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First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang wang Fen Guo kangxin wang Guangfu Jin Xiao Li Rong wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling Ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang Shuang Tong Shiqing Chen Xing Li Yongqian Shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu School Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of Medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of Medical Affairs 3D Medicines Inc.ShanghaiChina Shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

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濒危植物小勾儿茶大小孢子发生和雌雄配子体发育

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植物研究 2024年第5期44卷 662-669页

作者：王康鑫王仕沁王毅敏程志杰陈发菊王玉兵三峡大学生物技术研究中心宜昌443002 三峡植物园宜昌443111

运用石蜡切片技术对小勾儿茶(Berchemiella wilsonii)进行生殖生物学观察,探讨其大小孢子发生和雌雄配体发育过程是否存在濒危环节。结果显示:小勾儿茶的花具5个雄蕊和4个花药室,成熟的花药壁由花药内壁(1层)、中层(2层)和绒毡层(1层)... 详细信息

运用石蜡切片技术对小勾儿茶(Berchemiella wilsonii)进行生殖生物学观察,探讨其大小孢子发生和雌雄配体发育过程是否存在濒危环节。结果显示:小勾儿茶的花具5个雄蕊和4个花药室,成熟的花药壁由花药内壁(1层)、中层(2层)和绒毡层(1层)组成。绒毡层发育正常,细胞排列整齐规则,与中层细胞联系紧密,细胞中常多核。小孢子母细胞在减数分裂时胞质分裂方式为同时型,四分体主要以四面体形式存在,花粉粒在成熟时为二细胞型、圆形或椭圆形,多数有3根萌发管。花药发育过程中绒毡层发育存在少量异常,花粉存在少量败育。小勾儿茶子房2室,只发育1室。胚珠为倒生的双珠被和厚珠心,合点端大孢子发育成功能性大孢子,经过3次有丝分裂,进一步发育成具有7个细胞和8个核的胚囊,胚囊发育方式为蓼型。子房中的胚珠发育基本一致。小勾儿茶大小孢子发生和雌雄配子体发育基本正常,不是导致其结实率低的原因。

关键词：小勾儿茶胚胎学大小孢子发生雌雄配子体发育

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Comprehensive reutilization of herbal waste:Coproduction of magnolol,honokiol,and β-amyrin from Magnolia officinalis residue

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Green Energy & Environment 2024年第2期9卷 403-412页

作者： Lukun Xiao Anyi Zhao Jie Qiu An Liu Sha Chen Jinzhu Jiang Jun Zhang Cong Guo Jipeng Di Jintang Cheng Chang Chen kangxin Hou Aiping Zhang Yan Liu Caixia wang Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China School of Pharmacy Shanxi Medical UniversityTaiyuan030001China

Herbal extraction residues(HERs)cause serious environmental pollution and resource *** this study,a novel green route was designed for the comprehensive reutilization of all components in HERs,taking Magnolia officinalis residues(MOR)as an *** reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients(magnolol and honokiol)originally remaining in MOR and to make MOR more accessible for hydrolysis.A metal–organic frame material MIL-101(Cr)with a maximum absorption capacity of 255.64 mg g^(-1)was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions,and 40 g L^(-1)reducing sugars were obtained with 81.8%enzymatic hydrolysis rate at 10%MOR solid ***,382 mg L-1β-amyrin was produced from MOR hydrolysates by an engineered yeast *** total,1 kg honokiol,8 kg magnolol,and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

关键词： Magnolia officinalis residues(MOR) Comprehensive utilization Metal-organic frame material Biosynthesis

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Clinical significance of tumor marker for advanced gastric cancer with palliative chemotherapy: a retrospective study

Clinical significance of tumor marker for advanced gastric c...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Yahui Zhu Baorui Liu Jia Wei Juan Du Ju Yang Yan Yang kangxin wang Yang Yang Zhengyun Zou The Comprehensive Cancer Centre of Drum Tower Hospital Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University

