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Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

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Oncology Research 2024年第2期32卷 325-337页

作者： JIE ZHAO XUANTAO YANG HAIXI ZHANG XUEZHONG GU department of Hematology The First People’s Hospital of Yunnan ProvinceYunnan Province Clinical Research Center for Hematologic DiseaseYunnan Province Clinical Center for Hematologic DiseaseKunming650032China department of Pathology The First People’s Hospital of Yunnan ProvinceKunming650032China

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence *** is a new-generation proteasome inhibitor that is used as the first-line therapy for ***,the development of drug resistance is a pervasive obstacle to treating ***,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic *** elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM *** gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion *** upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion ***,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion ***,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor ***,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion *** suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor *** studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

关键词： Multiple myeloma Carfilzomib Drug resistance Major histocompatibility complex TNFRSF1A

Do changes in intracoronary pressure aid coronary spasm diagnosis using the spasm provocation test?

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World Journal of Cardiology 2024年第1期16卷 16-26页

作者： Hiroki Teragawa Chikage Oshita Yuko Uchimura department of cardiovascular Medicine JR Hiroshima HospitalHiroshima 732-0057Japan

BACKGROUND Although the spasm provocation test(SPT)can diagnose coronary spasms,it would be helpful if it could also predict their *** To investigate whether coronary spasms can be predicted using changes in intracoronary artery pressure measured using a pressure wire during the *** Seventy patients underwent SPTs with pressure-wire measurement of intracoronary artery *** each SPT,the pressure wire was advanced into the distal portion of the right coronary artery(RCA)and left anterior descending coronary artery,and the ratio of intracoronary pressure to aortic pressure(Pd/Pa)was *** spasm was defined as an arterial narrowing of>90%in response to the administration of acetylcholine(ACh),with chest symptoms and/or ischemic electrocardiographic *** was administered to the RCA at low,moderate,or high doses of 20,50,or 80μg,respectively,and to the left coronary artery(LCA)at low,moderate,or high doses of 50,100,or 200μg,*** arteries with coronary spasms at low doses of ACh were defined as group L,and those with coronary spasms at moderate or high doses were defined as group *** who did not occur coronary spasms at any ACh dose were designated as group *** Among the 132 coronary arteries assessed using a pressure wire,there were 49 in group N,25 in group L,and 58 in group *** Pd/Pa was the lowest in group L(P=0.001).The decrease in the Pd/Pa between baseline to low doses of ACh was lower in group MH than in group N(P<0.001).A receiver-operating characteristics analysis showed that the cutoff baseline Pd/Pa value for predicting group L was 0.95,with a sensitivity of 0.600(15/25)and a specificity of 0.713(76/107)and that the cutoff value of Pd/Pa from baseline to low doses of ACh for predicting group MH was−0.04,with a sensitivity of 0.741(43/58)and a specificity of 0.694(34/49).CONCLUSION These findings suggest that indices of intracoronary pressure during SPT may be useful means for

关键词： Acetylcholine Coronary spasm Intracoronary pressure Pressure wire Spasm provocation test Vasospastic angina

Surgical Repair of Ventricular Septal Defect in Neonates: Indications and Outcomes

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Congenital Heart disease 2024年第1期19卷 69-83页

作者： Jae Hong Lee Sungkyu Cho Jae Gun Kwak Hye Won Kwon Woong-Han Kim Mi Kyoung Song Sang-Yun Lee Gi Beom Kim Eun Jung Bae department of Thoracic and cardiovascular Surgery Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsanKorea department of Thoracic and cardiovascular Surgery Seoul National University Children’s HospitalSeoulKorea department of Pediatrics Seoul National University Children’s HospitalSeoulKorea

