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1.
Acta Pharmaceutica Sinica ; (12): 359-367, 2024.
Article in Chinese | WPRIM | ID: wpr-1016652

ABSTRACT

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

2.
Journal of Clinical Hepatology ; (12): 804-809, 2024.
Article in Chinese | WPRIM | ID: wpr-1016528

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease associated with obesity, insulin resistance, and dyslipidemia and has a complex pathogenesis. Studies have shown that gut microbiota dysbiosis is closely associated with the onset of NAFLD, and traditional Chinese medicine treatment can improve the laboratory markers and clinical symptoms of NAFLD patients by regulating intestinal microbiota and its metabolites. This article elaborates on the association between NAFLD and gut microbiota, the involvement of gut microbiota dysbiosis in the pathogenesis of NAFLD, and the possible mechanism of traditional Chinese medicine treatment in improving NAFLD from the perspective of gut microbiota, in order to provide new ideas for the treatment of NAFLD.

3.
Acta Pharmaceutica Sinica ; (12): 105-118, 2024.
Article in Chinese | WPRIM | ID: wpr-1005446

ABSTRACT

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

4.
Rev. bras. med. esporte ; 29: e2022_0338, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1407593

ABSTRACT

ABSTRACT Introduction: In competitive basketball sports, athletes must repeatedly perform movements of maximum intensity quickly, followed by rest. A training mode called high-intensity interval training (HIIT) has the same characteristics. Objective: Explore basketball players' energy supply characteristics and training changes under different exercise intensities. Methods: The effects of different recovery methods in the intermittent period on exercise capacity and aerobic metabolic energy supply of young male basketball players during high-intensity intermittent interval training (HIIT) were presented. Results: Increased aerobic energy production during HIIT was closely related to the acceleration of kinetics. However, although the time to exhaustion, a parameter characterizing exercise capacity, increased by 3.5% and 4.6%, respectively, in the HIITa group compared to HIITs and HIITp, there was no significant difference. After analyzing each group for the 30s, a gradual increase in strength was noticed. Conclusion: The use of HIIT as training is an important way to improve the physical performance of athletes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução: Na competição esportiva do basquete, os atletas precisam realizar repetidamente movimentos de intensidade máxima rapidamente, seguidos de repouso. Há um modo de treinamento chamado de treinamento de intervalo de alta intensidade (HIIT) que possui as mesmas características. Objetivo: Explorar as características de consumo de energia e as mudanças de treinamento dos jogadores de basquetebol sob diferentes intensidades de exercício. Métodos: Foram apresentados os efeitos de diferentes métodos de recuperação em período intermitente sobre a capacidade de exercício e fornecimento de energia metabólica aeróbica de jovens jogadores masculinos de basquetebol durante o treinamento intermitente de alta intensidade (HIIT). Resultados: O aumento da produção de energia aeróbica durante o HIIT foi estreitamente relacionado com a aceleração da cinética. Entretanto, embora o tempo de exaustão, parâmetro que caracteriza a capacidade de exercício, tenha aumentado em 3,5% e 4,6% respectivamente no grupo de HIITa em comparação com HIITs e HIITp, não houve diferença significativa. Depois de analisar cada grupo durante 30s, percebeu-se um aumento gradual da força. Conclusão: O uso do HIIT como treinamento demonstrou-se um meio importante para melhorar o desempenho físico dos atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción: En los deportes de baloncesto de competición, los atletas necesitan realizar repetidamente movimientos de máxima intensidad de forma rápida, seguidos de descanso. Existe una modalidad de entrenamiento llamada entrenamiento por intervalos de alta intensidad (HIIT) que tiene las mismas características. Objetivo: Explorar las características del suministro de energía y los cambios en el entrenamiento de los jugadores de baloncesto bajo diferentes intensidades de ejercicio. Métodos: Se presentaron los efectos de diferentes métodos de recuperación en período intermitente sobre la capacidad de ejercicio y el suministro de energía metabólica aeróbica de jóvenes jugadores de baloncesto durante el entrenamiento de intervalos intermitentes de alta intensidad (HIIT). Resultados: El aumento de la producción de energía aeróbica durante el HIIT estaba estrechamente relacionado con la aceleración de la cinética. Sin embargo, aunque el tiempo hasta el agotamiento, un parámetro que caracteriza la capacidad de ejercicio, aumentó un 3,5% y un 4,6% respectivamente en el grupo HIITa en comparación con los HIIT y HIITp, no hubo diferencias significativas. Tras analizar cada grupo durante 30 segundos, se percibió un aumento gradual de la fuerza. Conclusión: El uso del HIIT como entrenamiento ha demostrado ser una forma importante de mejorar el rendimiento físico de los atletas. Nivel de evidencia II;Estudios terapéuticos - investigación de los resultados del tratamiento.

5.
Rev. bras. med. esporte ; 29: e2022_0342, 2023. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1407582

ABSTRACT

ABSTRACT Introduction: Endurance is a quality that has been lacking in Chinese athletes. In most endurance sports training in China, there is a problem with attaching importance to high-intensity anaerobic training and ignoring aerobic training. The close combination of aerobic, strength and technical training is endurance training. A significant development trend in training. Objective: This study analyzes the relationship between aerobic training and physical endurance in basketball players. Methods: Basketball players were selected and randomly divided into groups through the analysis method with a questionnaire, observation method, and experimental method to analyze the relationship between aerobic exercise and physical endurance in basketball players. In this paper, the changes in physiological indicators of basketball players were recorded after aerobic exercise. Results: The physical endurance of basketball players were positively correlated with aerobic training time. The physiological indicators of basketball players and basketball skills after aerobic training were significantly improved (P<0.05). Conclusion: Aerobic exercise can improve basketball players' physical endurance and overall physical fitness, helping them achieve good results in competitions. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução: Resistência é uma qualidade que tem faltado aos atletas chineses. Na maioria dos treinos esportivos de resistência na China, há um problema para atribuir importância ao treino anaeróbico de alta intensidade e ignorar o treinamento aeróbico. A combinação próxima de treinamento aeróbico e força e treinamento técnico é o treinamento de resistência. Uma tendência de desenvolvimento significativa na formação. Objetivo: Este estudo tem como objetivo analisar a relação entre treinamento aeróbico e resistência física em praticantes do basquete. Métodos: Jogadores de basquete foram selecionados e aleatoriamente divididos entre grupos passando pelo método de análise com questionário, método de observação e método experimental para analisar a relação entre exercício aeróbico e resistência física dos jogadores de basquete. Neste artigo, as alterações dos indicadores fisiológicos dos jogadores de basquete foram registradas após exercício aeróbico. Resultados: A resistência física dos jogadores de basquete foi positivamente correlacionada com o tempo de treinamento aeróbico. Os indicadores fisiológicos dos jogadores de basquete e as habilidades de basquete após o treinamento aeróbico foram significativamente melhorados (P<0,05). Conclusão: O exercício aeróbico não só pode melhorar a resistência física dos jogadores de basquete como também sua aptidão física geral, ajudando-os a alcançarem bons resultados nas competições. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción: La resistencia es una cualidad de la que carecen los atletas chinos. En la mayoría de los entrenamientos de deportes de resistencia en China, existe el problema de dar importancia al entrenamiento anaeróbico de alta intensidad e ignorar el entrenamiento aeróbico. La estrecha combinación del entrenamiento aeróbico y el entrenamiento de fuerza y técnico es el entrenamiento de resistencia. Una tendencia de desarrollo importante en la formación. Objetivo: Este estudio pretende analizar la relación entre el entrenamiento aeróbico y la resistencia física en jugadores de baloncesto. Métodos: Se seleccionaron jugadores de baloncesto y se dividieron aleatoriamente entre grupos pasando por el método de análisis con cuestionario, método de observación y método experimental para analizar la relación entre el ejercicio aeróbico y la resistencia física en jugadores de baloncesto. En este trabajo se registraron los cambios de los indicadores fisiológicos de los jugadores de baloncesto después del ejercicio aeróbico. Resultados: La resistencia física de los jugadores de baloncesto se correlacionó positivamente con el tiempo de entrenamiento aeróbico. Los indicadores fisiológicos de los jugadores de baloncesto y las habilidades de baloncesto después del entrenamiento aeróbico mejoraron significativamente (P<0,05). Conclusión: El ejercicio aeróbico no sólo puede mejorar la resistencia física de los jugadores de baloncesto, sino también su estado físico general, ayudándoles a conseguir buenos resultados en las competiciones. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

6.
Acta Pharmaceutica Sinica ; (12): 3339-3348, 2023.
Article in Chinese | WPRIM | ID: wpr-999079

ABSTRACT

Isoliquiritigenin (ISL) is a flavonoid compound isolated from licorice. It possesses excellent antioxidant and anti-diabetic activities. This study aims to investigate the molecular mechanism underlying the alleviatory effect of ISL on energy metabolism imbalance caused by type 2 diabetes mellitus (T2DM). 8-week-old male C57BL/6J mice were used in in vivo experiments. The high-fat-high-glucose diet combined with intraperitoneal injection of streptozotocin was applied to establish T2DM animal model. All animal experiments were performed in accordance with the Institutional Guidelines of Laboratory Animal Administration issued by the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to examine the protein and mRNA levels of mitochondrial function-related targets. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in HepG2 cells were measured by the flow cytometry. Additionally, the molecular docking of ISL and key target proteins was analyzed. It was found that ISL significantly inhibited the activity of mitochondrial respiratory chain complex I and increased the protein levels of uncoupling protein 2 (UCP2) in the livers of mice and HepG2 cells. It also obviously decreased the ROS levels and increased the MMP levels in cultured HepG2 cells. In addition, ISL promoted mitochondrial biogenesis by activating proliferator-activated receptor gamma co-activator 1α (PGC-1α) and enhanced mitophagy by upregulating Parkin. It also improved mitochondrial fusion by increasing the mRNA and protein levels of mitofusin 2 (MFN2). In conclusion, ISL alleviates energy metabolism imbalance caused by T2DM through suppression of excessive mitochondrial oxidative phosphorylation and promotion of mitochondrial biogenesis, mitophagy, and fusion.

7.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 31-41, 2023.
Article in Chinese | WPRIM | ID: wpr-976537

ABSTRACT

Xiaoruwan is one of the classic prescriptions included in the Catalogue of Ancient Classic Prescriptions (the Second Batch of Pediatrics) published by the National Administration of Traditional Chinese Medicine(TCM) in 2022 with definite clinical efficacy, but it has not been converted into Chinese patent medicine preparations. The authors collected 173 pieces of data based on ancient literature on Xiaoruwan by the method of bibliometrics and selected 99 pieces of effective data, involving 46 ancient books of TCM. The study analyzed the historical development origin, prescription names, formulation rules, dosage, drug origin, preparation method and usage, indications and functions, and other aspects of Xiaoruwan. The results showed that Xiaoruwan was presumably derived from Ying Hai Miao Jue Lun(《婴孩妙诀论》) written by TANG Minwang, a doctor in the Song Dynasty. In the records of ancient medical books, there are names such as Xiaoshiwan,Yangshi Xiaoruwan, and Kuaige Xiaoshiwan, but they are mainly recorded in the name of Xiaoruwan. The prescription was composed of Cyperi Rhizoma, Amomi Fructus, Citri Reticulatae Pericarpium, Massa Medicata Fermentata, Hordei Fructus Germinatus, and Glycyrrhizae Radix et Rhizoma. In terms of processing method, Cyperi Rhizoma, Massa Medicata Fermentata, and Hordei Fructus Germinatus are fried, Glycyrrhizae Radix et Rhizoma is processed, and raw materials of Amomi Fructus and Citri Reticulatae Pericarpium are used directly. In terms of function, it is effective in warming the middle, improving digestion, stopping vomiting, and digesting milk and food. The main indications include vomiting, diarrhea, night crying, and other diseases caused by milk and food stagnation. The dosage of the most used prescription in the records of ancient books is Cyperi Rhizoma 41.30 g, Amomi Fructus 20.65 g, Citri Reticulatae Pericarpium 20.65 g, Massa Medicata Fermentata 20.65 g, Hordei Fructus Germinatus 20.65 g, and Glycyrrhizae Radix et Rhizoma 20.65 g, which are prepared into pills. In the taking method, it is recommended to take it with warm boiled water or ginger soup after meals. The study summarized the historical evolution of Xiaoruwan and identified the key information, with a view to providing a reference for the modern development and research of Xiaoruwan.

8.
Journal of Peking University(Health Sciences) ; (6): 543-547, 2023.
Article in Chinese | WPRIM | ID: wpr-986887

ABSTRACT

OBJECTIVE@#To analyze the composition, incidence and clinical characteristics of oral and maxillofacial infections in oral emergency.@*METHODS@#A retrospective study on patients with oral and maxillofacial infections who visited the Department of Oral Emergency in Peking University School and Hospital of Stomatology from January 2017 to December 2019 was conducted. General characteristics, such as disease composition, gender, age distribution and position of involved teeth were analyzed.@*RESULTS@#A total of 8 277 patients with oral and maxillofacial infections were finally collected, including 4 378 male patients (52.9%) and 3 899 female patients (47.1%), with gender ratio of 1.12:1. The common diseases were periodontal abscess (3 826 cases, 46.2%), alveolar abscess (3 537 cases, 42.7%), maxillofacial space infection (740 cases, 9.0%), sialadenitis (108 cases, 1.3%), furuncle & carbuncle (56 cases, 0.7%) and osteomyelitis (10 cases, 0.1%). Male patients were more easily affected by periodontal abscess, space infection and furuncle & carbuncle than female patients with the gender ratios 1.24:1, 1.26:1, 2.50:1 individually, while the incidence of alveolar abscess, sialadenitis, furuncle & carbuncle had no significant gender difference. Different diseases were prone to occur at different ages. The peak ages of alveolar abscess were 5-9 and 27-67 years, while the peak age of periodontal abscess was 30-64 years. Space infection tended to occur between 21-67 years. There were 7 363 patients with oral abscess (3 826 patients with periodontal abscess and 3 537 patients with alveolar abscess), accounting for 88.9% of all the patients with oral and maxillofacial infections, involving 7 999 teeth, including 717 deciduous teeth and 7 282 permanent teeth. Periodontal abscess usually occurred in permanent teeth, especially the molar teeth. Alveolar abscess may occur in both primary teeth and permanent teeth. In primary teeth, the most vulnerable sites were primary molar teeth and maxillary central incisors while in permanent teeth the most vulnerable sites were first molar teeth.@*CONCLUSION@#Understanding the incidence of oral and maxillofacial infection was conducive to the correct diagnosis and effective treatment of clinical diseases, as well as targeted education for patients of different ages and genders to prevent the occurrence of diseases.


Subject(s)
Humans , Male , Female , Animals , Adult , Middle Aged , Abscess , Retrospective Studies , Periodontal Abscess , Carbuncle , Furunculosis , Incisor , Sialadenitis/epidemiology
9.
China Pharmacy ; (12): 1172-1176, 2023.
Article in Chinese | WPRIM | ID: wpr-973614

ABSTRACT

OBJECTIVE To explore the construction of a new scientific management model for temporary drug purchase,and to provide a reference for hospitals to improve the level of rational drug use. METHODS Guided by clinical diagnosis and treatment needs and patient medication safety, our hospital carried out the whole process management practice of temporarily purchased drugs by optimizing the review process, creating a review team, formulating pre-audit and post follow-up evaluation standards based on comprehensive drug evaluation, and evaluated the practice effect through the number of temporary purchase applications, implementation rate, drug structure optimization and other indicators. RESULTS Since January 2021, our hospital had implemented a new mode of temporary drug purchase management. By December 2022, clinical pharmacists had reviewed 111 temporary drug procurement applications, effectively intercepted 13 irrational drug use applications (11.71%), reduced the overall implementation rate of temporary drug procurement by 8.36%,and proposed five batches of drug structure optimization suggestions; 24 drugs were successively introduced such as camrelizumab,sorafenib,busulfan. After optimizing the management mode,the number of temporary drug procurement applications decreased by more than half from 133 in 2019 and 138 in 2020 to 66 in 2021 and 45 in 2022. CONCLUSIONS The model is helpful to optimize the hospital drug catalog, strengthen rational drug use,ensure the safety of patients’ drug use, and fully reflects the professional value of clinical pharmacists in hospital pharmacy management and rational drug use.

10.
Journal of Peking University(Health Sciences) ; (6): 101-107, 2023.
Article in Chinese | WPRIM | ID: wpr-971280

ABSTRACT

OBJECTIVE@#To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration.@*METHODS@#Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not.@*RESULTS@#The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups.@*CONCLUSION@#The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.


Subject(s)
Humans , Centric Relation , Jaw Relation Record/methods , Denture, Complete , Mouth, Edentulous , Jaw, Edentulous
11.
Chinese Journal of Lung Cancer ; (12): 158-164, 2023.
Article in Chinese | WPRIM | ID: wpr-971190

ABSTRACT

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
.


Subject(s)
Humans , Bevacizumab , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Mutation , Protein Kinase Inhibitors
12.
Acta Physiologica Sinica ; (6): 328-338, 2023.
Article in Chinese | WPRIM | ID: wpr-981009

ABSTRACT

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.


Subject(s)
Animals , Dogs , Mice , Cysts/genetics , Inositol 1,4,5-Trisphosphate Receptors/pharmacology , Kidney/metabolism , Polycystic Kidney Diseases/metabolism , Polycystic Kidney, Autosomal Dominant/drug therapy , Madin Darby Canine Kidney Cells
13.
Chinese Acupuncture & Moxibustion ; (12): 691-696, 2023.
Article in Chinese | WPRIM | ID: wpr-980780

ABSTRACT

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.


Subject(s)
Humans , Ischemic Stroke , Chemokine CXCL12 , Acupuncture Therapy , Mesenchymal Stem Cells , Inflammation
14.
Acta Pharmaceutica Sinica ; (12): 1156-1164, 2023.
Article in Chinese | WPRIM | ID: wpr-978684

ABSTRACT

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

15.
Sichuan Mental Health ; (6): 143-149, 2023.
Article in Chinese | WPRIM | ID: wpr-986762

ABSTRACT

ObjectiveTo investigate the mediating role of loneliness and social anxiety in the relationship between basic psychological needs satisfaction and smartphone addiction among high school students, and to provide references for the intervention to smartphone addiction for high school students. MethodsIn April 2022, a total of 14 666 high school students from 5 middle schools in a county of Sichuan Province were included by random sampling method. Basic Psychological Needs Scales (BPNS), the UCLA Loneliness Scale-3 edition (UCLA-3), Interaction Anxiousness Scale (IAS) and the Mobile Phone Addiction Index (MPAI) were used for cross-sectional investigation. Bootstrap method was used to analyze the mediating role of loneliness and social anxiety in the relationship between the basic psychological needs satisfaction and smartphone addiction. Results① In this study, 14 036 valid questionnaires were returned, and 1 752 (12.48%, 95% CI: 0.114~0.136) high school students were found to be addicted to smartphone phone. The BPNS score was negatively correlated with UCLA-3, IAS and MPAI scores (r=-0.771, -0.486, -0.417, P<0.01). And MPAI score was positively correlated with IAS and UCLA-3 scores (r=0.403, 0.424, P<0.01). IAS score was positively correlated with UCLA-3 score (r=0.458, P<0.01). ②The degree of basic psychological needs satisfaction in high school students can directly negatively predict smartphone addiction (β=-0.383, P<0.05), and can also indirectly affect smartphone addiction through loneliness and social anxiety (β=-0.130, P<0.05). ③Loneliness (indirect effect value was -0.145) and social anxiety (indirect effect value was -0.074) partially mediate between the basic psychological needs satisfaction and smartphone addiction. Loneliness-social anxiety also has significant chain mediating effect (indirect effect value was -0.034), which accounted for 8.88%. ConclusionThe basic psychological needs satisfaction can not only directly affect the occurrence of smartphone addiction, but also indirectly affect the occurrence of smartphone addiction through the chain mediation of loneliness and social anxiety.

16.
Sichuan Mental Health ; (6): 137-142, 2023.
Article in Chinese | WPRIM | ID: wpr-986761

ABSTRACT

ObjectiveTo sort out and analyze the research progress of adolescent psychological resilience, and to grasp the research hotspots and frontiers in this field. MethodsCiteSpace was used to make a visual analysis of the number of publications, authors and institution, and co-occurrence, clustering and burst terms of keywords in literatures related to adolescent psychological resilience collected in CNKI database from January 1, 2012 to December 31, 2021. Results① For almost a decade, the research on adolescent psychological resilience was divided into a slow growth stage (2012-2018) and a rapid growth stage (2018-2021). ② The cooperation between authors were relatively close, and most of them were small and medium-sized cooperative organizations. There was less cooperation in scientific research institutions and most of them were normal universities. ③ In terms of co-occurrence analysis, hot keywords could be roughly divided into three categories: mental health status, influencing factors, and prevention and intervention research. ④ The related high-frequency keywords generate ten clusters, including academic emotions, learning burnout, adolescents, migrant children, mental health, internalized problems, social support, coping style, self-esteem and happiness. ⑤ The keywords with high burst intensity were coping style, mental health, mediation, regression analysis, social work, mental health and anxiety. ConclusionIn the future, cooperation between research institutions can be strengthened to improve the quality of the research on psychological resilience of adolescents. In addition, intervention research related to psychological resilience may become a hotspot in this field in the future.

17.
Chinese Journal of Hepatology ; (12): 582-588, 2023.
Article in Chinese | WPRIM | ID: wpr-986174

ABSTRACT

Objective: To investigate the effect of targeted carboxylesterase 1f (Ces1f) gene knockdown on the polarization activity of Kupffer cells (KC) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice with acute liver failure. Methods: The complex siRNA-EndoPorter formed by combining the small RNA (siRNA) carrying the Ces1f-targeting interference sequence and the polypeptide transport carrier (Endoporter) was wrapped in β-1, 3-D glucan shell to form complex particles (GeRPs). Thirty male C57BL/6 mice were randomly divided into a normal control group, a model group (LPS/D-GalN), a pretreatment group (GeRPs), a pretreatment model group (GeRPs+LPS/D-GalN), and an empty vector group (EndoPorter). Real-time fluorescent quantitative PCR and western blot were used to detect Ces1f mRNA and protein expression levels in the liver tissues of each mouse group. Real-time PCR was used to detect the expression levels of KC M1 polarization phenotypic differentiation cluster 86(CD86) mRNA and KC M2 polarization phenotypic differentiation cluster 163 (CD163) mRNA in each group. Immunofluorescence double staining technique was used to detect the expression of Ces1f protein and M1/M2 polarization phenotype CD86/CD163 protein in KC. Hematoxylin-eosin staining was used to observe the pathological damage to liver tissue. A one-way analysis of variance was used to compare the means among multiple groups, or an independent sample nonparametric rank sum test was used when the variances were uneven. Results: The relative expression levels of Ces1f mRNA/protein in liver tissue of the normal control group, model group, pretreatment group, and pretreatment model group were 1.00 ± 0.00, 0.80 ± 0.03/0.80 ± 0.14, 0.56 ± 0.08/0.52 ± 0.13, and 0.26 ± 0.05/0.29 ± 0.13, respectively, and the differences among the groups were statistically significant (F = 9.171/3.957, 20.740/9.315, 34.530/13.830, P < 0.01). The percentages of Ces1f-positive Kupffer cells in the normal control group, model group, pretreatment group, and pretreatment model group were 91.42%, ± 3.79%, 73.85% ± 7.03%, 48.70% ± 5.30%, and 25.68% ± 4.55%, respectively, and the differences between the groups were statistically significant (F = 6.333, 15.400, 23.700, P < 0.01). The relative expression levels of CD86 mRNA in the normal control group, model group, and pretreatment model group were 1.00 ± 0.00, 2.01 ± 0.04, and 4.17 ± 0.14, respectively, and the differences between the groups were statistically significant (F = 33.800, 106.500, P < 0.01). The relative expression levels of CD163 mRNA in the normal control group, the model group, and the pretreatment model group were 1.00 ± 0.00, 0.85 ± 0.01, and 0.65 ± 0.01, respectively, and the differences between the groups were statistically significant (F = 23.360, 55.350, P < 0.01). The percentages of (F4/80(+)CD86(+)) and (F4/80(+)CD163(+)) in the normal control group and model group and pretreatment model group were 10.67% ± 0.91% and 12.60% ± 1.67%, 20.02% ± 1.29% and 8.04% ± 0.76%, and 43.67% ± 2.71% and 5.43% ± 0.47%, respectively, and the differences among the groups were statistically significant (F = 11.130/8.379, 39.250/13.190, P < 0.01). The liver injury scores of the normal control group, the model group, and the pretreatment model group were 0.22 ± 0.08, 1.32 ± 0.36, and 2.17 ± 0.26, respectively, and the differences among the groups were statistically significant (F = 12.520 and 22.190, P < 0.01). Conclusion: Ces1f may be a hepatic inflammatory inhibitory molecule, and its inhibitory effect production may come from the molecule's maintenance of KC polarization phenotypic homeostasis.


