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Bifunctional small molecules targeting PD-L1/CXCL12 as dual immunotherapy for cancer treatment

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1351-1353页

作者： Binbin Cheng Wei Wang Ting Liu Hao Cao Wei Pan Yao Xiao Shuwen Liu Jianjun Chen School of Medicine Hubei Polytechnic UniversityHubei Key Laboratory for Kidney Disease Pathogenesis and InterventionHuangshi 435003China School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of New Drug ScreeningSouthern Medical UniversityGuangzhou 510515China Department of Cardiology The Sixth Affiliated HospitalSouth China University of TechnologyNanhai people’s HospitalFoshanGuangdong 528200China

Dear Editor,Inhibiting PD-1/PD-L1 interaction is a highly promising therapeutic modality.1 However,due to the low overall response rate in patients,researchers have attempted to combine PD-L1 inhibitors with other antitumor agents for cancer *** have shown that combination immunotherapy of PD-L1 antibodies with CXCL12 inhibitors exhibited synergistic and better antitumor efficacy than monotherapy,indicating the potential clinical utility of targeting both PD-L1 and CXCL12 as dual immunotherapy to treat cancer.2,3 However,there are several disadvantages for combination therapy,including unpredictable PK/PD and overlapping toxicities.A potential alternative to combination therapy would be to use a single molecule with dual or multi-targeting capability,as the PK/PD of a single molecule is easily *** example,dual-targeting bispecific antibodies(bsAbs)have gained significant attention in the field of anticancer drug discovery in recent *** PD-1/PD-L1-based bsAbs(e.g.,anti-PD-L1/TGF-β,anti-PD-1/CTLA-4,and anti-PD-1/LAG-3)have entered clinical trials as dual immunotherapy for treating cancer.

关键词： CXCL12 immunotherapy treatment

The Effects of therapeutic Horseback Riding Program on Motor Skills inChildren with Autism Spectrum Disorder

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International Journal of Mental Health Promotion 2022年第4期24卷 475-489页

作者： Mengxian Zhao Yonghao You Jinming Li Sean Healy Alyx Taylor Zhihao Zhang Linlin Li Liye Zou School of Physical Education Shenzhen UniversityShenzhen518060China Department of Sports Science Hefei Normal UniversityHefei230601China Body-brain-Mind Laboratory School of PsychologyShenzhen UniversityShenzhen518060China School of Nursing Psychotherapy and Community HealthDublin City UniversityGlasnevinDublin 9Ireland School of Rehabilitation Sport and PsychologyAECC University CollegeBournemouthBH5S2DFUK School of Sport Social Science Shandong Sport UniversityJinan250102China Key Laboratory of Adolescent Health Assessment and Exercise intervention of Ministry of Education East China Normal UniversityShanghai200241China

therapeutic horseback riding(THR)as an animal-assisted intervention is one of the innovative approaches emer-ging in the treatment for children with autism spectrum disorder(ASD).The current study was designed to inves-tigate the effects of a 12-week,twice a week THR program on motor skills in sixty-eight children with ASD aged 5–10 years *** participants selected met the DSM-V criteria for ASD,and a total ofﬁfty-three participants completed the study.A randomized controlled trial design was utilized for the *** was collected via a pre-THR test,interim-THR test,and post-THR test to investigate the possible changes in motor skills throughout the 12-week THR *** showed that the THR program signiﬁcantly improved overall motor skills across time points(pintervention is warranted.

关键词： therapeutic horseback riding animal-assisted intervention motor skills children with ASD autistic developmental disability equine-assisted activities and therapies

Nicotinic acetylcholine signaling is required for motor learning but not for rehabilitation from spinal cord injury

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Neural Regeneration Research 2023年第2期18卷 364-367页

