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Encoding and display technologies for combinatorial libraries in drug discovery:The coming of age from biology to therapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3362-3384页

作者： Yu Fan Ruibing Feng Xinya Zhang Zhen-Liang Wang Feng Xiong Shuihua Zhang Zhang-Feng Zhong Hua Yu Qing-Wen Zhang Zhang Zhang Yitao Wang Guodong Li Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of Education(MoE)of People’s Republic of ChinaCollege of PharmacyJinan UniversityGuangzhou 510632China Zhuhai UM Science and Technology Research Institute Zhuhai 519031China Department of Pharmacy Guangzhou Red Cross HospitalFaculty of Medical ScienceJinan UniversityGuangzhou 510632China Geriatric Medicine First People’s Hospital of XinXiang and the Fifth Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453100China Shenzhen Innovation center for Small Molecule Drug Discovery Co. Ltd.Shenzhen 518000China

Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge *** to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource *** review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical *** discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to *** also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market *** review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

关键词： Drug screening Phage display DNA-encoded chemical libraries Peptide-encoded chemical libraries Clinical drugs

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Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma

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World Journal of Gastroenterology 2012年第12期18卷 1379-1384页

作者： Hiroki Nishikawa Yukio Osaki Tadashi Inuzuka Haruhiko Takeda Jun Nakajima Fumihiro Matsuda Shinichiro Henmi Azusa Sakamoto Tetsuro Ishikawa Sumio Saito Ryuichi Kita Toru Kimura Department of Gastroenterology and Hepatology Osaka Red Cross Hospital

AIM： To examine the significance of branched-chain amino acid （BCAA） treatment before transcatheter arterial chemoembolization （rACE） for hepatocellular carcinoma （HCC）.METHODS： This study included 99 patients who underwent TACE therapy for HCC at our hospital and were followed up without treatment for at least 6 mo between January 2004 and January 2010. They were divided into 2 groups： those receiving BCAA granules （/7 = 40） or regular diet （n = 59, control）. Data obtained were retrospectively analyzed （prior to TACE, and 1 wk, 1, 3, and 6 mo after TACE） in terms of nutritional condition and clinical laboratory parameters （serum albumin level and Child-Pugh score）, both of which are determinants of hepatic functional reserve.RESULTS： The BCAA group comprised 27 males and 13 females with a mean age of 69,9 ：E 8,8 years, The patients of the BCAA group were classified as follows： Child-Pugh A/B/C in 22/15/3 patients, and Stage Ⅱ/Ⅲ/ /IVA HCC in 12/23/5 patients, respectively. The controlgroup comprised 32 males and 27 females with a mean age of 73.2 ± 10.1 years. In the control group, 9 patients had chronic hepatitis, Child-Pugh A/B/C in 39/10/1 patients, and Stage Ⅰ/Ⅱ/Ⅲ/IVA HCC in 1/11/35/12 patients, respectively. Overall, both serum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE （P 〈 0.05）. Further analysis was performed by the following categorization：（1） child-Pugh classification; （2） liver cirrhosis subgroup with a serum albumin level 〉 3.5 g/dL; and （3） epirubicin dose. A similar trend indicating a significant improvement of all variables in the BCAA group was noted （P 〈 0.05）.CONCLUSION： Treatment with BCAA granules in patients who have undergone TACE for HCC is considered useful to maintain their hepatic functional reserve.

关键词： Hepatocellular carcinoma Branched-chainamino acid granules Transcatheter arterial chemoembo-lization Liver function Improvement Cirrhosis Protein-energy malnutrition

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Detection of ARV-Resistant Mutants in HIV-1-Infected Individuals in a Context of Systematic Switching to an Association Based on Dolutegravir in Abidjan, Côte d’Ivoire

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American Journal of Molecular Biology 2024年第3期14卷 138-151页

作者： Odegue Kpadraux Danielle Kakou-Ngazoa Solange Dechi Jean-Jacques Renaud Diallo Zelica Sina Kouamé Mireille Sylla Aboubacar Tossea Koui Stéphane Kouakou Venance Adagba Marius Apia N’Chouo Kouamé Basile Touré Offianan André Dosso Mireille Molecular Biology Platform Institut Pasteur Abidjan Cte dIvoire Laboratory of the Regional blood Transfusion center Yamoussoukro Cte dIvoire Department of Infectious and Tropical Diseases University Hospital Treichville Abidjan Cte dIvoire Laboratory of the Regional blood Transfusion center San-Pdro Cte dIvoire Department of Epidemic Virus Institut Pasteur Abidjan Cte dIvoire Department of Parasitology Mycology Institut Pasteur Abidjan Cte dIvoire Department of Bacteriology-Virology Institut Pasteur Abidjan Cte dIvoire

The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://***/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.

