1.Research on the pathogenesis of humans infected with zoonotic influenza viruses
ZHU Wenfei ; YANG Lei ; WANG Dayan
China Tropical Medicine 2024;24(1):16-
Influenza viruses can infect humans, lead to epidemics within populations, and even cause global pandemics. During the non-pandemic period, there is a continuous threat as avian or swine influenza viruses cross the species barrier to infect humans, resulting in zoonotic influenza infections. For the purpose of pandemic preparation and control, it is crucial to strengthen surveillance, scientific research, and risk assessment of these zoonotic influenza viruses. Here, we focus on the latest zoonotic influenza viruses that have recently garnered significant attention, providing an overview of their latest epidemiological trends and research progress, thereby facilitating scientific risk assessment.
2.Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma.
Jiao XUE ; Yining ZHU ; Shuting BAI ; Chunting HE ; Guangsheng DU ; Yuandong ZHANG ; Yao ZHONG ; Wenfei CHEN ; Hairui WANG ; Xun SUN
Acta Pharmaceutica Sinica B 2022;12(6):2934-2949
Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
3.The experimental research of hypoxia-regulated NGF modified neural stem cells in acute spinal cord injury
Mengji CHEN ; Jiahui YE ; Yibo YING ; Min CHEN ; Haicheng DOU ; Wenfei NI ; Sipin ZHU
Chinese Journal of Orthopaedics 2020;40(10):669-679
Objective:To investigate the feasibility of transplantation of neural stem cells (NSCs) modified by hypoxia-regulated nerve growth factor (NGF) gene to treat acute spinal cord injury (SCI) and observe the functional repair after SCI.Methods:Adeno-associated virus (AAV) was used as the vector to construct gene-modified NSCs. Three days after SCI attack on the animal model, the NSCs modified by hypoxia-regulated NGF were transplanted to the site of SCI as the NGF group. The GFP-modified neural stem cell group (GFP group), sham group, SCI group were set up. Hindlimb motor function was assessed by Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale, inclined plane tests and footprint analysis at 10 time points on day 1, 3, 7, 10, 14, 21, 28, 35, 42 and 60 after transplantation. The video cassette recorder (VCR) image and quantitative measurement of the height of the rat from the ground, the foot error and plantar steps were used to test the hindlimb support and flexibility of the rats. The degree of spinal cord injury in rats was roughly measured by observing the visual map of the spinal cord. The neuronal repair and morphological changes in SCI area were evaluated by Nissl staining, HE staining and immunofluorescence. CM-DiI was used to trace neural stem cells and to analyze the differentiation of NSCs by immunofluorescence.Results:Two months after transplantation of genetically modified NSCs, the BBB, inclined plane tests and footprint Analytical scores of NGF group rats were higher than those of SCI group and GFP group ( P<0.05); Through VCR image analysis, the hindlimb support and mobility of the rats in the NGF group were better than those in the SCI group and GFP group, and the difference was statistically significant ( P<0.05). Visual analysis showed that the spinal cord of the rats in each group was visually compared to the NGF group, and the spine did not show significant atrophy and color deepening, and the degree of injury was lower than that of the SCI group and GFP group; Through Nissl staining, HE staining and immunofluorescence detection, obviously positive in NeuN at the transplant site was noted at NGF group, and evidently regenerated neural structure can be seen at the morphological level. The cavity in SCI was obviously reduced, neurons and Nissl bodies were distinctly increased ( P<0.05). CM-DiI was used to track NSCs, NeuN was used to mark neurons, and GFAP was used to mark astrocytes. It was found that neural stem cells could differentiate into neurons and astrocytes. Neural stem cells in GFP group were more differentiated into astrocytes, and neural stem cells in NGF group were more differentiated into neurons. Conclusion:NSC transplantation with oxygen-regulated NGF gene mediated by adeno-associated virus can treat SCI, NSCs can differentiate into neural stem cells and astrocytes to fill the damaged cavity, NSCs secrete NGF as the carrier, playing the protective role on adjacent damaged nerve cells and reducing the death of neurons, which is expected to provide new ideas for the treatment of acute spinal cord injury, and at the same time make new attempts for the development of NGF protein drugs.
