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.

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.

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.

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.

Non-Status Epilepticus female rats show seizure-like behaviors in the chronic phase of Pilocarpine experimental model / Ratas sem Status Epilepticus apresentam comportamento do tipo crise epiléptica na fase crônica do modelo experimental da Pilocarpina

Abstract Only few studies have focus on animals that received Pilocarpine (Pilo) and did not develop behavioral status epilepticus (SE) and, whether they may become epileptic in the model's chronic phase. Previews works observed mossy fiber sprouting in the hippocampus of Non-SE (NSE) rats, while others observed spontaneous and recurrent seizures (SRS) 6 - 8 months after animals received Pilo. It is known that neuronal excitability is influenced by female hormones, as well as, the occurrence of SE in castrated and non-castrated female rats. However, it is not known whether females that received Pilo and did not show SE, may have SRS. The aim of this work was to investigate whether castrated and non-castrated female rats that did not show behavioral SE after Pilo, will develop SRS in the following one-year. For that, animals received 360 mg/kg of Pilo and were video monitored for 12 months. SE females from castrated and non-castrated groups became epileptic since the first month after drug injection. Epileptic behaviors were identified watching video monitoring recordings in the fast speed. Castrated and Non-castrated NSE animals showed behaviors resembling seizures described by Racine Scale stages 1 - 3. Motor alterations showed by NSE groups could be observed only when recordings were analyzed in slow speed. In addition, behavioral manifestations as, rhythmic head movements, sudden head movements, whole body movements and immobility were also observed in both, SE and NSE groups. We concluded that NSE female rats may have become epileptic. Adding to it, slow speed analysis of motor alterations was essential for the observation of NSE findings, which suggests that possibly many motor alterations have been underestimated in epilepsy experimental research.

Resumo Poucos são os estudos com foco em animais que receberam Pilocarpina (Pilo) e não desenvolveram status epilepticus (SE) comportamental e, se os mesmos se tornarão epilépticos na fase crônica do modelo. Autores observaram o brotamento das fibras musgosas no hipocampo de ratos Não-SE (NSE), enquanto outros observaram crises espontâneas e recorrentes (CER) 6 - 8 meses após receberam a droga. A excitabilidade neuronal é influenciada pelos hormônios femininos e, da mesma forma, a ocorrência de SE em ratas castradas e não-castradas. Entretanto, não é sabido se as fêmeas que não apresentam SE terão CER. O objetivo deste trabalho foi investigar se fêmeas castradas e não castradas que não tiveram SE comportamental após a injeção de Pilo desenvolverão CER dentro de um ano. Para isto, os animais receberam 360 mg/kg de Pilo e foram videomonitorados por 12 meses. As fêmeas SE castradas e não-castradas se tornaram epilépticas desde o primeiro mês pós Pilo. O comportamento epiléptico foi identificado assistindo as gravações na velocidade rápida. As fêmeas NSE castradas e não-castradas apresentaram comportamentos similares aos estágios 1 - 3 da Escala de Racine. As alterações motoras nestes grupos (NSE) foram observadas apenas quando as videomonitoração foi analisada na velocidade lenta. Além destas, manifestações comportamentais como movimentos rítmicos da cabeça, movimentos súbitos da cabeça, movimentos de todo o corpo e imobilidade também foram observadas em ambos grupos, SE e NSE. Concluímos que as fêmeas NE podem ter se tornado epilépticas. Adicionado a isto, a análise das alterações motoras na velocidade lenta foi essencial para a observação dos achados das fêmeas NSE, o que sugere que possivelmente muitas alterações motoras têm sido subestimados na pesquisa em epilepsia experimental.

Xiangsha Liu Junzitang for Prevention and Treatment of Gastric Cancer： A Review / 中国实验方剂学杂志