关键词： Resistant Mutants Dolutegravir HIV-1 Antiretrovirals Côte d’Ivoire

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Short-term intravenous interferon therapy for chronic hepatitis B

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World Journal of Gastroenterology 2008年第19期14卷 3038-3043页

作者： Hiroaki Okushin Toru Ohnishi Kazuhiko Morii Koichi Uesaka Shiro Yuasa Department of Internal Medicine Himeji Red Cross Hospital

AIM:To investigate the therapeutic efficacy of short- term, multiple daily dosing of intravenous interferon (IFN) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS:IFN-β was intravenously administered at a total dose of 102 million international units (MIU) over a period of 28 d in 26 patients positive for HBeAg and HBV-DNA. IFN-beta was administered at doses of 2 MIU and 1 MIU on d 1, 3 MIU twice daily from d 2 to d 7, and 1 MIU thrice daily from d 8 to d 28. Patients were followed up for 24 wk after the end of treatment. RESULTS:Six months after the end of the treatment, loss of HBV-DNA occurred in 13 (50.0%) of the 26 patients, loss of HBeAg in 9 (34.6%), development of anti-HBe in 10 (38.5%), HBeAg seroconversion in 8 (30.8%), and normalization of alanine aminotransferase (ALT) levels in 11 (42.0%). CONCLUSION:This 4-wk long IFN-β therapy, which was much shorter than conventional therapy lasting 12 wk or even more than 1 year, produced therapeutic effects similar to those achieved by IFN-α or pegylated- IFN-α (peg-IFN). Fewer adverse effects, greater efficacy, and a shorter treatment period led to an improvement in patients’ quality of life. IFN-β is administered intravenously, whereas IFN-α is administered intramuscularly or subcutaneously. Because both interferons are known to bind to an identical receptor and exert antiviral effects through intracellular signal transduction, the excellent results of IFN-β found in this study may be attributed to the multiple doses allowed by the intravenous route.

关键词： Chronic hepatitis B Hepatitis B e antigen Hepatitis B virus Interferon beta Multiple daily dosing Short-term treatment Intravenous injection

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Wound healing of intestinal epithelial cells

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World Journal of Gastroenterology 2011年第17期17卷 2161-2171页

作者： Masahiro Iizuka Shiho Konno Akita Health Care center Akita Red Cross HospitalAkita 010-0001Japan

The intestinal epithelial cells(IECs) form a selective permeability barrier separating luminal content from underlying *** injury,the intestinal epithelium undergoes a wound healing *** wound healing is dependent on the balance of three cellular events;restitution,proliferation,and differentiation of epithelial cells adjacent to the wounded *** studies have shown that various regulatory peptides,including growth factors and cytokines,modulate intestinal epithelial wound *** studies have revealed that novel factors,which include toll-like receptors(TLRs),regulatory peptides,particular dietary factors,and some gastroprotective agents,also modulate intestinal epithelial wound *** these factors,the activation of TLRs by commensal bacteria is suggested to play an essential role in the maintenance of gut *** studies suggest that mutations and dysregulation of TLRs could be major contributing factors in the predisposition and perpetuation of inflammatory bowel ***,studies have shown that specific signaling pathways are involved in IEC wound *** this review,we summarize the function of IECs,the process of intestinal epithelial wound healing,and the functions and mechanisms of the various factors that contribute to gut homeostasis and intestinal epithelial wound healing.

关键词： Intestinal epithelial cell Wound healing Restitution Growth factors Toll-like receptor

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Efficacy of 1.2L polyethylene glycol plus ascorbic acid for bowel preparations

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World Journal of Clinical Cases 2019年第4期7卷 452-465页

作者： Hiroyuki Tamaki Teruyo Noda Masahiro Morita Akina Omura Atsushi Kubo Chikara Ogawa Toshihiro Matsunaka Mitsushige Shibatoge Department of Gastroenterology Takamatsu Red Cross Hospital

BACKGROUND A low-volume polyethylene glycol(PEG) solution that combines ascorbic acid with PEG-based electrolyte solution(PEG-ASC) is gaining mainstream acceptance for bowel preparation due to reduced volume and improved *** several reports showed that bowel preparation with PEG-ASC volume lower than 2.0 L with laxative agents could be an alternative to traditional preparation regimen, the cleansing protocols have not been fully *** To evaluate the cleansing efficacy of 1.2 L PEG-ASC solution comparing with 2.0 L PEG electrolyte(PEG-ELS) for bowel *** A randomized, single-blinded, open-label, single-center, non-inferiority study was conducted. In total, 312 Japanese adult patients(aged > 18 years) who underwent colonoscopy were enrolled. Patients were randomly allocated to bowel lavage with either 1.2 L of PEG-ASC solution with at least 0.6 L of an additional clear fluid(1.2 L PEG-ASC group) or 2.0 L of PEG-ELS(PEG-ELS group). Then, 48 mg of sennoside was administered at bedtime on the day before colonoscopy, and the designated drug solution was administered at the hospital on the day of colonoscopy. Bowel cleansing was evaluated using the Boston Bowel Preparation Scale(BBPS). The volume of fluid intake and required time for bowel preparation were evaluated. Furthermore, compliance, patient tolerance,and overall acceptability were evaluated using a patient questionnaire, which was assessed using a visual analog *** In total, 291 patients(1.2 L PEG-ASC group, 148; PEG-ELS group, 143) completed the study. There was no significant difference in successful cleansing, defined as a BBPS score ≥ 2 in each segment, between the two groups(1.2 L PEG-ASC group, 91.9%; PEG-ELS group, 90.2%; 95%CI:-0.03-0.09). The required time for bowel preparation was significantly shorter(164.95 min ± 68.95 min vs 202.16 min± 68.69 min, P < 0.001) and the total fluid intake volume was significantly lower(2.23 L ± 0.55 L vs 2.47 L ± 0.56 L, P

