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Engineering biomimetic nanosystem targeting multiple tumor radioresistance hallmarks for enhanced radiotherapy

Science China(Life Sciences) 2024年第7期67卷 1398-1412页

作者： Shuxiang Wang Hongmei Cao Cui-Cui Zhao Qian Wang Dianyu Wang Jinjian Liu Lijun Yang Jianfeng Liu State Key Laboratory of Advanced medical Materials and devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear MedicineKey Laboratory of Radiopharmacokinetics for Innovative DrugsTianjin Institutes of Health ScienceInstitute of Radiation MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Tianjin medical University Cancer institute and Hospital National Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy(Tianjin)Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China

Tumor cells establish a robust self-defense system characterized by hypoxia,antioxidant overexpression,DNA damage repair,and so forth to resist *** one of these features is insufficient to overcome radioresistance due to the feedback mechanisms initiated by tumor cells under ***,we herein developed an engineering biomimetic nanosystem(M@HHPt)masked with tumor cell membranes and loaded with a hybridized protein-based nanoparticle carrying oxygens(O_(2))and cisplatin prodrugs(Pt(Ⅳ))to target multiple tumor radioresistance hallmarks for enhanced *** administration,M@HHPt actively targeted and smoothly accumulated in tumor cells by virtue of its innate homing abilities to realize efficient co-delivery of O_(2)and Pt(Ⅳ).O_(2)introduction induced hypoxia alleviation cooperated with Pt(Ⅳ)reduction caused glutathione consumption greatly amplified radiotherapy-ignited cellular oxidative ***,the released cisplatin effectively hindered DNA damage repair by crosslinking with radiotherapy-produced DNA ***,M@HHPt-sensitized radiotherapy significantly suppressed the proliferation of lung cancer H1975 cells with an extremely high sensitizer enhancement ratio of 1.91 and the progression of H1975 tumor models with an excellent tumor inhibition rate of 94.7%.Overall,this work provided a feasible strategy for tumor radiosensitization by overcoming multiple radioresistance mechanisms.

关键词： biomimetic nanosystem hypoxia alleviation glutathione consumption oxidative stress amplification DNA damage fixation radiosensitization

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Superparamagnetic iron oxide nanoparticle regulates microbiota-gut-inner ear axis for hearing protection

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National Science Review 2024年第6期11卷 273-284页

作者： Zhanhang Guo Yunhao Wu Bo Chen Mengdie Kong Peng Xie Yan Li Dongfang Liu Renjie Chai Ning Gu Jiangsu Key Laboratory for Biomaterials and devices School of Biological Science and Medical EngineeringSoutheast University medical Science and Technology Innovation Center Shandong First Medical University &Shandong Academy of Medical Sciences State Key Laboratory of Digital medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast University institute of Materials Science and devices School of Materials Science and Engineering Suzhou University of Science and Technology Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging &Interventional Radiology & Vascular Surgery Department of Radiology Medical School Zhongda Hospital Southeast University Co-Innovation Center of Neuroregeneration Nantong University School of medical Technology Institute of Engineering MedicineBeijing Institute of Technology Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of China institute for Stem Cell and Regeneration Chinese Academy of Sciences Southeast university Shenzhen research institute Cardiovascular Disease Research Center Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Medical School Nanjing University

Noise-induced hearing loss(NIHL) is a highly prevalent form of sensorineural hearing damage that has significant negative effects on individuals of all ages and there are no effective drugs approved by the US Food and Drug Administration. In this study, we unveil the potential of superparamagnetic iron oxide nanoparticle assembly(SPIOCA) to reshape the dysbiosis of gut microbiota for treating NIHL. This modulation inhibits intestinal inflammation and oxidative stress responses, protecting the integrity of the intestinal barrier. Consequently, it reduces the transportation of pathogens and inflammatory factors from the bloodstream to the cochlea. Additionally, gut microbiota-modulated SPIOCA-induced metabolic reprogramming in the gut–inner ear axis mainly depends on the regulation of the sphingolipid metabolic pathway, which further contributes to the restoration of hearing function. Our study confirms the role of the microbiota–gut–inner ear axis in NIHL and provides a novel alternative for the treatment of NIHL and other microbiota dysbiosis-related diseases.

