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Phosphorylated protein chip combined with artificial intelligence tools for precise drug screening

Journal of Biomedical Research 2024年第3期38卷 195-205页

作者： Katsuhisa Horimoto Yuki Suyama Tadamasa sasaki Kazuhiko Fukui Lili Feng Meiling Sun Yamin Tang Yixuan Zhang Dongyin Chen Feng Han SOCIUM Inc. Tokyo 1350064Japan International medical center Saitama Medical UniversitySaitama 350-1298Japan Artificial Intelligence Research center National Institute of Advanced Industrial Science and TechnologyTokyo 1350064Japan Department of Informatics and Data Science Sanyo-Onoda City UniversityYamaguchi 7560884Japan International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China Department of Physiology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Gusu School Nanjing Medical UniversitySuzhouJiangsu 215001China National Vaccine Innovation Platform Nanjing Medical UniversityNanjingJiangsu 211166China

We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the *** protein array contains 1471 proteins from 273 known signaling *** to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same *** addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the *** Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors.

关键词： Phospho-Totum protein array signal transduction pathways artificial intelligence tools drug screening

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Microfocused Ultrasound for Nonablative Skin and Subdermal Tightening to the Periorbitum and Body Sites: Preliminary Report on Eighty-Two Patients

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Journal of Cosmetics, Dermatological Sciences and Applications 2012年第2期2卷 108-116页

作者： Gordon H. sasaki Ana Tevez Loma Linda University medical School Private Practice sasaki advanced aesthetic medical center

Lax crepey skin is a major unsightly finding throughout the face and body that occurs from chronological aging and environmental photodamage. Surgical lifting procedures are unable to induce sufficient neocollagenesis and also associated with visible scars, risks and recovery time. In this preliminary report, non-invasive delivery of microfocused ultrasonic thermal coagulation points at two levels of the dermis outside the orbital rims was effective in reduction of crepey, wrinkled and sagging skin for about 1 ? years in nineteen treated patients. Matched Orientation Mirror Imaging produced an average brow height elevation of 1 - 2 mm. Microfocused thermal coagulation points at multiple tissue levels also induced tissue tightening and reduction of crepey wrinkled skin in the décolletage, brachium, periumbilicus, inner thigh and knees. Investigator and Subject Global aesthetic Improvement Scale graded responses that correlated to the severity of the degree of crepiness and laxity. Pain management during the procedure included the use of infiltration of local anesthesia. No permanent adverse events were observed. Further innovations in the current technology are needed for more effective and safer delivery of energy to improve the appearance of crepey and lax tissue in the head, neck and body.

关键词： Crepey Focused Imaged Ultrasound Noninvasive Lifting Tightening

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Immunomodulatory Nanosystems:advanced Delivery Tools for Treating Chronic Wounds

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Research 2023年第4期6卷 55-77页

作者： Xiangyu Chu Yuan Xiong Samuel Knoedler Li Lu Adriana CPanayi Michael Alfertshofe Dongsheng Jiang Yuval Rinkevich Ze Lin Zhiming Zhao Guandong Daia Bobin Mi Guohui Liu Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China Division of Plastic Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02152USA institute of Regenerative Biology and Medicine Helmholtz Zentrum MunchenMax-Lebsche-Platz 3181377 MunichGermany Department of Hand Plastic and Reconstructive SurgeryMicrosurgeryBurn CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwig-Guttmann-Strasse 1367071 Ludwigshafen/Rhine Germany.Division of HandPlastic and Aesthetic SurgeryLudwig-Maximilian University MunichMunichGermany Department of Orthopedics Suizhou HospitalHubei University of MedicineSuizhou 441300China Pingshan District People'sHospitalof Shenzhen Pingshan General Hospital of Southern Medical UniversityShenzhenGuangdong 518118China

The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global *** of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this ***,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack *** highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of *** a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively ***,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of *** addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field.

