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Investigation of the feasibility of NRAV as a biomarker for hepatocellular carcinoma

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Oncology Research 2024年第4期32卷 717-726页

作者： JUN LIU WENLI LI RUYUE LU JIAQING XU CHUNHUI JIANG JUNLIN DUAN LINGZHI ZHANG GUANFU WANG JIAXI CHEN Department of Clinical laboratory Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical UniversityLinhaiChina Key laboratory of system Medicine and Precision diagnosis and treatment of Taizhou TaizhouChina Department of Clinical laboratory Dongguan Hospital of Traditional Chinese MedicineDongguanChina School of Basic Medical Sciences Forensic Medicine Hangzhou Medical CollegeHangzhouChina

The long non-coding RNA,Negative Regulator of Antiviral Response(NRAV)has been identified as a participant in both respiratory virus replication and immune checkpoints,however,its involvement in pan-cancer immune regulation and prognosis,particularly those of hepatocellular carcinoma(HCC),remains unclear.To address this knowledge gap,we analyzed expression profiles obtained from The Cancer Genome Atlas(TCGA)database,comparing normal and malignant tumor tissues.We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues.Kaplan-Meier(K-M)analysis revealed the prognostic power of NRAV,wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients.Furthermore,noteworthy associations were observed between NRAV,immune checkpoints,immune cell infiltration,genes related to autophagy,epithelial-mesenchymal transition(EMT),pyroptosis,tumor mutational burden(TMB),and microsatellite instability(MSI)across different cancer types,including HCC.Moreover,NRAV upregulation expression was associated with multiple pathological stages by clinical observations.Furthermore,our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells.The inhibition of NRAV resulted in the inhibition of cell proliferation,migration,and invasion in HCC cells,while also influencing the expression of CD274(PD-L1)and CD44,along with various biomarkers associated with EMT,autophagy,and pyroptosis.The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.

关键词： NRAV Hepatocellular carcinoma Prognosis Biomarker Pan-cancer

Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第1期18卷 68-80页

作者： Yanling Liu Xi He Yanchun Yuan Bin Li Zhen Liu Wanzhen Li Kaixuan Li Shuo Tan Quan Zhu Zhengyan Tang Feng Han Ziqiang Wu Lu Shen Hong Jiang Beisha Tang Jian Qiu Zhengmao Hu Junling Wang Department of Neurology Xiangya HospitalCentral South UniversityJiangxiNational Regional Center for Neurological DiseasesNanchang330038China provincial laboratory for diagnosis and treatment of genitourinary system disease Department of UrologyXiangya HospitalCentral South UniversityChangsha410078China Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhou310002China Department of Neurology Xiangya HospitalCentral South UniversityChangsha410078China National Clinical Research Center for Geriatric diseases Xiangya HospitalCentral South UniversityChangsha410008China Key laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha410008China Center for Medical Genetics School of Life SciencesCentral South UniversityChangsha410008China Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha410078China Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic diseases Changsha410078China Hunan Key laboratory of Molecular Precision Medicine Xiangya HospitalCentral South UniversityChangsha410078China

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons,and it demonstrates high clinical heterogeneity and complex genetic architecture.A variation within TRMT2B(c.1356G>T;p.K452N)was identified to be associated with ALS in a family comprising two patients with juvenile ALS(JALS).Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS,and three more variants were identified in a public ALS database including 3317 patients with ALS.A decreased number of mitochondria,swollen mitochondria,lower expression of ND1,decreased mitochondrial complex I activities,lower mitochondrial aerobic respiration,and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 cells.Further,TRMT2B variations overexpression cells also displayed decreased ND1.In conclusion,a novel JALS-associated gene called TRMT2B was identified,thus broadening the clinical and genetic spectrum of ALS.

