Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI cancers.

胃癌抗HER2治疗中国专家共识(2024年版)

胃癌是消化系统最常见的恶性肿瘤之一。人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)是胃癌治疗的重要靶点。近年来,抗HER2治疗药物在胃癌治疗中取得突破性进展,为胃癌患者提供了更多的治疗选择。为了更好地指导临床合理、有效、安全地应用抗HER2治疗药物,中国抗癌协会胃癌专业委员会组织国内胃癌领域专家进行多轮讨论,系统汇总国内外循证医学证据,并结合中国临床实际,从晚期治疗、围术期治疗、转化治疗和治疗期间需重点关注的问题等方面制订了《胃癌抗HER2治疗中国专家共识(2024年版)》,旨在进一步规范和指导胃癌抗HER2治疗临床实践。

二代测序在家族遗传性高危胃肠肿瘤筛查中的应用

目的:探索二代测序技术对家族遗传性高危胃肠肿瘤患者进行遗传筛查的意义及高危因素在筛选患者中的价值。方法:选取2016年3月至2016年4月收治于北京大学肿瘤医院的322例结直肠癌及胃癌患者,筛选出25例遗传性胃肠肿瘤高危患者,运用二代测序技术对患者的外周血白细胞DNA进行42个遗传性肿瘤综合征相关基因的胚系检测。结果:24%(6/25)患者检测出遗传性肿瘤相关基因的病理性胚系突变,其中50%(3/6)患者肿瘤组织的免疫组织化学检测表现为错配修复蛋白表达缺失,83%(5/6)患者发病年龄≤50岁且具有恶性肿瘤家族史。发生胚系突变的6例遗传性肿瘤相关基因分别为MYH基因错义突变1例,APC基因缺失突变1例和遗传性非息肉病性结直肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)相关基因的突变4例(包括MLH1、MLH3、TGFBR2的错义突变和MSH6的无义突变各1例),且提供了MLH3的胚系致病突变的家系验证。结论:通过二代测序技术对本研究入组的25例患者进行家族遗传性肿瘤综合征的筛查,检测出遗传性肿瘤相关基因的胚系致病突变6例,提示运用二代测序技术对家族遗传性高危消化道肿瘤患者进行遗传筛查具有提高检测阳性率的临床应用价值。

三药联合方案治疗晚期转移性结直肠癌的疗效和安全性比较

目的:探讨5-氟尿嘧啶(5-FU)/亚叶酸(leucovorin,LV)联合伊立替康和奥沙利铂(FOLFOXIRI)方案与卡培他滨联合伊立替康和奥沙利铂(CAPRINOX)方案一线应用于晚期不可切除结直肠癌的安全性及初步疗效的差异。方法:回顾性分析北京大学肿瘤医院2013年1月至2018年11月诊治的晚期转移性结直肠癌(metastatic colorectal cancer,mCRC)患者73例,所有患者均为一线化疗,按照治疗方案分为两组,其中45例为FOLFOXIRI方案组,28例为CAPRINOX方案组,根据化疗的客观缓解率(objective response rate,ORR)、转化根治性切除率及不良反应对比两种化疗方案的临床疗效和安全性。结果:FOLFOXIRI方法的ORR、中位无疾病进展时间(median progression free survival,mPFS)、R0切除的比例与CAPRINOX方法比较差异无统计学意义(60% vs.57.1%,7.7个月 vs.9.6个月,24.4% vs.17.9%;P>0.05)。所有患者在治疗期间,未出现治疗相关性死亡,两组主要不良反应包括白细胞减少、中性粒细胞减少、疲乏、恶心、呕吐、腹泻、脱发、转氨酶升高和周围神经毒性,FOLFOXIRI组3/4级不良反应发生率为33.3%(15/45),CAPRINOX组3/4级不良反应发生率为46.4%(13/28),差异无统计学意义(P=0.263)。结论:FOLFOXIRI和CAPRINOX均是一线治疗mCRC的有效方案,三药联合方案近期疗效高,不良反应可以耐受。

