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Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma:A single-arm, multicenter, prospective study

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Hepatobiliary & Pancreatic Diseases International 2022年第2期21卷 106-112页

作者： Ren-Yi Su Sun-Bin Ling qiao-Nan Shan Xu-Yong Wei Rui Wang Chang-Ku Jia Li Zhuang Tian Shen Li-Min Ding Zhi-Dan Xu Lai-Bang luo Li-Bo Sun Guang-Ming Li Tai-Shi Fang Nan Jiang Kun Zhang Zhao-jie Su Zhi-Hai Peng Ren Lang Tao Jiang qiang He Lin-Sen Ye Yang Yang Yu-Ting He Wen-Zhi Guo Liu-Gen Lan Xu-Yong Sun Dong Chen Zhi-Shui Chen Da-Wei Zhou Shao-Jun Ye qi-Fa Ye Min Tian Jian-Hua Shi Bo Wang Jiang Liu qian Lu Wei Rao Jin-Zhen Cai Tao Lv Jia-Yin Yang Pu-Sen Wang Lin Zhong Jing-Sheng Ma qi-Gen Li Sheng-Dong Wu Chang-Jiang Lu Cai-De Lu Dong-Hua Zhang Xuan Wang Zi-qiang Li Mu-Jian Teng Jun-jie Li Wen-Tao Jiang Jian-Hua Li Quan-Bao Zhang Ning-qi Zhu Zheng-Xin Wang Kang He qiang Xia Shao-Hua Song Zhi-Ren Fu Wei qiu Guo-Yue Lv Rui-Peng Song Ji-Zhou Wang Zheng Wang Jian Zhou Gang Chen Ying-Peng Zhao Li Li Ze-Min Hu qi-jie luo Zhong-Zhou Si Bin Xie Xiao-Shun He Zhi-Yong Guo Shu-Sen Zheng Xiao Xu Department of Hepatobiliary and Pancreatic Surgery The Center for Integrated Oncology and Precision MedicineAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalZhejiang Shuren University School of MedicineHangzhou 310022China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Transplantation Jiangxi Provincial People’s Hospital Affiliated to Nanchang UniversityNanchang 330006China Liver Transplantation Center Beijing You’an HospitalCapital Medical UniversityBeijing 100069China Department of Hepatic Surgery National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyShenzhen 518112China Department of General Surgery Xiang’an Hospital of Xiamen UniversityXiamen 361000China Deartment of Hepatobiliary and Pancreaticosplenic Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China Department of Hepatic Surgery and Liver Transplantation Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Liver Transplantation The Second Affiliated Hospital of Guangxi Medical UniversityNanning 530000China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Institute of Hepatobiliary Diseases of Wuhan University Transplant Center of Wuhan UniversityHubei Key Laboratory of Medical Technology on TransplantationZhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Hepatobiliary Surgery The First Affiliated Hos

Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.

关键词： Sirolimus Immunosuppressive agents Hepatocellular carcinoma Liver transplantation Conversion

Social function scores and influencing factors in patients with residual depressive symptoms

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World Journal of Psychiatry 2025年第1期15卷 117-127页

作者： Zong-Ling Liao Xiao-Li Pu Zhi-Yi Zheng jie luo Department 1 of Psychiatry Gele Mountain Hospital of Chongqing Mental Health CenterChongqing 400030China Department of Psychology Chongqing Jiangjin District Psychiatric HospitalChongqing 402260China Department of Psychiatry Chongqing Third Social Welfare InstituteChongqing 400036China Women and Children’s Mental Health Center Affiliated Hospital of Chongqing Population and Family Planning Research InstituteChongqing 400020China

BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still *** depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on *** the influencing factors of their social function is of great *** To explore the social function score and its influencing factors in patients with residual depressive *** This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December *** functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between *** influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±*** with the control group,the SDS scores and all items in the case group were *** scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥*** history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.C

关键词： Depressive Residual symptoms Social function Influence factors

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie qi Jinrong Lin Yaying Sun jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

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Neural Regeneration Research 2025年第3期20卷 845-857页

作者： Lin-Yan Huang Yi-De Zhang jie Chen Hai-Di Fan Wan Wang Bin Wang Ju-Yun Ma Peng-Peng Li Hai-Wei Pu Xin-Yian Guo Jian-Gang Shen Su-Hua qi School of Medical Technology Xuzhou Key Laboratory of Laboratory DiagnosticsXuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Pharmacy Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Laboratory Medicine Branch Hospital of Huai’an First People’s HospitalHuai’anJiangsu ProvinceChina Department of Laboratory Medicine the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina School of Chinese Medicine The University of Hong KongHong Kong Special Administrative RegionChina

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late ***,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain *** previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently *** simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic *** found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous ***,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid *** results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/***,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and *** suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion *** levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-*** transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear ***,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

关键词： cell differentiation cerebral ischemia/reperfusion injury chlorination hypochlorous acid microglia neural stem cell neurogenesis nuclear translocation stroke β-catenin

A general framework for computing maximal contractions

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Frontiers of Computer Science 2013年第1期7卷 83-94页

作者： jie luo State Key Laboratory of Software Development Environment School of Computer Science and Engineering Beihang University Beijing 100191 China

This paper investigates the problem of computing all maximal contractions of a given formula set F with re- spect to a consistent set A of atomic formulas and negations of atomic formulas. We first give a constructive definition of minimal inconsistent subsets and propose an algorithmic framework for computing all minimal inconsistent subsets of any given formula set. Then we present an algorithm to com- pute all maximal contractions from minimal inconsistent sub- sets. Based on the algorithmic framework and the algorithm, we propose a general framework for computing all maximal contractions. The computability of the minimal inconsistent subset and maximal contraction problems are discussed. Fi- nally, we demonstrate the ability of this framework by apply- ing it to the first-order language without variables and design an algorithm for the computation of all maximal contractions.

