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新型磁导航超声引导经右肝管行经皮肝穿刺胆管引流术治疗恶性梗阻性黄疸的初步临床应用

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中华内科杂志 2024年第3期63卷 284-290页

作者：卓晗吴琛谭忠明唐薇薇朱德明徐燕赵洁顾建平王学浩宋进华南京医科大学第一附属医院(江苏省人民医院)肝胆中心南京210029 南京医科大学附属南京医院(南京市第一医院)介入科南京210006

目的探讨一款新型磁导航超声技术联合数字减影血管造影(DSA)双引导经右肝管行经皮肝穿刺胆管引流术(PTCD)治疗恶性梗阻性黄疸的初步临床应用价值。方法随机对照试验。回顾性分析南京医科大学第一附属医院(江苏省人民医院)肝胆中心2018... 详细信息

目的探讨一款新型磁导航超声技术联合数字减影血管造影(DSA)双引导经右肝管行经皮肝穿刺胆管引流术(PTCD)治疗恶性梗阻性黄疸的初步临床应用价值。方法随机对照试验。回顾性分析南京医科大学第一附属医院(江苏省人民医院)肝胆中心2018年12月至2021年12月收治的64例因恶性梗阻性黄疸需从右肝管行PTCD的患者的临床资料,磁导航超声组患者为32例,采用新型磁导航超声(MNU)结合DSA进行双引导穿刺,对照组患者为32例,采用传统DSA引导进行穿刺。对比两组的手术时间、穿刺次数、胆管置管完成后DSA显示的X线剂量、患者对手术的耐受度、手术成功率、手术前后总胆红素及术后并发症发生率等情况。结果磁导航超声组手术时间明显短于对照组[(17.8±7.3)比(31.6±9.9)min,t=-6.35,P=0.001]。穿刺次数磁导航超声组明显减少[(1.7±0.6)比(6.3±3.9)次,t=-6.59,P=0.001]。胆管置管完成后DSA显示的X线剂量磁导航超声组少于对照组[(132±88)比(746±187)mGy,t=-16.81,P<0.001]。对照组有5例患者表示,因多次穿刺引发的疼痛或长时间的手术无法承受相关手术操作,2例因此停止手术,而磁导航超声组没有患者出现无法耐受手术的情况,全部完成手术,手术成功率磁导航超声组(100%,32/32)高于对照组(93.8%,30/32)。磁导航超声组患者胆管出血(25.0%,8/32)及感染的发生率(18.8%,6/32)明显低于对照组,对照组出血发生率53.1%(17/32)、感染发生率28.1%(9/32)。结论新型磁导航超声结合DSA双引导经右胆管行PTCD治疗恶性梗阻性黄疸安全、有效,具有较高的临床推广价值。

关键词：超声处理血管造影术,数字减影黄疸经皮经肝穿刺胆管引流术

Bromocriptine enhances the uptake of^(99m)Tc-MIBI in patients with hepatocellular carcinoma

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The Journal of Biomedical Research 2012年第3期26卷 165-169页

作者： Xiangting Chai Qiaoyu Liu Wenyu Shao Feng Zhang xuehao wang Hai wang Department of Internal Medicine Jiaonan People＇s Hospital of Shandong Province Jiaonan Shandong 266400 China Department of General Surgery the First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu 210029 China.

99mTc-methoxyisobutyl isonitrile （MIBI） is a suitable transport substrate for the multidrug resistance gene prod- uct P-glycoprotein （P-gp） and widely used for tumor imaging. Bromocriptine has been shown to inhibit the ATPase activity and the function of P-gp. We hypothesized that bromocriptine could promote the accumulation of MIBI by inhibiting P-gp activities, a feature that can be taken advantage of for enhancing 99mTc-MIBI imaging. In the cur- rent study, we sought to investigate whether bromocriptine enhanced the uptake of 99mTc-MIBI in hepatocellular carcinoma patients. Sixty primary hepatocellular carcinoma patients received 99mTc-MIBI single photon emission computer tomgraphy （SPECT） prior to surgery. 99mTc-MIBI SPECT was performed 15 and 120 min after injec- tion of 20 mCi 99mTc-MIBI, and early uptake, delayed uptake （L/Nd）, and washout rate （L/Nwr） of 99mTc-MIBI were obtained. In addition, a second 99mTc-MIBI SPECT was performed according to the same method 48 h after bromocriptine administration. We found that, prior to bromocriptine administration, significant MIBI uptake in tumor lesions was noted in only 10 （16.7%, 10/60） patients with hepatocellular carcinoma. No significant MIBI uptake was observed in the tumor lesions of the remaining 50 （83.3%, 50/60） hepatocellular carcinoma patients. Following bromocriptine administration, all the patients without apparent MIBI uptake demonstrated significant MIBI uptake on 99mTc-MIBI SPECT （P 〈 0.05）. Our findings indicate that bromocriptine enhances the uptake of 99mTc-MIBI in patients with hepatocellular carcinoma.

