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*

ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine（TCM） compounds， a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection（SHLI）， in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding， 72 SPF-grade SD male rats were randomly divided into blank group， SHLI standard group， Lonicerae Japonicae Flos（LJF） group， Scutellariae Radix（SR） group， Forsythiae Fructus（FF） group， and 7 groups of SHLI matching groups（groups 1-7）， with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state， high performance liquid chromatography（HPLC） characterization profiles of the testing drugs and plasma components in each group were established， and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay（ELISA） was used to determine the changes of immunoglobulin E（IgE）， histamine（HIS）， tryptase（TPS）， total complement（CH50） and terminal complement complex（C5b-9） in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets， and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that， compared with the blank group， groups 1-3 could significantly increase the IgE level， groups 1-2， groups 4-6 and SHLI standard group could significantly increase the HIS level， group 4 could significantly increase the CH50 level， groups 1， 3-4， LJF group and FF group could significantly increase the TPS level， SR group could significantly increase the C5b-9 level， and the differences were all statistically significant（P<0.05）. According to the retention time of chromatographic peaks， it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2， indicating that C6 had the greatest effect on the allergic reaction， and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS， indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network， this study clarified that component group C6 may be a potential allergen in SHLI， and the component group C2 may be a key node in the mechanism of drug action， which can provide new strategies and methods for the screening of allergens in TCM injections.

BACKGROUND:Connexin 43(Cx43),which is thought to be engaged in the gap junction process and build the structural groundwork for the development of direct material signaling channels between cells,is crucial for maintaining the homeostatic balance of tissue metabolism.Recent research,however,has revealed fresh information about its distinct hemichannel function and highlighted the significance of its subcellular localization and self-fragmentation for cellular physiological activities and pathological processes. OBJECTIVE:To systematically summarize the molecular characteristics and expression of Cx43 in a variety of cells,concentrate on the pathological and physiological roles of channel-dependent Cx43 and channel-independent Cx43,and investigate the potential value in disease treatment by reviewing the pertinent literature in the database. METHODS:The Chinese and English keywords were"gap junction,connexin 43(Cx43),hemichannel,channel-dependent Cx43,channel-independent Cx43,extracellular vesicles(EVs),mitochondria,GJA1-20k",which were searched in PubMed and CNKI.Finally,81 articles were selected for review. RESULTS AND CONCLUSION:(1)The canonical role of Cx43 is to form a gap junction channel.Channel-dependent Cx43 has primarily involved in disease physiopathological processes by directly constituting gap junction channels,but full attention should be paid to the issue of its structural and functional integrity.Adhesion is a crucial characteristic of gap junctions,which are strongly associated with barrier-like diseases.(2)The non-canonical role of Cx43 is non-gap junction channel-dependent effect.In addition to being localized at the plasma membrane,inner mitochondrial membrane,extracellular vesicle surface,and other structures,Cx43 hexamer has also been found to play a role in positive pro-inflammatory mechanisms,mitochondrial functional metabolism,and targeted uptake of extracellular vesicles in inflammatory diseases.Selective shortened segments control mitochondrial homeostasis by encouraging the polymerization of peri-mitochondrial actin and are involved in the targeted translocation of full-length Cx43 to intracellular structural domains.(3)The development of targeted medicines and the solving of issues like the mechanism of seed cell transformation in tissue engineering-based therapies are both made possible by these two categories of impacts.The interactions of various types of Cx43,however,are frequently not fully taken into account in some of the existing original studies,which confuses the overall characteristics and skews the results.(4)It is necessary to systematically frame the physiological characteristics of Cx43 in different forms and its potential mechanisms in various diseases,so as to provide a reference for the exploration of the Cx43 integrity mechanism and the diagnosis and treatment of multiple diseases.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Objective:To establish the fingerprints of Plantaginis Herba.Methods:The fingerprints were determined by UPLC. The peak areas of fingerprints of different parts and origins were analyzed by variance analysis and independent sample t-test. PCA, HCA, PLS-DA and other chemical patterns were analyzed by Simca14.1. The index weight was calculated by CRITIC, and the quality of plantain evaluation was combined with grey correlation degree.Results:The fingerprints of grass, stem, leaf and spike of Plantago depressa Willd. calibrated for 24, 16, 23 and 22 common peaks. The fingerprints of grass, stem, leaf and spike of Plantaginis Herba calibrated for 22, 10, 16 and 22 common peaks, and the fingerprints of commercial mixed plantain calibrated for 23 common peaks. 10 peaks were identified. The analysis of variance showed that there were differences in chromatographic peak areas between different parts of Plantago asiatica L. and Plantago depressa Willd.. And combinedede with PLS-DA, it showed that there were 16 important characteristic indexes in the classification, and the importance ranking was peak 3, 8, 28, 12, 14, 7, 5, 17, 6, 19, 23, 11, 22, 27, 9, 16. The quality evaluation results of critical method combined with grey correlation degree showed that among Plantago depressa Willd., Plantago asiatica L. and commercial mixed plantain herbs, the quality of Plantago asiatica L. was the best. Conclusion:The mixture of plantain exists in the market. The fingerprints established in this study can be used for the identification and quality evaluation of Plantaginis Herba from different sources.

