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New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO sOOK HEE HONG HYUNG sOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG sHIM JIN HYOUNG KANG Division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

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CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

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Genes & Diseases 2024年第4期11卷 381-399页

作者： Ming shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.Huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Department of Chemical Biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational Biology St.Jude Children's Research HospitalMemphisTN 38105USA Center for Proteomics and Metabolomics St.Jude Children's Research HospitalMemphisTN 38105USA Department of structural Biology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental Neurobiology St.Jude Children's Research HospitalMemphisTN 38105USA

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in cancer.However,it remains unclear whether CYP3A5 directly influences cancer progression.In this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma.Multi-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of GLUT1.Notably,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling pathway.CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer.Taken together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

关键词： Cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP

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Primary lateral sclerosis:more than just an upper motor neuron disease

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Neural Regeneration Research 2024年第9期19卷 1881-1882页

作者： Ee Ling Tan Jasmin Lope Peter Bede Computational Neuroimaging Group(CNG) School of MedicineTrinity College DublinIreland Department of Neurology St James’s HospitalDublinIreland

Advances in clinical care and recent research achievements:Primary lateral sclerosis(PLs)has traditionally been regarded as a pure upper motor neuron condition,a view perpetuated by most medical textbooks.

关键词： sclerosis clinical traditionally

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Using clinical cases to guide healthcare

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World Journal of Clinical Cases 2024年第9期12卷 1555-1559页

作者： Michael Colwill samantha Baillie Richard Pollok Andrew Poullis Department of Gastroenterology St George's University Hospital NHS Foundation TrustLondon SW170QTUnited Kingdom

Evidence-based practice(EBP)has been the gold standard in healthcare for nearly three centuries and aims to assist physicians in providing the safest and most effective healthcare for their patients.The well-established hierarchy of evidence lists systematic reviews and meta-analyses at the top however these methodologies are not always appropriate or possible and in these instances case-control studies,case series and case reports are utilised to support EBP.Case-control studies allow simultaneous study of multiple risk factors and can be performed rapidly and relatively cheaply.A recent example was during the Coronavirus pandemic where case-control studies were used to assess the efficacy of personal protective equipment for healthcare workers.Case series and case reports also play a role in EBP and are particularly useful to study rare diseases such as inflammatory bowel disease in transgender and gender non-conforming individuals.They are also vital in generating and disseminating early signals and encouraging further research.Whilst these methodologies have weaknesses,particularly with regards to bias and loss of patient confidentiality for rare pathologies,they have an important part to play in EBP and when appropriately utilised can significantly impact upon clinical practice.

关键词： Evidence based medicine Hierarchy of evidence Case reports Case series

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Uniportal video-assisted thoracoscopic fissureless right upper lobe anterior segmentectomy for inflammatory myofibroblastic tumor:A case report

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World Journal of Clinical Cases 2024年第2期12卷 425-430页

作者： seha Ahn Youngkyu Moon Department of Thoracic and Cardiovascular surgery Eunpyeong St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 03312South Korea

BACKGROUND Inflammatory myofibroblastic tumors(IMTs)are exceptionally rare neoplasms with intermediate malignant potential.surgery is the accepted treatment option,aiming for complete resection with clear margins.CAsE sUMMARY A 39-year-old woman presented with a growing solitary pulmonary nodule measuring 2.0 cm in the right upper lobe(RUL)of the lung.The patient underwent a RUL anterior segmentectomy using uniportal video-assisted thoracoscopy.A preliminary tissue diagnosis indicated malignancy;however,it was later revised to an IMTs.Due to the absence of a minor fissure between the right upper and middle lobes,an alternative resection approach was necessary.Therefore,we utilized indocyanine green injection to aid in delineating the intersegmental plane.Following an uneventful recovery,the patient was discharged on the third postoperative day.Thereafter,annual chest tomography scans were scheduled to monitor for potential local recurrence.CONCLUsION This case underscores the challenges in diagnosing and managing IMTs,showing the importance of accurate pathologic assessments and tailored surgical strategies.