关键词： liver cancer multidrug resistance P-glycoprotein 99mTc-MIBI bromocriptine

HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

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Signal Transduction and Targeted Therapy 2021年第3期6卷 988-1000页

作者： Qing Li Yong Ni Liren Zhang Runqiu Jiang Jing Xu Hong Yang Yuanchang Hu Jiannan Qiu Liyong Pu Jinhai Tang xuehao wang Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Living Donor Liver Transplantation(Nanjing Medical University)NanjingJiangsu ProvinceChina School of Medicine Southeast UniversityNanjingChina department of Hepatopancreatobiliary Surgery Shenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongChina Department of Hepatobiliary Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvincePeople's Republic of China Medical School of Nanjing University NanjingJiangsuChina Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Immunology Key Laboratory of Immune Microenvironment and DiseaseNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina

N6-methyladenosine(m6A),and its reader protein YTHDF1,play a pivotal role in human tumorigenesis by affecting nearly everystage of RNA *** activation is one of the ways by which cancer cells survive ***,the possibleinvolvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma(HCO).In this study,specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing,knockout,and-knockdownHCC cells,HCC organoids,and HCC patient-derived xenograft(PDX)murine ***1 expression and hypoxia inducedautophagy were significantly correlated in vitro;signifhcant overexpression of YTHDF1 in HCC tissues was associated with poorprognosis,Multivariate cox regression analysis identihed YTHDF1 expression as an independent prognostic factor in patients *** HC models conhrmed that YTHDF1 deficiency inhibited HCC autophagy,growth,and *** reporterassays and chromatin immunoprecipitation demonstrated that HlIF-1a regulated YTHDF1 transcription by directly binding to itspromoter region under *** results of methylated RNA immunoprecipitation sequencing,proteomics,and polysomeprofling indicated that YTHDF1 contibuted to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modifhed ATG2A and ATG14 mRNA,thus facilitating autophagy and autophagy-related malignancy of *** together,HlE-1d-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent *** fndings suggest thatYTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.

关键词： malignancy hepatocellular inhibited

The mechanisms of sorafenib resistance in hepatocellular carcinoma:theoretical basis and therapeutic aspects

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1713-1727页

作者： Weiwei Tang Ziyi Chen Wenling Zhang Ye Cheng Betty Zhang Fan Wu Qian wang Shouju wang Dawei Rong F.P.Reiter E.N.De Toni xuehao wang Department of General Surgery Nanjing First HospitalNanjing Medical UniversityNanjingChina Hepatobiliary/Liver Transplantation Center The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Living Donor TransplantationChinese Academy of Medical SciencesNanjingChina Department of Gastroenterology The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Michael G.DeGroote School of Medicine McMaster UniversityHamiltonONCanada Department of Radiology The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of Medicine II University HospitalLMUMunichGermany Liver Center Munich University HospitalLMUMunichGermany

Sorafenib is a multikinase inhibitor capable of facilitating apoptosis,mitigating angiogenesis and suppressing tumor cell *** late-stage hepatocellular carcinoma(HCC),sorafenib is currently an effective first-line ***,the development of drug resistance to sorafenib is becoming increasingly *** study aims to identify factors contributing to resistance and ways to mitigate *** studies have shown that epigenetics,transport processes,regulated cell death,and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC *** study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

关键词： sorafenib therapeutic hepatocellular

Biological features of intrahepatic CD4^(+)CD25^(+)T cells in the naturally tolerance of rat liver transplantation

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Frontiers of Medicine 2007年第4期1卷 373-376页

作者： LU Ling ZHANG Feng PU Liyong YAO Aihua YU Yue SUN Beicheng LI Guoqiang wang xuehao Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health Liver Transplantation CenterThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

