Blood PurificationPub Date : 2024-01-01Epub Date: 2023-11-08DOI: 10.1159/000534295
Takashi Yamamoto, Shun Kunomura, Takumi Taniguchi
{"title":"Cytokine Adsorption Effects of a Novel Hemofiltration Column for the Treatment of Experimental Endotoxemia.","authors":"Takashi Yamamoto, Shun Kunomura, Takumi Taniguchi","doi":"10.1159/000534295","DOIUrl":"10.1159/000534295","url":null,"abstract":"<p><strong>Introduction: </strong>The TKM-101 is a new hemofiltration column packed with a polymer alloy membrane consisting of polyethersulfone, polyvinylpyrrolidone, and sulfonated poly (arylene ether) copolymers. We examined the ability of the TKM-101 column to remove cytokines and humoral mediators from blood in vitro and the effects of extracorporeal treatment with the TKM-101 column on the mortality rate and inflammatory responses to endotoxic shock in vivo.</p><p><strong>Methods: </strong>In vitro and in vivo laboratory investigations were conducted. In the in vitro experiment, the adsorption abilities of TKM-101, AN69-ST, and control columns for cytokine-related sepsis in blood were compared using human serum samples. In the in vivo experiment, male Sprague-Dawley rats were anesthetized and injected with Escherichia coli endotoxin (15 mg/kg, intravenously). Afterward, the rats were assigned (in a double-blind manner) to one of three groups (n = 17 per group): apheresis with a control column (control group), apheresis with an AN69-ST column (AN69-ST group), or apheresis with a TKM-101 column (TKM-101 group). Outcomes were compared among the groups.</p><p><strong>Results: </strong>In vitro, the concentrations of all evaluated cytokines significantly decreased with the TKM-101 column compared to those with the control column; however, there were no significant differences between the TKM-101 and AN69-ST columns. In vivo, the mortality rates 8 h after endotoxin injection were 65%, 29%, and 29% for the control, AN69-ST, and TKM-101 groups, respectively. Hypotension and elevated plasma cytokine concentrations were less prominent in the TKM-101 and AN69-ST groups compared to those in the control group.</p><p><strong>Conclusions: </strong>TKM-101 effectively removed proteins of varying sizes, from small-sized proteins such as interleukin (IL)-8 to mid-sized protein such as IL-10 in vitro. Moreover, TKM-101 treatment reduced mortality and had inhibitory effects on inflammatory responses in endotoxemic rats. These findings suggest that TKM-101 treatment may be available for use in patients with sepsis and/or endotoxemia.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"61-70"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study.","authors":"Shiori Yoshida, Suguru Yamamoto, Daisuke Miyauchi, Ryohei Terashima, Atsushi Hashimoto, Haruna Miyazawa, Takahiro Tanaka, Masahiro Ishizawa, Mototsugu Tanaka, Yoshihiko Tomita, Ikuo Aoike, Shin Goto, Ichiei Narita","doi":"10.1159/000534459","DOIUrl":"10.1159/000534459","url":null,"abstract":"<p><strong>Introduction: </strong>The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and β2-microglobulin (β2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study.</p><p><strong>Methods: </strong>Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, β2-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment.</p><p><strong>Results: </strong>Clearance rates of α1-m at 60 min were -2.8 ± 5.2 mL/min with Pre-PS, -0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS.</p><p><strong>Conclusion: </strong>The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"123-129"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood PurificationPub Date : 2024-01-01Epub Date: 2024-08-30DOI: 10.1159/000541200
Nuri Baris Hasbal, Mustafa Sevinc, Vuslat Yilmaz, Abdullah Yilmaz, Hande Yuceer Korkmaz, Taner Basturk, Elbis Ahbap, Tamer Sakaci, Bengt Lindholm, Abdulkadir Unsal
