Clinical and Experimental Medicine最新文献

{"title":"Autophagy-based therapy for hepatocellular carcinoma: from standard treatments to combination therapy, oncolytic virotherapy, and targeted nanomedicines.","authors":"Fereshteh Rahdan, Fatemeh Abedi, Hassan Dianat-Moghadam, Maryam Zamani Sani, Mohammad Taghizadeh, Effat Alizadeh","doi":"10.1007/s10238-024-01527-5","DOIUrl":"10.1007/s10238-024-01527-5","url":null,"abstract":"<p><p>Human hepatocellular carcinoma (HCC) has been identified as a significant cause of mortality worldwide. In recent years, extensive research has been conducted to understand the underlying mechanisms of autophagy in the pathogenesis of the disease, with the aim of developing novel therapeutic agents. Targeting autophagy with conventional therapies in invasive HCC has opened up new opportunities for treatment. However, the emergence of resistance and the immunosuppressive tumor environment highlight the need for combination therapy or specific targeting, as well as an efficient drug delivery system to ensure targeted tumor areas receive sufficient doses without affecting normal cells or tissues. In this review, we discuss the findings of several studies that have explored autophagy as a potential therapeutic approach in HCC. We also outline the potential and limitations of standard therapies for autophagy modulation in HCC treatment. Additionally, we discuss how different combination therapies, nano-targeted strategies, and oncolytic virotherapy could enhance autophagy-based HCC treatment in future research.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"13"},"PeriodicalIF":3.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bispecific antibodies in clinical practice: Understanding recent advances and current place in cancer treatment landscape.","authors":"Vaibhav Verma, Geeti Sharma","doi":"10.1007/s10238-024-01520-y","DOIUrl":"10.1007/s10238-024-01520-y","url":null,"abstract":"<p><p>Immunotherapy has changed the treatment landscape of cancer in the past decade. Amongst various forms of immunotherapy, manipulating the T cell has shown promise in past few years. T cell manipulation can be done by CAR-T cell therapy or bispecific antibodies. These 2 therapeutic modalities have been studied and shown efficacy in hematologic malignancies in relapsed refractory setting. They have not been compared to each other in randomized control trials; hence, the adequate sequencing is not known. Although cross-trial comparison is not ideal, available evidence indicates toward similar efficacy and better tolerability of BiTEs compared to CAR-T cell therapy. Bispecific antibodies, though, have an advantage of being able to be used in an \"off the shelf\" manner considering these are not MHC specific and can be administered to all patients regardless of HLA type. There has been an explosive growth in the indications for bispecific antibodies in the recent past. In this article, we have reviewed recent approvals, indication and literature regarding efficacy and adverse effects of bispecific antibodies in all available indications. This will be a useful read for clinical practitioners to understand the mechanism of action and place of all available bispecific antibodies in the current oncology landscape.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"11"},"PeriodicalIF":3.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The bacterial microbiome and cancer: development, diagnosis, treatment, and future directions.","authors":"Hasnaa H Qasem, Wael M El-Sayed","doi":"10.1007/s10238-024-01523-9","DOIUrl":"10.1007/s10238-024-01523-9","url":null,"abstract":"<p><p>The term \"microbiome\" refers to the collection of bacterial species that reside in the human body's tissues. Sometimes, it is used to refer to all microbial entities (bacteria, viruses, fungi, and others) which colonize the human body. It is now generally acknowledged that the microbiome plays a critical role in the host's physiological processes and general well-being. Changes in the structure and/or function of the microbiome (dysbiosis) are linked to the development of many diseases including cancer. The claim that because of their negatively charged membrane, cancer cells are more vulnerable to some bacteria than normal cells and that is how the link between these bacteria and cancer evolved has been refuted. Furthermore, the relationship between the microbiome and cancer is more evident in the emerging field of cancer immunotherapy. In this narrative review, we detailed the correlation between the presence/absence of specific bacterial species and the development, diagnosis, prognosis, and treatment of some types of cancer including colorectal, lung, breast, and prostate cancer. In addition, we discussed the mechanisms of microbiome-cancer interactions including genotoxin production, the role of free radicals, modification of signaling pathways in host cells, immune modulation, and modulation of drug metabolism by microbiome. Future directions and clinical application of microbiome in the early detection, prognosis, and treatment of cancer emphasizing on the role of fecal transplantation, probiotics, prebiotics, and microbiome biomarkers were also considered.