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An intelligent prediction model of epidemic characters based on multi-feature

CAAI Transactions on Intelligence Technology 2024年第3期9卷 595-607页

作者： Xiaoying Wang Chunmei Li Yilei Wang Lin Yin Qilin Zhou Rui Zheng Qingwu Wu Yuqi Zhou Min Dai Information Center Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina School of Computer Science Qufu Normal UniversityRizhaoChina Department of Allergy Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhou China 4Department of Otorhinolaryngology‐Head and Neck Surgery Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina Department of Pulmonary and Critical Care Medicine Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina Department of Traditional Chinese Medicine Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouChina

The epidemic characters of Omicron(***-scale transmission)are significantly different from the initial variants of *** data generated by large-scale transmission is important to predict the trend of epidemic ***,the re-sults of current prediction models are inaccurate since they are not closely combined with the actual situation of Omicron *** consequence,these inaccurate results have negative impacts on the process of the manufacturing and the service industry,for example,the production of masks and the recovery of the tourism *** authors have studied the epidemic characters in two ways,that is,investigation and ***,a large amount of data is collected by utilising the Baidu index and conduct questionnaire survey concerning epidemic ***,theβ-SEIDR model is established,where the population is classified as Susceptible,Exposed,Infected,Dead andβ-Recovered persons,to intelligently predict the epidemic characters of *** thatβ-Recovered persons denote that the Recovered persons may become Sus-ceptible persons with probabilityβ.The simulation results show that the model can accurately predict the epidemic characters.

关键词： artificial intelligence big data data analysis evaluation feature extraction intelligent information processing medical applications

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High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

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Neural Regeneration Research 2024年第8期19卷 1772-1780页

作者： Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu Department of Rehabilitation Medicine The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Hepatobiliary Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction *** magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem ***,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic ***-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ***,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and *** effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem ***,we validated the effect of repetitive TMS on AKT *** found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin *** findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling *** study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro *** results provide a stro ng scientific foundation for the clinical application of repetitive ***,repetitive TMS treatment may not only be an efficient an

关键词： AKT/β-catenin signaling brain stimulation Ca2+influx cell proliferation ischemic stroke middle cerebral artery occlusion neural stem cells neurological rehabilitation repetitive transcranial magnetic stimulation

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Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2613-2630页

作者： Xuemin He Siying Wen Xixiang Tang Zheyao Wen Rui Zhang Shasha Li Rong Gao Jin Wang Yanhua Zhu Dong Fang Ting Li Ruiping Peng Zhaotian Zhang Shiyi Wen Li Zhou Heying Ai Yan Lu Shaochong Zhang Guojun Shi Yanming Chen Department of Endocrinology and Metabolic Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China VIP Medical Service Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Clinical Immunology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Ophthalmology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Department of Fundus Shenzhen Eye Hospital of Jinan UniversityShenzhen 518048China

Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)protect against diabetic cardiovascular diseases and ***,their activity in diabetic retinopathy(DR)remains *** retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications,suggesting their advantage in DR *** single-cell RNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1R in retinal endothelial cells,which was down-regulated under diabetic *** of GLP-1 RAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic *** and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 ***,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial *** of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular *** investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING *** study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

关键词： GLP-1 RAs STING signaling Retinal endothelial cells Mitochondrial leakage Retinal vascular dysfunction Diabetic retinopathy CREB Inflammation

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Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese Medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang Department of Hepatic Surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of General Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Organ Transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Renal Transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China Department of Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatic Surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury Liver transplantation

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Viral hepatitis E:Clinical manifestations,treatment,and prevention

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肝脏研究（英文） 2024年第1期8卷 11-21页

作者： Qiumin Luo Jia Chen Yeqiong Zhang Wenxiong Xu Ying Liu Chan Xie Liang Peng Department of Infectious Disease The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing *** the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)*** acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver ***,some immunocompromised patients are at risk of developing chronic HEV infection and *** screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis *** review focused on the clinical presentation,management,and prevention of hepatitis E.

关键词： Hepatitis E Chronic hepatitis Screening Antiviral therapy Vaccination

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Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK-STAT pathway

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2554-2566页

作者： Jingyi Tan Jiayu Zhang Cheng Hu Gongwei Wang Qianyao Ren Chaoqun Wang Jia Dan Zexin Zeng Jun Hu Wenbo Zhu Jiankai Liang Jing Cai Ying Liu Guangmei Yan Yuan Lin Department of Pharmacology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China The Sixth affiliated hospital Sun Yat-sen UniversityGuangzhou 510655China Department of Urology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Advanced Medical Technology Center the First Affiliated Hospital-Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Human Microbiome and Elderly Chronic Diseases Ministry of EducationGuangzhou 510655China Department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer *** traditional drugs composed of non-replicating compounds or biomolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further *** some pharmacokinetics studies of OVs,mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain ***,we characterized the pharmacokinetic profile of oncolytic virus M1(OVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of OVM *** suppressing the JAK-STAT pathway,early OVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor *** than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade,such as *** together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

关键词： Pharmacokinetics Oncolytic virus JAK-STAT Anticancer

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Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

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Chinese Journal of Cancer Research 2024年第2期36卷 114-123页

作者： Yupeng Ren Yuxuan Li Mingbo Cao Yongchang Tang Feng Yuan Gaoyuan Yang Zhiwei He Zheng Shi Xiaorui Su Zhicheng Yao Meihai Deng Department of Hepatobiliary Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of General Surgery Qilu HospitalShandong UniversityJinan 250012China Department of Hepatobiliary Surgery the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Hepatobiliary and Pancreatic Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of ***: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) *** OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher ***: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

关键词： Hepatocellular carcinoma lenvatinib low-dose cyclophosphamide pembrolizumab transarterial chemoembolization

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Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke

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Neuroscience Bulletin 2024年第1期40卷 65-78页

作者： Fangxi Liu Xi Cheng Chuansheng Zhao Xiaoqian Zhang Chang Liu Shanshan Zhong Zhouyang Liu Xinyu Lin Wei Qiu Xiuchun Zhang Department of Neurology.The First affiliated hospital of China Medical university Shenyang 110001China Department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Stroke Center The First Affiliated Hospital of China Medical UniversityShenyang 110001China

Interactions between brain-resident and periph-eral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ***,con-ventional bulk sequencing makes it challenging to depict this complex immune *** single-cell RNA sequencing,we mapped compositional and transcriptional features of peri-infarct immune *** were the predominant cell type in the peri-infarct region,displaying a more diverse activation pattern than the typical pro-and anti-inflammatory state,with axon tract-associated micro-glia(ATMs)being associated with neuronal *** inference suggested that infiltrated monocyte-derived macrophages(MDMs)exhibited a gradual fate trajectory transition to activated ***-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis,with SOX2 and related Akt/CREB signaling as the underlying *** description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

关键词： Ischemic stroke Monocyte-derived macrophage Microglia Neurogenesis Single-cell sequencing

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Early plasma exchange and continuous renal replacement therapy improve puerperal prognosis in hepatitis B virus-related acute-on-chronic liver failure in pregnancy

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Liver Research 2024年第2期8卷 118-126页

作者： Lijuan Li Mingming Fan Mi Zhou Pinglan Lu Jianrong Liu Huimin Yi Xuxia Wei Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Background and aim:Hepatitis B virus(HBV)-related gestational acute-on-chronic liver failure(ACLF)is a severe condition with limited treatment *** study aimed to evaluate the efficacy and ideal timing of plasma exchange and continuous renal replacement therapy(CRRT)in managing pregnant women with HBV-related ***:This study retrospectively analyzed 51 eligible patients with HBV-related gestational ACLF between 2009 and *** admitted to the study were divided into a conventional treatment group and a new treatment group according to whether they received the new management protocol,which included more aggressive plasma exchange(PE)and CRRT *** 19 pregnant women with hepatic encephalopathy(HE)were divided into an early treatment group and a non-early treatment group according to whether PE therapy was initiated within three *** study had two primary ***,we aimed to evaluate the impact of PE and CRRT on puerperal ***,we sought to assess the effects of early PE and CRRT regimens on puerperal survival in women with ***:The levels of total bilirubin on the second day postpartum(D3),the third day postpartum(D4),and the fifth day postpartum(D6)were significantly lower in the new treatment group compared to the conventional treatment group(P=0.02,0.01,and 0.02,respectively).The ALT of D3 was significantly elevated in the new treatment group compared to the conventional treatment group(P=0.02).The incidence of HE overall increased from prenatal to postpartum D4,peaked on D4,and then gradually decreased from the fourth day postpartum(D5)(P=0.027).The first week after delivery revealed a significant difference in survival rate between the two groups,the conventional treatment group had statistically higher mortality rates compared to the new treatment group(P=0.002).Similarly,the entire puerperal period mortality rate of the conventional treatment group was statistically higher than the new treatment

关键词： Acute-on-chronic liver failure(ACLF) Liver disease in pregnancy Hepatitis B virus(HBV) Plasma exchange(PE) Continuous renal replacement therapy(CRRT) Hepatic encephalopathy(HE)

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Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma

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肝脏研究（英文） 2024年第2期8卷 105-117页

作者： Huan Wei Songhao Luo Yanhua Bi Chunhong Liao Yifan Lian Jiajun Zhang Yuehua Huang Guangdong Provincial Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina School of Mathematics Sun Yat-sen UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina School of Public Health Sun Yat-sen UniversityGuangzhouChina School of Mathematics Sun Yat-sen UniversityGuangzhouChina Guangdong Province Key Laboratory of Computational Science Sun Yat-sen UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Background and aims:Hepatocellular carcinoma(HCC),which is prevalent worldwide and has a high mortality rate,needs to be effectively *** aimed to evaluate the significance of plasma microRNA-15a/16-1(miR-15a/16)as a biomarker of hepatitis B virus-related HCC(HBV-HCC)using the machine learning *** study was the first large-scale investigation of these two miRNAs in HCC plasma samples.Methods:Using quantitative polymerase chain reaction,we measured the plasma miR-15a/16 levels in a total of 766 participants,including 74 healthy controls,335 with chronic hepatitis B(CHB),47 with compensated liver cirrhosis,and 310 with *** diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein(AFP).Lastly,to validate the diagnostic efficiency of miR-15a/16,we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC.Results:Plasma miR-15a/16 was significantly decreased in HCC than in all control groups(P＜0.05 for all).In the training cohort,the area under the receiver operating characteristic curve(AUC),sensitivity,and average precision(AP)for the detection of HCC were higher for miR-15a(AUC=0.80,67.3％,AP=0.80)and miR-16(AUC=0.83,79.0％,AP=0.83)than for AFP(AUC=0.74,61.7％,AP=0.72).Combining miR-15a/16 with AFP increased the AUC to 0.86(sensitivity 85.9％)and the AP to 0.85 and was significantly superior to the other markers in this study(P＜0.05 for all),as further demonstrated by the detection error tradeoff ***,miR-15a/16 impressively showed potent diagnostic power in early-stage,small-tumor,and AFP-negative HCC.A validation cohort confirmed these ***,the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16.Conclusions:We developed and validated a plasma miR-15a/16-based machine learning model,which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

关键词： Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) microRNA-15a microRNA-16-1 Biomarker Machine learning Pseudotemporal ordering

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