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 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 analyze the lung function condition and the prevalence of pulmonary ventilation disorders in the occupational population of Wuhan, and to explore their influencing factors. Methods Physical examination data from the Wuhan Prevention and Treatment Center for Occupational Diseases were used in this study, and finally 9499 people were selected as the study subjects. The linear regression model and logistic regression model were used to analyze the influencing factors of pulmonary ventilation function and pulmonary dysfunction. The restricted cubic spline was used to explore the nonlinear relationship. Results The prevalence of pulmonary ventilation disorders was 1.7%, and the lung function indexes FVC, FEV1, and FEV1/FVC were significantly lower in the population aged >27 years than in the population aged <27 years (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in females than in males (P<0.001). The lung function indexes FVC and FEV1 were significantly lower in underweight occupational groups than in normal-weight groups (P<0.001), and FVC and FEV1 were significantly lower in dust-exposed occupational groups than in groups without dust exposure(P<0.05). Restricted cubic spline plots showed a nonlinear relationship between age and lung function indexes FVC and FEV1 (P_nonlinear< 0.05). Age and BMI were the risk factors for pulmonary ventilation disorders. Conclusion Age, gender, BMI, and dust exposure are risk factors for decreased FVC and FEV1. Age is the risk factor for decreased FEV1/FVC. Age and BMI are the risk factors for pulmonary ventilation disorders.

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 assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

Objective:To analyse the 3D-Flair MRI manifestations of the inner ear, vestibular function status, and their correlation with hearing treatment outcomes in patients with severe sudden sensorineural hearing loss (SSNHL), and to explore potential prognostic indicators for sudden deafness.Methods:The clinical data of adult patients with unilateral profound sudden sensorineural hearing loss were retrospectively analyzed in Otorhinolaryngology Department of Shandong Provincial ENT Hospital from March 2018 to August 2020. Patients were categorized based on the results of their inner ear 3D-Flair MRI into two groups: the normal MRI group and the abnormal MRI group. The abnormal group was further divided into three subgroups: those with non-absorbed high signal in the inner ear, those with absorbed high signal, and those with destruction of the blood-labyrinth barrier. SPSS 26.0 statistical software was applied to analyze the differences in hearing efficacy, caloric tests, vestibular evoked myogenic potentials (VEMP), video head impulse tests (vHIT), and the incidence of dizziness/vertigo among various patient groups.Results:A total of 191 patients with complete data were collected (97 males and 94 females, aged from 13 to 69 years old). There were 50 cases in the normal inner ear 3D-Flair MRI group. A total of 141 cases were found in the group with abnormal 3D-Flair MRI, including 50 cases of high signal unabsorbed, 71 cases of absorption high signal and 20 cases of blood labyrinth barrier destruction. There were no significant differences in age, sex, lateral ratio of hearing loss and course of disease among four groups (all P>0.05).The significant efficiencies of hearing recovery, in the group with normal 3D-FLAIR MRI were better than those in the abnormal group ( P<0.05) after treatment. Among the four groups, there were significant differences in the apparent efficiency and total effective rate between the normal group and the inner ear high signal absorption group ( χ2=4.007, P=0.045; χ2=6.925, P=0.009). The abnormal rates of bithermal caloric test, vHIT results and dizziness/vertigo symptoms in the abnormal group were higher than those in the normal group ( P<0.05). There were significant differences in oVEMP abnormality rate, vHIT abnormality rate and incidence of dizziness/vertigo among the three groups with 3D-FLAIR MRI abnormality ( P<0.05). There were significant differences in caloric test, oVEMP, vHIT abnormality rate and incidence of dizziness/vertigo among the four groups ( P<0.05). The positive rates of caloric test, cVEMP test and vHIT test in patients with dizziness/vertigo were higher than those in patients without dizziness/vertigo ( P<0.05). The abnormal rates of posterior semicircular canal and horizontal semicircular canal in patients with dizziness/vertigo were significantly increased ( P<0.05) than patients without dizziness/vertigo. The recovery rate, effective rate and total effective rate of patients without dizziness/vertigo were significantly better than those with dizziness/vertigo ( P<0.05). Conclusions:The 3D-Flair MRI of the inner ear and vestibular function tests have reference value for the prognosis assessment of patients with severe sudden sensorineural hearing loss. Abnormal 3D-FLAIR MRI of the inner ear, especially absorption high signal, is associated with high incidence of vestibular dysfunction and dizziness/vertigo, with poor prognosis. Patients with severe sudden sensorineural hearing loss who have symptoms of dizziness/vertigo are more likely to exhibit abnormal results in vestibular function tests, with a higher susceptibility to involvement of the posterior and horizontal semicircular canals.

