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Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection:

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 480-489 doi: 10.1007/s11684-017-0594-8

摘要：

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

关键词： human immunodeficiency virus type I     superinfection     incidence     immune response    

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Molecular network-based intervention brings us closer to ending the HIV pandemic

Xiaoxu Han, Bin Zhao, Minghui An, Ping Zhong, Hong Shang

《医学前沿（英文）》 2020年 第14卷 第2期   页码 136-148 doi: 10.1007/s11684-020-0756-y

摘要： Precise identification of HIV transmission among populations is a key step in public health responses. However, the HIV transmission network is usually difficult to determine. HIV molecular networks can be determined by phylogenetic approach, genetic distance-based approach, and a combination of both approaches. These approaches are increasingly used to identify transmission networks among populations, reconstruct the history of HIV spread, monitor the dynamics of HIV transmission, guide targeted intervention on key subpopulations, and assess the effects of interventions. Simulation and retrospective studies have demonstrated that these molecular network-based interventions are more cost-effective than random or traditional interventions. However, we still need to address several challenges to improve the practice of molecular network-guided targeting interventions to finally end the HIV epidemic. The data remain limited or difficult to obtain, and more automatic real-time tools are required. In addition, molecular and social networks must be combined, and technical parameters and ethnic issues warrant further studies.

关键词： human immunodeficiency virus type 1     molecular cluster     transmission cluster     risk network     targeted intervention     evaluation    

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Natural history of HIV infection in former plasma donors in rural China

Min ZHANG, Hong SHANG, Zhe WANG, Wei-Guo CUI, Qing-Hai HU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 346-350 doi: 10.1007/s11684-010-0102-x

摘要： Patients infected through commercial blood-selling practices (former plasma donors, FPDs) in China represent a unique patient population compared to individuals infected through sexual contact or intravenous drug use. FPDs all have an approximate time of human immunodeficiency virus (HIV) infection during the mid-1990s. Few studies about the natural history of HIV infection in these patients were performed. The current study focuses on characterizing the duration of asymptomatic infection as well as the time to disease and mortality of infected FPDs in China. A retrospective cohort study was conducted based on data collected from 5484 HIV-1 infected FPDs in Shangcai county, Henan province. Kaplan-Meier analysis was applied to estimate the asymptomatic duration from the time of infection to the onset of AIDS as well as the survival period from the onset of AIDS to the time of death. The estimated median asymptomatic phase was about 9.21 years, which is similar to that reported in other developing countries in Africa. The estimated median life span after the onset of symptoms was about 9.91 months, which is notably shorter than life spans reported elsewhere. This is the first large-scale retrospective study on the natural history of HIV infection in FPDs in rural China. The findings not only provide valuable insight into an understudied population, but should also serve as an important reference for patient management and care.

关键词： human immunodeficiency virus (HIV)     former plasma donor     natural history     China    

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Clinical significance of human papilloma virus infection in the cervical lesions

Shuang LI, Yu-Han MENG, Hu TING, Jian SHEN, Ding MA

《医学前沿（英文）》 2010年 第4卷 第3期   页码 264-270 doi: 10.1007/s11684-010-0094-6

摘要： Cervical lesions have been regarded as the common and frequently occurring diseases in China. Recently, the morbidity and youth tendency of cervical cancer have gradually increased. Cervical cancer, related with human papilloma virus (HPV) infection, has been one of the severest diseases threatening health and life of women, and is an infectious disease. The universality of HPV infection in the reproductive tract should not be ignored. The well-known risk factors of HPV infection in cervical lesions consist of high-risk sexual behaviors, immunosuppression, age, contraceptive methods, the concurrent infection of other sexually transmitted diseases, etc. The variation of cervical lesions induced by HPV infection is involved in the continuous pathological process, including the subclinical, latent, and persistent infection of high risk (HR)-HPV, chronic cervicitis with abnormal results of cytological examination, cervical intraepithelial neoplasia (CIN), and cervical cancer. The outcome of patients with HPV infection is influenced by many factors, such as HPV subtype dominance, persistent HPV infection, HPV loading dose, and multiple HPV infection. Controlling HR-HPV persistent infection should be an important strategy for reducing cervical lesions.