关键词： TRMT2B amyotrophic lateral sclerosis mitochondrial complex I tRNA methylation reactive oxygen species

Intraperitoneal injection but not oral administration of ellagic acid: A novel immunomodulator via targeting casein kinase 2 signaling pathway

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Food Science and Human Wellness 2024年

作者： Wen-Hui Qi Bing Han Ting-Ting Cui Pei-Xin Shen Zhuo-Hua Zhao Ya-Ping Yan Li-Bin Wang Xin-Yu Lu Yuan Zhang Xing Li Key laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University) The Ministry of Education College of Life Sciences Shaanxi Normal University Department of Pharmacology School of Pharmacy Fourth Military Medical University The Nervous system disease diagnosis and treatment Engineering Technology Research Center of Ningxia School of Medical Technology Xi'an Medical University

Immunosuppressants currently approved for the treatment of autoimmune diseases and organ transplant rejection present diverse adverse effects that impair the life quality of patients. Therefore， the development of novel immunomodulators with high efficiency and low toxicity is essential. Ellagic acid (EA)， a natural polyphenol compound widely distributed in berries， is metabolically transformed by gut microbiome to exert systemic health benefits. Here， we identified that intraperitoneal administration of EA with no cytotoxicity， beyond its well-known oral metabolic fate， effectively decreased clinical severity and CNS inflammation/demyelination in experimental autoimmune encephalomyelitis (EAE)， a mouse model of an autoimmune disease multiple sclerosis (MS). Interestingly， intraperitoneal EA administration at incredibly low doses (0.1 mg/kg/d) is dose-sparing with fingolimod (FTY720)， the first FDA-approved oral drug for MS. In addition， intraperitoneal EA also ameliorated the brain damage in a neuromyelitis optica (NMO) model， and significantly prevented the immune rejection of allograft skin graft. Evidence from pharmacological studies combined with RNA-seq indicate that prototype EA functions by a mechanism that involves direct inhibition of casein kinase II (CKII) to suppress the expression of IL-17 and promote the expression of Cpt1a to regulate Th17 differentiation. In conclusion， our study demonstrates that the prototype EA entering the blood circulation acts as a novel therapeutic immunomodulator for the treatment of autoimmune diseases and transplant rejection through the CKⅡ-mediated JAK/STAT/Cpt1a signaling pathway.

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Incidence and warning signs for complications of human brucellosis: a multi-center observational study from China

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Infectious diseases of Poverty 2024年第1期13卷 53-62页

作者： Qing-Nan Shi Hui-Jie Qin Qiao-Shan Lu hu Li Zhong-Fa Tao Meng-Guang Fan Mu-Heta Aishan Zeng-Qiang Kou Qiu-Lan Chen Wen-Wu Yin Yan-Ping Zhang National Key laboratory of Intelligent Tracking and Forecasting for Infectious diseases Chinese Center for Disease Control and PreventionChangbai RoadChangping DistrictBejing 102206China School of Public Health Guangxi Medical UniversityNanningChina Nanning Center for disease Control and Prevention NanningChina Guizhou Center for disease Control and Prevention GuiyangChina Inner Mongolia Center for disease Control and Prevention HohhotChina Xinjiang Uighur Autonomous Region Center for disease Control and Prevention UrumqiChina Shandong Center for disease Control and Prevention JinanChina

Background Brucellosis is a severe zoonotic disease that is often overlooked,particularly in impoverished countries.Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes.However,there is currently a lack of established indicators or biomarkers for diagnosing these complications.Therefore,this study aimed to investigate potential warning signs of focal complications in human brucellosis,with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of patients.Methods A multi-center cross-sectional study was conducted in China from December 2019 to August 2021.The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a ques-tionnaire survey and medical record system.The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models.Receiver operating characteristic(ROC)curves and the area under the curve(AUC)were used for variable screening and model evaluation.Results A total of 880 participants diagnosed with human brucellosis were enrolled.The median age of the patients Was 50 years[interquartile range(IQR):41.5-58.0],and 54.8%had complications.The most common organ system affected by complications was the osteoarticular system(43.1%),with peripheral arthritis(30.0%),spondylitis(16.6%),paravertebral abscess(5.0%),and sacroilitis(2.7%)being the most prevalent.Complications in other organ systems included the genitourinary system(4.7%),respiratory system(4.7%),and hematologic system(4.6%).Several fac-tors were found to be associated with focal brucellosis.These factors included a long delay in diagnosis odds ratio(OR)=3.963,95%confidence interval(CI):1.906-8.238 for>90 daysl,the presence of underlying disease(OR=1.675,95%CI:1.176-2.384),arthralgia(OR=3.197,95%CI:1.986-5.148),eye bulging pain(OR=3.482,95%CI:1.349-8.988),C-reactive protein(CRP)>10 mg/L(OR=1.910,95%CI:1.310-2.784)and erythrocyte sedimentation rate(ESR)el