Gastric cancer is one of the malignancies with high incidence in the world. Xiangsha Liu Junzitang，a common prescription for the prevention and treatment of gastric cancer，has the effects of moving Qi to relieve pain，drying dampness， and invigorating the spleen. It is especially indicated for gastric cancer of the spleen and stomach qi deficiency syndrome. Based on the databases such as CNKI，Wanfang Data，and PubMed，the clinical efficacy and experimental studies of Xiangsha Liu Junzitang for the prevention and treatment of gastric cancer were summarized and sorted out，and the mechanism of Xiangsha Liu Junzitang for the prevention and treatment of gastric cancer was elaborated in order to provide useful references for the clinical and basic research on Xiangsha Liu Junzitang in the field of gastric cancer in the future. In clinical practice，Xiangsha Liu Junzitang can treat gastric precancerous lesions，increase the body immunity of patients with gastric cancer，improve the symptoms of spleen and stomach weakness after gastric cancer surgery，and reduce the adverse reactions of the digestive tract after chemotherapy for gastric cancer. Its clinical efficacy is superior to that of western medicine alone whether it is combined with western medicine or used alone. In the experimental research，Xiangsha Liu Junzitang has the effects of regulating inflammatory factors，inhibiting the proliferation of gastric cancer cells，promoting the apoptosis of gastric cancer cells，and improving the activity of pepsin. Modern pharmacological research has shown that Xiangsha Liu Junzitang can conduct a comprehensive intervention with multiple components and multiple targets. The main components of a single drug contained include saponins，polysaccharides，lactones，volatile oils，organic acids，and others， with the effects of protecting gastric mucosa，regulating endocrine，and promoting apoptosis of epithelial cells in gastric mucosal dysplasia，reflecting the advantages and values of traditional Chinese medicine in the prevention and treatment of gastric cancer.

Effectiveness of dyadic intervention on discharge readiness of elderly stroke patients and family caregivers / 中国实用护理杂志

Objective:To explore the application effect of dyadic intervention scheme based on dyadic disease management theory and Information, Knowledge, Attitude, and Practice model in the discharge preparation of elderly stroke patients and family caregivers.Methods:The 92 pairs of elderly stroke patients and their caregivers hospitalized in the Department of Neurology in People′s Hospital of Zhengzhou University were conveniently selected. The non synchronous control method quasi experimental research was adopted. Totally 46 pairs of subjects who met the criteria for admission and discharge from May to July 2022 were set as the control group, and routine nursing was carried out; from August to October 2022, 46 pairs of subjects who met the criteria for admission and emission were set as the observation group to implement the dyadic intervention program. The scores of discharge readiness, self-efficacy and unplanned readmission rate of patients between the two groups were compared, and the scores of caregiver readiness, self-efficacy and caregiver stress between the two groups were compared.Results:Finally, 85 pairs of subjects completed the study, with 42 pairs in the control group and 43 pairs in the observation group. On discharge day, the total scores of discharge readiness and caregiver readiness in the observation group were (95.19 ± 4.47), (23.02 ± 2.20) points, respectively, which were higher than those in the control group (85.71 ± 5.31), (19.57 ± 1.65) points, with statistically significant differences ( t=8.91,8.16, both P<0.01); the self-efficacy levels of patients in the observation group at discharge and one month after discharge, as well as those of caregivers at discharge and one month after discharge were (73.86 ± 4.87), (75.91 ± 4.51), (75.67 ± 4.99), (79.21 ± 4.90) points, respectively, higher than those in the control group (71.62 ± 5.19), (73.33 ± 4.91), (73.48 ± 4.24), (75.48 ± 4.24) points, with statistically significant differences ( t values were from 2.05 to 3.75, all P<0.05); the pressure levels of caregivers in the observation group at discharge and one month after discharge were (7.51 ± 2.48), (6.28 ± 1.99) points, respectively, lower than those in the control group (8.76 ± 2.55), (7.45 ± 2.36) points, with statistically significant differences ( t=-2.29, -2.48, both P<0.05); the unplanned readmission rate of patients in the observation group one month after discharge was 7.0% (3/43), lower than the control group′s 23.8% (10/42), with statistically significant difference ( χ2=4.65, P<0.05). Conclusions:The implementation of dyadic intervention on elderly stroke patients and caregivers can make their discharge preparation process more adequate, thus reducing the caregiver′s care pressure, reducing the unplanned readmission rate of patients, and improving their health outcomes.

