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Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

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Chinese Journal of Cancer Research 2017年第1期29卷 18-24页

作者： Yan Zhang Zheng Wang Xuezhi Hao xingsheng hu Hongyu Wang Yan Wang Jianming Ying Department of Medical Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021 China Department of Pathology Beijing Hospital National Center of Gerontology Beijing 100730 China Departmentof Pathology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100021China

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these patients.Methods： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

关键词： Non-small cell lung cancer EGFR uncommon mutation target therapy

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A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

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Chinese Journal of Cancer Research 2016年第4期28卷 444-451页

作者： xingsheng hu Lin Wang Lin Lin Xiaohong Han Guifang Dou Zhiyun Meng Yuankai Shi Department of Medical Oncology Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted DrugsNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Laboratory of Drug Metabolism and Pharmacokinetics Beijing Institute of Transfusion MedicineBeijing 100850China

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

关键词： Chidamide HDAC inhibitor phase I paclitaxel and carboplatin non-small cell lung cancer

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First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China

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Chinese Journal of Cancer Research 2019年第5期31卷 749-758页

作者： Fei Qi xingsheng hu Yutao Liu Zhijie Wang Jianchun Duan Jie Wang Mei Dong Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were identified.Results: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed(12.3 vs. 4.8 vs. 8.6 months;P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy.Conclusions: First-line induction and maintenance therapy with Bev(7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

关键词： Bevacizumab pemetrexed non-squamous non-small cell lung cancer maintenance treatment propensity score matching

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The commensal consortium of the gut microbiome is associated with favorable responses to anti-programmed death protein 1 (PD-1) therapy in thoracic neoplasms

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Cancer Biology & Medicine 2021年第4期18卷 1040-1052页

作者： huihui Yin Lu Yang Gongxin Peng Ke Yang Yuling Mi xingsheng hu Xuezhi Hao Yuchen Jiao Xiaobing Wang Yan Wang State Key Laboratory of Molecular Oncology Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Center for Bioinformatics Institute of Basic Medical SciencesChinese Academy of Medical Sciences&School of Basic MedicinePeking Union Medical CollegeBeijing 100021China Department of Medical Oncology Cancer Hospital of Huanxing Chaoyang District BeijingBeijing 100122China Department of Medical Oncology Chaoyang Sanhuan Cancer HospitalBeijing 100021China

Objective:Immune checkpoint inhibitors have revolutionized cancer therapy for multiple types of solid tumors,but as expected,a large percentage of patients do not show durable responses.Biomarkers that can predict clinical responses to immunotherapies at diagnosis are therefore urgently needed.Herein,we determined the associations between baseline gut commensal microbes and the clinical treatment efficiencies of patients with thoracic neoplasms during anti-programmed death protein 1(PD-1)therapy.Methods:Forty-two patients with advanced thoracic carcinoma who received anti-PD-1 treatment were enrolled in the study.Baseline and time-serial stool samples were analyzed using 16S ribosomal RNA gene sequencing.Tumor responses,patient progression-free survival,and overall survival were used to measure clinical outcomes.Results:The diversities of the baseline gut microbiota were similar between responders(n=23)and nonresponders(n=19).The relative abundances of the Akkermansiaceae,Enterococcaceae,Enterobacteriaceae,Carnobacteriaceae and Clostridiales Family XI bacterial families were significantly higher in the responder group.These 5 bacterial families acted as a commensal consortium and better stratified patients according to clinical responses(P=0.014).Patients with a higher abundance of commensal microbes had prolonged PFS(P=0.00016).Using multivariable analysis,the abundance of the commensal consortium was identified as an independent predictor of anti-PD-1 immunotherapy in thoracic neoplasms(hazard ratio:0.17;95%confidence interval:0.05–0.55;P=0.003).Conclusions:Baseline gut microbiota may have a critical impact on anti-PD-1 treatment in thoracic neoplasms.The abundance of gut commensal microbes at diagnosis might be useful for the early prediction of anti-PD-1 immunotherapy responses.

关键词： Gut microbiota commensal microbes anti-PD-1 immunotherapy thoracic neoplasms

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振动能量采集型磁流变阻尼器发电性能研究

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工程设计学报 2024年第2期31卷 201-209页

作者：席兴盛胡国良朱文才喻理梵李刚华东交通大学载运工具与装备教育部重点实验室江西南昌330013

为了解决磁流变阻尼器对外部电源的过度依赖以及避免其断电失效的风险,设计了一种结构简单、可实现振动能量采集的磁流变阻尼器。该阻尼器由基于磁流变效应的减振装置和基于电磁感应原理的发电装置组成。首先,基于磁路欧姆定理建立了电... 详细信息

为了解决磁流变阻尼器对外部电源的过度依赖以及避免其断电失效的风险,设计了一种结构简单、可实现振动能量采集的磁流变阻尼器。该阻尼器由基于磁流变效应的减振装置和基于电磁感应原理的发电装置组成。首先,基于磁路欧姆定理建立了电磁感应发电装置的振动能量采集数学模型;其次,应用MATLAB软件进行发电装置发电性能分析,研究了装置发电性能与结构设计变量之间的关系;接着,采用COMSOl软件对2种不同永磁体组结构的发电装置进行了电磁仿真分析与对比,重点分析了发电装置永磁体组高度对发电性能的影响;最后,仿真分析了不同振动频率和幅值对装置发电性能的影响。结果表明:在一定范围内,感应线圈绕线槽高度值与发电性能指标值基本呈线性关系,永磁体组高度、导磁垫片高度与绕线筒径向厚度均存在最优值。无论在何种频率或幅值振动激励下,永磁体组高度为30 mm的发电装置单线圈感应电压的峰值比永磁体组高度为20 mm的大42.5%左右,输出功率峰值大22.3%左右。研究结果可为提高振动能量采集型磁流变阻尼器发电性能提供参考。

关键词：磁流变阻尼器能量采集电磁感应发电性能

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中国西南地区CCUS区域中心建设路径与政策建议

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天然气工业 2024年第4期44卷 171-179页

作者：文绍牧李森圣何润民敬兴胜王盟浩胡俊坤中国石油西南油气田公司中国石油西南油气田公司天然气经济研究所中国石油西南油气田公司发展计划部

西南地区正在加快推动成渝地区双城经济圈和国家天然气(页岩气)千亿立方米产能基地等国家战略实施,面临能源消费量增长硬需求和碳减排硬约束之间的矛盾,推动CCUS产业发展是解决该问题的必由之路,而建设CCUS区域中心是CCUS产业规模化、... 详细信息

西南地区正在加快推动成渝地区双城经济圈和国家天然气(页岩气)千亿立方米产能基地等国家战略实施,面临能源消费量增长硬需求和碳减排硬约束之间的矛盾,推动CCUS产业发展是解决该问题的必由之路,而建设CCUS区域中心是CCUS产业规模化、集群化发展的必然趋势,其中四川盆地是西南地区打造CCUS区域中心的最佳选择。为了加快建设中国西南地区CCUS区域中心,系统梳理了国外的经验做法,分析了其优势和挑战,结合我国西南地区的CO_(2)排放及分布情况、封存地质条件、源汇匹配关系,针对性提出了建设路径和政策建议。研究结果表明:①打造中国西南地区CCUS区域中心具有企业减碳和增产的需求巨大、高耗能行业企业碳源丰富且较为集中、地质封存潜力大且分布集中、源汇匹配情况较好、地方政府积极支持等5大优势;②当前面临的主要问题是缺乏顶层设计和统一规划、缺乏全产业链协同技术攻关的共享平台、缺乏碳减排的激励和约束政策体系等;③下一步应聚焦CCUS-EGR、CCS、DACCS等3条路径,分启动、扩展、规模化发展3个阶段打造西南地区CCUS区域中心,形成两个千万吨级产业集群和3个百万吨级产业集群,并比选技术路径和商业化路径。结论认为,要重点从完善顶层设计,出台统一的战略规划;强化科技攻关体系建设,加快形成技术成熟、经济可行的CCUS全链条技术;强化政策支持、推动国际合作等3个方面入手,加快推动中国西南地区CCUS区域中心建设。

关键词：西南地区四川盆地 CCUS 区域中心产业集群源汇匹配建设路径政策建议

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内外液流通道筒式磁流变制动器制动性能分析

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重庆交通大学学报（自然科学版） 2024年第1期43卷 107-115页

