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Clinical progress of nanomedicine-based RNA therapies

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Bioactive Materials 2022年第6期7卷 203-213页

作者： Siyoung A.Lim Alysia Cox Madelynn Tung eun ji chung Department of Biomedical Engineering University of Southern CaliforniaLos AngelesCAUSA Mork Family Department of Chemical Engineering and Materials Science University of Southern CaliforniaLos AngelesCAUSA Department of Medicine Division of Nephrology and HypertensionUniversity of Southern CaliforniaLos AngelesCAUSA Department of Surgery Division of Vascular Surgery and Endovascular TherapyUniversity of Southern CaliforniaLos AngelesCAUSA

The clinical application of nanoparticles(NPs)to deliver RNA for therapy has progressed rapidly since the FDA approval of Onpattro®in 2018 for the treatment of polyneuropathy associated with hereditary transthyretin *** emergency use authorization or approval and widespread global use of two mRNA-NP based vaccines developed by Moderna Therapeutics *** Pfizer-BioNTech in 2021 has highlighted the translatability of NP technology for RNA ***,in clinical trials,a wide variety of NP formulations have been found to extend the half-life of RNA molecules such as microRNA,small interfering RNA,and messenger RNA,with limited safety *** this review,we discuss the NP formulations that are already used in the clinic to deliver therapeutic RNA and highlight examples of RNA-NPs which are currently under evaluation for human *** also detail NP formulations that failed to progress through clinical trials,in hopes of guiding future successful translation of nanomedicine-based RNA therapeutics into the clinic.

关键词： Nanoparticles RNA therapy Drug delivery Nanomedicine Clinical trials COVID-19

Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

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Nano Research 2018年第10期11卷 5584-5595页

作者： Jonathan Wang Christopher Poon Deborah Chin Sarah Milkowski Vivian Lu Kenneth R. Hallows eun ji chung Department of Biomedical Engineering University of Southern California Los Angeles CA 90089 USA Division of Nephrology and Hypertension Department of Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA USC/UKRO Kidney Research Center Keck School of Medicine University of Southern California Los Angeles CA 90033 USA Norris Comprehensive Cancer Center University of Southern California Los Angeles CA 90033 USA Department of Stem Cell Biology and Regenerative Medicine University of Southern California Los Angeles CA 90033 USA Mork Family Department of Chemical Engineering and Materials Science University of Southern California Los Angeles CA 90089 USA

One in three Americans is at risk for developing chronic kidney disease （CKD） and end-stage renal disease （ESRD）, leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel kidney-targeting multimodal micelle （KM） system for drug delivery applications. SpecificaU~ we incorporated the kidney-targeting peptide （Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid）3-Lysine）（（KKEEE）3K） into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted （NT） control upon intravenous injection in wild-type C57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen （BUN） and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of （KKEEE）BK in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in CKD.

关键词： micelle kidney disease renal targeting biodistribution nanoparticle

Long-term, in vivo therapeutic effects of a single dose of miR-145 micelles for atherosclerosis

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Bioactive Materials 2023年第9期27卷 327-336页

作者： Deborah D.Chin Neil Patel Woori Lee Sonali Kanaya Jackson Cook eun ji chung Department of Biomedical Engineering University of Southern CaliforniaLos AngelesCA90089United States Division of Vascular Surgery and Endovascular Therapy Department of SurgeryKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Mork Family Department of Chemical Engineering and Materials Science University of Southern CaliforniaLos AngelesCA90089United States Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Division of Nephrology and Hypertension Department of MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90033United States Norris Comprehensive Cancer Center Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA90089United States

Atherosclerosis is a chronic inflammatory disease that is characterized by the build-up of lipid-rich plaques in the arterial walls. The standard treatment for patients with atherosclerosis is statin therapy aimed to lower serum lipid levels. Despite its widespread use, many patients taking statins continue to experience acute events. Thus, to develop improved and alternative therapies, we previously reported on microRNA-145 (miR-145 micelles) and its ability to inhibit atherosclerosis by targeting vascular smooth muscle cells (VSMCs). Importantly, one dose of miR-145 micelles significantly abrogated disease progression when evaluated two weeks post-administration. Thus, in this study, to evaluate how long the sustained effects of miR-145 micelles can be maintained and towards identifying a dosing regimen that is practical for patients with chronic disease, the therapeutic effects of a single dose of miR-145 micelles were evaluated for up to two months in vivo. After one and two months post-treatment, miR-145 micelles were found to reduce plaque size and overall lesion area compared to all other controls including statins without causing adverse effects. Furthermore, a single dose of miR-145 micelle treatment inhibited VSMC transdifferentiation into pathogenic macrophage-like and osteogenic cells in plaques. Together, our data shows the long-term efficacy and sustained effects of miR-145 micelles that is amenable using a dosing frequency relevant to chronic disease patients.

关键词： MicroRNA-145 Atherosclerosis Vascular smooth muscle cell Nanoparticle Gene therapy

Representation of global precipitation anomalies using four major climate patterns

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Science China(Technological Sciences) 2015年第5期58卷 927-934页

作者： CHEN ji chung ChiHang Department of Civil Engineering The University of Hong Kong

This study aims at finding the dominant climate patterns that influence the precipitation anomalies for different regions over the world. To this end, a multiple linear regression model is employed to represent the impact of four major climate patterns(El Ni?o-Southern Oscillation(ENSO), Indian Ocean Dipole(IOD), Arctic Oscillation(AO) and Antarctic Oscillation(AAO)) on the global precipitation anomalies. The normalized climate pattern indexes and normalized precipitation anomalies are used in the regression model. For the Northern Hemisphere, the three predictors used are the normalized NINO3.4 index(representing ENSO), normalized DMI(representing IOD) and normalized AO index; for the Southern Hemisphere, also three indexes are used as three predictors, and the normalized AO index is replaced by the normalized AAO index. The influences brought by each climate pattern can be represented by the magnitude of the corresponding regression coefficients, and the dominant climate patterns are those with the largest magnitude. The study results show that the precipitation anomalies in the northern part of South America and the northwestern part of Southeast Asia are mainly influenced by ENSO. The precipitation anomalies in East Africa and the southwestern part of Southeast Asia are mainly influenced by IOD. The precipitation anomalies in Europe and west coast of North America are mainly influenced by AO; the precipitation anomalies in the eastern part and southern part of South America, southern part of Africa, and the northeastern Australia are mainly influenced by AAO. These findings are consistent with the general understanding on the teleconnection features of the four climate patterns. Further, the regression model can be used for predicting precipitation anomalies through use of these major climate patterns.

关键词： normalized ENSO Southeast representing Australia southwestern Arctic trained instead brought

Midazolam dose is associated with recurrence of paradoxical reactions during endoscopy

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World Journal of Clinical Cases 2021年第29期9卷 8763-8772页

作者： eun Hyo jin ji Hyun Song Jooyoung Lee Jung Ho Bae Su jin chung Department of Internal Medicine Healthcare Research InstituteHealthcare System Gangnam CenterSeoul National University HospitalSeoul 06236South Korea

