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 analyze the medication reconciliation for the inpatients in cardiovascular medicine department ，to provide reference for the establishment of working mode of clinical pharmacists in the department of cardiovascular medicine and to provide a basis for clinical pharmacists and community pharmacists developing pharmaceutical care for patients after transfering to community health center. METHODS From October 2020 to September 2021，newly admitted or newly transferred inpatients with chronic disease were selected from Shiyan People ’s Hospital of Shenzhen Bao ’an District. Medication reconciliation was conducted by clinical pharmacists after pharmaceutical consultation. According to the Pharmaceutical Care Network Europe （PCNE） classification system V 9.1，the existing drug-related problems （DRPs）were classified and summarized. The effectiveness and safety evaluation，medication education and other measures were provided ，and the acceptance of intervention was analyzed at the same time. RESULTS A total of 100 patients were included ，including 54 males and 46 females. The average age was （60.21±9.69） years，the average number of chronic diseases was （2.84±0.83），and the median number of drugs was 5.00. Among them ，110 treatment drug deviations were found in 74 patients，involving 10 categories and 61 drugs. Top three drugs in the list of accumulative drug deviation were cardiovascular system drugs （35 deviations），digestive medicine drugs （16 deviations）and endocrine system drugs （15 deviations）. The above treatment drug deviation may cause 122 DRPs， mainly “treatment effectiveness”problems（74 DRPs），and the causes were “inappropriate medication time ormedication interval ”（32 DRPs）， followed by “inappropriate drug combination ”（10 DRPs）. Interventions to DRPs mainly concentrated on patient level ，drug level （58）and doctor level （58），155 of which （84.70％）were fully accepted and implemented. CONCLUSIONS Some patients have a weak awareness of medications according to doctor ’s advice；drug reconciliation led by clinical pharma- cists at admission can fully understand the potential drug problems of patients ，and help doctors improve the drug compliance of patients and ensure their medication safety .

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 .

OBJECTIVE:To identify lipid metabolites of endophytic fungus Aspergillus terreus from Polygonum capitatum, and to investigate their anti-multidrug resistant bacteria and anti-inflammatory effects. METHODS:GC-MS was used to analyze and identify lipid metabolites of A. terreus. MIC of lipid metabolites and main composition to 10 strains of multidrug resistant bacteria (Klebsiella pneumoniae,Proteus common,Staphylococcus epidermidis,Escherichia coli,Staphylococcus aureus,Enterobacter cloacae,Pseudomonas aeruginosa,Proteus mirabilis,Enterococcus faecium and Acinetobacter baumanii) were determined by 96-well plate microdilution method. The spread plate method was used to determine MBC of samples to bacteria. LPS-induced RAW264.7 inflammatory model was used to investigate the effects of different mass concentrations(50,100,200 μg/mL)of lipid metabolites on the release of NO and TNF-α after treated for 24 h. RESULTS:A total of 13 compounds were identified in lipid metabolites of A. terreus,among which palmitic acid,stearic acid,linoleic acid and oleic acid were main components,and relative percentages of them were 29.35％,10.87％,21.94％,34.85％. The lipid metabolites displayed anti-bacterial activity against E. coli and K. pneumonia with MICs of 12.5 mg/mL and 50 mg/mL,MBC of 25 mg/mL and 100 mg/mL,respectively. The main 4 compositions could inhibit the growth of E. coli,with MIC of 0.5-1 mg/mL,among which palmitic acid showed significant antibacterial activity,especially to E. faecium(MIC of 0.25 mg/mL). 50,100 μg/mL lipid metabolites could signifiantly inhibit the release of inflammatory factor of NO and TNF-α in RAW264.7 in vitro. CONCLUSIONS:The lipid metabolites of endophytic fungus A. terreus from P. capitatum show anti- multi-drug resistant bacteria and anti-inflammatory effects.

Objective To explore the monitoring results on serum concentration of valproic acid in 78 patients with epilepsy for promoting the clinical application and improving the curative effect of serum concentration.Methods The serum concentration of valproic acid was determined by fluorescence polarization immunoassay (FPIA). The serum concentration of valproic acid in 78 cases were analyzed,and the clinical efficacy and adverse reaction were observed. Results Among 78 cases, there were 55 cases (70.0%) whose serum concentration were in normal range,21 cases(27.0% ) in low range and 2 cases(3. 0% ) in high range. The clinical effective rate in 50～100mg/L group, ＜ 50mg/L group and ＞ 100mg/L group were 90.9% ,61.9% and 50.0%. The rate of adverse reaction in 50 ～ 100mg/L group, ＜ 50mg/L group and ＞ 100mg/L group were 1. 8%, 9. 5% and 100%.Conclusion There were significant individual differences among patients in serum concentration of valproic acid. Monitoring on serum concentration of valproic acid was the important measure which provide the basis for adopting individualizede administration and ensure the clinical effect and safety in the medical care.

OBJECTIVE: To establish the HPLC method for the content determination of baicalin in Xiaoer zhike granule. METHODS: YWG C18 (150 mm?4.6 mm,10 ?m) column was used and the mobile phase consisted of methnol-water-phosphoric acid (47 ∶ 53 ∶ 0.2) with the flow rate of 2.5 mL?min-1. The detection wavelength was set at 280 nm and injection volume was 10 ?L. RESULTS: The linear range of baicalin was 25～200 ?g?mL-1(r=0.999 6) with an average recovery of 99.57%(RSD=1.9%,n=6). CONCLUSION: This method is sensitive, simple and accurate for the quality control of Xiaoer zhike granule.