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Objective:To retrospectively analyze the clinical effects and complications of alcohol inactivation, irradiation inactivation, and liquid nitrogen inactivation in the treatment of femur osteosarcoma in children, in an attempt to provide a theoretical basis for clinical selection of in vitro inactivation methods of tumor bone segment. Methods:The clinical data of 93 children with femur osteosarcoma admitted to the Department of Bone and Soft Tissue, the Affi-liate Cancer Hospital of Zhengzhou University from January 2008 to December 2017 were retrospectively analyzed, and 40 children, including 21 males and 19 females, aged 8-18 (13.65±2.87) years, who were treated with in vitro inactivation and replantation of autogenous tumor bone segment, were screened.Among these children, there was alcohol inactivation in 15 cases, irradiation inactivation in 12 cases, and liquid nitrogen inactivation in 13 cases.A comparison was drawn on these 3 inactivation methods with respect to bone healing time, bone healing rate, tumor recurrence rate, infection rate, fracture or fixation failure rate, and revision rate. Results:All those 40 children were subject to valid medical followed-up, with the alcohol inactivation group for (102.60±16.55) months, the irradiation inactivation group for (59.33±6.39) months, and the liquid nitrogen inactivation for (36.85±6.49) months.The difference in follow-up time of 3 groups was statistically significant ( P<0.05). Compared with other 2 groups, the index of bone healing time, bone healing rate, infection rate and revision rate in the alcohol inactivation group were unfavorable, which showed a significant difference (all P<0.05); However, there was no significant difference in the recurrence rate, fracture rate or fixation failure rate compared with other 2 groups (all P>0.05); There was no significant difference in all above indexes between the irradiation group and the liquid nitrogen group (all P>0.05). Conclusions:Three in vitro inactivation methods for the treatment of tumor bone segment are safe and reliable.The alcohol inactivated bone has a long healing time and more complications.Both irradiation inactivation and liquid nitrogen inactivation are clinical options, but irradiation inactivation requires professional equipment, which may limit the clinical application.
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Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
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The aim of this study was to investigate the mechanism of luteolin regulating lipoxygenase pathway against oxygen-glucose deprivation/reperfusion(OGD/R) injury in H9 c2 cardiomyocytes. First, Discovery Studio 2019 was used for the molecular docking of luteolin with three key enzymes including lipoxygenase 5(ALOX5), lipoxygenase 12(ALOX12), and lipoxygenase 15(ALOX15) in lipoxygenase pathway. The docking results showed that luteolin had high docking score and similar functional groups with the original ligand. From this, H9 c2 cardiomyocytes were cultured in vitro, and then the injury model of H9 c2 cardiomyocytes was induced by deprivation of oxygen-glucose for 8 h, and rehabilitation of oxygen-glucose for 12 h. Cell viability was detected by tetrazolium(MTT) colorimetry. H9 c2 cardiomyocytes were observed with a fluorescence inverted microscope, and colorimetry was used to detect the level of lactate dehydrogenase(LDH) in cell supernatant. The results showed that luteolin could significantly protect the morphology of H9 c2 cells, significantly improve the survival rate of H9 c2 cardiomyocytes in OGD/R injury model, reduce the level of LDH in cell supernatant, inhibit cytotoxicity, and maintain the integrity of cell membrane. The inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay. Compared with the model group, luteolin can significantly reduce the release of IL-6 and TNF-α. Western blot was employed to detect the protein levels of ALOX5, ALOX12, and ALOX15 in lipoxygenase pathway. After luteolin intervention, the protein levels of ALOX5, ALOX12, and ALOX15 were significantly down-regulated compared with those in model group. These results indicate that luteolin can inhibit the release of IL-6 and TNF-α by restraining the activation of lipoxygenase pathway, thereby playing a protective role in the cardiomyocyte injury model induced by OGD/R.
Subject(s)
Humans , Apoptosis , Glucose , Lipoxygenases , Luteolin/pharmacology , Molecular Docking Simulation , Myocytes, Cardiac , Oxygen , Reperfusion Injury , Signal TransductionABSTRACT
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
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OBJECTIVE: To investigate the expression and clinical significance of Lin28 B in placenta of severe preeclampsia(SPE).METHODS: Forty SPE patients were admitted to Shengjing Hospital of China Medical University from August 2017 to August 2018,including 20 patients with early-onset severe preeclampsia(ESPE)and 20 patients with late onset severe preeclampsia(LSPE).Another 40 healthy pregnant women who had termination of pregnancy in late pregnancy due to various reasons were selected as the control group,including 20 cases in early-onset control group(N1) and 20 cases in late-onset control group(N2). RT-qPCR analysis,Western Blot analysis and immunohistochemistry were used to detect the Lin28 B expression levels in placenta of each group.RESULTS: The expression of Lin28 B in placenta was significantly lower in ESPE group than in N1 group(P0.05).The expression of Lin28 B in placenta of ESPE group was lower than that in LSPE group(P<0.05).CONCLUSION: The expression of Lin28 B in placenta of SPE patients is decreased,and the ESPE group was significantly lower than that in LSPE group,suggesting that Lin28 B may be associated with the pathogenesis and development of SPE.
