Design, synthesis and anticancer activity studies of oleanolic acidderivatives targeting mTOR / 药学学报

Ten novel oleanolic acid (OA) derivatives containing urea or thiourea group were designed and synthesized, the chemical structures were confirmed by 1H NMR, 13C NMR and HR-MS. All of these compounds were evaluated for the inhibitory activity against growth of HepG2 and SGC7901 cells. The results showed that compounds I3 and II3 exhibited significant antitumor activities with IC50 of 9.4 and 5.5 μmol·L-1, respectively. Molecular docking studies showed that all these compounds exhibit inhibitory ability against mTOR kinase. Compounds I3 and II3 were further evaluated for the inhibitory activity against mTOR kinase. The results showed that I3 and II3 exhibited strong inhibitory effect on mTOR kinase with IC50 values of 0.83 and 0.26 μmol·L-1.

Design, synthesis and anti-tumor activity studies of oleanolic acid derivatives using VEGFR as target / 药学学报

In this study, twenty containing ethylenediamine groups derivatives of oleanolic acid (OA) were synthesized, their structures were determined by 1H NMR, 13C NMR and HR-MS. The anti-tumor activities in HepG2 and SGC7901 cells were evaluated by MTT assay. The results showed that all compounds exhibited anti-tumor activity, compounds I6, I8 and I9 exhibited significant anti-tumor activities with IC50 values of 16.7, 9.8 and 6.3 μmol·L-1, respectively. Molecular docking studies showed that compounds I6-I9 produce higher combining ability with VEGFR. Compound I6-I9 were further evaluated for the inhibitory activity against VEGFR-2, the result showed I9 had a strong inhibitory effect on VEGFR with IC50 values of 0.56 μmol·L-1.

Re-optimized technology of protective ileostomy with no need of reversal / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the clinical application of aoptimizedtechniquebased onpreviouslyreported protecting stoma with no need forreversal.</p><p><b>METHODS</b>Thetechniquealso used "the assembly of drainage device" to performprotecting ileostomy. The original method includes enterotomy at the terminal ileum to placedrainage device, which was optimized as follows: two intestinal pursestring with 0.5 cm distance were placed 5 cm away from the ileocecal valve. Transverse enterotomy was performed in the anti-mesenteric side. The assembly was placed at the root of the appendix between two pursestring, and then the intestine purse suture was tighten. Ligation of the small intestine anastomosis between the anastomosis ring at both ends was carried out, and theanastomosis ring was deployed. From the root of the appendix in the cecum wall, the assembly was embedded about 2 cm and pulled out of abdominal cavitythough the Trocar hole.</p><p><b>RESULTS</b>Seventeen cases of ultra-low rectal cancer completed protecting stoma, including 11 cases through ileocecal protective stoma. All the anastomosis healed well. Defecation drainage tube was removed 3-5 weeks after anastomosis ring degradation. Drainage nozzle healed after 3 to 5 days, and no complications occurred.</p><p><b>CONCLUSION</b>The optimized ileocecal protective ileostomy has the following advantages: (1)wound healing time is significantly shorter. (2)secondary intestinal fistula can be prevented. (3)no need to fix ileum and less chance of subsequent volvulus, intestinal obstruction.</p>

Evaluation of nasal patency in patients with vasomotor rhinitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To measure the nasal patency in patients with vasomotor rhinitis (VMR) and healthy controls and to assess its correlation with visual analogue scale (VAS).</p><p><b>METHODS</b>A total of 105 patients with VMR and 71 healthy controls were included in this study. By using nasal rhinomanometry, the pressure-flow curve and got total nasal resistances of 75 Pa and 150 Pa were measured. By means of acoustic rhinometry, the area-distance curve before and after using nasal vasoconstrictor substance was obtained, got the nasal minimum cross-sectional area (MCA), then calculated nasal congestion index (NCI). The outcomes of nasal resistance and acoustic rhinometry in two groups were compared. The correlation between VAS and nasal patency of VMR was evaluated.</p><p><b>RESULTS</b>The correlation between the outcomes with nasal resistance and acoustic rhinometry and VAS of nasal symptom showed no statistical significance in VMR patients (all P > 0.05). MCA before and after decongestion showed no difference (Z value were -1.541 and -0.626, each P > 0.05), NCI had statistic differences in two groups (Z = -2.707, P < 0.05). Nasal resistance of 75 Pa had statistic differences in two groups (Z = -4.334, P < 0.05), 150 Pa showed no difference (Z = -1.314, P > 0.05).</p><p><b>CONCLUSIONS</b>Vasomotor rhinitis is one of the most common non-allergic rhinitis. Subjective symptoms has no correlation with objective nasal patency tests. In clinical practice, comprehensive evaluation of subjective symptoms and objective test results of the patient is required.</p>