新辅助免疫治疗对微卫星高度不稳定胃肠肿瘤的有效性和安全性病例探讨

目的:免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)现已被批准用于不可切除胃肠肿瘤的晚期姑息治疗。然而新辅助形式的免疫治疗的有效性和安全性还未被阐明。错配修复缺陷(deficient mismatch repair,dMMR)或微卫星高度不稳定(mic⁃rosatellite instability-high,MSI-H)患者群体是否能从术前ICIs联合手术治疗中获益,有待进一步探索。方法:选取2018年1月至2020年2月于北京大学肿瘤医院接受治疗,患有高分期、可切除、MSI-H胃肠肿瘤的6例患者,均接受了新辅助免疫治疗和后续手术。所有患者在治疗前和治疗后均接受完整临床评估和影像学检查。每例患者的活检标本均通过二代测序(next-generation se⁃quencing,NGS)、免疫组织化学染色(immunohistochemistry,IHC)和原位杂交(in situ hybridization,ISH)检测以获得各自的分子病理学信息。结果:新辅助免疫治疗dMMR/MSI-H胃肠肿瘤是安全且有效的。在6例患者均观察到病理学缓解,其中包括5例(83%)完全缓解,另1例患者也被证实在ICIs治疗后肿瘤TNM分期下降。3例患者(50%)发生了1~2度不良反应。所有纳入研究的患者均及时接受了手术,无特殊的围手术期或手术后并发症发生。截止到目前尚无肿瘤复发者。结论:新辅助免疫治疗在MSI-H胃肠肿瘤的患者中有良好的病理学缓解率和轻微的不良反应(trAEs)。这种术前治疗措施并不会妨碍手术治疗,需要开展大样本临床试验,以便于进一步验证新辅助免疫治疗在可切除dMMR/MSI-H胃肠肿瘤中的作用。

Immune checkpoint inhibitors for treatment of advanced gastric or gastroesophageal junction cancer:Current evidence and future perspectives

Despite the application of conventional therapies,the prognosis of advanced gastric cancer(GC)or gastroesophageal junction cancer(GEJC)is still poor.In recent years,immune checkpoint inhibitors(ICIs)have reshaped the paradigm of cancer therapy.Emerging evidence support the feasibility of programmed cell death-1(PD-1)and its ligand(PD-L1)inhibition in chemo-refractory GC/GEJC.Nivolumab and pembrolizumab have initially been approved in Japan and United States,respectively for the third-line treatment of progressive GC or GEJC.In March 2020,nivolumab has also been licensed in China for treating advanced GC/GEJC who received≥2 lines of systemic therapies.Current studies are moving forward to the first-line application or focusing on combination strategies,though data are insufficient and disputable.In this review,we summarize the recently reported and ongoing clinical trials in ICIs for advanced GC/GEJC.Molecular characteristics and clinical implications of different tumor subtypes are also reviewed.We further discuss the safety profile and biomarkers for predicting the response of ICIs,which has guiding values in clinical practice.

Current management of chemotherapy-induced neutropenia in adults:key points and new challenges

Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.

Vegetable Oil-Based Nanolubricants in Machining:From Physicochemical Properties to Application

