1.The View ofon Infertility
Yiyun LOU ; Ping FU ; Xiangguo DONG
Journal of Zhejiang Chinese Medical University 2017;41(1):52-54
Objective] To discuss the diagnosis and treatment of infertility according to the related comments in
2.Study on Protective Effects of Li Medicine Chushi Qufeng Decoction on Arthritis Model Rats Induced by Chicken TypeⅡCollagen
Li ZHANG ; Yiyun ZHANG ; Hong FU ; Kaiyu WANG ; Lingfang LEI ; Chuntao WANG
China Pharmacy 2016;27(22):3088-3090
OBJECTIVE:To study the protective effects of Li medicine Chushi qufeng decoction on arthritis model rats. METH-ODS:60 rats were randomly divided into normal group,model group,positive group and Chushi qufeng decoction high-dose,me-dium-dose and low-dose groups [45.9,22.95,11.48 g(crude drug)/kg]. Except for normal group,those groups were given chicken type Ⅱ collagen to induce arthritis model. After modeling,normal group and model group were given normal saline intragastrical-ly,once a day,for consecutive 12 d;Chushi qufeng decoction groups were given relevant medicine intragastrically;positive group was given leflunomide 4.5 mg/kg on 1st-3rd day and 1.8 mg/kg on 4th-12th day. The degree of joint lesion in rats were scored. The degree of joint swelling was determined as well as the serum levels of TNF-α,IL-1β and type Ⅱ collagen antibody. RESULTS:Compared with normal group,arthritis index,degree of joint swelling,the serum levels of TNF-α,IL-1βand typeⅡcollagen anti-body increased significantly in model group (P<0.01). Compared with model group,pathological score of positive group and Chushi qufeng decoction high-dose group decreased significantly,and serum levels of TNF-α,IL-1β and type Ⅱ collagen antibody decreased significantly in treatment groups(P<0.05 or P<0.01). CONCLUSIONS:Li medicine Chushi qufeng decoction has cer-tain protective effect on arthritis model rats induced by chicken typeⅡcollagen.
3.Impact and mechanism of leptin on bone marrow-derived dendritic cells(BMDCs)via NLRP3 inflammasome
Yiyun YU ; Sisi FU ; Lei LIU ; Jie YANG ; Lei HAN ; Ling Lü
Chinese Journal of Immunology 2017;33(7):971-975
Objective:To investigate the role and mechanism of leptin on dendritic cells by NLRP3 inflammasome.Methods: BMDCs were induced in vitro,leptin with scalar doses was cocultured with BMDCs,IL-1β and IL-18 mRNA expression and protein secretion level were measured by q-RT-PCR and ELISA respectively.Caspase-1 activity or ROS synthesis were tested with FLICA kit or ROS detection assay kit on flow cytometry.IL-1β or IL-18 were detected after caspase-1 was inhibited by Ac-YVAD-cmk or NLRP3 was interfered by siRNA or ROS inhibitor DPI or KCL were added.Results: Leptin promoted secretion of IL-1β and IL-18.Leptin up-regulated NLRP3 and activted caspase-1 to secret proinflammtory cytokine,which K+ efflux took part in.Conclusion: Leptin promotes secretion of IL-1β and IL-18 by activating NLRP3 inflammasome,and K+ efflux takes part in this,which hints us that leptin may be an activator of NLRP3 inflammasome.
4.Genetic Evolution of Neuraminidase Gene of Influenza A/H1N1 Virus
Jiang TIAN ; Jingjiao ZHOU ; Yiyun CHEN ; Yu LIANG ; Huijun YAN ; Junmei ZHOU ; Yan LIU ; Chunyun FU ; Hongli GAO ; Danyun FANG ; Biao DI ; Lifang JIANG
Journal of Sun Yat-sen University(Medical Sciences) 2010;31(2):207-212
[Objective]This study was designed to investigate the genetic evolution of the neuraminidase(NA)gene of seasonal A/H1N1 and 2009 novel A/H1N1 inflilenza virus,and discuss the genetic variation of influenza A virus.[Methods]The virus strains were separately isolated from the clinical samples collected in 2006 and 2009,and then identified as seasonal A/H1N1 and novel A/H1N1.The full length of the NA gene of these strains was amplified by RT-PCR.Then the genetic evolution and mutations of important functional sites were analyzed.[Results]The homology of NA gene between the 2009 novel A/H1N1 isolates and 2006 seasonal A/H1N1 isolates was low(77.9%~78.8%),so was the homology of NA gene between the 2009 novel A/H1N1 isolates and representative strains of different periods and 1979-2001 WHO recommended vaccine strains(78.1%~79.3%).But compared with the WHO recommended vaccine strains of 2009 novel A/H1N1,the homology reached more than 99%.The genetic evolution analysis revealed that NA gene of 2009 novel A/H1N1 had the closest genetic relationship with the swine influenza A virus(A/swine/Belgium/1/1983)from Eurasian Iineage,and some of the antigenic sites and neuraminidase active sites of NA gene of seasonal A/H1N1 were mutated after 2005.[Conclusion]The NA gene of 2009 novel A/H1N1 may originate from Eurasian Iineage of swine influenza virus.The variation of NA gene of seasonal A/H1N1 has occurred in a certain degree.Hence,it is very necessary to continuously monitor the variant of influenza A virus.
5.Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis.
Fei SU ; Ke ZHENG ; Yiyun FU ; Qian WU ; Yuan TANG ; Weiya WANG ; Lili JIANG
Chinese Journal of Lung Cancer 2018;21(5):389-396
BACKGROUND:
Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy.
METHODS:
ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed.
RESULTS:
The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS).
CONCLUSIONS
For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.
Adenocarcinoma
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blood
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drug therapy
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genetics
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mortality
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Adenocarcinoma of Lung
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Adult
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Aged
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Aged, 80 and over
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Cell-Free Nucleic Acids
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blood
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ErbB Receptors
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genetics
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Female
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Humans
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Lung Neoplasms
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blood
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drug therapy
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genetics
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mortality
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Male
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Middle Aged
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Molecular Targeted Therapy
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Mutation, Missense
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Prognosis
6.Discovery and development of brain-penetrant 18F-labeled radioligands for neuroimaging of the sigma-2 receptors.
Ying ZHANG ; Tao WANG ; Xiaojun ZHANG ; Winnie DEUTHER-CONRAD ; Hualong FU ; Mengchao CUI ; Jinming ZHANG ; Peter BRUST ; Yiyun HUANG ; Hongmei JIA
Acta Pharmaceutica Sinica B 2022;12(3):1406-1415
We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ 2) receptor ligands. Two ligands with high σ 2 receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [18F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ 2 receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [18F]9 to σ 2 receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [18F]9 in the brain that is consistent with the distribution pattern of σ 2 receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [18F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [18F]9 as the first highly specific and promising imaging agent for σ 2 receptors in the brain.