作者：胡国良应仕诚席兴盛舒慧杰喻理梵华东交通大学载运工具与装备教育部重点实验室江西南昌330013

针对传统磁流变制动器磁场利用率不高的问题,提出了一种具有内外液通道的筒式磁流变制动器;通过在缸筒和旋转套筒中增设非磁性器件,使得磁力线蜿蜒通过内外轴向液流通道的6段有效阻尼间隙,从而使该制动器在外形尺寸不变的前提下能产生... 详细信息

针对传统磁流变制动器磁场利用率不高的问题,提出了一种具有内外液通道的筒式磁流变制动器;通过在缸筒和旋转套筒中增设非磁性器件,使得磁力线蜿蜒通过内外轴向液流通道的6段有效阻尼间隙,从而使该制动器在外形尺寸不变的前提下能产生较好的转矩性能;阐述了内外液流通道筒式磁流变制动器的结构和工作原理,并对有效阻尼间隙在磁场作用下的磁路进行分析;同时推导建立了制动转矩和温度场数学模型;基于COMSOL软件对磁流变制动器电磁场和温度场进行了仿真分析。由电磁场仿真可知,在外加电流为2.0 A、转速400 r/min时,制动转矩可达101.96 N·m,转矩动态可调范围由1.00增加至29.69;由温度场仿真可知,在多次紧急制动下最高温度为42.88℃,符合磁流变液正常工作范围。

关键词：车辆工程磁流变制动器内外液流通道转矩特性温度场

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Prevalence and clinical significance of pathogenic germline BRCA1/2 mutations in Chinese non-small cell lung cancer patients

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Cancer Biology & Medicine 2019年第3期16卷 556-564页

作者： xingsheng hu Dongyong Yang Yalun Li Li Li Yan Wang Peng Chen Song Xu Xingxiang Pu Wei Zhu Pengbo Deng Junyi Ye Hanhan Zhang Analyn Lizaso Hao Liu Xinru Mao Hai huang Qian Chu Chengping hu Department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing100021China Department of Pulmonary Medicine Second Affiliated Hospital of Fujian Medical UniversityQuanzhou362100China Department of Respiratory Medicine West China HospitalSichuan UniversityChengdu610041China Department ofRespiratory Medicine Daping HospitalChongqing400042China Department of Respiratory Medicine Xinqiao HospitalArmy Medical UniversityChongqing400037China Department of Medical Oncology Tianjin Medical University CancerInstitute and HospitalNational Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Tianjin300060China Department of Thoracic Oncology TianjinMedical University General HospitalTianjin300052China Department of Medical Oncology Hunan Cancer HospitalChangsha410006China Department of Pathology Xiangya HospitalCentral South UniversityChangsha410008China Department of Respiratory Medicine Xiangya HospitalCentral South UniversityChangsha410008China Burning RockBiotech Guangzhou510300China Department of Oncology Tongji Hospital of Tongji Medical CollegeHuazhongUniversity of Science and TechnologyWuhan430022China

Objective: Germline alterations in the breast cancer susceptibility genes type 1 and 2, BRCA1 and BRCA2, predispose individuals to hereditary cancers, including breast, ovarian, prostate, pancreatic, and stomach cancers.Accumulating evidence suggests inherited genetic susceptibility to lung cancer.The present study aimed to survey the prevalence of pathogenic germline BRCA mutations(gBRCAm) and explore the potential association between gBRCAm and disease onset in Chinese advanced non-small cell lung cancer(NSCLC) patients.Methods: A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patients harboring germline BRCA1/2 mutations.Results: Out of the 6,220 patients screened, 1.03%(64/6,220) of the patients harbored the pathogenic gB RCAm, with BRCA2 mutations being the most predominant mutations(49/64, 76.5%).Patients who developed NSCLC before 50 years of age were more likely to carry gBRCAm(P = 0.036).Among the patients harboring classic lung cancer driver mutations, those with concurrent gBRCAm were significantly younger than those harboring the wild-type gBRCA(P = 0.029).By contrast, the age of patients with or without concurrent gBRCAm was comparable to those of patients without the driver mutations(P = 0.972).In addition, we identified EGFR-mutant patients with concurrent gBRCAm who showed comparable progression-free survival but significantly longer overall survival(P = 0.002) compared to EGFR-mutant patients with wild-type germline BRCA.Conclusions: Overall, our study is the largest survey of the prevalence of pathogenic gBRCAm in advanced Chinese NSCLC patients.Results suggested a lack of association between germline BRCA status and treatment outcome of EGFR-TKI.In addition,results showed a positive correlation between pathogenic gB RCAm and an early onset of NSCLC.