关键词： cervical lesion     high risk-human papilloma virus     persistent infection     loading dose     cervical intraepithelial neoplasia     cervical cancer    

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Universal influenza virus vaccines: what can we learn from the human immune response following exposure

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 471-479 doi: 10.1007/s11684-017-0602-z

摘要：

Several universal influenza virus vaccine candidates based on eliciting antibodies against the hemagglutinin stalk domain are in development. Typically, these vaccines induce responses that target group 1 or group 2 hemagglutinins with little to no cross-group reactivity and protection. Similarly, the majority of human anti-stalk monoclonal antibodies that have been isolated are directed against group 1 or group 2 hemagglutinins with very few that bind to hemagglutinins of both groups. Here we review what is known about the human humoral immune response to vaccination and infection with H7 subtype influenza viruses on a polyclonal and monoclonal level. It seems that unlike vaccination with H5 hemagglutinin, which induces antibody responses mostly restricted to the group 1 stalk domain, H7 exposure induces both group 2 and cross-group antibody responses. A better understanding of this phenomenon and the underlying mechanisms might help to develop future universal influenza virus vaccine candidates.

关键词： universal influenza virus vaccine     hemagglutinin stalk     H7N9    

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Metabolomics in human type 2 diabetes research

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《医学前沿（英文）》 2013年 第7卷 第1期   页码 4-13 doi: 10.1007/s11684-013-0248-4

摘要：

The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern society. Although scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades, little progress has been made toward curing the disease or even getting it under control, from a public health and overall societal standpoint. There is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses, highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic complications. The emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites, which are sensitive to the changes of both environmental and genetic factors and therefore, could be regarded as the link between genotypes and phenotypes. During the last decade, the progression made in metabolomics has provided insightful information on disease development and disease onset prediction. Recent studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered, including branched-chain and aromatic amino acids, such as isoleucine, leucine, valine, tyrosine and phenylalanine, as diagnostic or highly-significant predictors of future diabetes. This review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes, type 2 diabetes.

关键词： metabolomics     type 2 diabetes     metabolic pathway     mass spectrometry     nuclear magnetic resonance (NMR)    

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<i>RR1i> and <i>RR2i> gene deletion affects the immunogenicity of a live attenuated pseudorabiesvirus vaccine candidate in natural pig host

Shijun YAN,He YAN,Chaolin ZHANG,Tongyan WANG,Qingyuan YANG,Zhe SUN,Yan XIAO,Feifei TAN,Xiangdong LI,Kegong TIAN

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 81-86 doi: 10.15302/J-FASE-2016088

摘要： As virulence-determining genes, and encode the small subunit and large subunit of viral ribonucleotide reductase (RR) in pseudorabies virus which have been extensively studied in mice. However, their role in pigs has not been adequately investigated. In this study, we deleted and genes based on a / / triple gene-deleted pseudorabies virus and tested its efficacy in pigs as a vaccine candidate. The rescued virus showed similar growth properties and plaque size as its parent strain. In an animal study, the virus could elicit humoral immune responses shown by generation of gB-specific antibodies and virus neutralizing antibodies. However, vaccination could not provide protection against virulent pseudorabies virus challenge since vaccinated pigs showed clinical pseudorabies-specific syndromes. The deficiency in protection may due to the generation of late and low levels of gB antibodies and virus neutralizing antibodies.

关键词： pseudorabies virus     RR1 and RR2     ribonucleotide reductase     vaccine candidate    

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Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

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《医学前沿（英文）》 2014年 第8卷 第1期   页码 1-5 doi: 10.1007/s11684-014-0309-3

摘要：

Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

关键词： hyperthermia     HPV     immune response     virus     tumor    

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Epidemiological studies of women under age 30 infected with human papillomavirus

Zhihua LIU MD, Qing LI BM, Weihong LI BM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 459-462 doi: 10.1007/s11684-009-0084-8

摘要： The aim of this paper was to investigate the prevalence of human papilloma virus (HPV) infection in women under 30 years old with cervical intraepithelial neoplasia (CIN) or cervical cancer, in order to provide a basis for cervical cancer prevention and treatment. We recruited 2052 female cases from the education system in Futian District, Shenzhen city, from April 2006 to April 2008, with age ranging from 22 to 60 years old. Second-generation hybrid capture test was done for detection of female genital tract HPV and cervical colposcopy for screening CIN or cervical cancer. The prevalence of HPV and cervical precancerous lesions or cervical cancer was evaluated in different age groups of women. The HPV positive rate was 247/2052 (12.00%), and 35/2052 (1.71%) of the cases were≥CIN I by pathological diagnosis. In the 22―29-year-old age group, there were 291 cases, including 39HPV-positive cases (13.40%) and one case of pathological diagnosis≥CIN I (0.34%), and there were 1761 cases in the 30―60-year-old age group, including 208 HPV-positive cases (11.81%) and 34 cases of pathological diagnosis≥CIN I (1.93%). The HPV-positive rate of 22―29-year-old age group was higher than that of 30―60-year-old age group, but the difference was not significant ( = 0.5967, = 0.4398); the CIN and cervical cancer detection rate of the former group was lower than that of the latter one, and the difference was not significant either ( = 3.7519, = 0.0527). The cases in 30―60-year-old age group were divided into five age sub-groups, and the HPV-positive rate of the 22―29-year-old age group was compared with the remaining groups, and it was found that the HPV-positive rate of the former group (13.40%) was lower than that of the 40―44-year-old age group (14.70%) but higher than that of the other four groups. Moreover, the difference in the HPV-positive rate between the 22―29-year-old age group and the 50―60-year-old age group (6.06%) was significant ( = 5.545, = 0.018), but the difference between the 22― 29-year-old age group and each of the other four groups was not significant (>0.05). In addition, the CIN and cervical cancer detection rate of the 22―29-year-old age group (0.34%) was lower than that of the remaining five groups, and the difference between the 22―29-year-old age group and the 35―39-year-old age group (2.26%), and between 22―29-year-old age group and 40―44-year-old age group (2.30%) was significant ( = 4.446, = 0.0035; = 4.525, = 0.0363, respectively), but the difference between the 22―29-year-old age group and each of other three groups was not significant (>0.05). Furthermore, 80.00% (28/35) cases of pathological diagnosis≥CIN I and 90.91% (10/11) lesions of pathological diagnosis≥CIN II occurred at 35―49 years of age. For many young women below the age of 30 who were infected with high-risk HPV were one-off infections, so it was not appropriate to recommend HPV detection as cervical precancerous lesions or cancer screening program for women less than 30 years old. The prevention and treatment of cervical cancer should be focused on those women more than 35 years of age.

关键词： cervical cancer     human papilloma virus     cervical intraepithelial neoplasia    

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An experimental characterization of human torso motion

Daniele CAFOLLA,I-Ming CHEN,Marco CECCARELLI

《机械工程前沿（英文）》 2015年 第10卷 第4期   页码 311-325 doi: 10.1007/s11465-015-0352-z

摘要：

The torso plays an important role in the human-like operation of humanoids. In this paper, a method is proposed to analyze the behavior of the human torso by using inertial and magnetic sensing tools. Experiments are conducted to characterize the motion performance of the human torso during daily routine operations. Furthermore, the forces acting on the human body during these operations are evaluated to design and validate the performance of a humanoid robot.

关键词： experimental biomechanics     human torso     analysis     inertial sensor     characterization    

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Human monoclonal antibodies as candidate therapeutics against emerging viruses

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 462-470 doi: 10.1007/s11684-017-0596-6

摘要：

The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies (mAbs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-cell isolation. Consequently, an increasing number of mAbs, which exhibit high potency against emerging viruses in vitro and in animal models of infection, have been developed. In this paper, we summarize historical trends and recent developments in mAb discovery, compare the advantages and disadvantages of various approaches to mAb production, and discuss the potential use of such strategies for the development of antivirals against emerging diseases. We also review the application of recently developed human mAbs against SARS-CoV, MERS-CoV, and Ebola virus and discuss prospects for the development of mAbs as therapeutic agents against emerging viral diseases.

关键词： human monoclonal antibodies     emerging infectious diseases     SARS-CoV     MERS-CoV     Ebola virus    

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Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 399-411 doi: 10.1007/s11684-010-0170-y

摘要： β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway. In our study, we found that, in the development of hepatocellular carcinoma (HCC), β-catenin was correlated with hepatitis B virus (HBV) X gene encoded protein, which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis. The expression levels of wild-type β-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein (HBx), accompanied by destabilization of adherens junction. Reverse transcriptase PCR (RT-PCR), Northern and Western blot showed that reduction of wild-type β-catenin expression involved degradation of the protein. However, RNA interference (RNAi) and luciferase assay indicated that HBx enhanced β-catenin mediated signaling in HepG2 cells. In addition, immunohistochemical and Western blot analysis of β-catenin revealed that a decrease in the β-catenin protein level was found in 58.3% of HBV-related HCCs 19.2% of non-HBV-related tumors. Our data suggest that the expression of HBx contributed to the development of HCC, in part, by repressing the wild-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.

关键词： hepatocellular carcinoma     hepatitis B virus X protein     β     -catenin     cell adhesion     E-cadherin     transcriptional activation    

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NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 177-184 doi: 10.1007/s11684-010-0038-1

摘要： Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, five individuals showed 73€A→G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV 2, which might contribute to the development of LD.

