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Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion

International Journal of Ophthalmology(English edition) 2024年第10期17卷 1837-1842页

作者： Yuan-Yuan Zhong Chong Tang Lan-Yue Zhang Xue-Dong Zhang Shu-Lin Liu The First Affiliated Hospital of chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye DiseasesChongqing 400016China

AIM:To evaluate the efficacy,timing of retreatment and safety of dexamethasone(DEX)implant on macular edema(ME)secondary to diabetic retinopathy(DME)and retinal vein occlusion(RVO-ME)patients who were refractory to anti-vascular endothelial growth factor(VEGF)***:This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1,2019,and January 1,*** refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness(CRT).The best corrected visual acuity(BCVA)and CRT were measured at baseline,and at 1,3,4 and 6mo post-DEX implant *** events such as elevated intraocular pressure(IOP)and cataract were ***:For RVO cases(n=22),there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection(P<0.05)and CRT decreased from 472.1±90.6 to 240.5±39.0μm at 6mo(P<0.0001).DME cases(n=15)experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection(P=0.0098),with CRT reducing from 445.7±55.7 to 271.7±34.1μm at 6mo(P<0.0001).Elevated IOP occurred in 45.9%of patients but was well-controlled with topical *** cases of cataract or other adverse events were ***:DEX implants effectively improve BCVA and reduce CRT in refractory DME and *** research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

关键词： macular edema dexamethasone implant anti-vascular endothelial growth factor retinal vein occlusion diabetic retinopathy

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The role of proteasomes in tumorigenesis

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Genes & Diseases 2024年第4期11卷 155-169页

作者： Xiangyi Zhou Ruqing Xu Yue Wu Li Zhou Tingxiu Xiang Department of Oncology The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing 400030China

Protein homeostasis is the basis of normal life activities,and the proteasomefamily plays an extremely important function in this *** proteasome 2os is a concentric circle structure with twoαrings and twoβrings *** proteasome 2os can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits(such as 19S,11S,and 200 PA),which is performed by its active subunitβ1,β2,andβ*** proteasome can degrade misfolded,excess proteins tomaintain *** the same time,it can be utilized by tumors to degrade over-proliferate and unwanted proteins to support their *** can affect the development of tumors from several aspects including tumor signaling pathways such as NF-kB and p53,cell cycle,immune regulation,and drug ***-encoding genes have been found to be overexpressed in a variety of tumors,providing a potential novel target for cancer *** addition,proteasome inhibitors such as bortezomib,carfilzomib,and ixazomib have been put into clinical application as the first-line treatment of multiple *** and more studies have shown that it also has different therapeutic effects in other tumors such as hepatocellular carcinoma,non-small cell lung cancer,glioblastoma,and ***,proteasome inhibitors are not much effective due to their tolerance and singleness in other ***,further studies on their mechanisms of action and drug interactions are needed to investigate their therapeutic potential.

关键词： Bortezomib Cancer therapy Immunoproteasome Multiplemyeloma Proteasome 20S Proteasome inhibitor Thymoproteasom

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Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

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Research 2024年第3期7卷 775-790页

作者： Li Chen Jianye Yang Zhengwei Cai Yanran Huang Pengcheng Xiao Hong Chen Xiaoji Luo Wei Huang Wenguo Cui Ning Hu Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityOrthopedic Laboratory of Chongqing Medical UniversityChongqing 400016China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai 200025China.

Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.

关键词： spheres remove thereby

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PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α

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Genes & Diseases 2024年第4期11卷 353-367页

作者： Yu Wei Dian Zhang He Shi Husun Qian Hongling Chen Qian Zeng Fangfang Jin Yan Ye Zuli Ou Minkang Guo Bianqin Guo Tingmei Chen Key Laboratory of Clinical Laboratory Diagnostics(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing 400030China

Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its *** pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor *** study aims to elucidate how PDK1 pro-motes breast cancer *** found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)*** investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase ***,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer *** phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase *** also found that PDK1 enhanced HIF-1αtranscriptional *** summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto ***1 and HIF-1αform a positive feedback loop to promote breast cancer progression.

