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AIM: To investigate the effects on patients with chronic dacryocystitis treated with three methods: external dacryocystorhinostomy(EDCR), intranasal endoscopic dacryocystorhinostomy(IEDCR)and Nd:YAG laser dacryoplasty, and to explore the best operation method. METHODS:Totally 182 cases(202 eyes)were randomly divided into three groups, using EDCR, IEDCR and Nd:YAG laser dacryoplasty respectively, postoperative follow- up lasted 6-24months.RESULTS: The success rate of three groups were 93.9%, 92.3% and 71.1% respectively. There was not significant difference between group EDCR and group IEDCR(P>0.05). There was significant difference between group Nd:YAG laser dacryoplasty and other two groups(PCONCLUSION: EDCR and IEDCR are effective methods. Especially IEDCR is minimal invasive technique and worthy of promotion and application.

Activation of PI3K/AKT pathway is one of the most recurrent resistant mechanisms for BRAF-targeted therapy, and the combination of MAPK and PI3K/AKT inhibitors becomes one of the most promising regimens for BRAF-targeted relapsed melanoma patients. Although the potent drug efficacy was observed in preclinical experiments and early clinical trials, the dual-drug resistance is inevitable observed. In this study, we systematically explored the mechanisms of dual-drug resistance to MAPKi and PI3K/mTORi in melanoma. With transcriptomic dissection of dual-drug resistant models, we identified that the drug tolerance was mediated by ECM-integrins α3β1 and α11β1 signaling. Upon binding ECM, the integrins activated downstream kinase Src rather than FAK, WNT, or TGFβ. Knockdown of integrins α3, α11, and β1 significantly inhibited the proliferation of dual-drug resistant sublines while with trivial effects on parental cells. Although Src inhibition suppressed the phosphorylation of AKT, c-JUN, and p38, none of inhibitors targeting these kinases reversed the dual-drug resistance in model cells. Notably, Src inhibitor promoted the phosphorylations of LATS1 and YAP1, subsequently, re-localized YAP1 from nucleus to cytosol facilitating further degradation. Both small molecule inhibitors and shRNAs targeting YAP1 or Src overcame the MAPKi and PI3K/mTORi dual-drug resistance. In conclusion, our data not only illuminated an integrin-Src-YAP1 pathway mediated MAPKi and PI3K/mTORi dual-drug resistant mechanism but also provided a potential combinatorial regimen for the drug-relapsed melanoma patients.

Owing to their significant application potential in national defense and aerospace technology, the development of energetic materials with high heat resistance and high energy has attracted great attention recently. Herein, a zwitterionic strategy was explored for the preparation of a new heatresistant energetic material. Through this strategy, a zwitterionic energetic material, 2,6-diamino-9-iminio-3,5-dinitro-9H-dipyrazolo[1,5-a:50,10-d][1,3,5]triazin-4-ide (ZDPT), was prepared employing a simple method. The molecular and crystal structures of ZDPT were comprehensively examined using nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray diffraction. The unique zwitterionic structure of ZDPT is rarely observed in energetic materials. ZDPT exhibited exceptionally high thermal stability with an onset decomposition temperature of 347 °C and a peak temperature of 380 °C, which was higher than that of most traditional heat-resistant energetic materials and the highest among energetic zwitterions and energetic ion salts. Moreover, ZDPT exhibited excellent energy performance and surprisingly low sensitivity. The detonation velocity was 8390 m s-1, which outperformed that of many heat-resistant energetic materials. The impact sensitivity and fraction sensitivity of ZDPT were higher than 40 J and 360 N, respectively. The extremely high thermal stability and low mechanical sensitivity were strongly related to the zwitterionic structure and the presence of a large p electron conjugation system of ZDPT making ZDPT a potential candidate for heat-resistant energetic materials. [ABSTRACT FROM AUTHOR]