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Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

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中华医学杂志(英文版) 2024年第10期137卷 1207-1217页

作者： Pan Tianzhong Ding Peng Huang Aijie Tang Baolin Song Kaidi Sun Guangyu Wu Yue Yang Shiying Chen Xingchi Wang Dongyao Zhu Xiaoyu department of Hematology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Anhui Provincial Key Laboratory of blood Research and Applications Hefei Anhui China blood and Cell Therapy Institute Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui China

Background: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results: The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684,P = 0.039 andF = 5.583,P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93;P = 0.031).Conclusions: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

关键词： Umbilical cord blood transplantation Graft-versus-host disease Immune reconstitution Double negative T Hematological Malignancies Treg cell Breg cell

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The Place of blood transfusion in the Management of Obstetric Emergencies in the Gynaecology and Obstetrics department of the Reference Health Center of Fana (Mali)

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Open Journal of Obstetrics and Gynecology 2023年第4期13卷 780-791页

作者： Keita Sema Kone Bokary Sidi Fané Seydou Sylla Cheickna Samake Youssouf Traoré Momine Traoré Solomane Haidara Ramatoulaye Diabate Abdrahamane Sylla Yacouba Keita Mamadou Coulibaly Mahamoudou Haidara Mamadou Haidara Dramane Camara Daouda Fomba Dramane Kampo Mamadou Maiga Boubacar Dembele Sitapha Seydou Z. Dao Sanogo Siaka Amara Obstetrics and Gynecology department Fana Reference Health Centre Koulikoro Mali Mohamed VI Mother-Child Polyclinic in Bamako Bamako Mali department of Obstetrics and Gynecology Gabriel TOURE University Hospital Bamako Mali department of Gynecology and Obstetrics Reference Health Centre of Koulikoro Koulikoro Mali Diola Reference Health Centre Dioila Mali Obstetrics and Gynecology department Reference Health Centre of Commune I Bamako Mali Obstetrics and Gynecology department Commune VI Reference Health Centre Bamako Mali department of Gynecology and Obstetrics Kalaban Coro Reference Health Centre Bamako Mali department of Gynecology and Obstetrics Kati Reference Health Centre Kati Mali Obstetrics and Gynecology department Marakala Reference Health Centre Markala Mali department of Obstetrics and Gynecology Timbuktu Hospital Timbuktu Mali National blood transfusion Centre Bamako Mali department of Obstetrics and Gynecology Fousseyni Daou Hospital Kayes Mali Obstetrics and Gynecology department Reference Health Centre of Commune II Bamako Mali

This is a prospective and descriptive study carried out at the gynecology and obstetrics department of the reference health center of Fana from 01 May 2019 to 30 November or 7 months. The main objective was to study the role of blood transfusion in the management of obstetric emergencies. During the study period we recorded 434 cases of obstetric emergencies of which 116 cases required an emergency blood transfusion or 26.73%. The most frequently found indications for blood transfusion are hemorrhages of the immediate postpartum 46.6% followed by severe malaria on pregnancy 27.6%. blood remains the most prescribed and available Labile blood product in the department. Maternal prognosis was improved in 92.2%.

关键词： Obstetric Emergencies blood transfusion Hemovigilance

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Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2210-2227页

作者： Qing Zhao Junjie Feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong Yanfang Zou Jiali Ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles Guangzhou University of Chinese MedicineGuangzhou 510006China department of Laboratory Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai 519000China department of blood transfusion Guangdong Heyou International HospitalFoshan 528306China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关键词： Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling Naringin Bone morphogenetic protein 2 Runt-related transcription factor 2

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Extracorporeal organ support for critically ill patients:Overcoming the past,achieving the maximum at present,and redefining the future

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World Journal of Critical Care Medicine 2024年第2期13卷 19-28页

作者： Panagiotis Papamichalis Katerina G Oikonomou Maria Xanthoudaki Asimina Valsamaki Apostolia-Lemonia Skoura Sophia K Papathanasiou Achilleas Chovas Intensive Care Unit General Hospital of LarissaLarissa 41221Greece department of transfusion Medicine University Hospital of LarissaLarissa 41110Greece department of Internal Medicine General Hospital of LarissaLarissa 41221Greece

