1.Primary diffuse large B-cell lymphoma of central nervous system:clinical characteristics and prognostic analysis
Lianjie HU ; Fengyang LIN ; Xiaogong LIANG ; Wei LI ; Hong ZHANG ; Yongqian JIA
Journal of Leukemia & Lymphoma 2017;26(1):28-32,36
Objective To investigate the clinical characteristics and prognosis of primary diffuse large B-cell lymphoma of central nervous system ( PCNS DLBCL). Methods The data of 70 patients with PCNS DLBCL confirmed by pathology were retrospectively analyzed. Survival and prognostic analyses were further conducted in the 66 follow-up patients. Results Median age at diagnosis was 57 years old. The ratio of male and female was 1.3∶1. The time from having symptoms to seeking medical advice was less than 2 months in 54 (77.1%) patients. 44 (62.9 %) patients had increased intracranial pressure, and 26 (37.1 %) patients had limb weakness or hemiplegia symptoms. 37 (52.9%) patients were multiple lesions, 59 (84.3%) cases were supratentorial, and 46 (65.7%) cases showed involvement of deep-brain tissues. Among 66 follow-up patients 7 cases received supportive and palliative care, 27 cases received surgery, 6 cases received radiotherapy, 9 cases received chemotherapy alone, and 21 cases received radiotherapy in addition to chemotherapy. The median overall survival (OS) was 9 months (95 % CI 1-16 months), and the 2-year survival rate was 36.1 %. The median OSs of the supportive and palliative therapy group and the surgery group were 2 months and 3 months, respectively. The median OS of the chemotherapy, radiotherapy or combination group was 33 months (95%CI 22-43 months) and the 2-year OS rate was 56.9 %. The Cox multivariate regression analysis showed that the involvement of deep-brain tissues (P=0.04) and not receiving radiotherapy or chemotherapy (P=0.00) were related to poor prognosis. Conclusions PCNS DLBCL is a highly aggressive and malignant tumor. Patients undergoing only surgery have poor effect and short survival. The patients with involvement of deep brain tissues have a poor prognosis. The chemotherapy, radiotherapy or combination of them may improve the prognosis.
2.In Silico System Pharmacology for the Potential Bioactive Ingredients Contained in Xingnaojing Injection () and Its Material Basis for Sepsis Treatment.
Shi-Tang MA ; Cheng-Tao FENG ; You-Xi XIONG ; Xiao-Lin ZHANG ; Cheng-Gui MIAO ; Hao YU
Chinese journal of integrative medicine 2018;24(12):944-949
OBJECTIVE:
To elucidate the action mechanism of Xingnaojing Injection (, XNJI) for sepsis, and to target screen the potential bioactive ingredients.
METHODS:
An integrated protocol that combines in silico target screen (molecular docking) and database mapping was employed to find the potential inhibitors from XNJI for the sepsis-related targets and to establish the compound-target (C-T) interaction network. The XNJI's bioactive components database was investigated and the sepsis-associated targets were comprehensively constructed; the 3D structure of adenosine receptor A2a and 5-lipoxygenase proteins were established and evaluated with homology modeling method; system network pharmacology for sepsis treatment was studied between the bioactive ingredients and the sepsis targets using computational biology methods to distinguish inhibitors from non inhibitors for the selected sepsis-related targets and C-T network construction.
RESULTS:
Multiple bioactive compounds in the XNJI were found to interact with multiple sepsis targets. The 32 bioactive ingredients were generated from XNJI in pharmacological system, and 21 potential targets were predicted to the sepsis disease; the biological activities for some potential inhibitors had been experimentally confirmed, highlighting the reliability of in silico target screen. Further integrated C-T network showed that these bioactive components together probably display synergistic action for sepsis treatment.
CONCLUSIONS
The uncovered mechanism may offer a superior insight for understanding the theory of the Chinese herbal medicine for combating sepsis. Moreover, the potential inhibitors for the sepsis-related targets may provide a good source to find new lead compounds against sepsis disease.
Arachidonate 5-Lipoxygenase
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metabolism
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Computer Simulation
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Drug Evaluation, Preclinical
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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therapeutic use
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Humans
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Injections
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Phytochemicals
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therapeutic use
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Receptor, Adenosine A2A
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metabolism
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Reproducibility of Results
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Sepsis
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drug therapy
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metabolism
3.In silico target fishing for the potential bioactive components contained in Huanglian Jiedu Tang (HLJDD) and elucidating molecular mechanisms for the treatment of sepsis.
Shi-Tang MA ; Cheng-Tao FENG ; Guo-Liang DAI ; Yue SONG ; Guo-Liang ZHOU ; Xiao-Lin ZHANG ; Cheng-Gui MIAO ; Hao YU ; Wen-Zheng JU
Chinese Journal of Natural Medicines (English Ed.) 2015;13(1):30-40
The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction (HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2R proteins were established using the homology modelling (HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.
Anti-Inflammatory Agents, Non-Steroidal
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pharmacokinetics
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Berberine
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analogs & derivatives
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pharmacokinetics
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Dinoprostone
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biosynthesis
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Drugs, Chinese Herbal
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chemistry
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pharmacokinetics
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Humans
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KB Cells
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Platelet Membrane Glycoproteins
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drug effects
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Protein Transport
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Receptors, G-Protein-Coupled
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drug effects
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Receptors, Thromboxane A2, Prostaglandin H2
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drug effects
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Sepsis
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drug therapy
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metabolism
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Tetradecanoylphorbol Acetate
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pharmacokinetics