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Metal-organic frameworks nanoswitch:Toward photo-controllable endo/lysosomal rupture and release for enhanced cancer RNA interference

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Nano Research 2020年第1期13卷 238-245页

作者： Gan Lin Yang Zhang Long Zhang Junqing Wang Ye Tian Wen Cai Shangui Tang Chengchao Chu JiaJing Zhou Peng Mi Xiaoyuan Chen Gang Liu State key laboratory of Molecular Vaccinology and Molecular Diagnostics&Center for Molecular Imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen361102China The Department of Chemical Engineering The University of MelbourneParkvilleVictoria3010Australia School of Chemical and Biomedical Engineering Nanyang Technological UniversitySingapore637457Singapore State key laboratory of Biotherapy and cancer Center West China HospitalCollaborative Innovation Center for BiotherapySichuan UniversityChengdu610041China laboratory of Molecular Imaging and Nanomedicine National Institute of Biomedical Imaging and BioengineeringNational Institutes of HealthBethesdaMD20892USA

Endo/lysosomal escape and gene release are two critical bottlenecks in gene ***,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RNA(siRNA)*** single laser triggers the“off-to-on”switching of MOFs nanocomplexes,inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ions,which cooperatively contribute to remarkable endo/lysosomal rupture(∼90%).The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer ***,the“off-to-on”switching also activates fluorescence recovery for real-time monitoring siRNA *** nanoswitch could easily be extended to deliver other therapeutic agents(e.g.,DNA,protein,anticancer drug)for overcoming endo/lysosomal entrapment.

关键词： metal-organic frameworks endo/lysosomal rupture and release photo-controllable nanoswitch RNA interference cancer therapy

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Construction of functional neural network tissue combining CBD-NT3-modified linear-ordered collagen scaffold and TrkC-modified iPSC-derived neural stem cells for spinal cord injury repair

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Bioactive Materials 2024年第5期35卷 242-258页

作者： Zhaoping Wu Yi Zhou Xianglin Hou Weidong Liu Wen Yin Lei Wang Yudong Cao Zhipeng Jiang Youwei Guo Quan Chen Wen Xie Ziqiang Wang Ning Shi Yujun Liu Xiang Gao Longlong Luo Jianwu Dai Caiping Ren Xingjun Jiang Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan Province410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan Province410008China State key laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing100080China School of Basic Medical Science Central South UniversityChangshaHunan Province410078China The NHC key laboratory of Carcinogenesis and the key laboratory of Carcinogenesis and cancer Invasion of the Chinese Ministry of Education Central South UniversityChangshaHunan Province410078China College of Biology Hunan UniversityChangsha410000China State key laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing100080China

Induced pluripotent stem cells(iPSCs)can be personalized and differentiated into neural stem cells(NSCs),thereby effectively providing a source of transplanted cells for spinal cord injury(SCI).To further improve the repair efficiency of SCI,we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold(LOCS).We confirmed that transplantation of this tissue regenerated neurons and synapses,improved the microenvironment of the injured area,enhanced remodeling of the extracellular matrix,and promoted functional recovery of the hind limbs in a rat SCI model with complete *** sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating ***,we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first *** tissue can effectively improve the therapeutic effect of SCI,thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

关键词： Spinal cord injury Induced pluripotent stem cells LOCS Neural network tissue Neurotrophin-3

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Combining systemic inflammatory response index and albumin fibrinogen ratio to predict early serious complications and prognosis after resectable gastric cancer

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World Journal of gastrointestinal Oncology 2024年第3期16卷 732-749页

作者： Jing-Yao Ren Da Wang Li-Hui Zhu Shuo Liu Miao Yu Hui Cai School of Clinical Medicine Ningxia Medical UniversityYinchuan 750000Ningxia Hui Autonomous RegionChina General surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina key laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina NHC key laboratory of Diagnosis and Therapy of gastrointestinal Tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Medical College of Jiangsu University Jiangsu UniversityZhenjiang 212013Jiangsu ProvinceChina The First Clinical Medical School Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of ***,patient survival rates are still low,and the incidence of major postoperative complications cannot be *** systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer *** systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical *** To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer *** We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December *** calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative *** scored the patients and categorized them into three groups based on their SIRI and AFR *** analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric *** tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with *** Preoperative SIRI and AFR values were s

关键词： Inflammation Albumin fibrinogen ratio Gastric cancer Complications Prognosis

