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Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent

Acta Pharmaceutica Sinica B 2024年第2期14卷 729-750页

作者： xin Chen Xianggang mu Lele Ding Xi Wang Fei Mao Jinlian Wei Qian Liu Yixiang Xu Shuaishuai Ni Lijun Jia Jian Li State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismFrontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China College of Pharmacy Jinan UniversityGuangzhou 510632China

Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer *** intertwined adverse effects,brought by cancer and its complication,further complicate anticancer therapy and lead to diminished clinical *** supplementation of cardioprotective agents falls short in addressing these *** bifunctional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events *** repurposing was naturally endowed with co-therapeutic potential of two indications,implying a unique chance in the development of bi-functional ***,we further proposed a novel“trilogy of drug repurposing”strategy that comprises function-based,targetfocused,and scaffold-driven repurposing approaches,aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional *** function-based repurposing,a cardioprotective agent,carvedilol(CAR),was identified as a potential neddylation inhibitor to suppress lung cancer *** target-focused SAR studies and scaffold-driven drug design,we synthesized 44 CAR derivatives to achieve a balance between anticancer and ***,optimal derivative 43 displayed promising bi-functional effects,especially in various self-established heart failure mice models with and without ***,the present study validated the practicability of the“trilogy of drug repurposing”strategy in the development of bi-functional cotherapy agents.

关键词： Anticancer Heartfailure Complication Drug repurposing Bi-functional drug

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Emotional differences based on comments on doctor-patient disputes with varying levels of severity

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World Journal of Psychiatry 2024年第7期14卷 1068-1079页

作者： Jing-ru Lu Yu-Han Wei xin Wang Yu-Qing Zhang Jia-Yi Shao Jiang-Jie Sun School of Health Care Management Anhui Medical UniversityHefei 230032Anhui ProvinceChina School of Management Hefei University of TechnologyHefei 230039Anhui ProvinceChina

BACKGROUND The risks associated with negative doctor-patient relationships have seriously hindered the healthy development of medical and healthcare and aroused wide-spread concern in *** number of public comments on doctor-patient relationship risk events reflects the degree to which the public pays attention to such *** incidents of doctor-patient disputes were collected from Weibo and TikTok,and 3655 related comments were *** number of comment sentiment words was extracted,and the comment sentiment value was *** Kruskal-Wallis H test was used to compare differences between each variable group at different levels of ***’s correlation analysis was used to examine associations between *** analysis was used to explore factors influencing scores of comments on *** The study results showed that public comments on media reports of doctor-patient disputes at all levels are mainly dominated by“good”and“disgust”emotional *** was a significant difference in the comment scores and the number of partial emotion words between comments on varying levels of severity of doctor-patient *** comment score was positively correlated with the number of emotion words related to positive,good,and happy)and negatively correlated with the number of emotion words related to negative,anger,disgust,fear,and *** The number of emotion words related to negative,anger,disgust,fear,and sadness directly influences comment scores,and the severity of the incident level indirectly influences comment scores.

关键词： Doctor-patient relationship Doctor-patient dispute Comments Emotional differences Weibo TikTok

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Simultaneous type III congenital esophageal atresia and patent ductus arteriosus in a low-weight patient: A case report

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World Journal of Clinical Cases 2024年第3期12卷 560-564页

作者： Yong-Yu Ma Jun-ru Chen Shi-Wu Yang Shu-Yu Wang xin Cao Jun Wu Faculty of Pediatrics Children’s Hospital Affiliated to Kunming Medical UniversityKunming 650103Yunnan ProvinceChina Department of Cardiothoracic Surgery Kunming Children’s HospitalKunming 650103Yunnan ProvinceChina

BACKGROUND We report a low-birth-weight child(1.8 kg)with neonatal type III congenital esophageal atresia(CEA)combined with symptomatic patent ductus arteriosus(PDA).After comprehensive evaluation,esophageal anastomosis was performed on postnatal day 11 after excluding surgical contraindications,and arterial catheter ligation was performed at the same *** surgery for CEA combined with PDA has not been clearly reported in the *** SUMMARY We report a 6-day-old female child with type III CEA and *** patient presented with foam at the mouth after birth,cough and shortness of breath after *** another hospital,she was considered to have neonatal pneumonia,neonatal jaundice and congenital heart disease and transferred to our *** iodine oil radiography of the esophagus and echocardiography we con-firmed diagnosis of CEA and *** diameter of the PDA was 8 mm,with obvious left to right *** performed right rear extrapleural orificium fistula ligation and esophageal anastomosis,and ligation of PDA via left axilla straight incision after 5 d of *** operations were successful,and the incision healed after 12 d,and the patient was *** re-examined the patient 1 mo after *** did not vomit when she ate rice *** angiography showed no stricture of the anastomotic *** patient weighed 3.2 *** For CEA patients with multiple risk factors,comprehensive,timely and accurate diagnosis and evaluation,and early treatment may improve prognosis.

