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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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Internal limiting membrane peeling combined with silicone oil or air tamponade for highly myopic foveoschisis

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1079-1085页

作者： Jin Deng Wen-Tao sun Ke Gong Li-Ping Wang Feng-Zhi Li Xi’an People’s hospital(Xi’an Fourth hospital) Shaanxi Eye HospitalAffiliated People’s Hospital of Northwest UniversityXi’an 70004Shaanxi ProvinceChina

AIM:To compare the efficacy of pars plana vitrectomy(PPV)combined with internal limiting membrane(ILM)and silicone oil or sterile air tamponade for the treatment of myopic foveoschisis(MF)in highly myopic eyes.METHODs:This retrospective study included 48 myopic eyes of 40 patients with MF and axial lengths(ALs)ranging from 26-32 mm treated between January 2020 and January 2022.All patients were underwent PPV combined with ILM peeling followed by sterile air or silicone oil tamponade and followed up at least 12mo.Based on the features on spectral-domain optical coherence tomography(sD-OCT),the eyes were divided into the MF-only group(Group A,n=15 eyes),MF with central foveal detachment group(Group B,n=20 eyes),and MF with lamellar macular hole group(Group C,n=13 eyes).According to AL,eyes were further divided into three groups:Group D(26.01-28.00 mm,n=12 eyes),Group E(28.01-30.00 mm,n=26 eyes),and Group F(30.01-32.00 mm,n=10 eyes).The best-corrected visual acuity(BCVA),central foveal thickness(CFT),and complications were recorded.REsULTs:The patients included 16 males and 24 females with the mean age of 56±9.82y.The BCVA and CFT improved in all groups after surgery(Ps no significant difference of the CFT in Group A,B,and C postoperatively(P>0.05).The intergroup differences of BCVA and CFT postoperatively were statistically significant in Group D,E,and F.Twenty eyes were injected with sterile air,and 28 eyes were injected with silicone oil for tamponade based on the AL.However,there was no statistically significant difference among Groups D,E,and F in terms of the results of sterile air or silicone oil tamponade.The mean recovery time was 5.9mo for MF patients subjected to silicone oil tamponade and 7.7mo for patients subjected to sterile air tamponade,and the difference was not statistically significant.CONCLUsION:PPV and ILM peeling combined with silicone oil or sterile air tamponade can achieve good results for MF in highly myopic eyes with ALs≤32 mm.

关键词： axial length myopic foveoschisis highly myopic internal limiting membrane pars plana vitrectomy

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Myosin binding protein C:structural abnormalities in familial hypertrophic cardiomyopathy

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Cell Research 2004年第2期14卷 95-110页

作者： Cecily E OAKLEY Brett D HAMBLY Paul MG CURMI Louise J BROWN Department of Pathology University of sydney NsW 2006 Australia Initiative for Biomolecular structure school of Physics University of New south Wales NsW 2052 and Centre for Immunology st vincent’s hospital and University of New south Wales sydney NsW 2010 Australia.

The muscle protein myosin binding protein C (MyBPC) is a large multi-domain protein whose role in the sarcomere is complex and not yet fully understood. Mutations in MyBPC are strongly associated with the heart disease familial hypertrophic cardiomyopathy (FHC) and these experiments of nature have provided some insight into the intricate workings of this protein in the heart. While some regions of the MyBPC molecule have been assigned a function in the regulation of muscle contraction, the interaction of other regions with various parts of the myosin molecule and the sarcomeric proteins, actin and titin, remain obscure. In addition, several intra-domain interactions between adjacent MyBPC molecules have been identified. Although the basic structure of the molecule (a series of immunoglobulin and fibronectin domains) has been elucidated, the assembly of MyBPC in the sarcomere is a topic for debate. By analysing the MyBPC sequence with respect to FHC-causing mutations it is possible to identify individual

关键词： myosin binding protein C hypertrophic cardiomyopathy sarcomeric proteins immunoglobulin superfamily mutations.

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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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The application of the strip-shaped cymba conchae orthosis in the nonsurgical correction of complex auricular deformity

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Journal of Otology 2024年第1期19卷 24-29页

作者： Huijuan Xu shaoguang Ding Fei Zhang Zhifeng Zhang Xiangyu Chen Mingyang Li Haitao Yang Fugen Han Hongjian Liu Department of Otolaryngology Head and Neck surgery People’s Hospital of Henan UniversityHenan Provincial People’s HospitalZhengzhouChina Department of Otolaryngology Head and Neck surgery Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityPeople’s Hospital of Henan UniversityZhengzhouChina Department of Otolaryngology Head and Neck surgery Henan Children’s HospitalZhengzhouChina Department of Otolaryngology Head and Neck surgery The Third People’s Hospital of ZhengzhouZhengzhouChina Zheng Dong Mihuan Clinic ZhengzhouChina