关键词： Uniportal video-assisted thoracoscopic surgery Fissureless Anterior segmentectomy Inflammatory fibroblastic tumor Case report

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A cross-sectional study of breastfed infants referred for tongue tie assessment and frenotomy in one Canadian health region

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儿科学研究(英文) 2024年第1期8卷 53-60页

作者： Lee Tiffany A. Bishop Jessica Drover Anne Midodzi William K. Twells Laurie K. school of Pharmacy Memorial University of Newfoundland (MUN) St. John’s Canada Faculty of Medicine Memorial University of Newfoundland (MUN) St. John’s Canada

Importance: Tongue tie (TT) is a condition that can cause infant feeding difficulties due to restricted tongue movement. When TT presents as a significant barrier to breastfeeding, a frenotomy may be recommended. Universally accepted diagnostic criteria for TT are lacking and wide prevalence estimates are reported. New referral processes and a Frenotomy Assessment Tool were implemented in one Canadian health region to connect breastfeeding dyads with a provider for TT evaluation and frenotomy.Objective: To determine the proportion of babies with TT as well as the frequency of frenotomy.Methods: This cross-sectional study included infants who initiated breastfeeding at birth and were referred for TT evaluation over a 14-month period. Data were collected retrospectively by chart review and analyzed using sPss. Factors associated with frenotomy were examined using logistic regression.Results: Two hundred and forty-one babies were referred. Ninety-two percent (n = 222) were diagnosed with TT and 66.0% (n = 159) underwent frenotomy. In the multivariate model, nipple pain/trauma, inability to latch, inability to elevate tongue, and dimpling of tongue on extension were associated with frenotomy (P st referrals in our region resulted in a diagnosis of TT; however, the number of referrals was lower than expected, and of these two-thirds underwent frenotomy.Interpretation: TT is a relatively common finding among breastfed infants. Future research should examine whether a simplified assessment tool containing the four items associated with frenotomy in our multivariate model can identify breastfed infants with TT who require frenotomy.

关键词： Breastfeeding Nutrition Community health services Pediatrics

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Tenecteplase versus alteplase in treatment of acute st-segment elevation myocardial infarction:A randomized non-inferiority trial

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Chinese Medical Journal 2024年第3期137卷 312-319页

作者： Xingshan Zhao Yidan Zhu Zheng Zhang Guizhou Tao Haiyan Xu Guanchang Cheng Wen Gao Liping Ma Liping Qi Xiaoyan Yan Haibo Wang Qingde Xia Yuwang Yang Wanke Li Juwen Rong Limei Wang Yutian Ding Qiang Guo Wanjun Dang Chen Yao Qin Yang Runlin Gao Yangfeng Wu shubin Qiao Department of Cardiology Beijing Jishuitan HospitalCapital Medical UniversityThe Fourth Clinical Medical College of Peking UniversityBeijing 100035China Peking University Clinical Research Institute Peking University First HospitalBeijing 100191China Department of Cardiology The First Hospital of Lanzhou UniversityLanzhouGansu 730013China Department of Cardiology The First Affiliated Hospital of Liaoning Medical UniversityJinzhouLiaoning 110002China Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China Department of Cardiology Huaihe Hospital of Henan UniversityKaifengHenan 450001China Department of Cardiology Bayannur HospitalBayannurInner Mongolia 015208China Department of Cardiology Puyang People’s HospitalPuyangHenan 457099China Department of Cardiology Xingtai Third HospitalXingtaiHebei 054099China Department of Cardiology Lintao County People’s HospitalDingxiGansu 730599China Department of Cardiology Dancheng County People’s HospitalZhoukouHenan 477150China Department of Cardiology The First People’s Hospital of LingbaoSanmenxiaHenan 472500China Department of Cardiology Shanyin County People’s HospitalShuozhouShanxi 036999China Department of Cardiology Uxin Banner People’s HospitalOrdosInner Mongolia 017399China Department of Cardiology Lingqiu County People’s HospitalDatongShanxi 034499China Department of Cardiology Huaibin County People’s HospitalXinyangHenan 464411China Department of Cardiology Tianzhu County People’s HospitalWuweiGansu 733200China Guangzhou Recomgen Biotech Co. LtdGuangzhouGuangdong 510530China

Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in st elevation myocardial infarction(stEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with stEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute stEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to september 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute stEMI.Trial registration:www.ClinicalTrials.gov(No.NCT028355

关键词： Thrombolytic therapy rhTNK-tPA Randomized controlled trial st elevation myocardial infarction

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Etanercept-synthesizing adipose-derived stem cell secretome:A promising therapeutic option for inflammatory bowel disease

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World Journal of Gastrointestinal surgery 2024年第3期16卷 882-892页

