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Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

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Food Science and Human Wellness 2024年第4期13卷 1962-1973页

作者： Ishfaq Ahmed Suidong Ouyang Shengquan Wu Haochang Song Miaoyuan Zhang Renxing Luo Peishan Lu Jiaqi Deng Tingting Zheng Yanyan Wang Xinguang Liu Gonghua Huang Guangdong Provincial Key Laboratory of medical Molecular Diagnostics The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan 523808China Haide college Ocean University of ChinaLaoshan CampusQingdao 266100China School of medical Technology Guangdong Medical UniversityDongguan 523808China

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are *** this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western *** study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface *** digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 *** of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory *** knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

关键词： Ovalbumin Laccase Galactomannan Conformational structure Asthma

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Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

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Asian Journal of Andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-Ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo Yu-Tian Dai Fu-Biao Li Hao-Cheng Lin Zhi-Chao Zhang Department of Urology Peking University First HospitalBeijing 100000China Department of Urology Peking University Third HospitalBeijing 100191China Department of Urology Peking Union Medical College HospitalBeijing 100730China Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Departmentof Andrology Nanjing Drum Tower HospitalNanjing 210008China Department of Andrology The First Hospital of Jilin UniversityChangchun 130021China Andrology Center Department of UrologyPeking University First HospitalBeijing 100034China

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 ***-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and *** improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,*** Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,*** quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month ***-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

HyperArc performance in radiotherapy and its correlations with number and volume of multiple brain metastases

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Radiation Medicine and Protection 2024年第2期5卷 139-144页

作者： Hongtao Chen Zihuang Li Guixiang Liao Lijun Wang Xiaonian Deng Heli Zhong Department of Radiation Oncology Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen518020China

Objective:To assess the performance and advantages of HyperArc for radiotherapy of multiple brain metastases with dosimetric parameters with respect to coplanar volumetric modulated arc radiotherapy(c-VMAT),and characterize implicit correlations between tumor features and dosimetric ***:This retrospective study involved 40 patients with multiple brain metastases(4–16 tumors,12.8–240.8 cm3)who received simultaneous radiotherapy at the Department of Radiation Oncology,Shenzhen People's hospital from January 2019 to December *** HyperArc and c-VMAT plans were designed by the same and qualified physicist using the Eclipse system with Truebeam.A single isocenter and a 6 MV flattening filter-free(6FFF)photon beam were used for radiotherapy of multiple brain metastases in each *** parameters of tumors and organs at risk(OARs)were compared between HyperArc and c-VMAT ***-lations between tumor features(number and volume)and dosimetric parameters were revealed and ***,monitor units(MUs)of both plan types were recorded to assess rays utilization and delivery ***:Compared to c-VMAT plans,HyperArc plans achieved higher maximum dose(D_(max))(5.23%,t=7.87,P<0.01),but lower minimum dose(Dmin)(3.94%,t=-2.12,P=0.04)and mean dose(D_(mean))(1.05%,t=-3.29,P<0.01)for planning gross tumor volumes(PGTVs).The conformity index(CI),homogeneity index(HI),gradient index(GI)and R50%of PGTVs with HyperArc were better than those with c-VMAT,with the improve-ments of 20.78%,1.68%,19.83%and 36.20%,respectively(P<0.01).The dosimetric parameters of OARs were significantly improved in HyperArc plans compared to c-VMAT ***,the D_(max)and the D_(mean)to the brainstem decreased by 16.14%and 11.37%,*** D_(max)for eye_L decreased by 16.88%,for eye_R decreased by 11.67%,for optical nerve_L decreased by 12.56%,and for chiasm decreased by 18.12%.Few correlations were observed between the differences of CI/HI/GI

关键词： HyperArc Radiotherapy Multiple brain metastases Conformity

Recent progress in diagnostic imaging and therapeutics of osteosarcoma based on multifunctional nanoparticles

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Science China Chemistry 2024年第9期67卷 2864-2889页

作者： Xueke Yan Danmin Lin Dingyuan Yan Dong Wang Huifang Su Department of Orthopaedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Center for AIE Research College of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China

Osteosarcoma is one of the most common primary bone malignancies,mainly occurring in children and *** diagnosis imaging methods for osteosarcoma contain X-ray,computed tomography and magnetic resonance imaging,and traditional therapy protocols are surgical resection and ***,these strategies are complicated and *** imaging methods,despite their maturity,have drawbacks that prevent them from showing more *** is more,the prognosis for patients with osteosarcoma remains unsatisfactory due to side effects of chemotherapy,as well as incomplete surgical removal of the *** compensate for the shortcomings of traditional imaging and treatment strategies for osteosarcoma,various types of nanoparticles have been designed and synthesized to selectively target osteosarcoma cells without toxic side effects on healthy *** the same time,these nanoparticle-based technologies can integrate the imaging and treatment of *** review summarizes the application of nanotechnology in the imaging and treatment of osteosarcoma in recent years,and finally discusses the challenges and development prospects,aiming to provide ideas for future research.

