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Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway

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Chinese Medical Journal 2024年第6期137卷 711-719页

作者： Bo Jin Yemei Gao Yixian Fu Suxin Zhang Ke Zhang Yibing Su Department of Neurosurgery Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Department of Traditional Chinese Medicine Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China Department of Cardiology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Breast Surgical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:Mild traumatic brain injury(mTBI)is a common neurological trauma that can lead to cognitive impairment.The sirtuin-1(SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)pathway has been reported to have neuroprotective effects in rats with craniocerebral injury.We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI,focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods:We included forty 6-week-old male Sprague-Dawley rats in this study.Rats were randomly divided into four groups:controlled cortical impactor(CCI,n=10),sham operation(sham,n=10),electroacupuncture-treated CCI(CCI+EA,n=10),and electroacupuncture-treated sham(sham+EA,n=10)group.Randomization was performed by assigning a random number to each rat and using a random number table.The mTBI rat model was established using a controllable cortical impactor.Electroacupuncture therapy was performed on the back of rats,by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment.We evaluated spatial learning and memory functions with the Morris water maze test.We performed quantitative real-time polymerase chain reaction(qRT-PCR),western blotting,adenosine triphosphate(ATP)determination,and mitochondrial respiratory chain complex I(MRCC I)determination on rat hippocampal tissue.We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays,and compared differences between groups using bilateral Student’s t-tests.Results:Compared with the sham group,SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group(P<0.01).Although this expression was upregulated following electroacupuncture,it did not reach the levels observed in the sham group(P<0.05).Compared with the sham group,MRCC I and ATP levels in the CCI group were significantly reduced,and increased after electroacupuncture(P<0.01).In the Morris water maze,electroacupuncture reduced the incubation period of rats and

关键词： Electroacupuncture Cognitive impairment Sirtuin-1 Mild traumatic brain injury SIRT-1/PGC-1α/mitochondrial pathway

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG Han Lin XUE Yan Feng CUI Bao Qiu LIU Hong SHEN Xin Xin Shandong Provincial research center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province cancer hospital/Shanxi hospital Affiliated to cancer hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

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Circular RNAs in breast cancer diagnosis,treatment and prognosis

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Oncology research 2024年第2期32卷 241-249页

作者： XIAOJIA HUANG CAILU SONG JINHUI ZHANG LEWEI ZHU HAILIN TANG Department of Breast Oncology Surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou510095China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Breast Surgery The First People’s Hospital of FoshanFoshan528000China

Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

关键词： CircRNA Breast cancer Diagnosis Treatment Biomarker

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Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第6期30卷 565-578页

作者： Wen-Peng Wang Dan Shi Duo Yun Jun Hu Jie-Fu Wang Jia Liu Yan-Peng Yang Ming-Rui Li Jun-FengWang Da-Lu Kong Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Gastrointestinal Surgery Tianjin Nan Kai HospitalTianjin Medical UniversityTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM RepairInstitute of Integrative Medicine for Acute Abdominal DiseasesTianjin 300100China Department of Oncology The First Hospital of HohhotHohhot 010000Inner Mongolia Autonomous RegionChina Department of Endocrinology Dazhou Central HospitalDazhou 635000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

关键词： Esophageal squamous cell carcinoma JOSD2 Ubiquitination Biomarker Targeted therapy Drug resistance

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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 periodontitis.This 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 background.Materials 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 China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation 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%,respectively.Multiple 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 section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This 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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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 healing.Here,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 BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,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 hydrogel.Collectively,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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Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

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Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China research center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly understood.Here,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics data.As a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC.Among the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in cancer.Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras signaling.Next,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls.Mechanistically,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC risk.In summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

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Advances in regional nodal management of early-stage breast cancer

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Chinese Journal of cancer research 2024年第2期36卷 215-225页

作者： Zhao Bi Yongsheng Wang Breast cancer center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

关键词： Breast cancer sentinel lymph node biopsy internal mammary lymph node radiotherapy surgery

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Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

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cancer Biology & Medicine 2024年第3期21卷 204-212页

作者： Lei Yang Li Feng Yong Zhu Ning Wang Xinpu Lu Fanghui Gu Xiaotian Zhang Jiafu Ji Peking University cancer hospital(Inner Mongolia Campus)/Affiliated cancer hospital of Inner Mongolia Medical University Inner Mongolia Cancer CenterHohhot 010020China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Bejing) Bejing Office for Cancer Prevention and ControlPeking University Cancer Hospital&InstituteBejing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education) Peking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational research(Ministry of Education/Bejing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of Gastrointestinal cancers Bejing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI ca... 详细信息

关键词： esophageal colorectal gastrointestinal

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CSCO guidelines for colorectal cancer version 2024: Updates and discussions

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Chinese Journal of cancer research 2024年第3期36卷 233-239页

作者： Liubo Chen Hanguang Hu Ying Yuan Shanshan Weng Department of Medical Oncology(Key Laboratory of cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Sciences Zhejiang Province China) the Second Affiliated Hospital Zhejiang University School of Medicine Zhejiang Provincial clinical research center for cancer cancer center Zhejiang University

According to the latest global cancer statistics, colorectal cancer(CRC) is the most common malignancy of the digestive system and the second most lethal among all cancer types(1). In China, CRC is the second most prevalent cancer, following only after lung cancer(2). The first version of the Chinese Society of clinical Oncology(CSCO) guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research, drug accessibility and expert consensus(3-8).

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