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Gradient tumor microenvironment-promoted penetrating micelles for hypoxia relief and immunosuppression reversion in pancreatic cancer treatment

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ACTA BIOMATERIALIA 2023年第1期167卷 387-400页

作者： Luo, Yifan Li, Chao Zhang, Yiwen Liu, Peixin Chen, Hongyi Zhao, Zhenhao Wang, Yu Zhou, Zheng song, Haolin Su, Boyu Li, Chufeng Li, xuwen Zhang, Tongyu You, Haoyu Wu, Yuxing Tian, Zonghua Zhang, Shilin Guo, Yun Fan, Hongrui Chen, Qinjun Jiang, Chen Sun, Tao Fudan Univ Minhang Hosp Sch Pharm Dept Pharmaceut Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is the main block for the penetration of chemotherapy. In the tumor microenvironment, a dense matrix composed of fibrin is formed on the exterior, while the interior is featured by high reduction, hypoxia and low pH. How to match the special microenvironment to on-demand drug release is the key to improve chemotherapeutic efficacy. Herein, a microenvironment-responsive micellar system is developed to deepen tumoral penetration. Briefly, the conjugation of a fibrin-targeting peptide to PEG-poly amino acid has been utilized to achieve accumulation of micelles in the tumor stroma. By modification of micelles with hypoxia-reducible nitroimidazole which becomes protonated under acidic conditions, their surface charge is more positive, facilitating deeper penetration into tumors. Paclitaxel was loaded onto the micelles via a disulfide bond to enable glutathione (GSH)-responsive release. Therefore, the immunosuppressive microenvironment is relived through the alleviation of hypoxia and depletion of GSH. Hopefully, this work could establish paradigms by designing sophisticated drug-delivery systems to tactfully employ and retroact the tamed tumoral microenvironment to improve the therapeutic efficacy based on understanding the multiple hallmarks and learning the mutual regulation.

关键词： Pancreatic cancer Penetration Nitroimidazole Tumor hypoxia Gemcitabine

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黄色的蓝藻水华

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湖泊科学 2022年第4期34卷 1384-1391页

作者：宋挺张军毅李旭文朱家民胡俊江苏省无锡环境监测中心无锡214121 江苏省环境监测中心南京210008 上海市青浦区环境监测站上海201799

随着全球气候变化和水体富营养化,在过去几十年中蓝藻水华改变了全球的淡水生态系统.蓝藻因独有的藻蓝蛋白而大多呈现蓝绿色,因此其水华也常称为蓝绿藻水华.然而随着蓝藻水华关注度的不断提升,尤其是监测和研究的不断深入,经常在水体中... 详细信息

随着全球气候变化和水体富营养化,在过去几十年中蓝藻水华改变了全球的淡水生态系统.蓝藻因独有的藻蓝蛋白而大多呈现蓝绿色,因此其水华也常称为蓝绿藻水华.然而随着蓝藻水华关注度的不断提升,尤其是监测和研究的不断深入,经常在水体中发现蓝藻水华出现黄化的现象.例如,太湖出现的黄色蓝藻水华,冬春季以长孢藻属(Dolichospermum)水华为主,夏秋季以微囊藻属(Microcystis)水华为主.即使外观看起来是蓝绿色的蓝藻水华,但仔细观察形成蓝藻水华的群体颗粒,也有部分呈现黄色,反之亦然.实际上,鉴于色素组成的差异性,也许水体中就没有两个颜色完全一致的蓝藻群体颗粒.目前对于黄色的蓝藻水华及其形成机理,国内外鲜有报道和研究.光照和氮限制被认为是最有可能的原因.在关注蓝藻水华黄化的同时,更应该关注和研究这些颜色变化给蓝藻水华及水环境所带来的风险和挑战,尤其是对水生态管理工作的启发和意义.

关键词：蓝藻水华黄色叶绿素类胡萝卜素藻胆蛋白

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Gestational diabetes mellitus prediction model: A risk factors analysis of pregnant women with gestational diabetes mellitus but have normal oral glucose tolerance test results in the second trimester of pregnancy

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TECHNOLOGY AND HEALTH CARE 2021年第1_suppl期29卷 S57-S63页

作者： Lu, Jiayu Zhang, song Jiang, Hongqing Yang, Lin Hao, Dongmei Yang, Yimin Li, xuwen Chen, Aiqing Shao, Jing Liu, Xiaohong Beijing Univ Technol Fac Environm & Life Sci Beijing Int Base Sci & Technol Cooperat Intelligent Physiol Measurement & Clin Translat Beijing 100124 Peoples R China Haidian Maternal & Children Hlth Hosp Beijing 100080 Peoples R China Beijing Yes Med Devices Co Ltd Beijing 100152 Peoples R China

