of Traditional Chinese Medicine Hangzhou Shangcheng District People's HospitalHangzhou(310006)China department of Gynecology Hangzhou Women's HospitalHangzhou(310008)China

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G_1–S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9(P<0.05), and might play an anticancer role through Akt signaling pathway. Conclusions: Monotropein exerts its antitumor

关键词： monotropein Chinese medicine anticancer activity colorectal cancer cells network pharmacology

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Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

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Chinese Journal of Natural Medicines 2024年第4期22卷 375-384页

作者： ZENG Zhen ZHANG Chen HU jiadong WANG Feiyan WU Ziding WANG jing ZHANG Jun YANG Shuda CHEN Junfeng LI Mingming tong Qi QIU Shi CHEN Wansheng The SATCM Key Laboratory for New Resources&Quality Evaluation of Chinese Medicine Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China department of Pharmacy Second Affiliated Hospital of Navy Medical UniversityShanghai 200003China Kunming Plant Classification Biotechnology Co. Ltd.Kunming 650500China School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical UniversityKunming 650500China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Beijing100700China

The aerial parts of Mosla chinensis *** Mosla chinensis cv.'jiangxiangru'(MCJ)are widely utilized in traditional Chinese medicine(TCM),known collectively as ***,due to clinical effectiveness concerns and frequent misidentification,the original plants have increasingly been substituted by various species within the genera Elsholtzia and *** challenge in distinguishing between these genera arises from their similar morphological and metabolic *** address this issue,our study introduced a rapid method for metabolic characterization,employing high-resolution mass spectrometry-based *** detailed biosynthetic and chemometric analyses,we pinpointed five phenolic compounds—salviaflaside,cynaroside,scutellarein-7-O-D-glucoside,rutin,and vicenin-2—among 203 identified compounds,as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia *** methodology holds promise for broad application in the analysis of plant aerial parts,especially in verifying the authenticity of aromatic traditional medicinal *** findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

关键词： Genus Elsholtzia Genus Mosla Traditional Chinese medicine Xiang-ru Non-volatile phenolic compounds Liquid chromatography-mass spectrometry

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Randomised study of bailout intracranial angioplasty following thrombectomy for acute large vessel occlusion(ANGEL-REBOOT):protocol of a multicentre randomised controlled trial

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Stroke & Vascular Neurology 2024年第2期9卷 181-188页

作者： Feng Gao Xu tong Baixue jia Ming Yang Yuesong Pan Zeguang Ren William Scott Burgin Liping Liu Xingquan Zhao Yilong Wang Yongjun Wang Zhongrong Miao Interventional Neuroradiology Department of NeurologyBeijing Tiantan HospitalBeijingChina china National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalBeijingChina department of Neurosurgery University of South FloridaTampaFloridaUSA department of Neurology Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA Comprehensive Stroke Center Tampa General HospitalTampaFloridaUSA department of Neurology Beijing Tiantan HospitalBeijingChina

Rationale Unsuccessful thrombectomy of acute large vessel occlusions(LVOs)has been associated with unfavourable *** randomised controlled trials(RCTs)have reported a failure rate of 12%–41%for thrombectomy *** factors contribute to failed thrombectomy,including technical difficulties in accessing the occlusion,unsuccessful thrombus retrieval,thrombotic reocclusion and pre-existing intracranial atherosclerotic *** some studies have explored balloon dilation or permanent stenting as rescue intracranial angioplasty for failed thrombectomy in individual cases,there is currently no evidence from RCTs on this specific *** To evaluate the potential superiority of bailout angioplasty over standard treatment in cases of unsuccessful recanalisation(eTICI 0 to 2a)or residual severe stenosis(>70%)after thrombectomy in acute LVO patients within 24 hours of stroke *** This study is a multicentre,prospective,randomised,controlled clinical trial designed by *** compares bailout angioplasty with standard therapy and follows an open-label treatment approach while maintaining a blinded outcome assessment(PROBE design).Our objective is to allocate 348 patients in a 1:1 ratio to either receive bailout angioplasty as an intervention or standard therapy as a control,following unsuccessful *** The main measure of interest is the modified Rankin Scale(mRS)Score,which will be assessed in a blinded manner at 90(±14)days following *** primary effect size will be determined using ordered logistic regression to calculate the common OR,representing the shift on the six-category mRS Scale at the 90-day ***,the safety outcomes will be evaluated,including symptomatic intracranial haemorrhage within 18–36hours,severe procedure-related complications and mortality within 90(±14)days,among *** The ANGEL-REBOOT study aims to generate substantial evidence regarding the efficacy

关键词： angioplasty throm intracranial

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Association between Long-Term Exposure to PM_(2.5) Inorganic Chemical Compositions and Cardiopulmonary Mortality: A 22-Year Cohort Study in Northern china

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Environment & Health 2024年第8期2卷 530-540页

作者： Hongyue Sun Xi Chen Wenzhong Huang jing Wei Xueli Yang Anqi Shan Liwen Zhang Honglu Zhang jiayu He Chengjie Pan jingjing Li jing Wu tong Wang jie Chen Yuming Guo Shilu tong Guanghui Dong Nai-Jun Tang department of Occupational and Environmental Health School of Public HealthTianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Environment Nutrition and Public Health Tianjin Medical UniversityTianjin 300070China Center for International Collaborative Research on Environment Nutrition and Public Health Tianjin 300070China Key Laboratory of Prevention and Control of Major Diseases in the Population Ministry of EducationTianjin Medical UniversityTianjin 300070China Climate Air Quality Research UnitSchool of Public Health and Preventive MedicineMonash UniversityMelbourne 3004Australia department of Atmospheric and Oceanic Science Earth System Science Interdisciplinary CenterUniversity of MarylandCollege ParkMaryland 20740United States Shandong Provincial hospital Affiliated to Shandong First Medical university Ji nan 250021ShandongChina National Center for Chronic and Noncommunicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100050China department of Epidemiology and Biostatistics School of Public HealthTianjin Medical UniversityTianjin 300070China School of Public Health Shanxi Medical UniversityTaiyuan 030001China School of Public Health and Social Work Queensland University of TechnologyBrisbane 4072QLD Australia National Institute of Environmental Health Chinese Centre for Disease Control and PreventionBeijing 100021China Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment Department of Occupational and Environmental HealthSchool of Public HealthSun Yat-sen UniversityGuangzhou 510080China

Particulate matter with diameters≤2.5μm(PM_(2.5))has been identified as a significant air pollutant contributing to premature ***,the specific compositions within PM_(2.5) that play the most crucial role remain unclear,especially in areas with high pollution *** study aims to investigate the individual and joint mortality risks associated with PM_(2.5) inorganic chemical compositions and identify primary *** 1998,we conducted a prospective cohort study in four northern Chinese cities(Tianjin,Shenyang,Taiyuan,and Rizhao).Satellite-based machine learning models calculated PM_(2.5) inorganic chemical compositions,including sulfate(SO_(4)^(2–)),nitrate(NO_(3)^(–)),ammonium(NH_(4)^(+)),and chloride(Cl^(-)).A time-varying Cox proportional hazards model was applied to analyze associations between these compositions and cardiorespiratory mortality,encompassing nonaccidental causes,cardiovascular diseases(CVDs),nonmalignant respiratory diseases(RDs),and lung *** quantile-based g-computation model evaluated joint exposure effects and relative contributions of the *** analysis was used to identify vulnerable *** 785,807 person-years of follow-up,5812(15.5%)deaths occurred from nonaccidental causes,including 2932(7.8%)from all CVDs,479(1.3%)from nonmalignant RDs,and 552(1.4%)from lung *** interquartile range(IQR)increase in SO_(4)^(2–)was associated with mortality from nonaccidental causes(hazard ratio:1.860;95%confidence interval:1.809,1.911),CVDs(1.909;1.836,1.985),nonmalignant RDs(2.178;1.975,2.403),and lung cancer(1.773;1.624,1.937).In the joint exposure model,a simultaneous rise of one IQR in all four compositions increased the risk of cardiorespiratory mortality by at least 36.3%,with long-term exposure to SO_(4)^(2–)contributing the most to nonaccidental and cardiopulmonary *** with higher incomes and lower education levels were found to be more vulnerable.

关键词： PM_(2.5)inorganic chemical compositions mortality cohort study cardiorespiratory disease joint association

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Clostridium difficile infection following colon subtotal resection in a patient with gallstones: A case report and review of literature

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World Journal of Gastrointestinal Surgery 2024年第9期16卷 3048-3056页

作者： Feng Ke Zhen-Hua Dong Fan Bu Cheng-Nan Li Qi-tong He Zhi-Cheng Liu ji Lu Kai Yu Da-Guang Wang He-Nan Xu Chang-Tao Ye department of General Surgery Affiliated Hospital of Changchun University of Chinese MedicineChangchun 130000Jilin ProvinceChina department of Gastrointestinal Surgery The First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina department of Plastic and Aesthetic Surgery The First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina department of Encephalopathy Rehabilitation Chaoyi HospitalYanbian Korean Autonomous PrefectureYanji 133000Jilin ProvinceChina department of Urology The First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina

BACKGROUND Clostridium difficile(***)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical *** SUMMARY A patient experienced recurrent difficulty in bowel movements over the past ***,symptoms worsened within the last ten days,leading to a clinic visit due to *** patient was subsequently referred to our ***,the patient was diagnosed with obstructed colon accom-panied by *** antibiotics were administered both before and after surgery to prevent *** the fourth day post-surgery,symptoms of CDI *** cultures confirmed the presence of *** *** involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon ***,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months *** CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still *** infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation *** patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is *** and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.

关键词： Cholecystolithiasis Clostridium difficile Bile acid circulation Intestinal microenvironment Case report

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超声引导下区域神经阻滞用于腹腔镜减重手术后镇痛的研究进展

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临床麻醉学杂志 2024年第7期40卷 746-750页

作者：王迪丁颖纪木火童建华南京医科大学第二附属医院麻醉科 210011

接受减重手术的患者术后中重度疼痛发生率较高,而术后大剂量阿片类药物的应用易引起呼吸抑制、恶心呕吐等不良反应。以超声引导下区域神经阻滞为基础的多模式镇痛在减重手术的疼痛管理中逐渐展现出突出的优势,能够有效减少阿片类药物用... 详细信息

接受减重手术的患者术后中重度疼痛发生率较高,而术后大剂量阿片类药物的应用易引起呼吸抑制、恶心呕吐等不良反应。以超声引导下区域神经阻滞为基础的多模式镇痛在减重手术的疼痛管理中逐渐展现出突出的优势,能够有效减少阿片类药物用量,降低术后并发症发生率,提高术后恢复质量。近年来,不同的区域神经阻滞方法在减重手术中的应用相继报道。本文就腹腔镜减重手术后疼痛特点、不同神经阻滞技术的应用及效果和局限性进行综述,为临床应用提供参考。

关键词：减重手术术后镇痛神经阻滞腹腔镜

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