Superior vena cava syndrome and pulmonary artery stenosis in a patient with lung metastases of bladder cancer / 复旦学报（医学版）

Superior vena cava syndrome(SVCS)is a group of clinical syndromes caused by obstruction of the superior vena cava and its major branches from various causes.Pulmonary artery stenosis(PS)is a complication of lung cancer or mediastinal tumours.SVCS combined with PS due to pulmonary metastases from bladder cancer is extremely rare and has not been reported in the literature.Here we reported an old male patient with pulmonary metastases from bladder cancer presenting with swelling of the head,neck and both upper limbs.SVCS combined with PS was clarified by pulmonary artery computed tomography angiography(CTA)and digital subtraction angiography(DSA).Endovascular stenting was used to treat SVCS.Angiography also showed that PS had not caused pulmonary hypertension and did not need to be treated.The swelling of the patient's head,neck and upper limbs was gradually reduced after the procedure.

Huanglian Jiedutang Regulates HIF-1α/VEGF Signaling Pathway to Improve Learning and Memory Abilities of APP/PS1 Transgenic Mice / 中国实验方剂学杂志

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg-1·d-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg-1·d-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.

Mechanism of ellagic acid improving cognitive dysfunction in APP/PS double transgenic mice based on PI3K/AKT/GSK-3β signaling pathway / 中国药理学通报

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Validación de la escala de gravedad percibida de la violencia de pareja contra la mujer en población ecuatoriana

Introducción: La violencia de pareja contra la mujer (VPM) es un problema de salud pública a nivel global cuya prevalencia en Ecuador es de las más elevadas de Latinoamérica. La gravedad percibida de la VPM influye en las actitudes públicas hacia la VPM, como la aceptabilidad, el sentido de responsabilidad personal o la disposición a intervenir en casos de VPM. Método: En este estudio se presenta la adaptación de la escala española de gravedad percibida de la VPM (PS-IPVAW) al contexto cultural ecuatoriano, en una muestra de 652 participantes. Resultados: Los resultados mostraron que la escala PS-IPVAW tiene una buena consistencia interna, que sus ítems tienen una baja carga de deseabilidad social, que es invariante entre géneros y que se relaciona con la culpabilidad a la víctima, la aceptabilidad de la VPM y el sexismo hostil. Discusión: La escala PS-IPVAW es un instrumento con suficientes evidencias de fiabilidad y validez para evaluar la gravedad percibida de la VPM en Ecuador y representa un importante aporte para mejorar las estrategias de prevención, intervención y erradicación de este tipo de violencia en el contexto ecuatoriano.

Introduction: Intimate partner violence against women (IPVAW) is a global public health problem whose prevalence in Ecuador is among the highest in Latin America. The perceived severity of IPV influences public attitudes toward IPVAW, such as acceptability, sense of personal responsibility, or willingness to intervene in cases of IPV. Method: This study presents the adaptation of the Spanish scale of perceived severity of IPVAW (PS-IPVAW) to the Ecuadorian cultural context, in a sample of 652 participants. Results: Our results showed that the PS-IPVAW scale has good internal consistency, its items presented low loadings of social desirability, that it is invariant across genders and that it is related to victim blaming, acceptability of IPV and hostile sexism. Discussion: The PS-IPVAW scale showed adequate evidence.

Astragalin Inhibits Apoptosis of Cerebral Cortex Neurons in APP/PS1 Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the effect of Astragalin （AST） on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice. MethodsEighteen six-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group， APP/PS1+ 40 mg/kg AST group and APP/PS1+ 20 mg/kg Donepezil （DNP） group， with six mice in each group. At the same time， six male C57BL/6 mice were selected as the normal control group. After intraperitoneal injection of AST once a day and continuous administration for one month， we used Tunel staining to detect the apoptosis of neurons in the cerebral cortex of APP/PS1 mice； immunofluorescent staining to examine the expression of apoptosis-related proteins Bax， Bcl-2， Caspase9 and Cleaved-Caspase3 in the cerebral cortex neurons of APP/PS1 mice； Western blot method to evaluate the changes of the expression of Bax， Bcl-2， Caspase9 and Caspase3. ResultsTunel staining showed that 40 mg/kg AST and 20 mg/kg DNP both reduced the apoptosis of neurons in the cerebral cortex of APP/PS1 mice， AST with more significant inhibition effect. Immunofluorescent staining revealed that 40 mg/kg AST and 20 mg/kg DNP both inhibited the expression of Bax， Caspase9， and Cleaved-Caspase3， and icreased the expression of Bcl-2 in the cerebral cortex neurons of APP/PS1 mice. Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulated the expression of Bax （P < 0.05， P < 0.05）， Caspase9 （P < 0.005， P < 0.05） and Caspase3 （P < 0.0001， P < 0.0001） ， and up-regulated the expresstion of Bcl-2 （P < 0.05， P < 0.05） in the cerebral cortex neurons of APP/PS1 mice. ConclusionsAST can inhibit the apoptosis of cerebral cortex neurons in APP/PS1 mice.

