Toxins最新文献

{"title":"Muscle-Specific Dosing of OnabotulinumtoxinA in Post-Stroke Upper-Limb Spasticity: A Descriptive Literature Review.","authors":"Małgorzata Cisowska-Adamiak, Magdalena Mackiewicz-Milewska, Elżbieta Dorota Miller","doi":"10.3390/toxins18040192","DOIUrl":"https://doi.org/10.3390/toxins18040192","url":null,"abstract":"<p><strong>Background: </strong>Botulinum neurotoxin type A is widely used in the management of post-stroke upper-limb spasticity; however, many studies report total injected doses rather than muscle-specific dosing, limiting clinical applicability. This study aimed to evaluate how frequently muscle-level dosing protocols of onabotulinumtoxinA are reported and to assess consistency of dosing patterns across published studies.</p><p><strong>Methods: </strong>A literature search was conducted in PubMed, Wiley/Cochrane Library, and EBSCO/CINAHL using a structured search strategy informed by PRISMA guidelines. Studies published within the last 10 years reporting on onabotulinumtoxinA treatment in post-stroke upper-limb spasticity with muscle-specific dosing data were included. Studies not providing muscle-level dosing or not allowing extraction of post-stroke upper-limb data were excluded. Data were summarized descriptively and compared across studies.</p><p><strong>Results: </strong>Twenty-seven full-text articles were assessed, and five studies met the inclusion criteria. Muscle-specific dosing was consistently reported for commonly treated muscles such as biceps brachii and wrist and finger flexors, whereas other muscles were less frequently targeted. Variability in dosing between studies was observed, particularly in multicenter real-world datasets. Standardized high-dose protocols contrasted with individualized dosing strategies, which generally showed more moderate dose ranges. Expert recommendations often suggest higher doses than those observed in routine clinical practice.</p><p><strong>Conclusions: </strong>Muscle-specific dosing of onabotulinumtoxinA in post-stroke upper-limb spasticity is reported infrequently, and substantial variability exists between studies and clinical practice. Standardized reporting of muscle-level dosing and its relationship to baseline spasticity severity is needed to improve clinical applicability and reproducibility.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782031","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}

{"title":"Establishment of Laboratory Bioassay System for <i>Phyllotreta striolata</i> Larvae and Screening of Novel Bt Cry Proteins.","authors":"Leqi Wang, Zhenyi Liu, Ivan M Dubovskiy, Changlong Shu, Jie Zhang, Junjie Zhang, Wenmei Du, Qi Peng","doi":"10.3390/toxins18040191","DOIUrl":"https://doi.org/10.3390/toxins18040191","url":null,"abstract":"<p><p><i>Phyllotreta striolata</i> is a global pest of cruciferous vegetables, and controlling its soil-dwelling larvae is challenging. The lack of standardized larval bioassay methods hinders the screening of effective biocontrol agents. In this study, we established a stable and standardized laboratory-efficacy trial system for <i>P. striolata</i> larvae. Indoor rearing techniques were optimized for <i>Brassica juncea</i> var. <i>foliosa</i> and <i>Brassica juncea</i> var. <i>megarrhiza</i> were identified as the optimal host plants, with ideal oviposition conditions at 26-28 °C using black flannel substrate, and soil-cultured <i>Brassica rapa</i> var. <i>pekinensis</i> as the host plant. Based on these findings, a larval bioactivity assay was established using <i>B. juncea</i> var. <i>megarrhiza</i> slices on water-agar. This system maintained a natural larval mortality rate below 5% within 48 h, meeting the bioassay requirements. The reliability of the system was validated by evaluating the activity of the engineered <i>Bacillus thuringiensis</i> (Bt) strain G033A against larvae, where the LC₅₀ value decreased from 23.013 mg/mL to 7.295 mg/mL with an extended treatment time (12-48 h). Using this standardized method, novel Cry proteins with high activity against <i>P. striolata</i> larvae were screened. Cry8Ca and Cry8Ga proteins exhibited LC₅₀ values of 2.243 mg/mL and 1.649 mg/mL, respectively.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782034","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}

