Temporal evolution of postsurgical bone repair in a rabbit model: A [99mTc]Tc-MDP scintigraphic study

Abstract Bone regeneration is crucial for repairing bone tissue following various injuries. Research techniques that enable the study of metabolic changes in bone tissue under different conditions are important for understanding bone repair and remodeling. This study used bone scintigraphy to evaluate osteogenesis secondary to osteotomy in a preclinical model of New Zealand rabbits. For this purpose, we conducted a longitudinal, prospective, case-control study in which scintigraphic variables were measured in both the right forearm (case-operated) and the left forearm (control - non-operated). The study sample consisted of 10 rabbits subjected to osteotomy, followed by a 12-week postoperative evaluation period, divided into six imaging stages at 1, 2, 3, 4, 8, and 12 weeks. We observed that the operated forearm showed significantly higher external radiation than the control side, using the pinhole collimator, denoting an increase in the biodistribution and tropism of the radiopharmaceutical to the operated forearm. Among the three evaluated time points, osteoblastic activity was highest in the second week and presented a significant decline in the 8th and 12th weeks, denoting regeneration and resolution of the surgical injury; the control forearm was also influenced by the inactivity imposed by the operated forearm. This fact was notably evidenced by the reduction in the metabolic activity of osteoblasts in the left forearm. Our study suggested that bone scintigraphy was sensitive enough to semi-quantitatively differentiate the metabolic activity of osteoblasts in the operated forearm in the three temporal landmarks evaluated in the study.

Mechanism of Cuscutae Semen to Control Premature Ovarian Failure Based on Lipid and Atherosclerosis Pathways / 中国实验方剂学杂志

ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E2， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.

Effect of Longmu Piyan Prescription on Oxidative Stress in Atopic Dermatitis Mice / 中国实验方剂学杂志

ObjectiveThis study observes the intervention effect of Longmu Piyan prescription on oxidative stress in BALB/c mice with atopic dermatitis （AD） induced by 2，4-dinitrochlorobenzene （DNCB） and explores its mechanism. MethodThe AD model was established using the method of DNCB sensitization on the back skin of BALB/c mice. Forty male BALB/c mice were randomly divided into a blank group， a model group， a vitamin C control group （0.5×10-3 mg·kg-1）， and a Longmu Piyan prescription group （26 g·kg-1）. Except for the blank group， other groups were sensitized with different concentrations of DNCB on the back to induce AD， and the blank group was treated with matrix coating. The gastric administration was started on the seventh day after sensitization with 2% DNCB and on the 24th day after sensitization with 0.2% DNCB continuously for 21 days. The changes in skin lesions of each group were directly observed after the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin （IL）-4， tumor necrosis factor （TNF）-α， immunoglobulin E （IgE）， and reactive oxygen species （ROS） in the serum of each group. The total antioxidant capacity determination kit-trace method (ABTS method) was used to measure the level of total antioxidant capacity （TAOC） in serum. The Hematoxylin eosin （HE） staining method was used to observe the pathological and morphological changes of the skin lesion site. The immunohistochemical method was used to detect the expression of thymic stromal lymphopoietin （TSLP） in the skin lesion site. Western blot was used to detect the expression of filaggrin （FLG） in the dorsal skin lesions. ResultThe results showed that compared with the blank group， the skin lesion score of the model group mice was significantly increased （P<0.01）， and HE staining showed characteristic pathological changes of AD in the skin lesion site. At the same time， the expression of TSLP in the skin lesion was significantly increased， and that of FLG was reduced （P<0.05）. The levels of TNF-α， IL-4， IgE， and ROS in serum increased， while the activity of TAOC decreased （P<0.01）. Compared with the model group， the Longmu Piyan prescription group showed a significant decrease in skin lesion scores and a significant improvement in skin lesion pathology. At the same time， the expression of TSLP decreased， and the expression of FLG increased in the skin lesions （P<0.05）. In addition， compared with the model group， the serum levels of TNF-α， IL-4， IgE， and ROS also decreased to varying degrees （P<0.05，P<0.01）， and TAOC activity increased in the Longmu Piyan prescription group （P<0.01）. ConclusionThere is a significant correlation among the degree of oxidative stress， the severity of skin lesions in AD， and the levels of inflammatory cytokines. Longmu Piyandu prescription can improve AD-like skin lesions in BALB/c mice by promoting ROS clearance， enhancing TAOC， and inhibiting oxidative stress， thus protecting the skin barrier and reducing inflammation.

