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Abstract Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

The development of advanced and efficient anode catalysts to accelerate the kinetic rate of methanol oxidation plays an important role in the large-scale commercial application of the direct methanol fuel cells (DMFCs). Herein, we report the design and construction of small-sized rhodium nanocrystals decorated on 3D hybrid aerogels built from graphene and metal-organic framework (Rh/G-ZIF) via a solvothermal co-assembly method. Benefiting from the 3D rigid crosslinked architecture, abundant porous channels, and highly dispersed ultrafine Rh nanoparticles, the optimized Rh/G-ZIF aerogel exhibits a large electrochemically active surface area, high mass and specific activities, and excellent long-term durability toward the methanol electrooxidation, all of which are significantly superior to those of Rh catalysts supported by traditional carbon materials (such as carbon black, carbon nanotube, and graphene).

Objective To explore the optimal moment of surgical management for the anterior circulation aneurysms, and to summarize the experience of microsurgical treatment for the anterior circulation aneurysms. Methods The clinical data of 210 patients with anterior circulation aneurysms were retrospectively analyzed. In 183 patients with subarachnoid hemorrhage, there were 82 cases of grade Ⅰ -Ⅱ, 77 cases of grade Ⅲ, 21 cases of grade Ⅳ, 3 cases of grade Ⅴ according to Hunt⁃Hess grade. Results 199 patients underwent aneurysm clipping and 11 patients were underwent aneurysm wrapping. According to Glasgow Outcome Scale (GOS) classification criteria for the prognosis, 97 cases (46.19% ) cured, 80 cases (38.09%) had slight disability, 24 cases (11.43%) showed severe disability, and 9 cases (4.29%) died. Conclusion In the microsurgery for anterior circulation aneurysms, the patients should be early operated according to the individual clinical signs. The judgment and skills in surgery for the subtypes of anterior circulation aneurysms are the key points to cure intracranial aneurysms successfully. DOI：10.3969/j.issn.1672⁃6731.2012.01.012