Anatomical and computed tomographic analysis of the interaction between uncinate process and agger nasi cells / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the anatomical interaction between uncinate process and agger nasi cell to better understand the anatomy of the frontal sinus drainage pathway by endoscopy, spiral computed tomography (CT) and sectioning.</p><p><b>METHODS</b>Twenty-one skeletal skulls (forty-two sides) and one cadaver head (two sides) were studied by spiral CT together with endoscopy and collodion embedded thin sectioning at coronal plane. The sections with the thickness of 100 microm were stained with hemotoxylin and eosin.</p><p><b>RESULTS</b>Under endoscopy, a leaflet of bone to the middle turbinate, which is given off by uncinate process, forms the anterior insertion of the middle turbinate onto the lateral nasal wall. The middle portion of the uncinate process attached to the frontal process of the maxilla in all of the skeletal nasal cavities, as well as the lacrimal bone in 78.6% of the skeletal nasal cavities. On CT scans, the agger nasi cell is present in 90.5% of the skeletal nasal cavities. While the lateral wall of the agger nasi cell is formed by lacrimal bone, the medial wall of the agger nasi cell is formed by uncinate process. And the anterior wall is formed by the frontal process of the maxilla. The superior portion of the uncinate process forms the medial, posterior and top wall of the agger nasi cells. The superior portion of the uncinate extends into the frontal recess and may insert into lamina papyracea (33.3%), skull base (9.5%), middle turbinate, combination of these (57.2%).</p><p><b>CONCLUSIONS</b>The agger nasi cell is the key that unlocks the frontal recess.</p>

Impact of olfactory nerve transection on the apoptosis of mice olfactory receptor neurons / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyze the impact of olfactory nerve transection on the apoptosis of mice olfactory receptor neurons (ORN), and discuss the reliability of this experimental model.</p><p><b>METHODS</b>After olfactory nerve transection of mice, anterograde horseradish peroxidase (HRP) tracing was performed to confirm the completion of nerve transection. On 8 h, 2 d, 3 d and 5 d after surgery, TdT mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) was used to observe the apoptosis of ORN, while relative semi-quantitative RT-PCR and immunohistochemistry were used to reflect the expression of olfactory marker protein (OMP, special marker of mature ORN) in olfactory epithelium.</p><p><b>RESULTS</b>No HRP label was observed in olfactory bulb after olfactory nerve transaction. Both TUNEL-positive and OMP-positive cells were ORN. After the surgery, TUNEL-positive cells increased remarkably and peaked on 2 d after the surgery. Meanwhile OMP mRNA in olfactory epithelium began to decrease markedly till 5 d after the surgery, and the olfactory epithelium got thinner accordingly.</p><p><b>CONCLUSIONS</b>This experimental model can be used reliably to sever mice olfactory nerve and manipulate simultaneous apoptosis of mice ORN.</p>

Effect of intranasal interleukin-12 gene therapy for allergic rhinitis in murine model / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate whether the local application of IL-12 gene with EBV-plasmid vector to nasal mucosa could prevent allergic inflammation in murine allergic rhinitis model.</p><p><b>METHODS</b>Thirty-six BALB/C mice were randomly divided into allergic rhinitis group gene therapy group and control group. In mice with OVA-induced allergic rhinitis, the EBV/lipoplex (a novel cationic lipid combined with EBV-plasmid vector, pGEG. mIL-12) was locally administered into nasal mucosa before OVA challenge. The expression of IL-12 mRNA and protein, the change of eosinophilia and mast cell, and Th2 cytokine production in the nasal mucosa were measured.</p><p><b>RESULTS</b>The amounts of IL-12 mRNA positive cells and IL-12 positive cells in nasal mucosa of gene therapy group were significantly higher than that of allergic rhinitis group (P < 0.01 and P < 0.05). The amount of eosinophils, mast cells, and the level of IL-5 expression in nasal mucosa in allergic rhinitis group were significantly higher than those in gene therapy group and control group (P < 0.01). The level of total IgE of peripheral blood in allergic rhinitis group was significantly higher than that in gene therapy group and control group (F = 1216.21, P < 0.01).</p><p><b>CONCLUSIONS</b>These findings indicated that IL-12 mRNA and protein were expressed effectively after the local administration of pGEG. mIL-12 in the nasal mucosa. The local application of pGEG. mIL-12 is effective in modulating nasal allergic response and may be a convenient method for future approach to allergic rhinitis.</p>