Objective:To investigate the changes of brain energy metabolism and cognitive function in mice with specifically knocking out AMP-activated protein kinase α1 subunit ( AMPKα1) gene in the excitatory neurons by Cre-loxP recombination system. Methods:Sixteen 6-month-old mice with genotype AMPKα1 flox/flox/Camk2a-Cre/ERT2 obtained by hybrid breeding were randomly divided into AMPKα1 knockout group ( n=8) and AMPKα1 wild-type group ( n=8). Mice in the AMPKα1 knockout group were intraperitoneally injected 0.1 mL tamoxifen (20 mg/mL, dissolved in corn oil) daily for a consecutive 5 d to control AMPKα1 gene knockout in the excitatory neurons; and mice in the AMPKα1 wild-type group were intraperitoneally injected 0.1 mL corn oil daily for a consecutive 5 d. Seven d after that, Morris water maze and T maze experiments were employed to detect the spatial learning and memory abilities and spatial working memory of these mice; chemical exchange saturation transfer imaging (CEST) was used to observe the glucose metabolism in the hippocampus and cortex surrounding the hippocampus; Western blotting was used to detect the AMPKα1 and glutamate receptor 1 (GluR1) protein expressions in the hippocampus and cortex surrounding hippocampus of two groups. Results:(1) Morris water maze showed that, as compared with those in the AMPKα1 wild-type group, mice in the AMPKα1 knockout group had significantly prolonged escape latency ([13.90±3.72] s vs. [22.40±6.28] s; [11.95±3.86] s vs. [22.39±9.77] s]) on the 3 rd and 4 th d of experiment, statistically decreased times crossing the platform ([5.25±1.83] times vs. [1.75±1.28] times, P<0.05). (2) T-maze experiment showed that as compared with that of the AMPKα1 wild-type group, the free alternation rate in mice of the AMPKα1 knockout group was significantly decreased ([73.21±9.16]% vs. [48.21±11.29]%, P<0.05). (3) CEST showed that the glucose metabolism levels in the hippocampus and cortex surrounding the hippocampus of AMPKα1 knockout group were significantly lower than those in AMPKα1 wild-type group (1.51±0.81 vs. 2.77±0.67; 1.31±0.83 vs. 2.42±0.95, P<0.05). (4) Western blotting showed that the AMPKα1 and GluR1 protein expressions in the hippocampus and cortex surrounding the hippocampus of the AMPKα1 wild-type group were significantly higher than those of the AMPKα1 knockout group (AMPKα1: 0.70±0.05 vs. 0.49±0.03, 0.98±0.04 vs. 0.64±0.06; GluR1: 1.22±0.18 vs. 0.60±0.11, 0.96±0.08 vs. 0.79±0.04, P<0.05). Conclusion:Specifically knocking out AMPKα1 in excitatory neurons can result in abnormal glucose metabolism in the brain of mice, and thus cause cognitive dysfunction, whose mechanism may be related to excitatory synaptic disorder caused by energy metabolism disorder.

Objective:This article analyzed the current situation, similarities and differences and main problems of the registration and management systems of innovative medical devices in China and the United States.Methods:This article summarized the requirements and policies for the registration management of innovative medical devices in China and the United States, as well as the development and differences of the registration of innovative medical devices in China and the United States, and the main problems in the registration management of innovative medical devices in China.Results:At present, the development level of medical device industry in China and the United States was different, facing different development problems, and there were differences in the access standards and management methods of innovative medical devices. The registration management system established for innovative medical devices in China was gradually improving, and to a certain extent, it had promoted the enthusiasm of innovative product research and development and registration applications, but there were also problems such as unclear innovation evaluation scales, insufficient early intervention of review resources, and insufficient utilization of post-marketing data.Conclusions:Drawing on the beneficial experience of breakthrough device registration management in the United States, we will improve the registration management system for innovative products and shorten the review and approval cycle by clarifying the identification criteria for innovative medical devices, promoting the placement of review resources in the R&D stage, and further strengthening the use of post-marketing data and regulatory scientific research.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.