The predictive value of tumor markers has been previously reported a lot. However, the studies focused on advanced gastric cancer are few. In this paper, we focused on investigating the connection between clinical characteristics and the tumor markers of advanced gastric cancer, therapeutic effect of chemotherapy, and prognosis. A retrospective study including 146 advanced gastric cancer who had not received any previous anticancer therapy was performed. Blood samples for CEA, AFP, CA125, CA72-4, CA242 and CA19-9 were taken from patients before chemotherapy and monthly during their treatments. The tumor markers’ clinical value can be predicted through statistical analysis. An ROC value of 0.621 was yielded by CEA in predicting lymph node metastasis in gastric cancer, which was significantly higher than any of other markers. CA125 had the highest accuracy, specificity and sensitivity with peritoneal metastasis in gastric cancer patients. CEA and AFP were more frequently positive with hepatic metastases in gastric cancer patients. The response rate ofDecreasing, Stable and Increasing group based on CEA, CA19-9, CA125, CA72-4 and CA242 levels achieved the significance in statistic. Positive cases of CA125, CA242, CA19-9 and CA72-4 showed poor prognosis, and CA125 and CA242 indicated significant differences in 3 yearsurvival rates. These results indicated that different tumor markers in gastric cancer indicated different metastasis sites. CEA, CA242, CA19-9, CA125 and CA72-4 are predictive biomarkers in evaluating the effectiveness of chemotherapy. The elevated CA125, CA242, CA72-4 and CA19-9 levels at diagnosed had association with shorter overall survivals, especially CA125 and CA242.

关键词： advanced gastric cancer tumor markers survival metastasis therapy

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人外周血TIM3基因敲除T淋巴细胞的制备及其抗肿瘤作用

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中国肿瘤生物治疗杂志 2019年第4期26卷 374-380页

作者：王康馨赵阳苏舒邵洁魏嘉刘宝瑞南京大学医学院附属鼓楼医院肿瘤中心暨南京大学临床肿瘤研究所江苏南京210008

目的:通过CRISPR-Cas9基因编辑技术及质粒电转染技术制备T细胞免疫球蛋白黏液素3(TIM3)基因敲除的人外周血T淋巴细胞,探讨敲除TIM3基因后能否增强T细胞免疫功能及其抗肿瘤作用。方法:通过电转染法将hTIM3 sgRNA/Cas9双质粒共转染EBV阳... 详细信息

目的:通过CRISPR-Cas9基因编辑技术及质粒电转染技术制备T细胞免疫球蛋白黏液素3(TIM3)基因敲除的人外周血T淋巴细胞,探讨敲除TIM3基因后能否增强T细胞免疫功能及其抗肿瘤作用。方法:通过电转染法将hTIM3 sgRNA/Cas9双质粒共转染EBV阳性胃癌患者外周血T淋巴细胞,电转24 h后流式细胞术检测转染效率并利用荧光显微镜观察;体外培养过程中观察基因敲除后T细胞增殖活性,流式细胞术验证TIM3基因敲除效率以及细胞表型的变化。用肿瘤抗原肽活化T细胞检测TIM3基因敲除后T细胞分泌细胞因子水平及体外杀伤胃癌AGS-EBV细胞的能力。结果:电转染法能够有效地将hTIM3 sgRNA/Cas9双质粒敲除体系转入人外周血T淋巴细胞,其转染效率平均达(41.5±3.6)%,基因敲除效率波动在40.0%～50.0%(均P<0.01);经抗原活化后的基因敲除组T细胞的增殖活性和免疫表型未见明显变化,表面活化分子中仅见HLA-DR较对照组明显提高(P<0.05);TIM3基因敲除T细胞分泌TNF-α、IFN-γ的水平显著增高(P<0.01或P<0.05),体外杀伤胃癌AGS-EBV细胞的能力也明显增强(均P<0.05)。结论:用CRISPR-Cas9基因编辑及质粒电转染技术制备人外周血TIM3基因敲除T淋巴细胞的方法简易可行,在体外的扩增活化中保持TIM3基因水平下调并具有更高的免疫应答水平以及更强的抗肿瘤作用。这一新技术的研发为基因工程化细胞免疫治疗提供了新的思路。

关键词： CRISPR-Cas9 T细胞免疫球蛋白黏液素3(TIM3)基因 T淋巴细胞细胞治疗抗肿瘤作用

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53份大薯种质资源SRAP标记的遗传多样性分析

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分子植物育种 2015年第10期13卷 2230-2235页

作者：吴文嫱翟李楠许云王亚杰王康鑫黄小龙黄东益海南大学农学院海口570208

利用SRAP分子标记技术对中国南方53份大薯种质资源进行了遗传多样性的分析,筛选获得49对多态性SRAP引物。Genalex的分析结果表明,各位点差异等位基因(Na)平均为1.640,有效等位基因(Ne)平均为1.437,Shannon指数(I)平均为0.361,多样性平均... 详细信息

利用SRAP分子标记技术对中国南方53份大薯种质资源进行了遗传多样性的分析,筛选获得49对多态性SRAP引物。Genalex的分析结果表明,各位点差异等位基因(Na)平均为1.640,有效等位基因(Ne)平均为1.437,Shannon指数(I)平均为0.361,多样性平均(h)为0.246,多态性信息含量(p)为62.5%。聚类分析的结果表明,供试材料的遗传相似性系数在0.354 2~0.885 4之间,均值为0.630 0。在遗传相似性系数(GS)为0.60时将供试材料分为5类,来自同一地区的种质并未聚在一起。

关键词：大薯 SRAP SSR 遗传多样性

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基于GWO-XGBoost-SHAP的水库边坡稳定性预测

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四川水利 2024年第3期45卷 46-51页

作者：黄康鑫广西壮族自治区水利电力勘测设计研究院有限责任公司南宁530023

水库边坡稳定性对水库安全至关重要。为了更准确地判断边坡稳定性,文章提出了一种结合Grey Wolf Optimizer(GWO)优化eXtreme Gradient Boosting(XGBoost)预测模型与解释机器学习模型(SHAP)结合的混合模型。选取重度、黏聚力、摩擦角、... 详细信息

水库边坡稳定性对水库安全至关重要。为了更准确地判断边坡稳定性,文章提出了一种结合Grey Wolf Optimizer(GWO)优化eXtreme Gradient Boosting(XGBoost)预测模型与解释机器学习模型(SHAP)结合的混合模型。选取重度、黏聚力、摩擦角、坡角、坡高和孔隙压力比作为模型的输入特征,利用GWO-XGBoost对其安全系数进行预测,并使用SHAP对该模型进行解释。研究结果表明:GWO-XGBoost模型决定系数R~2为0.9517,预测精度远高于现有模型。使用SHAP对该模型预测解释发现,重度、坡角和孔隙压力比是边坡稳定性的主要影响因素。该模型为水库边坡稳定性提供了可靠的参考,有助于水库制定更有效的安全措施,从而提升水库整体安全水平。

关键词：边坡稳定性灰狼优化算法 XGBoost SHAP

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环境诱胖剂—肥胖病因研究的新思路

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环境卫生学杂志 2015年第1期5卷 80-84页

作者：王康馨王强吴晨光陆荣柱江苏大学医学院卫生检验系江苏大学医学院预防医学系江苏大学附属人民医院内分泌科

Obesogen是近年来肥胖病因研究的新观点和新成果,其将环境中存在的促进或诱发肥胖发生的某些环境污染物或人工合成物看作肥胖的重要病因之一,由于这一类物质在国内尚未获得统一的命名与概述,为此本文建议将这些化学物命名为环境诱胖剂... 详细信息

Obesogen是近年来肥胖病因研究的新观点和新成果,其将环境中存在的促进或诱发肥胖发生的某些环境污染物或人工合成物看作肥胖的重要病因之一,由于这一类物质在国内尚未获得统一的命名与概述,为此本文建议将这些化学物命名为环境诱胖剂。目前被确认的环境诱胖剂有双酚A、己烯雌酚、全氟烷基酸(PFOA)、有机氯、有机锡、邻苯二甲酸酯等二十多种(类)化学物或药物,其诱胖机制主要为改变脂质稳态平衡和脂肪储量,代谢机制的调定点,促进脂肪的积聚。环境诱胖剂普遍存在于食物、饮水、空气等生活、生产和娱乐环境中,无法达到零接触,因而在寻找更多的环境诱胖剂的同时,需要建立有效的控制措施,以尽量减少这些化学物的接触机会和接触水平,预防肥胖的发生。