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"12"},"PeriodicalIF":3.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hodgkin lymphoma: the role of EBV plasma viral load testing in an HIV-endemic setting.","authors":"J Opie, Z Mohamed, D Chetty, J Bailey, K Brown, E Verburgh, D Hardie","doi":"10.1007/s10238-024-01524-8","DOIUrl":"10.1007/s10238-024-01524-8","url":null,"abstract":"<p><p>South Africa has a high burden of human immune deficiency virus (HIV)-associated Hodgkin lymphoma (HL) which is typically Epstein-Barr virus (EBV) infected, detected by histological stains. Circulating plasma EBV derived from apoptotic EBV infected tumour cells is a potential biomarker. This study aimed to evaluate the role of plasma EBV load testing in newly diagnosed HL patients and correlate pretreatment plasma EBV levels, HIV status and EBV tumour status with overall survival (OS). Untreated HL patients were prospectively included. Polymerase chain reaction measured EBV plasma viral loads. Kaplan-Meier curves with log-rank tests estimated the impact of HIV, EBV tumour status and plasma EBV viral loads on OS. Multivariable analysis was performed using a Cox proportional hazards model. Receiver operative characteristic curve analysis determined cutoff plasma EBV DNA levels with optimal sensitivity, specificity and concordance with tumour EBV status. The 68 patients included 21 (31%) HIV +ve and 33 (49%) EBV tumour +ve. EBV plasma ≥ 10 000 IU/ml (P = 0.008), EBV +ve tumour (P = 0.014), HIV +ve status (P = 0.009) and age ≥ 45 years (P = 0.018) predicted poorer OS on univariate analysis. Plasma EBV levels > 762 IU/ml had 89.29% sensitivity and 96.77% specificity for detecting EBV +ve HL. High plasma EBV levels ≥ 10 000 IU/ml, HIV +ve status and EBV tumour +ve status predicted poorer OS. Plasma EBV levels > 762 IU/ml predicted EBV +ve tumour status with high sensitivity and specificity. Plasma EBV viral DNA testing is a promising biomarker for EBV +ve HL.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"10"},"PeriodicalIF":3.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of hepatocellular carcinoma organoid model recapitulating HIF-1A metabolic signature.","authors":"Mennatallah A Khedr, Zainab Mohamed, Azza M El-Derby, Malak M Soliman, Amira Abdel Fattah Edris, Eman Badr, Nagwa El-Badri","doi":"10.1007/s10238-024-01521-x","DOIUrl":"10.1007/s10238-024-01521-x","url":null,"abstract":"<p><p>Hypoxia is one of the main hallmarks of hepatocellular carcinoma (HCC) resulting from improper oxygenation and insufficient nourishment of the HCC microenvironment. The effect of hypoxia is mediated by hypoxia-inducible factor-1A (HIF-1A) via targeting various downstream pathways, including glycolysis, angiogenesis, and survival signaling. However, HCC cell lines in a 2-dimensional (2D) setting do not resemble the metabolic signature of HCC. Here we aim to overcome these limitations by developing an HCC organoid that recapitulates the HIF-1A metabolic shift. The enrichment analysis of the RNA-Seq data revealed that HIF-1A-driven glycolytic shift is of the significant pathways. The established organoid model, using xeno-free plasma-derived extracellular matrix (ECM) as a scaffold and nutritive biomatrix, maintained its structural integrity and viability for up to 14 days; the comparative analysis of the cobalt (II) chloride (CoCl₂)-treated organoids to the untreated ones unveiled reduced size and proliferative capacity. Interestingly, our organoid model showed an elevated expression of HIF-1A and glycolysis enzymes compared to their counterparts in the CoCl₂-treated organoids. HIF-1A molecular expression-translated biochemical signature is further assessed in our spontaneously growing organoids showing an increase in glucose uptake, intracellular pyruvate, extracellular lactate dehydrogenase expression, and extracellular lactate production, while hydrogen peroxide (H₂O₂), a marker for oxidative metabolism, is reduced. Our data confirmed the potency of the established organoid model to mimic the molecular and biochemical HIF-1A-driven metabolism, which validates its potential use as an in vitro HCC model. Our model naturally simulates hypoxic conditions and simultaneous HIF-1A-dependent glycolysis within HCC rather than using of CoCl₂-induced hypoxic conditions.