Clinical science最新文献

{"title":"Renal hypertrophy and hyperfiltration is enhanced in early-acquired compared to a congenital solitary function kidney model in sheep.","authors":"Zoe McArdle, Reetu R Singh, Sarah L Walton, Karen Moritz, Kate M Denton, Michiel F Schreuder","doi":"10.1042/CS20243031","DOIUrl":"https://doi.org/10.1042/CS20243031","url":null,"abstract":"<p><p>A congenital solitary functioning kidney (C-SFK) or an early acquired SFK (EA-SFK), due to childhood unilateral nephrectomy (unix), increases the risk of hypertension and kidney disease early in life. Evidence suggests that children with an EA-SFK may have a higher risk of future kidney disease compared to those with a C-SFK, but the precise underlying mechanisms need further investigation. C-SFK was induced by fetal unix at 100 days gestation (term=150 days) in male sheep fetuses and a sham procedure was performed. At 1 month of age, EA-SFK was induced by unix in male lambs. At 8 months of age total kidney weight was similar in all groups due to marked hypertrophy in the C-SFK and EA-SFK groups. Blood pressure was similar in EA-SFK and sham groups but ~12 mmHg higher in the C-SFK group compared with sham. Compared with the sham group, glomerular filtration rate (GFR) was ~9% less in the EA-SFK group and ~26% less in the C-SFK. GFR was ~23% greater in EA-SFK compared with the C-SFK group. Albuminuria was 67% greater in C-SFK sheep but similar in the EA-SFK group compared with sham sheep. However, like the C-SFK group, the renal blood flow response to nitric oxide blockade was attenuated in the EA-SFK group compared with sham. In conclusion, longer-term studies are needed to determine whether the greater hyperfiltration and disturbed vasodilator balance observed in EA-SFK sheep will cause an accelerated decline in renal function with aging.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522874","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}

{"title":"Persistent subclinical renal injury in female rats following renal ischemia-reperfusion injury.","authors":"Desmond Moronge, Hannah Godley, Victor Ayulo, Elisabeth Mellott, Mona Elgazzaz, Gibson Cooper, Riyaz Mohamed, Safia Ogbi, Ellen Gillis, Jessica L Faulkner, Jennifer C Sullivan","doi":"10.1042/CS20241851","DOIUrl":"10.1042/CS20241851","url":null,"abstract":"<p><p>The incidence of acute kidney injury (AKI) continues to rise in both men and women. Although creatinine levels return to normal quicker in females following AKI than in males, it remains unclear whether subclinical renal injury persists in young females post-AKI. This study tested the hypothesis that AKI results in subclinical renal injury in females despite plasma creatinine returning to sham levels. For the present study, 12-13-week-old female Sprague-Dawley (SD) rats were randomized to sham or 45-minute warm bilateral ischemia-reperfusion surgery as an experimental model of ischemic AKI. Rats were euthanized 1, 3, 7, 14, or 30 days post-AKI/sham. Plasma creatinine, cystatin C, kidney injury molecule 1 (KIM-1), and NGAL were quantified via assay kits or immunoblotting. Kidneys were processed for histological analysis to assess tubular injury and fibrosis, and for electron microscopy to examine mitochondrial morphology. Immunoblots on kidney homogenates were performed to determine oxidative stress and apoptosis. Plasma creatinine levels were increased 24 hours post-AKI but returned to sham control levels three days post-AKI. However, cystatin C, KIM-1, and NGAL were increased 30 days post-AKI compared with sham. Tubular injury, tubulointerstitial fibrosis, and mitochondrial dysfunction were all increased in 30-day post-AKI rats compared with sham. Additionally, 30-day post-AKI rats had higher p-JNK expression and lower antioxidant enzyme glutathione peroxidase and catalase levels compared with sham. AKI resulted in higher expression of cleaved caspase 3, TUNEL+ cells, and caspase 9 than sham. Despite the normalization of creatinine levels, our data support the hypothesis that subclinical renal injury persists following ischemia-reperfusion injury in young female rats.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122231","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}

