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Plasma-metabolite-based machine learning is a promising Diagnostic approach for esophageal squamous cell carcinoma investigation

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Journal of Pharmaceutical Analysis 2021年第4期11卷 505-514页

作者： Zhongjian Chen Xiancong Huang Yun Gao Su Zeng Weimin Mao Laboratory of Pharmaceutical Analysis and Drug Metabolism College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China The Cancer Research Institute The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou310022China

The aim of this study was to develop a Diagnostic strategy for esophageal squamous cell carcinoma(ESCC)that combines plasma metabolomics with machine learning algorithms.Plasma-based untargeted metabolomics analysis was performed with samples derived from 88 ESCC patients and 52 healthy controls.The dataset was split into a training set and a test set.After identification of differential metabolites in training set,single-metabolite-based receiver operating characteristic(ROC)curves and multiple-metabolite-based machine learning models were used to distinguish between ESCC patients and healthy controls.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic significance of the plasma metabolites.Finally,twelve differential plasma metabolites(six up-regulated and six down-regulated)were annotated.The predictive performance of the six most prevalent Diagnostic metabolites through the Diagnostic models in the test set were as follows:arachidonic acid(accuracy:0.887),sebacic acid(accuracy:0.867),indoxyl sulfate(accuracy:0.850),phosphatidylcholine(PC)(14:0/0:0)(accuracy:0.825),deoxycholic acid(accuracy:0.773),and trimethylamine N-oxide(accuracy:0.653).The prediction accuracies of the machine learning models in the test set were partial least-square(accuracy:0.947),random forest(accuracy:0.947),gradient boosting machine(accuracy:0.960),and support vector machine(accuracy:0.980).Additionally,survival analysis demonstrated that acetoacetic acid was an unfavorable prognostic factor(hazard ratio(HR):1.752),while PC(14:0/0:0)(HR:0.577)was a favorable prognostic factor for ESCC.This study devised an innovative strategy for ESCC diagnosis by combining plasma metabolomics with machine learning algorithms and revealed its potential to become a novel screening test for ESCC.

关键词： Diagnostic Esophageal squamous cell carcinoma(ESCC) Metabolomics Machine learning Prognostic

Human microbiome is a Diagnostic biomarker in hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 109-115页

作者： Ben-Chen Rao Jia-Min Lou Wei-Jie Wang Ang Li Guang-Ying Cui Zu-Jiang Yu Zhi-Gang Ren Department of Infectious Diseases the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Gene Hospital of Henan Province Precision Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Background:Hepatocellular carcinoma(HCC)is the third leading cause of cancer mortality worldwide.Increasing evidence indicates a close relationship between HCC and the human microbiota.Herein,we reviewed the important potential of the human microbiota as a Diagnostic biomarker of HCC.Data sources:Several innovative studies have investigated the characteristics of the gut and oral micro-biomes in patients with HCC and proposed that the human microbiome has the potential to be a diag-nostic biomarker of HCC.Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords"microbiota"or"microbiome"or"microbe"and"liver cancer"or"hepato-cellular carcinoma",and the results of clinical and experimental studies were analyzed.Results:Specific changes occur in the human microbiome of patients with HCC.Moreover,the gut mi-crobiome and oral microbiome can be used as non-invasive Diagnostic biomarkers for HCC.Furthermore,they also have certain Diagnostic potential for precancerous diseases of HCC.The Diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future.Conclusions:The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC.The human microbiome may be widely used in the diagnosis,treatment and prognosis for multiple system diseases or cancers in the future.

关键词： Human microbiome Gut microbiome Oral microbiome Hepatocellular carcinoma Diagnostic biomarker

^(68)Gallium-labelled PSMA-PET/CT as a Diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy

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Cancer Biology & Medicine 2019年第1期16卷 157-165页

作者： Janice S.H.Tan Charles X.Y.Goh Yen Sin Koh Youquan Li Jeffrey K.L.Tuan Eu Tiong Chua Terence W.K.Tan Michael L.C.Wang Lui Shiong Lee Kae Jack Tay Ravindran Kanesvaran Chee Keong Toh Aaron K.T.Tong Winnie W.C.Lam Melvin L.K.Chua Division of Radiation Oncology National Cancer Centre Singapore Department of Nuclear Medicine and Molecular Imaging Singapore General Hospital Radiological Sciences Academic Clinical Programme Duke-NUS Medical School Oncology Academic Clinical Programme Duke-NUS Medical School Department of Urology Singapore General Hospital Department of Surgery Sengkang General Hospital Division of Medical Oncology National Cancer Centre Singapore Division of Medical Sciences National Cancer Centre Singapore