Objective: This study aims to evaluate the efficacy and safety of using a strip-shaped cymba conchae orthosis for the nonsurgical correction of complex auricular deformities. Methods: Clinical data were collected from 2020 to 2021 for 6 patients who underwent correction using a stripshaped cymba conchae orthosis. The indications, corrective effects, and complications associated with use of the orthosis were analyzed. Results: There were four indications for treatment: cryptotia with helix adhesion;cryptotia with grade I microtia;cryptotia with excessive helix thickness;and auricular deformity beyond the treatment time window(≥6 months). Excellent corrective effects were observed in all 6 patients. Complications occurred in one patient, who recovered after symptomatic treatment. Conclusion: The use of a strip-shaped cymba conchae orthosis alone or combined with a U-shaped helix orthosis presents a feasible approach for correcting complex auricular deformities or deformities beyond the treatment time window in pediatric patients.

关键词： Cymba conchae Auricular deformity Cryptotia Nonsurgical correction Orthosis

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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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Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation

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Journal of Geriatric Cardiology 2024年第3期21卷 251-314页

作者： Chang-sheng MA shu-Lin WU shao-Wen LIU Ya-Ling HAN Chinese society of Cardiology Chinese Medical Association Heart Rhythm Committee of Chinese society of Biomedical Engineering Beijing Anzhen hospital Capital Medical University Guandong Provincial People’s hospital shanghai First People’s hospital General hospital of Northern Theater Command 不详

Atrial fibrillation(AF)is the most common sustained cardiac arrhythmia,significantly impacting patients’quality of life and increasing the risk of death,stroke,heart failure,and dementia.Over the past two decades,there have been significant breakthroughs in AF risk prediction and screening,stroke prevention,rhythm control,catheter ablation,and integrated management.During this period,the scale,quality,and experience of AF management in China have greatly improved,providing a solid foundation for the development of guidelines for the diagnosis and management of AF.To further promote standardized AF management,and apply new technologies and concepts to clinical practice in a timely and comprehensive manner,the Chinese society of Cardiology of the Chinese Medical Association and the Heart Rhythm Committee of the Chinese society of Biomedical Engineering have jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation.The guidelines have comprehensively elaborated on various aspects of AF management and proposed the CHA2Ds2-VAsc-60 stroke risk score based on the characteristics of AF in the Asian population.The guidelines have also reevaluated the clinical application of AF screening,emphasized the significance of early rhythm control,and highlighted the central role of catheter ablation in rhythm control.

关键词： prevention sustained diagnosis

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Primary pancreatic peripheral T-cell lymphoma:A case report

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1668-1675页

作者： Yan-Liang Bai Li-Jie Wang Hui Luo Ya-Bin Cui Jin-Hui Xu Hui-Jie Nan Pei-Yao Yang Jun-Wei Niu Ming-Yue shi Department of Hematology Zhengzhou University People's Hospital and Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina Department of Hematology Henan University People's Hospital and Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008Henan ProvinceChina

BACKGROUND Primary pancreatic lymphoma(PPL)is an exceedingly rare tumor with limited mention in scientific literature.The clinical manifestations of PPL are often nonspecific,making it challenging to distinguish this disease from other panc-reatic-related diseases.Chemotherapy remains the primary treatment for these individuals.CAsE sUMMARY In this case study,we present the clinical details of a 62-year-old woman who initially presented with vomiting,abdominal pain,and dorsal pain.On further evaluation through positron emission tomography-computed tomography,the patient was considered to have a pancreatic head mass.However,subsequent endoscopic ultrasonography-guided fine needle aspiration(EUs-FNA)revealed that the patient had pancreatic peripheral T-cell lymphoma,not otherwise specified(PTCL-NOs).There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin,decitabine,and oxaliplatin(brentuximab vedotin and Gemox).The patient had significant improvement in radiological findings at the end of the first cycle.CONCLUsION Primary pancreatic PTCL-NOs is a malignant and heterogeneous lymphoma,in which the clinical manifestations are often nonspecific.It is difficult to diagnose,and the prognosis is poor.Imaging can only be used for auxiliary diagnosis of other diseases.With the help of immunostaining,EUs-FNA could be used to aid in the diagnosis of PPL.After a clear diagnosis,chemotherapy is still the first-line treatment for such patients,and surgical resection is not recommended.A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma.However,identifying new CD30-targeted therapies for different types of lymphoma is urgently needed.In the future,further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

关键词： Pancreatic cancer Lymphoma Chemotherapy Primary pancreatic lymphoma Case report

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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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