关键词： Germline BRCA mutations non-small cell lung cancer prevalence BRCA1 BRCA2

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射频磁控溅射制备HfMoNbZrN_(x)薄膜的组织和性能

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工具技术 2024年第1期58卷 3-8页

作者：谢明强施杰李博海胡恒宁汪辉巫兴胜张丽苏齐家杜昊成都工具研究所有限公司贵州大学机械工程学院中国人民解放军93147部队中国船舶集团海装风电股份有限公司贵州大学公共大数据国家重点实验室

利用射频磁控溅射技术分别在单面抛光Si(001),Al_(2)O_(3)(0001)和硬质合金(WC-8 wt.%Co)基底表面沉积HfMoNbZrN_(x)薄膜,研究不同氮气流量R_(N)对HfMoNbZrN_(x)薄膜的组织和性能影响。结果表明,HfMoNbZr薄膜倾向于形成非晶态,随着R_(N... 详细信息

利用射频磁控溅射技术分别在单面抛光Si(001),Al_(2)O_(3)(0001)和硬质合金(WC-8 wt.%Co)基底表面沉积HfMoNbZrN_(x)薄膜,研究不同氮气流量R_(N)对HfMoNbZrN_(x)薄膜的组织和性能影响。结果表明,HfMoNbZr薄膜倾向于形成非晶态,随着R_(N)的增加,HfMoNbZrN高熵合金氮化薄膜转变为面心立方(FCC)结构并且沉积速率下降;当R_(N)=10%时,薄膜硬度和弹性模量最大,分别为21.8GPa±0.88GPa和293.5GPa±9.56GPa;所有薄膜均发生磨粒磨损,相较于多元合金薄膜,氮化物薄膜的磨损率下降了一个数量级,薄膜耐磨性显著提高。

关键词：射频磁控溅射 HfMoNbZrN_(x)薄膜微观结构硬度摩擦学

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天然气生产企业碳排放核算与预测方法研究--以四川盆地天然气开发为例

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天然气技术与经济 2024年第1期18卷 53-58页

作者：胡俊坤敬兴胜刘海峰纪文刘毅中国石油西南油气田公司四川成都610051 中国石油西南油气田公司安全环保与技术监督研究院四川成都610095

碳中和已成全球共识,世界能源体系正加速向低碳化演变。中国能源发展进入新时代,“双碳”目标成为经济社会发展根本遵循,作为碳排放主要来源的能源行业正大力实施绿色低碳发展战略,但要实现“双碳”目标,需建立统一规范的碳排放统计核... 详细信息

碳中和已成全球共识,世界能源体系正加速向低碳化演变。中国能源发展进入新时代,“双碳”目标成为经济社会发展根本遵循,作为碳排放主要来源的能源行业正大力实施绿色低碳发展战略,但要实现“双碳”目标,需建立统一规范的碳排放统计核算体系,并对碳排放量进行科学预测。选取天然气生产企业的碳排放核算及预测方法作为研究对象,基于天然气生产企业作业链,系统性梳理出天然气勘探、开发、处理、输送各环节的碳排放特征,并归类为化石燃料燃烧排放、火炬系统燃烧排放、工艺放空排放、电力消耗隐含排放等四大碳排放源,建立起碳排放核算与预测方法。通过选取四川盆地典型的常规气、页岩气、高含硫气藏进行实例测算与分析,研究结果表明:①鉴于不同类型气藏生产的碳排放结构和强度存在较大差异,为保证核算和预测结果的可靠性,对于涉及到多种类型气藏开发的企业,在碳排放核算和预测时要分类进行,并加强基础数据的统计与监测;②在能耗双控向碳排放双控转变的大趋势下,为促进油气行业的高质量发展,在建立碳排放双控指标时,应以碳排放强度指标为核心,以碳排放总量指标为辅,针对不同类型的气藏、建立不同的碳排放强度动态标准;③天然气生产企业既是甲烷的主要生产供应者、也是甲烷排放者,应加强对甲烷减排控排措施的研究。结论认为,该研究成果可以为天然气行业建立更为科学合理的碳排放核算与预测方法体系提供参考和借鉴。

关键词： “双碳”目标天然气生产常规气页岩气高含硫气碳排放核算碳排放预测

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