作者： Yue Li Edmund R.Hollis II Burke Neurological Institute White PlainsNYUSA Feil Family brain and Mind Research Institute Weill Cornell MedicineNew YorkNYUSA Current address:Department of Neuroscience University of Rochester Medical CenterRochesterNYUSA

therapeutic intervention for spinal cord injury is limited,with many approaches relying on strengthening the remaining substrate and driving recovery through rehabilitative *** compared with learning novel compensatory strategies,rehabilitation focuses on resto ring movements lost to *** rehabilitation of previously learned movements after spinal cord injury requires the molecular mechanisms of motor learning,or if it engages previously trained motor circuits without requiring novel learning remains an open *** this study,mice we re randomly assigned to receive intrape ritoneal injection with the pan-nicotinic,non-competitive antagonist mecamylamine and the nicotinicα7 subunit selective antagonist methyllycaconitine citrate salt or vehicle(normal saline)prior to motor learning assays,then randomly reassigned after motor learning for rehabilitation study *** rvical spinal co rd dorsal column lesion was used as a model of in complete *** of this study showed that nicotinic acetylcholine signaling was required for motor learning of the single pellet-reaching task but it was dispensable for the rehabilitation of the same task after *** findings indicate that critical diffe rences exist between the molecular mechanisms supporting compensatory motor learning strategies and the restoration of behavior lost to spinal cord injury.

关键词： acetylcholine basal forebrain corticospinal tract dorsal column lesion mecamylamine methyllycaconitine motor control rehabilitation rotarod single pellet-reaching task

Cancer-associated fibroblasts in breast cancer:Challenges and opportunities

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Cancer Communications 2022年第5期42卷 401-434页

作者： Dengdi Hu Zhaoqing Li Bin Zheng Xixi Lin Yuehong Pan Peirong Gong Wenying Zhuo Yujie Hu Cong Chen Lini Chen Jichun Zhou Linbo Wang Affiliated Cixi Hospital Wenzhou Medical UniversityNingboZhejiang 315300P.R.China Affiliated Sir Run Run Shaw Hospital Zhejiang University School of Medicine(Key Laboratory of Cancer Prevention and InterventionMinistry of Education)HangzhouZhejiang 310016P.R.China Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province HangzhouZhejiang 310016P.R.China

The tumor microenvironment is proposed to contribute substantially to the progression of cancers,including breast ***-associated fibroblasts(CAFs)are the most abundant components of the tumor *** have revealed that CAFs in breast cancer originate from several types of cells and promote breast cancer malignancy by secreting factors,generating exosomes,releasing nutrients,reshaping the extracellular matrix,and suppressing the function of immune *** are also becoming therapeutic targets for breast cancer due to their specific distribution in tumors and their unique *** interrupting the effect of CAFs on surrounding cells have been developed and applied in clinical ***,we reviewed studies examining the heterogeneity of CAFs in breast cancer and expression patterns of CAF markers in different subtypes of breast *** hope that summarizing CAFrelated studies from a historical perspective will help to accelerate the development of CAF-targeted therapeutic strategies for breast cancer.

关键词： Cancer-associated fibroblasts breast cancer therapeutic target tumor microenvironment biomarker tumor heterogeneity

Image-guided locoregional non-intravascular interventional treatments for hepatocellular carcinoma: Current status

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Journal of interventional Medicine 2021年第1期4卷 1-7页

作者： Kun Qian Feng Zhang Stephen K.Allison Chuansheng Zheng Xiaoming Yang Department of Radiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430022China Department of Radiology Image-Guided Biomolecular Intervention ResearchUniversity of Washington School of MedicineSeattleWA98109USA Division of interventional Radiology Department of RadiologyUniversity of Washington School of MedicineSeattleWA98109USA

Hepatocellular carcinoma(HCC) is one of the most deadly and frequent cancers worldwide,although great advancement in the treatment of this malignancy have been made within the past few *** continues to be a major health issue due to an increasing incidence and a poor *** majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or *** therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these *** chemoembolization(TACE),the most widely used locoregional therapeutic approach,used to be the mainstay of treatment for cases with unresectable cancer ***,for those patients with hypovascular tumors or impaired liver function reserve,TACE is a suboptimal treatment *** example,embolization does not result in complete coverage of a hypovascular tumor,and may rather promotes postoperative tumor recurrence,or leave residual tumor,in these TACE-resistance *** addition,TACE carries a higher risk of hepatic decompensation in patients with poor liver function or ***-vascular interventional locoregional therapies for HCC include radiofrequency ablation(RFA),microwave ablation(MWA),high-intensity focused ultrasound(HIFU),laser-induced thermotherapy(LITT),cryosurgical ablation(CSA),irreversible Electroporation(IRE),percutaneous ethanol injection(PEI),and *** advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for *** review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs,with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.