BACKGROUND: Oral glucose tolerance test (OGTT) is a standard for the diagnosis of gestational diabetes mellitus (GDM). However, clinically, some cases with normal results were diagnosed as GDM in the third trimester. OBJECTIVE: To establish a risk model based on energy metabolism, epidemiology, and biochemistry that could predict the GDM pregnant women with normal OGTT results in the second trimester. METHODS: Qualitative and quantitative data were analyzed to find out the risk factors, and the binary logistic backward LR regression was used to establish the prediction model of each factor and comprehensive factor, respectively. RESULTS: The risk factors including the rest energy expenditure per kilogram of body weight, oxygen consumption per kilogram of body weight, if more than the weight gain criteria of the Institute of Medicine, the increase of body mass index between the second trimester and pre-pregnancy, and fasting blood glucose. By comparison, the comprehensive model had the best prediction performance, indicating that 85% of high-risk individuals were correctly classified. CONCLUSION: Energy metabolism, epidemiology, and biochemistry had better recognition ability for the GDM pregnant women with normal OGTT results in the second trimester. The addition of metabolic factors in the second trimester also improved the overall prediction performance.

关键词： Prediction model gestational diabetes mellitus rest energy metabolism

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Transcytosis Mediated Deep Tumor Penetration for Enhanced Chemotherapy and Immune Activation of Pancreatic Cancer

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ADVANCED FUNCTIONAL MATERIALS 2023年第28期33卷

作者： Chen, Hongyi song, Haolin Luo, Yifan Li, Chufeng Wang, Yu Liu, Jie Luo, Feifei Fan, Hongrui Li, xuwen Sun, Tao Jiang, Chen Fudan Univ Sch Pharm Dept Pharmaceut Key Lab Smart Drug DeliveryState Key Lab Med Neur Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China Fudan Univ Huashan Hosp Dept Digest Dis Shanghai 200040 Peoples R China

The hyperproliferative tumor stroma of pancreatic ductal adenocarcinoma (PDAC) severely limits drug permeation and constructs an immunosuppressive microenvironment, causing resistance to chemotherapy and immunotherapy. Traditional nanomedicine mainly focuses on manipulating nanoparticles' particle size or electrical characteristics to penetrate deep PDAC through the paracellular pathway, but the transcellular pathway is often ignored. Therefore, a versatile drug-polymer conjugate PODEA-Gem-HMI is prepared and assembled into nanoparticles for the codelivery of chemotherapy drug gemcitabine and focal adhesion kinase (FAK) inhibitor defactinib. While sensing the mild acidity in the tumor microenvironment, the nanoparticle will disintegrate and release defactinib to modulate the tumor stroma. The PODEA block of the conjugate can bind with cell membranes reversibly and trigger adsorption-mediated transcytosis (AMT) for promoted tumor penetration and cellular uptake. The internalized conjugates will release gemcitabine responding to the overexpressed glutathione (GSH) for enhanced chemotherapy, and PHMI can condensate the STING monomers for prolonged spontaneous immune stimulation.

关键词： sting activation stroma modulation transcytosis tumor penetration

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Combining ¹H-NMR-based metabonomics and network pharmacology to dissect the mechanism of antidepression effect of Milletia speciosa Champ on mouse with chronic unpredictable mild stress-induced depression

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JOURNAL OF PHARMACY AND PHARMACOLOGY 2021年第7期73卷 881-892页

作者： Su, Zhiheng Ruan, Junxiang Liu, Xi Zheng, Hua Ruan, Jingzhou Lu, Yuying Cheng, Bang Wu, Fang Wu, Jinxia Liu, xuwen song, Fangming Chen, Zhaoni song, Hui Liang, Yonghong Guo, Hongwei Guangxi Med Univ Pharmaceut Coll Nanning 530021 Peoples R China Guangxi Yuhualing Technol Dev Co LTD Nanning Peoples R China Guangxi Med Univ Life Sci Inst Nanning Peoples R China Peoples Hosp Guangxi Zhuang Autonomous Reg Dept Pharm Nanning Peoples R China