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"9"},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic implications and oncogenic role of NSUN5 in clear cell renal cell carcinoma.","authors":"Chan Huang, Mu-Yang Luo, Neng-Qiao Wen, Yu-Man Chen, Li-Zhen Zhang, Yun Cao","doi":"10.1007/s10238-024-01507-9","DOIUrl":"10.1007/s10238-024-01507-9","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC), a predominant form of urinary malignancy, requires the identification of reliable biomarkers to enhance both prognostic outcomes and therapeutic developments specific to ccRCC. NSUN5, a member of the NOL1/NOP2/SUN domain (NSUN) family, plays a critical role in RNA stabilization and exhibits widespread expression across various tumor types. However, the exact function of NSUN5 in ccRCC remains insufficiently understood. Data were collated from cohorts of ccRCC patients who underwent nephrectomy, including those from the Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC), to evaluate the clinical relevance of NSUN5. Integrative models based on NSUN5 expression were subsequently developed to predict the prognosis of ccRCC within the TCGA and SYSUCC cohorts. Furthermore, the impact of NSUN5 on RCC cells and its association with cellular senescence were corroborated through in vitro experimental analyses. NSUN5 exhibited elevated expression in both ccRCC patients and renal cancer cell lines, whose upregulation significantly correlated with age, tumor size, TNM stage, WHO/International Society of Urological Pathology (ISUP) grade, presence of necrosis, and a poor prognosis. An accessible nomogram, incorporating NSUN5 along with various clinicopathological parameters, was adept at predicting outcomes for ccRCC patients. Additionally, in vitro findings indicated that reduced expression of NSUN5 enhanced tumor cell senescence and simultaneously inhibiting cell proliferation and migration. These observations suggest that elevated NSUN5 expression is linked to poorer overall survival (OS) and progression-free survival (PFS), positioning NSUN5 as a viable diagnostic and prognostic biomarker in ccRCC.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"8"},"PeriodicalIF":3.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current biological implications and clinical relevance of metastatic circulating tumor cells.","authors":"Reza Shahhosseini, SeyedAbbas Pakmehr, Anis Elhami, Maha Noori Shakir, Abdullah Ali Alzahrani, Mais Mazin Al-Hamdani, Munther Abosoda, Ali Alsalamy, Majid Mohammadi-Dehcheshmeh, Tahereh Ezazi Maleki, Hossein Saffarfar, Payam Ali-Khiavi","doi":"10.1007/s10238-024-01518-6","DOIUrl":"10.1007/s10238-024-01518-6","url":null,"abstract":"<p><p>Metastatic disease and cancer recurrence are the primary causes of cancer-related deaths. Circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) are the driving forces behind the spread of cancer cells. The emergence and development of liquid biopsy using rare CTCs as a minimally invasive strategy for early-stage tumor detection and improved tumor management is a promising advancement in recent years. However, before blood sample analysis and clinical translation, precise isolation of CTCs from patients' blood based on their biophysical properties, followed by molecular identification of CTCs using single-cell multi-omics technologies is necessary to understand tumor heterogeneity and provide effective diagnosis and monitoring of cancer progression. Additionally, understanding the origin, morphological variation, and interaction between CTCs and the primary and metastatic tumor niche, as well as and regulatory immune cells, will offer new insights into the development of CTC-based advanced tumor targeting in the future clinical trials.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"7"},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronobiological disruptions: unravelling the interplay of shift work, circadian rhythms, and vascular health in the context of stroke risk.","authors":"Xiaohong Li, Yanjin He, Dawu Wang, Mohammad Reza Momeni","doi":"10.1007/s10238-024-01514-w","DOIUrl":"10.1007/s10238-024-01514-w","url":null,"abstract":"<p><p>Shift work, particularly night shifts, disrupts circadian rhythms and increases stroke risk. This manuscript explores the mechanisms connecting shift work with stroke, focusing on circadian rhythms, hypertension, and diabetes. The circadian system, controlled by different mechanisms including central and peripheral clock genes, suprachiasmatic nuclei (SCN), and pineal gland (through melatonin production), regulates body functions and responds to environmental signals. Disruptions in this system affect endothelial cells, leading to blood pressure issues. Type 2 diabetes mellitus (T2DM) is significantly associated with night shifts, with circadian disturbances affecting glucose metabolism, insulin sensitivity, and hormone regulation. The manuscript examines the relationship between melatonin, insulin, and glucose balance, highlighting pathways that link T2DM to stroke risk. Additionally, dyslipidemia, particularly