Objective To investigate the possible pathway of FITC-dextran to the cochlea after post-aural injection.Methods The FITC-dextran(weight between 3 000~5 000) was chosen as a tracer in this study.A total of 200 suckling mice were randomly divided into four groups, with 50 in each group.Each animal was then administered with FITC-dextran or dextran via either post-auricular or intra-muscular injection, to a total dose of 20 μl (5 mg/ml).Samples were obtained at 0, 1/12, 1/4, 1/2, 1, 3, 5, 7, 12, and 24 hours after adminstmiceion, and the confocal technique was used to observe the distribution of the tracer.Taking into consideration the influence of spontaneous fluorescence, the fluorescence intensity ratio of the experimental and control groups was used as the final statistical data.Results FITC-dextran injected intramuscularly group: The fluorescence signal can be detected in the sigmoid sinus(SS) 3h after management, while in endolymphatic sac and cochlea at 12 h.FITC-dextran injected post-aurally group: After administration, an obvious fluorescence signal could be observed in the sigmoid sinus and endolymphatic sac immediately, cochlea at 30 min.The signal of the sigmoid sinus, endolymphatic sac and cochlea gradually increased successively, peaked at 5~15 min, 30 min and 60 min, and then decreased gradually.At 12 h, another small increases appeared, and the signal could not be detected at 24 h.Conclusion Compared with intramuscularly application, post-auricular injection can allow the drug to directly reach the endolymph.It is possible that the tracer first gathered in the SS via local blood circulation or infiltration, then entered the ES via micro-circulation around, and eventually arrived at the cochlea.

The dynamic behaviour of a microbubble confined within a rigid micro-tube was studied using finite element method. The results indicated that the microbubble oscillation was limited when constrained within the micro-tube. Both the expansion ratio of its effective radius and natural frequency decreased with the decrease of the tube radius. Meanwhile, the deformation of the microbubble was non-spherical and became more significant when the ultrasound pressure amplitude increased. The dynamic behaviour in micro-tube was different from that in infinite liquid.
Blood Vessels ; physiology ; Contrast Media ; Finite Element Analysis ; Microbubbles ; Microtubules ; Molecular Dynamics Simulation

ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease （CKD） and the effect of the therapy on the neutrophil-to-lymphocyte ratio （NLR） as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories， while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment， the clinical efficacy was assessed based on the changes in traditional Chinese medicine （TCM） symptom scores， renal function indicators， and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment （P<0.01）， and the decreases were more significant in the observation group than in the control group （P<0.05）. The total response rate of TCM symptoms in the observation group was 79.31% （23/29）， which was higher than that （62.96%， 17/27） in the control group （Z=0.604，P<0.05）. ② After treatment， the observation group showed declined serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， and cystatin C （Cys C） and increased glomerular filtration rate （GFR） （P<0.01）， and the control group showed lowered SCr level and increased GFR （P<0.05）. The observation group had lower SCr level and higher GFR than the control group after treatment （P<0.05）. The total response rate of renal function in the observation group was 79.31% （23/29）， which was higher than that （55.56%， 15/27） in the control group （Z=1.127，P<0.01）. ③ The NLR in the observation group decreased after treatment （P<0.05）， and it was lower than that in the control group （P<0.05）. ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.

Objective: To investigate the correlation between age-related hearing loss and cognitive impairment. Methods: 201 elderly patients, who were admitted to the Department of Otorhinolaryngology of Peking University People′s Hospital from March 1, 2017 to March 31, 2017, were evaluated with hearing screening and the Montreal Cognitive Assessment Scale. Among them, 101 were female and 100 were male, aged 60-90 years old. Taking the cognitive level as the dependent variable, and taking the age, sex, education, occupation, marital status, residence, and average hearing loss (average hearing threshold of 500, 1 000, 2 000, and 4 000 Hz), as well as the length of conscious hearing loss as the independent variables, the single factor analysis and multivariate linear regression analysis were used to screen the main factors affecting the cognitive level of the elderly. Results: Of the 201 elderly patients, 39 had normal hearing, 65 had mild hearing loss, 80 had moderate hearing loss, 16 had severe hearing loss, and 1 had profound hearing loss. The average degree of hearing loss was the influencing factor of cognitive impairment, and it mainly affected the directional force and abstract ability in the cognitive domains (P<0.05); The age, self-reported hearing loss, years of education, marital status, past ear diseases, and hypertension were relatively independent factors that affected the cognitive level(P<0.05). Conclusions Age-related hearing loss is the risk factor for the cognitive impairment, especially for abstraction and orientation, in the elderly. The self-reported hearing loss is an independent risk factor for cognitive impairment.