关键词：肥胖病因环境诱胖剂

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Synthesis of porous carbon from orange peel waste for effective volatile organic compounds adsorption: role of typical components

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Frontiers of Chemical Science and Engineering 2023年第7期17卷 942-953页

作者： Qiaoyan Zhou Huan Liu Yipeng wang kangxin Xiao Guangyan Yang Hong Yao School of Energy and Power Engineering Huazhong University of Science and TechnologyWuhan 430074China Research Institute of Huazhong University of Science and Technology in Shenzhen Shenzhen 518000China Universtar Science&Technology(Shenzhen)Co. Ltd.Shenzhen 518057China

Volatile organic compounds have posed a serious threat to the environment and human health,which require urgent and effective *** recent years,the preparation of porous carbon from biomass waste for volatile organic compounds adsorption has attracted increasing attention as a very cost-effective and promising *** this study,porous carbon was synthesized from orange peel by urea-assisted hydrothermal carbonization and KOH *** role of typical components(cellulose,hemicellulose,and lignin)in pore development and volatile organic compounds adsorption was *** the three components,hemicellulose was the major contributor to high porosity and abundant micropores in porous *** hemicellulose content led to more abundant–COOR,amine-N,and pyrrolic/pyridonic-N in the derived hydrochar,which were favorable for porosity formation during *** this case,the toluene adsorption capacity of the porous carbon improved from 382.8 to 485.3 mg·g^(–1).Unlike hemicellulose,cellulose reduced the>C=O,amine-N,and pyrrolic/pyridonic-N content of the hydrochar,which caused porosity deterioration and worse toluene adsorption *** bestowed the hydrochar with slightly increased–COOR,pyrrolic/pyridonic-N,and graphitic-N,and reduced>C=O,resulting in comparatively poor porosity and more abundant *** general,the obtained porous carbon possessed abundant micropores and high specific surface area,with the highest up to 2882 m^(2)·g^(–1).This study can provide guidance for selecting suitable biomass waste to synthesize porous carbon with better porosity for efficient volatile organic compounds adsorption.

关键词： biomass waste porous carbon feedstock composition urea-assisted hydrothermal carbonization toluene adsorption N-doped hydrochar

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Cytochrome P450 monooxygenase specific activity reduction in wheat Triticum aestivum induced by soil roxithromycin stress

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Frontiers of Environmental Science & Engineering 2016年第2期10卷 270-275页

作者： kangxin HE Qixing ZHOU MOE Key Laboratory of Pollution Processes and Environmental Criteria/Tianjin Engineering Center of Environmental Diagnosis and Contamination Remediation College of Environmental Science and Engineering Nankai University Tianjin 300071 China

Roxithromycin, livestock growth promoter, as widely used medicine and arouses concern because its occurrence and persistence in soil environments. However, effects of roxithromycin in higher plants are still vague. Accordingly, we hypothesized that roxithromycin-con- taminated soil may exhibits ecotoxicological effects in wheat （Triticum aestivum）. In this study, effects induced by a gradient concentration of roxithromycin stress （0.01, 0.1, 1, 10, and 100 ***-1） was investigated in a 7-d soil test in T. aestivum. Results indicated that the specific activity of cytochrome P450 （CYP450） monooxygenase was decreased dramatically with the concentration of roxithro- mycin in soil. The IC50 value was ***-1 of roxithromycin. On the contrary, the growth related endpoints （i.e., the germination percentage, the biomass and the height）, the content related endpoints （i.e., soluble protein content and CYP450 content）, and the superoxide dismutase （SOD） activity failed to reveal the roxithromy- cin-induced effects. Further analysis revealed that the CYP450 monooxygenase specific activity reduction was enzymatic mechanism mediated, other than oxidative stress induced. We conclude that the soil roxithromycin declined the CYP450 monooxygenase activity in T. aestivum by the inhibition of the enzymatic mechanism. Further efforts can include, but are not limited to, investigation of joint effects induced by combined exposure of roxithromycin and the pesticides and evalua- tion of the similar effects in other higher plants.

关键词： roxithromycin toxic effect cytochrome P450monooxygenase soil environment Triticum aestivum,biomarker

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