1.The serum proteomic analysis of the adefovir dipivoxil response in the chronic hepatitis B patients
Fang GUO ; Jiang-Hua WANG ; Hui-Ying RAO ; Song-Xia WANG ; Wen-Li GUAN ; Yan SUN ; Hao WANG ; Lai WEI ;
Chinese Journal of Laboratory Medicine 2001;0(01):-
Objective To compare the difference of the protein about the patient of hepatitis B who received adefovir dipivoxil(ADV)therapy,and seek the useful biomarker of effective therapy.Methods We used the two-dimensional gel electrophoresis technology to examine HBV infected serum samples aiming at searching protein's alteration after ADV therapy.Results After 1 year's treatment,haptoglobin, haptoglobin 2-alpha raised and alpha-l-antitrypsin precursor,Factor B,Chain B,transthyretin,glutathione peroxidase,alpha-2-HS-glycoprotein,retina]binding protein,retinol-binding protein precursor, apolipoprotein,apolipoprotein A-I precursor fell in viral response patients.Transthyretin raised and leucine- rich alpha-2-glyeoprotein,haptoglobin,alpha-2-actin,apolipoprotein A-I precursor fell in none viral response patients.To compare two groups:apolipoprotein A-I have the same change and haptoglobin, transthyretin have the opposite change.Conclusion Proteomics study can find the alteration of protein during the ADV treatment,and is helpful to searching the predictable biomarker to ADV.
2. Mechanism of Bawei Chenxiang powder in treatment of ischemie heart disease through mitophagy based on network pharmacology
Dong-Fang YUE ; Cai-Xia LI ; Min GUAN ; Yong-Fang LI
Chinese Pharmacological Bulletin 2023;39(10):1957-1965
Aim To explore the potential mechanism of Bawei Chenxiang powder against ischemie heart disease (IHD) through mitophagy based on network pharmacology, molecular docking and verification in vitro. Methods The targets of serum constituents of Bawei Chenxiang powder were mined by Swiss target predic-tion, and then the targets related to IHD and mitophagy were selected from Genecards, NCBI and OMIM data-bases to obtain the intersection targets of the three as the potential targets of Bawei Chenxiang powder for the treatment of IHD through mitophagy. Then the "ingre-dients-disease-potential target " network and " protein-protein interaction" (PPI) network were constructed to perform network analysis in order to screen the key ac-tive ingredients and core targets, using Autodock vina software for molecular docking operation. The targets CO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID databas-es. The effeets of Bawei Chenxiang powder containing serum on celi viability, levels expressions mitophagy and key signaling pathway related protein in H9C2 cells were investigated by hypoxia-induced injury of H9c2 myocardial cells model in vitro. Results The 9 key active compounds and 8 core targets of Bawei Chenxiang powder were screened; molecular docking showed a good binding ability of key active ingredients and core targets. KEGG pathway enrichment analysis showed that the effect of Bawei Chenxiang powder on IHD through mitophagy was related to EGFR, PI3K-Akt, MAPK, FoxO signaling pathway, etc. Celi ex-periments showed that Bawei Chenxiang powder containing serum treatment could significantly improve the survival rate by hypoxia-induced injury in H9c2, the expression of LC3II and p62 were significantly down-regulated, and the expressions of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated. Conclu-sions Bawei Chenxiang powder plays an anti-IHD role by regulating mitophagy, which may be involved in AKT1, STAT3, MAPK3 and EGFR and other targets, through quercetin, Kaempferol, Naringenin and De-hydrodiisoeugenol as well as other components. Its mechanism may be related to improving PI3K-AKT pathway.
3.One patient with metastastic colorectal cancer successfully treated by combination of targeted agents after failure of chemotherapy.
Liang-Ping XIA ; Pei-Hong WU ; Jian-Chuan XIA ; Bei ZHANG ; Zhong-Zhen GUAN ; De-Sen WAN ; Gui-Fang GUO ; Yi-Xin ZENG
Chinese Journal of Cancer 2010;29(12):1023-1028
Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 20 months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.
