[Discussion on exploitation of foreign traditional chinese medicine resources based on "the Belt and Road"].

At the beginning of the ancient "Silk Road", traditional Chinese medicine resources (TCM resources) have long been integrated into it, and it was once the "important part" of the ancient "Silk Road" in Chinese history, benefited from this, the political connections was strengthened, the economic and trade was developed, and Chinese medicine culture was spread. Before Qing Dynasty, people took out the "silk" and brought back "herbs" on the "Silk Road", which enriched China's medicinal resources. While in the later Qing Dynasty and the period of the Republic of China, more scientific and technological methods were brought back from abroad, and this in turn enriched the medical research methods. With more than 2 000 years' development, China's boundaries have changed countless times, therefore the word "Foreign" has different meanings in different historical periods. The import, development and utilization of foreign TCM resources is different in different historical periods, at present, with the continuous enhancement of China's comprehensiv national strength，especially the "Belt And Road" strategy, the communication and import of TCM resources with countries that participating in the "Belt and Road" initiativ became much easier. In order to actively respond to the "Belt and Road" initiative promote the development and utilization of foreign medicinal resources; serve people from the countries participating in the "Belt and Road" initiative we sorted out the foreign TCM resources from different periods in ancient and modern China, and based on this, we proposed the strategy of import of foreign TCM resources under the new situation, those are: "three levels, four steps, one support and one key". And "three levels" refers to intelligence collection level, field investigation level, scientific research level, "Four steps" refers to the original identification research, safety evaluation research, functional positioning research and medicinal properties research; "One support" refers to relying on overseas Chinese or Chinese enterprises with working foundation and network resources, "One key" refers to the protection of the intellectual property rights of foreign TCM resources at the policy level and to mobilize the initiative of all parties.

Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ.

BACKGROUND: Increasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ). However, whether miR-219 regulates CaMKIIγ expression in the dorsal root ganglia to mediate morphine tolerance remains unclear. RESULTS: MiR-219 expression was downregulated and CaMKIIγ expression was upregulated in mouse dorsal root ganglia following chronic morphine treatment. The changes in miR-219 and CaMKIIγ expression closely correlated with the development of morphine tolerance, which was measured using the reduction of percentage of maximum potential efficiency to thermal stimuli. Morphine tolerance was markedly delayed by upregulating miR-219 expression using miR-219 mimics or downregulating CaMKIIγ expression using CaMKIIγ small interfering RNA. The protein and mRNA expression of brain-derived neurotrophic factor were also induced in dorsal root ganglia by prolonged morphine exposure in a time-dependent manner, which were transcriptionally regulated by miR-219 and CaMKIIγ. Scavenging brain-derived neurotrophic factor via tyrosine receptor kinase B-Fc partially attenuated morphine tolerance. Moreover, functional inhibition of miR-219 via miR-219-sponge in naive mice elicited thermal hyperalgesia and spinal neuronal sensitization, which were both suppressed by CaMKIIγ small interfering RNA or tyrosine receptor kinase B-Fc. CONCLUSIONS: These results demonstrate that miR-219 contributes to the development of chronic tolerance to morphine analgesia in mouse dorsal root ganglia by targeting CaMKIIγ and enhancing CaMKIIγ-dependent brain-derived neurotrophic factor expression.