Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Objective:To study the characteristics of soil microbial composition in sheep sheds in agricultural and pastoral areas, and explore potential zoonotic pathogen species.Methods:Using cross-sectional survey method, soil samples from sheep sheds in the agricultural and pastoral areas of Darhan-Muminggan Joint County, Baotou City, Inner Mongolia Autonomous Region were collected from August to October 2023. Genomic DNA was extracted, and metagenomic second-generation sequencing was conducted. Microbial species annotation was carried out by Kaiju method, and the soil microbial composition and zoonotic pathogen species of sheep sheds in agricultural and pastoral areas were analyzed.Results:A total of 10 and 5 soil samples were collected from sheep sheds in agricultural and pastoral areas, respectively. The results of β diversity analysis showed that there was a significant separation trend in soil samples from sheep sheds in agricultural and pastoral areas, and the interpretation of principal co-ordinates analysis (PCoA) 1 and PCoA2 were 27.8% and 17.4%, respectively. There was no significant difference in the microbial composition of soil samples from sheep sheds in agricultural and pastoral areas ( R = 0.09, P = 0.242). At the phylum level, the dominant bacterial phyla were Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. At the genus level, the dominant bacterial genera were Corynebacterium, Luteimonas, Atopostipes, and Salinicoccus. A variety of zoonotic pathogens were detected, including Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani in 15 soil samples. Conclusion:The soil microorganisms in sheep sheds in agricultural and pastoral areas are diverse, and zoonotic pathogens such as Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani are detected.

Objective:To study the characteristics of soil microbial composition in sheep sheds in agricultural and pastoral areas, and explore potential zoonotic pathogen species.Methods:Using cross-sectional survey method, soil samples from sheep sheds in the agricultural and pastoral areas of Darhan-Muminggan Joint County, Baotou City, Inner Mongolia Autonomous Region were collected from August to October 2023. Genomic DNA was extracted, and metagenomic second-generation sequencing was conducted. Microbial species annotation was carried out by Kaiju method, and the soil microbial composition and zoonotic pathogen species of sheep sheds in agricultural and pastoral areas were analyzed.Results:A total of 10 and 5 soil samples were collected from sheep sheds in agricultural and pastoral areas, respectively. The results of β diversity analysis showed that there was a significant separation trend in soil samples from sheep sheds in agricultural and pastoral areas, and the interpretation of principal co-ordinates analysis (PCoA) 1 and PCoA2 were 27.8% and 17.4%, respectively. There was no significant difference in the microbial composition of soil samples from sheep sheds in agricultural and pastoral areas ( R = 0.09, P = 0.242). At the phylum level, the dominant bacterial phyla were Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. At the genus level, the dominant bacterial genera were Corynebacterium, Luteimonas, Atopostipes, and Salinicoccus. A variety of zoonotic pathogens were detected, including Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani in 15 soil samples. Conclusion:The soil microorganisms in sheep sheds in agricultural and pastoral areas are diverse, and zoonotic pathogens such as Brucella melitensis, Mycobacterium tuberculosis, and Clostridium tetani are detected.

Objective:To study the changes in serum small molecule metabolites after brucella infection in humans using untargeted metabolomics methods, and screening representative biomarkers. Methods:A total of 109 serum samples collected from January 2019 to December 2021 at the Brucellosis Clinic of the Baotou Center for Disease Control and Prevention were divided into acute phase group ( n = 40), chronic phase group ( n = 35) of brucellosis, and healthy group ( n = 34) based on clinical diagnosis. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry technology was used to test serum samples and screen for differential metabolites. Receiver operating characteristic curve was used to evaluate the predictive ability of differential metabolites for brucellosis. Enriched pathways were screened using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to identify metabolic pathways significantly affected. Results:A total of 17 differential metabolites were screened between the acute phase group and the healthy group, and 12 differential metabolites were screened between the chronic phase group and the healthy group. There were a total of 5 differential metabolites (oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid) statistically significant among the three groups ( F = 16.84, 17.52, 14.31, 13.01, 20.76, P < 0.05). KEGG pathway analysis showed that the differential metabolites in the acute phase group were enriched in metabolic pathways such as ether lipid metabolism, glycerophosphate metabolism, sphingolipid signal and sphingolipid metabolism. The differential metabolites in the chronic phase group were enriched in metabolic pathways such as glycerophosphate metabolism, ether lipid metabolism, protein digestion and absorption metabolism. Conclusion:Untargeted metabolomics methods can screen out serum small molecule metabolites that undergo changes after brucella infection in the human body, including oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid can serve as potential biomarkers to distinguish brucellosis patients from healthy people.