Adenocarcinoma
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diagnostic imaging
;
drug therapy
;
pathology
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secondary
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Angiogenesis Inhibitors
;
therapeutic use
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Antibodies, Monoclonal
;
therapeutic use
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Antibodies, Monoclonal, Humanized
;
therapeutic use
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Antineoplastic Agents
;
therapeutic use
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Antineoplastic Combined Chemotherapy Protocols
;
therapeutic use
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Bevacizumab
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Catheter Ablation
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Cetuximab
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Cytokine-Induced Killer Cells
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immunology
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Deoxycytidine
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analogs & derivatives
;
therapeutic use
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Disease-Free Survival
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Drug Delivery Systems
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Fluorouracil
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analogs & derivatives
;
therapeutic use
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Humans
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Immunotherapy, Adoptive
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Liver Neoplasms
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secondary
;
surgery
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Lung Neoplasms
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secondary
;
surgery
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Lymphatic Metastasis
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Male
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Middle Aged
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Multimodal Imaging
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Neoplasm Staging
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Positron-Emission Tomography
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Quality of Life
;
Quinazolines
;
therapeutic use
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Receptor, Epidermal Growth Factor
;
antagonists & inhibitors
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Sigmoid Neoplasms
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diagnostic imaging
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drug therapy
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pathology
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Tomography, X-Ray Computed
4.Clinical and pathological reassessment of 493 cases of non-Hodgkin's lymphomas according to current WHO classification of lymphoid neoplasms.
Chang XIAO ; Zu-lan SU ; Qiu-liang WU ; Hong-yi GAO ; Jian-chen FANG ; Zhong-jun XIA ; Zhong-zhen GUAN
Chinese Journal of Pathology 2005;34(1):22-27
OBJECTIVETo investigate the clinical and pathological features of non-Hodgkin's lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms.
METHODSAccording to the new WHO classification, a total of 500 cases of non-Hodgkin's lymphoma diagnosed during the period 1992 - 2003 were reviewed and reappraised with their morphological, immunological and clinical characteristics. Clinical survival analysis was performed in 156 cases that accompanied with follow-up data.
RESULTSAmong 500 cases previously diagnosed as lymphomas, 493 cases (98.6%) were confirmed to be NHL, of which B-cell neoplasms was 69.0% and T/NK-cell neoplasms 29.8%. Overall, 6 subtypes including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), unspecified peripheral T-cell lymphoma (PT-un), precursor T-lymphoblastic lymphoma (T-LBL), extranodal marginal zone B-cell lymphoma of MALT type (MALT) and B-small lymphocytic lymphoma (B-SLL) were among the most common subtypes. In pediatric and young patient populations, the most common subtypes were LBL, DLBCL and Burkitt's lymphoma. The frequency of LBL in all patients, especially in the juniors, was much higher than those reported outside Mainland China, and the frequency of FL was much higher than the reported in Mainland China. The frequency of FL was much higher than the reported in Mainland China. Clinical survivals among different histological subtypes of NHL varied considerably with statistic significance (P < 0.001). Marginal zone B-cell lymphoma and SLL demonstrated the best prognosis, LBL and PT-un both the worst, whereas DLBCL and FL had an intermediate prognosis, however, subgrouping of FL according to WHO classification did not reveal a significant survival difference (P > 0.05).
CONCLUSIONSBasing upon the results of a comprehensive survey on the morphologic features, immunophenotyping and clinical data of the above cases, the new WHO classification of lymphoid neoplasms is practical and easily applicable for routine pathological evaluation of lymphoproliferaive disorders and in guiding the clinical management. It appears that the diagnostic and grading criteria for FL in Mainland China need to be re-evaluated.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Burkitt Lymphoma ; epidemiology ; pathology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Killer Cells, Natural ; Lymphoma, B-Cell ; classification ; epidemiology ; pathology ; Lymphoma, Follicular ; classification ; epidemiology ; pathology ; Lymphoma, Large B-Cell, Diffuse ; epidemiology ; pathology ; Lymphoma, Non-Hodgkin ; classification ; epidemiology ; pathology ; Lymphoma, T-Cell ; classification ; pathology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; World Health Organization
5.Targeting knockout of DMD gene exon51 in HEK293T cell based on CRISPR/Cas9 system
Shuang LI ; Shan-Shan MA ; Si-Ying CUI ; Su-Zhen QU ; Ao-Jie CAI ; Fang-Xia GUAN ; Xiang-Dong KONG
Basic & Clinical Medicine 2018;38(3):375-380
Objective To knockout the exon51 of DMD gene in HEK293T cells using the CRISPR/Cas9 system. Methods Design the target sequences of sgRNA and clone them into plasmid PX459 respectively; transfer these plasmids into HEK293T cell and extract the total genome DNA; test the activity of sgRNAs with surveyor assay, choose the most efficient one in each end;construct plasmid PX459-2sgRNA and transfer it into HEK293T cells;check whether the exon51 has been knocked known with PCR and T vector sequencing. Results 50% of HEK293T cells' DMD gene exon51 were knocked out,showing a high gene editing efficiency. Conclusions We successfully establish a platform to target knockout the exon51 of DMD gene and provide an important experimental basis for the treatment of DMD and other genetic diseases.