4.A multicenter retrospective clinical study on "symptomatic facet of residual bone mass", a rare complication of percutaneous trasforaminal endoscopic discectomy
Liujun ZHAO ; Jihui ZHANG ; Baoshan XU ; Gang CHEN ; Feng QI ; Wenfei NI ; Huiming ZHU ; Yongjie GU ; Liang YU ; Fangcai LI
Chinese Journal of Orthopaedics 2018;38(19):1186-1194
Objective Retrospective study and report on cases of "symptomatic facet of residual bone mass" caused by percutaneous transforaminal endoscopic discectomy (PTED),to analysis of its causes and revision strategies.Methods Seven cases of "symptomatic facet of residual bone mass" after PTED were found in six medical centers from July 2015 to November 2017.Weintroduced the course of diagnosis and treatment,to analysis of the causes,clinical features and revision strategies of the rare complication.Results Seven patients came from different medical centers (2 cases in Ningbo No.6 Hospital and 1 case in each of the other medical centers).The average age of the subject is 67.29±9.64 years (range from 57-83 years).Among them there were 1 male and 6 female.PTED was performed for all cases with lumbar disc herniation or stenosis.The operative segments were 1 of L2,3,2 of L3,4,3 of L4,5,1 of L5S1.Symptoms occurred immediately after surgery in all cases except one after a week of operation and another one month later.Two cases were appeared symptom of contralateral irritation,and the rest were aggravated by the original symptoms.Two cerebrospinal fluid leakage caused by bone mass piercing the dural sac.The bone mass compressed the nerve root and caused 1 case of lower limb muscle weakness.Foraminoplasty was performed during PTED in all patients.After CT scan,5 cases of bone mass were found on the same side of operation,and 2 cases were in the contralateral side.The shortest time for revision was 2 days and the longest 3 months.After conservative treatment,the symptoms were relieved in only one case.Revision surgeries were performed for all the other 6 cases,2 with microendoscopic discectomy (MED),1 mobile microendoscopic discectomy (MMED),1 small incision operation,1 PTED and 1 with minimal invasive surgery of transforaminal lumbar intervertebral fusion (MIS-TLIF).The VAS scores of low back pain and leg pain was significantly relieved from 8.67±0.52 to 1.50±0.55.Conclusion FTED may lead to residual bone mass in lumbar foraminoplasty.The penetration of the bone mass block into the spinal canal can cause the compression symptoms of the corresponding segment.The patients showed the corresponding spinal canal stenosis and nerve root irritation symptoms.A revision operation is required to remove the oppressed bone mass to relieve the symptoms as soon as possible if the conservative treatment not effective.
5. Association of single nucleotide polymorphism of IL-6 gene with susceptibility to hepatitis B virus
Xiuyun ZHU ; Wenfei WANG ; Weigang WU ; Hongchun LI ; Weilong LIU ; Mingxia ZHANG ; Lei LIU
Chinese Journal of Experimental and Clinical Virology 2017;31(5):397-400
Objective:
Leukocyte mediated IL-6 (IL-6) plays an important role in chronic viral hepatitis pathogenesis and related liver diseases, We did a large sample-size case-control study and clinical data analysis to find association between IL-6 single nucleotide polymorphism and HBV susceptibility, and to achieve the detection of the body on the expression of IL-6 for the prevention and treatment of HBV infection.
Methods:
Totally 848 HBV patients and 894 healthy controls in Shenzhen were selected and rs1800796 genotypes were determined by TaqMan assays.
Results:
The result showed that rs1800796 polymorphism was associated with susceptibility to HBV infection (
6.Research Progress on Antiviral Activity of Interferon-induced Transmembrane Proteins.
Yongkun CHEN ; Wenfei ZHU ; Yuelong SHU
Chinese Journal of Virology 2016;32(2):222-228
Interferon-induced Transmembrane Proteins (IFITMs) were identified through small interference RNA (siRNA) screening method in 1980s. The antiviral properties of the IFITMs were firstly discovered in 1996. Recently, its antiviral effect and mechanism have become a research hotspot. Many studies have shown that IFITM can inhibit the replication of multiple pathogenic viruses, including influenza A virus (IAV), Human Immunodeficiency Virus (HIV-1), hepatitis C virus (HCV), Ebola virus (EBOV), West Nile virus and so on. IFITMs inhibit the replication of virus in the early stage of the viral life cycle, which occurred before the release of viral genomes into the cytosol. Recent studies indicate that IFITM proteins could block viral replication by mediate viral membrane fusion. However, the mechanism is still under investigation. Here we review the discovery and characterization of the IFITM proteins, elucidate their antiviral activities and the potential mechanisms.
