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Genes & Diseases 2023年第6期10卷 2622-2638页

作者： feng Wang Shitong Chen Shihan Peng Xujun Zhou Houyi Tang Hanghua Liang Xi Zhong He Yang Xiaoxue Ke MuHan Lü Hongjuan Cui State Key Laboratory of Silkworm Genome Biology Southwest UniversityChongqing 400716China Department of Gastroenterology The Affiliated Hospital of Southwest Medical University25 Taiping StreetJiangyang DistrictLuzhouSichuan 646000China Cancer Center Medical Research InstituteSouthwest UniversityChongqing 400716China Jinfeng Laboratory Chongqing 401329China

Protein arginine methyltransferase 1(PRMT1),a type I PRMT,is overexpressed in gastric cancer(GC)cells.To elucidate the function of PRMT1 in GC,PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA(shRNA)or inhibited by PRMT1 inhibitors(AMI-1 or DCLX069),which resulted in inhibition of GC cell proliferation,migration,invasion,and tumorigenesis in vitro and in vivo.MLX-interacting protein(MLXIP)and Kinectin 1(KTN1)were identified as PRMT1-binding proteins.PRMT1 recruited MLXIP to the promoter ofβ-catenin,which inducedβ-catenin transcription and activated theβ-catenin signaling pathway,promoting GC cell migration and metastasis.Furthermore,KTN1 inhibited the K48-linked ubiquitination of PRMT1 by decreasing the interaction between TRIM48 and PRMT1.Collectively,our findings reveal a mechanism by which PRMT1 promotes cell proliferation and metastasis mediated by theβ-catenin signaling pathway.

关键词： β-catenin signaling pathway Gastric cancer PRMT1 Transcriptional regulation Ubiquitination

Laboratory Safety of dupilumab,and Its Effect on Inflammatory Biomarkers,in Chinese Adults With Moderate-to-Severe Atopic Dermatitis:An Analysis of a Randomized,Double-Blind Phase III Study

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International Journal of Dermatology and Venereology 2022年第4期5卷 218-225页

作者： Yan Zhao Li-Ming Wu Qian-Jin Lu Xing-hua Gao Xiao-Hong Zhu Xu Yao Lin-feng Li Wei Li Yang-feng Ding Zhi-Qiang Song Ling-Ling Liu Ning-Ning Dang Chun-Lei Zhang Xiao-Ming Liu Jun Gu Jin-Yan Wang Song-Mei Geng Quan-Zhong Liu Yi-feng Guo Li Dong Shelley Li Christine Xu John T.O’Malley Elizabeth Laws Nikhil Amin Ashish Bansal Min Wang Jian-Zhong Zhang Department of Dermatology Peking University People’s HospitalBeijing 100044China Hangzhou First People’s hospital HangzhouZhejiang 310006China The Second Xiangya hospital of Central South University ChangshaHunan 410011China The First hospital of China Medical University ShenyangLiaoning 110001China Wuxi Second People’s hospital WuxiJiangsu 214002China hospital for Skin Diseases Institute of DermatologyChinese Academy of Medical SciencesNanjingJiangsu 210042China Beijing Friendship hospital Capital Medical UniversityBeijing 100050China huashan hospital Fudan UniversityShanghai 200040China Shanghai Skin Disease hospital Shanghai 200040China The southwest hospital of AMU Chongqing 400038China Peking University First hospital Beijing 100034China Jinan Central hospital JinanShandong 250013China Peking University Third hospital Beijing 100191China University of Hong Kong-Shenzhen hospital ShenzhenGuangdong 518040China Changhai hospital of Shanghai Shanghai 200433China Ningbo No.2 hospital NingboZhejiang 315099China The Second Affiliated hospital of Xi’an Jiaotong University Xi’anShaanxi 710004China Tianjin Medical University General hospital Tianjin 300052China Xinhua hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200092China Research&Development SanofiBridgewaterNJ 08807USA Research&Development RegeneronTarrytownNY 10591USA Medical Sanofi ChinaShanghai 200040China.

Objective:Limited information is available on the use of dupilumab for the treatment of atopic dermatitis(AD)in the Chinese population.Methods:We analyzed laboratory data from a previously published randomized,double-blind phase III trial(NCT03912259)to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD.The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks.Hematology,blood chemistry,serum thymus and activation-regulated chemokine(TARC),and total immunoglobulin E(IgE)were evaluated.Results:In total,82 participants received dupilumab and 83 received placebo.With the exception of eosinophil counts of>0.8×109/L,which were found less frequently with dupilumab(9.8%)than with placebo(18.7%),the hematology and blood chemistry values were generally stable in both treatment groups.There were no clinically significant differences between the dupilumab and placebo groups,and no participants developed treatment-emergent abnormalities of potential clinical significance.However,compared with placebo,greater decreases in serum lactate dehydrogenase(mean change,−97.4 vs.−33.5 IU/L),TARC(median percent change,−78.6%vs.−30.8%),and total IgE(median percent change,−53.4%vs.−0.2%)were observed with dupilumab than placebo at week 16.Conclusion:dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.