Maintenance of Shinva PS-100X Medical Low-Temperature Hydrogen Peroxide Plasma Sterilizer:8 case reports / 医疗卫生装备

The structure and working principle of Shinva PS-100X Medical Low-Temperature Hydrogen Peroxide Plasma Sterilizer were introduced.Eight cases of the sterilizer failures had their phenomena,causes and elimination described in detail.The importance of daily maintenance and periodical examination was pointed out for the sterilizer.References were provided for clinical engineers to treat similar failures.[Chinese Medical Equipment Journal,2023,44(9):117-120]

Serum metabolomics study of Psoraleae Fructus in improving learning and memory ability of APP/PS1 mice / 中国中药杂志

This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum. The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01), and increased the number of platform crossing and residence time in the target quadrant(P<0.01). The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01). Eighteen differential metabolites in serum were screened out by metabolomics, among which the levels of arachidonic acid, tryptophan, and glycerophospholipid decreased after drug administration, while the levels of glutamyltyrosine increased after drug administration. The metabolic pathways involved included arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Therefore, Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice, and its mechanism may be related to the effects in promoting energy metabolism, reducing oxidative damage, protecting central nervous system, reducing neuroinflammation, and reducing Aβ deposition. This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer's disease(AD) and further explain the mechanism of Psoraleae Fructus in the treatment of AD.

Platycladi Semen oil ameliorates Aβ_(25-35)-induced brain injury in mice based on network pharmacology and gut microbiota / 中国中药杂志

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

SuanZaoRen decoction amliorates mitochondrial dysfunction of APP/PS1 mice via activating AMPK/SIRT1/PGC-1α signaling pathway / 中国药理学通报

Aim To explore the effect of Suanzaoren decoction(SZRD) on mitochondrial dysfunction in AD model of APP/PS1 mice via AMPK/SIRT1/PGC-1α signaling pathway and to reveal the possible mechanism. Methods Thirty APP/PS1 mice were randomly divided into app /PS1 group, low-dose SZRD group(L-SZRD) and high-dose SZRD group(H-SZRD). Ten C57BL/6JNju mice were set as control group(WT). Morris water maze test was used to detect the learning and memory ability of mice. Thioflavin T staining was used to observe senile plaques hippocampus. Immunohistochemistry was performed to detect the expression level of Aβ in hippocampus. Transmission electron microscope was used to observe the mitochondrial morph hology in hippocampus. Kits were employed to detect the contents of ATP and ROS in hippocampus; Western blot was employed to detect the expression levels of AMPK, p-AMPKThrK172, SIRT1, PGC-1α, NRF1, NRF2 and TFAM in hippocampus. Results Compared to the APP/PS1 group, L-SZRD and H-SZRD induced mouse cognitive impairment, reduced the deposition of senile plaques, inhibited the expression of Aβ, improved the damage of mitochondrial structure, increased the content of ATP in the hippocampus, reduced the expression level of ROS in hippocampus and increased the expression of p-AMPK-ThrK172, SIRT1, PGC-1α, NRF1, NRF2, TFAM Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.