Plasticity in the glutamatergic synapses on striatal medium spiny neurons (MSNs) is not only essential for behavioral adaptation but also extremely vulnerable to drugs of abuse. Modulation on these synapses by even a single exposure to an addictive drug may interfere with the plasticity required by behavioral learning and thus produce impairment. In the present work, we found that the negative reinforcement learning, escaping mild foot-shocks by correct nose-poking, was impaired by a single in vivo exposure to 20 mg/kg cocaine 24 h before the learning in mice. Either a single exposure to cocaine or reinforcement learning potentiates the glutamatergic synapses on MSNs expressing the striatal dopamine 1 (D1) receptor (D1-MSNs). However, 24 h after the cocaine exposure, the potentiation required for reinforcement learning was disrupted. Specific manipulation of the activity of striatal D1-MSNs in D1-cre mice demonstrated that activation of these MSNs impaired reinforcement learning in normal D1-cre mice, but inhibition of these neurons reversed the reinforcement learning impairment induced by cocaine. The results suggest that cocaine potentiates the activity of direct pathway neurons in the dorsomedial striatum and this potentiation might disrupt the potentiation produced during and required for reinforcement learning.

OBJECTIVE To prepare hyperoside mixed nanomicelles （Hyp-F127/TPGS） and optimize its preparation technology，and to investigate its intestinal absorption characteristics. METHODS Hyp-F127/TPGS was prepared by thin film dispersion method. Based on single factor test and Plackett-Burman design ，combined with Box-Behnken response surface method ， the preparation process was optimized and validated using entrapped efficiency （EE）and drug loading （DL）as evaluation indexes ， F127-TPGS mass ratio ，hydration time and the amount of Hyp as factors. The appearance and microscopic morphology of Hyp-F127/TPGS obtained by the optimal technology were observed ，and the particle size ，polydispersity index （PDI）and Zeta potential were also determined. The critical micelle concentration （CMC）of blank micelle （F127/TPGS），in vitro release behavior and preliminary stability of Hyp-F 127/TPGS were investigated ，and absorption characteristics of Hyp-F 127/TPGS were investigated by in situ unidirectional intestinal perfusion model. RESULTS The optimal preparation technology of Hyp-F 127/TPGS included F127-TPGS mass ratio of 2∶1，hydration time of 2 h，and Hyp amount of 9 mg. Results of three validation tests showed that the EE of Hyp-F 127/TPGS was （87.20±0.99）％，and the DL was （5.02±1.20）％，deviations from predicted values were 0.92％ and 2.39％. The micelles prepared by optimal technology were yellow ，clear and transparent solution ，with good Tyndall effect ；under transmission electron microscope ，they were spherical ，complete and evenly distributed ；the particle size was （15.02±0.16）nm， the PDI was 0.092±0.031，and the Zeta potential was （－6.67±1.47）mV. The CMC of F 127/TPGS was 21 μg/mL，Hyp-F127/ TPGS was stable after 4 weeks of storage at 4 ℃，and the cumulative release rates of Hyp-F 127/TPGS and Hyp control were （66.30±2.93）％（96 h）and（99.24±0.27）％（60 h），respectively. Hyp-F 127/TPGS and Hyp reference were absorbed in each intestinal segment ，and the main absorption sites were jejunum and duodenum respectively ；drug absorption rate constant andapparent absorption coefficient of the former were significantly higher than those of the latter （P＜0.05 or P＜0.01）. E-mail：zhangyuhangxz@163.com CONCLUSIONS The optimized preparation technology of Hyp-F127/TPGS is stable and feasible ；prepared Hyp-F 127/ TPGS shows a sustained -release effect ，which promotes the intestinal absorption of H yp to a certain extent.