关键词： maximal contraction minimal inconsistent sub- set computability algorithms

Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

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Nano Research 2025年第1期18卷 607-617页

作者： Ruo-Lin Jiang Hui-Na Liu Yu-Fan Yang Zhi-Cheng Zhang qi Dai Xiao-Yan Bao Lin-jie Wu Ya-Xin qin Xin Tan Xiao-Yan Sun Xu-Fang Ying Zhi-qing Ben Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Polytechnic institute Zhejiang UniversityHangzhou 310015China

Traditionally,hyaluronic acid has been widely used for drug delivery,but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative,which makes it difficult to carry hydrophobic drugs and small interfering RNA(siRNA)with the same *** on previous studies,we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP(HSTD)for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic ***,N,N,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting ***,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.

关键词： zwitterionic hyaluronic acid N N N-trimethylcystamine small interfering RNA(siRNA) doxorubicin

1-methyl-4-phenylpyridinium ion induces endoplasmic reticulum stress through glycogen synthase kinase-3 beta activation in PC12 cells

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Neural Regeneration Research 2011年第11期6卷 805-810页

作者： Shengdong Wang Fucheng luo Yan Chen Lei qi jie Bai College of Life Science and Technology Kunming University of Science and Technology Kunming 650224 Yunnan Province China

1-methyl-4-phenylpyridinium ion （MPP^＋） induces endoplasmic reticulum stress and activates caspase-12 in PC12 cells, leading to neuronal apoptosis. However, the underlying molecular mechanism remains unknown. The present study investigated the regulatory effects of nerve growth factor （Akt activator） and lithium chloride （glycogen synthase kinase-3β inhibitor） on the endoplasmic reticulum stress signaling pathway. The results revealed that MPP＋ induced expression of Bip and C/EBP homologous protein. The upregulation of Bip and C/EBP homologous protein, as well as the decreased pro-caspase-12 level induced by MPP^＋ were inhibited by pretreatment of the nerve growth factor or lithium chloride. These results suggest that the phosphatidylinositol 3 kinase-Aktglycogen synthase kinase-3β pathway is involved in MPP-induced endoplasmic reticulum stress.

关键词： Parkinson's disease 1-methyl-4-phenylpyridinium ion endoplasmic reticulum stress glycogen synthase kinase-3β

Molecular dynamics simulation and micropillar compression of deformation behavior in iridium single crystals

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Rare Metals 2023年第10期42卷 3510-3517页

作者： Jia-qi Wu Rui Hu jie-Ren Yang Bin Gan Gong-Liao luo Yi Liu Xi-Ming luo State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an710072China State Key Laboratory of Advanced Technologies for Comprehensive Utilization of Platinum Metal Sino-platinum Metals Co.Ltd.Kunming Institute of Precious MetalsKunming650106China

The compression behaviors of iridium single crystals with different crystalline orientations were investigated by micropillar compression tests and molecular dynamics(MD) *** results indicated that the deformation process of iridium single crystals with [100]and [110] orientations was presented as the stacking faults expansion and the formation of Lomer-Cottrell *** the occurrence of Lomer-Cottrell locks was considered as the interaction of stacking faults on {111} planes by MD *** evolution of crystal structure in compression indicated that the Lomer-Cottrell locks might contribute to the large plastic deformation of iridium single ***,the deformation features in MD simulations showed that the elastic modulus(E) and yield stress(σ_(s)) of iridium single crystals were significantly influenced by the *** elastic modulus and yield stress gradually decreased with an increased temperature for all ***,the single crystal with a closely spaced lattice structure exhibited superior mechanical properties at a same temperature.

关键词： Iridium single crystal Crystalline orientation Deformation behavior Molecular dynamics Micropillar compression

Precision regulation of plant aromatic amino acid homeostasis

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Science China(Life Sciences) 2024年第6期67卷 1316-1317页

作者： jie luo Yazhouwan National Laboratory(YNL) Sanya 572025China School of Breeding and Multiplication(Sanya Institute of Breeding and Multiplication) Hainan UniversitySanya 572025China

The aromatic amino acids(AAAs)phenylalanine(Phe),tyrosine(Tyr),and tryptophan(Trp)are not only building blocks of proteins,but also precursors of numerous primary and specialized metabolites(Schenck and Maeda,2018).For instance,Trp is a precursor of the phytohormone auxin and the plant defense compounds indole glucosinolates,while Phe serves as a precursor of lignin,coumarin and *** plant natural products such as morphine and vitamin E are derived from Tyr,and have been employed in human medicine and nutrition(Schenck and Maeda,2018;Wu et al.,2022;Yokoyama et al.,2021).

关键词： aromatic instance coumarin