Pulmonary pharmacology & therapeutics最新文献

{"title":"Ensifentrine approval: A milestone in the treatment of COPD","authors":"Luigino Calzetta , Paola Rogliani","doi":"10.1016/j.pupt.2024.102318","DOIUrl":"10.1016/j.pupt.2024.102318","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102318"},"PeriodicalIF":3.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018427","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":"FTO promotes gefitinib-resistance by enhancing PELI3 expression and autophagy in non-small cell lung cancer","authors":"Yu-Zheng He ,&nbsp;Xiao-Ning Li ,&nbsp;Hai-Tao Li ,&nbsp;Xian-Hua Bai ,&nbsp;Yan-Chao Liu ,&nbsp;Fan-Nian Li ,&nbsp;Bao-Lei Lv ,&nbsp;Tian-Jie Qi ,&nbsp;Xiu-Min Zhao ,&nbsp;Shuai Li","doi":"10.1016/j.pupt.2024.102317","DOIUrl":"10.1016/j.pupt.2024.102317","url":null,"abstract":"<div><p>The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated <em>in vitro</em> and <em>in vivo</em>. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"87 ","pages":"Article 102317"},"PeriodicalIF":3.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000600","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":"Applicability of mouse models for induction of severe acute lung injury","authors":"Ana Paula Ferreira Leal ,&nbsp;Valentina Nieto Marín ,&nbsp;Vinícius Varzim Cabistany ,&nbsp;Júlia Morales ,&nbsp;Danieli Fernanda Buccini ,&nbsp;Octávio Luiz Franco","doi":"10.1016/j.pupt.2024.102316","DOIUrl":"10.1016/j.pupt.2024.102316","url":null,"abstract":"<div><p>Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40 % mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as <em>Pseudomonas aeruginosa</em>, <em>Mycobacterium tuberculosis</em>, and <em>Streptococcus pneumoniae</em>, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102316"},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788934","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 efficacy and safety of inhaled antibiotics for pneumonia: A systematic review and meta-analysis","authors":"Zengzeng Zhang ,&nbsp;Hong Li ,&nbsp;Yutao Hu ,&nbsp;Binhui Sun ,&nbsp;Tingting Ke ,&nbsp;Qihuan Wu ,&nbsp;Xiang Lian ,&nbsp;Wei Yu","doi":"10.1016/j.pupt.2024.102315","DOIUrl":"10.1016/j.pupt.2024.102315","url":null,"abstract":"<div><h3>Objectives</h3><p>The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis.</p></div><div><h3>Methods</h3><p>Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment.</p></div><div><h3>Results</h3><p>There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR) = 1.06, 95 % confidence interval (CI): 0.80–1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR = 1.47 95%CI: 0.82–2.66 in RCT studies and OR = 2.09, 95%CI: 1.36–3.21 in observational studies) and microbiological cure (OR = 7.00 in RCT studies and OR = 2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27–1.13; I-squared = 43.5 %, P = 0.124) and 0.63(95%CI: 0.26–1.11; I-squared = 69.0 %, P = 0.110) in RCT studies and observational studies, respectively.</p></div><div><h3>Conclusions</h3><p>Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102315"},"PeriodicalIF":3.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1094553924000312/pdfft?md5=5f0cf7dddad61179a42ab1db817fec41&pid=1-s2.0-S1094553924000312-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620800","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":"Differential distribution of ivacaftor and its metabolites in plasma and human airway epithelia","authors":"","doi":"10.1016/j.pupt.2024.102314","DOIUrl":"10.1016/j.pupt.2024.102314","url":null,"abstract":"<div><p>Ivacaftor is the first clinically approved monotherapy potentiator to treat <em>CFTR</em> channel dysfunction in people with cystic fibrosis. Ivacaftor (Iva) is a critical component for all current modulator therapies, including highly effective modulator therapies. Clinical studies show that CF patients on ivacaftor-containing therapies present various clinical responses, off-target effects, and adverse reactions, which could be related to metabolites of the compound. In this study, we reported the concentrations of Iva and two of its major metabolites (M1-Iva and M6-Iva) in capillary plasma and estimated M1-Iva and M6-Iva metabolic activity via the metabolite parent ratio in capillary plasma over 12 h. We also used the ratio of capillary plasma versus human nasal epithelial cell concentrations to evaluate entry into epithelial cells <em>in vivo</em>. M6-Iva was rarely detected by LC-MS/MS in epithelial cells from participants taking ivacaftor, although it was detected in plasma. To further explore this discrepancy, we performed <em>in vitro</em> studies, which showed that M1-Iva, but not M6-Iva, readily crossed 16HBE cell membranes. Our studies also suggest that metabolism of these compounds is unlikely to occur in airway epithelia despite evidence of expression of metabolism enzymes. Overall, our data provide evidence that there are differences between capillary and cellular concentrations of these compounds that may inform future studies of clinical response and off-target effects.