关键词： Congenital esophageal atresia Patent ductus arteriosus Low weight One-stage operation Case report

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High-strength antiswelling adhesive achieves both hemostasis and wound healing

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Journal of Pharmaceutical Analysis 2024年第6期14卷 781-784页

作者： xin Zhao Jinlong Luo Ying Huang Lei mu Jueying Chen Zhen Liang Zhanhai Yin Dake Chu Yong Han Baolin Guo State Key Laboratory for Mechanical Behavior of Materials Frontier Institute of Science and TechnologyXi'an Jiaotong UniversityXi'an710049China Department of Plastic Surgery Xijing HospitalAir Force Medical UniversityXi'an710032China Department of Orthopaedics The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of Gastroenterology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi'an Jiaotong UniversityXi'an710049China

Skin is one of the most vulnerable tissues,but there is a lack of injectable bioactive hydrogel dressings,which possess high strength,antiswelling capacity,and wet tissue adhesiveness,but also a rapid gelling process to enable rapid hemostasis,sutureless wound closure,and scarless healing of infected skin wounds[1e5].A new injectable,antibacterial,and multifunctional hydrogel dressings based on poly(citric acid-co-polyethylene glycol)-g-dopamine(PCPD)and amino-terminated Pluronic F127(APF)mi-celles loaded with astragaloside IV(AS)was developed for this pur-pose,as shown in Fig.1A[6].

关键词： healing wound stasis

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One-step controlled electrodeposition nickel sulfides heterointerfaces favoring the desorption of hydroxyl groups for efficient hydrogen generation

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Rare Metals 2024年第9期43卷 4377-4386页

作者： ru-Chun Li xin-Yue Zhang Ze-Yue Qu Feng-Yi Liu Quan-Qing Xu Zhao-Xia Hu Jing-Wei Li Mohamed-Nawfal Ghazzal Jin-Li Yu Faculty of Chemistry and Chemical Engineering Yunnan Normal University Foshan Gaoke Hechuang Technology Co. Ltd. School of Chemistry and Chemical Engineering Guangzhou University Universite′Paris-Saclay UMR 8000 CNRSInstitut de Chimie Physique Department of Chemistry City University of Hong Kong

The heterointerface engineering involving different components or phases represents a desirable strategy for enhancing the sluggish kinetics of hydrogen evolution reaction （HER）.However,constructing desired heterointerfaces and elucidating the reaction mechanisms on the interface remains a considerable *** this work,we propose a straightforward electrochemical synthesis strategy to prepare the nickel sulfide-based heterointerfaces for *** mechanism of electrochemical synthesis is revealed,wherein metal-thiourea species can be formed at the cathode potential and subsequently oxidized to nickel sulfides at the anode *** this mechanism,a range of nickel sulfides,including NiS,Ni3S2/NiS,Ni/Ni3S2and Ni3S2,have been successfully synthesized by tuning the potential range of cyclic *** these,the obtained Ni3S2/NiS@CC（CC:carbon cloth） exhibits the smallest overpotential of84 mV at 10 mA·cm-2and high *** calculations further reveal that the combination of NiS and Ni3S2induces electron redistribution at the interface,and thus the Volmer process is effectively promoted with faster water dissociation and OH desorption ***,the simplicity method coupled with a clear synthesis mechanism and outstanding HER performance highlights its promising potential for practical applications.

关键词： Electrochemical synthesis Heterointerfaces Hydrogen evolution reaction OH desorption kinetics

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Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography

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Journal of Geriatric Cardiology 2024年第4期21卷 431-442页

作者： Xian-Sai MENG Qing-Song WANG xin-Yan WANG Xu LU Yang mu Jing WANG Ting-Ting SONG Yun-Dai CHEN Tao CHEN Jun GUO Graduate School of Chinese PLA Medical College BeijingChina Senior Department of Cardiology the Sixth Med-ical CenterChinese PLA General HospitalBeijingChina

OBJECTIVE To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion(LAAO) guided by cardiac computed tomography angiography(CCTA).METHODS Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched(1:2). Each step of the LAAO procedure in the computed tomography(CT) guidance group(CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using *** A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years(P = 0.52), respectively. The procedure duration(45.6 ± 10.7 min vs. 58.8 ± 13.0 min,P < 0.001) and hospital stay(7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group(904.9 ± 348.0 m Gy vs.711.9 ± 211.2 m Gy, P = 0.002). There were no significant differences in periprocedural pericardial effusion(3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events(13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months *** CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.