关键词： nucleoside reverse transcriptase inhibitors     human immunodeficiency virus     mitochondrial DNA     D loop     mutation    

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correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human

《医学前沿（英文）》 2022年 第16卷 第4期   页码 584-595 doi: 10.1007/s11684-021-0844-7

摘要： Conventional therapies for hemophilia A (HA) are prophylactic or on-demand intravenous FVIII infusions. However, they are expensive and inconvenient to perform. Thus, better strategies for HA treatment must be developed. In this study, a recombinant FVIII cDNA encoding a human/rat hybrid FVIII with an enhanced procoagulant potential for adeno-associated virus (AAV)-delivered gene therapy was developed. Plasmids containing human FVIII heavy chain (hHC), human light chain (hLC), and rat light chain (rLC) were transfected into cells and hydrodynamically injected into HA mice. Purified AAV viruses were intravenously injected into HA mice at two doses. Results showed that the hHC+ rLC protein had a higher activity than the hHC+ hLC protein at comparable expression levels. The specific activity of hHC+ rLC was about 4- to 8-fold higher than that of their counterparts. Hydrodynamic injection experiments obtained consistent results. Notably, the HA mice undergoing the AAV-delivered hHC+ rLC treatment exhibited a visibly higher activity than those treated with hHC+ hLC, and the therapeutic effects lasted for up to 40 weeks. In conclusion, the application of the hybrid FVIII (hHC+ rLC) via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice. These data might be of help to the development of optimized FVIII expression cassette for HA gene therapy.

关键词： hemophilia A     adeno-associated virus (AAV)     human/rat hybrid factor VIII     gene therapy     dual chain strategy    

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A low cost wearable optical-based goniometer for human joint monitoring

Chee Kian LIM, Zhiqiang LUO, I-Ming CHEN, Song Huat YEO

《机械工程前沿（英文）》 2011年 第6卷 第1期   页码 13-22 doi: 10.1007/s11465-011-0201-7

摘要：

Widely used in the fields of physical and occupational therapy, goniometers are indispensible when it comes to angular measurement of the human joint. In both fields, there is a need to measure the range of motion associated with various joints and muscle groups. For example, a goniometer may be used to help determine the current status of the range of motion in bend the arm at the elbow, bending the knee, or bending at the waist. The device can help to establish the range of motion at the beginning of the treatment series, and also allow the therapist to monitor progress during subsequent sessions. Most commonly found are the mechanical goniometers which are inexpensive but bulky. As the parts are mechanically linked, accuracy and resolution are largely limited. On the other hand, electronic and optical fiber-based goniometers promise better performance over its mechanical counterpart but due to higher cost and setup requirements does not make it an attractive proposition as well. In this paper, we present a reliable and non-intrusive design of an optical-based goniometer for human joint measurement. This device will allow continuous and long-term monitoring of human joint motion in everyday setting. The proposed device was benchmarked against mechanical goniometer and optical based motion capture system to validate its performance. From the empirical results, it has been proven that this design can be use as a robust and effective wearable joint monitoring device.

关键词： optical     goniometer     human-joint measurement    

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标题 作者 时间 类型 操作

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection:

null

期刊论文

Molecular network-based intervention brings us closer to ending the HIV pandemic

Xiaoxu Han, Bin Zhao, Minghui An, Ping Zhong, Hong Shang

期刊论文

Natural history of HIV infection in former plasma donors in rural China

Min ZHANG, Hong SHANG, Zhe WANG, Wei-Guo CUI, Qing-Hai HU

期刊论文

Clinical significance of human papilloma virus infection in the cervical lesions

Shuang LI, Yu-Han MENG, Hu TING, Jian SHEN, Ding MA

期刊论文

Universal influenza virus vaccines: what can we learn from the human immune response following exposure

null

期刊论文

Metabolomics in human type 2 diabetes research

null

期刊论文

<i>RR1i> and <i>RR2i> gene deletion affects the immunogenicity of a live attenuated pseudorabiesvirus vaccine candidate in natural pig host

Shijun YAN,He YAN,Chaolin ZHANG,Tongyan WANG,Qingyuan YANG,Zhe SUN,Yan XIAO,Feifei TAN,Xiangdong LI,Kegong TIAN

期刊论文

Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

期刊论文

Epidemiological studies of women under age 30 infected with human papillomavirus

Zhihua LIU MD, Qing LI BM, Weihong LI BM,

期刊论文

An experimental characterization of human torso motion

Daniele CAFOLLA,I-Ming CHEN,Marco CECCARELLI

期刊论文

Human monoclonal antibodies as candidate therapeutics against emerging viruses

null

期刊论文

Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,

期刊论文

NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

期刊论文

correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FVIII composed of the human

期刊论文

A low cost wearable optical-based goniometer for human joint monitoring

Chee Kian LIM, Zhiqiang LUO, I-Ming CHEN, Song Huat YEO

期刊论文