Subject(s)
Animals , Male , Mice , Carboxylesterase/genetics , Galactosamine , Gene Knockdown Techniques , Kupffer Cells , Lipopolysaccharides/adverse effects , Liver Failure, Acute/chemically induced , Mice, Inbred C57BL , RNA, Messenger
18.
Chinese Journal of Internal Medicine ; (12): 833-840, 2023.
Article in Chinese | WPRIM | ID: wpr-985985

ABSTRACT

Objective: To explore the effect and mechanism of small GTP-binding protein GDP dissociation stimulator (SmgGDS) on the development of obesity. Methods: (1) 8-week-old C57BL/6J mice were randomly assigned to normal diet and high fat diet group, with 6 mice in each group. They were fed regular feed and a high fat diet containing 60% fat for 4 months, respectively. The expression of SmgGDS in epididymal adipose tissue (eWAT), liver, and skeletal muscle were measured using Western-blot. (2) 6-week-old wild-type (WT) and SmgGDS knockdown (KD) mice were divided into four groups, each receiving high fat diet for 4 months (7 in each group) and 7 months (9 in each group). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were conducted; The weight, adipose tissue, and liver weight of mice were recorded; HE staining examined adipose tissue structural changes; Western-blot determined extracellular signal-regulated kinase (ERK) 1/2 phosphorylation levels in eWAT; Real time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect mRNA levels of CCAAT/enhancer binding protein α (C/EBPα), C/EBPβ and peroxisome proliferator activated receptor γ (PPARγ) in eWAT. (3) Mouse embryonic fibroblasts (MEFs) extracted from WT and KD mice were induced for differentiation. Oil red O staining and Western-blot were used to detect lipid droplet and expression of SmgGDS and phospho-ERK; C/EBPα, C/EBPβ and PPARγ mRNA levels were measured using RT-qPCR. (4) 10-week-old C57BL/6J mice were randomly assigned into two groups, with 7 mice in each group. Mice were infected with SmgGDS overexpressing adeno-associated virus (AAV-SmgGDS) or empty vector intraperitoneally, then fed with high fat diet. After 4 weeks, performed GTT and ITT; Recorded the weight and adipose tissue weight of mice; HE staining was used to analyze structural changes of eWAT; Western-blot was used to detect the phosphorylation level of ERK in eWAT. Results: (1) The expression of SmgGDS was significantly upregulated in eWAT of high fat diet fed mice (normal diet group: 0.218±0.037, high fat diet group:0.439±0.072, t=2.74, P=0.034). (2) At 4 months of high fat diet intervention, the glucose tolerance (60 minutes after glucose injection, WT group: 528 mg/dl±21 mg/dl, KD group: 435 mg/dl±17 mg/dl, t=3.47, P=0.030; 90 minutes, WT group: 463 mg/dl±24 mg/dl, KD group: 366 mg/dl±18 mg/dl, t=3.23, P=0.047;120 minutes, WT group: 416 mg/dl±21 mg/dl, KD group: 297 mg/dl±16 mg/dl, t=4.49, P=0.005) and insulin sensitivity (15 minutes after insulin injection, WT group: 77.79%±3.45%, KD group: 54.30%±2.92%, t=3.49, P=0.005; 30 minutes, WT group: 62.27%±5.31%, KD group: 42.25%±1.85%, t=2.978, P=0.024; 90 minutes, WT group: 85.69%±6.63%, KD group: 64.71%±5.41%, t=3.120, P=0.016) of KD mice were significantly improved compared to the WT group, with an increase in eWAT weight ratio (WT: 4.19%±0.18%, KD: 5.12%±0.37%, t=2.28, P=0.042), but a decrease in average adipocyte area (WT group: 5221 μm²±241 μm², KD group: 4410 μm²±196 μm², t=2.61, P=0.026). After 7 months of high fat diet, the eWAT weight ratio of KD mice decreased (WT: 5.02%±0.20%, KD: 3.88%±0.21%, t=3.92, P=0.001) and adipocyte size decreased (WT group: 6 783 μm²±390 μm², KD group: 4785 μm²±303 μm², t=4.05, P=0.002). The phospho-ERK1 in eWAT increased (WT group: 0.174±0.056, KD group: 0.588±0.147, t=2.64, P=0.025), and mRNA level of PPARγ significantly decreased (WT group: 1.018±0.128, KD group: 0.029±0.015, t=7.70, P=0.015). (3) The expression of SmgGDS was significantly increased in differentiated MEF (undifferentiated: 6.789±0.511, differentiated: 10.170±0.523, t=4.63, P=0.010); SmgGDS knock-down inhibited lipid droplet formation in MEF (WT group: 1.00±0.02, KD group: 0.88±0.02, t=5.05, P=0.007) and increased ERK1 (WT group: 0.600±0.179, KD group: 1.325±0.102, t=3.52, P=0.025) and ERK2 (WT group: 2.179±0.687, KD group: 5.200±0.814, t=2.84, P=0.047) activity, which can be reversed by ERK1/2 inhibitor. (4) SmgGDS over expression resulted in weight gain, increased eWAT weight (control group: 3.29%±0.36%, AAV-SmgGDS group: 4.27%±0.26%, t=2.20, P=0.048) and adipocyte size (control group: 3525 μm²±454 μm², AAV-SmgGDS group: 5326 μm²±655 μm², t=2.26, P=0.047), impaired insulin sensitivity(30 minutes after insulin injection, control group: 44.03%±4.29%, AAV-SmgGDS group: 62.70%±2.81%, t=3.06, P=0.019), and decreased ERK1 (control group: 0.829±0.077, AAV-SmgGDS group: 0.326±0.036, t=5.96, P=0.001)and ERK2 (control group: 5.748±0.287, AAV-SmgGDS group: 2.999±0.845, t=3.08, P=0.022) activity in eWAT. Conclusion: SmgGDS knockdown improves obesity related glucose metabolism disorder by inhibiting adipogenesis and adipose tissue hypertrophy, which is associated with ERK activation.

19.
Chinese Journal of Surgery ; (12): 590-595, 2023.
Article in Chinese | WPRIM | ID: wpr-985813

ABSTRACT

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.


Subject(s)
Male , Female , Humans , Retrospective Studies , Acute Disease , Treatment Outcome , Calculi/pathology , Lithotripsy , Pancreatitis, Chronic/pathology , Pancreatic Diseases/complications , Pancreatic Ducts , Abdominal Pain/therapy
20.
Chinese Journal of Epidemiology ; (12): 1139-1145, 2023.
Article in Chinese | WPRIM | ID: wpr-985645

ABSTRACT

Objective: To construct a cervical cancer risk prediction model based on nested case-control study design and Yinzhou Health Information Platform in Ningbo, and provide reliable reference for self-risk assessment of cervical cancer in local women. Methods: In local women aged 25-75 years old who had no history of cervical cancer registered in Yinzhou before October 31, 2018, a follow up was conducted for at least three years, the patients who developed cervical cancer during the follow up period were selected as the case group and matched with a control group at a ratio of 1∶10. The prediction indicators before the onset was used in model construction. Variables were selected by Lasso-logistic regression, the variables with non-zero β were selected to fit the logistic regression model and Bootstrap was used for internal validation. The discrimination of the model was evaluated by area under the receiver operating characteristic curve(AUROC), and the calibration was evaluated by calibration curve and Hosmer-Lemeshow test. Results: The prediction indicators included in the final model were age, smoking status, history of cervicitis, history of adenomyosis, HPV testing, and thinprep cytologic test. The AUROC calculated in the internal validation was 0.740 (95%CI:0.739-0.740), and the calibration curve was almost identical with the ideal curve, P=0.991 in Hosmer-Lemeshow test, indicating that the model discrimination and calibration were good. Conclusions: In this study, a simple and practical cervical cancer risk prediction model was developed. The model can be used in general population with strong interpretability, good discrimination and calibration in internal validation, which can provide a reference for women to assess their risk of cervical cancer.

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