Background:The optimal surgical timing and clinical outcomes of ventricular septal defect(VSD)closure in neo-nates remain *** aimed to evaluate the clinical outcomes of VSD closure in neonates(age≤30 days).Methods:We retrospectively reviewed 50 consecutive neonates who underwent VSD closure for isolated VSDs between August 2003 and June *** for the procedure included congestive heart failure/failure to thrive and pulmonary *** adverse events(MAEs)were deﬁned as the composite of all-cause mortality,reoperation,persistent atrioventricular block,and signiﬁcant(≥grade 2)valvular ***:The median age and body weight at operation were 26.0 days(interquartile range[IQR],18.8–28.3)and 3.7 kg(IQR,3.3–4.2),*** median follow-up duration was 110.4 months(IQR,56.8–165.0).Seven patients required preoperative respiratory support,andﬁve had signiﬁcant(≥grade 2)preoperative valvular *** early mortality occurred due to irreversible cardiogenic shock;no late mortality was *** reopera-tion was due to hemodynamically signiﬁcant residual VSD at 103.8 months *** overall survival,freedom from reoperation,and freedom from MAE at 15-years were 98.0%,96.3%,and 94.4%,***-operative mechanical ventilation was associated with a longer duration of postoperative mechanical ventilation(p<0.001)and a longer length of intensive care unit stay(p<0.001).Conclusions:VSD closure with favorable outcomes without morbidities is feasible even in ***,neonates requiring preoperative respiratory support may require careful postoperative management considering the long-term postoperative ***,surgical VSD closure might be indicated earlier in neonates with respiratory compromise.

关键词： Ventricular septal defect neonate early surgery neonatal surgery

Direct reprogramming of fibroblasts into functional hepatocytes via CRISPRa activation of endogenous Gata4 and Foxa3

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Chinese Medical Journal 2024年第11期137卷 1351-1359页

作者： Jiacheng Li Ruopu Li Xue Bai Wenlong Zhang Yu Nie Shengshou Hu State Key Laboratory of cardiovascular disease Fuwai Hospital and Cardiovascular InstituteNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China department of Obstetrics and Gynecology Beijing Advanced Innovation Center for GenomicsThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China

Background:The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease *** regularly interspaced short palindromic repeats(CRISPR)activator(CRISPRa)is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously,providing a new strategy for cell fate *** main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver ***:The differentiation of mouse embryonic fibroblasts(MEFs)into functional induced hepatocyte-like cells(iHeps)was achieved by utilizing the CRISPRa synergistic activation mediator(SAM)system,which drove the combined expression of three endogenous transcription factors-Gata4,Foxa3,and Hnf1a-or alternatively,the expression of two transcription factors,Gata4 and *** vivo,we injected adeno-associated virus serotype 6(AAV6)carrying the CRISPRa SAM system into liver fibrotic Col1a1-Cre^(ER);Cas9^(fl/fl)mice,effectively activating the expression of endogenous Gata4 and Foxa3 in *** endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction(RT-qPCR)and RNA-seq,and the morphology and characteristics of the induced hepatocytes were observed through *** level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining,while the improvement of liver fibrosis is evaluated through Sirius red staining,alpha-smooth muscle actin(α-SMA)immunofluorescence staining,and blood alanine aminotransferase(ALT)***:Activation of only two factors,Gata4 and Foxa3,via CRISPRa was sufficient to successfully induce the transformation of MEFs into *** iHeps could be expanded in vitro and displayed functional characteristics similar to th

关键词： Liver fibrosis CRISPRa Cell reprogramming Transcriptional activation Hepatocytes

Assessment of post-myocardial infarction lipid levels and management:Results from a tertiary care hospital of Pakistan

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World Journal of Cardiology 2024年第5期16卷 282-292页

作者： Rubina Rauf Muhammad Ismail Soomro Muhamman Nauman Khan Mukesh Kumar Najia Aslam Soomro Khawar Abbas Kazmi department of Preventive Cardiology National Institute of Cardiovascular DiseasesKarachi 75510Pakistan department of Adult Cardiology National Institute of Cardiovascular DiseasesKarachi 75510Pakistan department of Cardiology Liaquat National HospitalKarachi 74800Pakistan

