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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng Qiu Wenyang Fu Weiwei Li Lei Cheng Qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu Department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China University of Health and Rehabilitation Sciences Qingdao 226000China Xiangya School of Medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China Department of Pediatrics Cangzhou Central HospitalCangzhou 061011China Department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China Department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China Department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second Hospital of shandong University Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel

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Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第13期30卷 1810-1814页

作者： Yan-Bo Yu Department of Gastroenterology Laboratory of Translational GastroenterologyQilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in *** focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment *** current standard treatment for SESCC is radical esophagectomy with lymph node ***,esophagectomy is associated with considerable morbidity and *** resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory ***,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of *** LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional *** studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with *** addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous *** comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

关键词： Superficial esophageal squamous cell carcinoma Endoscopic resection Lymph node metastasis Risk factors Tumor budding Predictive model

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Clinical application of eight-zone laparoscopic dissection strategy for rectal cancer:Experience and discussion

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World Journal of Gastroenterology 2024年第30期30卷 3574-3583页

作者： Chang Chen Xiang Zhang Xin Li Yan-Lei Wang Department of General Surgery Rongchang People's HospitalChongqing 250012China Department of Colorectal Surgery Qilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina Department of General Surgery Huantai Branch of Qilu Hospital of Shandong UniversityZibo 255000Shandong ProvinceChina

BACKGROUND The incidence of rectal cancer is increasing worldwide,and surgery remains the primary treatment *** the advent of total mesorectal excision(TME)technique,the probability of tumor recurrence post-surgery has significantly ***'focus has gradually shifted towards minimizing the impact of surgery on urinary and sexual *** these concerns,the optimal dissection of the rectal lateral ligaments and preservation of the pelvic floor neuro-vascular bundle have become *** explore the optimal surgical technique for TME and establish a standardized surgical protocol to minimize the impact on urinary and sexual functions,we propose the eight-zone dissection strategy for pelvic floor *** To compare the differences in surgical specimen integrity and postoperative quality of life satisfaction between the traditional pelvic floor dissection strategy and the innovative eight-zone dissection *** We analyzed the perioperative data of patients who underwent laparoscopic radical resection of rectal cancer at Qilu Hospital of shandong University between January 1,2021 and December 1,*** study included a total of 218 patients undergoing laparoscopic radical surgery for rectal cancer,among whom 109 patients underwent traditional pelvic floor dissection strategy,and 109 patients received the eight-zone dissection *** There were no significant differences in general characteristics between the two *** in the eight-zone dissection group had higher postoperative specimen integrity(88.1%vs 78.0%,P=0.047).At the 3-month followup,patients in the eight-zone surgery group had better scores in urinary issues(6.8±3.3 vs 5.3±2.5,P=0.045)and male sexual desire(2.2±0.6 vs 2.5±0.5,P=0.047)compared to the traditional surgery strategy *** This study demonstrates that the eight-zone dissection strategy for laparoscopic lateral ligament dissection of rectal cancer is safe and ***

关键词： Eight-zone dissection strategy Rectal cancer Lateral ligament dissection Nerve injury Total mesorectal excision surgery

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Chemotherapy induces breast cancer stem cell enrichment through repression of glutathione S-transferase Mu

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Genes & Diseases 2024年第2期11卷 528-531页

作者： Jing He Yiran Yu Yilin He Jie He Guangyu Ji Haiquan Lu The Second Hospital and Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanShandong 250012China Department of Nursing The First Affiliated Hospital of Shandong First Medical UniversityJinanShandong 250014China School of Medicine Xinjiang Medical UniversityUrumqiXinjiang 830054China School of Medicine Binzhou Medical UniversityYantaiShandong 264003China Oncology Department Jinan Zhangqiu District People's HospitalJinanShandong 250200China Key Laboratory for Experimental Teratology of the Ministry of Education Cheeloo College of MedicineShandong UniversityJinanShandong 250012China Center for Reproductive Medicine Shandong UniversityJinanShandong 250012China