6.Treating glioma with umbilical cord mesenchymal stem cells: mechanism of action, safety and future application
Xin-Kui ZHOU ; Shan-Shan MA ; Teng-Fei LIU ; Jian-Kang ZHOU ; Qu XING ; Tuan-Jie HUANG ; Ya-Ping WANG ; Bo YANG ; Fang-Xia GUAN
Chinese Journal of Tissue Engineering Research 2018;22(17):2740-2746
BACKGROUND: Umbilical cord mesenchymal stem cells (UC-MSCs) are a group of cells that have self-renewal, highly proliferative and multidrug differentiation potential. The properties of UC-MSCs and their tumor tropism make them an ideal tool for glioma cell therapy. These cells can act by paracrine or as a delivery system for genes and drugs. It has been demonstrated that UC-MSCs can inhibit the growth of glioma and improve the survival after transplantation into the brain. OBJECTIVE: To summarize the molecular mechanisms and safety of UC-MSCs in the treatment of glioma and to provide a useful reference for further research. METHODS: We searched the PubMed and CNKI databases from 2000 to 2017 with the English terms of "glioma; umbilical cord mesenchymal stem cells" and the Chinese terms of "glioma; umbilical cord mesenchymal stem cells; safety; molecular mechanism". Based on the inclusion and exclusion criteria, 55 articles were finally reserved for review. RESULTS AND CONCLUSION: UC-MSCs have obvious effect on treating glioma. These cells can treat glioma through homing mechanism and paracrine mechanism as gene carrier and co-culture. Moreover, UC-MSCs have certain safety in the treatment of glioma.
7.Preliminary application of quantitative assessment of emphysema using CT in subjective evaluation of normal population
Yuan FANG ; Yu GUAN ; Yi XIA ; Li FAN ; Shiyuan LIU ; Xiangsheng XIAO
Journal of Practical Radiology 2017;33(12):1939-1942,1946
Objective To explore the application value of quantitative assessment of emphysema using CT in CT subjective evaluation of normal population,and compare the quantitative parameters of emphysema among groups.Methods A total of 1 231 volunteers with negative results of subjective assessment in low dose CT screening were included in this study.The threshold of emphysema was set at -950 HU,and the total lung volume(TLV),total emphysema volume(TEV),emphysema index(EI)and 15th percentile lung density(PD15)were quantified.The presence of emphysema was defined by an EI higher than or equal to 5%.The volunteers were divided into different groups by gender and age,and the quantitative parameters were compared among different groups.Results A total of 102 cases of emphysema were detected in 1 231 volunteers,with a detection rate of 8.29%,with 76 male volunteers,accounting for 9.93%,and 26 female volunteers,accounting for 5.58%,respectively.There were statistically significant differences in TLV,TEV, EI and PD15 between genders and age groups,with TLV,TEV,EI higher and PD15 lower in male(P<0.001)and with TEV and EI higher in older than 60 years old group(P<0.001).Conclusion Quantitative assessment of emphysema using CT exhibites relatively high clinical value in CT subjective evaluation of normal population.There are statistically significant differences in the quantitative parameters of emphysema among different groups.
8.Exendin-4 alleviates diabetic cardiomyopathy in mice by regulating Sirt1/PGC1α.
Ying-Ying CAI ; Shao-Zhou ZOU ; Cun-Xia FAN ; Chun-Yan WU ; Shu FANG ; Ping LI ; Yao-Ming XUE ; Mei-Ping GUAN
Journal of Southern Medical University 2018;38(5):520-526
OBJECTIVETo investigate the protective effect of exendin-4 against diabetic cardiomyopathy in mice and explore the underlying mechanism.
METHODSC57BL/6J mice were randomly divided into normal control group with normal diet and diabetic group with high-fat diet for 4 weeks before streptozotocin injection. The successfully established diabetic mouse models were divided into diabetic group with exendin-4 treatment and diabetic control group for daily treatment with intraperitoneal injection of 1 nmol/kg exendin-4 and saline of equivalent volume for 8 weeks, respectively. The physiological parameters such as blood glucose and body weight were recorded. RT-PCR was used to examine the transcription levels of genes related with myocardial hypertrophy and fibrosis and the genes related with mitochondrial functions including PGC1α, NRF and CytoC. The expressions of oxidative stress markers and Sirt1/PGC1 proteins were measured using Western blotting. and HE staining was used to observe the myocardial structural changes in the mice.
