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Mitochondria-targeted nanoparticles overcome chemoresistance via downregulating BACH1/CD47 axis in ovarian carcinoma

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Chinese Chemical Letters 2024年第5期35卷 344-350页

作者： Ke Gong Jinghan Liao Jiangtao Lin Quan Wang Zhihua Wu Liting Wang Jiali Zhang Yi Dong Yourong Duan Jianhua Chen State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032China Department of Ultrasound Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Department of oncology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

The platinum-based chemotherapy is a routine strategy for the treatment of ovarian cancer,while it is prone to chemoresistance in clinical,which hinders the ***,it is urgently needed to elucidate the underlying mechanism of drug resistance and form the appropriate *** sequencing results showed that cisplatin(DDP)resistant ovarian cancer overexpressed BTB and CNC homology 1(BACH1),and up-regulated the“don’t eat me”signal *** identified that hemin,a BACH1 inhibitor,could effectively down-regulate BACH1 and simultaneously inhibit ***,hemin has a synergistic effect with *** designed a pH-responsive nanoparticle(H/D@FA-CaP-NPs)in which folic acid(FA)ensured targeting of ovarian cancer cells,while hemin inhibited BACH1 as well as down-regulated CD47,achieving the promotion of apoptosis of tumor cells and inducing phagocytosis of tumors by ***,hemin has a synergistic effect with DDP to promote apoptosis of tumor ***,hemin and DDP was encapsulated within hydrophobic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine(DSPE)to form a tight core,and hydrophilic polyethylene glycol 2000(PEG2000)and calcium phosphate(CaP)formed the outside shell,and FA was modified on the surface of *** terms of function,(a)FA enhanced the active targeting of nanoparticles to tumors;(b)NPs targeted mitochondria to induce reactive oxygen species(ROS)production;(c)hemin encapsulated in nanoparticles could specifically target BACH1,thereby down regulating CD47;(d)hemin had a synergistic effect with DDP,thus augmenting the ***,mitochondria-targeted nanoparticles H/D@FA-CaP-NPs promoted tumor apoptosis and mobilized phagocytosis to treat tumor,providing a novel scheme for clinical treatment of cisplatin-resistant ovarian carcinoma.

关键词： Cisplatin-resistant Hemin BACH1 CD47 Phagocytosis ROS Synergistic effect

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Real-World Evidence in Localized Pancreatic: Coping with Uncertainty in Unselected Populations

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Journal of Cancer Therapy 2024年第4期15卷 164-178页

作者： María I. Pamies Ramón Diana Ibarra Anguita Paula Rodríguez Payá Alvaro Muñoz Abad David Sánchez García María Valero Revert Beatriz Grau Mirete Mariano Martínez Marín Alicia Calero Amaro Lorena Rodríguez Cazalla Javier Gallego Plazas Medical oncology Department Elche University Hospital Elche (Alicante) Spain general Surgery Department Elche University Hospital Elche (Alicante) Spain general Surgery Department Vega Baja Hospital Orihuela (Alicante) Spain

Background: Localized pancreatic cancer, including resectable (R), borderline resectable (BR) and locally advanced unresectable disease (LAU), is considered in clinical guidelines for diverse treatment options based on clinical trials in selected populations. Hence, exploring with real world evidence (RWE) clinicians’ preferences for treatment options and their results seems pertinent. Methods: In a set of consecutive patients with localized pancreatic cancer assisted in a third level hospital from January 2013 to December 2022, medical records, symptoms, diagnostic process, distribution between subtypes, and treatment plans, with safety and efficacy results, were assessed. Results: A total of 152 patients with localized disease were included (43.4% R, 21.0% BR, 33.6% LAU). The population characteristics exemplified differences between daily practice and clinical trials. Tumor location and symptoms were as expected. Treatment plan was conditioned by PS or comorbidities in 23.0% of patients. In patients with R disease, surgery followed by different adjuvant chemotherapy (CT) regimes was the antineoplastic treatment of choice (64.8%) with efficacy results (OS 37.5 months;95% CI 18.4 - 56.7), in the range of contemporary standards. The common use of neoadjuvant CT for BR disease (94.4%), with surgery in 50% of them, and its results (OS 30.8 months;95% CI 10.5 - 51.2) reflected current controversies of treatment recommendations and evolution in this scenario. Paliative CT with or without radiotherapy was the standard specific treatment in LAU disease (95.1%) with survival results (PFS: 10.8 months;95% CI 8.8 - 12.7. OS: 20.3 months;95% CI 13.5 - 27.2) that justify the distinct character and the specific study of this entity. Conclusion: RWE for localized pancreatic cancer aroused from the analysis of this population confirms the distinct nature of patients assisted in daily practice, as well as mirrors the complexity of decision making in clinical assumptions in which a