BACKGROUND Midazolam is commonly used for sedation during gastrointestinal ***,some patients experience paradoxical reactions characterized by excessive movement or *** To investigate the rate of recurrence of paradoxical reactions to midazolam during an upper *** We retrospectively reviewed 122152 sedative endoscopies among a total of 58553 patients at the Seoul National University Hospital,Healthcare System Gangnam Center,from July 2013 to December *** them,361 patients with a history of paradoxical reaction during sedative upper endoscopy were *** characteristics of patients in the recurrent and non-recurrent groups were compared via multivariable analysis using logistic *** Paradoxical reactions occurred in 0.86%(1054/122152)of endoscopies,and in 1.51%(888/58553)of *** the 361 subjects with previous paradoxical reactions in sedative endoscopies,111(30.7%)experienced further paradoxical *** analysis revealed that the total midazolam dose used was higher in the recurrent group(6.74±2.58 mg)than in the non-recurrent group(5.49±2.04 mg;P<0.0001).Patients were administered a lower dose of midazolam than previous doses:1 mg less in the recurrent group and 2 mg less in the non-recurrent *** analysis showed that the midazolam dose difference was an independent risk factor for recurrent paradoxical reaction(odds ratio:1.213,95%CI:1.099-1.338,P=0.0001).CONCLUSION The rate of recurrence of paradoxical reactions is significantly associated with midazolam *** dose of midazolam administered to patients with previous paradoxical reactions should be less than that previously used.

关键词： Gastroscopy Endoscopy Conscious sedation Midazolam Flumazenil

Explainable Anomaly Detection Using Vision Transformer Based SVDD

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Computers, Materials & Continua 2023年第3期74卷 6573-6586页

作者： ji-Won Baek Kyungyong chung Department of Computer Science Kyonggi UniversitySuwon-si 16227Korea Division of AI Computer Science and Engineering Kyonggi UniversitySuwon-si 16227Korea

Explainable AI extracts a variety of patterns of data in the learning process and draws hidden information through the discovery of semantic *** is possible to offer the explainable basis of decision-making for inference *** the causality of risk factors that have an ambiguous association in big medical data,it is possible to increase transparency and reliability of explainable decision-making that helps to diagnose disease *** addition,the technique makes it possible to accurately predict disease risk for anomaly *** transformer for anomaly detection from image data makes classification through ***,in MLP,a vector value depends on patch sequence information,and thus a weight *** should solve the problem that there is a difference in the result value according to the change in the *** addition,since the deep learning model is a black box model,there is a problem that it is difficult to interpret the results determined by the ***,there is a need for an explainablemethod for the part where the disease *** solve the problem,this study proposes explainable anomaly detection using vision transformerbasedDeep Support Vector Data Description(SVDD).The proposed method applies the SVDD to solve the problem of MLP in which a result value is different depending on a weight change that is influenced by patch sequence information used in the vision *** order to draw the explainability of model results,it visualizes normal parts through *** health data,both medical staff and patients are able to identify abnormal parts *** addition,it is possible to improve the reliability of models and medical *** performance evaluation normal/abnormal classification accuracy and f-measure are evaluated,according to whether to apply *** Results The results of classification by applying the proposed SVDD are evaluated ***,through the proposed meth

关键词： Explainable AI anomaly detection vision transformer SVDD health care deep learning classification

Effects of dispersoid preforming via multistep sintering of oxide dispersion-strengthened CoCrFeMnNi high-entropy alloy

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Journal of Materials Science & Technology 2023年第9期140卷 187-200页

作者： SeungHyeok chung ji Ho Shin Ho jin Ryu Department of Nuclear and Quantum Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea Central Research Institute Korea Hydro and Nuclear Power Co.Ltd.(KHNP)Daejeon 34101Republic of Korea

Dispersoid formation and microstructural evolution in an oxide dispersion-strengthened CoCrFeMnNi high-entropy alloy(HEA)using a newly designed multistep sintering process are *** proposed multistep sintering consists of a dispersoid preforming heat treatment of as-milled 0.1 wt%Y_(2)O_(3)-CoCrFeMnNi high-entropy alloy powders at 800℃,followed by sintering at 800–1000℃ under uniaxial *** the conventional single-step sintered bulk,the coarsened BCC Y_(2)O_(3)dispersoids mainly form with an incoherent interface with the HEA *** contrast,finer FCC Y_(2)O_(3)dispersoids,an atypical form of Y_(2)O_(3),are formed in the matrix region after multistep *** of FCC Y_(2)O_(3)disper-soids is initiated on the favorable facet,the{111}plane of the austenitic matrix,with the formation of a semi-coherent interface with the matrix during the dispersoid preforming heat treatment and it maintains its refined size even after *** is found that dispersoid preforming prior to sintering appears promising to control the finer dispersoid formation and refined grain structure.