关键词： Tools healing herein

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Limb preservation with suprafascial and thin perforator flaps: salvaging osteomyelitis, Charcot collapse and critical limb ischemia

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Plastic and aesthetic Research 2019年第8期6卷 13-23页

作者： Shawn Diamond Andres F.Doval Benjamin Scott Matthew L.Iorio Division of Plastic and Reconstructive Surgery Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA Division of Plastic and Reconstructive Surgery University of Colorado Anschutz Medical CenterAuroraCO 80045USA.

AIM: There are limited reports in the United States demonstrating outcomes of primarily thinned fasciocutaneous flaps in the setting of critical limb ischemia, Charcot collapse and osteomyelitis. We hope to determine patient and flap related outcomes in advanced lower extremity disease. Methods: The authors conducted a retrospective review of fasciocutaneous free flaps of variable thickness for lower extremity salvage. Osteomyelitis and non-osteomyelitis patients were compared according to our primary outcome measures: functional ambulation, bone healing and complications to flap and patient. Subgroups with critical limb ischemia, Charcot collapse and diabetic foot were analyzed separately. Results: Fifty-nine patients underwent free flap reconstruction: osteomyelitis (n = 20, 34%), Charcot collapse (n = 22, 37%), and/or critical limb ischemia (n = 12, 20%). All patients underwent anterolateral thigh flaps tailored for defect-specific thicknesses: 17 superthin, 25 suprafascial, 17 subfascial. There were no significant differences between groups in terms of partial and complete flap loss (P = 1.000 and P = 0.108). Ninety-one percent of patients were ambulatory at follow up. Eighty-tive percent of individuals with osteomyelitis cleared their infection demonstrating radiographic bone healing. Two patients developed recalcitrant deep space infections ultimately requiring amputation. Subgroup analysis did not show any differences in flap related complications within the diabetic Charcot population. In multivariate regression, preoperative revascularization was independently associated with failure of limb salvage. ;Conclusion: Primarily thinned perforator flaps performed well in the setting of lower extremity limb salvage, critical limbischemia, osteomyelitis, and the Charcot foot - expanding their role in the armamentarium for lower extremity care.

关键词： Perforator flap diabetic foot limb salvage

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Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer:A multi-institutional study of Kansai Clinical Oncology Group

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Chinese Journal of Cancer Research 2020年第2期32卷 218-227页

作者： Satoshi Takeuchi Haruo Kuroboshi Taisuke Mori Kimihiko Ito Eiji Kondo Tsutomu Tabata Yoshio Itani Ryuji Kawaguchi Kyosuke Takeuchi Toshinori Soejima Ryohei sasaki Department of Obstetrics and Gynecology National Hospital Organization Kobe Medical CenterKobe 6540155Japan Division of Gynecologic Oncology Department of GynecologyWomen Health CareKobe Tokushukai HospitalKobe 6500017Japan Department of Obstetrics and Gynecology Kyoto Prefectural University of MedicineKyoto 6028566Japan Department of Obstetrics and Gynecology Kansai Rosai HospitalAmagasaki 6608511Japan Department of Obstetrics and Gynecology Mie University Graduate Medical School Faculty of MedicineTsu5148507Japan Department of Obstetrics and Gynecology Tokyo Women’s Medical UniversityTokyo 1628666Japan Department of Obstetrics and Gynecology Nara Prefectural Nara Hospital(Nara Prefectural General Medical Center)Nara 6308581Japan Department of Palliative Care Palliative Care Center of Yao-city HospitalOsaka 5810069Japan Department of Obstetrics and Gynecology Nara Medical UniversityNara 6348521Japan I0Department of Radiation Oncology Kobe University Graduate School of MedicineKobe 6500017Japan departm ent of Radiation Oncology Hyogo Ion Beam Medical Center Kobe Proton CenterKobe 6500047Japan

Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for *** chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic *** evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci ***:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,*** starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 ***,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in ***:Seventeen patients were *** for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and ***,the MTD of CPT-11 was defined as dose of 60 mg/m^*** recommended dose was decided as 50 mg/m^*** response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer ***:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/*** concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.

关键词： Concurrent chemoradiotherapy(CCRT) irinotecan hydrochloride(CPT-11) cervical adenocarcinoma endometrial cancer

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