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102314"},"PeriodicalIF":3.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535142","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":"NEK-mediated barrier regulation","authors":"Nektarios Barabutis","doi":"10.1016/j.pupt.2024.102313","DOIUrl":"10.1016/j.pupt.2024.102313","url":null,"abstract":"<div><p>Endothelial dysfunction has been associated with devastating outcomes which can eventually lead to permanent disability and death. Elucidation of the meticulously devised network orchestrating endothelial responses, provides information to develop new therapies towards endothelial-related disorders. NEK kinases - which have been involved in the development of human disease – promote vascular leak; suggesting the possibility that their inhibition may ameliorate medical conditions related to barrier derangement.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102313"},"PeriodicalIF":3.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443200","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":"Unveiling the protective role of sevoflurane in video-assisted thoracoscopic surgery associated-acute lung injury: Inhibition of ferroptosis","authors":"Yang Zhang ,&nbsp;Tianming Zha ,&nbsp;Guoxin Song ,&nbsp;Gulibositan Abudurousuli ,&nbsp;Jinxin Che ,&nbsp;Fei Zhao ,&nbsp;Lin Zhang ,&nbsp;Xing Zhang ,&nbsp;Bo Gui ,&nbsp;Linjia Zhu","doi":"10.1016/j.pupt.2024.102312","DOIUrl":"10.1016/j.pupt.2024.102312","url":null,"abstract":"<div><p>Acute lung injury (ALI) frequently occurs after video-assisted thoracoscopic surgery (VATS). Ferroptosis is implicated in several lung diseases. Therefore, the disparate effects and underlying mechanisms of the two commonly used anesthetics (sevoflurane (Sev) and propofol) on VATS-induced ALI need to be clarified. In the present study, enrolled patients were randomly allocated to receive Sev (group S) or propofol anesthesia (group P). Intraoperative oxygenation, morphology of the lung tissue, expression of ZO-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione (GSH), Fe²⁺, glutathione peroxidase 4 (GPX4), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the lung tissue as well as the expression of TNF-α and IL-6 in plasma were measured. Postoperative complications were recorded. Of the 85 initially screened patients scheduled for VATS, 62 were enrolled in either group S (n = 32) or P (n = 30). Compared with propofol, Sev substantially (1) improved intraoperative oxygenation; (2) relieved histopathological lung injury; (3) increased ZO-1 protein expression; (4) decreased the levels of TNF-α and IL-6 in both the lung tissue and plasma; (5) increased the contents of GSH and SOD but decreased Fe²⁺ concentration; (6) upregulated the protein expression of p-AKT, Nrf2, HO-1, and GPX4. No significant differences in the occurrence of postoperative outcomes were observed between both groups. In summary, Sev treatment, in comparison to propofol anesthesia, may suppress local lung and systemic inflammatory responses by activating the PI3K/Akt/Nrf2/HO-1 pathway and inhibiting ferroptosis. This cascade of effects contributes to the maintenance of pulmonary epithelial barrier permeability, alleviation of pulmonary injury, and enhancement of intraoperative oxygenation in patients undergoing VATS.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102312"},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437382","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 involvement of Sting in exacerbating acute lung injury in sepsis via the PARP-1/NLRP3 signaling pathway","authors":"Tingting Ying ,&nbsp;Yulong Yu ,&nbsp;Qimin Yu,&nbsp;Gang Zhou,&nbsp;Lingyang Chen,&nbsp;Yixiao Gu,&nbsp;Lijun Zhu,&nbsp;Haifeng Ying,&nbsp;Minjuan Chen","doi":"10.1016/j.pupt.2024.102303","DOIUrl":"10.1016/j.pupt.2024.102303","url":null,"abstract":"<div><h3>Background</h3><p>Interferon gene stimulator (Sting) is an indispensable adaptor protein that plays a crucial role in acute lung injury (ALI) induced by sepsis, and the PARP-1/NLRP3 signaling pathway may be an integral component of the inflammatory response mediated by Sting. However, the regulatory role of Sting in the PARP-1/NLRP3 pathway in ALI remains insufficiently elucidated.</p></div><div><h3>Methods</h3><p>Using lipopolysaccharide (LPS) to induce ALI in C57BL/6 mice and HUVEC cells, an <em>in vivo</em> and <em>in vitro</em> model was established. <em>In vivo</em>, Sting agonists and inhibitors were administered, while <em>in vitro</em>, Sting was knocked down using siRNA. ELISA was employed to quantify the levels of IL-1β, IL-6, and TNF-α. TUNEL staining was conducted to assess cellular apoptosis, while co-immunoprecipitation was utilized to investigate the interaction between Sting and NLRP3. Expression levels of Sting, NLRP3, PARP-1, among others, were assessed via Western blotting and RT-qPCR. Lung HE staining and lung wet/dry ratio were evaluated in the <em>in vivo</em> mouse model. To validate the role of the PARP-1/NLRP3 signaling pathway, PARP-1 inhibitors were employed both <em>in vivo</em> and <em>in vitro</em>.