Pub Date : 2024-08-08DOI: 10.1016/j.phrs.2024.107343
Psychosis is a characterizing feature of many mental disorders that dramatically affects human thoughts and perceptions, influencing the ability to distinguish between what is real and what is not. Both genetic and environmental factors, such as stressful events or drug use, play a pivotal role in the development of symptomatology and therefore changes in the epigenome may be of relevance in modeling a psychotic phenotype. According to the well-documented dysregulation of endocannabinoid and dopaminergic system genes in schizophrenia, we investigated DNA methylation cannabinoid type 1 receptor (CNR1) and dopamine D2 receptor (DRD2) genes in saliva samples from psychotic subjects using pyrosequencing. The epigenetic mark was significantly higher and directly correlated for both genes in psychotic subjects compared to healthy controls. We also showed that these DNA methylation levels were lower in psychotic subjects reporting current delta-9-tetrahydrocannabinol (THC) consumption, a well-known risk factor for developing psychosis throughout the lifespan, resembling those of controls at least for the DRD2 gene. Overall, our data confirm the key role of CNR1 and DRD2 gene regulation in psychosis and suggest DNA methylation levels at specific CpG sites as potential biomarkers, but just in those psychotic subjects not consuming THC.
精神病是许多精神疾病的特征之一,它会极大地影响人的思想和感知,影响人分辨真假的能力。遗传和环境因素(如压力事件或药物使用)在症状的发展中都起着关键作用,因此表观基因组的变化可能与精神病表型的建模有关。根据精神分裂症患者内大麻素和多巴胺能系统基因失调的文献记载,我们利用热释光测序技术研究了精神病患者唾液样本中大麻素1型受体(CNR1)和多巴胺D2受体(DRD2)基因的DNA甲基化情况。与健康对照组相比,精神病患者唾液样本中这两个基因的表观遗传标记都明显较高,并且直接相关。我们还发现,在报告目前服用δ-9-四氢大麻酚(THC)的精神病患者中,这些 DNA 甲基化水平较低,而δ-9-四氢大麻酚是众所周知的终生罹患精神病的风险因素。总之,我们的数据证实了 CNR1 和 DRD2 基因调控在精神病中的关键作用,并建议将特定 CpG 位点的 DNA 甲基化水平作为潜在的生物标志物,但仅限于未服用 THC 的精神病受试者。
{"title":"DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: Is there an effect of Cannabis use?","authors":"","doi":"10.1016/j.phrs.2024.107343","DOIUrl":"10.1016/j.phrs.2024.107343","url":null,"abstract":"<div><p>Psychosis is a characterizing feature of many mental disorders that dramatically affects human thoughts and perceptions, influencing the ability to distinguish between what is real and what is not. Both genetic and environmental factors, such as stressful events or drug use, play a pivotal role in the development of symptomatology and therefore changes in the epigenome may be of relevance in modeling a psychotic phenotype. According to the well-documented dysregulation of endocannabinoid and dopaminergic system genes in schizophrenia, we investigated DNA methylation cannabinoid type 1 receptor (<em>CNR1</em>) and dopamine D2 receptor (<em>DRD2</em>) genes in saliva samples from psychotic subjects using pyrosequencing. The epigenetic mark was significantly higher and directly correlated for both genes in psychotic subjects compared to healthy controls. We also showed that these DNA methylation levels were lower in psychotic subjects reporting current delta-9-tetrahydrocannabinol (THC) consumption, a well-known risk factor for developing psychosis throughout the lifespan, resembling those of controls at least for the <em>DRD2</em> gene. Overall, our data confirm the key role of <em>CNR1</em> and <em>DRD2</em> gene regulation in psychosis and suggest DNA methylation levels at specific CpG sites as potential biomarkers, but just in those psychotic subjects not consuming THC.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002883/pdfft?md5=3d231f3a3d5a9c8e3938f2b2c4956d33&pid=1-s2.0-S1043661824002883-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.phrs.2024.107329
Kaiqing Li, Xue Xia, Tong Fu, Ying Tong
{"title":"Commentary on \"Apabetalone, a BET protein inhibitor, inhibits kidney damage in diabetes by preventing pyroptosis via modulating the P300/H3K27ac/PLK1 axis\".","authors":"Kaiqing Li, Xue Xia, Tong Fu, Ying Tong","doi":"10.1016/j.phrs.2024.107329","DOIUrl":"10.1016/j.phrs.2024.107329","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1016/j.phrs.2024.107340
Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was −59.13 (-64.103, −54.153) (Adjusted p<0.0001) and −60.43 (-65.450, −55.416) (Adjusted p<0.0001), respectively. Meanwhile, the Ebronucimab group exhibited notably high rates in reaching LDL-C goals of each cardiovascular risk stratification. In addition, Ebronucimab effectively improved other lipid panel. During the double-blind treatment period, relatively frequently reported adverse events (AEs) were injection site reactions (ISR), urinary tract infection, and hyperuricemia (Incidence rate are 6.9 %, 4.8 % and 3.5 %). Among treatment-associated AEs, only injection site reactions (ISR) occurred more in the dose groups. In conclusion, Ebronucimab, with either 450 mg Q4W or 150 mg Q2W doses, demonstrated significant efficacy in lowering serum LDL-C level with a favorable safety and immunogenicity profile among hypercholesterolemic patients.
