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Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.
Subject(s)
Child , Female , Male , Infant, Newborn , Humans , Infant , Sodium Channel Blockers/adverse effects , Oxcarbazepine , Lacosamide , Retrospective Studies , Epilepsies, Partial/drug therapy , Seizures , Sodium , Anticonvulsants/adverse effectsABSTRACT
ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina (EVP) on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells, a human breast cancer cell line, into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 (Ck-19) gene in mouse bone marrow was determined by nested polymerase chain reaction(PCR) to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages (BMMs), we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB (RANK), Runt-related transcription factor 2 ( Runx2 ), phosphorylated Runx2 (p-Runx2), and matrix metalloproteinase-9 (MMP-9) in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases (MMPs). ResultCompared with that in the blank group, Ck-19 expression was down-regulated in EVP groups (P<0.05). The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand (sRANKL), which was inhibited by EVP (P<0.05). The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group, while EVP groups had lower cathepsin K levels than sRANKL group (P<0.05). Compared with the blank group, the sRANKL group showed up-regulated RANK expression, Runx2 phosphorylation, and MMP-9 expression (P<0.05), while the expression levels of RANK, p-Runx2, and MMP-9 were down-regulated when the cells were incubated with EVP (P<0.05). Furthermore, exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group (P<0.01), which, however, was reversed in EVP groups (P<0.05). ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells, which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.
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Objective To analyze the patterns of lymph nodes metastasis (LNM) in supraglottic laryngeal squamous cell carcinomas (SLSCC) patients with different tumor differentiation. Methods We retrospectively investigated the clinicopathological data of patients diagnosed as SLSCC. The LNM patterns were analyzed by different tumor differentiation degrees. Results A total of 79 patients were included and divided into poorly differentiated group (n=20), middle differentiated group (n=52) and well differentiated group (n=7). There were 38 patients in N0 stage, 8 patients in N1 stage, 28 patients in N2 stage and 5 patients in N3 stage; 36 patients with LNM in level Ⅱ, 21 patients with LNM in level Ⅲ, 7 patients with LNM in level Ⅳ and no patients with LNM in level Ⅴ or Ⅵ. Conclusion SLSCC patients can benefit from bilateral neck dissection, and the patients with poor or moderate differentiation can benefit from neck dissection (levelsⅡ-Ⅳ), while the patients with well differentiation dissection may be more appropriate for neck dissection (levels Ⅱ-Ⅲ).
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Objective:To investigate the inhibitory effects of Danshen injection against ovarian cancer cell proliferation induced by the interaction between platelets and cancer cells. Method:The induction of platelets on SKOV3 growth <italic>in vitro</italic> and the inhibitory effect of Danshen injection at 12,24,and 48 g·L<sup>-1</sup> were observed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. The content of transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>) in the platelet-tumor cell interaction system and platelet supernatant and the effect of Danshen injection on TGF-<italic>β</italic><sub>1 </sub>secretion were detected by enzyme-linked immunosorbent assay (ELISA). The influences of tumor cell culture supernatant on platelet aggregation and secretion and the inhibitory effect of Danshen injection were determined by microplate assay and ELISA. The effects of Danshen injection on platelet nuclear factor kappa B (NF-<italic>κ</italic>B) signaling pathway were assayed by Western Blot. Result:Compared with the blank group, the platelet induction group exhibited significantly elevated absorbance at <italic>A</italic><sub>570 </sub>(<italic>P</italic><0.01), while the absorbance at <italic>A</italic><sub>570</sub> in the platelet + Danshen injection group was significantly lower than that in the platelet induction group (<italic>P</italic><0.01). The comparison with the Danshen injection group revealed that the cell proliferation inhibitory rate in the platelet + Danshen injection group at the same dose was more significant (<italic>P</italic><0.01). The number of colonies in the