Cutting fluid is crucial in ensuring surface quality and machining accuracy during machining.However,traditional mineral oil-based cutting fluids no longer meet modern machining’s health and environmental protection require-ments.As a renewable,pollution-free alternative with excellent processing characteristics,vegetable oil has become an inevitable replacement.However,vegetable oil lacks oxidation stability,extreme pressure,and antiwear proper-ties,which are essential for machining requirements.The physicochemical characteristics of vegetable oils and the improved methods’application mechanism are not fully understood.This study aims to investigate the effects of viscosity,surface tension,and molecular structure of vegetable oil on cooling and lubricating properties.The mechanisms of autoxidation and high-temperature oxidation based on the molecular structure of vegetable oil are also discussed.The study further investigates the application mechanism and performance of chemical modification and antioxidant additives.The study shows that the propionic ester of methyl hydroxy-oleate obtained by epoxidation has an initial oxidation temperature of 175℃.The application mechanism and extreme pressure performance of conventional extreme pressure additives and nanoparticle additives were also investigated to solve the problem of insufficient oxidation resistance and extreme pressure performance of nanobiological lubricants.Finally,the study discusses the future prospects of vegetable oil for chemical modification and nanoparticle addition.The study provides theoretical guidance and technical support for the industrial application and scientific research of vegetable oil in the field of lubrication and cooling.It is expected to promote sustainable development in the manufacturing industry.

Timing of granite pegmatite-type high-purity quartz deposit in the Eastern Qinling,China:constraints from in-situ LA-ICP-MS trace analyses of quartz and monazite U–Pb dating

Eastern Qinling,China is one of the important rare metal metallogenic provinces with extensively distributed granite pegmatite dikes.The No.5 granite pegmatite intruded into the granitic gneiss of the Qinling Group,and the major minerals are quartz(39.8%),K-feldspar(18.8%),albite(36.3%),muscovite(3.4%),and garnet(1.1%).Monazite U–Pb isotopic dating indicates that the No.5 pegmatite from the Eastern Qinling was emplaced at ca.420.2±2.2 Ma,which confirms that highpurity quartz mineralization probably formed during the Early Devonian.In-situ laser ablation inductively coupled plasma mass spectrometry analysis of quartz show that quartz samples from Eastern Qinling have total trace element concentrations(Al,Ti,Sc,Li,B,Cr,Mn,and Fe)ranging from 23.2 to 52.8 ppm,slightly higher than the quartz(impurity element content from 13.4 to 25.9 ppm)of the Spruce Pine high-purity quartz deposit in western North Carolina.The No.5 pegmatite of Eastern Qinling could be defined as one high-purity quartz deposit of China.

Aneuploidy of chromosome 8 in circulating tumor cells correlates with prognosis in patients with advanced gastric cancer

Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.

Cytological and genetic analyses of a wheat-rye 2RL ditelosomic addition line with adult plant resistance to powdery mildew

Rye(Secale cereale genome RR),a close relative of common wheat,possesses valuable resistance genes for wheat improvement.Due to the co-evolution of pathogen virulence and host resistance,some resistance genes derived from rye have lost effectiveness.Development and identification of new,effective resistance genes from rye is thus required.In the current study,wheat-rye line WR56 was produced through distant hybridization,embryo rescue culture,chromosome doubling and backcrossing.WR56 was then proved to be a wheat-rye 2 RL ditelosomic addition line using GISH(genomic in situ hybridization),mc-FISH(multicolor fluorescence in situ hybridization),ND-FISH(non-denaturing FISH),mc-GISH(multicolor GISH)and rye chromosome arm-specific marker analysis.WR56 exhibited a high level of adult plant resistance to powdery mildew caused by Blumeria graminis f.sp.tritici(Bgt).This resistance was carried by the added 2 RL telosomes and presumed to be different from Pm7 which is also located on chromosome arm 2 RL but confers resistance at the seedling and adult stages.WR56 will be a promising bridging parent for transfer of the resistance to a more stable wheat breeding line.A newly developed2 RL-specific KASP(kompetitive allele specific PCR)marker should expedite that work.

Chinese quality control indices for standardized diagnosis and treatment of gastric cancer(2022 edition)

Gastric cancer is one of the most common malignancies of the digestive system,and the number of deaths continues to increase.The standardized management of the diagnosis and treatment of gastric cancer is challenging due to the great differences in the diagnosis and treatment of gastric cancer in different regions.The Gastric Cancer Expert Committee of the National Cancer Quality Control Center(NCQCC)identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of gastric cancer.The Gastric Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization,uniformity,and normalization of gastric cancer diagnosis and treatment,which ultimately improved the survival rate and quality of life of gastric cancer patients.A panel of experts with gastrointestinal cancer surgery,gastrointestinal cancer medicine,medical imaging,pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of gastric cancer.The authors then utilized a modified Delphi approach to generate consensus recommendations.

HER2 discordance between paired primary gastric cancer and metastasis:a meta-analysis

Background： A number of studies have examined human epidermal growth factor receptor 2 （HER2） status in primary gastric cancer （GC） and associated metastasis, some showed their great concordance in FIER2 expression, but others demonstrated notable discordance. There is still little consensus on HER2 discordance, therefore, a systematic review and meta-analysis was conducted to assess the status on HER2 discordance between primary GC and its paired metastasis. Methods： PubMed, EMBASE, ASCO and The Cochrane Library were searched for studies that explored the concordance between primary tumor and metastasis in patients with GC up to 10 March, 2014. Data of discordance of HER2 between primary GC and corresponding metastasis were extracted from the publications and random-effects models were used to estimate pooled discordance proportions. Results： Eighteen articles including 1,867 patients were included for the meta-analysis in accordance with the selection criteria. Pooled discordance proportions were 7% [95% confidence interval （CI）： 5-10%] for HER2 status. Pooled proportions of tumors shifting from positive to negative and from negative to positive were 17% （95% CI： 7-29%） and 4% （95% CI： 2-6%） respectively. No publication bias was found in the meta-analysis. Conclusions： The discordance of HER2 status is not rare in primary and metastatic GC through our metaanalysis. Prospective studies are needed to testify the clinical significance of the discordance of HER2 status.

Comparative population genomics dissects the genetic basis of seven domestication traits in jujube

Jujube(Ziziphus jujuba Mill.)is an important perennial fruit tree with a range of interesting horticultural traits.It was domesticated from wild jujube(Ziziphus acidojujuba),but the genomic variation dynamics and genetic changes underlying its horticultural traits during domestication are poorly understood.Here,we report a comprehensive genome variation map based on the resequencing of 350 accessions,including wild,semi-wild and cultivated jujube plants,at a>15×depth.Using the combination of a genome-wide association study(GWAS)and selective sweep analysis,we identified several candidate genes potentially involved in regulating seven domestication traits in jujube.For fruit shape and kernel shape,we integrated the GWAS approach with transcriptome profiling data,expression analysis and the transgenic validation of a candidate gene to identify a causal gene,ZjFS3,which encodes an ethyleneresponsive transcription factor.Similarly,we identified a candidate gene for bearing-shoot length and the number of leaves per bearing shoot and two candidate genes for the seed-setting rate using GWAS.In the selective sweep analysis,we also discovered several putative genes for the presence of prickles on bearing shoots and the postharvest shelf life of fleshy fruits.This study outlines the genetic basis of jujube domestication and evolution and provides a rich genomic resource for mining other horticulturally important genes in jujube.

胃癌胃镜活检标本HER-2检测中国专家共识(2023版)

胃癌是最常见的消化道恶性肿瘤之一。人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)是胃癌(包括胃食管结合部腺癌)临床治疗的重要靶点。规范、准确的胃镜活检标本HER2表达状态检测对于胃癌分子分型与选择抗HER-2靶向药物治疗具有重要意义。本共识基于循证医学证据和国际通行的Delphi法,在胃镜活检标本HER-2检测的临床意义、适用人群、活检操作规范、标本前期处理、检测方法、检测质量控制与多学科合作等方面达成初步统一,以期对临床工作提供指导。

Retrospective study of cetuximab in combination with chemotherapy for patients with colorectal cancer

Objective： To evaluate the efficacy and safety of cetuximab combined with chemotherapy in colorectal cancer （CRC）. Methods： 35 cases of CRC were retrospectively analyzed. Efficacy and adverse events were observed. Results： 29 cases of CRC were evaluated by RECIST criteria, showing 7 PR （partial response, 24.1%） and 15 SD （stable disease, 51.8%）, disease control rate （DC） was 75.9%. Subgroup analysis showed response rate （RR） of 36.4% and DC of 91% in the 1st line therapy, RR of 20% and DC of 70% in the 2rid line therapy, RR of 12.5% and DC of 62.5% in heavily pre-treated cases. Rash appeared in 74.3% of patients （grade 3 was 8.6%）, and the severity was relevant with disease control rate （DC）. Neutropenia of grade 3/4 was 14.3%, and infusion related reaction （IRR） of grade 3 happened in 1 case （2.9%）. Conclusion： Cetuximab combined with chemotherapy is safe and effective for patients with metastatic colorectal cancer. The combination therapy shows high DC, especially in 1st line therapy. Severity of rash may predict efficacy.

Alterations in DNA damage response and repair genes as potential biomarkers for immune checkpoint blockade in gastrointestinal cancer

Objective:Immune checkpoint inhibitors(ICIs)have achieved remarkable results in cancer treatments.However,there is no effective predictive biomarker for gastrointestinal(GI)cancer.Methods:We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the Memorial Sloan Kettering Cancer Center cohort(MSK-GI,n=227),the Janjigian cohort(n=40),and the Peking University Cancer Hospital&Institute cohort(PUCH,n=80)to determine the possible associations between DNA damage response and repair(DDR)gene mutations and clinical outcomes.Data from The Cancer Genome Atlas database were analyzed to determine the possible correlations between DDR gene mutations and the tumor microenvironment.Results:In the MSK cohort,the presence of≥2 DDR gene mutations was correlated with prolonged overall survival(OS).The Janjigian and PUCH cohorts further confirmed that subgroups with≥2 DDR gene mutations displayed a prolonged OS and a higher durable clinical benefit.Furthermore,the DDR gene mutation load could be considered as an independent prognostic factor,and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs.Mechanistically,we showed that the presence of≥2 DDR gene mutations was correlated with higher levels of tumor mutation burden,neoantigen,and T cell infiltration.Conclusions:The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs,which could serve as a potential biomarker to guide patient selection for immunotherapy.

Re–Os and Pb isotope features of pyrite in the Shihangli graphite deposit:implications of coal-generated graphite mineralization in central Hunan,South China

The coal metamorphism in Central Hunan pro-vides valuable information about hydrothermal activity and water/rock reactions.Learning how to collect age data on hydrothermal fluid systems is necessary for understanding the history and genetic mechanisms of large-scale coal-generated graphite deposits.The Shihangli graphite deposit,formed by significant siliceous hydrothermal alteration,is the most distinctive in Central Hunan.Re–Os dating of pyrite from the Shihangli graphite deposit demonstrates that the coal-generated graphite mineraliza-tion age is-127.6±3.8 Ma.Based on in-situ mineral analysis,the hydrothermal pyrite in the Shihangli graphite deposit is mostly enriched in Sb,As,Au,W,Ag,Cu,Pb,and Zn.Based on the pyrite Re–Os isochron,the initial(^(187)Os/^(188)Os)values of pyrite were 1.03±0.24 and the Os(t)values varied from 571.8 to 755.1.Pyrite from the Shihangli graphite deposit comprises a Pb isotope composition similar to that of the Madiyi Formation bulk rock and stibnite from the Xikuangshan Sb deposit.Based on the Re–Os,Sr,S,and Pb isotopic compositions of sul-fides in the graphite and Sb deposits in Central Hunan,the Madiyi Formation was likely the primary source of ore-forming elements(Sb,Au,and As).The Re–Os and Pb isotope compositions of pyrite most likely reflect when large-scale fluid migration and coal-generated graphite mineralization occurred in Central Hunan.