Alimentary Pharmacology & Therapeutics最新文献

{"title":"Editorial: Mesenchymal Stem Cell Therapy for Perianal Fistulising Crohn's Disease—Effective or Hype? Authors' Reply","authors":"Péter Bacsur, Klaudia Farkas, Tamás Molnár","doi":"10.1111/apt.18427","DOIUrl":"https://doi.org/10.1111/apt.18427","url":null,"abstract":"<p>We appreciate the thoughtful comments by Drs. McCurdy and Wong regarding our study on the effectiveness and safety of mesenchymal stem cell treatment for fistulising Crohn's disease. We analysed 223 patients in an international, multicentre setting, who underwent darvadstrocel treatment [<span>1, 2</span>]. They clearly highlighted the unmet need for new therapeutic approaches for perianal fistulising Crohn's disease (PFCD) in their editorial. We agree that discrepancies between the effectiveness results of large clinical trials and observational studies need to be carefully reconsidered to support position statements on the use of mesenchymal stem cell treatment in PFCD.</p>\u0000<p>First, in our real-world study, preparation—including curettage and seton placement—preceded the administration of darvadstrocel in all cases, in accordance with the protocols followed in pivotal clinical trials. Controlled, high-quality perianal surgery can achieve a high success rate, even in refractory cases, if performed in a highly experienced centre [<span>3</span>]. Due to the structural design of our real-world study, it is not possible to determine the exact contribution of darvadstrocel to the improvements observed in our patients, relative to the surgical intervention. However, the 62% closure rate is clearly higher than the closure rate seen in the placebo arm of the ADMIRE studies.</p>\u0000<p>Second, we acknowledge that increased effectiveness rates are often observed in real-world settings compared with randomised trials, particularly in the field of pharmacological sciences. This discrepancy is probably due to differences in population characteristics, inclusion criteria, study design, data collection methods and statistical considerations (such as the handling of confounders). We reported clinical remission rates of 72.2% at Week 26 and 62.3% at Week 52, which align with the cumulative effectiveness of 68.1%–77.2% in a systematic review of observational trials with darvadstrocel, with negligible between-study heterogeneity [<span>4</span>]. It is also worth noting that combined remission (defined as the MRI endpoint of absence of collections > 2 cm) was observed in 60.6% of patients at Week 26 and 52.3% at Week 52.</p>\u0000<p>Third, while evaluating combined remission can provide a robust end point, it has limitations. MRI assessment of PFCD requires expert interpretation, and the precise definitions of fistula healing remain inconclusive [<span>5</span>]. Furthermore, regular monitoring of fistula healing with MRI is not yet part of standard clinical practice, as evidenced by our real-world results. From a patients' perspective, the cessation of fistula drainage and the resolution of symptoms such as the feeling of uncleanliness are considered more important than MRI findings.</p>\u0000<p>Furthermore, we found that approximately 80% of patients expressed satisfaction with the treatment after 1 year, highlighting its positive impact on quality of life, especially","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"4 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: H. pylori Antimicrobial Susceptibility Testing—An Expanding Toolbox","authors":"Suvithan Rajadurai, Steven F. Moss","doi":"10.1111/apt.18395","DOIUrl":"https://doi.org/10.1111/apt.18395","url":null,"abstract":"<p><i>Helicobacter pylori</i> (<i>H. pylori</i>) is one of the most common bacterial infections globally and, due to its association with gastric cancer, the leading cause of infection-related malignancy worldwide [<span>1, 2</span>]. Effective eradication of <i>H. pylori</i> has long been challenged by empiric and complicated treatment regimens linked to increasing antimicrobial resistance [<span>3</span>]. Within the UnitedStates, resistance rates to metronidazole, clarithromycin and levofloxacin are 42.1%, 31.5% and 37.6%, respectively [<span>4</span>] leading to a recommendation in the recently published US guidelines against using clarithromycin or levofloxacin unless the strain is known to be sensitive [<span>5</span>].</p>\u0000<p><i>H. pylori</i> antimicrobial resistance testing is still rarely utilised in routine clinical practice as culture-based testing is slow (often taking one to 2 weeks), often unsuccessful and incontrovertible evidence is still lacking that a ‘tailored’ approach provides superior clinical outcomes over the continuing use of empiric regimens [<span>1</span>]. This is likely to change with the encouragement of more susceptibility testing by national and international authorities [<span>5, 6</span>], and the availability of rapid, sensitive and accurate molecular methods as increasingly used in clinical microbiology practice.