{"title":"Trbp inhibits cardiac fibrosis through TGF-β pathway mediated crosstalk between cardiomyocytes and fibroblasts.","authors":"Bo Pan, Di Hu, Yao Wei Lu, Jing Luo, Xiao Hui Hu, Haipeng Guo, Rui Deng, Zhuomin Liang, Yi Wang, Qing Ma, John David Mably, Jie Tian, Da-Zhi Wang","doi":"10.1042/CS20242397","DOIUrl":"https://doi.org/10.1042/CS20242397","url":null,"abstract":"<p><p>Cardiac remodeling in response to disease or tissue damage severely impairs heart function. Therefore, the description of the molecular mechanisms responsible is essential for the development of effective therapies. Trbp (Tarbp2) is a multi-functional RNA-binding protein (RBP) that is essential during heart development but its role in the adult heart and cardiac remodeling are unknown. We generated inducible conditional knockout mice to delete Trbp from cardiomyocytes in young adults (Trbp-cKOs). While Trbp-cKO mice did not display a detectable phenotype, under stress conditions induced by transverse aortic constriction (TAC) pressure overload, they rapidly developed severe heart failure; this was associated with maladaptive cardiac remodeling and increased interstitial fibrosis. RNA-seq revealed the induction of a fibrotic gene expression network and the TGF-β signaling pathway in Trbp-cKO hearts. In cultured neonatal rat ventricle cardiomyocytes (NRCMs), inhibition of Trbp resulted in an induction of the expression of both Tgfβ2 and Ltbp2; in contrast, Trbp overexpression repressed Tgfβ2 expression. Knockdown of Trbp in NRCMs that were co-cultured with neonatal rat cardiac fibroblasts (NRCFs) resulted in an increase of fibrotic gene expression. However, knockdown of Trbp in NRCMs combined with knockdown of Tgfβ2 in NRCFs using the same co-culture system failed to induce the same change in fibrotic gene expression. These data provide evidence for a critical role for Trbp in regulating cardiac fibrosis during cardiac remodeling mediated by crosstalk between cardiomyocytes and fibroblasts. The link to TGF-β signaling also highlights its importance and reveals a novel approach to intervention through targeting of Trbp.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448509","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}

{"title":"Harnessing 2D and 3D human endometrial cell culture models to investigate SARS-CoV-2 infection in early pregnancy.","authors":"Anna Liu, Natalia Ruetalo, Janet P Raja Xavier, Aditya Kumar Lankapalli, Jakob Admard, Miguel Camarena-Sainz, Sara Y Brucker, Yogesh Singh, Michael Schindler, Madhuri S Salker","doi":"10.1042/CS20241215","DOIUrl":"10.1042/CS20241215","url":null,"abstract":"<p><p>Vertical transmission of SARS-CoV-2 during human pregnancy remains highly controversial as most studies have focused on the third trimester or the peripartum period. Given the lack of early trimester data, determining the prevalence of vertical transmission during early pregnancy and assessing the potential risks for fetal morbidity and mortality pose a challenge. Therefore, we analysed the impact of SARS-CoV-2 infection on an endometrial 3D spheroid model system. The 3D spheroids are capable of decidualization and express angiotensin-converting enzyme 2 (ACE2) as well as transmembrane protease serine 2 (TMPRSS2), rendering them susceptible to SARS-CoV-2 infection. Employing this 3D cell model, we identified that SARS-CoV-2 can infect both non-decidualized and decidualized endometrial spheroids. Infection significantly increased the chemokine Monocyte chemoattractant protein-1 (MCP-1) compared to non-infected spheroids. Decidualized spheroids exhibited upregulated Interleukin (IL)-8 levels. Furthermore, RNA sequencing revealed dysregulation of several genes involved in tissue-specific immune response, Fc receptor signalling, angiotensin-activated signalling and actin function. Gene expression changes varied between SARS-CoV-2 infected non-decidualized and decidualized spheroids and genes associated with the innate immune system (CD38, LCN2 and NR4A3) were dysregulated as a potential mechanism for immune evasion of SARS-CoV-2. Altogether, our study demonstrates that endometrial spheroids are a useful model to examine the clinical implications of SARS-CoV-2 vertical transmission, warranting further investigations.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817511","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}

{"title":"Renal damage-induced hepcidin accumulation contributes to anemia in angiotensinogen-deficient mice.","authors":"André F Rodrigues, Laura Boreggio, Tetiana Lahuta, Fatimunnisa Qadri, Natalia Alenina, Carlos C Barros, Mihail Todiras, Michael Bader","doi":"10.1042/CS20241789","DOIUrl":"10.1042/CS20241789","url":null,"abstract":"<p><p>Angiotensin II (Ang II) is the most active peptide hormone produced by the renin-angiotensin system (RAS). Genetic deletion of genes that ultimately restrict Ang II formation has been shown to result in marked anemia in mice. In this study, adult mice with a genetic deletion of the RAS precursor protein angiotensinogen (Agt-KO) were used. Experimental analyses included capillary hematocrit, hemogram, plasma and tissue iron quantifications, expression analyses of genes encoding relevant proteins for body iron homeostasis in different organs, as well as plasma and urine hepcidin quantifications. As previously reported, Agt-KO were anemic with reduced red blood cell counts. Interestingly, we found that they presented microcytic anemia based on the reduced red blood cell volume. In agreement, plasma quantification of iron revealed lower levels of circulating iron in Agt-KO. The major body iron stores, namely in the liver and spleen, were also depleted in the RAS-deficient line. Hepatic hepcidin expression was reduced, as well as one of its major regulators, BMP6, as a result of the iron deficiency. However, plasma hepcidin levels were unexpectedly increased in Agt-KO. We confirm the typical morphological alterations and impaired renal function of Agt-KO and conclude that hepcidin accumulates in the circulation due to the reduced glomerular filtration in Agt-KO, and therefore identified the culprit of iron deficiency in Agt-KO. Collectively, the data demonstrated that the severe anemia developed in RAS-deficient mice is exacerbated by iron deficiency which is secondary to the renal damage-induced hepcidin accumulation in the circulation.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051952","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}