platelet induction group was obviously increased in contrast to that in the blank group(<italic>P</italic><0.05), while the number of colonies in the platelet + Danshen injection group was significantly lower than that in the platelet induction group(<italic>P</italic><0.05,<italic>P</italic><0.01). As demonstrated by comparison with the blank group, TGF-<italic>β</italic><sub>1 </sub>content in the supernatant of the platelet induction group rose remarkably(<italic>P</italic><0.01), whereas that in the platelet + Danshen injection group declined(<italic>P</italic><0.01). Compared with the Danshen injection (24 g·L<sup>-1</sup>) group, the platelet + Danshen injection group displayed more obvious inhibition(<italic>P</italic><0.01). Compared with the blank group, Danshen injection significantly reduced the TGF-<italic>β</italic><sub>1 </sub>content in platelet supernatant(<italic>P</italic><0.05,<italic>P</italic><0.01). There was no significant change in the content of TGF-<italic>β</italic><sub>1 </sub>in SKOV3 supernatant treated with Danshen injection. The platelet aggregation, thromboxane A<sub>2</sub>(TXB<sub>2</sub>), and serotonin (5-HT) secretion in the SKOV3 cell supernatant induction group were significantly increased as compared with those in the blank group (<italic>P</italic><0.01), while such indexes in the cell supernatant induction + Danshen injection group were obviously decreased (<italic>P</italic><0.01). Compared with the Danshen injection (24 g·L<sup>-1</sup>) group, the cell supernatant induction + Danshen injection group displayed more obvious inhibition at the same dose(<italic>P</italic><0.01). Compared with the blank group, the platelet induction group exhibited obviously up-regulated phosphorylated TGF-<italic>β</italic>-activated kinase-1 (TAK-1) and NF-<italic>κ</italic>B, but down-regulated phosphorylated inhibitory protein of NF-<italic>κ</italic>B (I<italic>κ</italic>B)(<italic>P</italic><0.01), which however were significantly reversed in the platelet + Danshen injection group<bold>(</bold><italic>P</italic><0.01). Conclusion:Danshen injection affect the proliferation of SKOV3 cells by inhibiting their interaction with platelets, which may be related to the inhibited secretion of TGF-<italic>β</italic><sub>1</sub>.
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Central nervous system injury leads to irreversible neuronal loss and glial scar formation, which ultimately results in persistent neurological dysfunction. Regenerative medicine suggests that replenishing missing neurons may be an ideal approach to repair the damage. Recent researches showed that many mature cells could be transdifferentiated into functional neurons by reprogramming. Therefore, reprogramming endogenous glia in situ to produce functional neurons shows great potential and unique advantage for repairing neuronal damage and treating neurodegenerative diseases. The present review summarized the current research progress on in situ transdifferentiation in the central nervous system, focusing on the cell types, characteristics and research progress of glial cells that could be transdifferentiated in situ, in order to provide theoretical basis for the development of new therapeutic strategies of neuronal injury and further clinical application.
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Humans , Cell Transdifferentiation , Cellular Reprogramming , Central Nervous System , Cell Biology , Neurodegenerative Diseases , Neuroglia , Cell Biology , Neurons , Cell BiologyABSTRACT
Objective·To study the effect of sumoylation on the structure,stability and activity of human thymine DNA glycosylase (TDG).Methods·Expression and purification systems were established for obtaining SUMO-1-TDG protein with high purity which can be used for crystal screening and activity detection.Structure of SUMO-1-TDG was solved after crystal screening,diffraction data collection and structure analysis.The change of TDG stability led by sumoylation was detected through a protein thermal shift assay.In addition,an activity assay was applied to investigate the effect of sumoylation on the activity of TDG.Results·A high-resolution structure of SUMO-1-TDG which could clearly describe the interaction between TDG and SUMO-1 was solved.The melting temperature ? value of SUMO-1-TDG increased by about 16 ℃ and the catalytic activity increased by 9.70%,comparing with TDG protein.Conclusion·SUMO-1 binds to TDG to modify the intermolecular interaction of amino acids near the binding site,and further participates in the regulation of the stability and catalytic activity of TDG protein.
