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Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 104-110 doi: 10.1007/s11684-016-0432-4

摘要：

Advances in next-generation sequencing and bioinformatics have begun to reveal the complex genetic landscape in human cancer genomes, including oral squamous cell carcinoma (OSCC). Sophisticated preclinical models that fully represent intra- and inter-tumoral heterogeneity are required to understand the molecular diversity of cancer and achieve the goal of personalized therapies. Patient-derived xenograft (PDX) models generated from human tumor samples that can retain the histological and genetic features of their donor tumors have been shown to be the preferred preclinical tool in translational cancer research compared with other conventional preclinical models. Specifically, genetically well-defined PDX models can be applied to accelerate targeted antitumor drug development and biomarker discovery. Recently, we have successfully established and characterized an OSCC PDX panel as part of our tumor bio-bank for translational cancer research. In this paper, we discuss the establishment, characterization, and preclinical applications of the PDX models. In particular, we focus on the classification and applications of the PDX models based on validated annotations, including clinicopathological features, genomic profiles, and pharmacological testing information. We also explore the translational value of this well-annotated PDX panel in the development of co-clinical trials for patient stratification and treatment optimization in the near future. Although various limitations still exist, this preclinical approach should be further tested and improved.

关键词： patient-derived xenograft models     personalized medicine     co-clinical trial     patient stratification     oral squamous cell carcinoma    

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A methodology for regulating fuel stratification and improving fuel economy of GCI mode via double main-injection

《能源前沿（英文）》 2023年 第17卷 第5期   页码 678-691 doi: 10.1007/s11708-022-0859-z

摘要： Gasoline compression ignition (GCI) combustion faces problems such as high maximum pressure rise rate (MPRR) and combustion deterioration at high loads. This paper aims to improve the engine performance of the GCI mode by regulating concentration stratification and promoting fuel-gas mixing by utilizing the double main-injection (DMI) strategy. Two direct injectors simultaneously injected gasoline with an octane number of 82.7 to investigate the energy ratio between the two main-injection and exhaust gas recirculation (EGR) on combustion and emissions. High-load experiments were conducted using the DMI strategy and compared with the single main-injection (SMI) strategy and conventional diesel combustion. The results indicate that the DMI strategy have a great potential to reduce the MPRR and improve the fuel economy of the GCI mode. At a 10 bar indicated mean effective pressure, increasing the main-injection-2 ratio (Rm-2) shortens the injection duration and increases the mean mixing time. Optimized Rm-2 could moderate the trade-off between the MPRR and the indicated specific fuel consumption with both reductions. An appropriate EGR should be adopted considering combustion and emissions. The DMI strategy achieves a highly efficient and stable combustion at high loads, with an indicated thermal efficiency (ITE) greater than 48%, CO and THC emissions at low levels, and MPRR within a reasonable range. Compared with the SMI strategy, the maximum improvement of the ITE is 1.5%, and the maximum reduction of MPRR is 1.5 bar/°CA.

关键词： gasoline compression ignition     injection strategy     fuel stratification     high efficiency     high load    

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Comparison of prechilling stratification and sulfuric acid scarification on seed germination of

Nan WANG, Jing GAO, Suiqi ZHANG, Feng YAN

《农业科学与工程前沿（英文）》 2017年 第4卷 第2期   页码 220-227 doi: 10.15302/J-FASE-2017146

摘要： In semi-arid regions of the Loess Plateau, water deficiency restricts plant performance. (switchgrass), which is a highly versatile grass, had been introduced to the Plateau as a restoration species. To determine if prechilling stratification (PCS) and sulfuric acid scarification (SAS) can optimize establishment, cvs Pathfinder, Trailblazer and Alamo were tested under different ambient water potentials by measuring germination and root and shoot growth along water potential gradients under laboratory conditions. Both PCS and SAS improved total germination percentage (TGP), with PCS being more beneficial. The effect of PCS and SAS on mean germination time (MGT) weakened gradually with increasing drought stress. Both PCS and SAS showed no obvious effect on promoting root and shoot growth. Both PCS and SAS reduced base water potential requirement for reaching 50% germination of Pathfinder and Trailblazer, with this effect greater for PCS. These results indicate that embryo dormancy may be a major factor limiting germination of under drought conditions. Pathfinder appears to be more suitable for a semi-arid environment, whereas Alamo appears to be unsuitable for drought conditions. Given the large difference between predicted value and measured value, the reliability and applicable scope of linear regression estimated Y needs further investigation, specification and optimization.