Triple-negative breast cancer(TNBC)has aggressive characteristics as exemplified by the high risk of recurrence,metastasis,and patient mortality.1 Cytotoxic chemotherapy may reduce tumor burden initially,but leave behind chemo-resistant breast cancer stem cells(BCSCs)that lead to tumor recurrence and metastasis.2 Chemotherapy induces BCsC enrichment through the activation of glutathione biosynthesis pathways,which increases intracellular glutathione levels and specifies the BCSC phenotype through complicated downstream signaling pathways.3 Glutathione S-transferases(GSTs),a superfamily(which contains seven cytosolic classes:Alpha,Kappa,Mu,Omega,Pi,Theta,and Zeta,and one microsomal class MGSTs)of phase Il enzymes that catalyze the conjugation of glutathione with electrophilic compounds,play a critical role in detoxification and chemotherapy resistance of cancer ***,the role of GSTs in the regulation of BCSCs is largely elusive.

关键词： chemotherapy breast metastasis

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Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2271-2283页

作者： Long-Chen Yu Ya-Ping Li Yue-Ming Xin Mai Mao Ya-Xin Pan Yi-Xuan Qu Zheng-Dong Luo Yi Zhang Xin Zhang Department of Clinical Laboratory Qilu Hospital of Shandong UniversityShandong Engineering Research Center of Biomarker and Artificial Intelligence ApplicationJinan 250012Shandong ProvinceChina

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human *** of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and *** nucleatum(***)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate *** development in novel research suggests that *** may function as a biomarker in GI *** the abundance of *** in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI *** editorial systematically describes the biological roles and mechanisms of *** in GI malignancies focusing on the application of *** as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of *** and GI tumors-related research.

关键词： Gastrointestinal malignancies Fusobacterium nucleatum Biomarker Diagnosis Prognosis

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Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2281-2297页

作者： Chongzheng Yan Ying Liu Guozhi Zhao Huatian Yang Huaiyou Lv Genju Li Yuhan Li Yaqing Fu Fengqin Sun Yafei Feng Yizhe Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Cuproptosis shows enormous application prospects in lung metastasis ***,the glycolysis,Cu^(+)efflux mechanisms,and insufficient lung drug accumulation severely restrict cuproptosis ***,an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)(OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA(siPDK)is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy,namely *** inhalation,OMP shows highly efficient lung accumulation and long-term retention,ascribing to the OPDEA-mediated pulmonary mucosa *** tumor cells,OMP is degraded to release Cu2+under acidic condition,which will be reduced to toxic Cu^(+)to induce cuproptosis under glutathione(GSH)***,siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate(ATP)production,then blocking the Cu^(+)efflux protein ATP7B,thereby rendering tumor cells more sensitive to OMP-mediated ***,OMP-mediated cuproptosis triggers immunogenic cell death(ICD)to promote dendritic cells(DCs)maturation and CD8^(+)T cells ***,OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1(PD-L1)expression and induces soluble PD-L1 secretion,and thus synergizes with anti-PD-L1 antibodies(aPD-L1)to reprogram immunosuppressive tumor microenvironment,finally yielding improved immunotherapy ***,OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

关键词： Cuproptosis Immunogenic cell death PD-L1 checkpoint blockade Copper-based metal-organic framework Immunotherapy Tumor microenvironment Transmucosal deliveryLung metastasis

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Beware of the serious harm of veterinary drug poisoning:a case report

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World Journal of Emergency Medicine 2024年第2期15卷 153-155页

作者： Ping Dai Jin Sun Tongyue Zhang Zhiqiang Zhou Zixi Wen Tianzi Jian Aerbusili Genjiafu Baotian Kan Xiangdong Jian Department of Poisoning and Occupational Diseases Emergency MedicineQilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012China Emergency Department Affiliated the Jianhu Clinical Medical College of Yangzhou UniversityYancheng 224700China Department of Occupational and Environmental Health School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China School of Nursing and Rehabilitation Cheeloo College of MedicineShandong UniversityNursing Theory&Practice Innovation Research Center of Shandong UniversityJinan 250012China Department of Geriatric Medicine Qilu HospitalNursing Theory Innovation and Research Center of Shandong UniversityCheeloo College of MedicineShandong UniversityJinan 250012China