Objective:To evaluate the sound localization ability of patients with different degrees of unilateral conductive hearing loss (UCHL) in quiet and noisy environments, and to explore the changes and characteristics of sound localization.Methods:This was a cross-sectional study. 41 patients with UCHL were hospitalized in Shandong Provincial ENT Hospital from January to April 2024, including 22 males and 19 females, aged 18-55 years old, with an average age of 36.9 years. According to the pure-tone average (PTA) of 500, 1000 and 2000 Hz in the suffered ear, subjects were divided into slight-mild UCHL group (20 numbers) and moderate-moderately severe UCHL group (21 numbers). 21 patients with normal hearing (NH) were enrolled as controls. All subjects were assessed through pure-tone audiometry, horizontal sound localization test (including azimuth identification test in quiet and noisy environments), Chinese edition short form of Spatial Hearing Questionnaire (C-SHQ12) and twelve-item version of Speech, Spatial, and Qualities of Hearing Scale (SSQ12). SPSS, version 26.0, was used for statistical analysis.Results:There were significant differences in the root-mean-square errors (RMSE) of the sound localization azimuth identification test in quiet and noisy environments among the NH group, slight-mild UCHL group, and moderate-moderately severe UCHL group (Quiet: F=29.109, P<0.001; Noisy: F=24.351, P<0.001). This presented statistically marked difference in the RMSEs between the two listening environments in the slight-mild UCHL group ( t=-4.911, P<0.001). There was a statistical difference in the RMSEs between the normal and affected sides of the subjects in the slight-mild UCHL group in the quiet environment ( t=-2.055, P<0.05), but not in the noisy environment. For moderate-moderately severe UCHL subjects, there were no differences in the RMSEs between the quiet and noisy environments ( P>0.05). What’s more，no significant differences were found between normal side and affected side in both environments ( P>0.05). The RMSEs of UCHL patients in quiet and noisy environments were positively correlated with PTA of air-conduction in the suffered ears (Quiet: r=0.681, P<0.001; Noisy: r=0.346, P<0.05). RMSEs in quiet and noisy environments were negatively correlated with the average localization scores in C-SHQ12 (Quiet: r=-0.576, P<0.001, Noisy: r=-0.613, P<0.001) and in SSQ12 (Quiet: r=-0.634, P<0.001, Noisy: r=-0.663, P<0.001). Conclusions:The sound localization ability of UCHL subjects decreased compared with those with normal hearing, and the RMSE gradually increased with the worse of air conduction hearing threshold. The localization ability of UCHL subjects was further reduced in the noisy environment compared with that in the quiet environment. The slight-mild UCHL subjects had better localization performance in the normal ears while worse in the suffered ears, however, when they were in noisy environment or their hearing loss deteriorated, the localization advantage of the normal ears was no longer obvious, and both sides of the subjects presented poor localization performance.

Objective:To explore the clinical efficacy of curcumin-mediated photodynamic therapy (PDT) for the treatment of cervical intraepithelial neoplasia (CIN) combined with human papillomavirus (HPV) infection.Methods:A prospective randomized controlled study was conducted. Eighty patients with CIN combined with HPV infection in Dingzhou People's Hospital from January 2022 to January 2023 were selected and divided into the observation group and the control group using the randomized numerical table method, with 40 cases in each group. The observation group was treated with curcumin-mediated PDT, and the control group was treated with recombinant human interferon α-2b suppository for topical application. The efficacy, HPV-DNA conversion rate, high-risk human papillomavirus (HR-HPV) load, recovery status, inflammatory cytokine level, expression of Ki-67, expression of Survivin, and occurrence of adverse reactions were compared between the two groups.Results:Eighty patients aged (35±4) years old. The age, disease duration, age of first sexual experience, CIN grading, HPV typing and other general data of the two groups were compared, and the differences were not statistically significant (all P > 0.05). The total effective rate of the observation group was higher than that of the control group [95.0% (38/40) vs. 75.0% (30/40)], and the difference was statistically significant ( χ2 = 6.28, P = 0.012). The HPV-DNA conversion rates in the observation group were higher than those in the control group at 1, 3 and 6 months after treatment [1 month: 65.0% (26/40) vs. 42.5% (17/40); 3 months: 87.5% (35/40) vs. 67.5% (27/40); 6 months: 95.0% (38/40) vs. 80.0% (32/40)], and the differences were statistically significant ( χ2 values were 4.07, 4.59 and 4.11, respectively, all P < 0.05). HR-HPV loads in the observation group were lower than those in the control group at 1, 3 and 6 months after treatment (1 month: 42.4±5.8 vs. 56.7±6.7; 3 months: 31.0±4.5 vs. 40.3±3.7; 6 months: 14.5±2.4 vs. 28.8±2.4), and the differences were statistically significant ( t values were 10.24, 10.17 and 26.77, respectively, all P < 0.001). The healing time of cervical wound in the observation group was shorter than that in the control group [(30±3) d vs. (39±5) d, t = 9.37, P < 0.001]. The levels of interleukin 4, interleukin 6, interleukin 10 and relative expressions of Ki-67 and Survivin in the observation group were lower than those in the control group at 6 months after treatment (all P < 0.001). The difference in the incidence of adverse reactions between the observation and control groups was not statistically significant [12.50% (5/40) vs. 7.50% (3/40), χ2 = 0.56, P = 0.456]. Conclusions:Curcumin-mediated PDT for the treatment of patients with CIN combined with HPV infection has a high total effective rate; it can reduce the HR-HPV load and inflammatory cytokine levels, and improve the HPV-DNA conversion rate.