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.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To develop a deep learning-based segmentation model MT-UNet to automatically segment bone metastases and benign bone lesions in bone scintigraphy with SPECT/CT.Methods:A total of 93 patients (48 males and 45 females, age 28-84 years) who underwent bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from June 2023 to December 2023 were enrolled retrospectively in this study, with a total of 184 bone lesions (94 benign lesions and 90 metastatic tumors). The MT-UNet was employed to segment bone lesions in SPECT, CT and SPECT/CT images respectively. Comparative analysis with 8 segmentation models was performed. The training set and validation set were divided by using 5-fold cross-validation and transfer learning was introduced to further enhance the robustness of the model. An additional cohort of 22 patients (15 males and 7 females, age 37-87 years) who received bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from April 2023 to May 2023 were included, comprising 40 bone lesions (22 benign lesions and 18 metastatic tumors) as the test set of MT-UNet. Segmentation performance of different models was assessed using accuracy, sensitivity, specificity, AUC, intersection over union and Dice similarity coefficient (DSC). Delong test was used to compare the segmentation efficacy among different models in the test set.Results:In the validation set, MT-UNet demonstrated DSC of 0.940, 0.962, and 0.963 for SPECT, CT, and SPECT/CT bone lesion segmentation, respectively, which were outperformed other models. Following transfer learning implementation, the SPECT/CT model′s DSC was improved to 0.984. In the test set, MT-UNet maintained comparable segmentation performance to the validation set, with significant AUC differences among the three models ( Z values: from -15.42 to -9.27, all P<0.01). Compared with conventional image interpretation, MT-UNet-based segmentation reduced physician interpretation time from 164min to 102min. Conclusion:MT-UNet has shown good performance in automatic segmentation of bone metastases and benign bone lesions, and is expected to become an important part of SPECT/CT image intelligent diagnosis system for bone metastases.

OBJECTIVE To explore the clinical effect of Kangfuxin solution on wound healing,wound stromal cell-derived factor-1a(SDF-1a),vascular endothelial growth factor(VEGF)and angiopoietin-2(ANG-2)of the peri-anal abscess patients complicated with wound infection.METHODS A total of 118 perianal abscess patients compli-cated with postoperative wound infection who were treated in Wuhan Eighth Hospital from Jun.2018 to Oct.2023 were enrolled in the study and were randomly divided into the Kangfuxin solution group and the potassium per-manganate group,with 59 cases in each group.Both groups were treated with debridement of infection foci in a timely manner,the potassium permanganate group was given potassium permanganate for daily cleaning and treat-ment,and the Kangfuxin solution group was given Kangfuxin solution for daily treatment.The wound healing time,time of disappearance of wound edema and shedding time of slough were recorded,and the reduced rate of wound surface was determined after the treatment.The pain degree was evaluated by visual analogue scale(VAS)after the treatment,and the levels of wound SDF-1a,VEGF and Ang-2 levels were detected.RESULTS The wound healing time[(12.53±2.57)days],time of disappearance of wound edema[(6.89±1.06)days]and shed-ding time of slough[(3.06±0.68)days]were shorter in the Kangfuxin solution group than in the potassium per-manganate group(P＜0.05).The reduced rates of wound surface were higher after the treatment for 2,7 and 14 days,the VAS score was lower,and there were significant differences(P＜0.05).The levels of SDF-1a,VEGF and Ang-2 of the two groups were higher after the treatment than before the treatment,the levels of SDF-1a,VEGF and Ang-2 of the Kangfuxin solution group were higher than those of the potassium permanganate group,and there were significant differences(P＜0.05).CONCLUSIONS Kangfuxin solution can be used for wound repair of the perianal abscess patients complicated with wound infection,which may accelerate the wound healing.The action mechanisms may be associated with the regulation of expressions of wound SDF-1a,VEGF and Ang-2.

Objective To investigate the correlation between hemoglobin A1c(HbA1c)levels and excessive daytime sleepiness(EDS)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 132 T2DM patients and 40 healthy people(NC group)who were treated in the outpatient department of Nanjing Meishan Hospital from December 2020 to December 2022 were selected.General clinical data of the subjects were collected,and their Epworth sleepiness scale(ESS)scores,Pittsburgh sleep quality index(PSQI),and apnea-hypopnea index(AHI)were measured.Based on ESS scores,T2DM patients were divided into simple T2DM group(ESS score<9,n=99)and EDS group(ESS score≥9,n=33)according to ESS score.The baseline data were compared for each group.Spearman correlation analysis and multivariate logistic regression model were used to evaluate the correlation between HbA1c levels and EDS.The receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)to evaluate the predictive value of HbA1c levels for EDS.Results HbA1c,fasting plasma glucose,AHI index and PSQI score in EDS group were higher than those in T2DM and NC group(P<0.05).Spearman correlation analysis showed that ESS score was positively correlated with HbA1c in T2DM patients(P<0.05).Multivariate logistic regression analysis revealed that elevated HbA1c levels emerged as a significant and independent risk factor for the onset of EDS.The ROC curve indicated that the AUC of HbA1c for predicting EDS was 0.736.Conclusions There is an independent positive correlation between HbA1c levels and EDS in T2DM patients,which provides clues for early identification and treatment of EDS in clinical practice.

Objective To investigate the correlation between hemoglobin A1c(HbA1c)levels and excessive daytime sleepiness(EDS)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 132 T2DM patients and 40 healthy people(NC group)who were treated in the outpatient department of Nanjing Meishan Hospital from December 2020 to December 2022 were selected.General clinical data of the subjects were collected,and their Epworth sleepiness scale(ESS)scores,Pittsburgh sleep quality index(PSQI),and apnea-hypopnea index(AHI)were measured.Based on ESS scores,T2DM patients were divided into simple T2DM group(ESS score<9,n=99)and EDS group(ESS score≥9,n=33)according to ESS score.The baseline data were compared for each group.Spearman correlation analysis and multivariate logistic regression model were used to evaluate the correlation between HbA1c levels and EDS.The receiver operating characteristic(ROC)curve was used to calculate the area under the curve(AUC)to evaluate the predictive value of HbA1c levels for EDS.Results HbA1c,fasting plasma glucose,AHI index and PSQI score in EDS group were higher than those in T2DM and NC group(P<0.05).Spearman correlation analysis showed that ESS score was positively correlated with HbA1c in T2DM patients(P<0.05).Multivariate logistic regression analysis revealed that elevated HbA1c levels emerged as a significant and independent risk factor for the onset of EDS.The ROC curve indicated that the AUC of HbA1c for predicting EDS was 0.736.Conclusions There is an independent positive correlation between HbA1c levels and EDS in T2DM patients,which provides clues for early identification and treatment of EDS in clinical practice.

OBJECTIVE To explore the clinical effect of Kangfuxin solution on wound healing,wound stromal cell-derived factor-1a(SDF-1a),vascular endothelial growth factor(VEGF)and angiopoietin-2(ANG-2)of the peri-anal abscess patients complicated with wound infection.METHODS A total of 118 perianal abscess patients compli-cated with postoperative wound infection who were treated in Wuhan Eighth Hospital from Jun.2018 to Oct.2023 were enrolled in the study and were randomly divided into the Kangfuxin solution group and the potassium per-manganate group,with 59 cases in each group.Both groups were treated with debridement of infection foci in a timely manner,the potassium permanganate group was given potassium permanganate for daily cleaning and treat-ment,and the Kangfuxin solution group was given Kangfuxin solution for daily treatment.The wound healing time,time of disappearance of wound edema and shedding time of slough were recorded,and the reduced rate of wound surface was determined after the treatment.The pain degree was evaluated by visual analogue scale(VAS)after the treatment,and the levels of wound SDF-1a,VEGF and Ang-2 levels were detected.RESULTS The wound healing time[(12.53±2.57)days],time of disappearance of wound edema[(6.89±1.06)days]and shed-ding time of slough[(3.06±0.68)days]were shorter in the Kangfuxin solution group than in the potassium per-manganate group(P＜0.05).The reduced rates of wound surface were higher after the treatment for 2,7 and 14 days,the VAS score was lower,and there were significant differences(P＜0.05).The levels of SDF-1a,VEGF and Ang-2 of the two groups were higher after the treatment than before the treatment,the levels of SDF-1a,VEGF and Ang-2 of the Kangfuxin solution group were higher than those of the potassium permanganate group,and there were significant differences(P＜0.05).CONCLUSIONS Kangfuxin solution can be used for wound repair of the perianal abscess patients complicated with wound infection,which may accelerate the wound healing.The action mechanisms may be associated with the regulation of expressions of wound SDF-1a,VEGF and Ang-2.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To develop a deep learning-based segmentation model MT-UNet to automatically segment bone metastases and benign bone lesions in bone scintigraphy with SPECT/CT.Methods:A total of 93 patients (48 males and 45 females, age 28-84 years) who underwent bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from June 2023 to December 2023 were enrolled retrospectively in this study, with a total of 184 bone lesions (94 benign lesions and 90 metastatic tumors). The MT-UNet was employed to segment bone lesions in SPECT, CT and SPECT/CT images respectively. Comparative analysis with 8 segmentation models was performed. The training set and validation set were divided by using 5-fold cross-validation and transfer learning was introduced to further enhance the robustness of the model. An additional cohort of 22 patients (15 males and 7 females, age 37-87 years) who received bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from April 2023 to May 2023 were included, comprising 40 bone lesions (22 benign lesions and 18 metastatic tumors) as the test set of MT-UNet. Segmentation performance of different models was assessed using accuracy, sensitivity, specificity, AUC, intersection over union and Dice similarity coefficient (DSC). Delong test was used to compare the segmentation efficacy among different models in the test set.Results:In the validation set, MT-UNet demonstrated DSC of 0.940, 0.962, and 0.963 for SPECT, CT, and SPECT/CT bone lesion segmentation, respectively, which were outperformed other models. Following transfer learning implementation, the SPECT/CT model′s DSC was improved to 0.984. In the test set, MT-UNet maintained comparable segmentation performance to the validation set, with significant AUC differences among the three models ( Z values: from -15.42 to -9.27, all P<0.01). Compared with conventional image interpretation, MT-UNet-based segmentation reduced physician interpretation time from 164min to 102min. Conclusion:MT-UNet has shown good performance in automatic segmentation of bone metastases and benign bone lesions, and is expected to become an important part of SPECT/CT image intelligent diagnosis system for bone metastases.

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.