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Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death

《医学前沿(英文)》 2022年 第16卷 第5期   页码 760-765 doi: 10.1007/s11684-021-0899-5

摘要: Voluntary contribution has become the only source of donor lungs in China since 2015. To elaborate the outcomes of patients awaiting lung transplantation (LTx) after the implementation of donation after brain death, we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1, 2015 to January 1, 2021. A total of 180 patients were enrolled in the study. The median waiting time was 1.25 months. Interstitial lung disease (ILD) (103/180, 57.2%) and chronic obstructive pulmonary disease (COPD) (56/180, 31.1%) were the most common diseases in our study population. The mean pulmonary artery pressure (mPAP) of patients in the died-waiting group was higher than that of the survivors (53.29±21.71 mmHg vs. 42.11±18.58 mmHg, P=0.002). The mortality of patients with ILD (34/103, 33.00%) was nearly twice that of patients with COPD (10/56, 17.86%) while awaiting LTx (P=0.041). In the died-waiting group, patients with ILD had a shorter median waiting time than patients with COPD after being listed (0.865 months vs. 4.720 months, P=0.030). ILD as primary disease and mPAP > 35 mmHg were two significant independent risk factors for waitlist mortality, with hazard ratios (HR) of 3.483 (95% CI 1.311–9.111; P=0.011) and 3.500 (95% CI 1.435–8.536; P=0.006). Hence, LTx is more urgently needed in patients with ILD and pulmonary hypertension.

关键词: lung transplantation     donation after brain death     waitlist    

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients

《医学前沿(英文)》 2023年 第17卷 第1期   页码 58-67 doi: 10.1007/s11684-022-0937-y

摘要: The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65–70 years (111 recipients, group 65–70) and 70 years (55 recipients, group 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group 70 (30.9% vs. 14.4% in group 65–70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65–70) and 7.3% (group 70) of patients. Kaplan–Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.

关键词: cardiac disease     mortality     aged population     lung transplantation    

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

《医学前沿(英文)》 2018年 第12卷 第2期   页码 224-228 doi: 10.1007/s11684-017-0538-3

摘要:

Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

关键词: bronchiolitis obliterans syndrome (BOS)     hematopoietic stem cell transplantation (HSCT)     lung transplantation (LTX)    

HLA and lung transplantation

Liya Ju, Caroline Suberbielle, Xiaofan Li, Nuala Mooney, Dominique Charron

《医学前沿(英文)》 2019年 第13卷 第3期   页码 298-313 doi: 10.1007/s11684-018-0636-x

摘要: Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.

关键词: human leukocyte antigen class I and II     lung transplantation     mismatch     obliterans bronchiolitis     alloantibody     antibody mediated rejection    

Curbing the burden of lung cancer

null

《医学前沿(英文)》 2016年 第10卷 第2期   页码 228-232 doi: 10.1007/s11684-016-0447-x

摘要:

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smoking-attributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

关键词: lung cancer     screening     risk factors     environmental    

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

《医学前沿(英文)》 2023年 第17卷 第4期   页码 714-728 doi: 10.1007/s11684-022-0959-5

摘要: FRMD6, a member of the 4.1 ezrin–radixin–moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6−/− gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

关键词: FRMD6     lung cancer     mTOR pathway    

Pathogenesis sequences in Gejiu miners with lung cancer: an introduction

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 344-349 doi: 10.1007/s11684-015-0399-6

摘要:

Tin miners in Gejiu, Yunnan Province, China are at high risk of developing lung cancer with significant occupational characteristics. Tissue samples from these miners presented pathological characteristics, such as fibroplasia in carcinomas, peri-cancerous tissue in lung cancers, and hyperplasia and dysplasia of epithelial cells in peri-cancerous tissue. Carcinomas induced by Yunnan tin mine dust in the animal experiment underwent inflammation, fibroplasia, hyperplasia, dysplasia, and carcinogenesis of epithelial cells. A correlated and synergistic relationship was observed between bronchial epithelial cell transformation and fibroblast activation in vitro induced by mine dust. Fibroblast hyperplasia and activation are important factors that promote the transformation and carcinogenesis of epithelial cells. Our findings suggested that pulmonary fibrosis may increase the risk and promote the occurrence of lung cancer, which can lead to lung fiber hyperplasia.