Effects of S1P/S1PR1 pathway on high glucose induced epithelial-mesenchymal transition of rat renal tubular epithelial cells by regulating ROS/NLRP3 / 中国药理学通报

Aim To explore the effect of S1P/S1PR1 signaling pathway on high glucose(HG)-induced epithelial-mesenchymal transition of rat renal tubular epithelial cells and its possible mechanism. Methods Cells were treated with different concentrations of glucose, and intracellular S1P expression was detected by ELISA and S1PR1 protein expression was detected by Western blot. The cells were divided into normal control group, HG group and HG + siS1PR1 group. The expression of E-cadherin, Vimentin, Fibronectin and Twist mRNA were detected by RT-qPCR and E-cadherin, α-SMA, Vimentin, NLRP3, ASC and NF-κB protein expression were detected by Western blot, and the levels of reactive oxygen species(ROS) were detected by flow cytometry. The cells were divided into normal control group, S1P group and S1P + siS1PR1 group. Vimentin, Snail, α-SMA, NLRP3, ASC and NF-κB protein expressions were detected by Western blot, and ROS levels were measured by fluorescence microscopy. Results ELISA results showed that the content of S1P in cells increased significantly under high glucose stimulation. Western blot results showed that S1PR1 protein expression was significantly higher at 30 mmol · L

S1P/S1P Receptor Pathway: A New Target for Treatment of Inflammatory Bowel Disease / 胃肠病学

The development of targeted oral drugs that can stably treat inflammatory bowel disease (IBD) is still a clinical problem to be solved. In recent years, studies have confirmed that sphingosine⁃1⁃phosphate (S1P)/S1P receptor pathway can regulate lymphocyte homing and immune regulation, inhibit intestinal inflammation, protect intestinal endothelial barrier, and affect intestinal microbial metabolism, which may play a key role in the treatment of IBD. This article reviewed the effect of S1P/S1P receptor pathway on IBD and its potential mechanism.

The risk of Alzheimer′s disease transmitted by blood transfusion based on APP/PS1 double transgenic mice / 中国输血杂志

【Objective】 To explore the risk of Alzheimer′s disease (AD) transmitted by blood transfusion. 【Methods】 There were 10 APP/PS1 mice of 3, 6 and 9 months old, half female and half male, and the cognitive and behavioral abilities of C57 mice of the same age were measured, and the blood of the oldest APP/PS1 mice with no behavioral changes were collected to detect the contents of Aβ40 and Aβ42. The polymers Aβ40 and Aβ42 were prepared and Western blotting analysis was conducted. Kunming mice aged from 6 to 7 months were randomly divided into 6 groups (10 mice/ group, half male and half female). The blood of APP/PS1 mice was injected intravenously in experimental group 1-2(100 μL/mouse) with high frequency injection (3 times/week) and low frequency injection (1 time/week), respectively. In experimental group 3-4, Aβ40 and Aβ42 polymerized mixture (100 μL/mouse) were injected in high frequency and low frequency, respectively. The control group 1-2 was injected with the same amount of normal saline, with high frequency and low frequency, respectively. The above groups were injected for 4 weeks, and the cognitive and behavioral abilities were tested and analyzed one week after injection. Finally, the contents of Aβ40 and Aβ42 in blood of Kunming mice were detected. 【Results】 Change in cognitive and behavioral ability showed in 9 months old APP/PS1 mice, but not in 3 and 6 months old APP/PS1 mice. The contents of Aβ40 and Aβ42 (pg/mL) in blood of 6-7 months old APP/PS1 mice were 418.40±2.18 and 15.68±0.20, respectively. Except for monomers, most of the polymerized mixtures of Aβ40 and Aβ42 were dimers and trimers. In both high frequency and low frequency, Kunming mice transfused with blood of APP/PS1 mice (experimental group 1-2) showed a certain degree of anxiety-like behavior and short-term memory shortening in open-field test and conditioned fear test, but without significant difference. There was no significant difference in open field test, new object recognition, Barnes maze and cognitive behavior analysis of conditioned fear between experimental group 3-4 and the control group. The levels of blood Aβ40 and Aβ42(pg/mL) of Kunming mice detected by ELISA were 10.30±0.08 and 3.360±0.005, respectively, and there was no significant difference between the two groups. 【Conclusion】 Blood transfusion of APP/PS1 mice and the mixture of Aβ40 and Aβ42 have no significant effect on the cognitive function of healthy Kunming mice in a short time, and the risk of AD transmission is relatively low.