关键词： Oxide dispersion strengthening High-Entropy alloy Multistep sintering Dispersoid preforming Microstructure evolution Interfacial structure

Microbiology and risk factors for gram-positive Cocci bacteremia in biliary infections

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Hepatobiliary & Pancreatic Diseases International 2020年第5期19卷 461-466页

作者： Ik Hyun Jo Yeon-ji Kim Woo Chul chung Jaeyoung Kim Seonhoo Kim eun Sun Lim Honggeun Ahn Seong Yul Ryu Division of Gastroenterology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwon 16247Korea

Background:The rapid antibiotics treatment targeted to a specific pathogen can improve clinical outcomes of *** aimed to evaluate the clinical characteristics and outcomes of biliary septicemia caused by cholangitis or cholecystitis according to causative ***:We performed a retrospective cohort study in 151 patients diagnosed with cholangitis or cholecystitis with bacterial septicemia from January 2013 to December *** patients showed clinical evidence of biliary tract infection and had blood isolates that demonstrated ***:Gram-negative,gram-positive,and both types of bacteria caused 84.1%(127/151),13.2%(20/151),and 2.6%(4/151)episodes of septicemia,*** most common infecting organisms were Escherichia coli among gram-negative bacteria and Enterococcus species(Enterococcus casseliflavus and Enterococcus faecalis)among gram-positive *** were no differences in mortality,re-admission rate,and need for emergency decompression procedures between the gram-positive and gram-negative septicemia *** univariate analysis,previous gastrectomy history was associated with gram-positive *** analysis also showed that previous gastrectomy history was strongly associated with gram-positive septicemia(Odds ratio=5.47,95%CI:1.19–25.23;P=0.029).Conclusions:Previous gastrectomy history was related to biliary septicemia induced by gram-positive *** information would aid the choice of empirical antibiotics.

关键词： Cholangitis Cholecystitis Septicemia Gram-positive bacterial infections

Median arcuate ligamentum syndrome:Four case reports

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World Journal of Clinical Cases 2022年第6期10卷 1991-1997页

作者： ji eun Kim Poong Lyul Rhee Division of Gastroenterology Samsung Medical CenterSeoul 06351South Korea

BACKGROUND Median arcuate ligamentum syndrome(MALS)is a disease entity with unclear *** it is not considered in advance,the clinical diagnosis of the disease is very difficult because patients complain of digestive discomfort including ***,this characteristic is not specific to *** have been no studies to assist in making a quick *** aim of this case series was to recognize that MALS must be considered as a differential factor in the cause of abdominal *** SUMMARY We described cases in which four patients complained of abdominal pain over a long period but in whom a diagnosis of MALS could not be *** the gastroenterologist does not take into account abdominal pain in advance,the patient is considered an asymptomatic gallstone patient and has their gallbladder removed despite imaging *** patient may also be considered a psychiatric patient and may be administered psychiatric drugs over a long *** all four cases in this report,the patients experienced abdominal *** three cases,the diagnosis was possible by the clinician’s judgment considering both clinical symptoms and imaging techniques shortly after the onset of ***,in one case that lasted over 20 years,a clear diagnosis was not *** after complaining of colicky pain and performing a cholecystectomy,the diagnosis was made only after the symptoms *** all four cases,the symptoms were relieved by *** MALS is a rare disease and it is easy to miss because it is not malignant,but patients can suffer from pain over a long *** the accurate diagnosis of a patient complaining of abdominal pain,the diagnosis must be *** addition,as there are asymptomatic patients,patients who need treatment should be carefully selected,and improvement with medical treatment can be ***-scale studies are also needed.

关键词： Median arcuate ligamentum syndrome Abdominal pain Missed diagnosis Neuromodulator Celiac artery compression Case report