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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei Sun Arabella H.Wan Shijia yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu ke Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Department of Hepatic Surgery and Liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial key Laboratory of Liver Disease Research Guangzhou 510630China Department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR Liver cancer

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Effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean section

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World Journal of Clinical Cases 2024年第28期12卷 6195-6203页

作者： Hong-Zhuan Chen Yi Gao ke-ke Li Li An Jing yan Hong Li Jin Zhang Department of Anesthesiology Hebei Key Laboratory of Maternal and Fetal MedicineShijiazhuang Key Laboratory of Reproductive HealthThe Fourth Hospital of ShijiazhuangShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Following cesarean section,a significant number of women encounter moderate to severe *** management of acute pain post-cesarean section can have far-reaching implications,adversely impacting maternal emotional wellbeing,daily activities,breastfeeding,and neonatal *** may also impede maternal organ function recovery,leading to escalated opioid usage,heightened risk of postpartum depression,and the development of chronic postoperative *** the Chinese Enhanced Recovery After Surgery(ERAS)guidelines and the American ERAS Society guidelines consistently advocate for the adoption of multimodal analgesia protocols in post-cesarean section pain ***,functioning as an antagonist of the N-Methyl-D-Aspartate receptor,has been validated for pain management in surgical patients and has exhibited effectiveness in depression *** has suggested that incorporating esketamine into postoperative pain management via pain pumps can lead to improvements in short-term depression and pain *** study aims to assess the efficacy and safety of administering a single dose of esketamine during cesarean *** To investigate the effect of intraoperative injection of esketamine on postoperative analgesia and postoperative rehabilitation after cesarean *** A total of 315 women undergoing elective cesarean section under combined spinal-epidural anesthesia were randomized into three groups:low-dose esketamine(0.15 mg/kg),high-dose esketamine(0.25 mg/kg),and control(saline).Postoperative Visual Analog Scale(VAS)scores were recorded at 6 hours,12 hours,24 hours,and 48 *** Postnatal Depression Scale(EPDS)scores were noted on 2 days,7 days and 42 *** sedation scores were assessed at specified intervals *** adverse reactions were also *** Low-dose group and high-dose group compared to control group,had significantly lower postoperative VAS pain scores at 6 h

关键词： Maternity Cesarean section Depression Esketamine Postoperative analgesia

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Comparison of ovarian preservation versus oophorectomy on fertility outcomes in patients with endometriosis post-laparoscopic surgery:A prospective study

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World Journal of Clinical Cases 2024年第21期12卷 4652-4660页

作者： Jin-Jin Zhou ke Yu Hai-yan Mao Cen Li Department of Gynecology Affiliated Hospital of Yangzhou UniversityYangzhou 225001Jiangsu ProvinceChina Department of Oncology Affiliated Hospital of Yangzhou UniversityYangzhou 225001Jiangsu ProvinceChina

BACKGROUND Endometriosis is a chronic inflammatory condition affecting a significant proportion of women of reproductive *** laparoscopic surgery is commonly the preferred treatment,the decision to preserve or remove the ovaries remains *** studies have yielded inconsistent results regarding the impact of ovarian preservation vs oophorectomy on fertility outcomes and disease *** prospective study aimed to address this knowledge gap by comparing the effects of these surgical approaches on spontaneous pregnancy rates,time to pregnancy,recurrence rates,and postoperative pain in patients with *** To compare the reproductive outcomes and recurrence rates between ovarian preservation and oophorectomy in women undergoing laparoscopic surgery for *** This study was conducted at a tertiary care hospital between January 2019 and December 2023.A total of 312 women aged 18 to 40 years,diagnosed with endometriosis and undergoing laparoscopic surgery,were *** patients were categorized into the ovarian preservation group(n=204)and the oophorectomy group(n=108).The primary outcome measure was the achievement of spontaneous pregnancy within 24 months *** outcomes included time to spontaneous pregnancy,recurrence rates,and postoperative pain *** The ovarian preservation group exhibited a significantly higher spontaneous pregnancy rate than that in the oophorectomy group(43.6%vs 28.7%,P=0.006).Moreover,the median time to spontaneous pregnancy was shorter in the ovarian preservation group(8.2 months vs 11.4 months,P=0.018).Nonetheless,endometriosis recurrence was more prevalent in the ovarian preservation group(22.1%vs 11.1%,P=0.014).The postoperative pain scores demonstrated similar improvements in both groups,with no significant differences *** analyses indicated that the benefit of ovarian preservation on spontaneous pregnancy rates was more evident among youn

关键词： Endometriosis Ovarian Pregnancy Oophorectomy Laparoscopic Spontaneous pregnancy