关键词： base water potential     data analysis method     embryo growth     germination    

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Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell

《医学前沿（英文）》 2022年 第16卷 第6期   页码 957-968 doi: 10.1007/s11684-021-0910-1

摘要： Skin and soft tissue infections (SSTIs) refer to infections involving the skin, subcutaneous tissue, fascia, and muscle. In transplant populations with hematological malignancies, an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly. However, to date, the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation (HSCT) patients remain unclear. This study included 228 patients (3.67%) who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital. The overall annual survival rate was 71.5%. We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure (PPGF), comorbidities of acute kidney injury (AKI), and hospital-acquired pneumonia (HAP) were independent risk factors for death in the study population. A PPGF–AKI–HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP. The areas under the curves of internal and external validation were 0.833 (95% CI 0.760–0.906) and 0.826 (95% CI 0.715–0.937), respectively. The calibration plot revealed the high consistency of the estimated risks, and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections     hematopoietic stem cell transplantation     risk stratification system     mortality    

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Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report

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《医学前沿（英文）》 2017年 第11卷 第2期   页码 284-286 doi: 10.1007/s11684-017-0514-y

摘要：

Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.

关键词： arsenic trioxide     APL     rhabdomyolysis    

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Chaotic behavior of LNG after stratification in main stream region of storage tank

WANG Jingjing, MA Xiaoqian

《能源前沿（英文）》 2008年 第2卷 第4期   页码 514-518 doi: 10.1007/s11708-008-0076-4

摘要： A study of the chaotic behavior of liquefied natural gas (LNG) after stratification in the main stream region of a storage tank was conducted. Based on non-linear dynamics, a 2-dimensional Rayleigh-Benard convection model was developed to simulate the convection, Lorenz equations of LNG convection were deduced from conservation equations, and the Runge-Kutta method was used to solve the equations. The results showed that when = 1.33, 106 < < 1470, chaos was obtained, which meant that the velocity field and the temperature field were highly unsteady. In addition, the influence of temperature and scale factor on the solutions and the corresponding range of parameters were studied. The results revealed that the chaos in LNG convection resulted from the interaction of buoyancy and viscid forces. A small quantity of heat impacting the storage tank would lead to a strong and unstable convection of LNG in the main stream region.

关键词： Runge-Kutta     non-linear     corresponding     temperature     addition    

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An investigation on patient dose in screen-film diagnostic radiology in Lhasa City, Xizang Autonomous

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《医学前沿（英文）》 2013年 第7卷 第4期   页码 506-509 doi: 10.1007/s11684-013-0294-y

摘要：

This study aimed to investigate patient dose in diagnostic screen-film radiographic examinations in the city of Lhasa, China. Seven out of the twenty-six hospitals registered with the Lhasa Health Bureau were included in the investigation. The entrance surface air Kerma (ESAK) of seven conventional screen-film radiology X-ray equipment in these hospitals was measured with a QA dosimeter in September 2012. The X-ray examinations were divided into three categories: PA (posterior-anterior) chest, upper/lower limb, and AP (anterior-posterior) lumbar spine. For each category, ESAKs were calculated and analyzed. The mean ESAK was 0.6 mGy for PA chest, 0.3 mGy for upper/lower limb, and 1.8 mGy for AP lumbar spine. In addition, the mean ESAK value recorded for PA chest X-ray examinations exceeded the corresponding value recommended by the International Atomic Energy Agency (0.4 mGy).

关键词： radiation dosage     radiology     radiation protection     radiography/statistics & numerical data    

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Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

《医学前沿（英文）》 2022年 第16卷 第1期   页码 150-155 doi: 10.1007/s11684-021-0846-5

摘要： Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G>A, p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C>G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C>G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.