关键词： Breast cancer HIF-1α PDK1 Protein phosphorylation Transcriptional activity

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Laparoscopic vs open surgery for gastric cancer: Assessing time, recovery, complications, and markers

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 40-48页

作者： Yun-Yao Lu Yun-Xiao Li Meng He Ya-Li Wang chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing 400030China

BACKGROUND Gastric cancer(GC)is one of the most common cancers *** and mortality have increased in recent years,making it an urgent issue to ***-paroscopic radical surgery(LRS)is a crucial method for treating patients with GC;However,its influence on tumor markers is still under *** data of 194 patients treated at chongqing University Cancer Hospital bet-ween January 2018 and January 2019 were retrospectively *** who underwent traditional open surgery and LRS were assigned to the control(n=90)and observation groups(n=104),*** sample t-tests andχ2 tests were used to compare the two groups based on clinical efficacy,changes in tumor marker levels after treatment,clinical data,and the incidence of posto-perative *** investigate the association between tumor marker levels and clinical efficacy in patients with GC,three-year recurrence rates in the two groups were *** Patients in the observation group had a shorter duration of operation,less in-traoperative blood loss,an earlier postoperative eating time,and a shorter hospital stay than those in the control group(P0.05).After treatment,the overall response rate in the control group was significantly lower than that in the observation group(P=0.001).Furthermore,after treatment,the levels of carbohydrate antigen 19-9,cancer antigen 72-4,carcinoembryonic antigen,and cancer antigen 125 decreased *** observation group also exhibited a significantly lower incidence rate of postoperative complications compared to the control group(P0.05).CONCLUSION LRS effectively treats early gastric cancer by reducing intraoperative bleeding,length of hospital stays,and postoperative complications.I

关键词： Laparoscopic radical surgery Gastric cancer Serum tumor markers Prognosis Recurrence Intraoperative bleeding

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The two sides of chromosomal instability:drivers and brakes in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1595-1624页

作者： Rendy Hosea Sharon Hillary Sumera Naqvi Shourong Wu Vivi Kasim Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400045China The 111 Project Laboratory of Biomechanics and Tissue Repair College of BioengineeringChongqing UniversityChongqing 400044China chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing UniversityChongqing 400030China

Chromosomal instability(CIN)is a hallmark of cancer and is associated with tumor cell *** triggers a chain reaction in cells leading to chromosomal abnormalities,including deviations from the normal chromosome number or structural changes in *** arises from errors in DNA replication and chromosome segregation during cell division,leading to the formation of cells with abnormal number and/or structure of *** in DNA replication result from abnormal replication licensing as well as replication stress,such as double-strand breaks and stalled replication forks;meanwhile,errors in chromosome segregation stem from defects in chromosome segregation machinery,including centrosome amplification,erroneous microtubule-kinetochore attachments,spindle assembly checkpoint,or defective sister chromatids *** normal cells,CiN is deleterious and is associated with DNA damage,proteotoxic stress,metabolic alteration,cell cycle arrest,and ***,despite these negative consequences,CiN is one of the hallmarks of cancer found in over 90%of solid tumors and in blood ***,CiN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity,thereby facilitating adaptive resistance to therapies;however,excessive CiN could induce tumor cells death,leading to the"just-right"model for CIN in *** the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor *** review provides an overview of causes and consequences of CIN,as well as the paradox of CIN,a phenomenon that continues to perplex ***,this review explores the potential of CIN-based anti-tumor therapy.