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Single-cell individualized electroporation with real-time impedance monitoring using a microelectrode array chip

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Microsystems & Nanoengineering 2020年第1期6卷 295-304页

作者： Zhizhong Zhang Tianyang Zheng Rong Zhu State key laboratory of Precision Measurement Technology and Instruments Department of Precision InstrumentTsinghua UniversityBeijing 100084China

The ability to precisely deliver molecules into single cells while maintaining good cell viability is of great importance to applications in therapeutics,diagnostics,and drug delivery as it is an advancement toward the promise of personalized *** paper reports a single-cell individualized electroporation method with real-time impedance monitoring to improve cell perforation efficiency and cell viability using a microelectrode array *** microchip contains a plurality of sextupole-electrode units patterned in an array,which are used to perform in situ electroporation and real-time impedance monitoring on single *** dynamic recovery processes of single cells under electroporation are tracked in real time via impedance measurement,which provide detailed transient cell states and facilitate understanding the whole recovery process at the level of single *** define single-cell impedance indicators to characterize cell perforation efficiency and cell viability,which are used to optimize *** applying the proposed electroporation method to different cell lines,including human cancer cell lines and normal human cell lines individually,optimum stimuli are determined for these cells,by which high transfection levels of enhanced green fluorescent protein(EGFP)plasmid into cells are *** results validate the effectiveness of the proposed single-cell individualized electroporation/transfection method and demonstrate promising potential in applications of cell reprogramming,induced pluripotent stem cells,adoptive cell therapy,and intracellular drug delivery technology.

关键词： impedance microelectrode monitoring

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Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

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World Journal of gastrointestinal Oncology 2023年第7期15卷 1283-1294页

作者： Rui Tang Guo-Feng Chen Kai Jin Guang-Qiang Zhang Jian-Jun Wu Shu-Gao Han Bin Li Ming Chao Department of Radiology The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of gastrointestinal surgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of *** with digestive obstruction are generally in a more advanced *** methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these *** To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced *** This study was a retrospective ***-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of *** oxaliplatin-based intra-arterial infusion regimen was applied in all *** systemic chemotherapy was used in combination with local *** clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)*** tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was *** survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient *** All patients finished cGAIC successfully without microcatheter displacement,as confirmed by *** median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST *** postoperative Stooler’s Dysphagia Score was significantly ***(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically *** median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68

关键词： Intra-arterial infusion chemotherapy Intravenous chemotherapy Interventional radiology Digestive obstruction Advanced gastric cancer Response evaluation criteria in solid tumors

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enhanced recovery after surgery:Current research insights and future direction

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World Journal of gastrointestinal surgery 2017年第2期9卷 37-45页

作者： Aliza Abeles Richard Mark Kwasnicki Ara Darzi Department of surgery and cancer St Mary’s HospitalImperial College LondonLondon W2 1NYUnited Kingdom

Since the concept of enhanced recovery after surgery(ERAS)was introduced in the late 1990 s the idea of implementing specific interventions throughout the perioperative period to improve patient recovery has been proven to be beneficial. Minimally invasive surgery is an integral component to ERAS and has dramatically improved post-operative outcomes. ERAS can be applicable to all surgical specialties with the core generic principles used together with added specialty specific interventions to allow for a comprehensive protocol,leading to improved clinical outcomes. Diffusion of ERAS into mainstream practice has been hindered due to minimal evidence to support individual facets and lack of method for monitoring and encouraging compliance. No single outcome measure fully captures recovery after surgery,rather multiple measures are necessary at each stage. More recently the pre-operative period has been the target of a number of strategies to improve clinical outcomes,described as prehabilitation. Innovation of technology in the surgical setting is also providing opportunities to overcome the challenges within ERAS,e.g.,the use of wearable activity monitors to record information and provide feedback and motivation to patients peri-operatively. Both modernising ERAS and providing evidence for key strategies across specialties will ultimately lead to better,more reliable patient outcomes.

