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

null

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

null

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

null

《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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Human monoclonal antibodies as candidate therapeutics against emerging viruses

null

《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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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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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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Removal of virus aerosols by the combination of filtration and UV-C irradiation

《环境科学与工程前沿（英文）》 2023年 第17卷 第3期 doi: 10.1007/s11783-023-1627-y

摘要：

● The removal of virus aerosols by filtration and UV-C irradiation was proposed.

关键词： Filtration system     UV-C irradiation     Virus aerosol     Public health     COVID-19    

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

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Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

《医学前沿（英文）》 2009年 第3卷 第2期   页码 158-163 doi: 10.1007/s11684-009-0042-5

摘要： The regulatory effect of basic fibroblast growth factor (bFGF) mediated by recombinant adeno-associated virus (AAV) was investigated. Recombinant plasmid pAAV-S3-bFGF, and pSVneo were co-transfected into BHK-21 cells, then the recombinant AAV genome was replicated and packaged with the helper virus HSV1-rc/ΔUL2. The titer of the recombinant rAAV2-tet-off-bFGF was determined by dot-blot assay. MC3T3-E1 cells were infected with rAAV2-tet-off-bFGF. Regulatory effects of Doxycycline (Dox) on bFGF and osteogenic factors were assayed quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The physical particle titer of rAAV2-tet-off-bFGF successfully constructed was 1.8×10 vector genomes/mL, and the virus could infect MC3T3-E1 cells effectively. In MC3T3-E1 cells treated with Dox, the expression levels of exogenous bFGF and osteogenic factors declined to varying degrees. It was concluded that rAAV2-tet-off-bFGF could infect MC3T3 cells efficiently, and this recombinant system could be regulated successfully by Dox .

关键词： tetracycline regulatory system     adeno-associated virus     basic fibroblast growth factor     gene regulation    

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Advances in newly developing therapy for chronic hepatitis C virus infection

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

《医学前沿（英文）》 2021年 第15卷 第3期   页码 404-415 doi: 10.1007/s11684-021-0834-9

摘要： Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain–Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.

关键词： Zika virus     clinical drugs     ZIKV inhibitors     antivirals     repurposing    

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标题 作者 时间 类型 操作

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

Epidemiological studies of women under age 30 infected with human papillomavirus

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

期刊论文

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

null

期刊论文

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

null

期刊论文

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

null

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

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

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

Removal of virus aerosols by the combination of filtration and UV-C irradiation

期刊论文

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

期刊论文

Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

期刊论文

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

Repurposing clinical drugs is a promising strategy to discover drugs against Zika virus infection

Weibao Song, Hongjuan Zhang, Yu Zhang, Rui Li, Yanxing Han, Yuan Lin, Jiandong Jiang

期刊论文