Veterinary drugs are substances(including pharmaceutical feed additives)used to prevent,treat,and diagnose diseases or regulate the physiological functions of *** drug poisoning in humans is relatively rare both in China and the rest of the ***,we report a case of death from veterinary drug poisoning from ***-closantel is a broad-spectrum antiparasitic drug,which has high efficacy against a variety of trematodes and nematodes.

关键词： drug drugs diseases

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Molecular Epidemiological Study of a Human Brucellosis Outbreak—Weihai City,shandong Province,China,2022

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China CDC weekly 2024年第12期6卷 230-234页

作者： Yan Li Yifan Yu Jian Zhao Shujun Ding Guoying Zhang Xiaolin Yu Zengqiang Kou shandong Provincial Center for Disease Control and Prevention Jinan CityShandong ProvinceChina shandong First Medical University Shandong Academy of Medical SciencesJinan CityShandong ProvinceChina Weihai Municipal Center for Disease Control and Prevention Weihai CityShandong ProvinceChina

What is already known about this topic?Brucellosis,mainly caused by Brucella melitensis(***),is regarded as a significant zoonotic disease in *** Weihai,located at the eastern end of the shandong Peninsula,brucellosis has been in a low epidemic phase for the past five *** is added by this report?This was the initial report of a brucellosis outbreak in the last five *** of *** bv.3 from Weihai and other cities showed a close genetic relationship,suggesting a potential common *** are the implications for public health practice?Epidemiological investigations depend on standardized and effective molecular typing methods and analysis tools for public health laboratories to identify and trace *** the circulation patterns of livestock in free-range households in heavily affected areas is essential for controlling the spread of brucellosis.

关键词： shandong China. break

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Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity

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Science China(Life Sciences) 2024年第1期67卷 51-66页

作者： Yonghui Jiang Xueying Gao Yue Liu Xueqi Yan Huangcong Shi Rusong Zhao Zi-Jiang Chen Fei Gao Han Zhao Shigang Zhao Center for Reproductive Medicine Shandong UniversityJinan 250012China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education Shandong UniversityJinan 250012China shandong Key Laboratory of Reproductive Medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250012China shandong Provincial Clinical Research Center for Reproductive Health Jinan 250012China National Research Center of Assisted Reproductive Technology and Reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215000China Center for reproductive medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics Shanghai 200127China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of ScienceBeijing 100101China

Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive *** ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly *** this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial ***,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral ***,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular *** differences can be explained by the differential expression pattern of the transcription factor ***,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.

关键词： obesity ovarian microenvironment snRNA-seq Stereo-seq Foxo1

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Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

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World Journal of Diabetes 2024年第6期15卷 1340-1352页

作者： Zi-Tian Liu Guang-Wei Yang Xiang Zhao Shuo-Hui Dong Yang Jiao Zheng Ge Ao Yu Xi-Qiang Zhang Xin-Zhen Xu Zhi-Qiang Cheng Xiang Zhang Ke-Xin Wang Department of General Surgery Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Department of General Surgery Shandong University of Qilu Hospital(Qingdao)Qingdao 266000Shandong ProvinceChina

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not *** To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat *** DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat *** adipose tissue was weighed and observed under *** inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose ***-sequencing was utilized to evaluate gene expression alterations *** hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the *** resistance was evaluated by *** After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue *** cell volume in both visceral adipose tissue(VAT)and SAT *** to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic *** circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT *** experiment showed that GH stimulated adiponectin secretion and improve insulin *** GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

关键词： Growth hormone Insulin resistance Bariatric surgery Adipose tissue Adiponectin

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