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Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu clinical School of the Tianjin Second People's Hospital Tianjin Medical University Department of Hepatology Tianjin Second People's Hospital Tianjin Institute of Hepatology Department of Hepatobiliary Oncology Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD) on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods: A total of 155 patients with CHB-related HCC who received ICI±based therapy(in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were *** were divided into two groups: MASLD concurrent with CHB [MASLD-CHB](n = 38), and CHB(n = 117).Results: The median progression-free survival(PFS, 6.9 months vs.9.3 months; P = 0.001), progressive disease(57.89% vs.37.61%; P = 0.028), and disease control rate(42.11% vs.62.39%; P = 0.028) in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56% vs.8.89%; P < 0.001) and CD8+PD1+ T cells(10.50% vs.7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD [hazard ratio(HR) = 1.921; 95% CI, 1.138±3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment(HR = 2.412; 95% CI, 1.360±4.279; P = 0.003) were independent risk factors for PFS in all ***: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B efficacy hepatocellular carcinoma immunotherapy

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Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina clinical research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 244-253页

作者： Feifei MAO Meng WANG Shuai ZHOU Yan ZHAO Jiaping HUANG Fengying YIN Haiping YANG Pei-hui DING Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310016China

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of *** study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic *** and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern *** them,complete periodontal charts were available for 69 Chinese patients with 103 *** and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,*** linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal ***:The prevalence of PMFM-DLR in Eastern China was relatively high in our *** morphological features of DLR were correlated with the periodontal status of mandibular first *** study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

关键词： Distolingual root Mandibular first molar Periodontal clinical parameter clinical attachment loss Cone beam computed tomography(CBCT)

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Role of mitochondrial dysfunction in kidney disease:Insights from the cGAS-STING signaling pathway

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Chinese Medical Journal 2024年第9期137卷 1044-1053页

作者： Lu Li Fei Liu Chunyue Feng Zhenjie Chen Nan Zhang Jianhua Mao Department of Nephrology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Pediatric Intensive Care Unit Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

Over the past decade,mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney ***,the precise molecular mechanisms linking mitochondrial damage to kidney disease remain *** recent insights into the cyclic guanosine monophosphate-adenosine monophosphate(GMP-AMP)synthetase(cGAS)-stimulator of interferon gene(STING)signaling pathway have revealed its involvement in many renal *** of these findings is that mitochondrial DNA(mtDNA)induces inflammatory responses via the cGAS-STING ***,we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage,focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney ***,we summarize the latest findings of cGAS-STING signaling pathway in cell,with a particular emphasis on its downstream signaling related to kidney *** review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway,kidney diseases,and mitochondrial dysfunction.

关键词： Mitochondrial dysfunction Mitochondrial DNA cGAS-STING pathway Kidney diseases Chronic kidney disease

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Hodgkin's lymphoma:2023 update on treatment

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Cancer Biology & Medicine 2024年第4期21卷 269-273页

作者： Sicong Zhang Xianming Liu Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Xianhuo Wang Huilai Zhang Department of Lymphoma Tianjin Medical University Cancer Institute&HospitalNational Key Laboratory of Druggability Evaluation and Systematic Translational MedicineNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China

Hodgkin's lymphoma(HL)is a common,malignant hematological tumor of the lymph nodes and lymphatic system,accounting for 10%of all *** comprises 2 main subtypes:classical HL(cHL)and nodular lymphocyte predominant HL.

关键词： lymphoma treatment predominant

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MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

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Bone research 2024年第1期12卷 153-164页

作者： Jiakang Yang Jing Shuai Lixuen Siow Jingyi Lu Miao Sun Wenyue An Mengfei Yu Baixiang Wang Qianming Chen Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310000China

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone ***,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of ***-146a was also found to inhibit osteoclast ***,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring ***,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.

关键词： inflammatory healing stimulation

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Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children:analysis of 571 patients

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World Journal of Pediatrics 2024年第3期20卷 250-258页

作者： Min He Jia-Bin Cai Xuan Wu Yin-Bing Tang Jin-Yan Wang Jun-Qin Mao Ji-Jun Chen Li-Feng Zhang Zhong-Hai Guan Jie-Ni Xiong Wan-Xin Peng Jin-Hu Wang Ting Tao Pediatric Cancer research center National Clinical Research Center for Child HealthHangzhouChina Department of Surgical Oncology Children's HospitalZhejiang University School of MedicineHangzhouChina Cancer center Zhejiang UniversityNo.3333 Binsheng RodeHangzhouChina

Background Surgery plays an important role in the treatment of *** complications may impact the course of neuroblastoma *** date,comprehensive analyses of complications and risk factors have been *** Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and *** data collected included clinical characteristics,operative details,operative complications and postopera-tive *** factors for perioperative complications of retroperitoneal neuroblastoma were *** A total of 571 patients were enrolled in this *** complications were observed in 255(44.7%)*** leakage(28.4%),diarrhea(13.5%),and injury(vascular,nerve and organ;7.5%)were the most frequent *** were three operation-related deaths(0.53%):massive hemorrhage(n=1),biliary tract perforation(n=1)and intestinal necrosis(n=1).The presence of image-defined risk factors(IDRFs)[odds ratio(OR)=2.09,P<0.01],high stage of the International Neuroblastoma Risk Group staging system(INRGSS)(OR=0.454,P=0.04),retroperitoneal lymph node metastasis(OR=2.433,P=0.026),superior mesenteric artery encasement(OR=3.346,P=0.003),and inferior mesenteric artery encasement(OR=2.218,P=0.019)were identified as independent risk factors for perioperative *** Despite the high incidence of perioperative complications,the associated mortality rate was quite ***-perative complications of retroperitoneal neuroblastoma were associated with IDRFs,INRGSS,retroperitoneal lymph node metastasis and vascular *** with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma.

关键词： Complication Neuroblastoma Risk factors Surgery

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Transcriptomic and cellular decoding of scaffolds-induced suture mesenchyme regeneration

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International Journal of Oral Science 2024年第2期16卷 306-321页

作者： Jiayi Wu Feifei Li Peng Yu Changhao Yu Chuyi Han Yitian Wang Fanyuan Yu Ling Ye State Key Laboratory of Oral Diseases&National center for Stomatology&National clinical research center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National center for Stomatology&National clinical research center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National center for Stomatology&National clinical research center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal *** extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances *** knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic *** to date,the absence of promising therapeutic biomaterials/scaffolds *** reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of *** address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial *** data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony ***,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were *** study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

关键词： injuries healing suture

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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