</p>\u0000<p>Vasapolli et al. have added to the emerging molecular choices by describing genotypic <i>H. pylori</i> clarithromycin and levofloxacin susceptibility testing by real-time PCR from gastric aspirates harvested at routine upper endoscopy [<span>7</span>]. The results, based on the common gyrase A and 23sRNA mutations that lead to levofloxacin and clarithromycin resistance respectively, [<span>8</span>] were highly concordant with those of conventional phenotypic testing. The rapidity, efficiency and accuracy of this approach could enable endoscopists to both diagnose <i>H. pylori</i> and choose an appropriate regimen based on antimicrobial susceptibility within hours of the procedure.</p>\u0000<p>Gastric aspirate susceptibility testing adds a potential new tool to the growing toolbox of molecular methods, some of which are commercially available. These include biopsy-based PCR, fluorescent in situ hybridisation and next generation sequencing. Stool-based testing (obviating the need for endoscopy) has also been investigated for clarithromycin resistance by PCR as well as for a wider panel of antibiotics by next generation sequencing [<span>9</span>].</p>\u0000<p>Research to this point has demonstrated the feasibility and robustness of these biopsy-dependent or stool-based molecular methods to evaluate <i>H. pylori's</i> susceptibility to clarithromycin and levofloxacin. Resistance to these antibiotics, which is due to a small group of well-defined mutations, is clearly correlated with clinical outcome. Whether molecular testing will be useful for the more complex question of metronidazole resistance remains ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Mesenchymal Stem Cell Therapy for Perianal Fistulising Crohn's Disease—Effective or Hype?","authors":"Jeffrey D McCurdy, Serre-yu Wong","doi":"10.1111/apt.18408","DOIUrl":"https://doi.org/10.1111/apt.18408","url":null,"abstract":"<p>Perianal fistulising Crohn's disease (PFCD) is a common yet challenging phenotype of Crohn's disease, due to its refractory nature and substantial impact on patients' health and quality of life [<span>1</span>]. PFCD is also associated with high direct health care costs that remain high for years beyond the initial presentation of perianal fistulas [<span>2</span>]. While studies have demonstrated the effectiveness of anti-tumour necrosis factor (TNF) therapy for this condition, a substantial proportion of patients remain symptomatic [<span>3</span>]. As a result, innovative treatment strategies are needed.</p>\u0000<p>Bacsur and colleagues reported on the effectiveness and safety of locally injected allogenic, adipose-derived mesenchymal stem cells (MSC) (Darvadstrocel) for treatment of complex PFCD [<span>4</span>]. Like the ADMIRE trials, patients underwent fistula tract conditioning by “rigorous” curettage and seton placement before surgical closure of the internal fistula opening and local injection of Darvadstrocel [<span>5, 6</span>]. Among the 204 patients who underwent treatment in this real-world study, 62% achieved fistula closure at week 52. Importantly, closure was determined clinically without radiologic evaluation. Furthermore, the proportion of patients with a perianal disease activity score (PDAI) of > 4 decreased from 58% at baseline to 20% at week 52 (<i>p</i> < 0.001). Only 14% of patients experienced an adverse event requiring hospitalisation; most involved perianal abscess or pain.</p>\u0000<p>The impressive rate of fistula closure reported in this study was higher than those reported in the ADMIRE trials (56% in ADMIRE I and 43% in ADMIRE II) [<span>6, 7</span>]. In addition to the open-label study design, the study population probably had a lower fistula disease burden overall given that 42% of patients had a PDAI score of 4 or lower at baseline. Furthermore, only 43% of patients had multiple fistula tracts, and 14% had branching tracts, both of which have been shown to be predictive of anti-TNF failure in PFCD [<span>8</span>].