Objective: Prostate cancers(PCa) in Asian individuals are molecularly distinct from those found in their Caucasian counterparts.There is no risk stratification tool for Asian men with rapid biochemical recurrence(BCR) following radical prostatectomy(Rad P). This study aims to assess the detection rate of ^(68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography(PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-Rad P.Methods: ^(68)Ga PSMA-PET and CT body with/without bone scan [conventional workup(CWU)] were performed in 55 Asian patients with BCR within 36 months post-Rad P. Two blinded reviewers assessed the images. Detection rates of ^(68)Ga PSMAPET/CT were evaluated, and impact on management was reviewed by comparison with CWU.Results: Median time to BCR post-Rad P was 8.1 months. Detection rate for ^(68)Ga PSMA-PET/CT was 80%(44/55). A positive scan was significantly associated with increasing prostate-specific antigen(PSA) level [odds ratio(OR) = 1.13(95% CI 1.05–1.30), P =0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, ^(68)Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44(56.8%) patients: 10 to hormonal therapy(HT) and whole pelvis radiotherapy(RT) in addition to bed RT, and 15 to palliative HT alone.Conclusions: In the present report, we demonstrated the Diagnostic and treatment decision utility of ^(68)Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels(< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

关键词： ^68Ga PSMA PET/CT prostate cancer Asian Diagnostic recurrence prostatectomy salvage radiotherapy

Diagnostic Accuracy of Chinese Medicine Diagnosis Scale of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease: A Study Protocol

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Chinese Journal of Integrative Medicine 2019年第7期25卷 515-520页

作者： LIU Xiao-qi PENG Dan-hong WANG Yan-ping XIE Rong CHEN Xin-lin YU Chun-quan LI Xian-tao School of Basic Medical Science Guangzhou University of Chinese Medicine Guangzhou (510006) China Journal Editorial Board Tianjin University of Traditional Chinese Medicine Tianjin (300193) China

Background Phlegm and blood stasis syndrome(PBSS) is one of the main syndromes in coronary heart disease(CHD). Syndromes of Chinese medicine(CM) are lack of quantitative and easyimplementation diagnosis standards. To quantify and standardize the diagnosis of PBSS, scales are usually applied. Objective: To evaluate the Diagnostic accuracy of CM diagnosis scale of PBSS in CHD. Methods: Six hundred patients with stable angina pectoris of CHD, 300 in case group and 300 in control group, will be recruited from 5 hospitals across China. Diagnosis from 2 experts will be considered as the "gold standard". The study design consists of 2 phases: pilot test is used to evaluate the reliability and validity, and Diagnostic test is used to assess the Diagnostic accuracy of the scale, including sensitivity, specificity, likelihood ratio and area under the receiver operator characteristic(ROC) curve. Discussion: This study will evaluate the Diagnostic accuracy of CM diagnosis scale of PBSS in CHD. The consensus of 2 experts may not be ideal as a "gold standard", and itself still requires further study.(No. ChiCTR-OOC-15006599).

关键词： Diagnostic accuracy phlegm and blood stasis diagnosis scale syndrome differentiation coronary heart disease study protocol

A non-invasive Diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity

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Chinese Medical Journal 2019年第6期132卷 647-652页

作者： Qiu-Xia Han Yong Wang Han-Yu Zhu Dong Zhang Jing Gao Zhang-Suo Liu Guang-Yan Cai Xiang-Mei Chen Department of Nephrology The First Affiliated Hospital of Zhengzhou University Research Institute of Nephrology in Zhengzhou University Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province Zhengzhou Henan 450052 China Department of Nephrology Chinese People's Liberation Army General Hospital Chinese People's Liberation Army Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases Beijing Key Laboratory of Kidney Diseases Beijing 100853 China Department of Clinical Biochemistry Chinese People's Liberation Army General Hospital Beijing 100853 China

Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive Diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. Methods: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the Diagnostic value of the clinical factors. Logistic regression was used to establish the Diagnostic model. Results: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all PDiagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of Ⅰ,Ⅱ,Ⅲ,Ⅳ, and Ⅴ accounted for 2.21 %, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade Ⅲ being the most prevalent. The levels of urea nitrogen (UN)(13.57土 5.95 vs. 6.06 土 3.63, 5.92 + 2.97, 5.41 ± 1.73, and 8.41 ±3.72μmol/L, respectively) and creatinine (Cr)(292.19± 162.21 vs. 80.42±24.75, 103.79±72.72, 96.41 ±33.79, and 163.04±47.51 μmol/L, res

关键词： Immunoglobulin A nephropathy Noninvasive Diagnostic model Severity

Optimized protocol of multiple post-processing techniques improves Diagnostic accuracy of multidetector computed tomography in assessment of small bowel obstruction compared with conventional axial and coronal reformations

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World Journal of Gastroenterology 2019年第9期25卷 1100-1115页

作者： Lian-Qin Kuang Wei Tang Ran Li Cheng Cheng Shuang-Yue Tang Yi Wang Department of Radiology Army Medical Center of PLA Army Medical University Sichuan Key Laboratory of Medical Imaging Department of Radiology Affiliated Hospital of North Sichuan Medical College

BACKGROUND Axial and coronal reformations have been a widely used image post-processing protocol for the ordinary multidetector computed tomography(MDCT)examination of patients with small bowel obstruction(SBO) or other abdominal diseases. The Diagnostic accuracy of MDCT for assessing SBO is expected to be further improved through the use of multiple post-processing techniques.AIM To systemically evaluate the Diagnostic accuracy and efficiency of an optimized protocol using multiple post-processing techniques for MDCT assessment of SBO and secondary bowel ischemia.METHODS This retrospective cross-sectional study included 106 patients with clinically suspected SBO. Two readers applied three protocols to image post-processing and interpretation of patients' MDCT volume data. We compared the three protocols based on time spent, number of images, Diagnostic self-confidence,agreement, detection rate, and accuracy of detection of SBO and secondary bowel ischemia.RESULTS Protocol 2 resulted in more time spent and number of images than protocols 1 and 3(P 0.05). Using protocol 3, both readers added multiple postprocessing techniques at frequencies of 29.2% and 34.9%, respectively, for obstruction cause, and 32.1% and 30.2%, respectively, for secondary bowel ischemia. Protocols 2 and 3 had higher total detection rates of obstruction cause and secondary bowel ischemia than protocol 1(P 0.05). The accuracy, sensitivity,specificity, positive predictive value and negative predictive value of protocols 2 and 3 were superior to those of protocol 1 for evaluating obstruction cause and secondary bowel ischemia.CONCLUSION Our optimized protocol of multiple post-processing techniques can both guarantee efficiency and improve Diagnostic accuracy of MDCT for assessing SBO and secondary bowel ischemia.

关键词： Intestine Intestinal obstruction Multidetector computed tomography Diagnostic techniques and procedures

Real-world fuel consumption of light-duty passenger vehicles using on-board Diagnostic (OBD) systems

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Frontiers of Environmental Science & Engineering 2020年第2期14卷 207-216页

作者： Xuan Zheng Sheng Lu Liuhanzi Yang Min Yan Guangyi Xu Xiaomeng Wu Lixin Fu Ye Wu College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China School of Environment State Key Joint Laboratory of Environment Simulation and Pollution ControlTsinghua UniversityBeijing 100084China International Council on Clean Transportation Beijing 100084China Shenzhen Research Academy of Environmental Sciences Shenzhen 518001China State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex Beijing 100084China

An increasing discrepancy between real-world and type-approval fuel consumption for light-duty passenger vehicles(LDPVs)has been reported by several studies.Normally,real-world fuel consumption is measured primarily by a portable emission measurement system.The on-board Diagnostic(OBD)approach,which is flexible and offers high-resolution data collection,is a promising fuel consumption monitoring method.Three LDPVs were tested with a laboratory dynamometer based on a type-approval cycle,the New European Driving Cycle(NEDC).Fuel consumption was measured by the OBD and constant-volume sampling system(CVS,a regulatory method)to verify the accuracy of the OBD values.The results of the OBD method and the regulatory carbon balance method exhibited a strong linear correlation(e.g.,R^2=0.906-0.977).Compared with the carbon balance results,the fuel consumption results using the OBD were 7.1%±4.3%lower on average.Furthermore,the real-world fuel consumption of six LDPVs was tested in Beijing using the OBD.The results showed that the normalized NEDC real-world fliel consumption of the tested vehicles was 13%±17%higher than the type-approval-based fuel consumption.Because the OBD values are lower than the actual fuel consumption,using a carbon balance method may result in a larger discrepancy between real-word and type-approval ftiel consumption.By means of the operating mode binning and micro trip methods,a strong relationship(R^2=0.984)was established between the average speed and relative fuel consumption.For congested roads(average vehicle speed less than 25 km/h),the fuel consumption of LDPVs is highly sensitive to changes in average speed.