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

OBJECTIVE：To analysis the correlation between chrom aticity value and quality index of Atractylodis chinensis decoction piece powder stir-fired with bran ，and to determine its processing time. METHODS ：The processed samples of 16 batches of A. chinensis decoction piece stir-fired with bran （S0-S15，S0 is the raw product of A. chinensis ）were prepared ，and chromaticity values of all samples were determined ，such as lightness value （L*），yellow blue value （b*），red green value （a*）. UPLC fingerprint of sample were analyzed ，and the contents of extract and volatile oil were also determined. Pearson correlation was used to analyze the correlation between the chromaticity value and quality index （relative peak area of each chromatographic peak in UPLC fingerprint ，water-soluble extract content ，alcohol-soluble extract content and volatile oil content ）. Multivariate statistical analysis （principal component analysis ，cluster analysis ，partial least squares discriminant analysis ）was carried out with chromaticity value and quality index ，and the processing time of A. chinensis decoction piece stir-fired with bran was determined by grey correlation method. RESULTS ：In the process of bran frying ，with the extension of processing time ，L* and b* of decoction pieces powder decreased ，and a* increased first and then decreased ；relative areas of peak 1 and peak 2 increased first and then decreased，while relative areas of peak 3（5-hydroxymethyl furfural ）increased，and the areas of the other peaks decreased. The content of the extract did not change significantly with time ，and the content of the volatile oil decreased. The results of correlation analysis showed that the relative peak area of peak 2-27，alcohol-soluble extract content and volatile oil content had a certain correlation with the chromaticity value ，while the relative peak area of peak 1 and water-soluble extract content had no linear correlation with the chromaticity value. Results of multivariate statistical analysis showed that the samples were divided into mild （S0-S5），excessive （S12-S15），moderate （S6-processing time of 18-33 min）. The results of grey correlation method showed that the processing time of A. chinensis decoction piece stir-fired w ith bran should be controlled in the range of 18-24 min，and the optimal processing time was 18 min. CONCLUSIONS ：There is a correlation between chromaticity value of A. chinensis decoction piece powder stir-fired with bran and the relative peak area of 27 chromatographic peaks ，and content of extract and volatile oil. It is suggested that the processing time should be 18 min.

Objective: To study the clinical significance of serum calcitonin in the diagnosis and treatment of medullary thyroid carcinoma and to analyze its cost-benefit. Methods: One hundred and forty one patients with medullary thyroid carcinoma who undertook calcitonin test and frozen pathological examination were enrolled in this study from Oct 2012 to Mar 2018. Using the method of χ² test, the positive rate of calcitonin test and frozen pathological examination in diagnosis of medullary thyroid carcinoma(MTC) were compared. Firstly, we compared the correct checkout cost of calcitonin test and that of frozen pathological examination (total number of patients×cost of examination/the correctly detected number of patients) . Secondly, we calculated whether calcitonin test help patients save money(average cost of treatment in hospital for MTC×number of patients who were evaluated to be candidate for surgery-cost of calcitonin test×total number of patients)/total number of patients. Results: 139 patients were positive in calcitonin test among 141 patients, and the positive rate was 98.58%. 91 patients were positive in frozen pathological examination, and the positive rate was 64.54% (χ²=97.821, P<0.000 1) . Cost-benefit analysis showed that the correct checkout cost of calcitonin test and frozen pathological examination were 71.01 yuan and 426.10 yuan, also,1 371 938.64 yuan could be saved totally and 9 730.06 yuan could be saved per patient because of calcitonin test. Conclusion Serum calcitonin test had a significant effect on the diagnosis and treatment of medullary thyroid carcinoma and was economical and practical.

Objective To explore the effect of nurse-led intensive nutritional intervention on nutritional risk,undernutrition and quality of life in hospitalized Alzheimer disease (AD) patients.Methods A total of 170 hospitalized AD patients who met the criteria of the protocol were enrolled and divided randomly into two groups as study group (n=86) and control group (n=84).The two groups received nurse-led intensive nutritional intervention and routine nutritional management respectively for six weeks.Nutritional risk,undernutrition and quality of life were measured by nutritional risk screening 2002 (NRS 2002) and quality of life-Alzheimer disease scale before and after the nutritional intervention.Results There was no significant difference in baseline data between the two groups.The suitable rate of NRS 2002 was 100％.After a 6-week intervention,the prevalence of nutritional risk (41.9％ vs.70.9％,P＜0.001) and undernutrition (17.4％ vs.30.2％,P =0.049) decreased significantly in study group.The prevalence of nutritional risk was significantly lower in study group than in control group (41.9％ vs.64.3％,P=0.003).The score of quality of life in study group significantly increased (34.12±5.91 vs.31.56±6.80,P=0.028) after the intervention,and was significantly higher than that of the control group (34.12±5.91 vs.31.63± 6.22,P=0.030).Conclusion The application of nurse-led intensive nutritional intervention can help to improve the nutritional status and quality of life in hospitalized AD patients.

Objective To investigate the correlation between nutritional status in elderly patients with Alzheimer disease (AD) and self-efficacy of their caregivers.Methods Ninety-two elderly patients with AD and 92 their caregivers were enrolled from a Peking Union Medical College in Beijing from March to October 2017,who were evaluated by the mini nutritional assessment short form (MNA-SF) and the general self-efficacy scale (GSES) respectively for the nutritional status of the AD patients and the self-efficacy of their caregivers,and the correlation between them was analyzed.Results The average MNA-SF score of the AD patients was 7.8± 2.5.The incidence of malnutrition risk and malnutrition were 34.8％ and 27.2％ respectively.The MNA-SF score of the AD patients decreased (F =4.589,P =0.009),and the incidence of malnutrition risk (x2 =7.319,P =0.026) and malnutrition (x2 =7.080,P =0.032) increased significantly with the aggravation of AD.The average self-efficacy score of the caregivers was 2.20±0.45.With the aggravation of AD,the GSES score of the caregivers decreased significantly (F=3.122,P=0.016).There was a positive correlation between the nutritional status of the AD patients and the self-efficacy of their caregivers (r =0.254,P =0.022).Conclusion The nutritional status in elderly patients with AD is positively correlated with the self-efficacy of their caregivers,that is,the higher GSES score of the caregiver is,the better nutritional status of the AD patient has.