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NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

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Current Medical Science 2024年第1期44卷 168-179页

作者： Wei XUE Ting WANG Wen-jing TIAN Si-qi pang hua-feng ZHANG Wei-dong JIA Department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

Current status of Mycoplasma pneumoniae infection in China

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World Journal of Pediatrics 2024年第1期20卷 1-4页

作者： Chao Yan Guan-hua Xue Han-Qing Zhao Yan-Ling Feng jing-hua Cui jing Yuan Department of Bacteriology Capital Institute of PediatricsNo.2Yabao RoadBeijing 100020People's Republicof China

Mycoplasma pneumoniae(M.pneumoniae)is one of the most important pathogens for community-acquired pneumonia worldwide,especially in children and adolescents[1,2].M.pneumoniae is easily transmitted through droplets or direct contact in densely populated,enclosed,or poorly ventilated environments.The incubation period is 1-3 weeks,and it is contagious from the incubation period to a few weeks after clinical symptom relief.M.pneumoniae infection can occur in any season,and there are differences in the epidemic seasons among regions in China[3].The most suitable culture temperature for M.pneumoniae is between 35℃C and 37 C,and therefore,hot weather may make it survive longer in the environment and spread further.Infection is more common in autumn and winter in northern China,while it is more prevalent in summer and autumn in southern China.

关键词： winter weather autumn

Clinical observation of gastrointestinal function recovery in patients after hepatobiliary surgery

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 76-84页

作者： hua-Jun Zeng jing-jing Liu Ying-Chun Yang Department of General Practice Nanyang First People's HospitalNanyang 473000Henan ProvinceChina Department of Anesthesiology Chinese People’s Armed Police Force Hospital of BeijingBeijing 100027China Department of Anesthesiology Beijing Fengtai HospitalBeijing 100071China

BACKGROUND The liver is an important metabolic and digestive organ in the human body,ca-pable of producing bile,clotting factors,and vitamins.AIM To investigate the recovery of gastrointestinal function in patients after hepato-biliary surgery and identify effective rehabilitation measures.METHODS A total of 200 patients who underwent hepatobiliary surgery in our hospital in 2022 were selected as the study subjects.They were divided into a control group and a study group based on the extent of the surgery,with 100 patients in each group.The control group received routine treatment,while the study group re-ceived targeted interventions,including early enteral nutrition support,drinking water before gas discharge,and large bowel enema,to promote postoperative gastrointestinal function recovery.The recovery of gastrointestinal function was compared between the two groups.RESULTS Compared with the control group,patients in the study group had better recovery of bowel sounds and less accumulation of fluids in the liver bed and gallbladder fossa(P<0.05).They also had shorter time to gas discharge and first meal(P<0.05),higher overall effective rate of gastrointestinal function recovery(P<0.05),and lower incidence of postoperative complications(P<0.05).CONCLUSION Targeted nursing interventions(early nutritional support,drinking water before gas discharge,and enema)can effectively promote gastrointestinal function recovery in patients undergoing hepatobiliary surgery and reduce the incidence of complications,which is worthy of promotion.

关键词： Liver and gallbladder patients Gastrointestinal function Postoperative recovery

Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction

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Journal of Geriatric Cardiology 2024年第4期21卷 421-430页

作者： jing TAN Jin SI Ke-Ling XIAO Ying-hua ZHANG Qi hua jing LI Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Department of Geriatric Medicine Xuanwu Hospital Capital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijingChina

BACKGROUND Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI) are available.METHODS We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months(interquartile range: 26–73 months) follow-up period were compared between patients with the low prealbumin level(< 170 mg/L) and those with the high prealbumin level(≥ 170 mg/L).RESULTS A total of 114 patients(4.9%) died during hospitalization. After propensity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class Ⅲ(9.9%vs. 4.4%, P = 0.034), cardiovascular death(8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events(19.2%vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level(< 170 mg/L) was an independent predictor of in-hospital major adverse cardiovascular events(odds ratio = 1.918, 95% CI: 1.250–2.942, P = 0.003). The cutoff value of prealbumin level for predicting in-hospital death was 170 mg/L(area under the curve = 0.703, 95% CI: 0.651–0.754, P< 0.001;sensitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level(170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results.CONCLUSIONS Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardio

关键词： patients admitted infarction

PDOL-Based Solid Electrolyte Toward Practical Application:Opportunities and Challenges

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Nano-Micro Letters 2024年第7期16卷 109-141页

作者： hua Yang Maoxiang jing Li Wang Hong Xu Xiaohong Yan Xiangming He Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiang 212013People’s Republic of China Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing 100084People’s Republic of China

Polymer solid-state lithium batteries(SSLB)are regarded as a promising energy storage technology to meet growing demand due to their high energy density and safety.Ion conductivity,interface stability and battery assembly process are still the main challenges to hurdle the commercialization of SSLB.As the main component of SSLB,poly(1,3-dioxolane)(PDOL)-based solid polymer electrolytes polymerized in-situ are becoming a promising candidate solid elec-trolyte,for their high ion conductivity at room temperature,good battery elec-trochemical performances,and simple assembly process.This review analyzes opportunities and challenges of PDOL electrolytes toward practical application for polymer SSLB.The focuses include exploring the polymerization mechanism of DOL,the performance of PDOL composite electrolytes,and the application of PDOL.Furthermore,we provide a perspective on future research directions that need to be emphasized for commercialization of PDOL-based electrolytes in SSLB.The exploration of these schemes facilitates a comprehensive and profound understanding of PDOL-based polymer electrolyte and provides new research ideas to boost them toward practical application in solid-state batteries.