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2003年江淮汛期多模式短期集合预报方法研究

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热带气象学报 2009年第4期25卷 449-457页

作者：陈超辉王铁谭言科李崇银许园春解放军理工大学气象学院江苏南京211101 中国科学院大气物理研究所大气科学与地球流体力学数值模拟国家重点实验室(LASG) 北京100029

利用AREM、MM5和WRF模式为试验模式,由对短期天气预报结果影响颇大的积云参数化方案和边界层方案构成15个集合预报成员,开展有限区域多模式短期集合预报在我国汛期时段的应用与研究。分别研究了单个模式集合预报和多模式集合预报在2003... 详细信息

利用AREM、MM5和WRF模式为试验模式,由对短期天气预报结果影响颇大的积云参数化方案和边界层方案构成15个集合预报成员,开展有限区域多模式短期集合预报在我国汛期时段的应用与研究。分别研究了单个模式集合预报和多模式集合预报在2003年汛期(7月)预报中的应用,预报对象主要包括降水、500 hPa位势高度和700 hPa相对湿度。试验结果表明:(1)由AREM、MM5和WRF模式构成的多模式集合对以上要素的集合预报总体效果比其任一单个模式的集合预报效果好;(2)对于降水的集合预报,单个模式的集合平均结果对多模式集合预报效果有影响。且对于不同的降水临界值影响不同;当降水临界值较小时,单模式集合平均结果对多模式集合效果影响较小;当降水临界值较大时,影响较大,甚至可以影响多模式集合的集合平均预报成败;(3)对于降水、500 hPa位势高度和700 hPa相对湿度,其单个模式以及多模式的48 h集合预报对确定性预报的改善度都比24 h的显著。(4)对于形势预报和相对湿度预报,多模式集合预报效果明显比同期T213模式的预报水平高。

关键词：数值模拟集合预报多模式集合江淮汛期汛期降水

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面向轴承润滑增效的内圈表面沟槽引流可视化仿真与试验研究

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摩擦学学报（中英文） 2024年第5期44卷 677-685页

作者：阎贝郭金道任乔睿闫柯长安大学工程机械学院陕西西安710064 西安交通大学现代设计及转子轴承系统教育部重点实验室陕西西安710049 沈阳航空航天大学航空发动机学院辽宁沈阳110136

高速轴承套圈表面添加沟槽是提升轴承润滑效率的有效手段.针对高速旋转套圈表面沟槽对润滑油流动的引导机理和影响规律研究,本文中通过可视化仿真和试验研究,监测对比了润滑油在轴承光滑内圈和带沟槽内圈表面的流动行为,基于内圈滚道内... 详细信息

高速轴承套圈表面添加沟槽是提升轴承润滑效率的有效手段.针对高速旋转套圈表面沟槽对润滑油流动的引导机理和影响规律研究,本文中通过可视化仿真和试验研究,监测对比了润滑油在轴承光滑内圈和带沟槽内圈表面的流动行为,基于内圈滚道内润滑油流量评估沟槽结构对润滑油的导向效果,最后通过轴承乏油状态下的温升试验验证了分析结果的合理性.结果表明,与光滑内圈相比,具有不同凹槽结构的内圈可能会增强/减弱润滑介质流动,合理/不合理的沟槽设计存在提高/降低轴承润滑效率的可能.

关键词：高速轴承沟槽结构润滑增效可视化试验数值仿真

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固定配比的钠化膨润土与土壤在不同pH条件下对重金属离子的吸附效果研究

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岩矿测试 2010年第4期29卷 411-413页

作者：谭科艳刘晓端黄园英陈燕芳国家地质实验测试中心北京100037

研究了固定配比的钠化膨润土与土壤在不同pH条件下对重金属离子的吸附效果。钠化膨润土与污染土壤按质量比1∶10和1∶20的比例混合,用碳酸氢铵-二乙三胺五乙酸(AB-DTPA)法提取土壤中有效态重金属。结果表明,在钠化膨润土与土壤质量比为1... 详细信息

研究了固定配比的钠化膨润土与土壤在不同pH条件下对重金属离子的吸附效果。钠化膨润土与污染土壤按质量比1∶10和1∶20的比例混合,用碳酸氢铵-二乙三胺五乙酸(AB-DTPA)法提取土壤中有效态重金属。结果表明,在钠化膨润土与土壤质量比为1∶20的条件下,取得了最佳的修复效果;在pH=9.14时该混合土壤对重金属的总体吸附效果最佳。在实际土壤修复中,针对不同重金属污染,应灵活调整修复材料与污染土壤的配比和土壤的pH条件。