Animals
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Humans
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Interferons
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genetics
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immunology
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Membrane Proteins
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genetics
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immunology
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Virus Diseases
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genetics
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immunology
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virology
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Viruses
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genetics
;
immunology
7.Preparation and Identification of High Immunogenic A/PR/8/34 Maternal Strain HA Protein for Influenza Virus Classical Reassortment.
Jing TANG ; Li XIN ; Junfeng GUO ; Wenfei ZHU ; Heyuan ZHANG ; Shaohui LANG ; Dayan WANG ; Yuelong SHU
Chinese Journal of Virology 2016;32(2):141-144
Preparation of maternal strain A/PR/8/34 HA antiserum for influenza virus classical reassortment. A/PR/8/34 virus was digested by bromelain after inactivation and purification. 5%-20% sucrose continuous density gradient centrifugation method was used to purify HA protein. SIRD method was used to select the target protein. SDS-PAGE method was used to identified HA protein. High Immunogenic A/PR/8/34 HA protein was successfully prepared and HI titer reached 10240. High purity HA antiserum was identified by SIRD method. The key reagent in the classical reassortment of influenza virus was prepared, and the complete set of technical methods were explored, which laid the foundation for the independent research and development of seasonal influenza vaccine strains of China.
Animals
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Antibodies, Viral
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immunology
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Electrophoresis, Polyacrylamide Gel
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Female
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Hemagglutination Inhibition Tests
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Hemagglutinin Glycoproteins, Influenza Virus
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analysis
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immunology
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Humans
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Influenza A Virus, H1N1 Subtype
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genetics
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immunology
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Influenza, Human
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immunology
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virology
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Rabbits
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Reassortant Viruses
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genetics
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immunology
8.Google Flu Trends--the initial application of big data in public health.
Xiaohui ZOU ; Wenfei ZHU ; Lei YANG ; Yuelong SHU ; Email: YSHU@CNIC.ORG.CN.
Chinese Journal of Preventive Medicine 2015;49(6):581-584
Google Flu Trends (GFT) was the first application of big data in the public health field. GFT was open online in 2009 and attracted worldwide attention immediately. However, GFT failed catching the 2009 pandemic H1N1 and kept overestimating the intensity of influenza-like illness in the 2012-2014 season in the United States. GFT model has been updated for three times since 2009, making its prediction bias controlled. Here, we summarized the mechanism GFT worked, the strategy GFT used to update, and its influence on public health.
Disease Outbreaks
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Humans
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Influenza A Virus, H1N1 Subtype
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Influenza, Human
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Internet
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Population Surveillance
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Public Health
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Statistics as Topic
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United States
9.Hemagglutinin stem reactive antibody response in individuals immunized with a seasonal influenza trivalent vaccine.
Xiaopeng ZHAO ; Kun QIN ; Jinlei GUO ; Donghong WANG ; Zi LI ; Wenfei ZHU ; Liqi LIU ; Dayan WANG ; Yuelong SHU ; Jianfang ZHOU
Protein & Cell 2015;6(6):453-457
Adult
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Antibodies, Viral
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blood
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immunology
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Cross Reactions
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Hemagglutinin Glycoproteins, Influenza Virus
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immunology
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Humans
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Influenza A Virus, H1N1 Subtype
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immunology
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Influenza A Virus, H3N2 Subtype
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immunology
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Influenza B virus
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immunology
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Influenza Vaccines
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immunology
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Orthomyxoviridae
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immunology
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Seasons
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Vaccination
10.AMPK/mTOR pathway and leucine resistance in sepsis
Wenfei LIU ; Zhenxin ZHU ; Ronglin YAN
Journal of Medical Postgraduates 2014;(12):1311-1314
Sepsis leads to inhibition of protein synthesis , known as leucine resistance .mTOR regulates protein synthesis by phosphorylation of S6K1 and 4E-BP1.AMPK is an important negative regulator of mTOR and its activity is in an abnormal state in sep-sis.This review briefly discusses the AMPK/mTOR pathway in Sepsis-induced leucine resistance .

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