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Baculoviruses as Vectors in Mammalian Cells

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中国病毒学 2007年第2期22卷 148-157页

作者： Chang-yong liang Xin-wen chen State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071China

The Baculoviridae are a large family of enveloped DNA viruses exclusively pathogenic to arthropods. Baculoviruses have been extensively used in insect cell-based recombinant protein expression system and as biological pesticides. They have been deomostrated to be safe to mammals, birds and fish. Recently, baculoviruses has been shown to transduce different mammalian cells in spite of the fact that they cannot replicate in mammalian cells (11, 73, 76). This has resulted in the development of baculoviruses as mammalian expression systems and even as vestors for gene therapy.

关键词：杆状病毒哺乳动物病毒细胞医学研究

Baculovirus-mediated Expression of p35 Confers Resistance to Apoptosis in Human Embryo Kidney 293 cells

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中国病毒学 2007年第5期22卷 389-396页

作者： Jian-hua SONG Chang-yong liang Xin-wen chen State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China

Baculovirus has many advantages as vectors for gene *** demonstrated that recombinant baculovirus vectors expressing p35(Ac-CMV-p35) and eGFP(Ac-CMV-GFP) could be transduced into human kidney 293 cells *** level of transgene expression was viral dose dependent and high-level expression of the target gene could be achieved under the heterogonous *** assay suggested that both Ac-CMV-p35 and Ac-CMV-GFP did not have cytotoxic effect on human embryo kidney 293 *** growth curve showed the Ac-CMV-p35 and Ac-CMV-GFP transduced and non-transduced cells had similar proliferation rate,so baculovirus-mediated p35 expression had no adverse effect on cell *** addition,baculovirus-mediated p35 gene expression protected human embryo kidney 293 cells against apoptosis induced by various apoptosis inducers such as Actinomycin D,UV or serum-free *** results suggested that the baculovirus vector mediated p35 gene expression was functional and it could be widely used in molecular research and even gene therapy.

关键词：细胞凋亡基因治疗 p35基因基因表达胚胎肾细胞杆状病毒

A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma

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Chinese Medical Journal 2016年第24期129卷 2920-2925页

作者： Li Yan yong-liang chen Ming Su Tian Liu Kai Xu Feng liang Wan-Qing Gu Shi-Chun Lu Department of Hepatobiliary Surgery Chinese PLA General Hospital Beijing 100853 China Department of General Surgery People's Hospital of Rizhao Rizhao Shandong 276800 China

Background： Locally advanced pancreatic carcinoma （LAPC） is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation （IRE） has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods： Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results： All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed （16%）： two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions： IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.

关键词： CA 19-9 Irreversible Electroporation Locally Advanced Pancreatic Carcinoma

Safety and feasibility of irreversible electroporation for the pancreatic head in a porcine model

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World Journal of Gastrointestinal Oncology 2022年第8期14卷 1499-1509页

作者： Li Yan Bin liang Jian Feng Hang-Yu Zhang Hao-Sheng Chang Bing Liu yong-liang chen Faculty of Hepato-Pancreato-Biliary Surgery Institute of Hepatobiliary Surgery of Chinese PLAKey Laboratory of Digital Hepetobiliary SurgeryThe First Medical CentreChinese PLA General HospitalBeijing 100853China Department of Hepatopancreatobiliary Surgery Peking University Shougang HospitalBeijing 100144China

BACKGROUND Irreversible electroporation(IRE)is a local non-thermal ablative technique which has been suggested as a potential cancer ***,the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this ***,the safety and feasibility of IRE in the pancreatic head region should be further *** To evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts,vessels,and adjacent gastrointestinal *** Eight landrace miniature pigs underwent IRE of pancreatic head tissue successfully,with a total of 16 lesions *** testing including white blood cell(WBC)count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1,7,14,and 28 d postablation were *** All pigs tolerated the ablation procedure without serious perioperative *** elevated WBC count and amylase were observed at 24 h post-IRE,suggesting an acute pancreatic tissue damage which was confirmed by pathological *** endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling *** was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation,while regeneration of new villous structures were observed at 7 and 28 d ***’s trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts,and even in the *** IRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital ***,risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.