关键词： enhanced recovery after surgery Laparoscopic surgery Prehabilitation Outcome measures Technology

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Circular RNA circVAPA promotes chemotherapy drug resistance in gastric cancer progression by regulating miR-125b-5p/STAT3 axis

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World Journal of Gastroenterology 2021年第6期27卷 487-500页

作者： Peng Deng Ming Sun Wen-Yan Zhao Bin Hou Kai Li Tao Zhang Feng Gu Department of Surgical Oncology and General surgery Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsMinistry of EducationThe First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Department of Urology Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Department of General surgery Shengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Department of Stem Cells and Regenerative Medicine China Medical UniversityShenyang 110122Liaoning ProvinceChina Department of Ophthalmology The First Affiliated Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina

BACKGROUND Gastric cancer(GC)is a prevalent malignancy,leading to a high incidence of cancer-associated ***(DDP)-based chemotherapy is the principal therapy for clinical GC treatment,but DDP resistance is a severe clinical challenge and the mechanism remains poorly *** RNAs(circRNAs)have been identified to play crucial roles in modulating the chemoresistance of gastric cancer *** To explore the effect of circVAPA on chemotherapy resistance during GC *** The effect of circVAPA on GC progression and chemotherapy resistance was analyzed by MTT assay,colony formation assay,Transwell assay,wound healing assay,and flow cytometry analysis in GC cells and DDP resistant GC cell lines,and tumorigenicity analysis in nude mice in *** mechanism was investigated by luciferase reporter assay,quantitative real-time PCR,and Western blot *** CircVAPA expression was up-regulated in clinical GC tissues compared with normal *** depletion inhibited proliferation,migration,and invasion and increased apoptosis of GC *** expression of circVAPA,STAT3,and STAT3 downstream genes was elevated in DDP resistant SGC7901/DDP cell *** knockdown attenuated the DDP resistance of GC ***,circVAPA was able to sponge miR-125b-5p,and miR-125b-5p could target STAT3 in the GC ***-125b-5p inhibitor reversed circVAPA depletion-enhanced inhibitory effect of DDP on GC cells,and STAT3 knockdown blocked circVAPA overexpression-induced proliferation of DDPtreated SGC7901/DDP *** depletion of STAT3 and miR-125b-5p inhibitor reversed circVAPA depletion-induced GC cell ***,circVAPA contributed to the tumor growth of SGC7901/DDP cells in *** CircVAPA promotes chemotherapy resistance and malignant progression in GC by miR-125b-5p/STAT3 *** findings present novel insights into the mechanism by which circVAPA regulates chemotherapy resistance of GC ***

关键词： Gastric cancer Progression Chemoresistance CircVAPA miR-125b-5p STAT3

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Asymptomatic low-grade appendiceal mucinous neoplasm:A case report

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World Journal of Clinical Cases 2024年第2期12卷 361-366页

作者： Min-Quan Yao Yu-Peng Jiang Yuan-Yu Wang Yi-Ping Mou Jin-Xing Fan Department of gastrointestinal surgery Tongxiang First People’s HospitalJiaxing 314500Zhejiang ProvinceChina Department of General surgery Zhejiang Provincial People’s HospitalHangzhou 310014Zhejiang ProvinceChina Endoscopy Center Tongxiang First People’s HospitalJiaxing 314500Zhejiang ProvinceChina

BACKGROUND Low-grade appendiceal neoplasms(LAMN)are characterized by low incidence and atypical clinical presentations,often leading to misdiagnosis as acute or chronic appendicitis before *** primary diagnostic tool for LAMN is abdominal computed tomography(CT)*** resection remains the cornerstone of LAMN management,necessitating en bloc tumor excision to minimize the risk of iatrogenic ***,known for its minimal invasiveness,reduced postoperative discomfort,and expedited recovery,is a safe and reliable approach for LAMN *** the possibility of pseudomyxoma peritonei development,appendectomy and partial appendectomy generally result in negative tumor margins and favorable outcomes,which can be attributed to the disease’s slow growth and lower *** SUMMARY A 71-year-old male patient was admitted to our hospital with a pelvic spaceoccupying lesion detected 1 mo *** examination showed a soft abdomen without tenderness or rebound and no palpable *** shifting dullness was noted,and digital rectal examination revealed no palpable *** revealed a raised,smooth-surfaced mass measuring 3.0 cm in the *** contrast-enhanced CT showed a markedly thickened and dilated appendix with visible cystic *** surgery was performed and revealed a significantly dilated appendix,leading to laparoscopic resection of the appendix and part of the ***-surgical pathologic analysis confirmed *** patient received symptomatic and supportive post-operative care and was discharged on postoperative day 4 without complications such as abdominal bleeding,intestinal obstruction,or incision *** tumor recurrence was observed during a 7-mo follow-up *** LAMN is a rare disease that lacks specific clinical *** CT plays a crucial role in diagnosing LAMN,and laparoscopic surgery is a safe and effective diagnostic and therapeutic approach.