The biological features of intrahepatic CD4^(+)CD25^(+)T regulatory cells in the naturally tolerance of rat liver transplantation were *** liver transplan-tation was performed in two allogeneic rat strain combina-tions,one with fatal immunosuppression despite a complete major histocompatibility complex *** subjects were divided into three groups according to different donors and recipients[Tolerance group:LEW-to-DA;Rejection group:DA-to-LEW;Syngegnic group(control group):DA-to-DA].The proportion of intrahepatic CD4^(+)CD25^(+)T cells from three groups was determined by flow cytometry(FCM)in different *** intrahepaitc CD4^(+)CD25^(+)T cells were isolated by magnetic activated cell sorting(MACS)method and identified by *** Foxp3 mRNA was detected by reverse transcriptase polymerase chain reaction(RT-PCR).And their suppression on the proliferation of CD4^(+)CD25^(-)T effector cells was analyzed by cell proliferation assay in *** immediately after transplantation,the proportion of Treg cells increased over time in both allogeneic groups but was significantly greater in the Rejection *** pro-portion of Treg cells declined after day 5,and such reduction was more dramatic in the Rejection group than in the Tole-rance *** in the Tolerance group showed a second increase in the proportion after day *** CD4^(+)CD25^(+)T cells isolated from spontaneous tolerance models inhibited the proliferation of mixed lymphocyte *** purity of CD4^(+)CD25^(+)Tcells sorted by MACS was 86%–93%.The CD4^(+)CD25^(+)T cells could specifically express the Foxp3 gene compared with CD4^(+)CD25^(-)T *** vitro,the spleen cells from LEW rats can irritate the proliferation of CD4^(+)CD25^(+)T cells more obviously than the syngegnic spleen ***4^(+)CD25^(+)Tr cells could suppress the proliferation of CD4^(+)CD25^(-)T cells,but the inhibition was reversed by exo-genous IL-2(200 U/mL).The CD4^(+)CD25^(+)T regulatory

关键词： liver transplantation immune tolerance T-lymphocytes,regulatory CD4^(+)CD25^(+)T regulatory cells

Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions

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Cellular & Molecular Immunology 2017年第6期14卷 521-528页

作者： Jian Gu Xuhao Ni Xiongxiong Pan Hao Lu Yunjie Lu Jie Zhao Song Guo Zheng Keli L Hippen xuehao wang Ling Lu Translational Medicine Research Center Affiliated Jiangning Hospital and Liver Transplantation Center First Affiliated Hospital Nanjing Medical University Nanjing 210029 China University of Minnesota Cancer Center and Division of Bone Marrow Transplantation Department of Pediatrics University of Minnesota Minneapolis MN 55455 USA Division of Rheumatology Penn State Milton S. Hershey Medical Center Hershey PA 17033 USA

Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Thl and Th17 cells. Studies have confirmed that natural CD4＋Foxp3＋ Tregs were unstable and dysfunctional in the presence of pro-inflammatory cytokines. In the current study, human CD39hi Tregs and CD39low Tregs were sorted from Tregs in vitro after 7 days of expansion. The functions of both Treg subsets were investigated under inflammatory conditions in vitro and in vivo. In the presence of IL-1β and IL-6, cultured CD4＋CD39hi Tregs maintained stable forkhead box protein 3 expression, whereas CD4＋CD39low Tregs lost Foxp3 expression and trans-differentiated into Thl or Th17 cells. Decreased IL-1βR and IL-6R expression on the CD39hi Tregs was the primary mechanism responsible for Treg stability. In addition, reduced activation of downstream molecules, such as STAT1 and STAT3, through the modulation of CpG demethylation played an important role. Finally, human CD4＋CD39hi Tregs but not CD4＋CD39low Tregs protected against xenograft versus host disease in model mice. These results strongly implied the physiological importance of CD39 expression and suggested that manipulation of CD39hi Tregs might represent a novel strategy for the treatment of autoimmune diseases.

