1.Hypericin inhibits the expression of NLRP3 in microglia of Parkinson's disease mice and alleviates the damage of DA-ergic neurons
Li-Shan FAN ; Jia ZHANG ; Si-Xiang NIU ; Qi XIAO ; Hui-Jie FAN ; Lei XU ; Li-Xia YANG ; Lu JIA ; Shao-Chen QIN ; Bao-Guo XIAO ; Cun-Gen MA ; Zhi CHAI
The Chinese Journal of Clinical Pharmacology 2024;40(17):2523-2527
Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9%NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P<0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.
2.Effect and possible mechanism of Wuzi Yanzong Pill on motor function of neurons in Parkinson's disease mice
Tao PAN ; Qi XIAO ; Hui-Jie FAN ; Lei XU ; Lu JIA ; Shao-Chen QIN ; Li-Ran WANG ; Cun-Gen MA ; Bo ZHANG ; Zhi CHAI
Medical Journal of Chinese People's Liberation Army 2024;49(5):550-556
Objective To observe the effects of Wuzi Yanzong Pill(WYP)on motor function in a mouse model of Parkinson's disease(PD)and to explore its potential mechanisms.Methods Twenty-four male C57BL/6 mice were randomly divided into control group,model group and WYP group,with 8 mice in each group.Mice in model and WYP group were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 7 consecutive days to establish a PD model.From the 1st day of model preparation,mice in WYP group were gavaged with WYP solution[16 g/(kg·d)]twice daily for 14 consecutive days.At the same time,mice in control group and model group were gavaged with 0.9%NaCl solution[50 ml/(kg·d)]twice a day.Gait experiment was utilized to assess the behavioral performance of mice in each group.Immunofluorescence staining was conducted to detect the number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra region,the fluorescence intensity of nuclear factor E2-related factor 2(Nrf2),and the number of NeuN neurons co-labeled with Nrf2 in each group.Western blotting was employed to determine the expression levels of TH,Kelch-like ECH-associated protein 1(Keap-1),Nrf2,and heme oxygenase-1(HO-1)in the brain tissue of mice in each group.Results The gait experiment results showed that,compared with control group,standing time of the left front paw,right front paw,left hind paw,and right hind paw of the mice in model group was significantly shortened(P<0.01),while swinging time of the left front paw,right front paw,left hind paw,and right hind paw was significantly prolonged(P<0.05).Compared with model group,standing time of the left front paw and right hind paw of the mice in WYP group was significantly prolonged(P<0.05),while swing time of the left front paw and right front paw was significantly shortened(P<0.05).Immunofluorescence staining and Western blotting results showed that,compared with control group,in model group the number of TH-positive cells,average fluorescence intensity of Nrf2,and HO-1 levels decreased(P<0.01),while the Keap-1 protein level increased(P<0.01),and the number of Nrf2 expression on NeuN neurons decreased(P<0.001).Compared with model group,the number of TH-positive cells,average fluorescence intensity of Nrf2,HO-1 level,and the number of Nrf2 expression on NeuN neurons in the brain tissue of mice in WYP group increased(P<0.05),while Keap-1 protein level decreased(P<0.05).Conclusions WYP could alleviate the motor dysfunction and protect dopaminergic neurons in PD mice.The underlying mechanism may be related to the regulation of Keap-1/Nrf2/HO-1 pathway to inhibit oxidative stress response.
3.Epidemic characteristics and food traceability of listeriosis in China,and the United States,and implications for China
Zhi-Fang ZHANG ; Xue-Jie LIU ; Sheng-Gen WU ; Qu-Wen LI ; Wei-Wei CHEN ; Yan-Qin DENG
Chinese Journal of Zoonoses 2024;40(7):636-643
This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4%(191/1 037),20.5%(185/902),and 22.4%(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8%to 89.6%.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.
4.Proanthocyanin B2 inhibits oxidative stress and alleviates H2O2 induced damage to human oligodendrocytes through NRF2/HO-1/xCT/GPX4 axis
Jian LIU ; Ying CHEN ; Ya-Jie LIANG ; Meng PU ; Zi-Wei ZHANG ; Lu-Lu ZHENG ; Zhi CHAI ; Ying XIAO ; Cun-Gen MA ; Qing WANG
Chinese Pharmacological Bulletin 2024;40(9):1735-1743
Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.
5.Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells.
Qing WANG ; Yang-Yang CHEN ; Zhi-Chao YANG ; Hai-Jun YUAN ; Yi-Wei DONG ; Qiang MIAO ; Yan-Qing LI ; Jing WANG ; Jie-Zhong YU ; Bao-Guo XIAO ; Cun-Gen MA
Chinese journal of integrative medicine 2023;29(5):394-404
OBJECTIVE:
To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.