关键词： Real-World Evidence Localized Pancreatic Cancer

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Identification of depressive symptoms:A cause-and-effect based machine learning study

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Chinese Medical Journal 2024年第10期137卷 1258-1260页

作者： Tiantian Wang Zijian Zhang Xilin Zhang Chuang Xue Tingting Cheng Department of Radiation oncology Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalChangshaHunan 410008China School of Science Hunan University of Technology and BusinessChangshaHunan 410205China School of Mathematical Sciences University of Science and Technology of ChinaHefeiAnhui 230026China Department of Physiotherapy Treatment Center Affiliated Mental Health Center&Hangzhou Seventh People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310000China Department of general practice Xiangya HospitalCentral South UniversityChangshaHunan 410008China

To the Editor:As society continues to advance,individuals are increasingly exposed to various stressors in their personal and professional *** World Health Organization claims that nearly 1 billion people worldwide suffer from mental disorders in 2019,including 14%of the world’s adolescents.[1]Depression among Chinese adults is a serious public health challenge that requires urgent *** to the combined inuence of various life stresses and unhealthy lifestyles,individuals face a signicantly increased risk of developing depression.[2]Depression is often misdiagnosed because its symptoms overlap with those of other mental health conditions.A misdiagnosis of depression can have a signicant impact on all aspects of an individual’s *** children,a misdiagnosis can lead to inappropriate academic interventions or unnecessary treatments that can adversely affect their school life and overall *** adults,a misdiagnosis can strain relationships.

关键词： continue overlap effect

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ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling

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oncology Research 2024年第7期32卷 1209-1219页

作者： XIA DA HAN GE JUNFENG SHI CHUNHUA ZHU GUOZHU WANG YUAN FANG JIN XU Department of Breast and Thyroid Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of general Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of oncology Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of Pathology Nanjing First HospitalNanjing Medical UniversityNanjingChina

Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and ***2 expression in TNBC cell lines was detected by PCR and Western blot *** migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were ***:ROR2 expression was high in metastatic TNBC ***2 knockdown suppressed the migration,invasion and chemoresistance of TNBC ***2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and ***,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to ***2 could activate PI3K/AKT/mTOR signaling in TNBC ***:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

关键词： Receptor tyrosine kinase-like orphan receptor 2 Triplet-negative breast cancer Proliferation Apoptosis PI3K/AKT/mTOR signaling Metastasis

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Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

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Journal of Innovative Optical Health Sciences 2024年第1期17卷 87-103页

作者： Shan Long Yibing Zhao Yuanyuan Xu Bo Wang Haixia Qiu Hongyou Zhao Jing Zeng Defu Chen Hui Li Jiakang Shao Xiaosong Li Ying Gu School of Medicine Nankai University Tianjin300072P.R.China Department of Laser Medicine The First Medical Center of Chinese PLA general Hospital Beijing 100853 P.R.China Department of oncology The Seventh Medical Center of Chinese PLA general Hospital Beijing 100039 P.R.China School of Basic Medicine Guizhou Medical University Guiyang 550025GuizhouP.R.China College of Medical Technology Beijing Institute of Technology Beijing 100081P.R.China Medical School of Chinese PLA Beijing 100853 P.R.China

Photodynamic therapy(PDT)has limited effects in treating metastatic breast *** checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is *** study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and *** checkpoints on T cells were analyzed byflow cytometry after *** combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were *** HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be *** checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT *** PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with ***-PDT could not combat metastatic breast ***1 and LAG-3 were upregulated after ***-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

关键词： Photodynamic therapy anti-PD1 antibody anti-LAG-3 antibody anti-tumor im-mune effects metastatic breast cancer

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Surgical treatment of a rare brachial artery aneurysm postarteriovenous fistula closure after kidney transplant:A case report

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World Journal of Clinical Cases 2024年第21期12卷 4755-4761页

作者： Nahit Arda Demirkan Yasemin Keskin Hakan Sevinç Ömer Arda Çetinkaya Department of general Surgery Ankara University School of MedicineAnkara 06100Türkiye Department of general Surgery Dr.Abdurrahman Yurtaslan Ankara Oncology Training and Research HospitalAnkara 06100Türkiye