BACKGROUND Lipid treatment practices and levels in post-acute myocardial infarction(AMI)patients,which are crucial for secondary *** To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction(MI)patients at a tertiary care hospital in *** In this cross-sectional study,we analyzed patients who had experienced their first AMI event in the past 3 *** assessed fasting and non-fasting lipid profiles,reviewed statin therapy prescriptions,and examined patient *** recommended dose was defined as rosuvastatin≥20 mg or atorvastatin≥40 mg,with target total cholesterol levels set at<160 mg/dL and target low-density lipoprotein cholesterol(LDL-C)at<55 mg/*** Among 195 patients,71.3%were male,and the mean age was 57.1±10.2 *** median duration since AMI was 36(interquartile range:10-48)months and 60% were diagnosed with ST-segment elevation *** 13.8% of patients were advised to undergo lipid profile testing after AMI,88.7% of patients were on the recommended statin therapy,and 91.8% of patients were compliant with statin *** 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target *** admission in the past 12 months was reported by 14.4%,and the readmission rate was significantly higher among non-compliant patients(37.5%vs 5.6%).Subsequent AMI event rate was also significantly higher among non-compliant patients(43.8%vs 11.7%).CONCLUSION Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose,the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.

关键词： Lipid profile Dyslipidemia Acute myocardial infarction Secondary prevention Lipid lowering therapy

Evaluation of Latent Tuberculosis Infection Using the ESAT6-CFP10 Skin Test Among International Freshmen With Diverse Skin Tones at a University—Nanjing City,Jiangsu Province,China,September 2023

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China CDC weekly 2024年第35期6卷 896-900,I0001页

作者： Peng Lu Rong Wang Jingjing Xu Jianming Wang Fangfang Du Guozhi Wang Shiming Cheng Limei Zhu department of Chronic Communicable disease Jiangsu Provincial Center for Disease Control and PreventionNanjing CityJiangsu ProvinceChina department of Epidemiology School of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina Nanjing City Center for disease Control and Prevention Nanjing CityJiangsu ProvinceChina Chinese Antituberculosis Association BeijingChina National Institutes for Food and Drug Control BeijingChina

Introduction:Newer skin tests,including the ESAT6-CFP10(EC)skin test,were recommended for diagnosing Mycobacterium tuberculosis(***)***,no data exist assessing the diagnostic performance of the EC skin test among foreign students with different skin ***:A cohort study at Nanjing Medical University screened incoming foreign *** EC skin test was used to assess for *** infection,and results were read at 24,48,72,and 96-hours ***:Among 96 participants,*** infection rates at 24,48,72,and 96-hours post-injection were 3.13%,7.29%,13.54%,and 9.38%,*** infection rates were lower among individuals with darker skin tones,the difference was not statistically significant(P=0.186),and variations were consistent across different measurement *** analysis revealed 5.3%in the continuousincreasing group,86.5%in the low-stable group,and 5.2%in the elevated-decreasing ***,participants in the elevated-decreasing group had lighter skin tones,with trajectory patterns consistent across different skin ***:The EC skin test is safe,and redness diameter is a more reliable indicator than *** should be collected within 48 to 72 hours,with verification at 72 hours crucial if initial results are ***,skin color does not affect EC skin test outcomes.

关键词： CFP10 Skin Nanjing

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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World Journal of Emergency Medicine 2024年第4期15卷 263-272页

作者： Yuhan Sun Baoqing Sun Zhigang Ren Mingshan Xue Changju Zhu Qi Liu Translational Medicine Center Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China State Key Laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Infectious disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Medical Key Laboratory of Emergency and Trauma Research Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality *** aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and ***:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April *** were allocated to the DM or non-DM group and paired with propensity score *** characteristics and clinical outcomes up to 90 days were *** primary outcome was the 10-day *** operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical ***:Among 152 enrolled patients,60 pairs were successfully *** was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml *** 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of *** cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,*** Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with ***:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

关键词： Community-acquired pneumonia Diabetes mellitus Heparin-binding protein Propensity score match

Identifying coronary artery bypass grafting patients at high risk for adverse long-term prognosis using serial health-related quality of life assessments

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Chinese Medical Journal 2024年第9期137卷 1069-1077页

作者： Juncheng Wang Hanning Liu Chao Yue Limeng Yang Kai Yang Yan Zhao Huan Ren Ying Zhang Zhe Zheng National Clinical Research Center for cardiovascular diseases State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China department of cardiovascular Surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China department of Vascular Surgery Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China department of Cardiac Surgery Wuhan Asia Heart HospitalWuhanHubei 430022China