关键词： impaired treatment irreversible

Treatment of primary hepatic carcinoma by transcatheter arterial perfusion of batroxobin combined with TACE:a preliminary clinical study

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The Chinese-German Journal of Clinical Oncology 2011年第2期10卷 96-99页

作者： Tianjun Gao Mingwu Lou Hui Wang Yi Fan Yunxia Shen Jiyin Ruan Hongguang Zhang Department of interventional Radiology Longgang District Central Hospital of Shenzhen Shenzhen 518116 China Department of intervention Tumour Hospital of Jilin Province Changchun 130012 China

Objective:The aim of the study was to explore the therapeutic efficacy and safety of batroxobin in patients with primary hepatic carcinoma(PHC) and the advantages of transcatheter arterial perfusion of batroxobin combined with transcatheter arterial chemoembolization(TACE).Methods:Forty patients with PHC were randomized into experimental group(transcatheter arterial perfusion of batroxobin combined with TACE treatment,20 patients) and control group(TACE alone group,20 patients).The patients were followed up and the data were recorded,compared and ***:(1) Compared with the control group,the FIB level in the experimental group was significantly decreased at the first month after treatment(P 0.05).Conclusion:Batroxobin can rapidly and effectively decrease the FIB level of the PHC *** it may be used as an effective and safe adjuvant drug for the treatment of primary hepatic *** arterial perfusion of batroxobin combined with TACE therapy has advantages in comparison with TACE alone *** could be taken as a new therapeutic regimen in the PHC treatment.

关键词： batroxobin liver neoplasms fibrinogen therapy transcatheter arterial chemoembolization(TACE)

Homeobox B8 Targets Sterile Alpha Motif Domain-Containing Protein 9 and Drives Glioma Progression

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Neuroscience Bulletin 2020年第4期36卷 359-371页

作者： Wenping Ma Hongze Jin Wenjie Liu Xiaojuan Li Xingang Zhou Xinwu Guo Runfa Tian Qi Cui Junjie Luo Yueying Jiao Youtao Yu Haifeng Yang Hongshan Zhao Department of Medical Genetics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Beijing Neurosurgical Institute Beijing 100050China The Second Affiliated Hospital of Zhejiang University School of Medicine Changxing CampusChangxing 313100China Department of Hepatobiliary Surgery National Cancer Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiology The First Hospital of Harbin Medical UniversityHarbin 150001China Department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Sansure Biotech Inc. Changsha 410205China Department of intervention Therapy The Fourth Medical Center of PLA General HospitalBeijing 100037China Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China

Gliomas are the most commonly occurring tumors of the central nervous system. Glioblastoma multiforme (GBM) is the most malignant and aggressive brain cancer in adults. Further understanding of the mechanisms underlying the aggressive nature of GBM is urgently needed. Here we identified homeobox B8(HOXB8), a member of the homeobox family, as a crucial contributor to the aggressiveness of GBM. Data mining of publicly accessible RNA sequence datasets and our patient cohorts confirmed a higher expression of HOXB8 in the tumor tissue of GBM patients, and a strong positive correlation between the expression level and pathological grading of tumors and a negative correlation between the expression level and the overall survival rate. We next showed that HOXB8 promotes the proliferation and migration of glioblastoma cells and is crucial for the activation of the PI3K/AKT pathway and expression of epithelial–mesenchymal transition-related genes, possibly through direct binding to the promoter of SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) and activating its transcription. Collectively, we identified HOXB8 as a critical contributor to the aggressiveness of GBM, which provides insights into a potential therapeutic target for GBM and opens new avenues for improving its treatment outcome.

