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Melittin analog p5RHH enhances recombinant adeno-associated virus transduction efficiency

Journal of Integrative Medicine 2024年第1期22卷 72-82页

作者： Jing-shun Meng Yun He Heng-bin Yang li-ping zhou Si-yuan Wang Xi-lin Feng Omar Yahya Al-shargi Xiao-min Yu li-qing Zhu Chang-quan ling Shanghai University of Traditional Chinese Medicine Shanghai 201203China Oncology Department of Traditional Chinese Medicine Changhai HospitalNaval Medical UniversityShanghai 200433China Faculty of Traditional Chinese Medicine Naval Medical UniversityShanghai 200043China State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology(Ministry of Education) School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200438China Yantai Fuheng Biological Technology Co. Ltd.YantaiShandong Province 264006China. Department of Clinical Laboratory the First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

Objective Melittin and its derivatives have been characterized to establish effective gene delivery systems.Their capability of facilitating endosomal release enhances the nanoparticles-based gene delivery.Nevertheless,little investigation has been conducted to explore its potential application in the context of viral vectors.Methods Various melittin-derived peptides were inserted into the loop VIII of the capsid proteins of recombinant adeno-associated virus vectors.These vectors carrying either gfp or fluc genes were subjected to qPCR assays and transduction assays of HEK293T cells to investigate the efficiency of vector production and gene delivery.In addition,the ability of a specific p5RHH-rAAV vector to deliver genes was examined through in vitro transduction of different cultured cells and in vivo tail vein administration to C57BL/6 mice.Finally,the intricate details of the vector-mediated transduction mechanisms were revealed by specific pharmacological inhibitors of every stage of the rAAV2 intracellular life cycle.Results A total of 76 melittin-related peptides were compiled from existing literature.Among them,cMA2,Melt13,p5RHH and aAR3 were found to significantly enhance the gene delivery efficiency of rAAV2 vectors.The p5RHH-rAAV2 vectors efficiently transduced not only rAAV-potent cell lines but also cell lines previously considered resistant to rAAV.Mechanistically,bafilomycin A1,a vacuolar endosome acidification inhibitor,completely inhibited the transgene expression mediated by the p5RHH-rAAV2 vectors.Most importantly,p5RHH-rAAV8 vectors also demonstrated increased hepatic transduction in vivo in C57BL/6 mice.Conclusion The incorporation of melittin analogues into the rAAV capsids results in a significant improvement in rAAV-mediated transgene expression.While further modifications remain an area of interest,our studies have substantially broadened the pharmacological prospects of melittin in the context of viral vector-mediated gene delivery.

关键词： Melittin Recombinant adeno-associated virus Capsid engineering Transduction efficiency

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Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats

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Neural Regeneration Research 2022年第11期17卷 2544-2550页

作者： Ci li Song-Yang liu li-ping zhou Tian-Tian Min Meng Zhang Wei Pi Yong-Qiang Wen Pei-Xun Zhang Department of Orthopedics and Trauma Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration Ministry of EducationBeijingChina National Center for Trauma Medicine BeijingChina Beijing Key Laboratory for Bioengineering and Sensing Technology School of Chemistry and Biological EngineeringUniversity of Science and Technology BeijingBeijingChina

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration.However,neurotrophic facto rs are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose,which limits their clinical benefits.Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth fa ctors and can activate the equivalent receptors but have simplified sequences and structures.In this study,we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth fa ctor mimetic peptides(Chi/PDA-Ps).We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides.In this study,we evaluated the biocompatibility of the Chi/P DA-Ps conduits.Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth fa ctor mimetic peptide synergistically promoted prolife ration of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro.The Chi/P DA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury.We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy.The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and re myelination was further resto red.These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

关键词： angiogenesis bioactive peptides nerve repair neurotrophic factor peripheral nerve injury peripheral nerve regeneration polydopamine surface modification synergistic effects tissue engineering

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Clinical diagnosis and treatment of intraorbital wooden foreign bodies

