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Chimeric antigen receptor T-cell (CAR-T) immunotherapy is one of the new models of tumor targeted therapy. However, the presence of cytokine release syndrome (CRS) after CAR-T infusion is a key obstacle limiting its therapeutic effects. Macrophage activation and pyrosis of target tumor cells can trigger the release of interleukin-6 and other inflammatory factors, and excessive inflammatory factors can lead to excessive activation of endothelial cells, which is a key molecular mechanism for the escalation of CRS and the occurrence of serious adverse events. Intervention in multiple stages of cytokine production and structural optimization of chimeric antigen receptor molecules are effective strategies to reduce CRS.
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OBJECTIVE: To further design and synthesize Desmosdumotin-C(Des-C) derivatives and investigate their antitumor activities. METHODS: QSAR study using the CoMFA method was performed on a set of reported Des-C derivatives to facilitate the elucidation of their SAR and discovery of new potent Des-C derivatives. Flow cytometry was used to investigate antitumor activity. RESULTS: The established model showed good predictive ability and aid in the design of potent Des-C derivatives. An efficient three-step synthetic strategy toward Des-C derivatives was developed and applied to synthesize 10 new derivatives which showed superior antitumor activities against A549 and HL60 cells in vitro. CONCLUSION: The structural modification of Des-C would significantly increase the antitumor activity. It is preliminarily confirmed that the derivatives are potent antitumor agents with apoptosis-inducing ability, which provides the basis for the further study.
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Objective:To develop a materials management information system for military hospital warehouse of combat readiness based on RFID so as to enhance the management of military medical corps for materials of war preparation.Methods:RFID(Radio Frequency Identification) tags were attached on war materials and the information could been read by bar-code reader. SQL Server 2005 was used as the backend database, and VC# was combined with RFID to develop the software system.Results: This research has developed a materials management information system for military hospital warehouse of combat readiness based on RFID and this system could achieve informatization for information management, management of out and in warehouse, emergency plans management and forewarning management. Through manoeuvre, the average time of war materiel out warehouse has saved 12min.Conclusion: The research and development of information management system for materiel information of hospital warehouse for combat readiness has reference value for the application of researching RBID technique in material management.
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Objective To study the inhibitory effects of TPP,a desmosdumotin-C B ring para-fluoro modified derivative,on human breast cancer MCF-7 cell proliferation,and investigate the possible mechanisms.Methods MTT assay was used to measure the proliferation suppression of MCF-7 cells after treated with 1.0,2.5,5.0,10.0,and 20.0 μg/mL TPP for 48 h,and then the cell apoptosis rate and expression rate of NF-κB P65 positive cells were tested by flow cytometry after 20.0 μg/mL TPP treatment for 0,24,and 48 h.Results MTT assay showed that,after treatment for 48 h,1.0,2.5,5.0,10.0,and 20.0 μg/mL TPP all exhibited the inhibitory effects and showed a dose-dependent relationship.Flow cytometry results showed that 20.0 μg/mL TPP induced cell apoptosis after treatment for 24 and 48 h.TPP (20.0 μg/mL) significantly reduced the rate ofNF-κB P65-positive cells in MCF-7 cells after treatment for 48 h.Conclusion TPP could inhibit the proliferation of MCF-7 cells,which may be induced by cell apoptosis.Down-regulation of NF-κB is possible to be related with apoptosis.
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Objective:To investigate the preventive effect of tetramethylpyrazine (TMP) on hypoxic pulmonary hypertension in rats and the underlying mechanism.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into three groups:the normal control group,hypobaric and hypoxic group and TMP group (100 mg·kg-1·d-1).After the animal models of hypobaric and hypoxic pulmonary hypertension were established,mean pulmonary artery pressure (mPAP),mean carotid artery pressure (mCAP),ratio of right ventricular/(lift ventricular + interventricular septum) (RVHI) and morphological changes of pulmonary vessels were observed and the rates of wall thickness/external diameter (WT%) and wall area/total vascular area (WA%) were calculated.The contents of nitric oxide (NO),endothelin-1 (ET-1),hypoxic-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) were detected in serum after the 21-day treatment with TMP.Results:The values of mPAP,RVHI,WT% and WA% of hypobaric and hypoxic group were significant higher than those of the normal control group (P0.05).The values of NO in serum of hypobaric and hypoxic group was lower than those of the normal control group (P<0.05) and those of TMP group were obviously higher than those of hypobaric and hypoxic group (P<0.05).The values of ET-1,HIF-1α and VEGF in serum of hypobaric and hypoxic group were higher than those of the normal control group (P<0.05) and those of TMP group were obviously lower than those of hypobaric and hypoxic group (P<0.05).Conclusion:TMP can effectively prevent pulmonary hypertension induced by hypobaric and hypoxic and structural remodeling of pulmonary arterioles.The mechanism may be related to the content up-regulation of NO and activity down-regulation of ET-1,HIF-1α and VEGF in serum of rats.
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Research progress of flavanone compounds synthesis was reviewed ,various types of synthesis methods of fla‐vanone compounds were summarized ,and methodological support for flavanone compounds in new drug research and develop‐ment was provided .Research progress in synthesis of flavanone compounds includes chalcone cyclization ,Friedel‐Crafts reac‐tion ,Knoevenagel condensation ,Hoesch single acetoxylation ,and asymmetric synthesis of flavanone compounds .Solvent‐free synthesis of flavanone compounds and other green chemistry methods were also introduced .
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<p><b>OBJECTIVES</b>To study the correlation and effect of smoking on the semen quality of men.</p><p><b>METHODS</b>61 men, non-smoker, who had one or more children as normal fertility control group and adult males attending the infertility clinic, including 110 non-smokers and 191 smokers, were recruited for the study. The smokers were divided into subgroups according to the amount and duration of smoking. Semen parameters(volume, sperm density, viability, motility and morphology) were examined and seminal plasma contents of Zn, Cu and superoxide dismutase (SOD) were determined.</p><p><b>RESULTS</b>The semen volume, pH, sperm density, viability and forward progression, as well as the seminal plasma contents of Zn, Cu and SOD were much lower in the medium, heavy and long-term smokers than in the non-smokers(P < 0.01). The sperm density, viability and forward progression, and the seminal plasma Zn, Cu and SOD levels were negatively correlation with the amount and duration of cigarette smoking(P < 0.001).</p><p><b>CONCLUSIONS</b>The effect of smoking on semen parameters of infertile men were dose-effect and time-effect relationship. Medium, heavy and long-term smoking adversely affected the semen quality in a population of men visiting the infertility clinic.</p>