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Objective To observe any curative effect of applying comprehensive pulmonary rehabilitation in moderate and severe cases of chronic obstructive pulmonary disease (COPD).Methods A total of 135 persons hospitalized with moderate or severe COPD were randomly divided into a rehabilitation group of 75 and acontrol group of 60.Both groups were given routine treatment,while the rehabilitation group was additionally provided with a comprehensive pulmonary rehabilitation regimen,including health education,exercise training,respiratory function training,respiratory muscle training,psychological support and nutritional intervention for six months.Before and after the treatment,both groups were evaluated using their walking distance within 6 minutes (6MWD),an anhelation index,a COPD assessment test (CAT),the Beck anxiety and depression scale,a nutritional assessment and indexes of pulmonary function and blood gases.Results After the intervention the average 6 MWD,anhelation index,CAT score,Beck anxiety and depression scores,forced expiratory volume,forced vital capacity and PaO2 of the rehabilitation group were all significantly better than before the treatment and better than those of the control group.Conclusion For moderate and severe COPD patients,comprehensive pulmonary rehabilitation effectively strengthens their moving ability,pulmonary function and arterial partial pressure of oxygen,while relieving anhelation,anxiety and depression.
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Objective: To study the effect of sumoylation on the structure, stability and activity of human thymine DNA glycosylase (TDG). Methods: Expression and purification systems were established for obtaining SUMO-1-TDG protein with high purity which can be used for crystal screening and activity detection. Structure of SUMO-1-TDG was solved after crystal screening, diffraction data collection and structure analysis. The change of TDG stability led by sumoylation was detected through a protein thermal shift assay. In addition, an activity assay was applied to investigate the effect of sumoylation on the activity of TDG. Results: A high-resolution structure of SUMO-1-TDG which could clearly describe the interaction between TDG and SUMO-1 was solved. The melting temperature (Tm) value of SUMO-1-TDG increased by about 16℃ and the catalytic activity increased by 9.70%, comparing with TDG protein. Conclusion: SUMO-1 binds to TDG to modify the intermolecular interaction of amino acids near the binding site, and further participates in the regulation of the stability and catalytic activity of TDG protein.
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Esomeprazole sodium is a widely used proton pump inhibitor which is mainly applied to the treatment of gastric ul-cer,duodenal ulcer,digestive esophagitis and gastritis. By reviewing the literature over the past decade on the asymmetric oxidation of esomeprazole sodium ,the paper summarizes the synthetic process and focuses on the comparison of the critical steps. To choose suit-able chiral catalyst to reduce the cost of synthesis of esomeprazole sodium,this paper compares beyond the yield,enantioselectivity and other aspects. The conclusion is that the catalysts used in the most of oxidation systems are with a large load and high cost ,and compared with the classical Kagan-Modena system,the Ti-salan catalyst has advantages in the synthesis of esomeprazole sodium,and can be widely used.
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To study the chemical constituents from the stems of Cipadessa cinerascens. The constituents were separated by column chromatography and their structures were elucidated by spectral data analyses. Seventeen chemical constituents were isolated from the EtOAc extract in the stems of C. cinerascens and their structures were identified as lanost-7-en-3-one-22, 25-epoxy-23, 24-acetone acetal (1), chisopanin M (2), 3β-hydroxy-5-en-stigmast (3), 7α-hydroxy-4-en-3-one-stigmast (4), 3β-hydroxy-5-en-7-one-stigmast (5), 7α-hydroxysitosterol (6), 22E-7α-methoxy-5α, 6α-epoxy-8 (14), 22-dien-3β-hydroxy-ergosta (7), 7β-hydroxy-4-en-3-one-cholest (8), 3β-acetyloxy-2β, 4β-dihydroxy-16-one-pregnan (9), 17α, 20R-dihydroxy-3, 16-dione-pregnan (10), 2β, 3β-dihydroxy-16-one-pregnan (11), 3β, 7α-dihydroxy-20-one-pregnan (12), 2α, 3β-dihydroxy-5-en-20-one-pregnan (13), 1, 4-dien-3, 16-dione-2-hydroxyandrosta (14), 5-en-17-one-3β, 16β-dihydroxyandrost (15), apegenin (16), and annuionone D (17). Conclusion All the compounds except 14 and 17 are obtained from this plant for the first time.