Objectives Milletia speciosa Champ (MS), a traditional Chinese medicine, has the abilities of antistress, antifatigue, anti-oxidation and so on. In our previous study, MS was found to antidepression while the underlying mechanism of which needs further elucidation. Methods Here, a proton nuclear magnetic resonance (H-1-NMR)-based metabonomics combined network pharmacology research approach was performed to investigate the antidepressive mechanism of MS act on mouse with chronic unpredictable mild stress-induced depression. Key findings Results showed that MS could alleviate the ethology of depression (including sucrose preference degree, crossing lattice numbers and stand-up times) and disordered biochemical parameters (5-hydroxytryptamine, norepinephrine and brain-derived neurotrophic factor). Metabonomics study and network pharmacology analysis showed that MS might improve depression through synergistically regulating five targets including Maoa, Maob, Ache, Ido1 and Comt, and three metabolic pathways such as tryptophan metabolism, synthesis of neurotransmitter and phospholipid metabolism. Conclusions This study for the first time preliminary clarified the potential antidepressive mechanism of MS and provided theoretical basis for developing MS into novel effective antidepressant.

关键词： metabonomics H-1-NMR network pharmacology depression chronic unpredictable mild stress Milletia speciosa Champ

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FETAL TYPE CLASSIFICATION BASED ON FETAL ELECTROCARDIOGRAPH IN NON-STRESS TESTS

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JOURNAL OF MECHANICS IN MEDICINE AND BIOLOGY 2021年第9期21卷 2140052-2140052页

作者： Liu, Jianli Yang, Yimin Zhang, song Li, xuwen Yang, Lin Hao, Dongmei Beijing Univ Technol Fac Environm & Life Beijing Int Sci & Technol Cooperat Base Intellige Beijing 100024 Peoples R China

Electronic fetal heart rate (FHR) monitoring is a technical means to evaluate the state of the fetus in the uterus by monitoring FHR. The main purpose is to detect intrauterine hypoxia and take corresponding medical measures timely. Because the fetus sleeps quietly for up to 1 hour sometimes, ultrasound Doppler is not easy to continuously detect for a long time. The electronic fetal monitor obtains the fetal heart rate, which not only improves the accuracy and comfort, but also the convenient implementation of long-term monitoring. It is beneficial to reduce perinatal fetal morbidity and mortality. This study used maternal-fetal Holter monitor which is based on the technology of fetal electrocardiograph (FECG) to collect the FHR, and then design algorithm to extract the baseline FHR, acceleration, variation, sleep-wake cycle and nonlinear parameters. There were significant differences in the 22 parameters between the normal and the suspicious group. Using the 22 characteristic parameters, the support vector machine was used to classify the normal and the suspected group of fetuses. 80% of the data was used to train a classification model. The remaining 20% of the data was used as a test set and its accuracy reached 93.75%.

关键词： Fetal Holter monitor fetal heart rate support vector machine

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医疗美容纠纷司法鉴定若干问题的研究

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中国卫生法制 2023年第4期31卷 26-30,39页

作者：宋健文刘斌周旭文广东司法警官职业学院广州510520 广东正理法医临床司法鉴定所广东揭阳市522000

当前医疗美容行业蓬勃发展,但由于相关法律法规不完善等问题,医疗美容纠纷频发。医疗美容造成损害后果而引发纠纷可以提起医疗损害责任纠纷诉讼。医疗损害鉴定意见作为科学证据,为医疗美容纠纷解决提供技术支持。然而,目前医疗损害鉴定... 详细信息

当前医疗美容行业蓬勃发展,但由于相关法律法规不完善等问题,医疗美容纠纷频发。医疗美容造成损害后果而引发纠纷可以提起医疗损害责任纠纷诉讼。医疗损害鉴定意见作为科学证据,为医疗美容纠纷解决提供技术支持。然而,目前医疗损害鉴定尚未建立系统的理论体系,也缺乏规范的鉴定程序,作为新兴行业的医疗美容,相关研究几乎空白。根据医疗美容的特点,结合相关案例及文献,围绕鉴定制度与管理、技术鉴定中常见的几个问题进行探讨,以期为鉴定实践提供参考。

关键词：医疗美容医疗损害鉴定医疗纠纷诊疗义务同行评议

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Establishment of a personalized fetal growth curve model

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TECHNOLOGY AND HEALTH CARE 2021年第1_suppl期29卷 S311-S317页

作者： Bao, Xinyu Wang, Yan Zhang, song Yang, Lin Liu, Guoli Yang, Yimin Li, xuwen Hao, Dongmei Chen, Aiqing Liu, Xiaohong Shao, Jing Beijing Univ Technol Fac Environm & Life Sci Beijing 100124 Peoples R China Beijing Int Sci & Technol Cooperat Base Intellige Beijing 100124 Peoples R China Peking Univ Peoples Hosp Beijing 100044 Peoples R China Beijing Yes Med Devices Co Ltd Beijing 100152 Peoples R China