{"title":"Ebronucimab in Chinese patients with hypercholesterolemia---A randomized double-blind placebo-controlled phase 3 trial to evaluate the efficacy and safety of ebronucimab","authors":"","doi":"10.1016/j.phrs.2024.107340","DOIUrl":"10.1016/j.phrs.2024.107340","url":null,"abstract":"<div><p>Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was −59.13 (-64.103, −54.153) (Adjusted p<0.0001) and −60.43 (-65.450, −55.416) (Adjusted p<0.0001), respectively. Meanwhile, the Ebronucimab group exhibited notably high rates in reaching LDL-C goals of each cardiovascular risk stratification. In addition, Ebronucimab effectively improved other lipid panel. During the double-blind treatment period, relatively frequently reported adverse events (AEs) were injection site reactions (ISR), urinary tract infection, and hyperuricemia (Incidence rate are 6.9 %, 4.8 % and 3.5 %). Among treatment-associated AEs, only injection site reactions (ISR) occurred more in the dose groups. In conclusion, Ebronucimab, with either 450 mg Q4W or 150 mg Q2W doses, demonstrated significant efficacy in lowering serum LDL-C level with a favorable safety and immunogenicity profile among hypercholesterolemic patients.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002858/pdfft?md5=d0c3bdba407c708545668d3dad1fb913&pid=1-s2.0-S1043661824002858-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1016/j.phrs.2024.107338
Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.
{"title":"Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis","authors":"","doi":"10.1016/j.phrs.2024.107338","DOIUrl":"10.1016/j.phrs.2024.107338","url":null,"abstract":"<div><p>Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002834/pdfft?md5=4a2f9fda108ea4f2880d4aafcc127693&pid=1-s2.0-S1043661824002834-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-04DOI: 10.1016/j.phrs.2024.107339
James E Barrett, Alvin V Terry
{"title":"IUPHAR Editorial: Emerging Targets for the Treatment of Pain: Moving towards non-addicting therapeutics and New Preclinical Directions.","authors":"James E Barrett, Alvin V Terry","doi":"10.1016/j.phrs.2024.107339","DOIUrl":"https://doi.org/10.1016/j.phrs.2024.107339","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1016/j.phrs.2024.107334
The intestinal microbiota represents a key element in maintaining the homeostasis and health conditions of the host. Vascular pathologies and other risk factors such as aging have been recently associated with dysbiosis. The qualitative and quantitative alteration of the intestinal microbiota hinders correct metabolic homeostasis, causing structural and functional changes of the intestinal wall itself. Impairment of the intestinal microbiota, combined with the reduction of the barrier function, worsen the pathological scenarios of peripheral tissues over time, including the vascular one. Several experimental evidence, collected in this review, describes in detail the changes of the intestinal microbiota in dysbiosis associated with vascular alterations, such as atherosclerosis, hypertension, and endothelial dysfunction, the resulting metabolic disorders and how these can impact on vascular health. In this context, the gut-vascular axis is considered, for the first time, as a merged unit involved in the development and progression of vascular pathologies and as a promising target. Current approaches for the management of dysbiosis such as probiotics, prebiotics and dietary modifications act mainly on the intestinal district. Postbiotics, described as preparation of inanimate microorganisms and/or their components that confers health benefits on the host, represent an innovative strategy for a dual management of intestinal dysbiosis and vascular pathologies. In this context, this review has the further purpose of defining the positive effects of the supplementation of bacterial strains metabolites (short‑chain fatty acids, exopolysaccharides, lipoteichoic acids, gallic acid, and protocatechuic acid) restoring intestinal homeostasis and acting directly on the vascular district through the gut-vascular axis.