关键词： CD39 stability Tregs xeno-GVHD

Diagnosis and treatment of biliary sludge,cast and stone following liver transplantation

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Journal of Nanjing Medical University 2006年第4期20卷 253-254,F0003页

作者： Lianbao Kong xuehao wang Fen Zhang The Liver Transplantation Center the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Objective： To investigate etiological facts and treatment of biliary sludge, cast and stone following orthotopic liver transplantation（OLT）. Methods： A review was made using data collected from 81 cases with OLTs performed in our center from February 2003 to January 2004, and confirmed by retrospective study. Etiological factors of biliary sludge, cast and stone following OLT were analyzed, and treatment of biliary sludge, cast and stone following OLT were discussed. Result： Nine cases of biliary sludge, cast and stone were diagnosed and the incidence rate was 11.1%. Of these, five were biliary sludge and cast, 2 were bile stone and 2 were necrotic debris. Two cases with hepatic artery embolism received retransplantation and survived. The other one with hepatic artery embolism was ameliorated with nasobiliary drainage by ERCP. Two cases with biliary sludge and cast were resolved by non-operative treatment. Four cases were reoperated, 2 resolved and 2 cases died. Conclusion： Biliary injury and ischemia reperfusion injury, reject reaction, infection and changes of bile kinetics are the important factors causing biliary sludge, cast and stone following OLT. Shortening the time of cold and heat ischemia reperfusion injury of liver, reducing the injury of the blood supply of donor bile duct, actively preventing and early treating of infection and rejection reaction might reduce the incidence rate of biliary sludge, cast and stone following OLT.

关键词： liver transplantation postoperative complications bfliary ducts calculi

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肝门部胆管癌的外科治疗及预后分析

中华外科杂志 2024年第4期62卷 290-301页

作者：李相成李长贤张慧成峰张峰浦立勇张传永王科孔连宝钱晓峰李东华陆文熊王平姚爱华白剑锋吴晓峰陈瑞翔王学浩南京医科大学第一附属医院肝胆中心南京210029

目的:探讨肝门部胆管癌的外科治疗效果及预后因素。方法:本研究为双向专病队列研究。回顾性收集2005年8月至2022年12月南京医科大学第一附属医院肝胆中心连续收治的首诊为肝门部胆管癌并接受外科手术切除的510例患者资料。男性324例,女... 详细信息

目的:探讨肝门部胆管癌的外科治疗效果及预后因素。方法:本研究为双向专病队列研究。回顾性收集2005年8月至2022年12月南京医科大学第一附属医院肝胆中心连续收治的首诊为肝门部胆管癌并接受外科手术切除的510例患者资料。男性324例,女性186例,年龄[ M(IQR)]63(13)岁(范围:25~85岁)。入院时肝功能Child-Pugh分级为A级343例(67.3%),B级167例(32.7%)。其中372例(72.9%)患者伴有黄疸症状,入院时总胆红素为126.3(197.6)μmol/L(范围:5.4~722.8 μmol/L),247例(48.4%)术前行经皮经肝穿刺胆道引流或内镜下鼻胆管引流减黄治疗,减黄组术前中位胆红素水平由186.4 μmol/L降至85.5 μmol/L。通过多因素Logistic回归识别根治性切除(R0切除)的影响因素,采用Cox比例风险模型筛选总体生存和无复发生存的预后因素。结果:510例患者中,Bismuth-Corlett Ⅲ~Ⅳ型366例(71.8%),其中86.1%(315/366)行半肝及以上切除;Ⅰ~Ⅱ型144例,其中81.9%(118/144)行单纯肝外胆管切除。510例患者的中位生存时间为22.8个月,1、3、5、10年总体生存率分别为72.2%、35.6%、24.8%、11.0%;中位无复发生存期为15.2个月,无复发生存率分别为66.0%、32.4%、20.9%、11.0%。R0切除率为64.5%(329/510),R0切除患者1、3、5、10年总体生存率分别为82.5%、48.6%、34.4%、15.2%。Clavien-Dindo并发症分级系统Ⅲ级及以上并发症发生率为26.1%(133/510),30 d内病死率为4.3%(22/510)。多因素Logistic回归分析结果提示,Bismuth-Corlett Ⅰ~Ⅲ型( P=0.009)、半肝及以上切除( P=0.001)及不伴有血管侵犯的T1~T2期患者更易获得R0切除[T2期比T1期: OR=1.43(0.61~3.35), P=0.413;T3期比T1期, OR=2.57(1.03~6.41), P=0.010;T4期比T1期: OR=3.77(1.37~10.38), P<0.01]。术前胆红素水平、Child-Pugh分级、肿瘤最大径、手术切缘、T分期、N分期、神经浸润和病理学分级是pM0期患者总体生存和无复发生存的独立预后因素( P值均<0.05)。结论:根治性手术切除是肝门部胆管癌患者获得长期生存的必要条件。行半肝及以上切除、区域淋巴结清扫,必要时合并血管切除重建可提高R0切除率。

关键词：胆管肿瘤外科手术根治性切除总体生存无复发生存

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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