关键词： Low-grade appendiceal mucinous neoplasm Pseudomyxoma peritonei Computed tomography Laparoscopy appendectomy Case report

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Reg4 regulates 5-fluorouracil sensitivity in gastric cancer through MAPK/Erk/Bim signaling pathway

Reg4 regulates 5-fluorouracil sensitivity in gastric cancer ...

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浙江省免疫学会第十次学术大会

作者： Jiaoyue Jin Fanrong Zhang Kaiyan Chen Nan Zhang Junzhou Wu Lisha Ying Dan Su cancer Research Institute Zhejiang Cancer Hospital and Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province

Aim:Reg4 is a member of the Reg multigene family,and is highly up-regulated in many gastrointestinal *** cancer cells with high Reg4 expression is resistant to 5-fluorouracil(5-FU),but the mechanism is not very *** the present study,we aimed to comfirm the role of Reg4 in GC cells once again,and further investigate the mechanism by which Reg4 regulates the 5-FU response in GC ***:Protein expression of Reg4 in gastric cancer cells was analyzed by western *** on over-expression and siRNA knockdown of Reg4 were conducted for 5-FU sensitivity and apoptosis analyses.5-FU metabolism and intracellular signaling were examined by real time PCR and western ***:Western blot showed Reg4 expression was low or null in SGC-7901,BGC-823 gastric cancer cell lines,and high in AGS,MKN28,MKN45 gastric cancer cell *** overexpression and knockdown of Reg4 demonstrated that low Reg4 expression promoted the sensitivity to 5-FU,and 5-FU-induced *** were no significant influences on the mRNA levels of thymidylate synthase,orotate phosphoribosyltransferase and dihydropyrimidine *** investigation showed enhanced Reg4 expression activated the P42/P44 phosphorylation,and regulated 5-FU sensitivity through MAPK/Erk/Bim signaling ***:The results indicate that Reg4 may play an important role in5-FU-induced cell ***,upregulation of Reg4 in response to 5-FU may represent an intrinsic mechanism of resistance to this anticancer drug.

关键词： Reg4 5-fluorouracil apoptosis gastric cancer

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Methionine Deficiency Facilitates Antitumor Immunity by Altering m6A Methylation of Immune Checkpoint Transcripts

Methionine Deficiency Facilitates Antitumor Immunity by Alte...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： Ting Li Tan Yue-Tao Yan-Xing Chen Xiao-Jun Zheng Wen Wang Kun Liao Hai-Yu Mo Junzhong Lin Wei Yang Hai-Long Piao Rui-Hua Xu Huai-Qiang Ju Sun Yat-sen University cancer Center Department of Gastroenterology and Urology Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Research Department of Medical Sciences Guangdong Provincial People's HospitalGuangdong Academy of Medical Sciences CAS key laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of Sciences Department of Colorectal surgery Sun Yat-sen University Cancer Center Guangdong Provincial key laboratory of Molecular Oncologic Pathology Southern Medical University Research Unit of Precision Diagnosis and Treatment for gastrointestinal cancer Chinese Academy of Medical Sciences

Objective:Methionine metabolism is involved in a myriad of cellular functions,including methylation reactions and redox ***,it remains unclear whether methionine metabolism,RNA methylation and antitumor immunity are molecularly ***:The antitumor immunity effect of methionine-restricted diet(MRD) feeding was assessed in murine *** mechanisms of methionine and YTH domain-containing family protein 1(YTHDF1) in tumor immune escape were determined in vitro and in ***,the MRD or YTHDF1 depletion synergizes with PD-1 blockade used to block tumor ***:We found that dietary methionine restriction reduced tumor growth and enhanced antitumor immunity by increasing the number and cytotoxicity of tumor-infiltrating CD8+ T cells in different mouse ***,the S-adenosylmethionine derived from methionine metabolism promoted the N6-methyladenosine(m6A) methylation and translation of immune checkpoints,including PD-L1 and VISTA,in tumor ***,a methionine-restricted diet or m6A-specific binding protein YTHDF1 depletion inhibited tumor growth by restoring the infiltration of CD8+ T cells,and synergized with PD-1blockade for better tumor ***,YTHDF1 expression correlated with poor prognosis and immunotherapy outcomes for cancer ***:Methionine and YTHDF1 play a critical role in anticancer immunity through regulating the functions of T *** methionine metabolism or YTHDF1 could be a potential new strategy for cancer immunotherapy.

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