Analysis of effective components of Agaricus blazei Murill extract by LC-MS and network pharmacology analysis in treatment of chronic myeloid leukemia / 中国药理学通报

Aim To explore the potential targets and related signaling pathways of Agaricus blazei Murill (AbM ) extract in the treatment of chronic myeloid leukemia (CML) based on liquid chromatography mass spectrometry ( LC-MS ), network pharmacology, molecular docking, and were further verified by experiments in vitro. Methods The active components of AbM extract were retrieved from LC-MS, Swiss Target Prediction database was used to predict related targets, and CML disease target genes were obtained from Gen- eCards and DisGeNET databases. After screening the common targets of drug and CML, the protein-protein interaction network of the common targets was performed by STRING, and GO and KEGG enrichment a- nalysis were done by DAVID database. Cytoscape software was used to construct the network of target protein. Molecular docking was carried out by DockThor, and the Pymol software was used to make a visual picture. The inhibitory effect of AbM extract on leukemia cells K562 was determined by CCK-8 experiment, and the effect of AbM extract on the expression and phosphorylation level of related proteins was verified by Western blot. Results The prediction results showed that 126 active components of AbM extract, and 172 common targets were collected. KEGG pathway analysis results showed that PI3K/Akt/mTOR signaling pathway might play an important role in the treatment of CML disease. The IC

A Ten-Year Comparative Study on Ethical Cognition of Experimental Animals among Medical Students in a University / 中国医学伦理学

The study was carried out to understand the changes in the ethical cognition status of laboratory animals and the effectiveness of laboratory animal ethics education among medical students in Xiangya School of Medicine of Central South University (CSU), and provide new enlightenment for further strengthening the ethical education of laboratory animals. In the study, the same self-compiled questionnaire was used to investigate the ethical cognition of experimental animals among medical students in Xiangya School of Medicine of CSU in 2011 and 2021, and 359 and 363 questionnaires were collected respectively. Through comparative analysis of the questionnaire results before and after ten years, it was found that medical students’ animal experiment operation and attitudes towards laboratory animals, cognition of experimental animal ethics knowledge and their attitude to animal experiment ethics education were significantly improved. It showed that the state of experimental animal ethics cognition among medical students in Xiangya School of Medicine of CSU had improved significantly in recent 10 years, but the cognition of experimental animal ethics knowledge was higher than the actual behavior of caring for experimental animals, and there was the phenomenon of "separation of knowledge and action". The ethics education of experimental animals needs to pay more attention to the development of students’ behavior of caring for experimental animals.