{"title":"Peripheral Blood Lymphocyte Subgroups in Patients Undergoing Hemodialysis with Medium Cutoff Membranes and High-Flux Membranes: THE SHE Continuation Study.","authors":"Nuri Baris Hasbal, Mustafa Sevinc, Vuslat Yilmaz, Abdullah Yilmaz, Hande Yuceer Korkmaz, Taner Basturk, Elbis Ahbap, Tamer Sakaci, Bengt Lindholm, Abdulkadir Unsal","doi":"10.1159/000541200","DOIUrl":"10.1159/000541200","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) poses a significant global health burden, with increasing prevalence and high morbidity and mortality rates, particularly in end-stage kidney disease (ESKD). While traditional risk factors contribute, the exact mechanisms remain elusive, with inflammation playing a pivotal role. Medium cutoff (MCO) membranes offer promise in improving dialysis outcomes by efficiently clearing uremic toxins without substantial albumin loss. We aimed to elucidate the impact of MCO and high-flux (HF) membranes on peripheral blood lymphocyte subpopulations in hemodialysis patients.</p><p><strong>Methods: </strong>Twenty-four ESKD patients underwent 36 sessions each with MCO and HF membranes. Immunophenotyping by flow cytometry was performed to analyze lymphocyte subsets.</p><p><strong>Results: </strong>NK cell percentages significantly increased with MCO, returning to baseline with HF. Th1 cells decreased post-HF, while Th2 and Tfh cells increased with MCO and persisted. Treg cells remained stable with MCO but decreased with HF.</p><p><strong>Conclusion: </strong>MCO dialysis induced an anti-inflammatory shift, evidenced by increased Th2 and Tfh cells and stable Treg cells. NK cells also responded favorably to MCO. These findings underscore MCO membranes' potential to modulate immune responses and improve patient outcomes in ESKD.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"937-946"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of Nanoparticles as Novel Adsorbents in Blood Purification Strategies.","authors":"Yue Shen, Yuqi Shen, Xiao Bi, Aiwen Shen, Yifeng Wang, Feng Ding","doi":"10.1159/000539286","DOIUrl":"10.1159/000539286","url":null,"abstract":"<p><strong>Background: </strong>Blood purification therapy for patients overloaded with metabolic toxins or drugs still needs improvement. Blood purification therapies, such as in hemodialysis or peritoneal dialysis can profit from a combined application with nanoparticles.</p><p><strong>Summary: </strong>In this review, the published literature is analyzed with respect to nanomaterials that have been customized and functionalized as nano-adsorbents during blood purification therapy. Liposomes possess a distinct combined structure composed of a hydrophobic lipid bilayer and a hydrophilic core. The liposomes which have enzymes in their aqueous core or obtain specific surface modifications of the lipid bilayer can offer appreciated advantages. Preclinical and clinical experiments with such modified liposomes show that they are highly efficient and generally safe. They may serve as indirect and direct adsorption materials both in hemodialysis and peritoneal dialysis treatment for patients with renal or hepatic failure. Apart from dialysis, nanoparticles made of specially designed metal and activated carbon have also been utilized to enhance the removal of solutes during hemoadsorption. Results are a superior adsorption capacity and good hemocompatibility shown during the treatment of patients with toxication or end-stage renal disease. In summary, nanomaterials are promising tools for improving the treatment efficacy of organ failure or toxication.</p><p><strong>Key messages: </strong>(i) The pH-transmembrane liposomes and enzyme-loaded liposomes are two representatives of liposomes with modified aqueous inner core which have been put into practice in dialysis. (ii) Unmodified or physiochemically modified liposomal bilayers are ideal binders for lipophilic protein-bound uremic toxins or cholestatic solutes, thus liposome-supported dialysis could become the next-generation hemodialysis treatment of artificial liver support system. (iii) Novel nano-based sorbents featuring large surface area, high adsorption capacity and decent biocompatibility have shown promise in the treatment of uremia, hyperbilirubinemia, intoxication, and sepsis. (vi) A major challenge of production lies in avoiding changes in physical and chemical properties induced by manufacturing and sterilizing procedures.