关键词： Brucellosis Complications Clinical spectrum Warning signs

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Incidence and risk factors of in-hospital venous thromboembolism in non-oncological urological inpatients:A single center experience

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Asian Journal of Urology 2023年第4期10卷 546-554页

作者： Zhao Wang Kaixuan Li Quan Zhu Haozhen Li Ziqiang Wu Xuesong Liu Zhengyan Tang Department of Urology Xiangya HospitalCentral South UniversityChangshaChina provincial laboratory for diagnosis and treatment of genitourinary system disease ChangshaChina

Objective To determine incidence and risk factors for venous thromboembolism(VTE)development of in-hospital VTE in urological inpatients who underwent non-oncological surgery in a tertiary hospital in China.Methods Consecutive 1453 inpatients who were admitted to a non-oncological urological ward in the tertiary hospital from January 1,2018 to December 31,2018 were enrolled in the study,and the VTE events were diagnosed by ultrasound or computed tomographic pulmonary angiography.Patients’occurrence of VTE and characteristics which may contribute to the development of VTE were collected and analyzed as incidence and risk factors.Results The incidence of VTE in non-oncological urological inpatients is 2.3%.In our cohort,patients who experienced previous VTE(adjusted odds ratios[aOR]14.272,95%CI 3.620-56.275),taking anticoagulants or antiplatelet agents before admission(aOR 10.181,95%CI 2.453-42.256),D-dimer(max)≥1μg/mL(aOR 22.456,95%CI 6.468-77.967),lower extremity swelling(aOR 10.264,95%CI 2.242-46.994),chest symptoms(aOR 79.182,95%CI 7.132-879.076),operation time of more than or equal to 180 min(aOR 10.690,95%CI 1.356-84.300),and Caprini score(max)of more than or equal to 5(aOR 34.241,95%CI 1.831-640.235)were considered as risk factors for VTE.Conclusion In this study,we found that the incidence of VTE in non-oncological surgery was about 2.3%,which was higher than some previous studies.Risk factors could be used for early detection and diagnosis of VTE.

关键词： Venous thromboembolism Non-oncological surgery Urological inpatient Incidence Risk factor

整合素α6靶向自组装促凋亡纳米多肽对中枢神经系统急性淋巴细胞白血病的靶向治疗

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Engineering 2024年第4期35卷 226-240页

作者： Jia-Cong Ye Wan-Qiong Li Mei-Ling Chen Qian-Kun Shi Hua Wang Xin-Ling Li Ying-He Li Jie Yang Qiao-Li Wang Fang Hu Yan-Feng Gao Shu-Wen Liu Mu-Sheng Zeng Guo-Kai Feng Guangdong provincial Key laboratory of New Drug Screening&NMPA Key laboratory of Drug Metabolism Research and Evaluation School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China State Key laboratory of Oncology in South China&Guangdong Key laboratory of Nasopharyngeal Carcinoma diagnosis and Therapy Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China Guangdong provincial Key laboratory of Construction and Detection in Tissue Engineering Biomaterials Research CenterSchool of Biomedical EngineeringSouthern Medical UniversityGuangzhou 510515China State Key laboratory of Organ Failure Research Guangdong Provincial Institute of NephrologySouthern Medical UniversityGuangzhou 510515China

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.

关键词： Central nervous system acute lymphoblastic leukemia Integrinα6 Targeted peptide Proapoptotic Nanopeptide

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Clinical outcomes of transperitoneal laparoscopic unroofing and fenestration under seminal vesiculoscopy for seminal vesicle cysts

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Asian Journal of Andrology 2018年第6期20卷 621-625页

作者： Rui Zhi Xue Zheng-Yan Tang Zhi Chen Liang Huang Department of Urology Xiangya Hospital of Central South University Changsha 410000 China provincial laboratory for diagnosis and treatment of genitourinary system disease Changsha 410000 China