Network pharmacological mechanism and experimental validation of Yinjiushu in the treatment of non-alcoholic fatty liver disease based on the homology of medicine and food / 国际中医中药杂志

Objective:To the molecular mechanism of Yinjiushu in the treatment of non-alcoholic fatty liver disease (NAFLD) by network pharmacology based on the theory of homology of medicine and food; To conduct experimental verification.Methods:The active components and targets of the Yinjiushu were screened through the TCMSP platform. Cytoscape 3.7.2 was used to construct the "Chinese materia medica-component-target" network of Yinjiushu. The potential targets of NAFLD were obtained by using TTD, GeneCards database and DisGeNET database, and the intersection targets of Yinjiushu and NAFLD were obtained by mapping targets with Venn diagram. The high confidence interaction relationship of intersection targets was obtained in STRING database, and the core targets of Yinjiushu in treating NAFLD were screened out. GO function and KEGG pathway enrichment of common targets were analyzed by David database, and the above results were further verified by animal experiments. The rats were divided into blank group, model group, Western medicine group and Yinjiushu high-, medium- and low-dosage groups according to random number table method, with 8 rats in each group. Except the blank group, rats in other groups were fed with high-fat diet to prepare NAFLD model. Each group was given corresponding drugs for intervention. The rats were weighed regularly. The serum contents of GPT, GOT, TC, TG, IL-6, TNF-α, MPO of rats were detected by ELISA. The liver index was calculated. The degree of fatty degeneration of hepatocytes was observed by HE. The expressions of CAT, NOS3, SOD, PI3K, p-Akt, Akt protein were detected by Western blot.Results:A total of 8 418 NAFLD-related targets, 118 kinds of active components from Yinjiushu, and 137 targets acting on NAFLD were screened. The core targets included IL-6, TNF, VEGFA, TP53, JUN, CAT, NOS3, SOD, etc. 20 related signaling pathways were screened from KEGG enrichment pathway, among which PI3K/Akt pathway, calcium ion pathway, cAMP pathway and TNF pathway may play key roles in the treatment. Yinjiushu was closely related to inflammatory reaction, oxidative stress, angiogenesis, autophagy, cell proliferation, differentiation, metabolism, apoptosis, etc., or it could treat NAFLD by promoting cell apoptosis, inhibiting cell proliferation, inhibiting cell migration, etc. The animal experiment proved that Yinjiushu could reduce the body weight, wet liver weight and liver-body ratio of NAFLD rats, reduce some liver function and blood lipid indexes (GPT, GOT, TG, TC), down-regulate serum IL-6, TNF-α and MPO, up-regulate the expression of CAT, NOS3 and SOD in hepatocytes, and activate the expression of PI3K/Akt key protein.Conclusion:Yinjiushu can play a role in treating NAFLD by inhibiting the release of inflammatory mediators, improving lipid metabolism disorder of hepatocytes, repairing oxidative stress injury and promoting the recovery of liver function.

Study on the anti-inflammatory and analgesic pharmacodynamics of Zhonghua Dida Pill and its effect on inflammation in arthritis model rats / 国际中医中药杂志

Objective:To investigate the anti-inflammatory and analgesic effects of Zhonghua Dieda Pills; To preliminarily explore its mechanism on adjuvant arthritis model rats.Methods:Three inflammatory models and two pain models were used to investigate the anti-inflammatory and analgesic effects of Zhonghua Dieda Pills. After establishing the adjuvant arthritis rat model, the rats were divided into normal group, model group, dexamethasone group (0.8 mg/kg), and Zhonghua Dieda Pills (2.0, 1.0, 0.5 g/kg) groups according to random number table method. Each group was given corresponding drugs once a day for 5 weeks. The toe volume was measured at 1, 3 and 5 weeks after administration, and the swelling degree was calculated; the organ indices of rats were calculated and the histopathological changes of articular cartilage were observed by HE staining; the expressions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in joint tissues were detected by immunohistochemistry.Results:Zhonghua Dieda Pills (2.0 g/kg) group significantly reduced the swelling of foot and plantar of rats, reduced the swelling of ear of mice, and reduced the dry weight of granuloma of rats ( P<0.05); Zhonghua Dieda Pills (1.4 g/kg) group significantly reduced the number of twisting of rats, and the pain threshold after 3 h of administration was significantly higher than that of the control group ( P<0.05); Zhonghua Dieda Pills (2.0 g/kg) group significantly reduced the swelling of the foot and metatarsal of arthritic rats after 3-5 weeks of administration ( P<0.05), decreased the thymus index ( P<0.05), and reduced the expression levels of IL-1β, TNF-α and TGF-β in joint tissues ( P<0.05). Conclusion:Zhonghua Dieda Pills have confirmed anti-inflammatory and analgesic effects, which may play a therapeutic role in adjuvant arthritis model rats by reducing the levels of inflammatory factors such as IL-1β, TNF-α and TGF-β.

