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 disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.

Objective To investigate the impact of hemoglobin(Hb)level on the risk of all-cause mortality in elderly patients with stable coronary artery disease(SCAD)treated by percutaneous coronary intervention(PCI).Methods A retrospective cohort study was conducted on 195 elderly SCAD patients treated by PCI in our hospital from June 2016 to December 2017,a total of 180 case were followed up.They were divided into four groups based on quartiles of Hb levels:Q1 group[≤122(108.28±12.53)g/L,n=47],Q2 group[122＜Hb≤137(130.07±4.33)g/L,n=43],Q3 group[137＜Hb≤148(142.67±3.10)g/L,n=46],and Q4 group[＞148(158.36±8.50)g/L,n=44].Their clinical data were collected and compared among the groups.All patients were followed up,with all-cause mortality as endpoint.Cox regression analysis was used to evaluate the impact of Hb level on all-cause mortality in elderly SCAD patients treated by PCI.Results For the 180 patients with complete follow-up,the median follow-up time was 703(415,1121)d,and the incidence of all-cause mortality was 10.00％(totally 18 deaths).And the incidence was 25.50％(12 deaths),7.00％(3 death),4.30％(2 deaths)and 2.30％(1 death)in Q1,Q2,Q3,and Q4 groups,respectively,with statistically significant differences(P＜0.01).Univariate Cox regression analysis showed age was a risk factor for all-cause death(P＜0.01),while Hb level,BMI,smoking history,dyslipidemia,and aspirin use were a risk facotr for all-cause death(P＜0.05,P＜0.01).Further multivariate Cox regression analysis revealed Hb level was a risk facotr for all-cause death(HR=0.96,95％CI:0.93-0.99,P＜0.01).The risk of all-cause mortality was 3.68 times higher in the Q1 group than the Q2 group(HR=3.68,95％CI:1.01-13.45,P＜0.05),and there was no correlation in the incidence between the Q3 and Q4 groups(P＞0.05).Conclusion Low Hb level is an independent predictor for all-cause mortality in elderly SCAD pa-tients after PCI.

Objective:To investigate the phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B/Victoria lineage (BV) viruses in Beijing during the 2021-2022 influenza surveillance season, and to analyze whether the circulating BV viruses match the vaccine strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) cases in the 2021-2022 influenza surveillance season were collected from surveillance network labs in Beijing and cultured in MDCK cells and chicken embryo to isolate BV viruses. Nucleic acids of the viruses were extracted, and the HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity of the HA gene was analyzed using MEGA5.0 software. A phylogenetic tree of HA gene was constructed using the maximum likelihood method. The N-glycosylation sites in HA were predicted online. Three-dimensional structure of HA was constructed using SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) test was performed to analyze the antigenicity of BV viruses.Results:A total of 402 BV viruses were collected and 58 strains with full-length HA gene sequences were chosen for further analysis. Compared with the HA gene of this year′s vaccine strain (B/Washington/02/2019), there were 27 amino acid mutations, 11 of which were located in four different antigenic determinants. The phylogenetic analysis revealed that three subgroups of 1A.3, 1A.3a1, and 1A.3a2 co-circulated in Beijing with 54 strains (54/58, 93.10%) clustered to the Clade 1A.3a2, two strains (2/58, 3.45%) clustered to the Clade 1A.3a1, and two strains (2/58, 3.45%) in the same subgroup (Clade 1A.3) as the vaccine component BV strain in 2021-2022. Compared with the vaccine strain (B/Washington/02/2019), two BV strains had an additional N-glycosylation site at residue 197, while the other 56 strains showed no change in N-glycosylation sites. Antigenic analysis showed that 35 BV strains (35/58, 60.34%) were antigenically similar to the vaccine strain and 23 strains (23/58, 39.66%) were low-response strains.Conclusions:Three subgroups of BV viruses co-circulated in Beijing during the 2021-2022 influenza surveillance season. The predominant subgroup was Clade 1A.3a2 (93.10%), showing a certain genetic distance with the vaccine strain (B/Washington/02/2019). Nearly 40% (39.66%) of the viruses were low-response strains. This study indicated that continuous monitoring of the variations of influenza epidemic strains and timely providing laboratory basis for screening vaccine component strains were the basic technical guarantee for coping with influenza pandemic.