关键词: Yunnan tin mine     miners     lung cancer    

The epidemic status and risk factors of lung cancer in Xuanwei City, Yunnan Province, China

null

《医学前沿(英文)》 2012年 第6卷 第4期   页码 388-394 doi: 10.1007/s11684-012-0233-3

摘要:

Xuanwei City (formerly known as Xuanwei County) locates in the northeastern of Yunnan Province and is rich in coal, iron, copper and other mines, especially the smoky (bituminous) coal. Unfortunately, the lung cancer morbidity and mortality rates in this region are among China’s highest, with a clear upward trend from the mid-1970s to mid-2000s. In 2004–2005, the crude death rate of lung cancer was 91.3 per 100 000 in the whole Xuanwei City, while that for Laibin Town in this city was 241.14 per 100 000. The epidemiologic distribution (clustering patterns by population, time, and space) of lung cancer in Xuanwei has some special features, e.g., high incidence in rural areas, high incidence in females, and an early age peak in lung cancer deaths. The main factor that associates with a high rate of lung cancer incidence was found to be indoor air pollution caused by the indoor burning of smoky coal. To a certain extent, genetic defects are also associated with the high incidence of lung cancer in Xuanwei. Taken together, lung cancer in this smoky coal combustion region is a unique model for environmental factor-related human cancer, and the current studies indicate that abandoning the use of smoky coal is the key to diminish lung cancer morbidity and mortality.

关键词: lung cancer     Xuanwei     smoky coal combustion     polycyclic aromatic hydrocarbons     epidemiology    

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneicperipheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿(英文)》 2021年 第15卷 第1期   页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要: Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词: post-transplantation cyclophosphamide     allogeneic hematopoietic stem cell transplantation     lymphoid malignancies    

Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

Bo PENG BA , Jinnong ZHANG MD , Jamile S. WOODS MD , Wei PENG MD, PhD

《医学前沿(英文)》 2009年 第3卷 第3期   页码 245-255 doi: 10.1007/s11684-009-0044-3

摘要: Lung cancer is one of the most common human cancers and the number one cancer killer in the United States. In general, lung cancer includes small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but NSCLC accounts for approximately 90% of lung cancer. The early diagnosis and therapy of lung cancer still presents a big challenge because validated screening tools, which can improve current early detection to reduce mortality from lung cancer, do not exist. Over the last decade, molecular genetic abnormalities have been described in NSCLC, including chromosomal aberrations, overexpression of oncogenes, and deletion and/or mutations in tumor suppressor genes. These molecular markers in NSCLC demonstrated close associations with the development of lung cancer such as Ras, the epidermal growth factor receptor (EGFR, or c-erbB-1), HER2 (c-erbB-2), c-Met, and Bcl-2. Therefore, this information may be applied for early cancer detection, classification, novel targeted therapy, and prognosis in NSCLC. Recent clinical data have revealed that targeted therapy might be the second-line therapy as an alternative approach. Currently, the targeted therapies are mainly focused on two lung cancer pathways, the EGFR and the vascular endothelial growth factor (VEGF) pathways. Some clinical trials are very encouraging, but some of them are not. However, these trials have not identified a subgroup of NSCLC with biomarkers. Therefore, it is very important to select NSCLC patients with biomarkers to match targeted agents so that we can further identify effectiveness of targeted therapy in the future.

关键词: lung cancer     carcinoma     non-small cell lung cancer     molecular markers     targeted therapy    

MicroRNAs and lung cancers: from pathogenesis to clinical implications

null

《医学前沿(英文)》 2012年 第6卷 第2期   页码 134-155 doi: 10.1007/s11684-012-0188-4

摘要:

Lung cancer is the leading cause of cancer-related deaths in the US and worldwide. Better understanding of the disease is warranted for improvement in clinical management. Here we summarize the functions of small-RNA-based, posttranscriptional gene regulators, i.e. microRNAs, in the pathogenesis of lung cancers. We discuss the microRNAs that play oncogenic as well as tumor suppressive roles. We also touch on the value of microRNAs as markers for diagnosis, prognosis and the promising field of microRNA-based novel therapies for lung cancers.