{"title":"Blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis.","authors":"Jin-Ling Huo, Wenjia Fu, Qi Feng, Shaokang Pan, Dongwei Liu, Zhangsuo Liu","doi":"10.1042/CS20243221","DOIUrl":"10.1042/CS20243221","url":null,"abstract":"<p><p>Neddylation is a process of attaching neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) to substrates for the protein function modulation via enzymatic cascades involving NEDD8-activating enzyme (E1), NEDD8-conjugating enzyme (E2), and NEDD8 ligase (E3). Defective in cullin neddylation 1 (DCN1) serves as a co-E3 ligase, which can simultaneously bind E2 UBE2M and cullin proteins to stabilize the catalytic center of the Cullin-Ring E3 ligase complex, thereby promoting cullin neddylation. Neddylation is reported to be activated in diverse human diseases, and inhibition of protein neddylation has been regarded as a promising anticancer therapy. However, whether neddylation participates in renal fibrosis and whether blockade of neddylation through targeted inhibition of DCN1 play effects on renal fibrosis remains unknown. In the present study, an NEDD8 overexpressed plasmid, DCN1 small interfering RNAs, DCN1-specific inhibitor NAcM-OPT, human renal tubular epithelial cells (HK-2), rat kidney fibroblasts (NRK-49F), RNA sequencing, unilateral ureteral obstruction (UUO), and unilateral ischemia-reperfusion injury (UIRI) mouse renal fibrosis models were used. Herein, we first showed that neddylation was activated in renal fibrosis. Neddylation blockade through DCN1 deficiency alleviated TGFβ1-induced up-regulation of fibronectin and α-SMA in HK-2 and NRK-49F cells. Importantly, DCN1 inhibition attenuated UUO- and UIRI-induced mouse renal fibrosis. Further studies revealed that DCN1 loss selectively inhibited cullin3 neddylation and induced its substrate NRF2 accumulation, thereby inhibiting TGFβ-Smad2/3 signaling pathway. Overall, blockade of neddylation through targeted inhibition of DCN1 contributes to alleviating renal fibrosis in vitro and in vivo, which may constitute a novel therapeutic strategy for renal fibrosis.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045735","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}

{"title":"Restoring lung renin-angiotensin system balance through blood pressure control.","authors":"Gabriela Catão D Braga, Joao Carlos Ribeiro-Silva, Andreia Boaro, Flavia Leticia Martins, Thais Mauad, Caio A M Tavares, Lisete Ribeiro Teixeira, Bruno Caramelli, Adriana C C Girardi","doi":"10.1042/CS20241155","DOIUrl":"https://doi.org/10.1042/CS20241155","url":null,"abstract":"<p><p>Dysregulated renin-angiotensin system (RAS) signaling contributes to elevated blood pressure (BP), inflammation, and organ damage in systemic arterial hypertension (HTN). We have demonstrated that hypertensive humans and rats exhibit higher expression of classic RAS components and lower expression of counterregulatory RAS components in the lungs compared with normotensive counterparts. Here, we investigated whether BP control could restore the balance between classic [angiotensin I-converting enzyme 2 (ACE)/angiotensin II (Ang II)] and counterregulatory [angiotensin I-converting enzyme 2 (ACE2)/Ang (1-7)] RAS, thereby mitigating lung inflammation. Male spontaneously hypertensive rats (SHRs) were treated with either losartan or amlodipine, both of which effectively reduced BP. These interventions up-regulated lung Ace2 and down-regulated Ace gene expression. Pulmonary membrane ACE2 abundance and activity were higher in losartan- and amlodipine-treated SHRs than in vehicle-treated SHRs, whereas ACE protein and function remained unchanged. Drug-treated SHRs exhibited lower levels of lung Ang II and higher levels of Ang (1-7) than vehicle-treated SHRs. Rebalancing the pulmonary RAS remarkably reduced macrophage number and down-regulated pro-inflammatory genes in SHR lungs, with lower expression of lung pro-inflammatory genes correlating with lower circulating levels of ACE2. Serum analysis in healthy and hypertensive individuals supported these findings, showing higher ACE2 levels in uncontrolled compared with controlled hypertension and normotension. Collectively, these findings suggest that high blood pressure may induce lung inflammation via an ACE/ACE2 imbalance. BP control with either an RAS inhibitor or a calcium channel blocker rebalances RAS in SHR lungs and alleviates inflammation. Furthermore, this study provides a mechanistic link between inflammatory lung diseases (such as COVID-19) and hypertension as a major risk factor.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 3","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188549","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}