{"title":"Homology Analysis of <i>Polistes dominula</i> and <i>Vespula</i> spp. Venoms: A Comparative In Vitro and In Silico Study.","authors":"María Morales, Alicia Jordá Marín, Bárbara Cases, Louise Wallace, Dolores Hernández Fernández De Rojas","doi":"10.3390/toxins18040190","DOIUrl":"https://doi.org/10.3390/toxins18040190","url":null,"abstract":"<p><p>A homologous classification for vespid venoms is missing. This study compared <i>Polistes dominula</i> and <i>Vespula</i> spp. venoms to evaluate their homology level. <i>P. dominula</i> and <i>Vespula</i> spp. extracts, including <i>V. germanica</i>, <i>V. maculifrons</i>, <i>V. pensylvanica</i>, <i>V. alascensis</i>, and <i>V. squamosa</i> in equal proportions, were generated from venom sacs and were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot using <i>Vespula</i>-positive sera. Bands described as allergenic were excised and sequenced through Liquid Chromatography-Mass Spectrometry tandem analysis (LC-MS/MS) to confirm their identity. Phospholipase (group 1) and hyaluronidase (group 2) enzymatic activities were measured. Group 1 and 5 3-D structures and sequence identity were analyzed in silico. The results showed that the <i>P. dominula</i> and <i>Vespula</i> spp. venom extracts exhibit similar protein profiles and comparable allergen composition, with phospholipase and hyaluronidase activities. The structures of Pol d 1 and Ves v 1 and Pol d 5 and Ves v 5 were highly similar, and the identity levels were high across and within the <i>Polistes</i> and <i>Vespula</i> genera (≥50%). These results suggest the inclusion of venoms from <i>Polistes</i> and <i>Vespula</i> genera as candidates to create a new homologous group for wasp venoms and indicate that the currently described homologous groups require revision.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782013","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}

{"title":"Purification and Characterization of His-Tagged Recombinant <i>Bacteroides fragilis</i> Toxin-2 Variants In Vitro and In Vivo.","authors":"Woo-Seung Kim, Soohyun Lee, Ki-Ju Kwon, So-Min Kim, Ki-Jong Rhee","doi":"10.3390/toxins18040189","DOIUrl":"https://doi.org/10.3390/toxins18040189","url":null,"abstract":"<p><p><i>Bacteroides fragilis</i> is a major commensal bacterium of the human colon. However, enterotoxigenic <i>B. fragilis</i> (ETBF) secretes <i>B. fragilis</i> toxin (BFT), a zinc-dependent metalloprotease that cleaves E-cadherin and promotes chronic inflammation and colorectal tumorigenesis. Despite extensive research, the cellular receptor for BFT remains unidentified. In this study, we developed His-tagged recombinant BFT variants including both catalytically active and inactive forms to facilitate biochemical and functional analyses. Functional assays confirmed that the active variant retained proteolytic activity and induced characteristic cellular responses, while the inactive variant served as an effective negative control. These results establish a robust experimental platform for BFT receptor identification and mechanistic studies of BFT-host interactions. The active and inactive BFT variants provide essential molecular tools for investigating ETBF pathogenicity and developing therapeutic interventions.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780938","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}

{"title":"Five-Year Real-World Outcomes of Hymenoptera Venom Immunotherapy: Clinical Effectiveness and Immunological Modifications.","authors":"Claudia Panzera, Sebastiano Gangemi, Luisa Ricciardi","doi":"10.3390/toxins18040187","DOIUrl":"https://doi.org/10.3390/toxins18040187","url":null,"abstract":"<p><p>Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients' daily lives due to the constant fear of accidental stings. Venom immunotherapy (VIT) is the only treatment capable of preventing severe systemic reactions (SSRs). Limited long-term real-life data are available, integrating both clinical and immunological outcomes. A five-year prospective observational study was conducted on 35 patients with a history of SSR who underwent VIT at a tertiary allergy center in Southern Italy; two of them had a diagnosis of systemic mastocytosis. Most patients were sensitized to Vespula, but others to Apis, <i>Polistes dominula</i> and <i>Vespa crabro</i>, reflecting the exposure pattern characteristic of Mediterranean regions. Clinical outcomes following accidental re-stings and serological trends, including total IgE, venom-specific IgE, and baseline serum tryptase, were assessed at treatment initiation and after five years of maintenance therapy. During the entire follow-up, all patients tolerated VIT. No SSRs occurred after accidental stings in 17/35 patients, confirming clinical protection achieved with VIT. Vespula serum-specific IgE presented a highly significant decrease; total IgE, tryptase and specific IgE for Apis, <i>Polistes dominula</i> and <i>Vespa crabro</i> showed a statistically significant decrease. Our findings reinforce the role of VIT as a well-tolerated, effective and disease-modifying treatment in a real-world setting.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781962","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}