Objective:To investigate the prognostic significance of anemia in elderly patients with stable coronary artery disease treated by percutaneous coronary intervention(PCI).Methods:In this retrospective cohort study, 180 patients with stable coronary artery disease aged ≥60 years undergone percutaneous coronary intervention and with complete clinical data, admitted to Nanjing Meishan Hospital between June 2016 and December 2017, were selected.Baseline clinical data of the patients were collected, including hemoglobin, C-reactive protein, lipids, fasting glucose, glycated hemoglobin, blood creatinine, and left ventricular ejection fraction on cardiac color ultrasound.The endpoints of the follow-up included major adverse cardiac events(MACE), such as all-cause death, non-fatal myocardial infarction, and non-fatal stroke.According to the hemoglobin level, participants were divided into an anemia group(n=32)and a non-anemia group(n=148). Clinical data of the two groups were compared, and the Kaplan-Meier method and multivariate analysis with the Cox regression method were used to evaluate the effect of anemia on the occurrence of MACE in elderly patients with stable coronary artery disease treated by PCI.Results:The median duration of the follow-up of the 180 patients was 702.5 days and MACE occurred in 27(15.0%). Compared with the non-anemia group, the anemia group had a higher age, C-reactive protein level and MACE ratio, lower levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and the glomerular filtration rate, and higher proportions of patients with smoking history and patients with dyslipidemia( P<0.05). Kaplan-Meier curves suggested that the incidence of MACE in the anemia group was higher than that in the non-anemia group[37.5%(12/32) vs.10.1%(15/148), P<0.05]. Multivariate analysis with the Cox regression method showed that the risk of MACE in the anemia group was 2.91 times higher than that in the non-anemia group( HR=2.91, 95% CI: 1.13-7.48, P<0.05). Conclusions:Anemia is an independent predictor of MACE in elderly patients with stable coronary artery disease after PCI.

Objective:To explore the parenting characteristics of children with attention deficit hyperactivity disorder (ADHD) and conduct problems.Methods:This was a cross-sectional study involving 84 ADHD children with conduct problems and 75 ADHD children without conduct problems treated in the Outpatient Department of Children′s Health and Mental Health Center, Shenzhen Children′s Hospital from September 2017 to December 2019, and 54 healthy control children (healthy children in ordinary primary and secondary schools in Shenzhen) were included.The Egna Minnen av Barndoms Uppfostran (EMBU) scale was used to access the parenting styles of participants. ANCOVA was used to compare the different score of all factors in EMBU among these 3 groups and Tukey′s post-hoc comparisons were also performed.All comparisons were corrected for age and sex. Results:Among the factor scores of EMBU scale, ADHD children with conduct problems scored significantly higher on parental and maternal harsh/punishment [Parental (22.10±4.92) scores vs.(19.40±4.01) scores vs.(17.40±2.51) scores; Maternal (15.10±3.54) scores vs.(13.70±2.78) scores vs.(12.40±1.97) scores] and the reject/deny factors [Parental(10.60±2.49)scores vs.(9.40±2.06)scores vs.(8.90±1.61)scores, Maternal(13.90±3.28)scores vs.(12.40±2.64)scores vs.(11.60±2.19)scores] than ADHD children without conduct problems and the healthy control group (all P<0.001). On parental overprotection factors, both ADHD groups scored higher than the healthy control group [(10.30±2.03) scores vs.(9.80±2.13) scores vs.(8.70±1.92) scores, P<0.001], while on maternal over-interference factor, ADHD children with conduct problem scored significantly higher than ADHD children without conduct problems and the healthy controls [(36.00±4.64) scores vs.(34.60±4.38) scores vs.(33.30±4.92) scores, P=0.009]. Conclusions:Parents of ADHD children with conduct problems tend to use more negative parenting skills like punishment, over-interference, rejection and denial.This kind of negative parenting style, to some extent, causes the conduct problems in children with ADHD.