La importancia del desarrollo de las habilidades comunicacionales en estudiantes del área de la salud / The importance of developing communication skills in students in the health área

INTRODUCION Estos últimos años la Educación Superior ha tenido que incorporar en su curricular el desarrollo de habilidades comunicacionales, siendo actualmente considerada por la Asociación de Colegios Médicos Americanos (AAMC), Asociación Americana de Escuelas de Medicina(AAME) y Escuela de aprendizaje, conductual y de habilidades (EACH) como una competencia básica del profesional del área salud y que en ocasiones determina el éxito o fracaso del proceso asistencial, existiendo evidencia que el proceso comunicativo que se da en los centros de atención médica referida a la interacción médico-paciente determina la precisión del diagnóstico, toma de decisiones y adherencia del tratamiento que permite una excelente práctica médica. Frente a esta necesidad las Universidades han implementado diversas actividades realizadas en países anglosajones que deben ser ajustadas a las necesidades y contexto social chileno.

In recent years, Higher Education has had to incorporate in its curriculum the development of communication skills, being currently considered by the Association of American Medical Colleges (AAMC), American Association of Medical Schools (AAME) and School of Learning, Behavioral and Skills (EACH) as a basic competence of the health professional and that sometimes determines the success or failure of the care process, there is evidence that the communicative process that occurs in health care centers related to doctor-patient interaction determines the accuracy of diagnosis, decision making and adherence to treatment that allows excellent medical practice. Faced with this need, the Universities have implemented various activities carried out in Anglo Saxon countries that must be adjusted to the needs and social context of Chile

SASA: una escala sencilla de mortalidad postoperatoria explorada en un centro de atención de tercer nivel en México / SASA: a simple scale of postoperative mortality explored in a third-level care center in Mexico

Resumen: Introducción: Las complicaciones postquirúrgicas han sido causa importante de muerte. Por lo tanto, el uso de predictores sencillos de mortalidad con una nueva escala llamada SASA podría indicar un riesgo postoperatorio de mortalidad a los 30 días aplicado en una muestra en población mexicana. Material y métodos: Exploramos una asociación entre la clasificación de estado físico de la Sociedad Americana de Anestesiólogos (ASA-PS), el Apgar quirúrgico (sAs) y la puntuación de SASA con un análisis univariado en 371 pacientes estimando la relación de probabilidades (OR) y graficando las curvas de operación característica del receptor (receiver-operating-characteristic [ROC]) para cada escala. Resultados: Obtuvimos los valores de dos; [sensibilidad; 81.82% (IC del 95%: 48.2-97.72), especificidad; 40.56% (IC del 95%: 35.44-45.83)], 6; [sensibilidad; 81.82% (IC del 95 %: 48.2-97.72), especificidad; 77.5% (IC del 95%: 72.83-81.71)] y 10; [sensibilidad; 81.82% (IC del 95%: 48.2-97.72), especificidad; 83.6% (IC del 95%: 78.77-86.78)] como los mejores puntos de corte para el ASA-PS, sAs y SASA respectivamente. Conclusiones: el cálculo de SASA obtuvo la misma sensibilidad, pero mejor especificidad y área bajo la curva cuando se comparó con el ASA-PS y el sAs.

Abstract: Introduction: Post-surgical complications have been a significant cause of death. Therefore, the use of easy preoperative mortality predictors is recommended. A new SASA score could indicate a perioperative risk more globally at 30-days of the postoperative period applied in a Mexican sample. Material and methods: 371 patients were analyzed. We explore an association between the American Society of Anesthesiologists physical status classification (ASA-PS), the surgical Apgar score (sAs), and the new SASA score to assess 30-days mortality after surgery using univariate analysis to estimate the odds ratio (OR). Receiver-operating-characteristic (ROC) curves were plotted for each scale. Results: We obtained values of two; [sensitivity; 81.82% (95% CI: 48.2-97.72), specificity; 40.56% (95% CI: 35.44-45.83)] 6; [sensitivity; 81.82% (95% CI: 48.2-97.72), specificity; 77.5% (95% CI: 72.83-81.71)] and 10; [sensitivity; 81.82% (95% CI: 48.2-97.72), specificity; 83.6% (95% CI: 78.77-86.78)] as the best cut-off points for ASA-PS, sAs and SASA respectively. Conclusions: To predict postoperative 30-days mortality, SASA calculation as a new score obtained the same sensitivity but better specificity and area under the curve (AUC) for the ROC compared with the ASA-PS and the sAs.

Polystyrene-b-poly (acrylic acid) nanovesicles coated by modified chitosans for encapsulation of minoxidil

Abstract In this work, polystyrene-b-poly (acrylic acid) (PS-b-PAA) nanovesicles were coated by modified chitosans aiming at studying its physicochemical parameters. The chitosan (CS) was chemically modified to add hydrophilic and/or hydrophobic groups, obtaining three modified chitosans. The PS-b-PAA nanovesicles were obtained by organic (1,4-dioxane) cosolvent method in water, resulting in nanovesicles with less than 150 nm of diameter (polydispersibility index - PDI at 90° = 0.106), measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and negative zeta potential (-37.5 ± 3.2 mV), allowing the coating of its surface with oppositely charged polysaccharides, such as the CS and the modified chitosans. The coating process was made by mixing the colloidal suspensions with the CS and the modified chitosans at specific ENT#091;CS-xENT#093;/ENT#091;PS-b-PAAENT#093; ratios (0.001 to 1.0 wt %) and measuring the change in size and surface charge by DLS and zeta potential. Upon reaching maximum adsorption, the zeta potential parameter was positively stabilized (+26.7 ± 4.1 mV) with a hydrodynamic diameter slightly longer (< 200 nm of diameter). The encapsulation efficiency (EE) of minoxidil, quantified by capillary electrophoresis, was 50.7%, confirming their potential as drug delivery carriers and the coating process showed the possibility of controlling the surface charge nature of these nanovesicles

Time dependent expression profiling of PTK2B and its relationship with Aβ, Tau and LRP-1 in hippocampus and blood of APPswe/PS1dE9 double-transgenic mouse / 中国应用生理学杂志

Objective: To uncover the time-dependent expression pattern of ptk2b gene and ptk2b-encoded protein, protein tyrosine kinase 2 beta(PTK2B), in the brain tissues of transgenic animal models of Alzheimer's disease (AD) and its relationship with the levels of Aβ1-42, phosphorylation of Tau (p-Tau) and low density lipoprotein receptor-related protein-1(LRP-1) in blood and brain tissues. Methods: In this study, 5-, 10- and 15-month-old APPswe/PS1dE9 double-transgenic mice harboring the genotype of AD confirmed by the gene test were divided into the 5-, 10- and 15-month-old experiment groups, and simultaneously, age-matched C57BL/6J mice were placed into the corresponding control groups, with 8 mice in each group. All mice were subjected to the Morris Water Maze for test of cognitive and behavioral ability. Expression profiles of PTK2B, Aβ1-42, p-Tau/Tau and LRP-1 in the hippocampus or blood of mice were quantified by using the immunohistochemistry staining, Western blot or enzyme-linked immunosorbent assay (ELISA), while the mRNA expression of ptk2b in the hippocampus was quantified by using the real-time quantitative polymerase chain reaction (qRT-PCR). Results: Results of experiment groups demonstrated that as mice aged, the expression levels of PTK2B, ptk2b mRNA, Aβ1-42 and p-Tau/Tau in the hippocampus were increased, and the expression of LRP-1 was decreased gradually. While in the blood, the level of Aβ1-42 was decreased, and the cognitive and behavioral ability was decreased in an age-dependent manner (all P＜ 0.05). However, comparisons among the control groups, only the age-dependent downregulation of LRP-1 were observed in hippocampus(P＜0.05), but other indicators had no significant differences (P＞0.05). Conclusion: In the hippocampus of APP/PS1 double-transgenic mice, the expressions of PTK2B, Aβ1-42 and p-Tau/Tau are upregulated, LRP-1 is downregulated, while cognitive and behavioral ability is decreased, and such changes are presented in a time-dependent manner.

Agerelated changes in Alzheimer’s disease-like pathology in male APP/PS1/Tau triple transgenic mice / 中风与神经疾病杂志

@#Objective Immunohistochemical methods were used to observe the age-related changes of Alzheimer’s disease-related pathology in the hippocampus and sensory cortex in male APP/PS1/Tau triple transgenic mice aged 2-15 months.Methods Male 3xTg-AD mice were randomly divided into 7 groups according to the age of 2，4，6，8，10，12 and 15 months，with 3 mice in each group as the experimental group；age-matched male C5B7L/6J mice Randomly divided into 7 groups according to the age of 2，4，6，8，10，12 and 15 months，with 3 mice in each group as a control group. The immunohistochemical method was used to detect the pathological age-related changes in the hippocampus and sensory cortex of each mouse brain tissue with age，closely related to Alzheimer’s disease，including Aβ，phosphorylated tau，transgenic products of human tau P301L mutant，astrogliosis，neuron markers.Results Compared with C5B7L/6J mice，the intensity of immunostaining of Aβ cells（6E10），p-tau（AT8，Ser202/Thr205） and tau（HT7） astrocytes（GFAP） in APP/PS1/Tau triple transgenic mice is significantly enhanced，P<0.0001.The hippocampus and sensory cortex of male APP/PS1/Tau triple transgenic mice aged 2-15 months did not have obvious amyloid plaque deposition. The staining degree of Aβ cells in the CA1 area of the hippocampus gradually increased at the age of 8 months，and the staining degree of the sensory cortex remained unchanged，P<0.05. The staining degree of Tau (HT7) in the CA1 area has weak staining at 2 to 6 months of ageand the staining degree remained stable from 6 months to 15 months；The degree of staining in the sensory cortex increased from 2 to 4 months old，and the degree of staining remained stable at 4 to 15 months，P<0.05.The phosphorylation of AT8 in CA1 area began to increase at 6 months，and the phosphorylation of sensory cortex began to increase at 12 months，P<0.05.Astrocytes（GFAP） in CA1 area and sensory cortex area gradually increase in reactivity from 2 months to 15 months. The number of mature neuron markers（NEUN） in CA1 area gradually decreased from 2 months to 6 months，and was stable from 6 months to 15 months. The number of NEUN in CA-3 area gradually decreased from 2 months to 15 months，P<0.05.Conclusion 3xTg-AD mice show a clear interaction between age and phenotype development，which makes it an important tool for studying the role of aging in disease pathogenesis.

Study on the Effects of Tenuifolin on Brain Mitochondrial Autophagy in AD Model Mice Based on PINK 1/Parkin Signaling Pathway / 中国药房

OBJECTIVE：To investig ate the effects of tenuifolin （TEN）on brain mitochondrial autophagy in Aizheimer ’s disease（AD）model mice. METHODS ：Totally 50 male APP/PS1 double transgenic mice were randomly divided into model group，TEN medium-dose+ 3-MA group [TEN 40 mg/（kg·d）+autophagy inhibitor 3-MA 30 mg/（kg·d）] and TEN low-dose ， medium-dose and high-dose groups [ 20，40，80 mg/（kg·d）]，with 10 mice in each group. In addition ，10 wild-type homologous mice were included in normal control group. Administration groups were intragastrically given corresponding drug solution ；normal control group and model group were intragastrically given 0.3％ sodium carboxymethyl cellulose solution ，once a day ，0.01 mL/g， for consecutive 3 months. After last administration ，positive expression [measured by integrated optical density （IOD）] of microtubule associated protein 1 light chain 3（LC3）in neuron was detected ；mRNA expressions of LC3，ubiquitin-binding protein p62，Cathepsin D ，Rab7，phosphatase and tensin homolog deleted on chromosome ten gene-induced putative kinase 1（PINK1） and E 3 ligase（Parkin）as well as protein expressions of LC 3，p62，PINK1 and Parkin were detected in brain mitochondria. RESULTS：Compared with normal control group ，IOD value of LC 3 in neuron as well as mRNA and protein expressions of LC 3， p62，PINK1 and Parkin in brain mitochondria were all increased significantly in model group （P＜0.05 or P＜0.01），while mRNA expressions of Cathepsin D and Rab 7 were decreased significantly （P＜0.05 or P＜0.01）. Compared wit h model group ，IOD values of LC 3（except for TEN low-dose and medium-dose groups ） in neuron ，mRNA expressions of LC 3，Cathepsin D ，Rab7， PINK1（except for TEN low-dose group ）and Parkin （except for TEN low-dose group ） in brain mitochondria as well as protein expressions of LC 3 （except for TEN medium-dose group），PINK1（except fo r TEN high-dose group decreased significantly）and Parkin （except for TEN low-dose group decreased significantly ）were increased significantly in TEN low-dose ， medium-dose and high-dose groups （P＜0.05 or P＜0.01）；mRNA（except for TEN low-dose group ）and protein expressions of p62 were decreased significantly （P＜0.05 or P＜0.01）. Compared with TEN medium-dose group ，the changes of above indexes were inhibited significantly in TEN medium-dose + 3-MA group （P＜0.05 or P＜0.01）. CONCLUSIONS ：TEN can induce mitophagy in brain tissue of AD model mice by activating PINK 1/Parkin signaling pathway and improve lysosome function.