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OBJECTIVE@#To observe the effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.@*METHODS@#Human intestinal cancer cell HT29 xenograft of nude mice model was established. The expression of EGF, VEGF, gastric cancer tumor growth in mice were observed.@*RESULTS@#Protein kinase C expression in in the Yiqi Jianpi group and Yiqi Jianpi anti-tumor group was significantly better than the model group (P<0.01, P<0.05). There was significantly more apoptotic cells in Yiqi Jianpi anti-tumor group than Yiqi Jianpi group and model group (P<0.01). Epidermal growth factor and vascular endothelial growth factor expression in Yiqi Jianpi group was significantly lower than Yiqi Jianpi group and model group (P<0.05).@*CONCLUSIONS@#Tumor can inhibit the expression of PKC inhibition. Yiqi Jianpi and anticancer treatment can reduce this inhibition. Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.
Subject(s)
Animals , Humans , Mice , Antineoplastic Agents , Pharmacology , Apoptosis , Colorectal Neoplasms , Drugs, Chinese Herbal , Pharmacology , HT29 Cells , Mice, Nude , Spleen , Xenograft Model Antitumor AssaysABSTRACT
AIM:To investigate the effects of down-regulated miR-9 expression on the proliferation , invasion and migration of nasopharyngeal carcinoma (NPC) cells.METHODS:Human NPC CNE1 and CNE2 cells were transfect-ed with the inhibitor of miR-9 by Lipofectamine to down-regulate the expression of miR-9, and the cells transfected with an inhibitor control were also set up .The cell proliferation and cell cycle were evaluated by CCK-8 assay and flow cytometry . The cell invasion and migration abilities were detected by Transwell invasion and wound -healing assays .Immunoblotting was applied to analyze the levels of the proteins .RESULTS:Compared with control group , inhibition of miR-9 expression in the NPC cells by transfection of the miR-9 inhibitor significantly decreased the proliferation ability (P<0.05).The per-centages of the cells in G 0/G1 phase [ CNE2: ( 57.96 ±1.39 )% vs ( 47.93 ±1.76 )%, P<0.05; CNE1: ( 51.24 ± 0.88)%vs (48.29 ±0.39)%, P<0.05] were significantly increased.The migration distances [CNE2: (186.50 ± 7.94)μm vs (247.56 ±15.56)μm, P<0.05;CNE1:(139.06 ±16.73)μm vs (230.66 ±14.27)μm, P<0.01] and the invasion ability of the CNE2 cells (43.00 ±3.17 vs 65.80 ±5.20, P<0.01) were also significantly inhibited .Moreo-ver, the tumor cells transfected with the inhibitors produced lower β-catenin.CONCLUSION:Inhibition of miR-9 expres-sion suppresses the proliferation , invasion and migration of nasopharyngeal carcinoma cells .
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<p><b>OBJECTIVE</b>To investigate the effects of down-regulated miR-9 expression on ultraviolet rays (UV)-induced reactive oxygen species (ROS) damage in nasopharyngeal carcinoma (NPC) cells.</p><p><b>METHODS</b>The NPC cells were transfected with inhibitors of miR-9 by lipofectamine to decrease the expression of miR-9, and the cells transfected with inhibitor control as the control. ROS levels following UV exposure were examined with DCF-DA method and the concentration of glutathione was analyzed via the benzoic acid method; DNA damage and apoptosis also were evaluated.</p><p><b>RESULTS</b>There was significant difference in ROS levels between miR-9 expression-inhibited cells and control cells (26 895 ± 218 vs 15 765 ± 927, t = 39.754, P < 0.001), and also there were significant differences in DNA damage rates (28.0% ± 10.0% vs 23.6% ± 9.2%) and in apoptosis rates (8.0% ± 0.9% vs 4.5% ± 0.8%) following UV exposure between two groups of cells. The miR-9 expression-inhibited cells showed lower level (1.87 ± 0.15) µmol/L of glutathione compared with the control cells (9.85 ± 0.15) µmol/L (t = -48.832, P < 0.001).</p><p><b>CONCLUSION</b>Inhibition of miR-9 expression promoted UV-induced ROS damage in nasopharyngeal carcinoma cells.</p>