关键词： HOXB8 Glioma Aggressiveness SAMD9 Treatment

Comparison of the postoperative pain change and spinal stenosis rate between percutaneous vertebroplasty combined with radiofrequency ablation and with ^(125)I particle implantation in the treatment of metastatic spinal cord compression:A retrospective st

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Journal of interventional Medicine 2021年第4期4卷 197-202页

作者： Yu He Shilong Han Chungen Wu Fei Ge Jianbo Wang Department of interventional Radiology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong UniversityShanghaiChina Department of intervention and Vascular Surgery Shanghai Tenth People's Hospital Affiliated to Shanghai Tongji University School of MedicineShanghaiChina Medical Department Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong UniversityShanghaiChina

Background context:Metastatic spinal cord compression(MSCC)seriously affects the survival ***:The therapeutic effects of two treatment strategies for MSCC:percutaneous vertebroplasty(PVP)combined with radiofrequency ablation(RFA)and PVP combined with^(125)I particle implantation,were *** design:Retrospective *** sample:40 patients with MSCC were divided into two groups:19 cases in the RFA group and 21 cases in the^(125)I ***:All patients were accessed to determine the differences in pain,which was evaluated using the visual analog scale(VAS)at 1 week,1 month,and 3 months after the operation,and spinal stenosis rates(SSRs),which were measured at 1 and 3 months after the operation,between the two ***:The VAS scores and SSRs at baseline were comparable between the RFA group and the^(125)I group(7.19±2.07 vs 7.42±1.95,37.7%±11.2%vs 41.1%±11.4%).The VAS scores and SSRs at 1 month and 3 months after the operation were significantly reduced in both groups,compared with those at *** VAS scores and SSRs in the^(125)I group were lower than those in the RFA group at 3 months after the operation(1.09±0.97 vs 1.75±1.06 p=0.048 and 12.3%±6.4%vs 18.1%±10.1%p=0.034),while the VAS scores at1 week after the operation in the RFA group were lower than those in the^(125)I group(4.39±1.34 vs 5.05±1.82 p=0.049).Conclusion:PVP combined with RFA has a slight advantage in relieving pain in the short term,while PVP combined with^(125)I particle implantation may have a better effect in the relieving pain and decreasing the SSRs at 3 months after the operation.

关键词： Metastatic spinal cord compression Pain management Vertebroplasty Radiofrequency ablation ^(125)I particle

therapeutic values of chick early amniotic fluid(ceAF)that facilitates wound healing via potentiating a SASP-mediated transient senescence

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Genes & Diseases 2022年第5期9卷 1345-1356页

作者： Mashaal Ahmad Yandi Sun Xueyao Jia Jingjia Li Lihong Zhang Ze Yang Yindan Lin Xueyun Zhang Zara Ahmad Khan Jin Qian Yan Luo Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital Key Laboratory of Cancer Prevention and Intervention of China National MOEZhejiang University School of MedicineHangzhouZhejiang 310058PR China State Key Laboratory of Oncogenes and Related Genes Institute for Personalized MedicineSchool of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200240PR China Zhejiang HygeianCells BioMedical Co.Ltd. HangzhouZhejiang 310000PR China

Inflammatory,proliferative and remodeling phases constitute a cutaneous wound healing *** applications and medication are available;however,they commonly are comprised of fortified preservatives that might prolong the healing *** early amniotic fluids(ceAF)contain native therapeutic factors with balanced chemokines,cytokines and growth-related factors;their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo ***,they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other *** both in vitro and in vivo models,we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence,known to be intimately intermingled with Senescence Associated Secretory Phenotypes(SASP)that function in addition to or in conjunction with ceAF to facilitate wound *** our cutaneous wound healing models,a low dose of ceAF exhibited the best efficacies;however,higher doses attenuated the wound healing presumably by inducing p16 expression over a *** studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing,suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence,expediting cellular proliferation,migration,and describing a homeostatic and balanced dosage strategy in medical intervention.

关键词： Amniotic fluids Chick early embryo Cutaneous wound healing Senescence associated secretory phenotypes (transient)Senescence