关键词： Irreversible electroporation Pancreatic head Duodenum Safety Feasibility Stress injury

NIR-IIb-triggered photodynamic therapy combined with chemotherapy platform based on rare-earth-doped nanoparticles

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Rare Metals 2024年第7期43卷 3220-3231页

作者： Zhuo Tu yong Wan Juan Ge chen-chen Li Tao liang Zhen Li Chemistry and Chemical Engineering Hubei UniversityWuhan 430062China

Photodynamic therapy(PDT),with high spatiotemporal selectivity,minimal side effects and less drug resistance,has emerged as a promising approach for the treatment of ***,inadequate penetration depth and poor efficacy seriously restrict its practical *** address these challenges,we developed a combined therapy platform(RENP@C/D-FA)based on rare-earth-doped nanoparticles(RENPs)with a structure of NaErF_(4):Tm(0.5%)@NaYF_(4),on which photosensitizer Ce6(chlorin e6)and chemo-therapeutic drug(DOX)(doxorubicin)were loaded by encapsulating with an amphiphilic polymer distearoyl phosphatidylethanolamine-polyethylene glycol-folic acid(DSPE-PEG-FA).RENPs with NaErF_(4) as the matrix possess multiple excitation/emission peaks,enabling activation of PDT under near-infrared-Ⅱb(NIR-Ⅱb,1500-1700 nm)excitation and luminescence imaging in NIR-Ⅱb region by absorbing 808 nm near-infrared ***,DOX can be selectively released in the acidic microenvironment of *** from the tumor targeting capability of folic acid,this platform can successfully ablate tumor cells and inhibit tumor growth by combining PDT and *** innovative approach holds great promise as a powerful tool for cancer treatment,showing the potential to revolutionize PDT.

关键词： Photodynamic therapy Rare-earth-doped nanoparticles NIR-IIb Chemotherapy Combined therapy

Post-pancreaticoduodenectomy hemorrhage:risk factors, managements and outcomes

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Hepatobiliary & Pancreatic Diseases International 2014年第5期13卷 513-522页

作者： Jian Feng yong-liang chen Jia-Hong Dong Ming-Yi chen Shou-Wang Cai Zhi-Qiang Huang Institute of Hepatobiliary Surgery Chinese PLA General Hospital

BACKGROUND： Post-pancreaticoduodenectomy（PD） hemorrhage（PPH） is an uncommon but serious complication. This retrospective study analyzed the risk factors, managements and outcomes of the patients with ***： A total of 840 patients with PD between 2000 and2010 were retrospectively analyzed. Among them, 73 patients had PPH： 19 patients had early PPH and 54 had late *** assessment included the preoperative history of disease,pancreatic status and surgical techniques. Other postoperative complications were also ***： The incidence of PPH was 8.7%（73/840）. There were no independent risk factors for early PPH. Male gender（OR=4.40, P0.02）, diameter of pancreatic duct（OR=0.64,P0.01）, end-to-side invagination pancreaticojejunostomy（OR=5.65, P0.01）, pancreatic fistula（OR=2.33, P0.04）and intra-abdominal abscess（OR=12.19, P0.01） were the independent risk factors for late PPH. Four patients with early PPH received conservative treatment and 12 were treated surgically. As for patients with late PPH, the success rate of medical therapy was 27.8%（15/54）. Initial endoscopy was operated in 12 patients（22.2%）, initial angiography in 19（35.2%）,and relaparotomy in 15（27.8%）. Eventually, PPH resulted in 19 deaths. The main causes of death were multiple organ failure,hemorrhagic shock, sepsis and uncontrolled ***： Careful and ongoing observation of hemorrhagic signs, especially within the first 24 hours after PD or within the course of pancreatic fistula or intra-abdominal abscess, is recommended for patients with PD and a prompt management is necessary. Although endoscopy and angiography are the standard procedures for the management of PPH,surgical approach is still irreplaceable. Aggressive prevention of hemorrhagic shock and re-hemorrhage is the key to treat PPH.

