The clinical observation on mechanical ventilation combined with different doses of sildenafil in the treatment of persistent pulmonary hypertension of newborn / 中国医师进修杂志

Objective:To observe the efficacy and safety of mechanical ventilation combined with different doses of sildenafil in the treatment of persistent pulmonary hypertension of newborn (PPHN).Methods:A total of 160 children with PPHN admitted to Dezhou Maternal and Child Health Hospital from January 2018 to December 2019 were selected and divided into group A, B, C and D by random stratification, with 40 cases in each group. All the children in the group were actively corrected for acidosis, provided with intravenous nutrition support, warmth, anti-infection and other measures, and adopted ventilator to assist mechanical ventilation. Group A, B, and C were given different doses of sildenafil 0.5, 1.0, and 2.0 mg/(kg·time) respectively, while group D was not given sildenafil treatment, but only mechanical ventilation. Blood gas analysis indexes including partial arterial oxygenpressure (PaO 2), partial arterial carbon dioxide pressure (PaCO 2), saturationoxygen (SaO 2), and pulmonary artery pressure (SPAP), systemic blood pressure (SBP) of children were tested before the treatment and 72 h after the treatment. The treatment time, hospitalization time, hospitalization expenses and the incidence of adverse reactions of mechanical ventilation in 4 groups were recorded and compared. Results:The effective rate in the group A, B and C was higher than that in the group D: 80.0%(32/40), 85.0%(34/40), 87.5%(35/40) vs. 57.5%(23/40), the difference was statistically significant ( P<0.05). Before treatment, the levels of blood gas analysis indexes in 4 groups had no significant differences ( P>0.05). After treatment, the level of PaO 2 in the group A, B and C was significantly higher than that in the group D ( P<0.05), the level of PaCO 2 in the group B and C was significantly lower than that in group D ( P<0.05), and the level of SaO 2 in the group B and C was significantly higher than that in the group D ( P<0.05). After treatment, the level of SPAP in group B and C was significantly lower than that in the group D: (28.56 ± 3.93), (27.14 ± 3.32) mmHg(1 mmHg = 0.133 kPa) vs. (33.57 ± 4.68) mmHg, P<0.05, and the level of SBP in 4 groups had no significant difference ( P>0.05). The hospitalization time and mechanical ventilation time in group A, B and C were significantly shorter than those in group D ( P<0.05). No drug-related adverse reactions, pulmonary hemorrhage, hypotension, arrhythmia, pneumothorax and other complications occurred during the treatment in the 4 groups. Conclusions:Mechanical ventilation combined with sildenafil can significantly reduce pulmonary artery pressure and improve pulmonary oxygenation in children with PPHN. In the range of 0.5 - 1.0 mg/kg, the efficacy is more obvious when increasing the dose of sildenafil.

Progress in regulatory effects of thymic stromal lymphopoietin on immune cells / 中华微生物学和免疫学杂志

Thymic stromal lymphopoietin (TSLP), as a pleiotropic cell growth factor, not only participants in the processes of human skin fibrosis, epidermal proliferation and angiogenesis, but also plays a critical role in regulating a variety of immune cells in immune-related diseases (such as respiratory diseases and allergic diseases). TSLP regulates various innate immune cells (such as dendritic cells, mast cells, macrophages, eosinophils, basophils, natural killer T cells and innate lymphocytes) and adaptive immune cells (T lymphocytes and B lymphocytes) mainly through JAK/STAT, NF-κB and other signal pathways mediated by TSLP receptor. This paper summarized the progress in the regulatory roles of TSLP in the proliferation, differentiation and function of various immune cells.

The Complement Inhibition of Ursolic Acid and Tetrandrine on Tumor Related Signaling Pathways and Their Synergistic Antitumor Proliferation Effects / 浙江中医药大学学报

[Objective]This study was aimed to research the synergistic antitumor proliferation effects and their best proportion of ursolic acid(UA) and tetrandrine(Tet), a pair of compounds isolated from Chinese herbs which showed complement inhibition on the multiple signal pathways. [Methods] The reporter assays on tumor-related signal pathways for MAPK/ERK, MAPK/JNK, NF-κB, Wnt, Notch, Cell Cycle, Myc/Max and Hypoxia were used to study the effect of five different Chinese herbal compounds on tumor proliferation,it was concluded cepharanthine(Cep), Tet, 18α-glycyrrhetinic acid(18α-Gly), UA and luteolin(Lut). MTT assay and crystal violet staining were used to study the antiproliferative effect of 15 different compounds for the tumor cells of MDA-MB-231,SW480,MG63,PC3,DU145,HCT116,143B and MDA-MB-468, which is consisted with Cep, Tet, 18α-Gly, UA and Lut for the 15 different compounds. Coefficient of drug interaction(CDI) method was used to detect the synergistic effect of the two compounds. Combination of index(CI) and isobologram method was used to screen the best ratio of compounds in their antiproliferative effects. [Results] The signal pathway reporter assay showed that UA and Tet could complementarily inhibit tumor-related signaling pathways. And the results also showed that UA and Tet could induce synergetic anti-tumor cell proliferation in vitro. Furthermore, the optimal ratio of UA and Tet was 9:1 by using isobologram and CI method. [Conclusion] UA and Tet can be inhibited and complemented by 8 tumor-related signaling pathways, and we used MTT assay and crystal violet staining or other methods to confirm the synergistic antitumor proliferation effects, furthermore, the optimal proportion for UA and Tet were screened, and it provided a new insight to develop new anticancer formula in research.

Bioluminescent Monitoring the Influence of Cepharanthine on Colon Cancer Growth in Mouse Xenograft Tumor Model / 浙江中医药大学学报

[Objective]To investigate the anti-proliferative effects of CEP on HCT116 cells and in mouse xenograft model. [Methods]The in vivo anti-cancer activity of CEP was determined with Xenogen bioluminescence imaging in a xenograft tumor model. The cel-based multiple signaling pathway reporter assays were carried out to determine the effects of CEP on these pathways. [Results] CEP inhibited growth of human cancer cells, the IC 50 was 0.8~11.5 μM. CEP induced cellcycle arrest in S and G2/M phase. CEP also inhibited xenograft tumor growth in athymic nude mice bearing HCT116 cells. The xenograft tumor size was significantly reduced upon the treatment with CEP(10 or 20 mg·kg-1 body weight) for up to 3 weeks. Pathway-spe-cific reporter assays indicated that CEP effectively suppressed the NF-κB and MAPK/ERK signaling pathways. [Conclusions] Our results suggest that the anticancer activity of CEP in colon cancer cells may be mediated through targeting NF-κB and MAPK/ERK signaling pathways.