关键词： chromosomal consequences thereby

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Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 798-809页

作者： Dong-Qin Xia Yong Zhou Shuang Yang Fang-Fei Li Li-Ya Tian Yan-Hua Li Hai-Yan Xu Cai-Zhi Xiao Wei Wang Oncology treatment Center of Traditional Chinese Medicine Chongqing University Cancer HospitalChongqing 400030China Department of Oncology Chongqing Weisiteng Biotech Translational Research InstituteChongqing 430039China chongqing Key Laboratory on Big Data for Bio Intelligence Chongqing University of Posts and TelecommunicationsChongqing 430065China

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social *** To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized treatment,chongqing University Cancer *** study specifically assessed CA19-9 levels and tumor size before and after *** A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this *** average age was 65.4±10.6 years and 72(46.2%)patients were *** survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR0.5 and*** regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR0.5 and*** on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)***-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic ***,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with *** This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

关键词： Pancreatic ductal adenocarcinoma Carbohydrate antigen 19-9 Tumor size Pathologic response Biomarkers

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Antimicrobial Resistance Analysis and Whole-Genome Sequencing of Salmonella Isolates from Environmental Sewage — Guangzhou City, Guangdong Province, China, 2022–2023

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China CDC weekly 2024年第13期6卷 254-260页

作者： Bihui Su Guanghong Du Shuiping Hou Zongqiu Chen Xiaoying Wu Gang He Jun Yuan Chaojun Xie tuberculosis Management and treatment Department Guangzhou Chest HospitalGuangzhou CityGuangdong ProvinceChina School of Public Health Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Guangzhou Center for Disease Control and prevention Guangzhou CityGuangdong ProvinceChina Office of the Director Huadu District Center for Disease Control and PreventionGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?S.1,4,[5],12:i:-and *** are emerging serotypes of Salmonella that require close monitoring for antimicrobial resistance and containment of their *** is added by this report?The study aimed to identify antimicrobial resistance genes(ARGs)in S.1,4,[5],12:i:-and *** strains isolated from environmental sewage in Guangzhou City,Guangdong Province,China.A phylogenetic tree was constructed using single nucleotide polymorphism data to assess genetic relatedness among strains,offering insights for Salmonella infection outbreak investigations in the *** are the implications for public health practice?It is crucial to implement strategies,such as integrating different networks,to control the spread of drugresistant *** technologies must be utilized to disinfect sewage and eliminate *** food safety and proper sewage disinfection are essential to curb the dissemination of Salmonella.

关键词： Whole offering integrating

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Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

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Zoological Research 2024年第1期45卷 95-107页

作者： Hai-Yang Wang Lan-Xiang Liu Xue-Yi Chen Yang-Dong Zhang Wen-Xia Li Wen-Wen Li Lian Wang Xiao-Long Mo Hong Wei Ping Ji Peng Xie NHC Key Laboratory of Diagnosis and treatment on Brain Functional Diseases First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China College of Stomatology and Affiliated Stomatological Hospital of chongqing Medical University Chongqing 401147China chongqing Key Laboratory for Oral Diseases and Biomedical Sciences Chongqing 401147China Department of Neurology Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China Department of Pathology Faculty of Basic MedicineChongqing Medical UniversityChongqing 400016China Department of Neurology First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Yu-Yue Pathology Scientific Research Center Chongqing 401329China

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many ***,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain *** study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any *** conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF *** results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of *** bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF *** constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular *** correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational *** correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular *** study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

关键词： Gut microbiota Hippocampal protein Post-translational modifications Succinylation Acetylation Phosphorylation

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How can we establish animal models of HIV-associated lymphoma?

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Animal Models and Experimental Medicine 2024年第4期7卷 484-496页

作者： Qing Xiao Liuyue Zhai Xiaomei Zhang Yi Liu Jun Li Xiaoqing Xie Guofa Xu Sanxiu He Huihui Fu Yifeng Tang Fujie Zhang Yao Liu chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized treatment Department of Hematology-OncologyChongqing University Cancer HospitalChongqingChina Beijing Ditan Hospital Capital Medical UniversityBeijingChina

Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of *** mirror the natural course of human HIV infection,animal models have been *** models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication ***,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing *** re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

关键词： animal model HIV-associated lymphoma(HAL) human immunodeficiency virus(HIV) immunodeficient mice primate model

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