BACKGROUND: Fetal weight is one of the important indicators for judging whether fetal growth and development are normal. Fetal weight exceeding the normal range may lead to poor delivery outcomes. OBJECTIVE: We aimed to establish a personalized fetal growth curve in order to effectively monitor fetal growth during pregnancy. Fetal weight can be monitored while fetal growth and development are assessed. METHODS: This study retrospectively analyzed the birth weight and ultrasound database of 3,093 newborns delivered at normal term. The personalized fetal growth curve model was generated based on the birth weight formula established by Gardosi combined with the proportional weight equation. RESULTS: (1) The average birth weight of the single fetus at normal term was 3,457g. (2) According to the regression results of the proportion of fetal weight in full-term pregnancy and gestational week, the proportional weight equation is Weight% = 500.9 + 51.60GA + 1.727GA(2) 0.01718GA(3) (GA is gestational week), R-2 is 98%, P < 0.001. CONCLUSIONS: In this study, the normal birth weight of newborns and normal range of fetal weight can be estimated by using the personalized fetal growth curve model.

关键词： Fetal weight fetal growth curve birth weight proportional weight equation normal range

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微生物燃料电池工作原理及产电性能提升策略

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环境工程技术学报 2024年第2期14卷 699-709页

作者：蒋进元张月何绪文谭伟宋浩洋石冬妮赵洪兵中国环境科学研究院环境污染控制工程技术研究中心中国矿业大学(北京)化学与环境工程学院四川省广元生态环境监测中心站

微生物燃料电池(MFC)是一种解决其他能源在环境方面不足的新技术,目前低能量输出是MFC实际应用的关键瓶颈。基于MFC工作原理,提出微生物活性差、电子迁移阻力、质子传输阻力及阴极还原反应缓慢是MFC能量输出的限制因素,并从以下5个方面... 详细信息

微生物燃料电池(MFC)是一种解决其他能源在环境方面不足的新技术,目前低能量输出是MFC实际应用的关键瓶颈。基于MFC工作原理,提出微生物活性差、电子迁移阻力、质子传输阻力及阴极还原反应缓慢是MFC能量输出的限制因素,并从以下5个方面综述了提升MFC产电性能策略:调节pH和选择最佳盐度,加强微生物代谢活性;改性阳极材料,降低电子迁移阻力;增强电解液电导率、优化隔膜材料及缩短电极间距减小质子传输阻力;制备高效阴极催化剂和选择优异电子受体加快阴极还原反应速率;改进MFC反应器构型,提高整体产电性能。未来,可在合成新型阴极催化剂、降低膜污染、优化微生物生长环境、制备优异的电极材料和改进MFC反应器配置5个方面开展重点研究。

关键词：微生物燃料电池(MFC) 产电性能输出功率微生物活性策略

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Fetal growth prediction: Establishing fetal growth prediction curves in the second trimester

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TECHNOLOGY AND HEALTH CARE 2021年第1_suppl期29卷 S345-S350页

作者： Wang, Yan Bao, Xinyu Zhang, song Yang, Lin Liu, Guoli Yang, Yimin Li, xuwen Hao, Dongmei Chen, Aiqing Liu, Xiaohong Shao, Jing Peking Univ Peoples Hosp Beijing 100044 Peoples R China Beijing Univ Technol Fac Environm & Life Sci Beijing 100124 Peoples R China Beijing Int Sci & Technol Cooperat Base Intellige Beijing 100124 Peoples R China Beijing Yes Med Devices Co Ltd Beijing 100152 Peoples R China

BACKGROUND: Monitoring fetal weight during pregnancy has a guiding role in prenatal care. OBJECTIVE: To establish a personalized fetal growth curve for effectively monitoring fetal growth during pregnancy. METHODS: (1) This study retrospectively analyzed the birth weight database of 2,474 singleton newborns delivered normally at term. The personalized fetal growth curve model was formed by combining the estimating birth weight of newborns with the proportional weight formula. (2) Multiple linear stepwise regression method was used to estimate the birth weight of newborns. RESULTS: (1) Delivery gestational age, weight at first visit, maternal height, pre-pregnancy body mass index, fetal sex, parity had significant effects on birth weight. Based on these parameters, the formula for calculating term optimal weight was obtained (R-2 = 22.8%, P < 0.001). (2) The personalized fetal growth curve was obtained according to the epidemiological factors input model of each pregnant woman. CONCLUSIONS: A model of personalized fetal growth curve can be established, and be used to evaluate fetal growth and development through estimated fetal weight monitoring.

关键词： Fetal weight growth charts personal health services

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