{"title":"Microbiota alterations associated with vascular diseases: postbiotics as a next-generation magic bullet for gut-vascular axis","authors":"","doi":"10.1016/j.phrs.2024.107334","DOIUrl":"10.1016/j.phrs.2024.107334","url":null,"abstract":"<div><p>The intestinal microbiota represents a key element in maintaining the homeostasis and health conditions of the host. Vascular pathologies and other risk factors such as aging have been recently associated with dysbiosis. The qualitative and quantitative alteration of the intestinal microbiota hinders correct metabolic homeostasis, causing structural and functional changes of the intestinal wall itself. Impairment of the intestinal microbiota, combined with the reduction of the barrier function, worsen the pathological scenarios of peripheral tissues over time, including the vascular one. Several experimental evidence, collected in this review, describes in detail the changes of the intestinal microbiota in dysbiosis associated with vascular alterations, such as atherosclerosis, hypertension, and endothelial dysfunction, the resulting metabolic disorders and how these can impact on vascular health. In this context, the gut-vascular axis is considered, for the first time, as a merged unit involved in the development and progression of vascular pathologies and as a promising target. Current approaches for the management of dysbiosis such as probiotics, prebiotics and dietary modifications act mainly on the intestinal district. Postbiotics, described as preparation of inanimate microorganisms and/or their components that confers health benefits on the host, represent an innovative strategy for a dual management of intestinal dysbiosis and vascular pathologies. In this context, this review has the further purpose of defining the positive effects of the supplementation of bacterial strains metabolites (short‑chain fatty acids, exopolysaccharides, lipoteichoic acids, gallic acid, and protocatechuic acid) restoring intestinal homeostasis and acting directly on the vascular district through the gut-vascular axis.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002792/pdfft?md5=050b7bb5b029c3b4054e1a27e2391210&pid=1-s2.0-S1043661824002792-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.phrs.2024.107331
{"title":"Bugs as drugs: Extended clinical applications and potential translational trends of Akkermansia muciniphila in oncology and comprehensive clinical investigation panorama of therapeutic microbiome modulators in gastric cancer treatment","authors":"","doi":"10.1016/j.phrs.2024.107331","DOIUrl":"10.1016/j.phrs.2024.107331","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002767/pdfft?md5=ad7aa629071854d9ba29d81589ed450c&pid=1-s2.0-S1043661824002767-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.phrs.2024.107336
G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Validation of selected targets of GPS2-mediated regulation, including the RNA-binding protein PABPC1 and translation factors RPS1, RACK1 and eIF3M, revealed a mitochondrial-specific strategy for regulating the translation of nuclear-encoded mitochondrial proteins via non-proteolytic ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the import-coupled translation of selected mRNAs leading to the increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.
{"title":"Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation","authors":"","doi":"10.1016/j.phrs.2024.107336","DOIUrl":"10.1016/j.phrs.2024.107336","url":null,"abstract":"<div><p>G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Validation of selected targets of GPS2-mediated regulation, including the RNA-binding protein PABPC1 and translation factors RPS1, RACK1 and eIF3M, revealed a mitochondrial-specific strategy for regulating the translation of nuclear-encoded mitochondrial proteins via non-proteolytic ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the import-coupled translation of selected mRNAs leading to the increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002810/pdfft?md5=de10e2be72e2dcdef2779cc9aec02b2c&pid=1-s2.0-S1043661824002810-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.phrs.2024.107337
{"title":"The current status and future trends of BTK inhibitor for diffuse large B cell lymphoma","authors":"","doi":"10.1016/j.phrs.2024.107337","DOIUrl":"10.1016/j.phrs.2024.107337","url":null,"abstract":"","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824002822/pdfft?md5=fa30e1ca1d139feb6d689b40f91ddf7f&pid=1-s2.0-S1043661824002822-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}