Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Objective To compare the efficacy of programmed intermittent epidural bolus and continuous epidural infusion of ropivacaine in labor analgesia.Methods From May 2014 to May 2017,170 patients,24 -32 years,for full-term primipara in the Maternal and Child Health Care Hospital of Quzhou were selected as study objects,and they were randomly divided into intermittent epidural injection group (T group) and continuous epidural pump group(C group) by computer random software,with 85 cases in each group.All patients were epidurally injected 2%lidocaine 3mL and 0.2% ropivacaine 2mL at the opening of the uterus,less than 3cm.T group was given programmed intermittent epidural bolus 0.1% ropivacaine 6mL/h.C group was given continuous epidural infusion 0.1%ropivacaine 6mL/h.The pain of maternal(NRS score) and motor block situation of maternal (Bromage score) were monitored.The number of PCEA,PCEA pressure times,the rate of instrumental delivery and APGAR score were also recorded.Results The number of Bromage score≥2 in C group was higher than that of T group at 4-10h after labor analgesia (3 cases vs.11 cases,3 cases vs.15 cases,4 cases vs.17 cases,4 cases vs.18 cases,6 cases vs. 19 cases,6 cases vs.21 cases,7 cases vs.22 cases;χ2＝4.982,8.947,9.182,10.230,7.926,9.907,9.354,all P＜0.05).There was no statistically significant difference in NRS score between the two groups (P＞0.05).The number of PCEA,PCEA pressure times and the rate of instrumental delivery in T group were lower than those in C group [8 cases vs.18 cases,22 cases vs.41 cases,(3.5 ±1.5) times vs.(4.9 ±2.2) times;χ2＝4.541,9.104;t＝2.666,all P＜0.05].There was no statistically significant difference in Apgar score between the two groups (P＞0.05).Conclusion Compared with continuous epidural infusion,programmed intermittent bolus of ropivacaine for labor analgesia exerts good analgesic effect,it has minor effects on exercise function and can decrease the rate of instrumental delivery .

OBJECTIVETo explore the effect of different functional groups on self-assembled monolayers on the biological characteristics of rabbit skeletal muscle cells in vitro.

METHODSRabbit skeletal muscle cells were cultured on self-assembled monolayers of gold on which different terminal chemical groups including methyl groups (-CH(3)), amino(-NH(2)), hydroxyl(-OH) and carboxyl (-COOH ) were anchored with self-assembled methods. Contact angle measurements and atomic force microscopy were employed to confirm the similar density of different functional groups occupation. Fluorescence microscopy, MTT assay, flow cytometry, and scanning electron microscopy (SEM) were used to analyze the morphological and biological alterations of the cells.

RESULTSSEM results revealed that the chemical groups on the surface of the monolayer modulated the structure of skeletal muscle cells and the cell morphology. Skeletal muscle cells cultured on the monolayer with -CH3 exhibited the smallest contact area with a spherical morphology, while the cells on the monolayers with -NH(2), -OH and -COOH showed much larger contact area and flatter morphology. The functional groups -NH(2) and -COOH obviously promoted cell adhesion and proliferation, while -CH(3) group produced significantly greater toxicity than -NH(2), -OH and -COOH groups to inhibit the cell growth and adhesion and promote cell death. Cell attachment and growth was enhanced, in the order the magnitude of the effect, by -NH(2)>-COOH>-OH>-CH(3), and the toxicity decreased in the order of -NH(2)>-COOH>-OH>-CH(3).

CONCLUSIONThe terminal chemical groups can obviously affect the phenotype of skeletal muscle cells in vitro, and this finding provides a theoretical basis for surface design of biomaterials.

Animals ; Cell Adhesion ; Cell Proliferation ; Cells, Cultured ; Microscopy, Atomic Force ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Muscle Fibers, Skeletal ; cytology ; Rabbits

Objective To analyze the characteristic influence and deviations caused by the face effect to the survey outcomes of the patient perceived value (PPV) of medical treatment.Methods Based on the theoretical research,a PPV test & evaluation plan is designed for two groups of patients.Comparative study of outcomes of the two groups aims at identifying patterns in this regard.Results Findings of the patients evaluation showed that the face effect poses strong interference for the survey outcomes,as it significantly raises the evaluation outcomes.Among the factors causing face effect,characteristics of the investigator in the survey are found to be the most important stimulating,which include the power distance and the strength of relationship between patients and the hospital.Such factor will push higher the subjective PPV of the patient,while the general satisfaction of the medical workers in the survey can be 0.24 higher than that of third-party survey.In addition,friends and patients in the same wards are also an important factor to cause the face effect of the patient,while such factor works at a wide range to push higher both objective and subjective estimation value of the patient.For joint actions of the investigator and the reference group,the general satisfaction between the two-high scenario and the two-low one can be up to 39.43％.Conclusion The PPV surveys should minimize interference of the face effect by means of evaluating environment redesign,avoidance of the friends and relatives,and selection of optimal investigators,for the purpose of eliminating interference of the face effect.