关键词： superparamagnetic iron oxide nanoparticle hearing loss gut microbiota inflammation sphingolipid metabolism microbiota–gut–inner ear axis

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Association of Human Whole-blood NAD+Levels with Nabothian Cyst

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Biomedical and Environmental Sciences 2024年第5期37卷 471-478页

作者： XU Ling WANG Yue Xuan WANG Wei FAN Xue CHEN Xue Yu ZHOU Tian Yun LIU Yu He YU Ye YANG Fan JU Zhen Yu ZHOU Yong WANG Deng Liang Clinical Research institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China NHC Key Lab of Reproduction Regulation Shanghai Engineering Research Center of Reproductive Health Drugs and DevicesShanghai Institute for Biomedical and Pharmaceutical TechnologiesShanghai 200237China Department of Applied Statistics Johannes Kepler University LinzLinz 4040Austria Hematology Center Beijing Key Laboratory of Pediatric Hematology OncologyNational Key Discipline of Pediatrics(Capital Medical University)Key Laboratory of Major Diseases in ChildrenMinistry of EducationBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Biostatistics School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012ShandongChina Clinical Medicine School of Basic MedicineShanghai Medical College Fudan UniversityShanghai 200032China Department of Biochemistry and Molecular Biology Hengyang Medical SchoolUniversity of South ChinaHengyang 421001HunanChina Administrative Office Total Quality Management OfficeTotal Quality Management InstituteShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China The First Affiliated Hospital of Jinan University Institute of Aging and Regenerative MedicineJinan UniversityJinan 510632GuangzhouChina Department of Scientific Research The First Affiliated Hospital of Huzhou UniversityHuzhou 313000ZhejiangChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated HospitalFujian Medical UniversityFuzhou 350209FujianChina Fujian Provincial institutes of Brain Disorders and Brain Sciences The First Affiliated HospitalFujian Medical UniversityFuzhou 350005FujianChina Fujian Provincial Clinical Research Center for Neurological

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian *** study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese *** Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian *** The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/*** cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,*** total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)*** compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian *** risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/***:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.

关键词： Nicotinamide adenine dinucleotide Nabothian cyst Female Risk factor

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The Globalization of Traditional Medicines: Perspectives Related to the European Union Regulatory Environment

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Engineering 2019年第1期5卷 22-31页

作者： Werner Knoess Jacqueline Wiesner federal institute for drugs and medical devices Bonn 53175 Germany

In the Member States of the European Union (EU), a harmonized legislation on medicinal products has been enforced, which specifically defines herbal medicinal products and traditional herbal medicinal products. The scope was to create a regulatory environment that takes into account the particular characteristics of herbal medicinal products. The harmonization of standards is intended to harmonize assessment and facilitate access to the market in different Member States. The standards defined by the EU herbal monographs of the Committee on Herbal Medicinal Products (HMPC) and the quality requirements laid down in the European Pharmacopoeia represent an excellent model of multinational harmonization of the regulatory environment for herbal and traditional medicines. It has also been demonstrated that this framework is at least partially applicable for herbal and traditional medicines from traditional Chinese medicine (TCM) to gain access to the EU market. Moreover, the HMPC provides specific guidance documents and pilot projects on monographs on the safety and efficacy of Chinese herbal drugs. In the European Pharmacopoeia, the number of quality monographs of herbal drugs with an origin in TCM is continuously growing. These developments indicate that globalization of traditional medicines is an ongoing process. Communication and cooperation between regulators, the scientific community, and interested stakeholders will set the stage for the convergence of diverse regulatory environments. This will contribute to worldwide availability of traditional medicines based on appropriate standards.

关键词： Traditional medicine Traditional Chinese medicine Committee on Herbal Medicinal Products Herbal medicines Traditional medicines Regulation Globalization

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Guidelines for application of high-content screening in traditional Chinese medicine:concept,equipment,and troubleshooting

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Acupuncture and Herbal Medicine 2024年第1期4卷 1-15页

作者： Xuechun Chen Lu Li Mingxu Zhang Jian Yang ChunMing Lyu Yizhou Xu Yang Yang Yi Wang Pharmaceutical Informatics institute College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina Department of Cardiology Hangzhou First People’s HospitalHangzhouChina National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxingChina Molecular devices Shanghai Corporation ShanghaiChina National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Science and Technology Experiment Center Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Innovative Anticancer drugs Ministry of Educationhangzhou China

High-content screening(HCS)technology combines automated high-speed imaging hardware and single-cell quantitative *** can greatly accelerate data acquisition in cellular fluorescence imaging and is a powerful research technique in traditional Chinese medicine(TCM).An increasing number of laboratories and platforms,including TCM laboratories,have begun utilizing HCS ***,this technology is still in its infancy in TCM research and there is a lack of sufficient experience with the associated concepts,instrument configurations,and analysis *** improve the understanding of HCS among researchers in the field of TCM,this paper summarizes the concept of HCS,software and hardware configuration,the overall research process,as well as common problems and related solutions of HCS in TCM research based on our team’s previous research experience,providing several research examples and an outlook on future perspectives,aiming to provide a technical guide for HCS in TCM research.