Research progress in treatment of post-stroke depression with Bushen Shugan method / 国际中医中药杂志

Traditional Chinese Medicine (TCM) has its own unique features in the treatment of post-stroke depression (PSD). The kidney is the congenital foundation and is closely related to the brain. Kidney deficiency runs through the entire course of stroke. Liver regulates the normal operation of qi in the human body, which is closely related to depression syndrome. Kidney deficiency and liver depression affect each other. The treatment of PSD with the Bushen Shugan (tonifying the kidney and soothing the liver) method has achieved good efficacy in clinic. The method of tonifying kidney and soothing liver can not only reflect the holistic view of TCM and the association of viscera, but also coordinate the relationship between body and spirit. In the future, the development direction of PSD in TCM research should be to further strengthen the concept of co-regulation of body and spirit and integration of brain and viscera.

Discussion on mechanism and experimental validation of Bupiwei Xieyinhuo Shengyang Prescription in treatment of gastroesophageal reflux disease based on network pharmacology / 国际中医中药杂志

Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.

Network pharmacology and validation by experiment of Shuerjing Capsule in the treatment of primary dysmenorrhea / 国际中医中药杂志

Objective:To explore the mechanism of Shuerjing Capsule in treating primary dysmenorrhea based on molecular docking of network pharmacology and in vivo experiment.Methods:By using TCMSP to screen the active components and targets of Shuerjing Capsule; by using GeneCards and DrungBank databases to retrieve targeted proteins of primary dysmenorrhea, and the intersection targets of drugs and diseases were obtained through Weishengxin online platform; by using Cytoscape 3.9.1 software to produce component-target network of Shuerjing Capsule for the treatment of primary dysmenorrhea; by STRING databases to construct drug-disease target PPI network; by DAVID database to perform GO and KEGG pathway enrichment analysis.The key active components of the drug and the core targets of the disease were obtained with molecular docking. The rats were randomly divided into control group, model group, the low-dose group, medium-dose group and high-dose group of Shujing Capsule (0.15, 0.21, 0.42 g/kg), and ibuprofen group (20 mg/kg), with 10 rats in each group. The animal model of primary dysmenorrhea was established by subcutaneous injection of estradiol benzoate and intervented by drugs. The number of writhing reaction, uterine contractile inhibition rate and uterine index of rats were observed. The expressions of TNF-α, IL-6 and IL-1 in serum and the levels of PTGS2 and VEGFA in uterine tissue were detected by ELISA.Results:A total of 188 active ingredients of Shuerjing Capsule were screened, and 51 targets of Shuerjing Capsule and primary dysmenorrhea were identified. TNF, IL-6, AKT1 and TP53 may be the key targets of Shuerjing Capsule in the treatment of primary dysmenorrhea. A total of 519 GO biological processes and 119 related signaling pathways were obtained, among which estrogen, IL-17, HIF-1 and other signaling pathways were closely related to the treatment of primary dysmenorrhea. The results of molecular docking were good, among which stigmasterol had the strongest binding ability to TP53. The experimental results showed that compared with the model group, the uterine index and the number of torsion were decreased in the low -, medium - and high-dose Shuojing Capsule groups ( P<0.05), the uterine contraction inhibition rate increased ( P<0.05); Serum levels of TNF-α, IL-6 and IL-1 of medium and high dose group decreased ( P<0.05), the levels of PTGS2 and VEGFA in uterine tissues decreased ( P<0.05). Conclusion:Shuerjing Capsule has the effect of anti-inflammatation and improveing hypoxia, which may be related to the inhibition of TNF-α, IL-6 and IL-1 inflammatory factors in serum and the expression of PTGS2 and VEGFA proteins in uterine tissues.

Mechanism of Tripterygium wilfordii in treating renal cell carcinoma using network pharmacology / 国际生物医学工程杂志