Total Saponins of Dioscorea Mitigate Nonalcoholic Steatohepatitis in Mice by Regulating AMPK/SREBP-1c/ACC Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the role and mechanism of total saponins of Dioscorea （TSD） in mitigating nonalcoholic steatohepatitis （NASH） in mice. MethodForty-eight C57BL/6J mice were randomized into a normal group and a modeling group. The mice for modeling were fed with a high-fat and high-cholesterol diet + 20% fructose solution for 16 weeks and randomized into model， atorvastatin （4 mg·kg-1·d-1）， and high-， medium-， and low-dose （200， 60， and 20 mg·kg-1·d-1） TSD groups. The mice were administrated with corresponding doses of drugs by gavage for 8 weeks. The mouse activity， liver index， levels of total cholesterol （TC）， triglycerides （TG）， and free fatty acids （FFAs） in the liver， and levels of TC， TG， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， γ-glutamyl transferase （GGT）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were measured. Hematoxylin-eosin staining， Masson staining， oil red O staining， and transmission electron microscopy were employed to observe the pathological changes， lipid accumulation， and morphological changes of liver ultrastructure. Western blot was employed to determine the protein levels of AMP-activated protein kinase （AMPK）， sterol regulatory element-binding protein-1c （SREBP-1c）， acetyl-CoA carboxylase （ACC）， and phosphorylated ACC （p-ACC） in the liver tissue. ResultCompared with the normal group, the activity of mice in the model group decreased(P<0.05， P<0.01), the levels of TC, TG, FFA and serum TC, TG, ALT, AST, GGT, IL-1β and TNF-α, liver coefficient and liver pathology scores were significantly increased, the expression of p-AMPK/AMPK and p-ACC proteins in liver tissues was significantly reduced, and the expressions of SREBP-1c and ACC proteins were significantly increased (P<0.01). Compared with the model group， atorvastatin increased the mouse activity （P<0.05）， while each dose of TSD caused no significant changed in the mouse activity. The levels of TC, TG, FFA in liver and serum TC, TG, ALT, AST, GGT, IL-1β, TNF-α, liver coefficient and liver pathological score in TSD and atorvastatin groups were significantly decreased, and the expressions of p-AMPK/AMPK and p-ACC in liver tissue were significantly increased. The expressions of SREBP-1c and ACC were significantly decreased (P<0.05,P<0.01). ConclusionTSD may alleviate NASH in mice by regulating the AMPK/SREBP-1c/ACC signaling pathway to reduce lipid synthesis.

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization / 神经科学通报·英文版

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.

RPG Imersiva saúde do idoso: uma nova possibilidade de construção de aprendizagem em saúde? / Immersive RPG Elderly Health: A New Possibility for Constructing Health Learning?

Resumo Objetivo Avaliar a aplicabilidade e a efetividade de um jogo com elementos de Roleplaying Game (RPG) enquanto ferramenta didático pedagógica para o ensino em saúde. Método A população deste estudo foi de discentes de cursos de graduação e pós-graduação, da área da saúde, da Universidade Federal do Rio Grande do Sul, Brasil. Trata-se de uma pesquisa qualitativa. O estudo foi realizado entre os meses de abril a junho de 2018, em duas etapas. Primeiramente foi realizado o RPG com as turmas envolvidas, e após uma semana, entrevistas de GF para a obtenção de informações, contando com voluntários dessas turmas que aceitaram participar da pesquisa. A análise das informações foi baseada em aspectos da Teoria Fundamentada nos Dados (TFD). Resultados Da análise emergiram as categorias:1) Criação do jogo, 2) Impacto da experiência no ensino aprendizagem, 3) Reflexão acerca do jogo. Os resultados demonstram que o uso do jogo com elementos de RPG tem um enorme potencial a ser explorado no processo de ensino-aprendizagem na área da saúde. Trata-se de um método inovador e ainda pouco utilizado na área da saúde. É importante seguir algumas premissas para que a ferramenta seja utilizada de forma potente. Conclusão Nessa direção entende-se que o jogo auxilia na formação em saúde, enriquecendo conhecimentos e habilidades através de uma experiência desafiadora e conectada com a realidade.

Abstract Objective To assess the applicability and effectiveness of a game incorporating Roleplaying Game (RPG) elements as a pedagogical tool for health education. Method The study population comprised undergraduate and postgraduate students in the health field at the Universidade Federal do Rio Grande do Sul, Brazil. This qualitative research was conducted between April and June 2018 in two stages. Initially, the RPG was implemented with the involved classes, followed by Focus Group interviews conducted a week later to gather information, with volunteers from these classes who willingly participated in the research. Information analysis was grounded in aspects of Grounded Theory (GT). Results The analysis yielded the following categories: 1) Game creation, 2) Impact of the experience on teaching and learning, 3) Reflection on the game. The results demonstrate that the use of RPG-influenced games holds significant untapped potential in the health education process. This innovative method remains underutilized within the health domain, necessitating adherence to specific premises for its potent application. Conclusion In this context, it is understood that the game contributes to health education, enhancing knowledge and skills through a challenging and reality-connected experience.