关键词： pancreaticoduodenectomy hemorrhage risk factors management outcome

Portal venous arterialization resulting in increased portal inflow and portal vein wall thickness in rats

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World Journal of Gastroenterology 2008年第43期14卷 6681-6688页

作者： Wen-Gang Li yong-liang chen Jing-Xi chen Lei Qu Bin-Dang Xue Zhi-Hai Peng Zhi-Qiang Huang Department of Hepatobiliary Pancreas and Vessel Surgery Xiamen First Hospital Attached Fujian Medical University Xiamen 361003 Fujian Province China Institute of Hepatobiliary Surgery General Hospital ofPLA Beijing 100853 China Image Processing Centre Beijing University of Aeronautics and Astronautics Beijing 100083 China

AIM： To explore the influence of portal vein hemodynamic changes after portal venous arterialization （PVA） on peribiliary vascular plexus （PVP） morphological structure and hepatic pathology, and to establish a theoretical basis for the clinical application of PVA. METHODS： Sprague-Dawley rats were randomly divided into control and PVA groups. After PVA, hemodynamic changes of the portal vein and morphological structure of hepatohilar PVP were observed using Doppler ultrasound, liver function tests, ink perfusion transparency management and three-dimensional reconstruction of computer microvisualization, and pathological examination was performed on tissue from the bile duct wall and the liver. RESULTS： After PVA, the cross-sectional area and blood flow of the portal vein were increased, and the increase became more significant over time, in a certain range. If the measure to limit the flow in PVA was not adopted, the high blood flow would lead to dilatation of intrahepatic portal vein and its branches, increase in collagen and fiber degeneration in tunica intima. Except glutamic pyruvic transaminase （GPT）, other liver function tests were normal. CONCLUSION： Blood with a certain flow and oxygen content is important for filling the PVP and meeting the oxygen requirement of the bile duct wall. After PVA, It is the anatomic basis to maintain normal morphology of hepatohilar bile duct wall that the blood with high oxygen content and high flow in arterialized portal vein may fill PVP by collateral vessel reflux. A adequate measure to limit blood flow is necessary in PVA.

关键词： Peribiliary vascular plexus Portal venous arterialization Liver transplantation Bile duct neoplasms Three-dimensional reconstruction Hemodynamics

Histological analysis of human pancreatic carcinoma following irreversible electroporation in a nude mouse model

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World Journal of Gastrointestinal Oncology 2018年第12期10卷 476-486页

作者： Jun-Jun Su Kai Xu Peng-Fei Wang Hao-Yun Zhang yong-liang chen Division of Gastroenterological Surgery Depart-ment of SurgeryShanxi Provincial People’s Hospital Department of Hepatobiliary Surgery Chinese People’s Liberation Army General Hospital

AIM To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation(IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment. METHODS IRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining(HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse *** IRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents. CONCLUSION IRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.

关键词： Irreversible electroporation Pancreatic carcinoma Pathological evaluation Transplantation model Nude mouse

Mirizzi syndrome:Problems and strategies

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 234-240页

作者： Jun Wu Shuang-yong Cai Xu-liang chen Zhi-Tao chen Shao-Hua Shi Department of Hepatobiliary and Pancreatic Surgery People’s Hospital of Jiulongpo DistrictChongqing 400050China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310003China

Mirizzi syndrome is a serious complication of gallstone *** is caused by the impacted stones in the gallbladder neck or cystic *** of the features of Mirizzi syndrome is severe inflammation or dense fibrosis at the Calot’s *** our clinical practice,bile duct,branches of right hepatic artery and right portal vein clinging to gallbladder infundibulum are often observed due to gallbladder infundibulum adhered to right hepatic *** intraoperative damage of branches of right hepatic artery occurs more easily than that of bile duct,all of which are hidden pitfalls for *** resonance cholangiopancreatography(MRCP)and endoscopic retrograde cholangiopancreatography(ERCP)are the preferable tools for the diagnosis of Mirizzi *** cholecystectomy in Mirizzi syndrome is easy to damage branches of right hepatic artery and bile duct due to gallbladder infundibulum adhered to right hepatic *** cholecystectomy is an easy,safe and definitive approach to Mirizzi *** combined with the application of ERCP,a laparoscopic management of Mirizzi syndrome by well-trained surgeons is feasible and *** objective of this review was to highlight its existing problems:(1)low preoperative diagnostic rate,(2)easy to damage bile duct and branches of right hepatic artery,and(3)high concomitant gallbladder ***,the review aimed to discuss the possible therapeutic strategies:(1)to enhance its preoperative recognition by imaging findings,and(2)to avoid potential pitfalls during surgery.

关键词： Mirizzi syndrome Bile duct injury Artery injury Surgical treatment Subtotal cholecystectomy