reduced HDL-c levels, results from shift work and contributes to stroke development. High lipid levels cause oxidative stress, inflammation, and endothelial dysfunction, increasing cerebrovascular risks. The manuscript details the effects of dyslipidemia on brain functions, including disruptions in blood flow, blood-brain barrier integrity, and neural cell death. This comprehensive analysis emphasizes the complex interplay of circadian disruption, hypertension, diabetes, and dyslipidemia in increasing stroke risk among shift workers. Understanding these mechanisms is essential for developing targeted interventions to reduce stroke susceptibility and improve cerebrovascular health in this vulnerable population.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"6"},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and prognosis analysis of pseudomonas aeruginosa bloodstream infection in adults: a retrospective study.","authors":"Xiaoya Huang, Jiahai Ding, Xin Yang, Bingxin Tian, Runli Yu, Min Lyu, Wen Liu, Qin Ding","doi":"10.1007/s10238-024-01517-7","DOIUrl":"10.1007/s10238-024-01517-7","url":null,"abstract":"<p><p>Pseudomonas aeruginosa bloodstream infections (PA BSIs) in adults, especially those complicated by sepsis, are associated with high rates of morbidity and mortality. Early identification of risk factors for both mortality and sepsis-induced coagulopathy (SIC) is critical to optimizing patient management and improving outcomes. We conducted a retrospective analysis of 118 adult patients diagnosed with PA BSIs at the Affiliated Hospital of Xuzhou Medical University from January 2022 to February 2024. Univariate analysis was employed to identify significant clinical factors, followed by multivariate stepwise logistic regression to determine independent predictors of mortality and SIC. Based on these findings, nomogram models were constructed and evaluated using the area under the receiver operating characteristic curve (AUC), Bootstrap resampling, and calibration plots to assess model performance. Empiric sensitive antibiotic therapy (ESAT) (OR = 0.039, P < 0.001), coronary artery disease (CAD) (OR = 10.315, P = 0.010), and invasive mechanical ventilation (OR = 3.926, P = 0.020) emerged as significant predictors of mortality. In contrast, elevated C-reactive protein (CRP) (OR = 1.011, P = 0.003), procalcitonin (PCT) (OR = 1.030, P = 0.005), and lower hemoglobin levels (OR = 0.963, P = 0.004) were independently associated with SIC. The AUC of mortality prediction model is 0.908, while the SIC prediction model yielded an AUC of 0.817. The predictive models developed in this study demonstrate early identification of mortality rates and SIC risk in PA BSI patients, which may have the potential to guide timely therapeutic interventions and improve clinical outcomes in this high-risk population.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"5"},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of the endothelial-immune candidate biomarker endoglin in rheumatic diseases.","authors":"Arduino A Mangoni, Angelo Zinellu","doi":"10.1007/s10238-024-01519-5","DOIUrl":"10.1007/s10238-024-01519-5","url":null,"abstract":"<p><p>Existing challenges in accurately diagnosing various rheumatic diseases (RDs) have stimulated the search for novel biomarkers to aid clinical evaluation and monitoring. We conducted a systematic review and meta-analysis of studies investigating the candidate biomarker endoglin (CD105), a transmembrane glycoprotein expressed in endothelial, myeloid, and lymphoid cells, in RD patients and healthy controls. We searched PubMed, Scopus, and Web of Science from inception to 10 August 2024 to identify relevant studies. We evaluated the risk of bias using the JBI Critical Appraisal Checklist and the certainty of evidence using GRADE (PROSPERO registration number: CRD42023581008). Overall, circulating endoglin concentrations were significantly higher in RD patients compared to controls (13 studies; standard mean difference, SMD = 0.64, 95% CI 0.13 to 1.14, p = 0.014; low certainty of evidence). The effect size of the between-group differences in endoglin concentrations was not significantly associated with age, male-to-female ratio, year of publication, number of participants, or mean RD duration. By contrast, the effect size was statistically significant in studies conducted in the European region (p = 0.033), involving patients with systemic sclerosis (p = 0.032), and measuring serum (p = 0.019). The results of this systematic review and meta-analysis suggest the potential pathophysiological role of endoglin in RDs. This, however, requires further investigation in prospective studies, particularly in patients with systemic sclerosis.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"25 1","pages":"4"},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}