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Chinese Journal of Traumatology 2016年第6期19卷 322-325页

作者： Jia li li-ping zhou Jing Jin Hong-Feng Yuan Department of Ophthalmology Daping Hospital/Research Institute of Surgery Third Military Medical University Chongqing 400042 China

OBJECTIVE:The intraorbital wooden foreign body is often misdiagnosed or missed on computed tomog- raphy (CT) scan, due to the invisible or unclear images. The residual foreign bodies often occur during surgical removal. The clinical manifestations, imaging features and treatment of intraorbital wooden foreign bodies were discussed in this study.;METHODS:We retrospectively analyzed 14 cases of intraorbital wooden foreign bodies managed at our hospital between January 2007 and May 2015. All patients underwent orbital CT examination before surgery, and surgery was performed under general anesthesia with orbital wound debridement and suture, as well as exploration and removal of wooden foreign bodies.;RESULTS:At first, 11 cases underwent removal of foreign bodies, including 1 case with incomplete removal and then receiving a secondary surgery. Foreign bodies were not found in three cases with preoperative misdiagnosis and orbital MRI found residual foreign bodies in the orbit. Operations were performed via primary wound approach in eight cases, conjunctival approach in two cases, and anterior orbitotomy in four cases. Postoperatively, one case was complicated with eye injuries, three cases with ocular muscle injuries, eight cases with visual loss, and eight cases with orbital abscess. The length of foreign bodies ranged from 1.8 cm to 11.0 cm. The maximum of four foreign bodies were removed at the same time.;CONCLUSIONS:Because the imaging of orbital wooden foreign bodies is complex and varied, MRI should be combined when they are invisible on CT scan. At the same time injuries trajectory and clinical mani- festations of patients should be taken into account. Surgical exploration should be extensive and thor- ough, and foreign bodies and orbital abscess must be cleared.

关键词：异物木质临床诊断治疗手术切除 CT检查临床表现 CT扫描

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New indicators in evaluation of hemolysis,elevated liver enzymes,and low platelet syndrome:A case-control study

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World Journal of Clinical Cases 2021年第6期9卷 1259-1270页

作者： Su-Ya Kang Yun Wang li-ping zhou Hong Zhang Department of Obstetrics Suzhou Affiliated Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalSuzhou 215002Jiangsu ProvinceChina Department of Gynecology and Obstetrics The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina

BACKGROUND Indices such as the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),mean platelet volume(MPV),platelet distribution width(PDW),and red cell distribution width(RDW)are considered new markers of the systemic inflammatory response(SIR),and have been widely implemented for the diagnosis of patients with inflammatory diseases.These new indicators have also been widely investigated in preeclampsia(PE)but less analyzed in hemolysis,elevated liver enzymes,and low platelet(HELLP)syndrome.AIM To compare SIR markers among HELLP patients,PE only patients,and healthy gravidae.METHODS This retrospective case-control study enrolled 630 cases,including 210 patients with HELLP syndrome(HELLP group),210 patients with only PE(PE group)and 210 healthy gravidae(control group).The three groups were matched by age,parity,status of assisted reproduction,and multiple pregnancies.Birthweight,gestational age at complete blood count collection,gestational age at delivery,mode of delivery,etc.were recorded.The main indices as NLR,PLR,MPV,PDW,and RDW among the groups were compared,as well as some secondary outcomes including neutrophil,platelets,and hemoglobin.RESULTS The NLR(6.4 vs 4.3 vs 3.5),MPV(11.9 vs 11.2 vs 10.7),PDW(16.4 vs 13.3 vs 14.2),leukocyte(12.4×10^(9)/L vs 9.7×10^(9)/L vs 8.7×10^(9)/L)and neutrophil count(9.9×10^(9)/L vs 7.3×10^(9)/L vs 6.1×10^(9)/L)were highest in the HELLP group,lower in the PE group,and lowest in the control group.Both the overall comparisons between the three groups(all bPlicited statistically significant differences(all dP<0.01,except control vs PE:cP<0.05 in PDW).The average lymphocyte counts were 1.4(1.1,2.0)×10^(9)/L in the HELLP group,1.6(1.3,2.0)×10^(9)/L in the PE group and 1.7(1.4,2.0)×10^(9)/L in the control group.The overall comparison of lymphocyte count within the three groups had statistically significant differences(P=0.000).The pairwise comparisons between every two groups demonstrated that the HELLP gr