关键词： Ascorbic acid Bowel preparation Colonoscopy Efficacy Polyethylene glycol Tolerability

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Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with diabetes mellitus

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Chinese Journal of Cancer Research 2014年第3期26卷 341-344页

作者： Young Ae Kim Sol Lee Ji Woong Jung Yu Jin Kwon Gyeong Bok Lee Dong Gue Shin Sang Su Park Jin Yun Yong-Seog Jang Dong Hui Cho Department of Surgery Seoul Medical CenterSeoulKorea Department of Surgery Red Cross HospitalSeoulKorea

The side effects of tamoxifen are generally mild, including the effect on lipoprotein metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia. Hypertriglyceridemia is a marked risk factor for acute pancreatitis and approximately 2% to 5% of cases of acute pancreatitis are related to drugs. We report on tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 40 years old woman with type 2 diabetes mellitus occurred by dexamethasone. She was treated with insulin infusion and fenofibrate, and goserelin acetate was started instead of tamoxifen after discharge from the hospital. Also, probable pathogenic hypotheses about the correlation between tamoxifen and dexamethasone induced type 2 diabetes mellitus on severe acute pancreatitis are provided. Clinicians should take care of risks of severe acute pancreatitis on using tamoxifen, especially for patients with dexamethasone induced diabetes mellitus. These individuals should undergo pre-post tamoxifen lipid screening and careful history taking of drugs, including dexamethasone.

关键词： Tamoxifen acute pancreatitis hypertriglyceridemia type 2 diabetes mellitus dexamethasone

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Improving witness interviewing for the investigation of disappeared persons due to armed conflict

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Forensic Sciences Research 2022年第3期7卷 334-345页

作者： Derek Congram Maria Mikellide Matthew Vennemeyer International Committee of the red cross China

Investigating missing persons who are presumed dead in conflict contexts almost always involves witness *** can be critical both to locating burial sites and to positively identifying bodies that are *** the importance of interviews,the authors have found that investigators in these contexts seldom have formal training on *** article highlights three principal problems that the authors have experienced relative to interviewing as part of missing persons investigations in armed conflict contexts:that interviewing is not treated as a professional activity;the tendency to overvalue technical tools in the search for burial sites;and a lack of awareness about cultural and contextual factors that impact *** article concludes with five recommendations on how to improve witness interviewing.

关键词： Forensic sciences missing persons witness interview humanitarian forensics

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Effects of Chinese Herbal Medicine Combined with He-Ne Laser on Lipoperoxide and Superoxide Dismutase in Chloasma Patients

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Journal of Traditional Chinese Medicine 2009年第3期29卷 163-166页

作者：吴艳华李其林杨秀文陈正秋 Departments of Chinese Medicine and Dermatology Guangzhou Red Cross Hospital

Objective: To observe the effects of Chinese decoction and ligustrazin hydrochloride injection combined with He-Ne laser on lipoperoxide (LPO) and Superoxide dismutase (SOD) in patients with chloasma. Methods: 90 cases of chloasma were randomly divided into the following two groups: a treatment group (of 54 cases) treated by a self-prepared prescription for toning the kidneys and relieving the depressed liver to remove blood stasis, ligustrazin hydrochloricde injection and He-Ne laser therapy, and a control group (of 36 cases) treated with oral administration of Vitamin E and Vitamin C plus external application of 20% Azelaic acid cream. Results: The total effective rate in the treatment group was 79.6%, which was significantly higher than that of the control group (Pred (P<0.01), and the SOD level was significantly elevated (P<0.05). Conclusion: The therapeutic methods adopted in the treatment group may show the action of antioxidation, providing good clinical effects for treating chloasma.

关键词： Chloasma TCM therapy Lipoperoxide He-Ne laser Ligustrazin

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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Cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno Division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical Genomics National Cancer Center Research InstituteTokyoJapan Laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan Laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of Medical Oncology and Cancer center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan Division of Medical AI Research and Development National Cancer Center Research InstituteTokyoJapan center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of Medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan Division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan Division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan Division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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