Extracorporeal organ support(ECOS)has made remarkable progress over the last few years.Renal replacement therapy,introduced a few decades ago,was the first available application of ECOS.The subsequent evolution of ECOS enabled the enhanced support to many other organs,including the heart[veno-arterial extracorporeal membrane oxygenation(ECMO),slow continuous ultrafiltration],the lungs(veno-venous ECMO,extracorporeal carbon dioxide removal),and the liver(blood purification techniques for the detoxification of liver toxins).Moreover,additional indications of these methods,including the suppression of excessive inflammatory response occurring in severe disorders such as sepsis,coronavirus disease 2019,pancreatitis,and trauma(blood purification techniques for the removal of exotoxins,endotoxins,or cytokines),have arisen.Multiple organ support therapy is crucial since a vast majority of critically ill patients present not with a single but with multiple organ failure(MOF),whereas,traditional therapeutic approaches(mechanical ventilation for acute respiratory failure,antibiotics for sepsis,and inotropes for cardiac dysfunction)have reached the maximum efficacy and cannot be improved further.However,several issues remain to be clarified,such as the complexity and cost of ECOS systems,standardization of indications,therapeutic protocols and initiation time,choice of the patients who will benefit most from these interventions,while evidence from randomized controlled trials supporting their use is still limited.Nevertheless,these methods are currently a part of routine clinical practice in intensive care units.This editorial presents the past,present,and future considerations,as well as perspectives regarding these therapies.Our better understanding of these methods,the pathophysiology of MOF,the crosstalk between native organs resulting in MOF,and the crosstalk between native organs and artificial organ support systems when applied sequentially or simultaneously,will lead to the multiplication of their effects and the mi

关键词： Kidney-liver replacement therapy Heart-lung support blood purification Native–artificial organ crosstalk Multiple organ support therapy Extracorporeal organ support

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EBV-associated lymphoproliferative disease post-CAR-T cell therapy

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Frontiers of Medicine 2024年第2期18卷 394-398页

作者： Shiyuan Zhang Xiaoxi Zhou Shangkun Zhang Na Wang Tongcun Zhang Donghua Zhang Qilin Ao Yang Cao Liang Huang department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Immunotherapy Research Center for Hematologic Diseases of Hubei Province Wuhan430030China Institute of Biology and Medicine College of Life and Health SciencesWuhan University of Science and TechnologyWuhan430081China department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin300020China Tianjin Institutes of Health Science Tianjin301600China

Epstein–Barr virus(EBV)-associated lymphoproliferative diseases(EBV-LPDs)are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation(HSCT).However,their occurrence and treatment post-chimeric antigen receptor-modified T(CAR-T)cell therapy has not been reported.Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment.After receiving CAR-T cell therapy in tandem with autologous HSCT,the patients achieved complete remission.However,with a median time of 38.5 months after CAR-T cell therapy,B-cell-derived EBV-LPDs were diagnosed,and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents.Collectively,our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy,especially in patients who previously had EBV-positive disorders,and they can be resolved by immune normalization strategy or B-cell depleting therapy.

关键词： EBV-associated lymphoproliferative disease chimeric antigen receptor T-cell autologous stem cell transplantation immune checkpoint inhibitor

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Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

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Genes & Diseases 2024年第4期11卷 314-326页

作者： Yinyin Chen Yushun Gong Jia Zou Guoli Li Fan Zhang Yiya Yang Yumei Liang Wenni Dai Liyu He Hengcheng Lu department of Nephrology Hunan Provincial People's HospitalThe First Affliated Hospital of Hunan Normal UniversityHunan Clinical Research Center for Chronic Kidney DiseaseChangshaHunan 410000China department of Nephrology The Second Xiangya Hospital of Central South UniversityHunan Key Laboratory of Kidney Disease and Blood PurificationChangshaHunan 410011China Cardiovascular Research Institute of Jiangxi Province Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi 330006China

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

关键词： Fluid shear stress Inflammation Obesity-related glomerulopathy Oxidative phosphorylation Single-cell RNA seq