La suplementación con zinc favorece el crecimiento intrauterino en fetos de ratas diabéticas / Zinc supplementation favours intrauterine growth in diabetic rat fetuses

La deficiencia de zinc puede ser un factor mediador en los trastornos del crecimiento fetal en la descendencia de la gestante diabética. Se persiguió como objetivo determinar la influencia de un suplemento con zinc sobre la morfometría externa corporal y craneofacial en fetos de ratas diabéticas con hiperglucemias moderadas. Durante la gestación, ratas diabéticas y controles fueron suplementadas por vía oral con sulfato de zinc (50 mg/kg-pc) o no recibieron tratamiento. Los fetos descendientes del grupo diabético suplementado presentaron niveles similares a los controles en las variables de crecimiento somático determinadas. La suplementación con zinc a ratas diabéticas favoreció el crecimiento intrauterino en los fetos. Los resultados de esta investigación constituyen aportes para dilucidar los requerimientos de zinc que permitan prevenir los trastornos del crecimiento fetal en la descendencia de gestantes diabéticas.

Zinc deficiency may be a mediating factor in fetal growth disorders in the offspring of diabetic pregnant women. The objective was to determine the influence of a zinc supplement on external body and craniofacial morphometry in diabetic rat fetuses with moderate hyperglycemia. During gestation, diabetic and control rats were orally supplemented with zinc sulphate (50 mg/kg bw) or received no treatment. The fetuses descendants of the supplemented diabetic group had levels similar to the control ones in the determined somatic growth variables. Zinc supplementation to diabetic rats favoured intrauterine growth in fetuses. The results of this research constitute a contribution to elucidate zinc requirements that allow preventing fetal growth disorders in the offspring of diabetic pregnant women.

Effects of nutritional profile system and front labeling in food selection during purchases: a systematic review / Efecto de los sistemas de perfilado nutricional y etiquetado frontal en la selección de alimentos durante la compra: una revisión sistemática

Introduction. Nutritional profiling systems (NPS) are mainly used in front-end labeling policies in order to make the purchase and consumption choice conscious and healthy. Objetive. This study systematically reviewed evidence from interventions on the effect of NPS in the front-of- package on food purchases. Materials and methods. A bibliographic search was carried out in electronic sources from Medline, Elsevier, Scielo and Lilacs, of experimental studies and intervention between 2012 and 2022. A total of 14 articles were included in the review. They were analyzed according to the intervention modality used: 4 studies analyzed the effect of NPS in a real purchase situation and 10 evaluated purchase perception/intention. Results. According to the modality of intervention, the 6 studies that analyzed the NPS-warning system, all recorded healthier purchases compared to the control groups. While for the NPS-NutriScore, Health Star Rating and Multiple Traffic Lights were effective in the decision to purchase healthier foods, in 5 of 7 studies for the first NPS, in 4 of 7 for the second and in 4 of 8 for the third, compared with control groups. Conclusions. Findings of this study suggest that NPSs may be effective for healthy purchase choices, even so it is necessary to strengthen the system and policies with nutritional food education campaigns(AU)

Introducción. Los sistemas de perfilado nutricional (SPN) son utilizados principalmente en políticas de etiquetado frontal con la finalidad de que la elección de compra y consumo sea consciente y saludable. Objetivo. Este estudio revisó sistemáticamente la evidencia de las intervenciones sobre el efecto de SPN en el frente del paquete en las compras de alimentos. Materiales y métodos. Se realizó una búsqueda bibliográfica en fuentes electrónicas de Medline, Elsevier, Scielo y Lilacs, de estudios experimentales e intervenciones entre 2012 y 2022. Se incluyeron un total de 14 artículos en la revisión. Fueron analizados según la modalidad de intervención utilizada: 4 estudios analizaron el efecto de los SPN en una situación de compra real y 10 evaluaron percepción/intención de compra. Resultados. Según la modalidad de intervención, los 6 estudios que analizaron el SPN-sistema de advertencia, todos registraron compras más saludables en comparación con grupo controles. Mientras que para los SPN-NutriScore, Estrellas de Salud y Semáforo Tricolor Múltiple fueron efectivas en la decisión de compra de alimentos más saludables, en 5 de 7 estudios para el primer SPN, en 4 de 7 para el segundo y en 4 de 8 para el tercero, comparados con grupo controles. Conclusiones. Los hallazgos de este estudio sugieren que los SPN pueden ser efectivos para elecciones de compras saludables, aun así, es necesario reforzar el sistema y las políticas con campañas de educación alimentaria nutricional(AU)

Jogo de tabuleiro para crianças com autismo: desenvolvendo autonomia e habilidades sociais / Board game for children with autism: developing autonomy and social skills

This is a methodological study that aimed to develop a board game to develop autonomy and social skills in children with autism. The game's development was supported by the toy library of the Hospital Universitário Júlio Bandeira [Julio Bandeira University Hospital]. Models were collected through an integrative review and an interview with mothers of autistic children. The game was based on methods extracted from articles, from the Picture Exchange Communication System, Social Stories, and the difficulties encountered during the interview. It has a board with 32 squares, 22 cards (three different models), one die, and small cars used to advance through the squares on the board. Due to their playful nature, board games have the potential to be used by children with autism to develop autonomy and social skills. It was concluded that the production of care-educational technologies aimed at the autistic public is essential for cognitive and social development.

Trata-se de estudo metodológico que objetivou elaborar um jogo de tabuleiro para desenvolver a autonomia e as habilidades sociais nas crianças com autismo. A produção do jogo contou com o apoio da brinquedoteca do Hospital Universitário Júlio Bandeira. Captaram-se modelos mediante uma revisão integrativa e uma entrevista com mães de crianças autistas. O jogo se baseou nos métodos extraídos dos artigos, no Picture Exchange Communication System, nas Histórias Sociais e nas dificuldades encontradas na entrevista. Ele conta com um tabuleiro de 32 casas, 22 cartas (3 modelos diferentes), 1 dado e carrinhos utilizados para avançar as casas do tabuleiro. Devido ao seu caráter lúdico, os jogos de tabuleiro têm potencial de ser usados por crianças com autismo para desenvolver a autonomia e habilidades sociais. Concluiu-se que a produção de tecnologias cuidativo-educacionais voltadas para o público autista é fundamental para o desenvolvimento cognitivo e social.

La solidez de la investigación homeopática fundamental / The strength of fundamental homeopathic research

La investigación fundamental en homeopatía ha avanzado considerablemente en los últimos 20 años: desde estudios exploratorios con animales y plantas hasta la caracterización de los efectos sistémicos de los medicamentos homeopáticos y estudios in vitro con sistemas celulares aislados para evaluar los cambios en los mecanismos de adaptación celular y señalización intracelular frente a tratamientos homeopáticos variables. El número de artículos publicados a lo largo del tiempo ha permitido realizar varias revisiones sistemáticas. Recientemente, la demostración de que los medicamentos homeopáticos podrían modificar las funciones celulares a través de mecanismos epigenéticos (metilación y desmetilación de ADN) preparó el camino para un campo de investigación completamente nuevo. En paralelo, el descubrimiento de las nanopartículas y propiedades físicas específicas de las diluciones homeopáticas ha arrojado luz hacia un campo antes poco conocido, dado que se consideraba que las diluciones homeopáticas no consistían más que de agua. Así las cosas, los retos para el futuro conciernen a la demostración, o no, de la interrelación entre ambos fenómenos.

