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Objective To investigate the molecular mechanism by which the circadian clock gene Period2 (PER2) downregulates extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) phosphorylation levels in nasopharyngeal carcinoma (NPC). Methods Cells were infected with lentivirus to construct cell lines. The expression of PER2 protein was validated using label-free proteomic analysis. Different concentrations of the ERK pathway activator Ceramide C6 were used to intervene with the cells, and the optimal drug concentration and treatment time were determined based on cell proliferation assessed by MTT assay. Western blotting was performed to detect the expression of PER2, ERK, p38 MAPK, p-ERK, and p-p38 MAPK proteins in cells after intervention with Ceramide C6, with the normal control group treated with an equal amount of drug solvent. Flow cytometry was used to analyze the cell cycle, and Transwell assay was conducted to evaluate cell invasion ability, further elucidating the mechanism by which PER2 regulates ERK and MAPK phosphorylation. Immunohistochemistry was employed to detect the expression of PER2 and p-ERK proteins in human NPC samples, and the correlation between PER2, p-ERK expression, and clinical characteristics of NPC was analyzed. Results Proteomic analysis showed that the expression of PER2 protein was significantly higher in the PER2 overexpression (OE) group compared to the negative virus control group and blank control group (P＜0.05). The top 20 differentially expressed proteins revealed that MAPK3 exhibited significant differences between the PER2 OE group and control group (P＜0.05). MTT assay results indicated that the optimal drug concentration was 10 μM, with the optimal treatment time being 24 hours. Western blotting results showed that PER2 overexpression downregulated the expression of p-ERK and p-p38 MAPK proteins, and intervention with Ceramide C6 led to upregulation of p-ERK and p-p38 MAPK protein expression levels in the PER2-OE group, with significant differences before and after intervention (P＜0.01). Cell cycle analysis revealed that intervention with Ceramide C6 increased the proportion of cells in the G1 phase and decreased the number of cells in the G2 phase. Transwell assay results demonstrated that PER2 overexpression inhibited cell invasion ability, which could not be reversed by kinase. Immunohistochemistry showed significant differences in the expression rates of PER2 and p-ERK proteins in NPC tissues and nasopharyngeal mucosa (P＜0.05). The expression of PER2 protein was correlated with tumor T stage (P＜0.05) and positively correlated with p-ERK protein expression in NPC tissues (P＜0.05). Conclusion PER2 overexpression downregulates ERK/MAPK phosphorylation levels, possibly not by directly affecting the phosphorylation sites of ERK and p38 MAPK, but by regulating key nodes of ERK and p38 MAPK. PER2 protein is downregulated and p-ERK protein is upregulated in NPC tissues, and they are correlated, closely related to the occurrence and development of tumors. [ABSTRACT FROM AUTHOR]

The influence of the cell wall material strain hardening effect on the deformation mode and cushioning properties of regular hexagonal honeycomb under in-plane impact loadings was investigated by numerical simulation. In order to quantify the strain hardening effect of the cell wall material, hardening parameter. E is defined. By keeping the honeycombs' configuration parameters were fixed and setting different loading velocities,the finite element models of honeycomb specimens with different values of E were established. Then a great deal of simulation calculations were performed and the related deformation mode and responses curves were obtained. These results showed that there are three kinds of deformation modes, such as X-shape,V-shape and l-shape with the increase of the impact velocity,and the deformation tends to be homogenized caused by the strain hardening effect of the cell wall material. The stress-strain curve,dynamic peak stress curve and energy absorption curve of the honeycomb core were also obtained by post-processing. Based on these mechanical response curves,we can conclude that honeycomb plateau stress and energy absorption would increase because of the strain hardening effect of the cell wall material. But this influence would be restrained with the increase of the impact velocity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the clinical efficacy of magnesium sulfate combined with low-dose aspirin in treatment of pregnancy-induced hypertension. METHODS: 100 patients with pregnancy-induced hypertension admitted from Aug. 2014 to Aug. 2015 were selected to be divided into control group and observation group via the random number table, with 50 cases in each. The control group were treated with 25% intravenous infusion of magnesium sulfate in 1-1.5 g per hour, 20 g for a day; the observation group additionally received oral aspirin based on the control group, 50 mg for a day. After treatment of 3 d, the efficacy, related laboratory indicators and adverse drug reactions in two groups were observed . RESULTS: The total effective rate of observation group was 94.00% (47/50), significantly higher than that in the control group 60.00% (30/50), the difference was statistically significant (P <0.05). After treatment, the blood viscosity, hematocrit, urinary protein excretion, peak-to-valley ratio of umbilical artery blood flow velocity and vascular resistance indicators of umbilical artery in observation group had been significantly improved compared with before treatment, and the improvement degree was better than that of control group, with statistically significant difference (P<0.05). The incidence of adverse drug reactions was 16.00%(8/50), significantly lower than that of control group 44.00% (22/50), with statistically significant difference (P<0.05) .CONCLUSIONS: The effects of magnesium sulfate combined with low-dose aspirin in treatment of pregnancy-induced hypertension is remarkable, which can significantly improve the clinical symptoms in patients with high safety. It is worthy of clinical application and promotion. [ABSTRACT FROM AUTHOR]

目的 探讨经颅磁刺激联合医痫丸辅助治疗颅脑外伤继发性癫痫的临床疗效及其可能的机制。方法 选择颅脑外伤继发性癫痫患者132例,随机分为对照组、磁刺激组和联合组各44例。三组均予常规治疗(注射苯巴比妥钠或口服丙戊酸钠片,癫痫发作时口服氯硝西泮片)12周;磁刺激组在常规治疗的基础上行经颅磁刺激连续治疗1周;联合组在磁刺激基础上口服医痫丸,共12周。三组治疗12周评价临床疗效,计算总有效率。比较两组治疗前及治疗12周癫痫持续状态严重程度量表(STESS)评分及癫痫持续状态的发作持续时间、发作频率,生活质量调查表31(QOLIE-31)评分以及血清ROS、NF-κB、IL-1β、TNF-α水平(采用ELISA法检测)。记录三组治疗期间不良反应发生情况。结果 对照组总有效率为70.45%,磁刺激组为75.00%,联合组为90.91%;联合组总有效率高于对照组及磁刺激组(P均<0.05)。三组治疗后STESS评分、发作持续时间、发作频率及血清ROS、NF-κB、IL-1β、TNF-α水平均低于治疗前,QOLIE-31评分均高于治疗前,但联合组变化更明显(P均<0.01),对照组与磁刺激组治疗后上述指标比较差异均无统计学意义(P均>0.05)。三组不良反应发生率比较差异均无统计学意义(P均>0.05)。结论 经颅磁刺激联合医痫辅助治疗颅脑外伤性继发癫痫效果确切且较为安全;抑制氧化应激及炎性反应可能是其作用机制。 [ABSTRACT FROM AUTHOR]