</p>\u0000<p>While these results are promising, this study was uncontrolled. As a result, it is unclear if fistula closure was a result of MSC therapy itself, the surgical intervention that accompanied MSC treatment (curettage and closure of the internal fistula track opening), and/or the natural history of PFCD after seton removal. These are important considerations considering the results of the ADMIRE-II trial. This was a large phase III randomised controlled trial, which found that MSC therapy (Darvadstrocel) administered after fistula tract conditioning and surgical closure was no more effective in achieving combined clinical and radiologic remission at week 24 than fistula tract conditioning and surgical closure alone (49% vs. 46%, <i>p</i> = 0.57) [<span>6</span>]. In contrast, in ADMIRE-I, MSC therapy was significantly more effective than fistula tract conditioning and surgical closure alone (50% ","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leucine-Rich Alpha-2 Glycoprotein Is Associated With Transmural Inflammation Assessed by Intestinal Ultrasound in Patients With Crohn's Disease","authors":"Moeko Komatsu, Shintaro Sagami, Aya Hojo, Ryo Karashima, Masa Maeda, Yoko Yamana, Kanade Serizawa, Satoko Umeda, Kunio Asonuma, Masaru Nakano, Toshifumi Hibi, Takahisa Matsuda, Taku Kobayashi","doi":"10.1111/apt.18430","DOIUrl":"https://doi.org/10.1111/apt.18430","url":null,"abstract":"Intestinal ultrasound (IUS) is a non-invasive tool for evaluating transmural inflammation in Crohn's disease (CD). However, its utility is constrained by operator dependency and limited accessibility.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality of Acute Kidney Injury in Cirrhosis: A Systematic Review and Meta-Analysis of Over 5 Million Patients Across Different Clinical Settings","authors":"Vasileios Lekakis, Florence Wong, Aikaterini Gkoufa, George V. Papatheodoridis, Evangelos Cholongitas","doi":"10.1111/apt.18426","DOIUrl":"https://doi.org/10.1111/apt.18426","url":null,"abstract":"Acute kidney injury (AKI) represents a commonly seen condition in the natural course of cirrhosis associated with unfavourable outcomes.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"226 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Real-Life Evaluation of Effectiveness of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease Emphasises Importance of Appropriate Patient Selection and Centre Expertise—Authors' Reply","authors":"Péter Bacsur, Klaudia Farkas, Tamás Molnár","doi":"10.1111/apt.18432","DOIUrl":"https://doi.org/10.1111/apt.18432","url":null,"abstract":"<p>We are grateful to Drs. Gao and Segal for their letter concerning our article [<span>1, 2</span>]. As pointed out, patient selection, concurrent medication and an experienced medical centre are the important pillars of successful outcomes of mesenchymal stem cell (MSC) treatment in perianal fistulising Crohn's disease (PFCD). Despite the evolving evidence, it is still unclear whether MSC treatment should be used early or late in the disease process, how can we optimise patients prior to receiving stem cell therapy and whether there are any clinical or biochemical predictors of treatment success [<span>3</span>].</p>\u0000<p>Conflicting results between ADMIRE trials with real-life data highlight the need to better understand the factors associated with successful treatment. However, our results suggest that, as in case of luminal CD [<span>4</span>], early intervention in PFCD is crucial for improving therapeutic outcomes. Furthermore, analysing the discrepancies between ADMIRE results emphasises the importance of population characteristics, as pointed out by Drs. Gao and Segal. An additional important consideration is that the inclusion of milder cases, compared to the ADMIRE trials, is likely to significantly enhance the effectiveness of darvadstrocel. Based on this, we believe that appropriately positioning a clinically proven, effective therapy is certainly a better alternative than completely abandoning an option that, according to real-world data, provides a significant improvement in quality of life for most patients in a highly restrictive setting.</p>\u0000<p>The growing therapeutic arsenal for inflammatory bowel disease clearly underscores the need for patient care in centres with well-trained specialists who have appropriate expertise in the management of difficult-to-treat patients. This applies not only to the use of biological therapies and small molecules but also to the application of darvadstrocel for treating PFCD.</p>\u0000<p>We agree with Drs. Gao and Segal that further well-designed, real-world clinical studies are needed to better define the role of MSC therapy and help to position it within the treatment protocols for PFCD.</p>","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"79 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter: Real-Life Evaluation of Effectiveness of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease Emphasises the Importance of Appropriate Patient Selection and Centre Expertise","authors":"Weilun Gao, Jonathan P. Segal","doi":"10.1111/apt.18411","DOIUrl":"https://doi.org/10.1111/apt.18411","url":null,"abstract":"&lt;p&gt;Managing complex perianal fistulas in Crohn's disease is challenging as the condition is often refractory to conventional medical treatment strategies and surgery may be associated with significant compromise to quality of life [&lt;span&gt;1&lt;/span&gt;]. The real-world retrospective multicentre cohort study by Bacsur et al. [&lt;span&gt;2&lt;/span&gt;] offers