Objective To explore the optimal storage methods to maintain serum clozapine (CZP) and N-desmethylclozapine (N-CZP) concentration in a long-term stablility. Methods Ten fresh clinical blood samples were collected, and each sample's serum was separated at volume of 0.5 ml into five pieces of 10 ml conic glass cen-trifuge tubes with cocks; then CZP and N-CZP were beth assayed with HPLC in samples collected on sampling day, stored at 4 ℃ and -20 ℃ for 12 weeks and 24 weeks,respectively. Results There was no significant difference in CZP among samples stored at 4 ℃ for 12 weeks[(525.1±124.3) μg/L] ,at -20 ℃ for 12 weeks[ (535.5± 126.7) and 24 weeks[ (532.5±126.7) μg/L] ,as well as collected on sampling day[(542.7±135.0) μg/L] (P>0.05); There was also no significant difference in N-CZP among samples stored at -20 ℃ for 12 weeks [(226.2±50. 7) μg/L] and 24 weeks[ (224.9±44.8) μg/L] and collected on sampling day[(236.9± 66.6) μL] (P>0.05). Conclusion CZP and N-CZP concentration would be maintained stable within 24 weeks under the refrigerated storage temperature of -20 ℃ at a fixed volume.

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.

Objective:To explore the mechanism of turnover intention of junior nurses after adverse events from three aspects: work pressure, leadership style and personal characteristics.Methods:This study was a cross-sectional survey, using the convenience sampling method, 289 nurses from Shanxi Bethune Hospital from December 2020 to March 2022 were selected as the research subjects, and the general data questionnaire, the Separation Tendency Scale, the Nurses′ Work Stressor Scale, the Service-oriented Leadership Style Scale, and the Prospective Personality Scale were used to survey them.Results:Structural equation model showed that nurses′ job stressor level positively predicted turnover intention, with a path coefficient of 0.74, P<0.01, while service-oriented leadership style and forward-looking personality negatively predicted turnover intention, with path coefficients of -0.60 and -0.37, respectively, both P<0.01. Hierarchical regression analysis showed that both service-oriented leadership style and forward-looking personality negatively moderated the promotion of job stressors on turnover intention, and the moderating effect regression coefficients were -0.146, -0.215, both P<0.01. Conclusions:Hospitals should improve the prospective personality traits of junior nurses and cultivate the service-oriented leadership style of nursing managers after adverse events, so as to reduce the turnover tendency of junior nurses as the second victim, promote the improvement of nursing quality, and stabilize nursing team development.

The contents of chlorogenic acid, 3,5-O-caffeoylquinic acid, galuteolin and quercitrin in Sanvitalia procumbens and Chrysanthemum morifolium cv. 'Hangju' and 'Gongju' were determined by RP-HPLC. The main active ingredient of S. procumbens was similar to C. morifolium cv. 'Hangju' and 'Gongju'. The content varied significantly. The contents of chlorogenic acid, quercitrin and galuteolin in S. procumbens were 7.46, 46.58, 26.01 mg x g(-1), respectively, and they were the highest among the samples. The content of 3,5-O-caffeoylquinic acid in C. morifolium cv. 'Hangju' was 14.70 mg x g(-1), it was the highest among the samples. The data of the study provide a basis for further research and development of S. procumbens.
Asteraceae ; chemistry ; Chlorogenic Acid ; analogs & derivatives ; analysis ; Chromatography, High Pressure Liquid ; Chrysanthemum ; chemistry ; Drugs, Chinese Herbal ; analysis ; Quinic Acid ; analogs & derivatives ; analysis

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

The common Japanese Kampo medicine issued by MHLW was sorted and analyzed, record total ingredients, average dosage, total dosage of general prescription, maximal and minimal dosage of general prescription of Japanese Kampo was originated from the classic prescription. The ingredients of each prescription medicine was relatively less, and mostly composed of 4 to 9 ingredients. The average dosage was less, around 15-25 g and the average dosage of single drug was 3.16 g. The dose of Japanese Kampo medicine was relatively less, and it was only about 1/4 of the drug used in Chinese mainland. The reasons were related to many factors like historical evolution of Chinese prescription, the habit of taking medicine, people’s constitution of different nations and so on.

The treatment of articular cartilage (AC) injury caused by various reasons is still a major clinical problem. The emergence of cartilage tissue engineering brings new hope for the treatment of AC injury. In general, AC tissue engineering can be divided into two categories, including cell-based tissue engineering and cell-free tissue engineering. Although cell-based tissue engineering can repair cartilage damage to a certain extent, existing therapeutic strategies still suffer from limited cell sources, high costs, risk of disease transmission, and complex procedures. However, the cell-free tissue engineering avoids these shortcomings and brings hope for in-situ AC regeneration. Non-cellular tissue engineering is mainly used to recruit endogenous stem cells/progenitor cells (SCPCs) to reach the site of cartilage injury, and provide a suitable regenerative microenvironment to promote cell proliferation and chondrogenic differentiation, then the maturation of new cartilage tissue was promoted. Therefore, it is also called as cell-homing in situ tissue engineering. Successful recruitment of endogenous SCPCs is the first step in in-situ cartilage tissue engineering. This review aims to introduce chemokine response of cartilage injury, systematically summarize traditional chemoattractant (chemokines and growth factors etc.) and emerging chemoattractant (functional peptides, exosomes and nucleic acid adapters etc.), evaluate the combination mode between chemoattractant and delivery devices, discuss the prospects and challenges of chemoattractant-mediated in situ tissue engineering and provide theoretical basis for the design of endogenous SCPCs homing-based in situ tissue engineering.

As a natural plant source of artemisinin,a first-line drug against malaria,Artemisia annua directly affects the extraction process of artemisinin and the source of artemisinin. At present,traditional breeding methods combined with tissue culture are often used to breed high-yield artemisinin-containing new varieties of A. annua. However,the breeding method has the disadvantages of low efficiency and continuous selection. In this study,heavy ion beam irradiation technology was used to observe the specific germplasm resources of A. annua,and the morphological characteristics,agronomic traits and artemisinin content were used as indicators to observe the selection materials and materials. The cultivated new varieties were compared with trials and regional trials. In addition,the new variety of A. annua was identified by SRAP molecular marker technology. The results showed that the new variety of A. annua, " Kehao No.1",had an average yield of 235. 0 kg of dry leaf per mu,which was more than 20% higher than that of the control. Especially,the average artemisinin content was 2. 0%,which was 45% higher than that of the control,and the " Kehao No.1" has high anti-white powder disease,high-yield and high-quality new varieties. Therefore,mutagenic breeding of heavy ion beam irradiation can significantly improve the yield and artemisinin content of the " Kehao No. 1" and it has a good promotion value.
Artemisia annua/genetics* ; Artemisinins/analysis* ; Heavy Ions ; Mutagenesis ; Phenotype ; Plant Breeding ; Plants, Medicinal/genetics*

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment