Geology, geochronology and geochemistry of large Duobaoshan Cu-Mo-Au orefield in NE China: Magma genesis and regional tectonic implications

Duobaoshan is the largest porphyry-related Cu-Mo-Au orefield in northeastern(NE)Asia,and hosts a number of large-medium porphyry Cu(PCDs),epithermal Au and Fe-Cu skarn deposits.Formation ages of these deposits,from the oldest(Ordovician)to youngest(Jurassic),have spanned across over 300 Ma.No similar orefields of such size and geological complexity are found in NE Asia,which reflects its metallogenic uniqueness in forming and preserving porphyry-related deposits.In this study,we explore the actual number and timing of magmatic/mineralization phases,their respective magma genesis,fertility,and regional tectonic connection,together with the preservation of PCDs.We present new data on the magmatic/mineralization ages(LA-ICP-MS zircon U-Pb,pyrite and molybdenite Re-Os dating),whole-rock geochemistry,and zircon trace element compositions on four representative deposits in the Duobaoshan orefield,i.e.,Duobaoshan PCD,Tongshan PCD,Sankuanggou Fe-Cu skarn,and Zhengguang epithermal Au deposits,and compiled published ones from these and other mineral occurrences in the orefield.In terms of geochronology,we have newly summarized seven magmatic phases in the orefield:(1)Middle-Late Cambrian(506-491 Ma),(2)Early and Middle Ordovician(485-471 Ma and~462 Ma),(3)Late Ordovician(450-447 Ma),(4)Early Carboniferous and Late-Carboniferous to Early Permian(351-345 and 323-291 Ma),(5)Middle-Late Triassic(244-223 Ma),(6)Early-Middle and Late Jurassic(178-168 Ma and~150 Ma),and(7)Early Cretaceous(~112 Ma).Three of these seven major magmatic phases were coeval with ore formation,including(1)Early Ordovician(485-473 Ma)porphyry-type Cu-Mo-(Au),(2)Early-Middle Triassic(246-229 Ma)porphyry-related epithermal Au-(Cu-Mo),and(3)Early Jurassic(177-173 Ma)Fe-Cu skarn mineralization.Some deposits in the orefield,notably Tongshan and Zhengguang,were likely formed by more than one mineralization events.In terms of geochemistry,ore-causative granitoids in the orefield exhibit adakite-like or adakite-normal arc transitional signatures,but those forming the porphyry-/epithermal-type Cu-Mo-Au mineralization are largely confined to the former.The varying but high Sr/Y,Sm/Yb and La/Yb ratios suggest that the ore-forming magmas were mainly crustal sourced and formed at different depths(clinopyroxene-/amphibole-/garnet-stability fields).The adakite-like suites may have formed by partial melting of the thickened lower crust at 35-40 km(for the Early Ordovician arc)and>40 km(for the Middle-Late Triassic arc)depths.The Early Jurassic Fe-Cu skarn orecausative granitoids show an adakitic-normal arc transitional geochemical affinity.These granitoids were likely formed by partial melting of the juvenile lower crust(35-40 km depth),and subsequently modified by assimilation and fractional crystallization(AFC)processes.In light of the geological,geochronological and geochemical information,we proposed the following tectonometallogenic model for the Duobaoshan orefield.The Ordovician Duobaoshan may have been in a continental arc setting during the subduction of the Paleo-Asian Ocean,and formed the porphyry-related deposits at Duobaoshan,Tongshan and Zhengguang.Subduction may have ceased in the latest Ordovician,and the regional tectonics passed into long subsidence and extension till the latest Carboniferous.This extensional tectonic regime and the Silurian terrestrial-shallow marine sedimentation had likely buried and preserved the Ordovician Duobaoshan magmatic-hydrothermal system.The south-dipping Mongol-Okhotsk Ocean subduction from north of the orefield had generated the Middle-Late Triassic continental arc magmatism and the associated Tongshan PCD and Zhengguang epithermal Au mineralization(which superimposed on the Ordovician PCD system).The Middle Jurassic closure of Mongol-Okhotsk Ocean in the northwestern Amuria block(Erguna terrane),and the accompanying Siberia-Amuria collision,may have placed the Paleo-Pacific subduction system in NE China(including the orefield)under compression,and formed the granodiorite-tonalite and Fe-Cu skarn deposits at Sankuanggou and Xiaoduobaoshan.From the Middle Jurassic,the consecutive accretion of Paleo-Pacific arc terranes(e.g.,Sikhote-Alin and Nadanhada)onto the NE Asian continental margin may have gradually distant the Duobaoshan orefield from the subduction front,and consequently arc-type magmatism and the related mineralization faded.The minor Late Jurassic and Cretaceous unmineralized magmatism in the orefield may have triggered mainly by the far-field extension led by the post-collisional(Siberia-Amuria)gravitational collapse and/or Paleo-Pacific backarc-basin opening.

Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14):A case report

BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

Nomogram for prediction of fatal outcome in patients with severe COVID-19:a multicenter study

Background:To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019(COVID-19)patients.Methods:Between February 20,2020 and April 4,2020,consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study.All patients received chest computed tomography(CT)and serological examinations at admission.Laboratory tests included routine blood tests,liver function,renal function,coagulation profile,C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),and arterial blood gas.The SaO2 was measured using pulse oxygen saturation in room air at resting status.Independent high-risk factors associated with death were analyzed using Cox proportional hazard model.A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients.Results:There were 124 severe patients in the training cohort,and there were 71 and 76 severe patients in the two independent validation cohorts,respectively.Multivariate Cox analysis indicated that age≥70 years(HR=1.184,95%CI 1.061–1.321),panting(breathing rate≥30/min)(HR=3.300,95%CI 2.509–6.286),lymphocyte count<1.0×109/L(HR=2.283,95%CI 1.779–3.267),and interleukin-6(IL-6)>10pg/ml(HR=3.029,95%CI 1.567–7.116)were independent high-risk factors associated with fatal outcome.We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort(AUC=0.900,95%CI 0.841–0.960,sensitivity 95.5%,specificity 77.5%);in validation cohort 1(AUC=0.811,95%CI 0.763–0.961,sensitivity 77.3%,specificity 73.5%);in validation cohort 2(AUC=0.862,95%CI 0.698–0.924,sensitivity 92.9%,specificity 64.5%).The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation.The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts,but without difference(P=0.105 for training cohort,P=0.133 for validation cohort 1,and P=0.210 for validation cohort 2).Conclusions:This nomogram could help clinicians to identify severe patients who have high risk of death,and to develop more appropriate treatment strategies to reduce the mortality of severe patients.Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.

THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP,and its upregulation participates in preeclampsia

Preeclampsia is a pregnancy complication which threatens the survival of mothers and fetuses.It originates from abnormal placentation,especially insufficient fusion of the cytotrophoblast cells to form the syncytiotrophoblast.In this study,we found that THBS1,a matricellular protein that mediates cell-to-cell and cell-to-matrix interactions,is downregulated during the fusion of primary cytotrophoblast and BeWo cells,but upregulated in the placenta of pregnancies complicated by preeclampsia.Also,THBS1 was observed to interact with CD36,a membrane signal receptor and activator of the cAMP signaling pathway,to regulate the fusion of cytotrophoblast cells.Overexpression of THBS1 inhibited the cAMP signaling pathway and reduced the BeWo cells fusion ratio,while the effects of THBS1 were abolished by a CD36-blocking antibody.Our results suggest that THBS1 signals through a CD36-mediated cAMP pathway to regulate syncytialization of the cytotrophoblast cells,and that its upregulation impairs placental formation to cause preeclampsia.Thus,THBS1 can serve as a therapeutic target regarding the mitigation of abnormal syncytialization and preeclampsia.