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

The impact of human umbilical cord-derived mesenchymal stem cells on the pancreatic function of type 2 diabetic mice and their regulatory role on NLRP3 inflammasomes / 中华内科杂志

Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

Correlation of neutrophil extracellular traps with T cells differentiation in Hashimoto′s thyroiditis mice and vitamin D′s relief effect / 中华内分泌代谢杂志

Objective:To investigate correlation between neutrophil extracellular traps(NETs) formation and T cell subsets in mice with experimental autoimmune thyroiditis(EAT) and the impact of active vitamin D intervention.Methods:Six-week-old female BALB/c mice were randomly divided into Control group, EAT group and 1, 25 dihydroxy vitamin D 3[1, 25(OH) 2D 3] treatment group(VitD group; n=6/group). HE staining was used to observe thyroid pathology. Plasma thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and 1, 25(OH) 2D 3 were measured by ELISA. Peripheral NETs formation, Th1, Th2, and Th17 cell ratio from spleen were measured by flow cytometry. Correlation between NETs formation rate and Th1, Th2, and Th17 cell ratio was analyzed. Results:Compared with Control group, mice in EAT group had significantly increased thyroid inflammation scores, thyroiditis morbidity, TPOAb, TGAb levels, NETs formation rate, Th2(CD4 + IL-4 + or CD4 + IL-13 + )and Th17 cell proportions( P were <0.001, 0.002, 0.007, <0.001, <0.001, 0.003, 0.001, and 0.002, respectively), and significant decreased 1, 25(OH) 2D 3, Th1 cell proportions, Th1/Th2(CD4 + IL-4 + ), Th1/Th2(CD4 + IL-13 + ), and Th1/Th17 ratios( P were 0.010, 0.018, 0.010, 0.005, and 0.007, respectively). Compared with the EAT group, the VitD group had lower thyroid inflammation scores, TPOAb, TGAb levels, NETs formation rate, Th2(CD4 + IL-4 + or CD4 + IL-13 + ) and Th17 cell proportions( P were 0.044, 0.007, <0.001, 0.001, 0.014, 0.008, and 0.001, respectively), and significant higher Th1 cell ratio, Th1/Th2(CD4 + IL-13 + ) and Th1/Th17 ratio( P were 0.011, 0.009, and 0.003, respectively). The Th1/Th2(CD4 + IL-4 + ) was not significantly increased in VitD group compared with EAT group( P=0.174). NETs formation rate was positively correlated with Th2(CD4 + IL-4 + or CD4 + IL-13 + ) and Th17 cell proportion( r were 0.65, 0.59, and 0.61; and P were 0.004, 0.010, and 0.007, respectively), but not with Th1 cell proportion( r=-0.47, P=0.051). Conclusion:EAT mice were more prone to NETs formation. Active vitamin D may relieve immune imbalance with increased Th2 and Th17 cell ratio and decreased Th1 cell ratio by reducing the formation of NETs in EAT mice. Vitamin D played the protective role in thyroid by reducing thyroid pathological damage and thyroid autoantibody levels, and relived overall lymphocyte imbalance.

Blood and synovial tissue metabolomics of rheumatoid arthritis rats treated with less polar ginsenosides / 中华风湿病学杂志

Objective:The therapeutic effect of less polar ginsenosides on rats with rheumatoid arthritis was studied, and the metabolic pathway that produce anti-inflammatory effect of less polar ginsenosides was identified.Methods:Rats were randomly divided into the control group, the model group, methotrexate treatment group, and high dose, medium dose, and low dose less polar ginsenosides groups. After 30 days of oral administration, less polar ginsenosides reduced the disease activity significantly in rats with rheumatoid arthritis. Blood and ankle synovial tissue metabolisms were measured by ultra performance liquid chromatography (UPLC) tandem mass spectrometry (MS) to explore the mechanism of less polar ginsenosides.The resulting data were subjected to principal component analysis and orthogonal partial least squares discriminant analysis(OPLS-DA).Results:Compared with the model group, erythrocyte sedimentation rate and RF decreased significantly in the high dose of less polar ginsenosides ( P<0.01). Metabolomics showed that R2X and R2Y of serum OPLS-DA were 0.626 and 0.904 respectively. The R2X and R2Y of synovial OPLS-DA were 0.429 and 0.689 respectively. Major differential metabolites were identified in the model group of rats, including arachidonic acid, valine, linoleic acid, and guanine nucleoside, etc. The main differential metabolites were identified in rats in the high dose group of less polar ginsenosides, including linoleic acid, betaine, eicosapentaenoic acid, alanine, methionine sulfoxide, isoleucine, etc. Conclusion:The metabolic spectrum has shown that inflammation is associated with linoleic acid metabolism, valine, leucine and isoleucine degradation, arachidonic acid metabolism. Less polar ginsenosides regulatethe linolenic acid metabolism, methionine metabolism and glucose alanine cycle.