关键词： Fuel consumption Light-duty passenger vehicles On-board Diagnostic systems

New fecal test for non-invasive Helicobacter pylori detection:A Diagnostic accuracy study

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World Journal of Gastroenterology 2018年第27期24卷 3021-3029页

作者： Andrea Iannone Floriana Giorgio Francesco Russo Giuseppe Riezzo Bruna Girardi Maria Pricci Suetonia C Palmer Michele Barone Mariabeatrice Principi Giovanni FM Strippoli Alfredo Di Leo Enzo Ierardi Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Emergency and Organ Transplantation University of BariBari 70124Italy THD SpA Correggio(Reggio Emilia)42015Italy National Institute of Gastroenterology “S De Bellis”Research HospitalCastellanaGrotte(Bari)70013Italy Department of Medicine University of Otago ChristchurchChristchurch 8011New Zealand Diaverum Academy Lund 22229Sweden Diaverum Medical Scientific Office Lund 22229Sweden Sydney School of Public Health University of SydneySydney NSW-2000Australia Section of Nephrology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy

AIM To assess the Diagnostic accuracy of a new fecal test for detecting Helicobacter pylori(H. pylori), using ^(13)Curea breath test as the reference standard, and explore bacterial antibiotic resistance. METHODS We conducted a prospective two-center Diagnostic test accuracy study. We enrolled consecutive people≥ 18 years without previous diagnosis of H. pylori infection, referred for dyspepsia between February and October 2017. At enrollment, all participants underwent 13 C-urea breath test. Participants aged over 50 years were scheduled to undergo upper endoscopy with histology. Participants collected stool samples 1-3 d after enrollment for a new fecal investigation(THD fecal test). The detection of bacterial 23 S rRNA subunit gene indicated H. pylori infection. We also used the index Diagnostic test to examine mutations conferring resistance to clarithromycin and levofloxacin. Independent investigators analyzed index test and reference test standard results blinded to the other test findings. We estimated sensitivity, specificity, positive(PPV) and negative(NPV) predictive value, Diagnostic accuracy, positive and negative likelihood ratio(LR), together with 95% confidence intervals(CI).RESULTS We enrolled 294 consecutive participants(age: Median 37.0 years, IQR: 29.0-46.0 years; men: 39.8%). Ninetyfive(32.3%) participants had a positive ^(13)C-urea breath test. Twenty-three(7.8%) participants underwent upper endoscopy with histology, with a full concordance between ^(13)C-urea breath test and histology in detecting H. pylori infection. Four(1.4%) out of the 294 participants withdrew from the study after the enrollment visit and did not undergo THD fecal testing. In the 290 participants who completed the study, the THD fecal test sensitivity was 90.2%(CI: 84.2%-96.3%), specificity 98.5%(CI:96.8%-100%), PPV 96.5%(CI: 92.6%-100%), NPV 95.6%(CI: 92.8%-98.4%), accuracy 95.9%(CI: 93.6%-98.2%), positive LR 59.5(CI: 19.3-183.4), negative LR 0.10(CI: 0.05-0.18). Out of 83 infected participants identified with the THD

关键词： Helicobacter pylori Fecal test Feces Stools 23S rRNA Molecular analysis Antibiotic resistance Diagnostic accuracy

Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors

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World Journal of Gastroenterology 2019年第34期25卷 5026-5048页

作者： Orsolya Galamb Barbara K Barták Alexandra Kalmár Zsófia B Nagy Krisztina A Szigeti Zsolt Tulassay Peter Igaz Béla Molnár Molecular Medicine Research Group Hungarian Academy of SciencesBudapest H-1088Hungary 2nd Department of Internal Medicine Semmelweis UniversityBudapest H-1088Hungary

Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early Diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based Diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as Diagnostic or prognostic biomarkers for CRC.

关键词： Long non-coding RNA Colorectal cancer Colorectal adenoma Circulating long non-coding RNAs Exosome Biomarker Diagnostic marker Prognostic marker