Symptomatic seminal vesicle cysts （SVCs）, especially those of a large size, can be removed by surgical treatments. Currently, open surgeries for SVC are rarely performed due to their extensive surgical trauma, and minimally invasive surgical therapies for treating seminal vesicle cysts are still in the early stages. In addition, relevant studies are mostly confined to case reports. In this study, we retrospectively reviewed 53 patients who had received transperitoneal laparoscopic unroofing or fenestration under seminal vesiculoscopy for SVC in our institution. Both surgeries decreased the cyst volume to a significant extent; however, according to the remnant lesion size after rechecking images, seminal vesiculoscopic fenestration tended to have a higher recurrence than laparoscopic unroofing. Regarding complications, two individuals in the laparoscopic unroofing group experienced ureteral injury and rectal injury, while patients in the fenestration group only had temporary hemospermia, which indicates that fenestration surgery tends to have less severe complications than laparoscopic unroofing. There was no solid evidence confirming semen improvement after these surgical therapies in our study. Future studies with a prospective design, larger sample size, and longer follow-up period are required to verify and further explore our findings.

关键词： cyst fenestration laparoscopy seminal vesicle unroofing vesiculoscopy

DNA framework signal amplification platform-based highthroughput systemic immune monitoring

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1115-1131页

作者： Ye Chen Xingyu Chen Bowen Zhang Yuxin Zhang Songhang Li Zhiqiang Liu Yang Gao Yuxuan Zhao Lin Yan Yi Li Taoran Tian Yunfeng Lin State Key laboratory of Oral diseases National Center for StomatologyNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041 SichuanPR China Department of Prosthodontics Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjin 300041PR China Department of laboratory Medicine West China HospitalSichuan UniversityChengdu 610041 SichuanPR China Sichuan provincial Engineering Research Center of Oral Biomaterials Chengdu 610041 SichuanChina

systemic immune monitoring is a crucial clinical tool for disease early diagnosis,prognosis and treatment planning by quantitative analysis of immune cells.However,conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing,especially in mass health screenings,because of time-consuming,technical-sensitive and high-cost features.However,the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring technology.To address this bottleneck,we constructed a generally applicable DNA framework signal amplification platform(DSAP)based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells,including CD4+,CD8+T-lymphocytes,and monocytes(down to 1/100μl).Based on this advanced detection platform,we present a novel high-throughput immune-cell phenotyping system,DSAP,achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and cost.As a proof-of-concept,DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients(AUC>0.97)within 30 min,which can be applied in HIV infection monitoring and screening.Therefore,we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

关键词： diagnosis monitoring initially

The role of acute normovolemic hemodilution in reducing allogeneic blood transfusion in glioblastoma surgery:a case-control study

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Chinese Neurosurgical Journal 2024年第1期10卷 35-41页

作者： Ping Chen Xin‑Huang Zhang Ying Wang Xian‑Zhong Lin De‑Zhi Kang Qing‑Song Lin Department of Anesthesiology The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina Department of Neurosurgery The First Affiliated Hospital of Fujian Medical UniversityNo.20 Chazhong RdTaijiang DistrictFuzhou 350005FujianChina Department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated Hospital of Fujian Medical UniversityFuzhou 350209FujianChina Fujian provincial Institutes of Brain Disorders and Brain Sciences The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina Fujian provincial Clinical Research Center for Neurological diseases The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina Fujian provincial Key laboratory of Precision Medicine for Cancer The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina

Background Acute normovolemic hemodilution(ANH)was first introduced in glioblastoma surgery,and its role in reducing allogeneic blood transfusion was investigated in this study.Methods This study enrolled supratentorial glioblastoma patients who received total resection.In the ANH group,the patients were required to draw blood before the operation,and the blood will be transfused back to the patient during the operation.The association between ANH and clinical features was investigated.Results Sixty supratentorial glioblastoma patients were enrolled in this study,25 patients were allocated in the ANH group,and another 35 patients were included in the control group.ANH dramatically reduced the need for allogeneic blood transfusion(3[12%]vs 12[34.3%],P=0.049),and the blood transfusion per total of patients was dramatically decreased by the application of ANH(0.40±1.15 units vs 1.06±1.59 units,P=0.069).Furthermore,ANH also markedly reduced the requirement of fresh frozen plasma(FFP)transfusion(2[8%]vs 11[31.4%],P=0.030)and the volume of FFP transfusion per total of patients(32.00±114.46 mL vs 115.71±181.00 mL,P=0.033).The complication rate was similar between the two groups.Conclusions ANH was a safe and effective blood conservation technique in glioblastoma surgery.

关键词： Glioblastoma Acute normovolemic hemodilution Surgery Blood transfusion

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