Background:Patients who undergo coronary artery bypass grafting(CABG)are known to be at a significant risk of experiencing long-term adverse events,emphasizing the importance of regular *** health-related quality of life(HRQoL)serves as a direct method to gauge *** objective is to ascertain the prognostic significance of consecutive HRQoL assessments using the Physical Component Summary(PCS)and Mental Component Summary(MCS)derived from the Short-Form 36(SF-36)health survey in CABG ***:The study population consisted of 433 patients who underwent isolated elective CABG at Fuwai Hospital between 2012 and ***-36 assessments were conducted during both the hospitalization period and *** primary endpoint of the study was all-cause mortality,while the secondary outcome was a composite measure including death,myocardial infarction,stroke,and repeat *** assessed the relationships between the PCS and MCS at baseline,as well as their changes during the first 6 months after the surgery(referred to asΔPCS andΔMCS,respectively),and the observed ***:The patients were followed for an average of 6.28 years,during which 35 individuals(35/433,8.1%)*** adjusting for clinical variables,it was observed that baseline MCS scores(hazard ratio[HR]for a 1-standard deviation[SD]decrease,1.57;95%confidence interval[CI],1.07-2.30)andΔMCS(HR for a 1-SD decrease,1.67;95%CI,1.09-2.56)were associated with all-cause ***,baseline PCS scores andΔPCS did not exhibit a significant relationship with all-cause ***,there was a dose-response relationship observed betweenΔMCS and the likelihood of all-cause mortality(HRs for the 2nd,3rd and 4th quartiles compared to the 1st quartile,0.33,0.45 and 0.11,respectively).Conclusions:Baseline MCS and changes in MCS were independent predictors for long-term mortality of *** mental health status and recovery indicated better prognosis.

关键词： Coronary artery bypass grafting Coronary artery disease Prognosis Quality of life Short-Form 36 Risk factor Serial measurements

A nanoplatform with oxygen self-supplying and heat-sensitizing capabilities enhances the efficacy of photodynamic therapy in eradicating multidrug-resistant biofilms

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Journal of Materials Science & Technology 2024年第2期169卷 209-219页

作者： Haixin Zhang Yi Zou Kunyan Lu Yan Wu Yuancheng Lin Jingjing Cheng Chunxia Liu Hong Chen Yanxia Zhang Qian Yu State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China department of cardiovascular Surgery of the First Affiliated Hospital and Institute for cardiovascular Science Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215007China

Bacterial biofilms,especially those caused by multidrug-resistant bacteria,have emerged as one of the greatest dangers to global public *** acceleration of antimicrobial resistance to conventional an-tibiotics and the severe lack of new drugs necessitates the development of novel agents for biofilm *** therapy(PDT)is a promising non-antibiotic method for treating bacterial ***,its application in biofilm eradication is hampered by the hypoxic microenvironment of biofilms and the physical protection of extracellular polymeric *** this study,we develop a composite nanoplatform with oxygen(O_(2))self-supplying and heat-sensitizing capabilities to improve the PDT efficacy against ***_(2)/ICG@PDA nanoparticles(CIP NPs)are fabricated by combining calcium peroxide(CaO_(2))with the photosensitizer indocyanine green(ICG)via electrostatic interactions,followed by coating with polydopamine(PDA).The CIP NPs can gradually generate O_(2)in response to the acidic microenvironment of the biofilm,thereby alleviating its hypoxic *** near-infrared(NIR)irradiation,the nanoplatform converts O_(2)into a significant amount of singlet oxygen(^(1)O_(2))and heat to eradicate *** generated heat enhances the release of O_(2),accelerates the generation of^(1)O_(2)in PDT,increases cell membrane permeability,and increases bacterial sensitivity to^(1)O_(2).This nanoplatform significantly improves the efficacy of PDT in eradicating biofilm-dwelling bacteria without fostering drug *** on biofilm eradication demonstrate that this nanoplatform can eradicate over 99.9999%of methicillin-resistant Staphylococcus aureus(MRSA)biofilms under 5-min NIR ***,these integrated advantages enable the system to promote the healing of MRSA biofilm-infected wounds with negligible toxicity in vivo,indicating great promise for overcoming the obstacles associated with bacterial biofilm eradication.

关键词： Bacterial biofilm Multidrug-resistant bacteria Photodynamic therapy Oxygen supplying Photothermal therapy