关键词： High-content imaging High-content screening Traditional Chinese medicine

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Comparison of Granules for Prescription and Classical Decoctions by High-performance Thin-layer Chromatography-fingerprint Analysis

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World Journal of Traditional Chinese Medicine 2018年第1期4卷 1-7页

作者： Katharina Schiller Jorg Heilmann Detlef Manns Gerhard Franz Department of Pharmaceutical Biology Institute of PharmacyUniversity of Regensburg federal institute for drugs and Medicinal devices(BfArM)

Objective: The so?called granules for prescription have been developed about 20 years ago as a new form of modernizing and simplification of the classical decoction common in Traditional Chinese Medicine (TCM) practice. Due to actual problems in Germany/Europe, which are caused by the lack of quality monographs and judicial classification of granules for prescription, the aim of the study was a comparison of the chemical composition of commercial granules versus decoctions. Taking an example, decoctions, commercial granules, and organic extracts of two well?established TCM herbal drugs, Scrophulariae Radix and Xanthii Fructus, were examined in their specific composition. Methods: Using high?performance thin?layer chromatography (HPTLC) for fingerprint analysis of different batches of herbal drugs and samples from various suppliers of Xanthii Fructus and Scrophulariae Radix were critically examined. The decoctions were prepared according to traditional rules, while the granules were dissolved in water in accordance with actual regulations. Furthermore, organic extracts of the plant material were examined and compared with aqueous extracts. Results: It could be demonstrated, that in some cases, there are remarkable differences in the specific composition between granules from different suppliers, the classical aqueous decoction and the organic extract used for the HPTLC fingerprinting. On the other hand, few examples exist for good comparability of decoctions and commercial granules. Conclusion: After critical evaluation of the above results, it can be questioned, if there is a so?called phytoequivalence between decoctions and commercial granules for prescription used in TCM practice.

关键词： Granules for prescription phytoequivalence quality control quality monographs Scrophulariae Radix Xanthii Fructus

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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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Animal Models and Experimental Medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina National Center of Stomatology BeijingChina National Clinical Research Center for Oral Diseases BeijingChina Beijing Key Laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina Peking University International Cancer institute Peking University Health Science CenterPeking UniversityBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina National Engineering Research Center of Oral Biomaterials and Digital medical devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone ***,current anti-resorptive drugs carry a risk of various *** deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression *** study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone ***:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary ***-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also *** underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),***:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of *** BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting ***:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

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Pubertal exposure to bisphenol A affects the reproduction of male mice and sex ratio of offspring

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Journal of Reproduction and Contraception 2015年第1期26卷 14-21页

作者： Yu-hua LI Fei DUAN Fen YANG Xiao-yu ZHOU Hong-jie PAN Yang LI Runsheng LI Department of Pathophysiology Norman Bethune College of Medical Sciences Jilin University National Population and Family Planning Key Laboratory of Contraceptives drugs & devices Shanghai Institute of Planned Parenthood Research

Objective To study the effects of pubertal exposure to bisphenol A （BPA） on the reproduction of male mice in adulthood and subsequent generation mice. Methods Male mice aged 21 d were exposed to BPA at a dose of 50 mg/kg per day for 7 d by intraperitoneal injection. Sperm count, sperm deformity rate and testis histology were evaluated 35 d after exposure. Male fertility index and newborns were further observed by mating with the normal female mice. Results The epididymal sperm number was decreased by 20.6% in BPA exposure group compared with the control （P〈O. 01）. Sperm deformity rate in BPA group was increased by 9.65% compared with the control （P〈O.05）. Testis seminiferous tubules were abnormal with sloughing of germ cells; BPA exposure had no significant effects on the fertility of male mice in adulthood; sex ratio of male to female offspring was increased. Conclusion Pubertal exposure to BPA disrupted spermatogenesis in adult mice, and the proportion of male offspring was increased compared with the control.