BACKGROUND Brachial artery aneurysms are defined as dilations greater than 50%of the normal diameter,which are rare among all peripheral arterial *** they are often present as pseudoaneurysms,true brachial artery aneurysms are also detected *** this case report,the surgical repair method of true brachial artery aneurysms,which is a rare condition,is *** SUMMARY Herein,we present a 61-year-old male patient with complaints of swelling and pain in the right arm antecubital region that had been progressing over 6 *** the diagnosis of a true brachial artery aneurysm associated with arteriovenous fistula,the aneurysm was surgically repaired with an autologous saphenous vein *** patient was discharged without any neurovascular complications *** True brachial artery aneurysms are rare and there are not any recommendations for their management in the current *** though the treatment of true aneurysms in this artery is primarily based on a surgical treatment,endovascular repair also might be an option.

关键词： Brachial artery aneurysm Arteriovenous fistula Kidney transplantation Surgical repair Autologous vein interposition Case report

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Stereotactic body radiotherapy in pancreatic adenocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 14-19页

作者： Carolina de la Pinta Radiation oncology Department Ramón y Cajal University HospitalIRYCISAlcaláUniversity28034 MadridSpain

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding *** review aimed at the SBRT application in the treatment of pancreatic *** sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December *** used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were *** articles were assessed for validity and relevant ***:Optimal doses and fractionation have not yet been ***,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to ***,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic ***:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease *** opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

关键词： Chemoradiotherapy Pancreatic adenocarcinoma Radiotherapy Stereotactic body radiotherapy Stereotactic ablative radiotherapy

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High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

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World Journal of Gastrointestinal oncology 2024年第3期16卷 787-797页

作者： Peng-Yang Zhou De-Xiang Zhu Yi-Jiao Chen Qing-Yang Feng Yi-Hao Mao Ao-Bo Zhuang Jian-Min Xu Department of general Surgery Zhongshan Hospital Fudan UniversityShanghai 200032China

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer *** studies have focused on its roles as an antioxidant and in lipid ***,the role of PNPLA8 in colorectal cancer(CRC)progression is *** To explore the prognostic effects of PNPLA8 expression in *** A retrospective cohort containing 751 consecutive CRC patients was ***8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive *** patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile *** prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression *** over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank *** PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter *** patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant *** analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

关键词： Biomarker Colorectal cancer Expression level Overall survival Patatin like phospholipase domain containing 8 Prognosis

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Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2655-2663页

作者： Zhi-Min Fan Dao-Lei Wu Neng-Wen Xu Li Ye Li-Ping Yan Lin-Jie Li Jun-Yu Zhang Department of Hematology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina Department of Ophthalmology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina Department of general practice Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina Department of Pathology Lishui Municipal Central HospitalLishui 323000Zhejiang ProvinceChina

BACKGROUND High-grade B-cell lymphoma(HGBL)is an unusual malignancy that includes myelocytomatosis viral oncogene(MYC),B-cell lymphoma-2(BCL-2),and/or BCL-6 rearrangements,termed double-hit or triple-hit lymphomas,and HGBL-not otherwise specific(HGBL-NOS),which are morphologically characteristic of HGBL but lack MYC,BCL-2,or BCL-6 *** is partially transformed by follicular lymphoma and other indolent lymphoma,with few cases of marginal zone lymphoma(MZL)*** often has a poor prognosis and intensive therapy is currently mainly advocated,but there is no good treatment for these patients who cannot tolerate *** SUMMARY We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase *** analysis revealed the gene expression profile was identical in the pre-and post-transformed tissues,suggesting that the two diseases are homologous,not secondary *** chemotherapy was ineffective and the side effect was severe,so we tried combination therapy including venetoclax and *** patient tolerated treatment well,and reached partial *** patient had recurrence of hepatocellular carcinoma and died of multifunctional organ *** survived for 12 months after *** Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients,who are unsuitable for chemotherapy.

关键词： Marginal zone lymphoma High-grade B-cell lymphoma Terminal deoxynucleotidyl transferase Venetoclax TP53 mutation Case report

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi Liu Jianye Xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi Department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of general practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic ***,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in ***,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic *** metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ***,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel ***-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in *** results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor *** findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

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