</p></div><div><h3>Results</h3><p><em>In vitro</em> experiments revealed that the Sting agonist group exacerbated LPS-induced pulmonary pathological damage, pulmonary edema, inflammatory response (increased levels of IL-6, TNF-α, and IL-1β), and cellular injury, whereas the Sting inhibitor group significantly ameliorated the aforementioned injuries, with further improvement observed in the combination therapy of Sting inhibitor and PARP-1 inhibitor. Western blotting and RT-qPCR results demonstrated significant suppression of ICAM-1, VCAM-1, NLRP3, and PARP-1 expression in the Sting inhibitor group, with this reduction further enhanced in the Sting inhibitor + PARP-1 inhibitor treatment group, exhibiting opposite outcomes to the agonist. Furthermore, <em>in vitro</em> experiments using HUVEC cell lines validated these findings.</p></div><div><h3>Conclusions</h3><p>Our study provides new insights into the roles of Sting and the PARP-1/NLRP3 signaling pathway in inflammatory responses, offering novel targets for the development of therapeutic interventions against inflammatory reactions.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102303"},"PeriodicalIF":3.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288513","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":"Repeated doses of captopril induce airway hyperresponsiveness by modulating the TRPV1 receptor in rats","authors":"Janiana Raíza Jentsch Matias de Oliveira ,&nbsp;Mayara Alves Amorim ,&nbsp;Vitor Hélio de Souza Oliveira ,&nbsp;Daniela de Almeida Cabrini ,&nbsp;Michel Fleith Otuki ,&nbsp;Claudia Martins Galindo ,&nbsp;Bruna Barbosa da Luz ,&nbsp;Maria Fernanda de Paula Werner ,&nbsp;João Batista Calixto ,&nbsp;Eunice André","doi":"10.1016/j.pupt.2024.102302","DOIUrl":"10.1016/j.pupt.2024.102302","url":null,"abstract":"<div><p>Although TRPV1 receptors play an essential role in the adverse effects on the airways following captopril treatment, there is no available evidence of their involvement in treatment regimens involving repeated doses of captopril. Comparing the difference in these two treatment regimens is essential since captopril is a continuous-use medication. Thus, this study explored the role of the transient receptor potential vanilloid 1 (TRPV1) in the effects of captopril on rat airways using two treatment regimens. Airway resistance, bronchoalveolar lavage (BAL), and histological and immunohistochemical analyses were conducted in rats administered with single or repeated doses of captopril. This study showed that the hyperresponsiveness to bradykinin and capsaicin in captopril-treated rats was acute. Treatment with the selective B₂ antagonist, HOE140 reduced bradykinin hyperresponsiveness and abolished capsaicin exacerbation in single-dose captopril-treated rats. Likewise, degeneration of TRPV1-positive neurones also reduced hyperresponsiveness to bradykinin. Single-dose captopril treatment increased leukocyte infiltration in the BAL when compared with the vehicle and this increase was reduced by TRPV1-positive neurone degeneration. However, when compared with the vehicle treatment, animals treated with repeated doses of captopril showed an increase in leukocyte influx as early as 1 h after the last captopril treatment, but this effect disappeared after 24 h. Additionally, an increase in TRPV1 expression occurred only in animals who received repeated captopril doses and the degeneration of TRPV1-positive neurones attenuated TRPV1 upregulation. In conclusion, these data strongly indicate that a treatment regimen involving multiple doses of captopril not only enhances sensitisation but also upregulates TRPV1 expression. Consequently, targeting TRPV1 could serve as a promising strategy to reduce the negative impact of captopril on the airways.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102302"},"PeriodicalIF":3.2,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186760","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":"Pharmacokinetic variability of CFTR modulators from standard and alternative regimens","authors":"Natalie R. Rose,&nbsp;Ashritha R. Chalamalla,&nbsp;Bryan A. Garcia,&nbsp;Stefanie Krick,&nbsp;Jonathan Bergeron,&nbsp;Hossein Sadeghi,&nbsp;Dennis E. Schellhase,&nbsp;Kevin J. Ryan,&nbsp;Alexander E. Dowell,&nbsp;Edward P. Acosta,&nbsp;Jennifer S. Guimbellot","doi":"10.1016/j.pupt.2024.102301","DOIUrl":"10.1016/j.pupt.2024.102301","url":null,"abstract":"<div><p>Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.</p></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"86 ","pages":"Article 102301"},"PeriodicalIF":3.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154719","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}