The eye irritation test and pharmacokinetic study of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits / 药学实践杂志

Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.

Impact of vaccination on the COVID-19 pandemic: Evidence from U.S. states

Governments worldwide are implementing mass vaccination programs in an effort to end the novel coronavirus (COVID-19) pandemic. Although the approved vaccines exhibited high efficacies in randomized controlled trials1,2, their population effectiveness in the real world remains less clear, thus casting uncertainty over the prospects for herd immunity. In this study, we evaluated the effectiveness of the COVID-19 vaccination program and predicted the path to herd immunity in the U.S. Using data from 12 October 2020 to 7 March 2021, we estimated that vaccination reduced the total number of new cases by 4.4 million (from 33.0 to 28.6 million), prevented approximately 0.12 million hospitalizations (from 0.89 to 0.78 million), and decreased the population infection rate by 1.34 percentage points (from 10.10% to 8.76%). We then built a Susceptible-Infected-Recovered (SIR) model with vaccination to predict herd immunity. Our model predicts that if the average vaccination pace between January and early March 2021 (2.08 doses per 100 people per week) is maintained, the U.S. can achieve herd immunity by the last week of July 2021, with a cumulative vaccination coverage of 60.2%. Herd immunity could be achieved earlier with a faster vaccination pace, lower vaccine hesitancy, or higher vaccine effectiveness. These findings improve our understanding of the impact of COVID-19 vaccines and can inform future public health policies regarding vaccination, especially in countries with ongoing vaccination programs.

Preparation of propranolol hydrochloride cubosomes by pH gradient method / 药学实践杂志

Objective To prepare propranolol hydrochloride loaded cubosomes (PPL-Cubs) with high entrapment efficiency. Methods PPL-Cubs was prepared by pH gradient method. Pressure and cycles of high pressure homogenization, dosage of glyceryl monooleate and poloxamer 407 were optimized to prepare blank cubosomes with particle size and polydispersity index as the indexes. The influences of various factors, including exterior pH values, internal pH values, the ratio of carrier to drug, particle size and polydispersity index of blank cubosomes, incubation temperature and time, and drug concentration on the entrapment efficiency were investigated. Results The blank cubosomes with small particle size and polydispersity index was prepared under homogenization conditions of 900 bar for 7 cycles, glyceryl monooleate dosage of 25%, and poloxamer 407 dosage of 5%. PPL-Cubs showed high entrapment efficiency with exterior pH value of 8.5, internal pH value of 3.0, ratio of carrier to drug of 6∶1, incubation temperature of 20 ℃, and incubation time of 15 min, and drug concentration of 1%. The particle size and polydispersity index of blank cubosomes showed no influence on entrapment efficiency. Conclusion PPL-Cubs with high entrapment efficiency could be prepared under the pH gradient method.

Exploration and practice of undergraduate tutorial system in clinical medical colleges / 中华医学教育探索杂志

Objective:To explore the necessity and feasibility of undergraduate tutorial system in clinical medical colleges.Methods:A questionnaire survey on the scientific research situation was conducted among 64 students from the long-term class and the base class of the Fourth Clinical Medical College of Capital Medical University from September 2015 to February 2018. The undergraduate tutorial system was tested in two classes for one year. After that, the questionnaire survey was conducted again to compare it with the system before implementation and analyze the trial situation of the tutorial system.Results:During the practice of the undergraduate tutorial system, it was found that most of the students wanted to participate in scientific research and were guided by tutors to improve their scientific research capabilities, but at the same time, it was also discovered that tutors were busy with their work and were unable to give insufficient guidance to the students. In terms of medical papers writing, from September 2015 to February 2018, 20 students in the long-term class participating in the tutorial system wrote 23 papers in total, and 9 students in the base class totally wrote 9 papers, with a significant difference ( P<0.05). From September 2015 to February 2018, 9 students from the base class wrote 9 papers, and from March 2018 to March 2019, there were 18 students from the base class who totally wrote 27 papers, with a significant difference ( P<0.05). Conclusion:It's feasible and necessary to implement the undergraduate tutorial system in clinical medical colleges.