关键词： cystic fibrosis     CFTR     splicing mutation     minigene    

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》 2022年 第16卷 第4期   页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint     Siglec10     kidney renal clear cell carcinoma    

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Xingnao Kaiqiao acupuncture combined with Angong Niuhuang Wan for a patient under persistent vegetative

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《医学前沿（英文）》 2018年 第12卷 第3期   页码 334-339 doi: 10.1007/s11684-017-0539-2

摘要：

Persistent vegetative state (PVS) is a clinical condition wherein the cerebral cortex loses its function although brain stem function remains relatively intact. It has high mortality and disability rates. Although treatment for PVS is extensively studied in developed countries, little breakthrough has been made. In China, many PVS patients who were treated with traditional Chinese medicine (TCM) and acupuncture therapy were reported to have regained consciousness. In our department, we have been investigating TCM diagnosis and treatment methods for PVS for many years and have summarized a set of curative programs. Our patient is a male and 5 years and 3 months of age. He had traumatic brain injury and had been unconscious for three months on admission. Considering his condition, we adopted Xingnao Kaiqiao acupuncture, oral Angong Niuhuang Wan, and Xingnaojing intravenous drip. After the 50-day treatment, his health significantly improved and is nearly similar to that of a healthy child, indicating that the treatment is effective for PVS. Therefore, we decided to report the case and treatment methods.

关键词： PVS     stubborn disease     Xingnao Kaiqiao     Angong Niuhuang Wan     TCM     acupuncture    

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Ventricular tachycardia in a disseminated MDR-TB patient: a case report and brief review of literature

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 259-263 doi: 10.1007/s11684-014-0321-7

摘要：

Although significant breakthroughs have been achieved in tuberculosis management, we still encounter numerous difficulties in diagnosis and treatment of the disease. Additionally, a new challenge, multidrug-resistant tuberculosis (MDR-TB) with unspecific clinical presentation, often results in delayed diagnosis. In this paper, we reported a case of disseminated tuberculosis with rare presentation of ventricular fibrillation, which proved resistant to both isoniazid and rifampicin. A review of literature showed that ventricular fibrillation or tachycardia in tuberculosis patients with pericarditis or myocarditis has been sporadically reported in the past, but none has been conducted involving patients with MDR-TB infections.

关键词： tuberculosis     MDR-TB     ventricular tachycardia    

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Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 250-253 doi: 10.1007/s11684-014-0333-3

摘要：

The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery.

关键词： acute-on-chronic liver failure     submassive necrosis     viral hepatitis B     esophageal variceal bleeding     liver transplantation    

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Reverse engineering in the construction of numerical simulation oriented patient-specific model of stented

Xianlong MENG, Wenyu FU, Yun ZHANG, Aike QIAO,

《机械工程前沿（英文）》 2010年 第5卷 第3期   页码 328-335 doi: 10.1007/s11465-010-0026-9

摘要： Patient-specific models are widely used in hemodynamic simulations. The flow in the boundary layer changes so strongly that fine meshes in the boundary layer are required in numerical simulations, especially for the calculation of wall shear stress and its gradient. To precisely analyze hemodynamics, it is necessary to investigate the approaches to the reconstruction of a numerical simulation-oriented patient-specific model for aortic arch aneurysm that can perform particular meshing in the boundary layer. Based on a surface model of aortic arch aneurysm in STL format, reverse engineering concept was applied to reconstruct a solid model using CAD software Geomagic and Pro/E, and a simplified model of stent for the intervention of aortic arch aneurysm was also created. After these models were imported to ANSYS, a block modeling approach was employed to divide the whole model into several domain blocks to adopt different meshing strategies. Particular meshing was performed especially in the boundary layer and around the stents. The finite element model particularly suitable for numerical simulation of hemodynamics was obtained. Hemodynamic simulation was performed, using the constructed finite element model to verify its applicability. The results indicate that reverse engineering concept and the proposed block modeling approach can be used to divide the solid model of aortic arch aneurysm into multiple volumes, which can be meshed according to particular requirements in each volume; the finite element model of stented aortic arch aneurysm can be employed to simulate hemodynamics. The approaches of modeling were applicable not only for aortic arch aneurysm, but also for similar model reconstruction as a reference in hemodynamic simulation investigations.

关键词： reverse engineering     aortic arch aneurysm     surface model     meshing     finite element model    

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Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

SUN Ledong, SUN Jing, ZENG Kang, MENG Fanyi, DIAO Youtao, XU Dan, HUANG Liang, ZHAO Jie, Liu Qifa

《医学前沿（英文）》 2008年 第2卷 第2期   页码 191-194 doi: 10.1007/s11684-008-0036-8

摘要： The aim of this study is to explore the effectiveness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus. A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities. The diagnosis of pemphigus was made on the basis of the clinical, histologic and immunofluorescence findings. The patient had shown resistance to conventional therapy with glucocorticoid and immunosuppressive agents. Two months before admission, he complained of hip joint pain. X-ray and CT scan revealed aseptic necrosis of the femoral head. Stem-cell mobilization was achieved by treatment with cyclophosphamide, granulocyte colony-stimulating factor (G-CSF) and rituximab. Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use. Immunoablation was accomplished by using cyclophosphamide (200 mg/kg; divided into 50 mg/kg on days -5, -4, -3, and -2), antithymocyte globulin (ATG; 10 mg/kg; divided into 2.5 mg/kg on days -6, -5, -4, and -3), and rituximab (1200 mg/d; divided into 600 mg/d on days 0 and 7). Autologous peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system which was monitored by flow cytometry. The glucocorticoid was withdrawn immediately after transplantation. The pemphigus titer turned negative 6 weeks after transplantation and remained negative. The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of follow-up. The patient’s response suggests that autologous peripheral hematopoietic stem cell transplantation may be a potential “cure” for refractory pemphigus. However, further studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resistance to conventional therapy.

关键词： serological activity     leukapheresis     peripheral hematopoietic     cyclophosphamide     resistance    

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Catheterization via direct cannulation of superior vena cava for a hemodialysis patient with an original

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 445-448 doi: 10.1007/s11684-017-0520-0

摘要：

Establishing a long-term vascular access in patients exhibiting vascular access exhaustion is challenging. In this study, we reported a case of a direct catheterization in the superior vena cava of a hemodialysis patient with vascular access exhaustion and original dysfunctional catheter inserted via the left internal jugular vein. The direct catheterization was performed with cuffed tunnel catheter (CUFF) and guided by digital subtraction angiography (DSA) and multidetector computed tomography venography (MDCTV). The DSA and MDCTV results revealed an occlusion in the right innominate vein and thromboses in the left innominate, right internal jugular, subclavian, and femoral veins. The distal end of the superior vena cava was localized clearly by the original CUFF under DSA. Directed at the distal end of the superior vena cava, a 0.5-cm secondary puncture was introduced below the lateral head of the sternocleidomastoid muscle via the right neck area. This study is one of the few reports regarding direct catheterization of CUFF via the superior vena cava of a patient with vascular access exhaustion and CUFF dysfunction on the left internal jugular vein. We believe that our study can provide a new alternative for inserting central venous catheter for such patient.

关键词： superior vena cava     intervention     vascular access exhaustion     catheterization     tunneled cuffed hemodialysis catheter    

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标题 作者 时间 类型 操作

Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research

null

期刊论文

A methodology for regulating fuel stratification and improving fuel economy of GCI mode via double main-injection

期刊论文

Comparison of prechilling stratification and sulfuric acid scarification on seed germination of

Nan WANG, Jing GAO, Suiqi ZHANG, Feng YAN

期刊论文

Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell

期刊论文

Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report

null

期刊论文

Chaotic behavior of LNG after stratification in main stream region of storage tank

WANG Jingjing, MA Xiaoqian

期刊论文

An investigation on patient dose in screen-film diagnostic radiology in Lhasa City, Xizang Autonomous

null

期刊论文

Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

期刊论文

Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

期刊论文

Xingnao Kaiqiao acupuncture combined with Angong Niuhuang Wan for a patient under persistent vegetative

null

期刊论文

Ventricular tachycardia in a disseminated MDR-TB patient: a case report and brief review of literature

null

期刊论文

Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report

null

期刊论文

Reverse engineering in the construction of numerical simulation oriented patient-specific model of stented

Xianlong MENG, Wenyu FU, Yun ZHANG, Aike QIAO,

期刊论文

Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

SUN Ledong, SUN Jing, ZENG Kang, MENG Fanyi, DIAO Youtao, XU Dan, HUANG Liang, ZHAO Jie, Liu Qifa

期刊论文

Catheterization via direct cannulation of superior vena cava for a hemodialysis patient with an original

null

期刊论文