{"title":"PDCD10/CCM3, a potential target for pancreatic ductal adenocarcinoma?","authors":"Hendrik Ungefroren","doi":"10.1042/CS20241916","DOIUrl":"https://doi.org/10.1042/CS20241916","url":null,"abstract":"<p><p>Malignant progression of pancreatic ductal adenocarcinoma (PDAC) is driven by transforming growth factor (TGF)-β1 through extensive cross-talk with other signalling pathways. Prompted by the observation that the ubiquitous protein programmed cell death 10 (PDCD10) is more abundantly expressed in PDAC tumour tissue compared with normal pancreas and highly correlated with reduced patient survival, authors examined its function as a modulator of TGF-β signalling in PDAC. Cytotoxicity assays with PDAC-derived tumour cell lines, PaTu8902 (DPC4+/+) and PaTu8988t (DPC4-/-) engineered to homozygously lack PDCD10 showed that PDCD10 renders cells more chemoresistant to anticancer drugs. Moreover, PDCD10 promoted TGF-β1-dependent proliferation by inactivating the retinoblastoma 1 protein (pRb) via a SMAD4-dependent pathway, and TGF-β1-driven EMT by increasing ERK1/2 activation via a non-SMAD4 pathway. Phosphorylation of pRB and ERK by PDCD10 is facilitated by binding of PDCD10 to MST4. Targeting PDCD10 in PDAC patients may represent a promising new strategy to improve TGF-β targeted therapies.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 3","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381808","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}

{"title":"Therapeutic strategies to ameliorate mitochondrial oxidative stress in ischaemia-reperfusion injury: A narrative review.","authors":"Khalid Alotaibi, Nishkantha Arulkumaran, Alex Dyson, Mervyn Singer","doi":"10.1042/CS20242074","DOIUrl":"10.1042/CS20242074","url":null,"abstract":"<p><p>Mitochondrial reactive oxygen species (mROS) play a crucial physiological role in intracellular signalling. However, high levels of ROS can overwhelm antioxidant defences and lead to detrimental modifications in protein, lipid and DNA structure and function. Ischaemia-reperfusion injury is a multifaceted pathological state characterised by excessive production of mROS. There is a significant clinical need for therapies mitigating mitochondrial oxidative stress. To date, a variety of strategies have been investigated, ranging from enhancing antioxidant reserve capacity to metabolism reduction. While success has been achieved in non-clinical models, no intervention has yet successfully transitioned into routine clinical practice. In this article, we explore the different strategies investigated and discuss the possible reasons for the lack of translation.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 3","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078791","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}

{"title":"Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.","authors":"Pierre Couvineau, Catherine Llorens-Cortes","doi":"10.1042/CS20240955","DOIUrl":"https://doi.org/10.1042/CS20240955","url":null,"abstract":"<p><p>Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present. Apelin and vasopressin interact at the brain and renal levels to maintain body fluid homeostasis by regulating diuresis in opposite directions. Apelin and angiotensin II have opposite effects on the regulation of blood pressure (BP). Angiotensin II, by binding to AT1 receptors present in VSMCs, induces intracellular calcium mobilization and vasoconstriction, while apelin, by binding to Apelin-R present on vascular endothelium, increases nitric oxide production and induces vasodilation. Apelin also plays a crucial role in the regulation of cardiac function. Apelin-deficient and Apelin-R-deficient mice develop progressive myocardial dysfunction with ageing and are susceptible to heart failure in response to pressure overload. Since the half-life of apelin is very short in vivo (in the minute range), several metabolically stable apelin analogs and non-peptidic Apelin-R agonists have been developed, with potential applications in diverse diseases. In this review, we highlight the interaction between apelin and vasopressin in the regulation of water balance and that between apelin and angiotensin II in the regulation of BP. Additionally, we underline the protective effects of apelin in cardiac function. Lastly, we discuss the beneficial effects of Apelin-R activation in different pathological states such as hyponatremia, hypertension, and heart failure.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 2","pages":"131-149"},"PeriodicalIF":6.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058271","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}