关键词： atopic dermatitis dupilumab laboratory safety Chinese

Effects of preconditioning with hyperbaric oxygen on expression of GFAP and Nestin after spinal cord injury in rats

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Effects of preconditioning with hyperbaric oxygen on express...

第十六届国际高气压医学学术会议暨第十七届全国高压氧医学...

作者： Peigang Lu hua feng Yongzhi Xia Weihua Chu Guoqi Gong Department of Neurosurgery southwest hospital Third Military Medical University

＜正＞Objective:To study the effects of preconditioning with hyperbaric oxygen on expression of GFAP and Nestin after spinal cord injury in rats at different time.Methods:fifty-five adult Sprague-Dawley adult rats, weighing from 250 to 300g,were randomly divided into 3 groups,hyperbaric oxygen preconditional group（25,n=5）,normal injury group（25,n=5）and control group（5,n=5）.In the experimental groups,the rat

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降钙素原在化脓性脊柱炎中的诊断价值分析

实用医院临床杂志 2024年第3期21卷 30-33页

作者：包羽生雷飞周庆忠冯大雄西南医科大学附属医院骨科四川泸州646000

目的探讨降钙素原(PCT)对化脓性脊柱炎(PS)的诊断价值。方法收集2022年1月至2023年12月我院确诊的PS患者96例(A组)、脊柱结核(TBS)91例(B组)及骨质疏松性压缩骨折(OVCF)100例(C组)的PCT、C反应蛋白(CRP)、红细胞沉降率(ESR)检测结果,比... 详细信息

目的探讨降钙素原(PCT)对化脓性脊柱炎(PS)的诊断价值。方法收集2022年1月至2023年12月我院确诊的PS患者96例(A组)、脊柱结核(TBS)91例(B组)及骨质疏松性压缩骨折(OVCF)100例(C组)的PCT、C反应蛋白(CRP)、红细胞沉降率(ESR)检测结果,比较三者分别与联合检测对PS、TBS、OVCF诊断敏感度和特异性。计算ROC曲线下面积(AUC),评估三者分别与联合对化脓性脊柱炎的诊断价值。结果C组的发病年龄明显大于A、B组(P0.05);三组PCT、CRP及ESR检测值均数比较差异有统计学意义(PB组>C组。A组的PCT、CRP、ESR特异度为77.5%、64.4%、57.1%、联合诊断82.7%,敏感度为80.2%、88.5%、88.5%、联合诊断94.7%,AUC分别为0.820、0.720、0.779、联合诊断0.804,均有诊断价值(AUC>0.5),其中,PCT>ESR、PCT>CRP、三者联合>CRP(P0.05)。B组PCT、CRP、ESR的特异度为59.2%、51.0%、49.0%、联合诊断75.2%,敏感度为43.9%、62.6%、73.6%、联合诊断81.3%,AUC分别为0.740、0.664、0.624、联合诊断0.663,均有诊断价值(AUC>0.5),其中,PCT>ESR、PCT>CRP、PCT>三者联合(P0.05)。结论(1)PCT、CRP、ESR及三者联合在诊断PS均具有一定的临床价值,PCT和PCT联合CRP、ESR对PS诊断的特异性优于CRP、ESR。(2)PCT和PCT联合CRP、ESR对PS鉴别TBS及OVCF均有较高的诊断效能。

关键词：化脓性脊柱炎脊柱结核骨质疏松性压缩骨折 C反应蛋白红细胞沉降率降钙素原

ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro

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Neural Regeneration Research 2016年第6期11卷 983-987页

作者： Xu-feng Jia Fei Ye Yan-bo Wang Da-xiong feng Department of Orthopedic Surgery Jianyang People's Hospital of Sichuan Province lianyang Sichuan Province China Department of Spine Surgery the Affiliated Hospital of Southwest Medical University Luzhou Sichuan Province China

Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase （ROCK） pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway.