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Objective To investigate the clinical effect of irradiated-host bone ends' union after transplantation of pedicled vascularized fibular periosteum in the treatment of Children's tibia sarcoma.Methods From June,2016 to December,2016,there were 5 children of tibia sarcoma,which were 2 boys and 3 girls,aged of 9-15 years (mean,12 years).They were treated by the re-transplantation of extracorporal irradiated segmental autograft,and used ipsilateral pedicled vascularized fibular periosteum cover the ends of irradiated-host bone to shorten the bone union time of irradiated tibia autograft and prevent nonunion.Patients were 3 cases of osteosarcoma,1 of Ewing's sarcoma,and 1 of relapse of Langerhans's cell histocytosis in tibia.The length of resect bone was 14.0-20.0 cm (mean,17.2cm),constitute of 2 osteoarticular resections and 3 intercalary resections.The method of inactivation of bone segment was intraoperative extracorporal irradiation.Regular followed-up were done postoperative.The X-ray and CT were applied to observe the function of affect limb.The bone union time and complication were record.Results All patients were followed-up of 12-18 months (mean,14.2 months).Eight ends of irradiated-host bone in 5 patients healed completely in 7.8 (6-10) months postoperative.The region of ends were covered by periosteum and showed excellent osteogenic power.There was no leg length discrepancy occurred in patients who received intercalary inactivation because of the preservation of growth plate.But the other 2 osteoarticular inactivated patients suffered leg length discrepancy of 1.0 cm and 1.5 cm respectively because of the inactivation of growth plate.At the follow-up of 12 months post-operation,the mean MTSS of affect limb was 25.8(22-28),and the mean of MTSS％ was 86％(73％-93％).Conclusion Transplantation of pedicled vascularized fibular periosteum can promote effectively healing of irradiated tibia bone after replantation in Children,with simple operation and less complications.
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AIM:To investigate the effect of piceatannol on the viability, and the abilities of migration and invasion in the prostate cancer cells.METHODS:DU145 cells were treated with piceatannol at different doses (0, 5, 10, 20, 40 and 80 μmol/L) for different time (12, 24, 36 and 48 h) as indicated.The cell viability was assessed by CCK-8 assay.The migration and invasion abilities of the cells were analyzed by wound healing assay and Transwell assay, respectively.The protein levels of p-JAK2 and p-STAT3 were detected by Western blot.RESULTS:Piceatannol dose-dependently decreased the cell viability.After treatment with piceatannol, the abilities of migration and invasion of the cells were significantly inhibited.Moreover, treatment with piceatannol resulted in marked decreases in the protein levels of p-JAK2 and p-STAT3.CONCLUSION:Piceatannol inhibits the viability, migration and invasion of the prostate cancer cells via regulating the JAK2/STAT3 signaling pathway.
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Objective To explore whether intravenous injection of hydrogen‐rich saline having the protective effect on sodium taurocholate induced severe acute pancreatitis(SAP) associated lung injury(APALI) in rats and its possible mechanisms .Methods Fifty‐four healthy male SD rats were randomly divided into sham‐operation group (Sham group) ,model group (SAP+ NS group) and hydrogen water treatment group (SAP + HRS group) ,and each group was subdivided into 6 ,12 ,24 h subgroups .Six rats were killed at each time point for collecting serum ,lung tissue and pancreas tissue .Serum TNF‐αand IL‐1βlevels ,lung wet /dry weight ratio ,expression of TNF‐αmRNA and IL‐1βmRNA in the lung tissue were detected .The pathological evaluation of pancreas and lung tissue injury was performed .Results (1)The levels of TNF‐α and IL‐1β in serum ,pancreas and lung tissue pathological scores ,TNF‐αmRNA and IL‐1βmRNA expression levels in the lung tissue and lung wet dry weight ratio at the time points of 6 , 12 ,24 h in the SAP+NS group and the SAP+ HRS group were higher than those in the sham group (P<0 .05) .(2) Compared with the SAP+NS group ,the levels of serum TNF‐α,TNF‐αmRNA expression level in the lung tissue and lung wet dry weight ra‐tio at all time points in the SAP+ HRS group were lower(P<0 .05);the levels of serum IL‐1β,pancreas and lung tissue pathologi‐cal score and IL‐1β‐mRNA expression at 6 h in the lung tissue had no statistical difference between the SAP+NS group and SAP+HRS group ,but which at time points of 12 ,24 h in the SAP+ HRS group were lower than those in the SAP+NS group(P<0 .05) . Conclusion HRS realize the protection on APALI possibly via its elective anti‐oxidation action for inhibiting oxidative stress injury related cytokines expression .