RESULTSCompared with the normal control mice, the mice in diabetic control group showed significantly increased blood glucose and blood lipid levels (P<0.001), which were obviously improved by Exendin-4 treatment. The expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 were significantly increased (P<0.05) while Sirt1, PGC1α, NRF and SOD1 expression were markedly decreased in the myocardial tissue of the diabetic mice (P<0.05). Exendin-4 treatment resulted in obviously reduced expressions of ANP, BNP, TGFβ1, CytoC1 and NOX1 (P<0.05) and increased expressions of Sirt1, PGC1α, NRF and SOD1 (P<0.05) in the diabetic mice.
CONCLUSIONSExendin-4 protects against myocardial injury in diabetic mice by improving mitochondrial function and inhibiting oxidative stress through the Sirt1/PGC1α signaling pathway.
9.Low-radiation-dose CT:quantitative research for lung volume using iterative model reconstruction
Yuan FANG ; Yu GUAN ; Yi XIA ; Rutan CHEN ; Li FAN ; Shiyuan LIU ; Xiangsheng XIAO
Journal of Practical Radiology 2017;33(10):1600-1604
Objective To investigate the impact of quantitative measurement for lung volume using iterative model reconstruction (IMR),hybrid iterative reconstruction (iDose4 )and filtered back projection (FBP),and to compare the image noise between different reconstruction methods.Methods 70 subjects were performed with low-dose chest CT scan (Philips Brilliance 256 iCT),and the original data were reconstructed with IMR (algorithm:Routine,SharpPlus,Soft Tissue,level:1 - 3 ),iDose4 and FBP respectively.We set less than -950 HU as emphysema threshold,calculated the total lung volume (TLV),total emphysema volume (TEV),emphysema index (EI)and objective image noise (OIN),and then compared the quantitative parameters and OIN between different groups.Results All parameters showed a significantly statistical difference (P =0.000)except TLV (P =1.000).The TEV and EI are significant higher in IMR-S group than in other groups.The OIN in IMR-S-L1 group was the highest,and the FBP group was the second-highest.OIN in iDose4 group was lower than that in IMR-S groups but higher than that in IMR-R and IMR-ST group.Conclusion SharpPlus algorithm of IMR will affect the quantitative measurement of lung volume under low-radiation-dose condition,and the OIN in IMR-S groups is obvious.Therefore SharpPlus algorithm is not recommended for quantitative analysis of lung volume.The Routine and Soft Tissue algorithm will not affect the quantitative measurement,and can distinctly reduce the OIN compared with idose4 and FBP.
10.Association of p53 codon 72 polymorphism with liver metastases of colorectal cancers positive for p53 overexpression.
Zhong-Zheng ZHU ; Bing LIU ; Ai-Zhong WANG ; Hang-Ruo JIA ; Xia-Xiang JIN ; Xiang-Lei HE ; Li-Fang HOU ; Guan-Shan ZHU
Journal of Zhejiang University. Science. B 2008;9(11):847-852
OBJECTIVETo evaluate the association between p53 codon 72 polymorphism (R72P) and the risk of colorectal liver metastases.
METHODSThe p53 R72P genotype was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 78 consecutive colorectal cancer patients with liver metastases and 214 age- and sex-matched cases with nonmetastatic colorectal cancer.
RESULTSThe R allele of the p53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P=0.075). Carriers of the 72R allele had a 2.25-fold (95% CI (confidence interval)=1.05 to approximately 4.83) increased risk of liver metastases. On the stratification analysis, 72R-carrying genotype conferred a 3.46-fold (95% CI=1.02 to approximately 11.72) and a 1.05-fold (95% CI=0.36 to approximately 3.08) increased risk of liver metastases for p53 overexpression-positive and negative colorectal cancers, respectively.
CONCLUSIONThese results demonstrate for the first time that the 72R allele of the p53 polymorphism has an increased risk for liver metastases in colorectal cancers positive for p53 overexpression.
Adenocarcinoma ; genetics ; metabolism ; pathology ; secondary ; Case-Control Studies ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; DNA, Neoplasm ; blood ; genetics ; Female ; Genes, p53 ; Genetic Predisposition to Disease ; Genotype ; Humans ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Tumor Suppressor Protein p53 ; biosynthesis ; genetics