New discovery and short-term effect analysis of tensor tympani muscle tenotomy for Meniere's disease under otoscope / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.

Effect of TAK1 gene silencing on the apoptosis of Kasumi-1 cells induced by arsenic trioxide / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the effect of transforming growth factor-β activated kinase-1 (TAK1) gene silencing on the proliferation and apoptosis of Kasumi-1 cells induced by arsenic trioxide (As₂O₃).</p><p><b>METHODS</b>Acute myeloid leukemia with t(8;21) cell line Kasumi-1 cells were treated with As₂O₃ or in combination with TAK1 siRNA interference technology. The experiment was divided into four groups: Kasumi-1 cells without any treatment, TAK1 specific siRNA transfection alone, Kasumi-1 cells treated with different concentration of As₂O₃, TAK1siRNA transfection combined with As₂O₃. CCK-8 was used to detect the cell viability. The expression of phosphorylated c-Jun N-terminal kinase (P-JNK) was determined by Western Blot. Cell apoptosis and growth were examined by morphological and colony formation assay.</p><p><b>RESULTS</b>After Kasumi-1 cells were treated with As₂O₃, the rate of cell inhibition was concentration-dependent, and the 50% inhibitory concentration was 3.5 μmol/L. The highest expression level of P-JNK appeared in 30 minutes after cells were treated with As₂O₃. The apoptosis rates of Kasumi-1 cells without any treatment, TAK1 siRNA interference alone group, As₂O₃ alone group and the combined group were (5.02 ± 1.13)%, (6.18 ± 0.28)%, (48.33 ± 2.70)% and (86.07 ± 2.21)%; colony formation rates were (73.83 ± 2.78)%, (76.03 ± 1.46)%, (55.07 ± 1.50)% and (22.20 ± 1.15)%; apoptosis rate of TAK1 siRNA group and the untreated group has no significant difference (P = 0.052); colony formation rate between TAk1 siRNA group and the untreated group has no significant difference (P = 0.179), but the difference in other groups was significant (P = 0.000).</p><p><b>CONCLUSION</b>Silencing the expression of TAK1 can enhance the anti-proliferative and pro-apoptotic effect of As₂O₃ on Kasumi-1 cells, and its mechanism may be through the TAK1 downstream JNK signal pathway.</p>

Advances in the study of tumor pH-responsive polymeric micelles for cancer drug targeting delivery / 药学学报

This review presents the state of the art of pH-responsive polymeric micelles for cancer drug delivery. Solid tumors have a weakly acidic extracellular pH (pH < 7), and cancer cells have even more acidic pH in endosomes and lysosomes (pH 4-6). The pH-gradients in tumor can be explored for tumor targeting and drug release in cancer drug delivery by applying pH-responsive polymeric micelles. The pH-responsive polymeric micelles consist of a corona and a core, and are made of amphiphilic copolymers, in which there are pH-responsive polymeric blocks. Two types of pH-responsive polymers-protonizable polymers and acid-labile polymers have been mainly used to make pH-responsive micelles for drug delivery. The protonizable polymers are polybases or polyacids, and their water-soluble/insoluble or charge states undergo changes with the protonation or deprotonation stimulated by external acidity, while the acid-labile polymers change their physical properties by chemical reaction stimulated by the acidity. Polymeric micelles whose core or coronas respond to the tumor extracellular acidity can be explored for triggering the fast release of the carried drug, activating the targeting group and accelerating the endocytosis of drug-loaded polymeric micelles, and those whose core or coronas respond to the tumor lysosomal acidity can be used for facilitating their escape from the lysosomes and targeting the nucleus. Various in vivo and in vitro experiments demonstrated that pH-responsive polymeric micelles are effective for cellular targeting, internalization, fast drug release and nuclear localization, and hence enhancing the therapeutic efficacy and reducing the side effect of cancer chemical therapy.