Objective:To explore the mechanism of Tripterygium wilfordii in treating renal cell carcinoma using network pharmacology and experimental validation. Methods:The traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform was utilized to screen the active ingredients of T. wilfordii and predict the targets using the Swiss database. Renal cell carcinoma related targets were collected from DisGeNET, GeneCards, and OMIM databases, and intersecting targets were obtained through Venny 2.1.0. Protein-protein interaction (PPI) networks were mapped using the STRING database and Cytoscape software, and gene ontology (GO) and kyoto encyclopedia of genes and genomics (KEGG) enrichment analyses were performed. Component-target-pathway networks were constructed using Cytoscape software. To induce the subcutaneous transplantation tumor model of renal cell carcinoma, nude mice were randomly divided into a control group and a treatment group, with 5 mice in each group. In the treatment group, mice were gastrically instilled with 615 mg/ml of T. wilfordii solution (1 845 mg T. wilfordii granules dissolved into 3 ml water) 2.46 g/kg, 10 μl/time, once daily for 21 d. In the control group, mice were gastrically instilled with an equal amount of saline. Tumor volume was measured once every 5 days, and the expression of serine/threonine protein kinase 1 (AKT1), signal transduction and transcription activator 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), JUN, mitogen-activated protein kinase 8 (MAPK8), and MAPK14 was detected by enzyme-linked immunoassay. Results:Twenty-eight active pharmaceutical ingredients and 117 potential targets of T. wilfordii were screened; 13 425 related disease targets were identified; and finally, 113 drug-disease intersecting targets were obtained. In the PPI network, AKT1, STAT3, TNF, TP53, JUN, MAPK8, and MAPK14 were the core targets. GO analysis showed that BP mainly included nuclear receptor activity, ligand-activated transcription factor activity, RNA polymerase-specific DNA-binding transcription factor binding, nuclear steroid receptor activity, and adrenergic receptor activity, etc. CC mainly included the response to hormones, the cellular response to lipids, the positive regulation of cell migration, the response to TNF, the inflammatory response, the cellular response to hormonal stimulation, the response to hypoxia, the response to metal ions, etc. MF involves membrane rafts, membrane microregions, the outer side of the plasma membrane, the lateral side of the membrane, plasma membrane rafts, presynaptic membranes, vesicles, transcriptional regulatory complexes, post-synaptic membranes, synaptic membranes, etc. KEGG analysis showed that T. wilfordii treatment of RCC involves signaling pathways such as lipid and atherosclerosis, advanced glycosylation end product-receptor for advanced glycosylation end products (AGE-RAGE), TNF, Toll-like receptor, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and MAPK. The experimental validation results showed that the tumor volume was reduced after treatment with tretinoin ( P < 0.05), the expression of TP53 protein was increased ( P < 0.001), and the expression of AKT1, STAT3, TNF, JUN, MAPK8, and MAPK14 proteins were all reduced (all P < 0.001). Conclusions:In this study, the target and signaling pathways of T. wilfordii treatment of renal cell carcinoma were initially predicted, providing a reference basis for further research on its protective mechanism and clinical application.

Mechanism of action of Coptis chinensis in the treatment of dental caries based on network pharmacology and experimental validation / 国际生物医学工程杂志

Objective:To explore the mechanism of action of Coptis chinensis in the treatment of dental caries using a network pharmacology approach and animal experiments. Methods:The active ingredients of C. chinensis and their targets were screened by the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform, and the targets were searched online through the GeneCards database. The intersecting targets of C. chinensis and dental caries were screened at Venny 2.1, and the intersection targets were analyzed online for protein-protein interaction analysis and gene ontology (GO) and kyoto encyclopedia of genes and genomics (KEGG) enrichment. Then, Cytoscape was used to create a "component-target-pathway" network diagram. Rats were randomly divided into the model group and the C. chinensis group to establish a rat model of dental caries. Rats in the model group were repeatedly rubbed with a cotton ball soaked in 150 μl of 0.9% NaCl solution for 5 min, and rats in the C. chinensis group were repeatedly rubbed with a cotton ball soaked in C. chinensis (5.8 mg of C. chinensis in 150 μl of 0.9% NaCl solution) for 5 min. The two groups of rats were treated once a week for four consecutive weeks. The number of Streptococcus mutans colonies was counted, and serum serine/threonine protein kinase 1 (AKT1), JUN, interleukin-6 (IL-6), tumor necrosis factor (TNF), and B-cell lymphoma-2 (Bcl-2) were detected by enzyme immunoassay. Results:A total of 11 active ingredients in C. chinensis were found, which regulate multiple molecular pathways by intervening in 54 targets, thereby treating dental caries. Quercetin, berberine, flavodoxin, berberine infusion, and tetrahydroberberine were the core components, and AKT1, JUN, IL-6, TNF, and Bcl-2 were the core targets. GO analysis showed that BP mainly included cytokine activity, signaling receptor activator activity, signaling receptor modulator activity, cytokine receptor binding, and receptor ligand activity, etc.; and CC mainly included the response to lipopolysaccharides, the response to bacterial molecules, cellular responses to lipids, inflammatory responses, and negative regulation of cell population proliferation; MF mainly includes membrane rafts, membrane microregions, extracellular matrix, external encapsulated structures, and plasma membrane protein complexes, etc. KEGG analysis showed that advanced glycosylation end product-receptor for advanced glycosylation end products (AGE-RAGE), TNF, IL-17, Toll-like receptor, hypoxia-inducible factor-1 (HIF-1), mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), epidermal growth factor receptor (EGFR), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathways have been associated with C. chinensis treatment. The results of animal experiments showed that serum Bcl-2 protein expression increased and serum AKT1, JUN, IL-6, TNF, and other proteins decreased after the C. chinensis treatment. Conclusions:C. chinensis can be involved in regulating the targets of dental caries through multiple pathways, with good therapeutic effects and a wide range of mechanisms of action, and is expected to be an important component in the development of proprietary Chinese medicines for the treatment of dental caries.

Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of Tripterygium wilfordii polyglycoside tablets （TWPT） in the prevention and treatment of kidney injury in diabetic nephropathy （DN） through the nuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathway. MethodForty-two male SD rats of SPF grade were selected and randomly divided into a normal group （n=8） and an experimental group （n=34） after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin （STZ） following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated， the remaining 24 model rats were randomly divided into model group， valsartan （8.33 mg·kg-1·d-1） group， and TWPT （5 mg·kg-1·d-1） group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks， body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta， and then the rats were sacrificed for sampling. Biochemical indicators， such as serum blood urea nitrogen （BUN）， serum creatinine （SCr）， alanine aminotransferase （ALT）， blood lipid， blood glucose， and 24-hour urine total protein （24 h UTP）， were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay （ELISA） was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were adopted to detect NFAT2， COX-2 protein and mRNA expression in kidney tissues， respectively. ResultCompared with the normal group， the model group showed elevated 24 h UTP， BUN， SCr， CHO， TG， and FBG， increased serum NFAT2 and COX-2 production and expression （P<0.01）， and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. In addition， the pathology of the kidney showed enlarged glomeruli， mild proliferation of mesangial cells， and widened mesangial stroma. Compared with the model group， the TWPT group showed decreased 24 h UTP， BUN， SCr， CHO， TG， and FBG （P<0.05，P<0.01）， basically normal glomerular morphology， decreased expression of serum NFAT2 and COX-2 （P<0.01）， and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （P<0.01）. ConclusionTWPT can alleviate 24 h UTP in DN model rats， protect renal function， and improve renal pathology， and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To explore the specific pharmacological molecular mechanisms of Kai Xin San (KXS) on treating Alzheimer's disease (AD) based on network pharmacology and experimental validation.@*METHODS@#The chemical compounds of KXS and their corresponding targets were screened using the Encyclopedia of Traditional Chinese Medicine (ETCM) database. AD-related target proteins were obtained from MalaCards database and DisGeNET databases. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis. Functional enrichment analysis predicted the potential key signaling pathways involved in the treatment of AD with KXS. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, the predicted key signaling pathway was validated experimentally. Positioning navigation and space search experiments were conducted to evaluate the cognitive improvement effect of KXS on AD rats. Western blot was used to further examine and investigate the expression of the key target proteins related to the predicted pathway.@*RESULTS@#In total, 38 active compounds and 469 corresponding targets of KXS were screened, and 264 target proteins associated with AD were identified. The compound-target-disease and PPI networks identified key active ingredients and protein targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested a potential effect of KXS in the treatment of AD via the amyloid beta (A β)-glycogen synthase kinase-3 beta (GSK3 β)-Tau pathway. Molecular docking revealed a high binding affinity between the key ingredients and targets. In vivo, KXS treatment significantly improved cognitive deficits in AD rats induced by Aβ1-42, decreased the levels of Aβ, p-GSK3β, p-Tau and cyclin-dependent kinase 5, and increased the expressions of protein phosphatase 1 alpha (PP1A) and PP2A (P<0.05 or P<0.01).@*CONCLUSION@#KXS exerted neuroprotective effects by regulating the Aβ -GSK3β-Tau signaling pathway, which provides novel insights into the therapeutic mechanism of KXS and a feasible pharmacological strategy for the treatment of AD.