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Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 919-942页

作者： Ren-Yong Wang Jia-Ling Yang Ning Xu Jia Xu Shao-Hua Yang Dao-Ming Liang Jin-Ze Li Hong Zhu Second Affiliated Hospital of Kunming Medical University Kunming 650106Yunnan ProvinceChina School of Basic Medical Sciences Nanjing Medical UniversityNanjing 211166Jiangsu ProvinceChina Wuhan blood Center Wuhan 430030Hubei ProvinceChina department of Gastrointestinal Surgery The Third People's Hospital of Hubei ProvinceWuhan 430071Hubei ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.

关键词： Hepatocellular carcinoma Lipid metabolism Immune microenvironment Prognostic markers Metabolic reprogramming

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Severe dengue in the intensive care unit

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Journal of Intensive Medicine 2024年第1期4卷 16-33页

作者： Alexandre Mestre Tejo Debora Toshie Hamasaki Letícia Mattos Menezes Yeh-Li Ho Intensive Care Unit Department of Intensive Medicine of the Cancer Institute of the State of São PauloHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão PauloBrazil transfusion Medicine and Cell Therapy department A.C.Camargo Cancer CenterSão PauloBrazil Intensive Care Unit of Infectious Disease department Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão PauloBrazil

Dengue fever is considered the most prolific vector-borne disease in the world,with its transmission rate increasing more than eight times in the last two decades.While most cases present mild to moderate symptoms,5%of patients can develop severe disease.Although the mechanisms are yet not fully comprehended,immune-mediated activation leading to excessive cytokine expression is suggested as a cause of the two main findings in critical patients:increased vascular permeability that may shock and thrombocytopenia,and coagulopathy that can induce hemorrhage.The risk factors of severe disease include previous infection by a different serotype,specific genotypes associated with more efficient replication,certain genetic polymorphisms,and comorbidities such as diabetes,obesity,and cardiovascular disease.The World Health Organization recommends careful monitoring and prompt hospitalization of patients with warning signs or propensity for severe disease to reduce mortality.This review aims to update the diagnosis and management of patients with severe dengue in the intensive care unit.

关键词： Severe dengue Intensive care units Shock Pathogenesis Diagnosis Management

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The impact of female sex hormones on cardiovascular disease:from mechanisms to hormone therapy

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Journal of Geriatric Cardiology 2024年第6期21卷 669-681页

作者： Yi KAN Yu-Lu PENG Ze-Hao ZHAO Shu-Tong DONG Yin-Xiao XU Xiao-Teng MA Xiao-Li LIU Yu-Yang LIU Yu-Jie ZHOU department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of Heart Lung and Blood Vessel DiseaseBeijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic DiseaseClinical Center for Coronary Heart DiseaseCapital Medical UniversityBeijingChina

Cardiovascular disease remains the leading cause of mortality in women,yet it has not raised the awareness from the public.The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones.Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects.Before menopause,cardiovascular protective effects of estrogens have been well described.Progestogens were often used in combination with estrogens in hormone therapy.Fluctuations in sex hormone levels,particularly estrogen deficiency,were considered the specific risk factor in women’s cardiovascular disease.However,considerable heterogeneity in the impact of hormone therapy was observed in clinical trials.The heterogeneity is likely closely associated with factors such as the initial time,administration route,dosage,and formulation of hormone therapy.This review will delve into the pathogenesis and hormone therapy,summarizing the effect of female sex hormones on hypertension,pre-eclampsia,coronary heart disease,heart failure with preserved ejection fraction,and cardiovascular risk factors specific to women.

关键词： impact dosage protective

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TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

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Current Medical Science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI Yan-hong LIAO department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic Medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage.Notably,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal fibrosis.However,the regulatory impact of TRPC6 on renal fibrosis remains unclear.Methods In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham operation.Kidneys and serum were collected on days 7,14,21,and 28 after euthanasia.In vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 h.The anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western blotting.Results Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ1.TRPC6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro.Additionally,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 deletion.Conclusion These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3βpathway.Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

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