关键词： anesthesia matched approach

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A deep learning-based global tropical cyclogenesis prediction model and its interpretability analysis

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Science China Earth Sciences 2024年

作者： Bin mu xin WANG Shijin YUAN Yuxuan CHEN Guansong WANG Bo QIN Guanbo ZHOU School of Software Engineering Tongji University Department of Atmospheric and Oceanic Sciences & Institute of Atmospheric Sciences Fudan University National Meteorological Center Shanghai Typhoon Institute China Meteorological Administration

Tropical cloud clusters (TCCs) can potentially develop into tropical cyclones (TCs),leading to significant casualties and economic *** prediction of tropical cyclogenesis (TCG) is crucial for early *** traditional deep learning methods applied to TCG prediction rely on predictors from a single time point,neglect the ocean-atmosphere interactions,and exhibit low model *** study proposes the Tropical Cyclogenesis Prediction-Net (TCGP-Net) based on the Swin Transformer,which leverages convolutional operations and attention mechanisms to encode spatiotemporal features and capture the temporal evolution of *** model incorporates the coupled ocean-atmosphere interactions,including multiple variables such as sea surface ***,causal inference and integrated gradients are employed to validate the effectiveness of the predictors and provide an interpretability analysis of the model’s decision-making *** model is trained using GridSat satellite data and ERA5 reanalysis *** results demonstrate that TCGP-Net achieves high accuracy and stability,with a detection rate of 97.9%and a false alarm rate of 2.2%for predicting TCG 24 hours in advance,significantly outperforming existing *** indicates that TCGP-Net is a reliable tool for tropical cyclogenesis prediction.

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Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress

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Journal of Integrative Medicine 2024年第4期22卷 493-502页

作者： Qian-zhuo Liu Hui Han xin-ru Fang Lu-yao Wang Dan Zhao Miao-zhu Yin Nian Zhang Peng-yu Jiang Zhi-hui Ji Li-min Wu Department of Neurology the First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031Anhui ProvinceChina Center for Reproduction and Genetics the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031Anhui ProvinceChina

Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for ***:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) ***:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) ***:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

关键词： Berberine Hepatolenticular degeneration Copper deposition Ferroptosis Endoplasmic reticulum stress

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Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan mu xin Zhang Dongquan Liang Jugao Fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Beijing 100730China Pepperdine University Graduate School of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central Laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively ***: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low ***: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(Pmutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

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Variation Characteristics of Root Traits of Different Alfalfa Cultivars under Saline-Alkaline Stress and their Relationship with Soil Environmental Factors

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Phyton-International Journal of Experimental Botany 2024年第1期93卷 29-43页

作者： Tian-Jiao Wei Guang Li Yan-ru Cui Jiao Xie xing-Ai Gao xing Teng xin-Ying Zhao Fa-Chun Guan Zheng-Wei Liang Northeast Agricultural Research Center of China Jilin Academy of Agricultural SciencesChangchun130033China Northeast Institute of Geography and Agroecology Chinese Academy of SciencesChangchun130102China

Soil salinization is the main factor that threatens the growth and development of plants and limits the increase of *** is of great significance to study the key soil environmental factors affecting plant root traits to reveal the adaptation strategies of plants to saline-alkaline-stressed soil *** this study,the root biomass,root morphological parameters and root mineral nutrient content of two alfalfa cultivars with different sensitivities to alkaline stress were analyzed with black soil as the control group and the mixed saline-alkaline soil with a ratio of 7:3 between black soil and saline-alkaline soil as the saline-alkaline treatment *** the same time,the correlation analysis of soil salinity indexes,soil nutrient indexes and the activities of key enzymes involved in soil carbon,nitrogen and phosphorus cycles was carried *** results showed that compared with the control group,the pH,EC,and urease(URE)of the soil surrounding the roots of two alfalfa cultivars were significantly increased,while soil total nitrogen(TN),total phosphorus(TP),organic carbon(SOC),andα-glucosidase activity(AGC)were significantly decreased under saline-alkaline *** was no significant difference in root biomass and root morphological parameters of saline-alkaline tolerant cultivar GN under saline-alkaline *** number of root tips(RT),root surface area(RS)and root volume(RV)of AG were reduced by 61.16%,44.54%,and 45.31%,respectively,compared with control *** ratios of K^(+)/Na^(+),Ca^(2+)/Na^(+)and Mg^(2+)/Na^(+)of GN were significantly higher than those of AG(p<0.05).The root fresh weight(RFW)and dry weight(RDW),root length(RL),RV and RT of alfalfa were positively regulated by soil SOC and TN,but negatively regulated by soil pH,EC,and URE(p<0.01).Root Ca^(2+)/Na+ratio was significantly positively correlated with soil TN,TP and SOC(p<0.01).The absorption of Mg and Ca ions in roots is significantly negatively regulated by soilβ-glucosidase ac

关键词： Saline-alkaline stress alfalfa root traits soil environmental factors correlation analysis

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