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"743-754"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine Learning-Aided Decision-Making Model for the Discontinuation of Continuous Renal Replacement Therapy.","authors":"Siyi Zhu, Jing Yan, Shijin Gong, Xue Feng, Gangmin Ning, Liang Xu","doi":"10.1159/000539787","DOIUrl":"10.1159/000539787","url":null,"abstract":"<p><strong>Introduction: </strong>Continuous renal replacement therapy (CRRT) is a primary form of renal support for patients with acute kidney injury in an intensive care unit. Making an accurate decision of discontinuation is crucial for the prognosis of patients. Previous research has mostly focused on the univariate and multivariate analysis of factors in CRRT, without the capacity to capture the complexity of the decision-making process. The present study thus developed a dynamic, interpretable decision model for CRRT discontinuation.</p><p><strong>Method: </strong>The study adopted a cohort of 1,234 adult patients admitted to an intensive care unit in the MIMIC-IV database. We used the eXtreme Gradient Boosting (XGBoost) machine learning algorithm to construct dynamic discontinuation decision models across 4 time points. SHapley Additive exPlanation (SHAP) analysis was conducted to exhibit the contributions of individual features to the model output.</p><p><strong>Result: </strong>Of the 1,234 included patients with CRRT, 596 (48.3%) successfully discontinued CRRT. The dynamic prediction by the XGBoost model produced an area under the curve of 0.848, with accuracy, sensitivity, and specificity of 0.782, 0.786, and 0.776, respectively. The performance of the XGBoost model was far superior to other test models. SHAP demonstrated that the features that contributed most to the model results were the Sequential Organ Failure Assessment score, serum lactate level, and 24-h urine output.</p><p><strong>Conclusion: </strong>Dynamic decision models supported by machine learning are capable of dealing with complex factors in CRRT and effectively predicting the outcome of discontinuation.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"704-715"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effects of Early-Phase, Low- or Standard-Intensity Continuous Renal Replacement Therapy on Acid-Base Control and Clinical Outcomes: An Observational Study.","authors":"Kosuke Yagi, Tomoko Fujii, Akira Kageyama, Toshishige Takagi, Junpei Ikeda, Shoichi Uezono","doi":"10.1159/000539810","DOIUrl":"10.1159/000539810","url":null,"abstract":"<p><strong>Introduction: </strong>The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline recommends administering an effluent volume of 20-25 mL/kg/h during continuous renal replacement therapy (CRRT) for acute kidney injury. Recent evidence on CRRT initiation showed that less intervention might be beneficial for renal recovery. This study aimed to explore the association between early-phase low CRRT intensity and acid-base balance corrections and clinical outcomes.</p><p><strong>Methods: </strong>This was a single-centre, retrospective, observational study at a tertiary intensive care unit (ICU) in Japan. All adult patients requiring CRRT in the ICU were included. Eligible patients were classified into the Low group (dialysate flow rate [QD] 10.0-19.9 mL/kg/h) and the Standard group (QD ≥20 mL/kg/h) by the intensity of CRRT at the beginning. The primary outcomes were acid-base parameters 6 h after CRRT initiation. We used an inverse probability of treatment weighting analysis to estimate the association between the intensity group and the outcomes.</p><p><strong>Results: </strong>Overall, 194 patients were classified into the Low group (n = 144) and the Standard group (n = 50). The Standard group presented with more severe acid-base disturbances, including lower pH and base excess (BE) at baseline. At 6 h after CRRT initiation, pH, BE, and strong ion difference values were comparable, even after adjusting for baseline severity. Despite the efficient correction, no evident differences were observed in clinical outcomes between the two groups.</p><p><strong>Conclusions: </strong>The initial standard intensity appeared to be efficient in correcting acid-base imbalance at the early phase of CRRT; however, further studies are needed to assess the impact on clinical outcomes.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"716-724"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood PurificationPub Date : 2024-01-01Epub Date: 2024-07-18DOI: 10.1159/000540302