关键词： Poly(1,3-dioxolane) Solid electrolyte Polymerization mechanism Composite electrolyte Practical application

Atomic force microscopy-based nanoscale infrared techniques for liquid environments

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Science Bulletin 2024年第2期69卷 151-153页

作者： Jian Li jing Liang Mu-Hao Lan Xing-hua Xia State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Infrared(IR)light energy matches well with the vibration and rotation of chemical bonds in molecules,hence IR spectroscopy is commonly used for accurate molecular identification[1].Conventional IR analysis involves bulk samples,providing averaged information of the entire sample.The spatially-resolved investigation of heterogeneous sample properties is constrained by the micrometer-level spatial resolution of optical IR microscopy.

关键词： spatially hence rotation

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Effectivity and safety of trifocal intraocular lenses and capsular tension rings implantation for cataract patients with axial high myopia

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 499-508页

作者： Shan hua Qiu-Xia Xie Hu Wang jing-Xiang Zhong Dongguan Aier Eye Hospital Jinan UniversityDongguan 523106Guangdong ProvinceChina Department of Ophthalmology the First Affiliated Hospital of Jinan UniversityGuangzhou 510630Guangdong ProvinceChina Department of Ophthalmology the Sixth Affiliated Hospital of Jinan UniversityDongguan 523576Guangdong ProvinceChina

●AIM:To assess effectivity and safety of trifocal intraocular lenses(IOLs)and capsular tension rings in treating cataract patients with axial high myopia.●METHODS:A prospective nonrandomized controlled clinical trial was conducted.Totally 98 eyes(74 patients)who underwent femtosecond laser-assisted cataract surgery(FLACS)with trifocal IOLs were enrolled in the study and followed up for 2y after surgery:46 eyes(33 patients)with capsular tension ring implantation in the long axial lengths(AL)group(260.05).The dysfunctional lens index and total modulation transfer function(MTF)average height were similar between the two groups.The postoperative internal coma aberrations in the axial high myopia eyes were significantly higher than that in the normal AL group(P<0.05).The total satisfaction score in the long AL group(91.32±2.76)was slightly higher than that in the normal AL group(90.36±3.47),but there was no difference(P=0.136).A statistically negative correlation was found between corrected distance visual acuity(CDVA)and dysfunctional lens index(r=-0.382,P=0.009),and between CDVA and the total MTF average height(r=-0.374,P=0.01).But there was no significant correlation between CDVA and total satisfaction score(r=0.059,P=0.696).Postoperative complications mainly presented as posterior capsular opacity(PCO),retinal detachment and cystoid macular edema.There was no difference in the incidence of fundus disease(6.5%vs 3.8%,P=0.663)or PCO(1

关键词： trifocal intraocular lenses capsular tension ring axial high myopia cataract visual quality

Intestinal microecological transplantation for a patient with chronic radiation enteritis:A case report

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World Journal of Gastroenterology 2024年第19期30卷 2603-2611页

作者： Lin Wang Yan Li Yu-jing Zhang Li-hua Peng Department of Gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Gastroenterology and Hepatology Chinese PLA Medical SchoolBeijing 100853China

BACKGROUND The gut microbiota is strongly associated with radiation-induced gut damage.This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.CASE SUMMARY A 64-year-old female with cervical cancer developed abdominal pain,diarrhea,and blood in the stool 1 year after radiotherapy.An electronic colonoscopy was performed to diagnose chronic radiation enteritis.Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed.The patient experienced short-and long-term relief from symptoms without adverse effects.Whole 16S rRNA sequencing revealed significant differences in the intestinal flora’s composition between patient and healthy donors.Pathogenic bacteria,such as Escherichia fergusonii and Romboutsia timonensis,were more in the patient.Beneficial bacteria such as Faecalibacterium prausnitzii,Fusicatenibacter saccharivorans,Ruminococcus bromii,and Bifidobacterium longum were more in the healthy donors.Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition.The composition converged with the donor's flora,with an increase in core beneficial intestinal bacteria,such as Eubacterium rectale,and a decrease in pathogenic bacteria.Changes in the intestinal flora corresponded with the patients'alleviating clinical symptoms.CONCLUSION Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora.This study provides a new approach for treating patients with chronic radiation enteritis.

关键词： Chronic radiation enteritis Gut microbial transplantation Intestinal microecology Cancer Quality of life Case report