78c can alleviate coliagen-induced arthritis and restore immune balance in rheumatoid arthritis / 中华风湿病学杂志

Objective:To explored the effect of 78c in treating collagen-induced arthritis (CIA) mice and to investigate its mechanism of effects.Methods:CIA mice model and CD38 +NK cells were treated with 78c. Cytokine concentrations and lymphocyte subtypes were measured in the mice peripheral blood and culture medium using flow cytometry. Mikenyi cell isolation kit was used to isolate CD4 + T cells and NK cells from peripheral blood mononuclear cells of healthy volunteers. CD38 + NK cells were enriched using the Miltenyi CD38 microbeads from the extracted NK cells. CD38 + NK cells with 78c pretreatment or not were cocultured with CD4 +T cells in transwells. The least significant difference (LSD) method was used for comparison between the two groups, and one-way analysis of variance was used for multi-group significance. Pearson correlation analysis was used for correlation analysis. Results:78c treatment significantly suppressed joint inflammation, inhibited the toe thickness of CIA mice, and reduced the number of while cell, neutrophils, platelets, and concentrations of IFN-γ, IL-6 and TNF-α ( t=6.10, P<0.001; t=4.00, P=0.002; t=3.09, P=0.012; t=2.31, P=0.043; t=3.58, P=0.005; t=2.68, P=0.002) in the CIA mice. The proportion of CD38 +NK cells decreased from (3.9±0.9)% to (2.4±0.3)% ( t=2.49, P=0.032), the proportion of regulatory T cell (Treg) increased from (0.81±0.33)% to (1.41±0.26)% ( t=2.74, P=0.021), and the concentration of IL-10 also increased from (99±37) pg/ml to (199±9) pg/ml( t=2.76 , P=0.020). The proportion of Treg in CD4 +T cells cocultured with 78c-pretreated CD38 +NK cells increased from (0.52±0.04)% to (0.69±0.08)% ( t=3.33, P=0.029) , the T helper cells (Th)17/Treg ratio decreased from (4.44±0.26) to (2.59±0.64) ( t=4.76 , P=0.009), and the Th1/Th2 ratio decreased from (14.8±1.6) to (8.1±1.3)( t=5.70 , P=0.005). Conclusion:78c can reduce the proportion of CD38 +NK cells, thereby reducing the inhibition of CD38 +NK cells on CD4 +T cell differentiation into Treg cells, leading to the restoration of immune balance. The results of this study suggest that 78c is a potential therapeutic agent for rheumatoid arthritis.