关键词： nerve regeneration spinal cord injury neural stem cells Rho signalingpathway neurite outgrowth myelin YAP neural regeneration

Competing endogenous RNAs in lung cancer

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Cancer Biology & Medicine 2021年第1期18卷 1-20页

作者： Meilian Zhao Jianguo feng Liling Tang Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China Department of Anesthesiology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

Competing endogenous RNAs(ce RNAs)containing micro RNA response elements can competitively interact with micro RNA via mi RNA response elements,which can combine non-coding RNAs with protein-coding RNAs through complex ce RNA networks.Ce RNAs include non-coding RNAs(long non-coding RNAs,circular RNAs,and transcribed pseudogenes)and protein-coding RNAs(m RNAs).Molecular interactions in ce RNA networks can coordinate many biological processes;however,they may also lead to ce RNA network imbalance and thus contribute to cancer occurrence when disturbed.Recent studies indicate that many dysregulated RNAs derived from lung cancer may function as ce RNAs to regulate multitudinous biological functions for lung cancer,including tumor cell proliferation,apoptosis,growth,invasion,migration,and metastasis.This study therefore reviewed the research progress in the field of non-coding and protein-coding RNAs as ce RNAs in lung cancer,and highlighted validated ce RNAs involved in biological lung cancer functions.Furthermore,the roles of ce RNAs as novel prognostic and diagnostic biomarkers were also discussed.Interpreting the involvement of ce RNAs networks in lung cancer will provide new insight into cancer pathogenesis and treatment strategies.

关键词： CeRNA lung cancer biological functions biomarker

MiR-214-3p Prevents the Development of Perioperative Neurocognitive Disorders in Elderly Rats

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Current Medical Science 2022年第4期42卷 871-884页

作者： Yu-hao WANG Yong-wang CHEN Wan-li XIAO Xue-lian LI Lan feng Yu-lin LIU Xiao-xia duAN Department of Anesthesiology the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China Laboratory of Anesthesiology Southwest Medical UniversityLuzhou 646000China Department of Anesthesiology Southwest Medical UniversityLuzhou 646000China

Objective:This study aimed to identify microRNAs(miRNAs)involved in the development of perioperative neurocognitive disorders(PND).Methods:Plasma exosomal miRNA expression was examined in patients before and after cardiopulmonary bypass(CPB)using microarray and qRT-PCR and these patients were diagnosed as PND later.Elderly rats were subjected to CPB,and the cognitive functions were examined.Bioinformatics analysis was conducted to predict the targets of miR-214-3p.Rats were administered rno-miR-214-3p agomir before or after CPB to investigate the role of miR-214-3p in PND development.Results:We identified 76 differentially expressed plasma exosomal miRNAs in PND patients after surgery(P0.58),including the upregulated hsa-miR-214-3p(P=0.002399392).Prostaglandin-endoperoxide synthase 2(PTGS2)was predicted as a miR-214-3p target.In rats,CPB reduced the platform crossing numbers and target quadrant stay time,accompanied with hippocampal neuronal necrosis.The rno-miR-214-3p level was significantly increased in plasma exosomes but decreased in rat hippocampus after surgery,exhibiting a negative correlation(P<0.001,r=-0.762).A negative correlation between miR-214-3p and PTGS2 protein expression was also observed in the hippocampus after surgery.Importantly,rno-miR-214-3p agomir treatment,before or after surgery,significantly increased the platform crossing numbers(P=0.035)and target quadrant stay time(P=0.029)compared with negative control.Hippocampal PTGS2 protein level was increased in the untreated surgery group and decreased in response to rno-miR-214-3p agomir treatment before or after surgery(both P<0.05 vs.negative control).Conclusion:These data suggest that miR-214-3p/PTGS2 signaling contributes to the development of PND,serving as a potential therapeutic target for PND.

关键词： perioperative neurocognitive disorder sexosome hippocampus miR-214-3p prostaglandin-endoperoxide synthase 2

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基于跨任务一致性的半监督肝脏CT图像分割

计算机技术与发展 2024年第2期34卷 65-70页

作者：李明漾王庆凤陈立伟黄俊周莹西南科技大学计算机科学与技术学院四川绵阳621000 绵阳市中心医院放射科四川绵阳621000

目前基于深度学习的医学图像分割方法往往需要大量带标记数据训练网络模型,然而医学影像的标记数据获取通常非常昂贵,半监督学习能使模型利用大量未标记数据和少量标记数据学习。该文提出了一种基于跨任务一致性的半监督学习框架来降低... 详细信息

目前基于深度学习的医学图像分割方法往往需要大量带标记数据训练网络模型,然而医学影像的标记数据获取通常非常昂贵,半监督学习能使模型利用大量未标记数据和少量标记数据学习。该文提出了一种基于跨任务一致性的半监督学习框架来降低神经网络模型训练时需要的标记数据成本。该方法利用V-Net网络作为主干框架并添加两个辅助解码器,同时在解码器中引入一个辅助回归任务,提高模型分割性能,并在主副解码器的分割任务和回归任务之间施加正则化约束的跨任务一致性损失,该框架能够学习到大量未标记数据的几何先验信息。在LiTS2017 Challenges数据集上验证了该方法的有效性。在使用20%标记数据的实验中,该方法的Dice系数和Jaccard指数分别达到了93.95%和88.87%,相比全监督V-Net网络模型训练下的Dice系数和Jaccard系数分别提高了3.60百分点和5.78百分点。实验结果表明,该方法在使用少量带标记数据情况下达到接近100%带标记数据训练分割肝脏的精度,与其他的半监督方法相比分割精度更优。

关键词：医学影像半监督学习神经网络回归任务一致性损失

Current strategies for improving limitations of proteolysis targeting chimeras

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Chinese Chemical Letters 2023年第6期34卷 144-156页

作者： Chunlan Pu Shirui Wang Lei Liu Zhonghui feng Hongjia Zhang Qianyuan Gong Yueshan Sun Yuanbiao Guo Rui Li Medical Research Center The Third People’s Hospital of ChengduThe Affiliated Hospital of Southwest Jiaotong UniversityThe Second Chengdu Hospital Affiliated to Chongqing Medical UniversityChengdu 610031China State Key Laboratory of Biotherapy Collaborative Innovation Center of Biotherapy and Cancer CenterWest China Hospital of Sichuan UniversityChengdu 610041China

Proteolysis targeting chimeras(PROTACs)are bifunctional degrader molecules via hijacking the ubiquitinproteasome system(UPS)to specifically eliminate targeted proteins.PROTACs have gained momentum as a new modality of attractive technologies in the drug discovery landscape,since it allows to degrade disease-related proteins effectively.Although some PROTACs drugs reached the clinical research,they are still facing some bottlenecks and challenges that should not be neglected,such as poor oral bioavailability and potential toxic side effects.To overcome these limitations,herein,we provide an overview of recent strategies for improving the durability of PROTACs by enhancing cell permeability and reducing toxic side effects.Meanwhile,the impact of these strategies on improving oral bioavailability as well as their advantages and drawbacks will also be discussed.This review will give a useful reference toolbox for PROTACs design and further promote its clinical application.

关键词： PROTACs Targeted protein degradation Oral bioavailability Cell permeability Tumor targeting

A clinical study on salvage hepatectomy for treating recurrent liver cancer after radiofrequency ablation

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Oncology and Translational Medicine 2015年第6期1卷 256-260页

作者： Qing Xiong Xiaobin feng Jun Yan feng Xia Xiaowu Li Kuansheng Ma Ping Bie Institute of Hepatobiliary Surgery Southwest Hospital Third Military Medical University

Objective We studied the efficacy of salvage hepatectomy for treating recurrent hepatic cancer after radiofrequency ablation(RFA). Methods A retrospective analysis of 67 patients who had recurrent liver cancer after RFA treatment and received salvage hepatectomy in the Department of Hepatobiliary Surgery, southwest hospital, Third Military Medical University(China), from January 2006 to January 2014, was performed. The analysis included patient gender, age, hepatitis type, alpha-fetoprotein(AFP), and TNM stage prior to RFA and salvage hepatectomy, overall survival rates, and tumor-free survival rates after salvage hepatectomy. Results Among the 67 patients, there were 57 cases of hepatitis B, two cases of hepatitis C, and eight cases did not have hepatitis. AFP levels in patients ranged from 3 to 4521 ng/m L(median 33 ng/m L). Before RFA, 54 cases were stage I tumors, and 13 were stage II tumors. Tumor sizes varied from 0.82 to 4.83 cm(median 3.0 cm). In 20 cases, one RFA was performed, and for 47 cases, RFA was repeated. RFAablated region diameters ranged from 3.8 to 5.2 cm(median 4.5 cm). The interval between the salvage surgical resection and RFA was 3–37 months. Before salvage hepatectomy, 23 stage I tumors, 12 stage II tumors, and 32 stage III tumors were present(size ranged 4.83–11.84 cm; median 6.3 cm). For salvage hepatectomy, laparotomy was performed for 56 cases, and laparoscopy was performed for 28 cases. Inflow clamping was performed for 39 cases(15–45 min). Surgery was 219–370 min and intraoperative blood loss was 100–2100 m L. For 13 cases, intraoperative blood transfusion was required. Tumor pathological data revealed 31, 35, and 1 poorly, moderately, and well differentiated tumors, respectively. No patients died due to operative complications, and hospital stays were 8–10 days. Overall and tumor-free survival rates were 85% and 79% for 1 year, 50% and 20% for 3 years, and 39% and 19% for 5 years, respectively. KaplanMeier analysis and Cox regression confirmed that tumor number and size prior to sa

关键词：抢救治疗切除术肝癌复发临床射频消融手术切除丙型肝炎