{"title":"AI-Based Quantification of Botulinum Neurotoxin-Induced Facial Changes: Wrinkle Reduction, Region-Specific Effects, and Functional Correlates of Facial Muscle Activity.","authors":"Ibrahim Güler, Armin Kraus, Gerrit Grieb, Henrik Stelling","doi":"10.3390/toxins18040188","DOIUrl":"https://doi.org/10.3390/toxins18040188","url":null,"abstract":"<p><p>Botulinum neurotoxin (BoNT) treatment outcomes are commonly assessed through visual evaluation of facial wrinkle patterns, a process that remains inherently subjective despite structured grading systems. This study evaluated whether contemporary multimodal artificial intelligence (AI) systems can identify facial changes associated with BoNT treatment, using region-specific wrinkle patterns as surrogate markers of underlying muscle activity. A dataset of 46 facial images (23 pre-treatment, 23 post-treatment) was analyzed using four multimodal models, each assessed across five independent runs. Models were tasked with classifying treatment state from single images, detecting wrinkle presence in the forehead, glabella, and periorbital regions, and generating exploratory severity scores and age estimates. Two models achieved 100% accuracy in distinguishing pre- from post-treatment images in this dataset, while region-specific wrinkle detection was variable and frequently did not exceed majority-class baselines. Inter-run reliability varied substantially across models. Exploratory wrinkle severity scores showed directional differences between treatment states, whereas apparent age estimates demonstrated minimal systematic variation. These findings suggest that global facial changes associated with BoNT treatment appear to be detectable in model outputs, but region-specific assessment remains limited, underscoring the need for cautious interpretation and further validation.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781909","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}

{"title":"Interference of Large Clostridial Glucosyltransferases with the Endolysosomal Pathway: Toxin-Induced Imbalance of Early Endosomes, Functional Lysosomes and Autophagosomes.","authors":"Anna Langejürgen, Gudula Schmidt, Leon Unsöld, Helma Tatge, Ethel Oyson, Ralf Gerhard","doi":"10.3390/toxins18040186","DOIUrl":"https://doi.org/10.3390/toxins18040186","url":null,"abstract":"<p><p>Toxin A and B from Clostridioides difficile are the main pathogenicity factors for clinical symptoms of C. difficile infections. Receptor-mediated endocytosis and endosomal escape are required for targeting substrate proteins of the Rho-GTPase family. We previously reported that Toxin B (TcdB) affects endo-lysosomal transport and autophagic flux of target cells. These effects are independent from pathogenic Rho inhibition. Here, we aimed at further characterization of this event by immunofluorescent characterization of the vesicular structures that are affected. We found large aggregates of damaged endolysosomal structures positive for EEA1, LAMP1, CHMP4B and TcdB, as well as an increase in perinuclear concentration of non-mature autophagosomes (amphisomes) positive for SQSTM, Rab7, and LC3B. We investigated whether Rab7, a regulator of late endosome transport, is causative for decreased lysosome function. Although TcdB induced an increase in active Rab7, as tested by an RILP pull-down assay, inhibition of Rab7 did not prevent TcdB-induced decrease in cathepsin D as a surrogate for lysosome dysfunction. It also indicates that the observed increase in Rab7 positive amphisomes is secondary to lysosomal dysfunction. By applying an autoproteolytic deficient mutant of TcdB we proved that the release of the glucosyltransferase domain is mandatory for triggering all of these effects. This suggests that after membrane perforation the toxin remnants leave an open leak in endolysosomes affecting ion homeostasis. Investigation of all large clostridial glucosyltransferases and other toxins revealed lysosomal dysfunction as a general effect of many but not of all toxins that integrate into the endosome membrane.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782006","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}

{"title":"Entomopathogenic Nematode <i>Steinernema carpocapsae</i> Venom Proteins Disrupt Developmental Physiology and Reproduction of <i>Spodoptera frugiperda</i> (Lepidoptera: Noctuidae).","authors":"Manisha Mishra, Leonor Georgette Farias, Steven Song, Steven Nguyen, Purav Shah, Adler R Dillman","doi":"10.3390/toxins18040185","DOIUrl":"https://doi.org/10.3390/toxins18040185","url":null,"abstract":"<p><p>The use of <i>Steinernema carpocapsae</i> infective juveniles as biological control agents is a long-standing practice, yet the oral impact of their secreted venom proteins on crop pests remains largely unknown. We evaluated the oral toxicity of <i>S. carpocapsae</i> venom proteins against <i>Spodoptera frugiperda</i> using artificial diet assays. Ingestion caused significant dose-dependent toxicity in early-instar larvae, resulting in mortality and a prolonged developmental duration. Carry-over effects were profound; treated pupae were smaller and malformed, with only 19% of larvae fed on 1000 ng g^-1 venom protein-supplemented diet reaching adulthood compared to 92% in controls. Surviving adults lived 30% fewer days and laid over 90% fewer morphologically normal eggs. These physiological disruptions coincided with elevated oxidative stress and detoxification enzyme activity, suggesting the venom induces oxidative and detoxification responses, which may be associated with the observed phenotypic alterations. This study provides the first demonstration of the oral toxicity of entomopathogenic nematode venom proteins, positioning them as a promising resource for the discovery of novel insecticidal proteins for sustainable pest management.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781931","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}