关键词： Hemolysis,elevated liver enzymes,and low platelet syndrome Neutrophil-tolymphocyte ratio Platelet-to-lymphocyte ratio Mean platelet volume Platelet distribution width Red cell distribution width

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乙醇催化氧化实验的改进

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化学教育（中英文） 2024年第11期45卷 113-115页

作者：庞立霞李周平滨州市教育科学研究院山东滨州256600 首都师范大学附属滨州中学山东滨州256600

针对教材中乙醇催化氧化实验的不足,对教材中实验进行改进。借助滴有希夫试剂的棉签、铜片和短颈漏斗进行实验。改进后的实验符合科学性、安全性、实用性、节约性等原则。

关键词：无水乙醇铜片希夫试剂实验改进

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Implantable Electrochemical Microsensors for In Vivo Monitoring of Animal Physiological Information

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Nano-Micro Letters 2024年第3期16卷 183-211页

作者： Jin zhou Shenghan zhou Peidi Fan Xunjia li Yibin Ying Jianfeng ping Yuxiang Pan Laboratory of Agricultural Information Intelligent Sensing College of Biosystems Engineering and Food ScienceZhejiang UniversityHangzhou 310058People’s Republic of China ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhou 311200People’s Republic of China

In vivo monitoring of animal physiological information plays a crucial role in promptly alerting humans to potential diseases in animals and aiding in the exploration of mechanisms underlying human diseases.Currently,implantable electrochemical microsensors have emerged as a prominent area of research.These microsensors not only fulfill the technical requirements for monitoring animal physiological information but also offer an ideal platform for integration.They have been extensively studied for their ability to monitor animal physiological information in a minimally invasive manner,characterized by their bloodless,painless features,and exceptional performance.The development of implantable electrochemical microsensors for in vivo monitoring of animal physiological information has witnessed significant scientific and technological advancements through dedicated efforts.This review commenced with a comprehensive discussion of the construction of microsensors,including the materials utilized and the methods employed for fabrication.Following this,we proceeded to explore the various implantation technologies employed for electrochemical microsensors.In addition,a comprehensive overview was provided of the various applications of implantable electrochemical microsensors,specifically in the monitoring of diseases and the investigation of disease mechanisms.Lastly,a concise conclusion was conducted on the recent advancements and significant obstacles pertaining to the practical implementation of implantable electrochemical microsensors.

关键词： Electrochemical microsensors Implantable sensors In vivo monitoring Animal physiological information

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A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus

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Hepatobiliary Surgery and Nutrition 2021年第6期10卷 782-795,I0003-I0005页

作者： Wan Yee Lau Kang Wang Xiu-ping Zhang Le-Qun li Tian-Fu Wen Min-Shan Chen Wei-Dong Jia li Xu Jie Shi Wei-Xing Guo Ju-Xian Sun Zhen-Hua Chen Lei Guo Xu-Biao Wei Chong-De Lu Jie Xue li-ping zhou Ya-Xing Zheng Meng Wang Meng-Chao Wu Shu-Qun Cheng Department of Hepatic Surgery VI Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghaiChina Faculty of Medicine The Chinese University of Hong KongHong KongChina Faculty of Hepato-Pancreato-Biliary Surgery The First Medical Center of Chinese People’s Liberation Army(PLA)General HospitalBeijingChina Department of Hepatobiliary Surgery Affiliated Tumor Hospital of Guangxi Medical UniversityNanningChina Department of liver Surgery&Transplantation Center West China Hospital of Sichuan UniversityChengduChina Department of Hepatobiliary Surgery Sun Yat-sen University Cancer CenterGuangzhouChina Department of General Surgery Affiliated Provincial HospitalAnhui Medical UniversityHefeiChina Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery HefeiChina