Effect of Modified Shuyuwan on Neuroinflammation in APP/PS1 Dementia Mice Based on Nlrp3/ASC/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 （APP/PS1） dementia mice on cognitive and memory impairment and to explore its mechanism. Method:The 40 APP/PS1 mice were divided into model group （given Physiological saline）， low and high-dose modified Shuyuwan （14，64 g·kg^-1）group， and donepezil group （1 mg·kg^-1） and 10 wild mice were set as the blank control group （given Physiological saline）. All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze， the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of <italic>β </italic>amyloid 1-42（A<italic>β</italic>_1-42） in mouse hippocampus was detected by immunohistochemistry， and the expression of ionized calcium-binding adapter molecule 1（Iba1）， a marker of hippocampal microglia （MG） and Nitric oxide synthase（iNOS）， a marker of actived MG， were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3（Nlrp3）， Apoptosis-associated speck-like protein containing a Caspase-recruitment domain （ASC）， cysteine protease-1（Caspase-1）and interleukin-1 beta （IL-1<italic>β</italic>） were detected by Western blot， and the expression of IL-1<italic>β</italic>， tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>）and interleukin-18 （IL-18） mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the blank control group， the memory and space exploration ability of the model group were significantly reduced （<italic>P</italic><0.05）， the number of hippocampal neurons decreased， the deposition of A<italic>β</italic>_1-42 increased， the markers of actived MG Iba1，iNOS increased， the protein expression of Nlrp3， ASC， Caspase-1， IL-1<italic>β</italic> increased significantly （<italic>P</italic><0.05）， and the mRNA expression of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> increased significantly （<italic>P</italic><0.05）. Compared with model group， the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability （<italic>P</italic><0.05）， increase the number of hippocampal neurons， reduce A<italic>β</italic>_1-42 deposition， reduce the activation of MG， and reduce the protein expression of Nlrp3， ASC， Caspase-1 and IL-1<italic>β</italic> （<italic>P</italic><0.05）， and reduced the expression of IL-1<italic>β</italic> mRNA （<italic>P</italic><0.05）. Conclusion:Modified Shuyuwan can reduce the expression of IL-1<italic>β</italic> and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway， and relieve nerve inflammation and pathological injury of AD.

Effect of glucosinolates on improvement of cognitive impairment in APP/PS1 double transgenic mice by regulating AKT/NFkB pathway / 中国药理学通报

Aim To investigate the effects of acteoside (AS) on BRAIN AKT and NFkB in APP/PS1 double transgenic mice. Methods Fifty healthy APP/PS1 transgenic mice, half male and half female, and 10 control C57 mice were given the drug by gavage for 60 consecutive days. During the period of administration, and new object recognition experiments were conducted to detect the expression of AKT and NFkB related proteins in the hippocampus and cortex of the mice. Results Compared with model group, AS could significantly improve the nesting behavior of mice and en- hance the interest of exploring new objects in mice with Alzheimer' s disease. At the same time, compared with model group, AS significantly reduced the ratio of NFkB p-p65 /NFkB p65 in hippocampus and cortical tissues, and increased the ratio of p-AKT-308 /AKT and p-AKT473 /AKT. Conclusions AS may inhibit the apoptosis of nerve cells and protect nerve cells through the regulation of AKT and NFkB to treat neurodegenerative diseases.