关键词： bisphenol A (BPA) spermatogensis sex ratio

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ICSI treatment of severe male infertility can achieve prospective embryo quality compared with IVF of fertile donor sperm on sibling oocytes

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Asian Journal of Andrology 2015年第5期17卷 845-849,I0011页

作者： Ju-Fen Zheng Xiao-Bao Chen Lei-Wen Zhao Min-Zhi Gao Jie Peng Xian-Qin Qu Hui-Juan Shi Xing-Liang Jin China National Population and Family Planning Key Laboratory of Contraceptive drugs and devices SIPPR Shanghai China Department of Reproductive Medicine Renji Hospital Shanghai Jiao Tong University Shanghai China Sydney Centre for Regenerative and Developmental Medicine Kolling Institute for Medical Research Sydney Medical School University of Sydney St. Leonards NSW Australia

Azoospermia, cryptozoospermia and necrospermia can markedly decrease the ability of males to achieve pregnancy in fertile females. However, patients with these severe conditions still have the option to be treated by intracytoplasmic sperm injection （ICSI） to become biological fathers. This study analyzed the fertilization ability and the developmental viabilities of the derived embryos after ICSI treatment of the sperm from these patients compared with in vitro fertilization （IVF） treatment of the proven-fertile donor sperm on sibling oocytes as a control. On the day of oocyte retrieval, the number of sperm suitable for ICSI collected from two ejaculates or testicular sperm extraction was lower than the oocytes, and therefore, excess sibling oocytes were treated by IVF with donor sperm. From 72 couples （73 cycles）, 1117 metaphase Ⅱ oocytes were divided into 512 for ICSI and 605 for IVF. Compared with the control, husbands＇ sperm produced a lower fertilization rate in nonobstructive azoospermia （65.4% vs 83.2%; P〈 0.001）, crytozoospermia （68.8% vs 75.5%; P〈 0.05） and necrospermia （65.0% vs 85.2%; P〈 0.05）. The zygotes derived in nonobstructive azoospermia had a lower cleavage rate （96.4% vs 99.4%; P 〈 0.05）, but the rate of resultant good-quality embryos was not different. Analysis of the rates of cleaved and good-quality embryos in crytozoospermia and necrospermia did not exhibit a significant difference from the control. In conclusion, although the sperm from severe male infertility reduced the fertilization ability, the derived embryos had potential developmental viabilities that might be predictive for the expected clinical outcomes.

关键词： azoospermia cryptozoospermia embryonic development fertilization infertility necrospermia sibling oocytes

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Couple＇s infertility in relation to male smoking in a Chinese rural area

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Asian Journal of Andrology 2017年第3期19卷 311-315页

作者： Fen Yang Lin Li Jian-Ping Chen Xiao-Qin Liu Chun-Li Zhong Yuan Yang Yan-Feng Ren Wei Yuan Hong Liang Mao-Hua Miao Department of Reproductive Epidemiology and Social Science National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices Shanghai Institute of Planned Parenthood Research Shanghai China Shanghai medical College Fudan University Shanghai China Guizhou Family Planning Research institute Guiyang China Department of Health Statistics School of Public Health and Management Weifang Medical College Weifang China

Smoking is a well-known risk factor of reproductive health. However, the effect of paternal smoking on fertility has been less extensively examined. We conducted a cross-sectional study in a mountainous area of South-West China to assess the effect of male smoking on couples＇ fertility. A total of 8200 couples aged 18-49 years in the study area were invited to participate in the study. An in-person interview was performed to collect demographic characteristics of the couples, and husbands＇ life style factors including smoking and drinking habits. Information on time to pregnancy （TTP） was collected retrospectively. Infertility was defined as failure to achieve clinical pregnancy after regular unprotected intercourse for 〉12 months. Logistic regression model was used to estimate the association between male smoking and infertility. A total of 7025 couples were included in the final analysis. After adjusting for potential confounders, the couples were more likely to suffer from infertility if the husbands smoked （adjusted odds ratio [aOR] =1.28, 95% CI： 1.08-1.52） before the first pregnancy. After the analyses were performed according to husbands＇ smoking duration, an increased risk started at a relatively longer smoking duration of 5-10 years （aOR = 1.58, 95% CI. 1.26-1.99） and a stronger association （aOR = 3.34, 95% CI. 2.45-4.56） was observed in the group of 〉10 years. Similar patterns were found for the number of cigarettes smoked per day and the total amount of cigarettes smoked. From our findings, we conclude that male smoking may have an adverse impact on couples＇ infertility.

关键词： cross-sectional study infertility male smoking

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