METHODS:
This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.
RESULTS:
GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).
CONCLUSION
GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.
Mice
;
Animals
;
Encephalomyelitis, Autoimmune, Experimental/pathology*
;
Grape Seed Extract/therapeutic use*
;
Interleukin-17
;
Interleukin-1beta
;
Tumor Necrosis Factor-alpha/metabolism*
;
Interleukin-6/metabolism*
;
Th1 Cells
;
Mice, Inbred C57BL
;
Interferon-gamma/therapeutic use*
;
Th17 Cells/metabolism*
;
Interleukin-12/therapeutic use*
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Cytokines/metabolism*
6.Protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae against myocardial injury in septic mice.
Yuan YUAN ; Feng NIAN ; Hui Hui LI ; Hui Juan YANG ; Yu Zhi WU ; Meng Xi MA ; Kai Gui WANG ; Xue Ling CHEN ; Zi Qiang ZHANG ; Gen LI ; Xiao Di YANG ; Qiang WU
Journal of Southern Medical University 2022;42(6):824-831
OBJECTIVE:
To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice.
METHODS:
Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR.
RESULTS:
Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05).
CONCLUSION
Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.
Animals
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Cytokines
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Dexamethasone
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Heart Injuries
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Interleukin-10
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Interleukin-6
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Larva
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Male
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Mice
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Mice, Inbred BALB C
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Myocardium
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Sepsis
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Transforming Growth Factor beta
;
Trichinella spiralis
;
Tumor Necrosis Factor-alpha
7.Efficacy and prognostic factors of Ranibizumab in the treatment of macular edema secondary to retinal vein occlusion
Zhi-Jun SHEN ; Hong WANG ; Rui CHEN ; Gen-Lin LI
International Eye Science 2022;22(10):1693-1697
AIM:To evaluate the therapeutic efficacy of intravitreal injections of ranibizumab for macular edema secondary to retinal vein occlusion(RVO)and the prognostic factors for this disorder.METHODS:A retrospective case study. There were 61 patients(61 eyes)with macular edema secondary to RVO who treated in our hospital from April 2020 to February 2021, including 30 cases(30 eyes)of branch retinal vein occlusion(BRVO)patients and 31 cases(31 eyes)of central retinal vein occlusion(CRVO)patients. All patients received 3 times of intravitreal injections of ranibizumab(0.5mg), and some eyes underwent retinal laser therapy. The patients were followed up for 3mo after treatment(the first intravitreal injection)to observe the visual acuity, intraocular pressure, central retinal thickness(CRT)and record the occurrence of ocular and systemic complications.RESULTS: The visual acuity of the included patients after treatment was significantly improved compared with that before treatment, and the CRT was significantly decreased compared with that before treatment(P<0.01), and after 3 times of intravitreal injections, the visual acuity of BRVO and CRVO patients with pre-treatment visual acuity≤1(LogMAR)was better than that of the patients with pre-treatment visual acuity>1(P<0.01), but there was no difference in CRT(all P >0.05). Among BRVO and CRVO patients, 12 and 8 eyes received retinal laser treatment during 3 times of intravitreal injections, respectively. The difference in visual acuity and CRT among the eyes treated with laser and those that were untreated was not significant(P>0.05). No ocular and systemic serious complications emerged during follow-up.CONCLUSIONS: Ranibizumab has high efficacy and safety in the treatment of macular edema secondary to RVO, while visual acuity at baseline may help predict the prognosis.
8.Onset of Coronary Heart Disease is Associated with HCMV Infection and Increased CD14 CD16 Monocytes in a Population of Weifang, China.
Hong Zheng LI ; Qin WANG ; Yi Yuan ZHANG ; Jin Dong WANG ; Hong Juan WU ; Mo Gen ZHANG ; Ji Chen LI ; Zhi Jun LIU
Biomedical and Environmental Sciences 2020;33(8):573-582
Objective:
To investigate the relationship between human cytomegalovirus (HCMV) infection and peripheral blood CD14 CD16 monocytes in the pathogenesis of coronary heart disease (CHD), and to elucidate the mechanism of pathogenesis in CHD by analyzing the correlation between infection, inflammation, and CHD, to provide a basis for the prevention, evaluation, and treatment of the disease.
Methods:
In total, 192 patients with CHD were divided into three groups: latent CHD, angina pectoris, and myocardial infarction. HCMV-IgM and -IgG antibodies were assessed using ELISA; CD14 CD16 monocytes were counted using a five-type automated hematology analyzer; mononuclear cells were assessed using fluorescence-activated cell sorting; and an automatic biochemical analyzer was used to measure the levels of triglyceride, cholesterol, high- and low-density lipoprotein cholesterols, lipoprotein, hs-CRp and Hcy.