作者： say-June Kim Ok-Hee Kim Ha-Eun Hong Ji Hyeon Ju Do sang Lee Department of surgery Seoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Catholic Central Laboratory of surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Division of Rheumatology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(AsCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from AsCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(Dss)-induced IBD mouse model.METHODs AsCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a Dss-induced IBD mouse model.REsULTs This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing AsCs[Etanercept-secretome(Et-sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-sec).Moreover,the Et-sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-sec.CONCLUsION These results suggest that the secretome derived from AsCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the AsC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

关键词： Adipose-derived stem cells Etanercept Inflammatory bowel disease secretome Tumor necrosis factor-α

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Factors affecting length of stay according to bronchopulmonary dysplasia severity:a nationwide cohort study in Korea

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World Journal of Pediatrics 2024年第5期20卷 470-480页

作者： Hye Mi Lee Jeongmin shin sae Yun Kim so Young Kim Department of Pediatrics College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea Department of Pediatrics Yeouido St.Mary’s HospitalCollege of MedicineThe Catholic University of Korea1063-roYeongdeungpo-guSeoul07345Republic of Korea

Background Longer hospitalizations for preterm infants with bronchopulmonary dysplasia(BPD)delay developmental outcomes,increase the risk for hospital-acquired complications,and exert a substantial socioeconomic burden.This study aimed to identify factors associated with an extended length of stay(LOs)at different levels of severity of BPD.Methods A cohort study was conducted using the Korean Neonatal Network registry of very low birth weight infants with BPD between 2013 and 2017 through retrospective analysis.Results A total of 4263 infants were diagnosed with BPD.For mild BPD,infants requiring surgical treatment for patent ductus arteriosus needed a longer LOs[eadjustedβcoefficients(adjβ)1.041;95%confidence interval(CI):0.01–0.08]and hydrocephalus(eadjβ1.094;95%CI 0.01–0.17).In moderate BPD,infants administered steroids or with intraventricular hemorrhage required a longer LOs(eadjβ1.041;95%CI 0.00–0.07 and eadjβ1.271;95%CI 0.11–0.38,respectively).In severe BPD,infants with comorbidities required a longer LOs:pulmonary hypertension(eadjβ1.174;95%CI 0.09–0.23),administrated steroid for BPD(eadjβ1.116;95%CI 0.07–0.14),sepsis(eadjβ1.062;95%CI 0.01–0.11),patent ductus arteriosus requiring surgical ligation(eadjβ1.041;95%CI 0.00–0.08),and intraventricular hemorrhage(eadjβ1.016;95%CI 0.05–0.26).Additionally,the higher the clinical risk index score,the longer the LOs needed for infants in all groups.Conclusions The factors affecting LOs differed according to the severity of BPD.Individualized approaches to reducing LOs may be devised using knowledge of the various risk factors affecting LOs by BPD severity.

关键词： Bronchopulmonary dysplasia Length of stay Very low birth weight

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A case report of bilateral lateral ventricle calcified pseudoneoplasm of the neuraxins

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Chinese Neurosurgical Journal 2024年第1期10卷 67-72页

作者： Xiaolong Qiao Yinan Chen Ying Ji Chaoshi Niu Chuandong Cheng Anhui University of science and Technology HuainanAnhui 232001People’s Republic of China Department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China1st Tianehu RoadHefeiAnhui 230031People’s Republic of China

Background Calcifying pseudoneoplasm of the neuraxis(CAPNON)is indeed a rare central nervous system lesion that can occur in central nervous system(CNs).Due to its infrequency and limited literature reports,it is challenging to diagnose and manage CAPNON.Case presentation In this intriguing study,we embarked on a quest to uncover the story of a 16-year-old girl who experienced bothersome headaches.Through advanced imaging techniques like computed tomography(CT)and magnetic resonance imaging(MRI),we glimpsed a delicate calcified growth within the lateral ventricles’posterior horn.Motivated by our unwavering commitment to solving mysteries,we embarked on a surgical journey that not only freed the young patient from her ailment but also shed light on the true nature of her puzzling adversary—a remarkable CAPNON.Conclusions For patients with CAPNON who have multiple or non-respectable lesions,the primary goal is to alleviate symptoms.After alleviating the symptoms with partial resection,close monitoring of any residual lesions is essential.If there is no evidence for disease progression,a strategy of continued close observation is appropriate.

关键词： CAPNON Imaging Pathology Operation

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