A new mouse model to study the empathic fear and pain behavior / 中国药理学与毒理学杂志

OBJECTIVE Human beings possess the ability to indirectly acquire the emotions of others.This also known as emotional contagion or empathy,enables us to rapidly perceive the emotions of others.However,an excessive empathy may result in heightened fear and sensitivity to pain.Therefore,the establishment of appropri-ate animal models for analyzing neural mechanisms underlying empathy would contribute to pharmacological research on pain sensitivity caused by psychological sus-ceptibility.METHODS We used the observed fear para-digm for assessing contagion of negative emotions in mice.To minimize the impact of emotional contagion dif-ferences caused by the subject change,we established a bilateral observation area and the two mice were trained to observe fear simultaneously.First,two observer(OB)mice were placed on either side of the observational area.Next,a demonstrator(DM)mouse was introduced into the cylindrical shock cage located at the center of the apparatus.The shock cage is made of transparent organic plastic with air holes and has provided ample space for free movement by the DM mouse.During the shock stage,DM mice were subjected to electric stimulation while the behaviors of OB mice on both sides was observed,including freezing,the side and corner time,social interaction behavior.Additionally,c-Fos staining was utilized to confirm distinct local brain activities.RESULTS In the habituation stage,OB mice on both sides showed more social preference for DM mouse,as evidenced by an increase in duration time in the designat-ed interaction zone.During the shock phase,OB mice observed the DM mouse receiving electric shocks and displayed significantly higher levels of fear contagion;however,their fear behavior was not entirely consistent.Some mice exhibited a significant increase in freezing time,while others demonstrated a significant increase in corner and side exploration time.We utilized Z-normal-ization to evaluate changes in emotionality across vari-ous behaviors and identified mice with distinct susceptibil-ities.Fos-positive neurons exhibited higher expression levels in susceptible OB mice,primarily concentrated within brain regions associated with the ascending path-ways of pain perception,such as thalamus,the anterior insular cortex,and anterior cingulate cortex.CONCLU-SION In this study,we have developed an innovative experimental facility that integrates various behavioral tests to evaluate empathic behavior in mice.Our findings highlight the robustness of emotionality measures obtained from individual mice by combining this experi-mental model with the Z-scoring method,facilitating screening for empathic fear or pain-susceptible mice and will helpful for pharmacological evaluation.

Application of case-based learning combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals / 中华医学教育探索杂志

Objective:To investigate the application effect of case-based learning (CBL) combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals. Methods:The cluster random sampling method was used to select the class of 2019 in the eight-year program and the class of 2020 in the five-year program, with the major of stomatology in Air Force Medical University. The 24 students in the observation group received CBL combined flipped classroom, and the 37 students in the control group received traditional teaching. The two groups were compared in terms of theoretical assessment score, classroom assessment score, comprehensive ability, self-learning ability, and degree of satisfaction with teaching. SPSS 22.0 was used for the t-test. Results:The observation group had a significantly higher theoretical assessment score than the control group [(74.88±3.46) vs. (71.89±4.45), P<0.05]. The observation group had significantly better scores of practical skill assessment than the control group ( P<0.05). Compared with the control group, the observation group had significantly better scores of comprehensive ability and self-learning ability ( P<0.05). The observation group had significantly better scores of satisfaction with teaching than the control group ( P<0.05). Conclusion:The application of CBL combined with flipped classroom in the teaching of experimental diagnostics in the integrated course of Diagnosis and Treatment Fundamentals can improve theoretical knowledge, practical skills, comprehensive quality, and satisfaction with teaching among students, and therefore, it holds promise for application in teaching.

Implementation and evaluation of network experimental teaching in basic medicine / 中华医学教育探索杂志

The experimental class is a very important part of teaching process for medical students. Relying on the medical virtual simulation experiment center of Henan University, in this study, we select the appropriate experimental items and related knowledge content of the medical virtual simulation experiment center and post them to the students. Students are required to log in to the experimental center to strengthen the study of basic medical experimental knowledge by watching experimental videos and learning experimental principles, and then carry out virtual experimental operations. In terms of the teaching content, the required experimental virtual operation are required to complete, and in terms of teaching form, we adopt the combination of online experimental teaching course and webcast course teaching. This experimental teaching method is easy for students to accept, stimulates high enthusiasm for learning, and inspires curiosity for basic medical knowledge for the students, which significantly improves the teaching effect.

Exploration on multifunctional linkage and scientific use of medical colleges psychological experimental teaching center based on the network background / 中华医学教育探索杂志

The experimental teaching of psychology is not only an important course in the undergraduate and graduate education of applied psychology, but also can assist the practical teaching of quite a few other subjects. It clearly divides three basic functions of experimental psychology teaching center: teaching, scientific research and service, which play an important role in facilitating teachers and students to understand corresponding courses. At the same time, it is discussed and proposed to strengthen the internal and external scientific linkage of the experimental center under the network background, and put forward the use of Internet technology, in order to improve the scientific use of the experimental teaching center, and reflect its maximum value, thereby achieving the purpose of university laboratory joint construction and serve the university to cultivate innovative and compound personnels.