Blood-brain barrier (BBB) is the major obstacle for drug delivery into the central nervous system (CNS). However, there is no ideal model animal for the study of BBB permeability till now. Currently zebrafish (Danio rerio) has emerged as a powerful model organism for the study of vertebrate biology. In this study, the feasibility of using zebrafish as model animal was investigated for BBB permeability by comparing the results of administration of BBB-penetrating peptide and protein to mouse and zebrafish. The results showed that the BBBs of mouse and zebrafish were similar in molecular permeability. Additionally, zebrafish has advantageous features as a model animal, such as small size, fertile and easy to breed. Therefore, it is suggested that zebrafish may be a favored model for the study of BBB permeability.

Objective:To establish and verify a model to predict histologic chorioamnionitis (HCA) for women during expected management of preterm premature rupture of membranes (PPROM) at 24-34 weeks of gestation.Methods:This retrospective study enrolled 493 pregnant women who were diagnosed with PPROM at 24-33 +6 weeks of gestation and delivered in Peking University Third Hospital from January 1, 2012, to December 31, 2020. They were randomly divided into the modeling set ( n=345) and validation set ( n=148) at a ratio of 7∶3. Basic information, risk factors, clinical treatment, and maternal and infant outcomes were compared between participants with and without HCA using Chi-square test, t test, or Mann-Whitney U test. Multivariate logistic regression analysis was performed to analyze the independent risk factors for HCA. The predictive values of different indexes for HCA were compared and the predictive model was then established and verified using the receiver operating characteristic (ROC) curve and area under curve (AUC). Results:There were no significant differences in the basic information, common risk factors for premature rupture of membranes (PROM), or the use of tocolytics, antibiotics or dexamethasone between women in the HCA and non-HCA groups (all P>0.05). Compared with the non-HCA group, the HCA group showed an earlier onset of PROM [31.3 (24.0-33.9) vs 32.3 (27.0-33.9) gestational weeks, U=4 103.00, P=0.017], longer expected treatment [66.5 (0.7-895.3) vs 18.0 (0.3-1 123.0) h, U=1 791.00, P<0.001] and higher incidence of neonatal asphyxia, sepsis, and intracranial hemorrhage [24.3% (58/239) vs 13.2% (14/106), χ 2=5.44; 9.6% (23/239) vs 2.8% (3/106), χ 2=4.86; 41.0% (98/239) vs 17.9% (19/106), χ 2=17.45; all P<0.05]. Moreover, the positive rate of bacterial culture, C-reactive protein (CRP) level, neutrophil/lymphocyte ratio (NLR), white blood cell (WBC) and neutrophil counts were significantly increased in the HCA group [37.2% (89/239) vs 22.6% (24/106), χ 2=7.10; 8.2 (0.0-273.0) vs 5.0 (0.0-218.9) ng/ml, U=2 419.00; 5.6 (1.2-58.6) vs 4.6 (1.7-18.7), U=2 357.50; 11.9 (4.5-30.0)×10 9/L vs 10.1 (5.8-21.8)×10 9/L, U=4 074.50; 9.5 (2.5-28.1)×10 9/L vs 7.6 (3.5-18.5)×10 9/L, U=4 021.50; all P<0.05], while the lymphocyte count was decreased [1.5 (0.5-3.7)×10 9/L vs 1.6 (0.7-3.9)×10 9/L, U=4 237.00, P=0.017]. CRP level, NLR, the gestational week at the onset of PROM and the duration of expected treatment were independent risk factors for HCA ( OR=1.069, 95% CI: 1.024-1.117; OR=1.192, 95% CI: 1.048-1.356; OR=0.906, 95% CI: 0.867-0.947; OR=1.017, 95% CI: 1.007-1.026). Based on the four risk factors, the predictive model was established and ROC curve was drawn. AUC for evaluating the performance of the predictive model was 0.880, which indicated a clinical significance. Conclusion:The model established based on the four risk factors, which were CRP level, NLR, the gestational week at onset of PROM and the duration of expected treatment, performs well in the prediction of HCA in women with PPROM during expected treatment and has good clinical practical value.

Objective To evaluate the effect of amitriptyline on the phosphorylation of histone deacetylase 5 (HDAC5) in the basolateral amygdala (BLA) of rats with neuropathic pain.Methods Thirty healthy male Wistar rats,weighing 250-300 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (S group),neuropathic pain group (NP group) and amitriptyline group (A group).Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized rats.Amitriptyline 10 mg/kg was intraperitoneally injected every day on 14-35 days after establishing the model in group A,while the equal volume of normal saline was given instead of amitriptyline in S and NP groups.The mechanical paw withdrawal threshold (MWT) was measured on 3,7,14,21,28 and 35 days after establishing the model in each group.The forced swimming test was performed on day 36 after establishing the model,and immobility time,climbing time and swimming time were recorded.The rats were then sacrificed,and brain tissues in BLA were obtained for determination of the expression of HDAC5 and phosphorylated HDAC5 (p-HDAC5) (by Western blot) and expressionof HDAC5 mRNA (by real-time quantitative polymerase chain reaction).Results Compared with group S,the MWT was significantly decreased at each time point,the immobility time was prolonged,and the swimming time and climbing time were shortened in group NP,and the MWT was significantly decreased on days 14,21 and 28 after establishing the model,the expression of p-HDAC5 was down-regulated,and the expression of HDAC5 mRNA was up-regulated in group A (P＜0.05).Compared with group NP,the MWT was significantly increased on days 21,28 and 35 after establishing the model,the immobility time was shortened,the climbing time was prolonged,the expression of p-HDAC5 was up-regulated,and the expression of HDAC5 mRNA was down-regulated in group A (P＜0.05or 0.01).Conclusion The mechanism by which amitriptyline improves depression is associated with promoting the phosphorylation of HDAC5 in BLA of rats with NP.

Objective:Care bundles for critically ill patients with early enteral nutrition up to goal was constructed. Its purpose was to improve early enteral nutrition, prognosis and provide reference basis for improving the rate of standard of early enteral nutrition in critically ill patients.Methods:By conducting systematic searching of domestic and foreign Chinese and English databases, related guide websites, relevant documents on early enteral nutrition in critically ill patients up to goal, which were obtained, evaluated, extracted, summarized and graded. After discussion by the research group, the first draft was prepared. Delphi method was used to conduct two rounds of expert correspondence, and the final draft of the proposal was established through the reliability analysis of correspondence results.Results:Twenty experts participated finally, and their opinions tended to be consistent after two rounds of expert inquiry. The authority coefficients were 0.92 and 0.91 respectively. The variation coefficients of the importance and operability of the two rounds of correspondence items were 0.05-0.20 and 0.05-0.21, 0.00-0.17 and 0.00-0.20 respectively. The Kendall concordance coefficients for the importance and operability of the two rounds of correspondence items were 0.16 and 0.13, 0.27 and 0.18 respectively. The differences were statistically significant ( χ2 values were 117.01-228.43, all P<0.05). Finally, the final draft of bundle of care for early enteral nutrition up to goal in critically ill patients was established which included three aspects related to evaluation, implementation, and effectiveness monitoring, besides care bundle included 12 intervention perspectives and 29 specific intervention measures. Conclusions:Based on evidence-based and delphi method constructing care bundles for critically ill patients with early enteral nutrition up to goal was scientific, reliable and practical which could provide theoretical and practical guidance for bundled nursing interventions to meet early enteral nutrition standards in critically ill patients.