Esha Sondhi, Martha Stewart, Jenna Harper, Leslie Konyk, Coleen McSteen, Kelli L Crowley, Nahmah Kim-Campbell, Anthony Fabio, Dana Y Fuhrman
{"title":"A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy.","authors":"Esha Sondhi, Martha Stewart, Jenna Harper, Leslie Konyk, Coleen McSteen, Kelli L Crowley, Nahmah Kim-Campbell, Anthony Fabio, Dana Y Fuhrman","doi":"10.1159/000540302","DOIUrl":"10.1159/000540302","url":null,"abstract":"<p><strong>Introduction: </strong>Anticoagulants are used in continuous renal replacement therapy (CRRT) to prolong filter life. There are no prior investigations directly comparing epoprostenol to more commonly used forms of anticoagulation in children. Therefore, the primary aim of this study was to assess the efficacy and safety of epoprostenol as compared to heparin and citrate anticoagulation in a pediatric cohort.</p><p><strong>Methods: </strong>We performed a retrospective analysis of all patients <18 years of age admitted to an academic quaternary care children's hospital from 2017-2022 who received epoprostenol, heparin, or citrate exclusively for CRRT anticoagulation. Efficacy was evaluated by comparing the hours to the first unintended filter change and the ratio of filters used to CRRT days. Safety was assessed by evaluating changes in platelet count and vasoactive-ionotropic score (VIS).</p><p><strong>Results: </strong>Of 101 patients, 44 received epoprostenol (43.6%), 38 received heparin (37.6%), and 19 received citrate (18.8%). The first filter change was more commonly planned in patients receiving anticoagulation with epoprostenol (43%) as compared to citrate (11%) or heparin (29%) (p = 0.034). Of those patients where the first filter change was unintended (n = 33), there were greater median hours until the filter was replaced in those receiving epoprostenol (29) when compared to citrate (21) (p = 0.002) or heparin (18) (p = 0.003). There was a smaller median ratio of filters used to days on therapy in the patients that received epoprostenol (0.53) when compared to citrate (1) (p = 0.003) or heparin (0.75) (p = 0.001). For those receiving epoprostenol, there was no significant decrease in platelet count when comparing values prior to CRRT initiation through 7 days of therapy. There was no significant difference in VIS when comparing values prior to CRRT initiation through the first 2 days of CRRT.</p><p><strong>Conclusions: </strong>Epoprostenol-based anticoagulation is effective when compared to other anticoagulation strategies used in pediatric CRRT with a favorable side effect profile.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"838-846"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood PurificationPub Date : 2024-01-01Epub Date: 2024-07-19DOI: 10.1159/000540403
Hinpetch Daungsupawong, Viroj Wiwanitkit
{"title":"Comment on \"Evaluating ChatGPT's Accuracy in Responding to Patient Education Questions on Acute Kidney Injury and Continuous Renal Replacement Therapy\".","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1159/000540403","DOIUrl":"10.1159/000540403","url":null,"abstract":"","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"847-848"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood PurificationPub Date : 2024-01-01Epub Date: 2024-08-22DOI: 10.1159/000540416
{"title":"Selected abstracts from the 42nd Vicenza Course AKI-CRRT-ECOS and Critical Care Nephrology.","authors":"","doi":"10.1159/000540416","DOIUrl":"https://doi.org/10.1159/000540416","url":null,"abstract":"<p><p>Selected abstracts from the 42nd Vicenza Course AKI-CRRT-ECOS and Critical Care Nephrology.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":"53 Suppl 1","pages":"1-89"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood PurificationPub Date : 2024-01-01Epub Date: 2024-08-22DOI: 10.1159/000540416
{"title":"Selected abstracts from the 42nd Vicenza Course AKI-CRRT-ECOS and Critical Care Nephrology.","authors":"","doi":"10.1159/000540416","DOIUrl":"https://doi.org/10.1159/000540416","url":null,"abstract":"<p><p>Selected abstracts from the 42nd Vicenza Course AKI-CRRT-ECOS and Critical Care Nephrology.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":"53 Suppl 1 ","pages":"1-89"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}