关键词: lung biology     lung cancer     microRNA    

Partial liver transplantation

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 1-7 doi: 10.1007/s11684-010-0105-7

摘要:

Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situto ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

关键词: partial liver transplantation     reduced-size liver transplantation     split liver transplantation     living donor liver transplantation    

Successful kidney transplantation in highly sensitized patients

null

《医学前沿(英文)》 2011年 第5卷 第1期   页码 80-85 doi: 10.1007/s11684-011-0115-0

摘要:

Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panel-reactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novoproduction of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients.

关键词: Kidney transplantation     desensitization    

Diffuse cystic lung diseases

null

《医学前沿(英文)》 2013年 第7卷 第3期   页码 316-327 doi: 10.1007/s11684-013-0269-z

摘要:

Diffuse cystic lung diseases are uncommon but can present a diagnostic challenge because increasing number of diseases have been associated with this presentation. Cyst in the lung is defined as a round parenchymal lucency with a well-defined thin wall (<2 mm thickness). Focal or multifocal cystic lesions include blebs, bullae, pneumatoceles, congenital cystic lesions, traumatic lesions, and several infectious processes such as coccidioidomycosis, Pneumocystis jiroveci pneumonia, and hydatid disease. “Diffuse” distribution in the lung implies involvement of all lobes. Diffuse lung involvement with cystic lesions can be seen in pulmonary lymphangioleiomyomatosis, pulmonary Langerhans’ cell histiocytosis, lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, amyloidosis, light chain deposition disease, honeycomb lung associated with advanced fibrosis, and several other rare causes including metastatic disease. High-resolution computed tomography of the chest helps define morphologic features of the lung lesions as well as their distribution and associated features such as intrathoracic lymphadenopathy. Correlating the tempo of the disease process and clinical context with chest imaging findings serve as important clues to defining the underlying nature of the cystic lung disease and guide diagnostic evaluation as well as management.

关键词: cyst     lung disease     interstitial lung disease     lymphangioleiomyomatosis     Langerhans’ cell histiocytosis     Birt-Hogg-Dubé syndrome    

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical

《医学前沿(英文)》 2022年 第16卷 第3期   页码 389-402 doi: 10.1007/s11684-021-0856-3

摘要: Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2=0.033; P=0.018), followed by acute kidney injury (AKI; R2=0.032; P=0.011) and plasma MIP-1β level (R2=0.027; P=0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients’ lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

关键词: severe community-acquired pneumonia     lung microbiota     clinical improvements     7-category ordinal scale     Prevotellaceae    

标题 作者 时间 类型 操作

Outcomes of patients awaiting lung transplantation after the implementation of donation after brain death

期刊论文

Association of cardiac disease with the risk of post-lung transplantation mortality in Chinese recipients

期刊论文

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation

null

期刊论文

HLA and lung transplantation

Liya Ju, Caroline Suberbielle, Xiaofan Li, Nuala Mooney, Dominique Charron

期刊论文

Curbing the burden of lung cancer

null

期刊论文

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

期刊论文

Pathogenesis sequences in Gejiu miners with lung cancer: an introduction

null

期刊论文

The epidemic status and risk factors of lung cancer in Xuanwei City, Yunnan Province, China

null

期刊论文

Fludarabine and intravenous busulfan conditioning with post-transplantation cyclophosphamide for allogeneicperipheral stem cell transplantation for adult patients with lymphoid malignancies: a prospective single-arm

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

期刊论文

Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

Bo PENG BA , Jinnong ZHANG MD , Jamile S. WOODS MD , Wei PENG MD, PhD

期刊论文

MicroRNAs and lung cancers: from pathogenesis to clinical implications

null

期刊论文

Partial liver transplantation

null

期刊论文

Successful kidney transplantation in highly sensitized patients

null

期刊论文

Diffuse cystic lung diseases

null

期刊论文

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical

期刊论文