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<p><b>AIM</b>To synthesize oxazolindinone derivatives and test their antibacterial activities.</p><p><b>METHODS</b>3-Halo-4-methylaniline was acylated with benzyl chloroformate, followed by cyclization with (R)-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NaN3, reduction with H2 + Pd/C or P(OMe)3 + HCl, acylation with Ac2O, and bromination with NBS to form bromides VIIIa and VIIIb, Substitution of the bromides with various amines including aliphatic amine and aromatic amine provided the target compounds IXa and IXb. The in vitro antibacterial activity of the target compounds was tested.</p><p><b>RESULTS</b>Fifty one new compounds were designed and synthesized. And their structures were confirmed by 1H NMR and elemental analyses or MS. Some physical constants such as [alpha]D25 were reported also. Compounds VIIb, IXa1, IXa2, IXa7, IXb1, IXb3, IXb10, IXb16 and IXb23 had moderate in vitro antibacterial activity against G+ bacteria but they were less active than linezolid or norfloxacin.</p><p><b>CONCLUSION</b>Insertion of methylene group between 4-position of phenyl and morpholinyl group in linezolid derivatives can not increase the antibacterial activity.</p>
Subject(s)
Acetamides , Pharmacology , Anti-Bacterial Agents , Chemistry , Pharmacology , Linezolid , Microbial Sensitivity Tests , Molecular Structure , Oxazolidinones , Chemistry , Pharmacology , Staphylococcus , StreptococcusABSTRACT
Objective To investigate the characteristics of pulmonary infection and susceptible factors following orthotopic liver transplantation (OLT). Methods Clinical data of 128 patients who underwent OLT from Feb. 1999 to Dec. 2004 were studied retrospectively in order to analyze primary pathogens, infectious time and susceptible factors.Results Forty-eight ( 37.5 %) of 128 patients had pulmonary infections and 27 ( 56.3 %) of them developed within postoperative 7 days. Thirty-four ( 70.8 %) cases suffered from mixed infection and 6 ( 12.5 %) died in the hospital after OLT. The primary pathogenic germs included Pseudomonas aeruginosa, Acinetobacter baumannii/haenolyticus, Golden staphylococcus, Aspergilosis and so on.Conclusion Pulmonary infection can be caused by various pathogens and associated with patients' constitution, mechanical ventilation, immunosuppressive drugs and so on.
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<p><b>AIM</b>To study the absorption of zedoary oil in intestine of rat.</p><p><b>METHODS</b>In situ single pass perfusion model was used and the concentrations of three components in perfusate were determined by HPLC in combination with diode array detection.</p><p><b>RESULTS</b>The P(app) s of curcumol, curdione and germacrone were all low and had no significant difference (P > 0.05) at zedoary oil concentration of 0.4, 0.8 and 1.2 mg x mL(-1) in transmucosal fluid or in four different regions of intestine of rat [duodenum, jejunum, ileum, colon]. The absorption rates of germacrone and curdione were faster than curcumol's in this study.</p><p><b>CONCLUSION</b>The zedoary oil concentration in transmucosal fluid had no significant effect on the P(app) s within the scope of 0.4-1.2 mg x mL(-1). The absorption of curcumol, curdione and germacrone showed the passive diffusion process, and didn't contain a special absorption window.</p>
Subject(s)
Animals , Male , Rats , Biological Transport , Colon , Metabolism , Curcuma , Chemistry , Duodenum , Metabolism , Ileum , Metabolism , In Vitro Techniques , Intestinal Absorption , Jejunum , Metabolism , Perfusion , Plant Oils , Chemistry , Pharmacokinetics , Plants, Medicinal , Chemistry , Rats, Wistar , Sesquiterpenes , Pharmacokinetics , Sesquiterpenes, Germacrane , PharmacokineticsABSTRACT
The effect of dark tea fermentation liquid with Eurotium Cristatum on the activity of digestive enzyme was researched, as fellowing amylase, protease, lipase. The results showed that dark tea fermentation liquid with Eurotium Cristatum may increase remarkably the activity of ?-amylase and protease, but decrease efficiently the activity of lipase. The fermentation liquid improves the digestion and absorption of starch and protein, but inhibits the decomposition and absorption of fat, so it can explain the mechanism of Fu-brick tea's health functions.