关键词：重金属钠化膨润土修复配比 pH条件土壤

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Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2726-2737页

作者： Bo Liu Honghui Liu Pu Han Xiaoyun Wang Chunmei Wang Xinxin yan Wenwen Lei ke Xu Jianjie Zhou Jianxun Qi Ruiwen Fan Guizhen Wu Wen-xia Tian George F.Gao Qihui Wang College of Veterinary Medicine Shanxi Agricultural University030801 JinzhongChina CAS key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)100101 BeijingChina School of Life Sciences Yunnan University650504 KunmingYunnan ProvinceChina NHC key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)102206 BeijingChina Savaid Medical School University of Chinese Academy of Sciences101408 BeijingChina

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its *** suggests that highly conserved epitopes are crucial for the development of neutralizing ***,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its ***-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S *** neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S ***,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus *** to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in *** intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

关键词： doses prevention conserved

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-yang Liu Song Dong Xue-Ning yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong yan Li-Xu yan Qiang Nie Hai-yan Tu Bin-Chao Wang Jin-Ji yang Qing Zhou Hong-Rui Li ke Liu Wendy Wu Si-yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2404-2418页

作者： Jie Song Xiang-Xiu yan Fang-Liang Zhang Yong-Yi Lei Zi-Yin ke Fang Li Kai Zhang Yu-Qi He Wei Li Chao Li Yuan-Ming Pan Department of Gastroenterology Dongying People’s HospitalDongying Hospital of Shandong Provincial Hospital GroupDongying 257000Shandong ProvinceChina Gastrointestinal Surgery Department Suining Central HospitalSuining 629000Sichuan ProvinceChina Obstetrical Department Suining Central HospitalSuining 629000Sichuan ProvinceChina School of Medicine Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107Guangdong ProvinceChina Department of Pathology Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049China General Department Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China Department of Gastroenterology Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China Department of Thoracic Surgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina Department of Gastroenterology Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049China Cancer Research Center Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China

BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative *** To investigate the prognosis of GMA and develop predictive *** From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with *** random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s *** This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test *** packaged it into Windows software for doctors’use and uploaded *** gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA *** surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.

关键词： Deep learning Gastrointestinal mucous adenocarcinoma Overall survival Surgery Clinical tool

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两类El Nio对应的印度洋偶极子事件的比较研究

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热带气象学报 2017年第4期33卷 467-477页

作者：钱景李崇银谭言科桂发银黎鑫解放军理工大学气象海洋学院江苏南京211101 LASG国家重点实验室/中国科学院大气物理研究所北京100029

利用多种大气和海洋再分析资料,采用合成分析及2.5层简化海洋模型数值模拟等方法,研究了1951—2012年期间,与东部和中部型El Nio事件相伴随的热带印度洋海温偶极子(Indian Ocean Dipole,IOD)出现时,热带印度洋海温异常增暖及其上空海... 详细信息

利用多种大气和海洋再分析资料,采用合成分析及2.5层简化海洋模型数值模拟等方法,研究了1951—2012年期间,与东部和中部型El Nio事件相伴随的热带印度洋海温偶极子(Indian Ocean Dipole,IOD)出现时,热带印度洋海温异常增暖及其上空海气耦合特征的物理机制。结果表明:夏秋季节,伴随东部型El Nio而发生的IOD事件(EP-IOD)和伴随中部型El Nio而发生的IOD事件(CP-IOD)中,热带印度洋海温正异常的强度与空间分布具有很大差异。对于EP-IOD事件,夏季,海温正异常中心最先出现在热带西北印度洋;随后秋季,海温正异常向东南发展并扩大至热带中南印度洋,强度较强。对于CP-IOD事件,夏季和秋季,海温正异常中心都位于热带中南印度洋,呈东西向带状分布,但海温正异常强度较EP-IOD事件中弱。进一步分析表明,在EP-IOD事件中,夏季,热带西北印度洋海区西南季风偏弱,通过影响夹卷混合过程导致热带西北印度洋海温上升;秋季,热带西北印度洋上空的异常偏东风导致垂向夹卷混合的正异常,对热带西北印度洋增暖的维持起到重要作用;热带中南印度洋的增暖主要受赤道东南印度洋西传的暖性Rossby波影响。而在CP-IOD事件中,夏秋两季,热带中南印度洋海区出现显著的西北风异常,其上空风速的负异常是增温的主要原因;同时赤道东南印度洋西传的暖性Rossby波对热带中南印度洋的增暖也起到重要作用。

关键词：两类El Nino 印度洋 IOD 季节演变 2.5层简化海洋模型

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