promising results in the application of CX601 mesenchymal stem cell (MSC) treatment (Darvadstrocel). It is worth examining the superior results compared to two previous significant phase III multicentre randomised control trials by the ADMIRE-CD group [&lt;span&gt;3, 4&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Bacsur et al. demonstrated higher rates of perianal clinical remission defined as closure of all treated fistulas (72.2% at W26 and 62.3% at W52) surpassing secondary endpoints in the treatment cohort of the ADMIRE CD trial (55% at W24) [&lt;span&gt;3&lt;/span&gt;] and the more recent ADMIRE CD II trial treatment group (49.8% and 43.1% at W24 and W52, respectively) [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Several factors probably contributed to these improved outcomes. Differences in baseline disease severity and degree of prior advanced therapy use are key considerations. Patients in the ADMIRE-CD trials generally experienced longer delay during stable disease prior to commencing darvadstrocel (6 months vs. 3 months in Bacsur study) with longer established fistulas (draining for at least 6 weeks) and higher baseline mean Crohn's Disease Activity Index scores (88.7 vs. 51.1 in the Bacsur study). Moreover, ADMIRE CD excluded patients who had recently received corticosteroids, and had a higher proportion of baseline advanced therapy use (78% anti-TNF usage vs. 42.6% in Bacsur et al.), indicating a focus on patients with more severe disease [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;The experience level of treating centres may also play a critical role. Bacsur et al. conducted their study in six high-volume centres, some with over 100 prior MSC administrations; ADMIRE CD treated 86 patients (vs. 223 in Bascur et al.) spanning 49 centres. This is in line with earlier findings from a Phase II trial that reported 71% fistula closure at 8 weeks focused in three specialised centres. This suggests the importance of centre expertise in allowing for precise MSC administration, post-procedural management and treatment success [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Variations in assessment methods of perianal fistula closure can also lead to disparities in reported results. ADMIRE CD employed masked gastroenterologists who used both visual inspection and manual compression to evaluate fistula closure rigorously [&lt;span&gt;3&lt;/span&gt;] while the assessment criteria in the present study was not fully detailed. Moreover, in Bascur et al., treating colorectal surgeons were also allowed to participate in evaluating the outcomes in an un-masked fashion possibly introducing confirmation bias [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Bacsur et al. offers valuable insights into the real-world application of MSC therapy for Crohn's disease","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"16 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Association Between Eosinophilic Oesophagitis and Oesophageal Cancer in US Adults: A Case–Control Study","authors":"Natasha Albaneze, Cary C. Cotton, Chelsea Anderson, David A. Katzka, Evan S. Dellon","doi":"10.1111/apt.18431","DOIUrl":"https://doi.org/10.1111/apt.18431","url":null,"abstract":"While inflammation is implicated in the development of numerous cancers, whether eosinophilic oesophagitis (EoE) increases the risk of oesophageal cancer (OCa) remains understudied.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful Amendment of an Existing Hepatitis B Screening Programme by a Guideline Recommended Hepatitis D Screening in the Primary Care Setting","authors":"Toni Herta, Anna Joachim-Richter, David Petroff, Benno Wölk, Ingmar Wolffram, Thomas Berg, Jan Kramer, Olaf Bätz, Johannes Wiegand","doi":"10.1111/apt.18424","DOIUrl":"https://doi.org/10.1111/apt.18424","url":null,"abstract":"Despite European guidelines recommending anti-hepatitis D virus (HDV) screening for all hepatitis B surface antigen (HBsAg)-positive cases, screening rates remain insufficient.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"27 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early HBcrAg and Anti-HBc Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation—A Pooled Analysis of Two Clinical Trials","authors":"Edo J. Dongelmans, Jordan J. Feld, André Boonstra, Sylvia M. Brakenhoff, David Wong, Colina Yim, Mark Claassen, Pieter Honkoop, Bettina E. Hansen, Robert A. de Man, Scott Fung, Thomas Berg, Florian van Bömmel, Harry L. A. Janssen, Milan J. Sonneveld","doi":"10.1111/apt.18416","DOIUrl":"https://doi.org/10.1111/apt.18416","url":null,"abstract":"Severe flares (ALT ≥ 10×ULN) are a well-recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance.","PeriodicalId":121,"journal":{"name":"Alimentary Pharmacology & Therapeutics","volume":"12 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}