{"title":"Patient Perceptions of a Preventive Effect of Long-Term Botulinum Neurotoxin Therapy in Cervical Dystonia.","authors":"Harald Hefter, Sara Samadzadeh","doi":"10.3390/toxins18040184","DOIUrl":"https://doi.org/10.3390/toxins18040184","url":null,"abstract":"<p><p>Patients with cervical dystonia (CD) often believe that disease severity would have progressed beyond the pre-treatment level if botulinum neurotoxin (BoNT) therapy had not been initiated. The aim of the present study was to assess the perceptions of long-term BoNT-treated patients with CD regarding the expected course of disease severity over the next 10 years under the hypothetical assumption that BoNT therapy is discontinued. Fifty patients with idiopathic CD receiving long-term BoNT therapy were screened, and 43 patients were included. Disease severity at the day of recruitment was assessed as a percentage of CD severity at the onset of BoNT therapy (PAS-%). Patients also generated, in a standardized manner, a graph illustrating the development of CD severity since initiation of BoNT therapy. Subsequently, patients estimated the expected severity of CD after 10 years, expressed as a percentage of severity at BoNT therapy onset (PAS-STD), under the hypothetical assumption that BoNT therapy was discontinued at the time of recruitment. They additionally drew a graph depicting the anticipated progression of CD severity over the subsequent 10 years under this assumption. Furthermore, 33 of these 43 patients had previously assessed the expected development of CD severity under the assumption that no BoNT therapy had ever been performed (PAS-NO%) in an earlier study. Mean PAS-STD was significantly higher than mean PAS-% (<i>p</i> < 0.001). Comparison of mean PAS-STD with mean PAS-NO% in the 33 patients who participated in both studies demonstrated that mean PAS-STD was significantly lower than mean PAS-NO% (<i>p</i> < 0.001). Long-term BoNT-treated patients with CD believe that disease severity would worsen again if BoNT therapy were discontinued. However, they do not expect CD severity to deteriorate to the level that they believe would have been reached if no BoNT therapy had been administered. We interpret this finding as suggesting that patients perceive a preventive effect of long-term BoNT therapy.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782011","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}

{"title":"Free-Living Bacteria May Utilize Chromosomal Toxin-Antitoxin Systems to Mediate K Sensing and Control by Continuously Modulating the Ratio of Injury: Repair Throughout the Life Cycle.","authors":"Stephen J Knabel, Aubrey Mendonca","doi":"10.3390/toxins18040183","DOIUrl":"https://doi.org/10.3390/toxins18040183","url":null,"abstract":"<p><p>A recent publication proposed that the main biological function of chromosomal toxin-antitoxin systems (TASs) in free-living bacteria is to optimize fitness by mediating K Sensing and Control via a Nutrient-Responsive Cybernetic System. Viable cell density data were consistent with analog (continuous) regulation of population dynamics and cellular physiology throughout the life cycle; however, exactly how bacteria utilize TASs to regulate this was not explained in that publication. Two different concepts of injury have been proposed in the field of microbiology: (1) injury due to external physical and chemical stresses, which lead to sublethal (reversible) or lethal (irreversible) injury depending on the degree of injury, and (2) injury due to internal, self-inflicted stresses mediated by TA toxins. While self-inflicted injury due to TA toxins has been recognized as playing a role in growth arrest and dormancy, which can be reversed by repair, there is little support for TA toxins causing irreversible programmed cell death under normal physiological conditions. The purpose of the present paper was to explain how merging the above two concepts of injury might reveal how TASs optimize the fitness of free-living bacteria under normal physiological conditions by continuously regulating the ratio of injury: repair throughout the life cycle.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"18 4","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782047","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}