Preparation and in vitro release of tacrolimus-loaded cationic nanoemulsion-based in-situ gel / 药学实践杂志

Objective In order to improve the problems of poor water-solubility and low bioavailability of ocular tacrolimus, a cationic nanoemulsion in-situ gel of tacrolimus was developed and its drug release behavior in vitro was studied to provide a basis for further research. Methods Tacrolimus-loaded cationic nanoemulsion was prepared by high pressure homogenization and dispersed in poloxamer 407 and poloxamer 188 to prepare tacrolimus-loaded cationic nanoemulsion-based in-situ gel. The membraneless dissolution model was used to study the in vitro drug release behavior. Results The inverse glass bottle method was used to determine the gelation temperature. The optimal formulation of gel matrix was screened out as 26% poloxamer 407 and 12% poloxamer 188. The in vitro release results showed that the rate of gel dissolution determined the in vitro drug release. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel is successfully prepared. Its in vitro drug release is stable. It meets the requirement of ophthalmic formulation and shows good prospects for ocular application.

Surgical strategy for patients with small acoustic neuroma / 中国耳鼻咽喉头颈外科

OBJECTIVE To summarize surgical treatment effects and to discuss surgical strategy for Small acoustic neuroma.METHODS The clinical data of 26 patients with small acoustic neuroma treated with surgery in our department were analyzed retrospectively.25 patients with preoperative hearing grading of C and D received the labyrinthine approach acoustic neuroma resection,and 1 patient with preoperative hearing grading of B received middle fossa approach acoustic neuroma resection.The preoperative and postoperative hearing level,incidence of tinnitus,balance disturbance and weakness of facial muscles were analyzed retrospectively.The control and recurrence of the tumor,the incidence of complications were recorded.RESULTS Total resection was achieved in 25 cases (96％),and in 1 cases achieved sub total resection due to the fact that the tumor was too adhesive to the facial nerve The follow-up time ranged from 6 months to 7 years with 7 cases lost contact.No deaths nor intracranial infection were encountered.Cerebrospinal fluid rhinorrhea was found in 1 cases after the operation and eustachian tube blockage was performed.All patients(100％) had their facial nerve reserved and 16 patients (88％) had their cochlea nerve reserved.17patients(89.5％) had intact facial nerve function and 2 patients suffered from level Ⅲ facial nerve paralysis (House-Brackmann grade) post operatively.6 patients suffered from vertigo pre-operatively and 5 of them reported disappearance of vertigo after the surgery.Of the 13 patients who did not have vertigo before the surgery,1 patient complained sense of dizziness and unsteady walking post-operatively.5 patients (33.3％) reported disappeared or alleviated tinnitus,8 patients (53％) had the same degree of tinnitus and 2 patients reported worsened tinnitus post-operatively.For patients who did not have tinnitus before the surgery,no tinnitus was reported post-operatively.CONCLUSION treatment strategy for small acoustic neuroma requires personalized setting based on the age of the patient,the combined systemic disease,the severity of the symptoms and the growth rate of the tumor.For patients without practical hearing,the tumor could be removed with labyrinthine approach,and the integrity of the cochlear nerve should be preserved as far as possible,for further reconstruction of hearing ability and cochlear implantation.

Folate-conjugated polyspermine for lung cancer-targeted gene therapy

Biodegradable polyamines have long been studied as potential recombinant viral gene vectors. Spermine (SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol) (PEG) diacrylate (SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid (FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector (FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamine(®) 2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors (FRs). Moreover, in vivo delivery of green fluorescent protein (GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.

SOX1 and tumor / 国际肿瘤学杂志

SOX1,a member of the SOX transcript factor super family,has been demonstrated having the functions of regulating the development of human embryonic neural system and crystalline lens,and the additional function of SOX1 in tumors are attracting more and more attention as well.It is reported in resent years that SOX1 is detected lowly expressed in many kinds of tumor issues,which owns to the methylation of SOX1.SOX1 can also regulate the abilities of tumors on proliferation,invasion and migration.Besides,SOX1 may play a crucial role in regulation of the differentiation of cancer stem cells.Further research of SOX1 and its function among related pathways may contribute to seeking for new therapies for tumor treatment.