Laughing gas (Nitrogen monoxide) is currently abused due to its low price and easy availability. This article discussed the clinical manifestations of a patient with subacute combined degeneration of the spinal cord caused by inhalation of laughing gas. The patient developed numbness of extremities, unstable walking, and decreased serum vitamin B 12 level. MRI of the cervical spine showed abnormal signals in the lateral and posterior cords of the cervical spinal cord (C2-6) , neuroelectrophysiological examination showed peripheral nerve damage in the extremities. After treatment with vitamin B 12 supplementation, the patient's condition gradually improved. Clinicians diagnose subacute combined degeneration of the spinal cord, especially when the patient has no gastrointestinal disease, diet, malnutrition, etc., they need to carefully inquire about the history of nitrous oxide inhalation to avoid missed diagnosis.

Laughing gas (Nitrogen monoxide) is currently abused due to its low price and easy availability. This article discussed the clinical manifestations of a patient with subacute combined degeneration of the spinal cord caused by inhalation of laughing gas. The patient developed numbness of extremities, unstable walking, and decreased serum vitamin B 12 level. MRI of the cervical spine showed abnormal signals in the lateral and posterior cords of the cervical spinal cord (C2-6) , neuroelectrophysiological examination showed peripheral nerve damage in the extremities. After treatment with vitamin B 12 supplementation, the patient's condition gradually improved. Clinicians diagnose subacute combined degeneration of the spinal cord, especially when the patient has no gastrointestinal disease, diet, malnutrition, etc., they need to carefully inquire about the history of nitrous oxide inhalation to avoid missed diagnosis.

Objective To assess the value of pulmonary artery CT obstruction index for the evaluation of the severity of pulmonary embolism (PE),and to investigate the relation between pulmonary artery CT obstruction index and D-dimer levels.Methods 125 patients were diagnosed as PE by computed tomographic pulmonary angiography (CTPA)and D-dimer.Patients were separated into high-risk group and non-high risk group.CT obstruction index,D-dimer levels,diameter of the pulmonary artery were compared between two groups. Spearman’s rank correlation coefficients were used to assess the correlation between the CT obstruction index and the D-dimer levels,diameter of the pulmonary artery.Results CT congestion index of high-risk PE group was obviously higher than that of the non-high risk group (P=0.000).The diameter of pulmonary artery in high-risk PE group was obviously greater than that of the non-high risk group,the difference was statistically significant (P=0.000).No statistically significant difference was found in D-dimer levels between the two groups (P=0.103).There was no correction with CT congestion index and D-dimer levels(P=0.71).Conclusion The D-dimer levels of serum was a predictor of pulmonary embolism,cannot evaluate the severity of PE.CT obstruction index can reflect the severity of PE in some extent as an indicator of PE,there was no correlation with CT obstruction index and D-dimer levels.

Objective To explore the protective effects of quercetin on damage induced by oxidative stress and to clari?fy its molecular mechanism. Methods Chang liver cell cultures were randomly divided into control groups, H2O2 group and 3 doses of quercetin groups. Cell survival rate was detected with MTT. Cell apoptotic rate was measured by FACS(Fluores?cence-activated cell sorting). Intracellular reactive oxygen species (ROS) level in Chang liver cells were tested by flow cy?tometer. The DCF fluorescence intensity of DCFH-DA-stained intracellular ROS was observed by fluorescence microscope. The levels of malondialdehyde (MDA), superoxide dismutase(SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in liver cells using commercial available kits. The expression of Nrf2 were detected by Western blot. Re?sults Compared with control, cell survival rate and levels of SOD, CAT and GSH-Px decreased significantly in H2O2 group (P < 0.05 ),while cell appotosis rate, content of MDA and mean fluorescence intensity(MFI) increased in H2O2 group (P <0.05). In comparison with H2O2, expression of Nrf2 protein was higher in all three quercetin treatment groups (P<0.05). Con?clusion Quercetin protected Chang liver cells from H2O2-induced oxidative stress, which may be caused by the increased ex?pressions of down stream antioxidant genes via activating the Nrf2-ARE signaling pathway.