Background:A new staging system for patients with hepatocellular carcinoma(HCC)associated with portal vein tumor thrombus(PVTT)was developed by incorporating the good points of the BCLC classification of HCC,and by improving on the currently existing classifications of HCC associated with PVTT.Methods:Univariate and multivariate analysis with Waldχ2 test were used to determinate the clinical prognostic factors for overall survival(OS)in patients with HCC and PVTT in the training cohort.Then the conditional inference trees analysis was applied to establish a new staging system.Results:A training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system.The system was established by incorporating liver function,general health status,tumor resectability,extrahepatic metastasis and extent of PVTT.This staging system had a good discriminatory ability to separate patients into different stages and substages.The median OS for the two cohorts were 57.1(37.2-76.9),12.1(11.0-13.2),5.7(5.1-6.2),4.0(3.3-4.6)and 2.5(1.7-3.3)months for the stages 0 to IV,respectively(Plidation cohort were 6.4(4.9-7.9),2.8(1.3-4.4),10.8(9.3-12.4),and 1.5(1.3-1.7)months for the stages II to IV,respectively(Plished which provided a good discriminatory ability to separate patients into different stages and substages after treatment.It can be used to supplement the other HCC staging systems.

关键词： Hepatocellular carcinoma(HCC) portal vein tumor thrombus(PVTT) staging system overall survival(OS)

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Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative Medicine 2024年第2期22卷 188-198页

作者： Meng li Yang zhou Hui Zhu lie-ming Xu Jian ping Institute of liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of Traditional Chinese Medicine Shanghai 201203China Key Laboratory of liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver fibrosis.Methods:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver fibrosis.DHQ was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related proteins.Real-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-mice.In addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 expression.Cholangiocytes overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell activation.The intervention effect of DHQ on these processes was also investigated.HSCs overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of DHQ.Results:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 phosphorylation.This formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in HSCs.The overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these effects.Conclusion:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Mdr2-/-mice by inhibiting H19 upregulation in chol

关键词： liver cirrhosis biliary Long non-coding RNA H19 Danhongqing formula Cholangiocyte Hepatic stellate cells STAT3 transcription factor

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Spherical Confinement Generates Entropic Force to Accelerate Polymer Chain Detachment

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Chinese Journal of Polymer Science 2024年第3期42卷 407-416,I0010页

作者： Yu-Shan Zheng Jian-ping zhou Yan Xu Kai li Mechanical Engineering Xinjiang UniversityUrumqi 830002China

To understand the dynamic process of polymer detachment, it is necessary to determine the mean detachment time of a single breakable link, which is modeled as a spring. Normally, this time can be viewed as the escape of a Brownian particle from the potential well of the spring. However, as the free dangling length of the polymer chain increases, the conformational entropy of the chain is affected by geometric confinement. It means that the wall exerts a repulsive force on the chain, resulting in accelerated link detachment from a macroscopic perspective. In this work, we investigate the effect of entropy on the detachment rate in the case where the substrate is spherical. We demonstrate that spherical confinement accelerates chain detachment both inside and outside the sphere. An analytical expression for the mean detachment time of breakable links is given, which includes an additional pre-factor that is related to the partition function. Additionally, we analyze the expressions for entropic forces inside the sphere, outside the sphere, and on a flat wall, comparing their magnitudes to explain the difference in mean detachment time.

关键词： Polymer detachment Breakable link Entropic force Mean first passage time

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Precision targeting in hepatocellular carcinoma:Exploring ligandreceptor mediated nanotherapy

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World Journal of Hepatology 2024年第2期16卷 164-176页

作者： Xia-Qing zhou Ya-ping li Shuang-Suo Dang Department of Infectious Diseases Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710004Shaanxi ProvinceChina

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.

关键词： Targeting Hepatocellular carcinoma Receptor Nanomedicine Chemotherapy

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