Results:
The positive rates of HCMV-IgM and -IgG were significantly higher in the CHD groups than in the control group. HCMV infection affects lipid metabolism to promote immune and inflammatory responses.
Conclusion
HCMV infection has a specific correlation with the occurrence and development of CHD. The expression of CD14 CD16 mononuclear cells in the CHD group was increased accordingly and correlated with acute HCMV infection. Thus, HCMV antibody as well as peripheral blood CD14 CD16 mononuclear cells can be used to monitor the occurrence and development of CHD.
Angina Pectoris
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epidemiology
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virology
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China
;
epidemiology
;
Coronary Disease
;
epidemiology
;
virology
;
Cytomegalovirus
;
physiology
;
Cytomegalovirus Infections
;
complications
;
Humans
;
Incidence
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Inflammation
;
epidemiology
;
etiology
;
Leukocyte Count
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Monocytes
;
metabolism
;
Myocardial Infarction
;
epidemiology
;
virology
9.Genome survey and characteristic analysis of SSR in Callicarpa nudiflora.
Fu-Lai YU ; Mei HUANG ; Ying-Bo ZHANG ; Zhen-Xia CHEN ; Yu-Xin PANG ; Zhi-Xin GU ; Wei LI ; You-Gen WU
China Journal of Chinese Materia Medica 2019;44(18):3974-3978
Callicarpa nudiflora,which is a big brand of Li nationality medicine with Hainan characteristics,has the effects of dissolving stasis,hemostasis,anti-inflammatory and antibacterial. At present,there is a lack of information about the reference genome of C. nudiflora. The study of the genome size,heterozygosity rate and characteristics of SSR of C. nudiflora,can provide an effective basis for the formulation of the whole genome de novo sequencing strategy and development of SSR molecular markers of C. nudiflora. To realize this purpose,high throughput sequencing platform Illumina Hiseq was used to sequence the genome structure of C. nudiflora and K-mer analysis was applied to estimate genome size,repeat sequences and heterozygosity rate. Simple-sequence repeat( SSR) loci that are suitable as markers were identified by MISA software. The results showed the estimated genome size of C. nudiflora was 822. 43 Mb,with a 0. 85% heterozygosity rate and 71. 67% repeats,and the GC content of genome was about 49. 20%. Therefore,C. nudiflora belongs to a complex genome with high heterozygosity and repetition. SSR molecular genetic markers were analyzed in the genome sequence,and a total of 206 049 SSRs were identified,among which mono-nucleotide,di-nucleotide and tri-nucleotide repetitive motifs summed up to 198 993,accounting for 96. 57% of the total SSRs. Among the 2-6 nucleotide repeats,AT/AT,AAT/ATT,AGCC/CTGG,AAAAT/ATTTT and AGATAT/ATATCT have the largest number,respectively. This report represents the first genome-wide characterization of C. nudiflora,and provides a reference for the construction of the library for the fine sequencing of the genome,and a molecular basis for the development of SSR molecular markers as well as for the protection and utilization of gene resources.
Callicarpa/genetics*
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Genetic Markers
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Genome, Plant
;
Microsatellite Repeats
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Polymorphism, Genetic
10.Avian influenza viruses (AIVs) H9N2 are in the course of reassorting into novel AIVs.
Hui-Ping CHANG ; Li PENG ; Liang CHEN ; Lu-Fang JIANG ; Zhi-Jie ZHANG ; Cheng-Long XIONG ; Gen-Ming ZHAO ; Yue CHEN ; Qing-Wu JIANG
Journal of Zhejiang University. Science. B 2018;19(5):409-414
In 2013, two episodes of influenza emerged in China and caused worldwide concern. A new H7N9 avian influenza virus (AIV) first appeared in China on February 19, 2013. By August 31, 2013, the virus had spread to ten provinces and two metropolitan cities. Of 134 patients with H7N9 influenza, 45 died. From then on, epidemics emerged sporadically in China and resulted in several victims. On November 30, 2013, a 73-year-old woman presented with an influenza-like illness. She developed multiple organ failure and died 9 d after the onset of disease. A novel reassortant AIV, H10N8, was isolated from a tracheal aspirate specimen that was obtained from the patient 7 d after onset. This case was the first human case of influenza A subtype H10N8. On 4 February, 2014, another death due to H10N8 avian influenza was reported in Jiangxi Province, China.
Aged
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China
;
epidemiology
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Female
;
Humans
;
Influenza A Virus, H10N8 Subtype
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classification
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Influenza A Virus, H7N9 Subtype
;
classification
;
Influenza A Virus, H9N2 Subtype
;
classification
;
Influenza, Human
;
epidemiology
;
virology
;
Phylogeny
;
Reassortant Viruses
;
classification

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