MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC₅₀ values in vitro. However, the structure-activity relationship remains unclear. Herein, we adopted a "relative symmetry with electronegativity of different key-groups" strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC₅₀ in vitro and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the "relative symmetry with electronegativity of different key-groups" strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.

Objective:To establish a nested PCR method to detect the 2019 novel coronavirus (2019-nCoV), as a supplement to the real-time fluorescent PCR method, and discuss the preliminary application value of this method in clinical diagnosis.Methods:According to the conservative sequences of the 2019-nCoV gene, the nested PCR primers including N gene and S gene, were designed on line. By optimizing the nested PCR reaction systems, the qualitative detection was established by testing N gene and sequencing its PCR product while the preliminary type identification was established by testing S gene and sequencing its PCR product. The sensitivity was evaluated by the gradient dilution of 2019-nCoV positive samples’ nucleic acid and the specificity was evaluated by detecting the human coronavirus OC43, 229E, HKU1, NL63, influenza virus positive samples. The established method was applied to 15 samples with Ct >33 and 15 samples with Ct <33 screened by real-time fluorescent PCR, and the positive amplification result were sequenced and analyzed to verify the result. Results:The established nested PCR method could amplify specific bands of 355 bp N gene fragment and 449 bp S gene fragment. No amplifications occurred in other human coronaviruses samples including 229E、OC43、HKU1、NL63 or in influenza virus samples including H3N2, H1N1(pdm) and B. The minimum detection limit of the N gene fragment could reach Ct value about 37.21. Among the 30 COVID-19 positive samples, the N gene positive coincidence rate detected by nested PCR was 100% (30/30); the S gene positive coincidence rate reached 60% (18/30). 28 samples’ sequences of N gene fragment were completely consistent with 2019-nCoV by BLAST, and the characteristic result of site mutations of 12 samples’ S gene was obtained. Conclusions:A nested PCR method for the specific detection of 2019-nCoV was established, and some characteristic mutations on S gene could be analyzed by sequencing the PCR amplified products. It could be used as a supplement to the real-time fluorescent PCR method.

We have adopted various smart tools and applied multiple teaching models to smoothly carry out our on-line teaching. Aiming at encouraging students' self-learning and independent thinking, the first task is to cultivate students' self-learning ability and independent thinking way of clinical microbiology. Our online teaching model is based on the asynchronous small private online course (SPOC) of the Chinese University MOOC, the core part of our teaching model, and supplemented by the Sojump questionnaire test and WeChat, the inter-action channels among teachers and students. All of these build up an integrated teaching system which fully embodies the "student-oriented" teaching concept and pushes forward the promotion and application of online teaching in college specialized courses.

Objective To explore the effects of quasi-collective education in chronic renal failure dialysis patients before discharge. Methods A total of 94 cases of first hemodialysis patients in the First Affiliated Hospital of Harbin Medical University from April 2016 to March 2017 were selected as the research objects by convenience sampling method. According to the admission date, 45 patients admitted from April to September 2016 were assigned to control group, and 49 patients admitted from Octorber 2016 to March 2017 were assigned to observation group. Routine discharge health education was applied in the control group, while quasi-collective education was adopted in the observation group. The growth rate of body mass index (BMI), the incidence of complications, the average education time and patient satisfaction with education were compared between the two groups. Results On the 30th day of discharge, the growth rate of BMI of the observation group was lower than that of the control group, while the compliance was higher than that of the control group, and the differences were statistically significant (t=5.289, Z=4.566; P<0.01). The incidence of dialysis complications in the observation group was lower than that in the control group, and the average education time was higher than that in the control group. Patients' satisfaction with education in time consuming, freedom, autonomy and richness in the observation group were statistically significantly higher than those of the control group (P<0.01). Conclusions Quasi-collective education can significantly improve the discharge education effectiveness in chronic renal failure dialysis patients, so as to improve the treatment effect.