关键词： osteosarcoma nanotechnology imaging diagnosis therapy

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Clinical observation of extraction-site incisional hernia after laparoscopic colorectal surgery

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 710-716页

作者： Bao-Hang Fan Ke-Li Zhong Li-Jin Zhu Zhao Chen Fang Li Wen-Fei Wu Second Clinical medical college of Jinan university Jinan UniversityShenzhen 518020Guangdong ProvinceChina Department of Gastrointestinal Surgery Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina Department of Radiation Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina

BACKGROUND Laparoscopic colorectal cancer surgery increases the risk of incisional hernia(IH)at the tumor extraction *** To investigate the incidence of IH at extraction sites following laparoscopic colo-rectal cancer surgery and identify the risk factors for IH *** This study retrospectively analyzed the data of 1614 patients who underwent la-paroscopic radical colorectal cancer surgery with tumor extraction through the abdominal wall at our center between January 2017 and December ***-rences in the incidence of postoperative IH at different extraction sites and the risk factors for IH incidence were *** Among the 1614 patients who underwent laparoscopic radical colorectal cancer surgery,303(18.8%),923(57.2%),171(10.6%),and 217(13.4%)tumors were ex-tracted through supraumbilical midline,infraumbilical midline,umbilical,and off-midline *** these,52 patients developed IH in the abdominal wall,with an incidence of 3.2%.The incidence of postoperative IH was significantly higher in the off-midline incision group(8.8%)than in the middle incision groups[the supraumbilical midline(2.6%),infraumbilical midline(2.2%),and umbilical incision(2.9%)groups](χ^(2)=24.985;P<0.05).Univariate analysis showed that IH occurrence was associated with age,obesity,sex,chronic cough,incision infection,and combined diabetes,anemia,and hypopro-teinemia(P<0.05).Similarly,multivariate analysis showed that off-midline incision,age,sex(female),obesity,incision infection,combined chronic cough,and hypoproteinemia were independent risk factors for IH at the site of laparoscopic colorectal cancer surgery(P<0.05).CONCLUSION The incidence of postoperative IH differs between extraction sites for laparoscopic colorectal cancer *** infraumbilical midline incision is associated with a lower hernia rate and is thus a suitable tumor extraction site.

关键词： Incisional hernia Laparoscopy Colorectal cancer Incision infection

RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2

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Science China Life Sciences 2024年第10期67卷 2186-2197页

作者： Lili Zhi Chaoqun Chen Ge Zhang Tian Huang Wenxia He Jinrui Zhang Dan Chen Jiayi Liu Jinyao Zhao Yangfan Qi Guiying Wang Wenjing Zhang Yang Wang Sino-US Research Center for Cancer Translational Medicine of the Second affiliated hospital of Dalian medical university & Institute of Cancer Stem Cell Dalian Medical University Department of Immunology College of Basic Medical SciencesDalian Medical University Institute of Cancer Stem Cell Dalian Medical University Department of Pathology the First Affiliated Hospital of Dalian Medical UniversityDalian Medical University Department of General Surgery the Second Hospital of Hebei Medical University The Second Department of General Surgery the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for Digestive System Carcinoma

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3'splice site(ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3′ ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target.

关键词： RBM25 colon cancer alternative splicing MNK2

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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the first affiliated hospital and Department of Cell Biology Zhejiang University School of Medicine Department of medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang university MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

Colorectal cancer’s burden attributable to a diet high in processed meat in the Belt and Road Initiative countries

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 182-196页

作者： Gu Liu Chang-Min Li Fei Xie Qi-Lai Li Liang-Yan Liao Wen-Jun Jiang Xiao-Pan Li Guan-Ming Lu Department of Gastrointestinal Surgery The First Affiliated HospitalJinan UniversityGuangzhou 510630Guangdong ProvinceChina Department of Gastrointestinal Surgery Chenzhou Third People’s HospitalChenzhou 423000Hunan ProvinceChina Department of Gastrointestinal Surgery Chenzhou First People’s Hospital and the First Affiliated Hospital of Xiangnan UniversityChenzhou423000 Hunan ProvinceChina Department of Breast and Thyroid Surgery the Affiliated Hospital of Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Department of Health Management Center Zhongshan HospitalShanghai Medical College of Fudan UniversityShanghai 200032China

BACKGROUND Colorectal cancer(CRC)plays a significant role in morbidity,mortality,and economic cost in the Belt and Road Initiative(“B and R”)*** addition,these countries have a substantial consumption of processed ***,the burden and trend of CRC in relation to the consumption of a diet high in processed meat(DHPM-CRC)in these“B and R”countries remain *** To analyze the burden and trend of DHPM-CRC in the“B and R”countries from 1990 to *** We used the 2019 Global Burden of Disease Study to collate information regarding the burden of *** and age-standardized rates(ASRs)of deaths along with the disability-adjusted life years(DALYs)were determined among the“B and R”countries in 1990 and *** joinpoint regression analysis,the average annual percent change(AAPC)was used to analyze the temporal trends of age-standardized DALYs rate(ASDALR)from 1990 to 2019 and in the final decade(2010–2019).RESULTS We found geographical differences in the burden of DHPM-CRC among“B and R”countries,with the three highest-ranking countries being the Russian Federation,China,and Ukraine in 1990,and China,the Russian Federation,and Poland in *** burden of DHPM-CRC generally increased in most member countries from 1990 to 2019(all P<0.05).The absolute number of deaths and DALYs in DHPM-CRC were 3151.15[95%uncertainty interval(UI)665.74-5696.64]and 83249.31(95%UI 15628.64-151956.31)in China in ***,the number of deaths(2627.57-2528.51)and DALYs(65867.39-55378.65)for DHPM-CRC in the Russian Federation has *** fastest increase in ASDALR for DHPM-CRC was observed in Vietnam,Southeast Asia,with an AAPC value of 3.90%[95%confidence interval(CI):3.63%-4.16%],whereas the fastest decline was observed in Kyrgyzstan,Central Asia,with an AAPC value of-2.05%(95%CI:-2.37%to-1.73%).A substantial upward trend in ASR of mortality,years lived with disability,years of life lost,and DALYs from DHPM-CRC changes in 1990-2019 and the final de

关键词： Belt and Road Initiative countries Colorectal cancer Burden of disease Dietary risk factors Processed meat Disability-adjusted life years Trend analysis

Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for Clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The first affiliated hospital of Guizhou university of Traditional Chinese Medicine Guiyang 550001PR China School of Clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite