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 explore the relationship between sleep characteristics, physical activity patterns, with depressive and anxiety symptoms in college students, so as to provide reference for student mental health promotion. Methods: From September to November 2023, a convenience sampling method was used to select 7 954 college students aged 18-22 years from 9 universities in Shanghai, Hubei, and Jiangxi. Assessments were conducted using the International Physical Activity Questionnaire Short-Form (IPAQ-SF), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI) to evaluate physical activity, depressive and anxiety symptoms, and sleep quality, respectively. Logistic regression analysis was employed to explore the impact of sleep characteristics and physical activity patterns on depressive and anxiety symptoms and their comorbidity among college students. Results: The detection rates for depressive symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms were 25.67%, 35.39%, and 23.15%, respectively. Factors such as gender, grade, household registration, parental education level, annual family income, family structure, and dietary habits were all associated with the detection rates of depressive and anxiety symptoms and their comorbidity (χ2=4.41-118.39, P<0.05). Physical activity patterns, sleep duration, sleep quality, and sleepwake characteristics were also associated with the occurrence of depressive and anxiety symptoms and their comorbidity (χ2=9.66-627.70, P<0.05). Logistic regression analysis showed that college students who stayed up late and slept less than 7 had the highest risk of depressive and anxiety symptoms and their comorbidity (OR=1.93, 1.85, 1.88, P<0.05). Compared to regular physical activity patterns, insufficient physical activity patterns were associated with an increased risk of depressive and anxiety symptoms (all OR=1.18, P<0.05). Further stratified analysis results showed that the risk of depression, anxiety and their comorbidity increased in college students who stayed up late and slept less than 7 h, went to bed before midnight and slept less than 7 h, or went to bed before midnight and slept more than 7 h but did not have sufficient physical activity (P<0.05). Conclusions Sleep characteristics and physical activity patterns significantly affect depressive and anxiety symptoms in college students. Universities should strengthen sleep management and implement flexible physical activity interventions to help students establish healthy lifestyles.

Abstract As a systematic psychological intervention method, bibliotherapy possesses advantages such as low cost, high accessibility, and significant efficacy. The paper systematically reviews the recent research progress of bibliotherapy in the field of adolescent mental health intervention including covering preventive, therapeutic, developmental, personalized, and comprehensive approaches. It discusses the effectiveness and key influencing factors of these interventions. Findings indicate that bibliotherapy can effectively reduce the risk of depressive and anxiety symptoms in adolescents, and improve their emotional regulation skills and social adaptability. Different types of interventions demonstrate varied effects across different populations. Personalized and comprehensive intervention models can further enhance the outcomes, to provide theoretical basis and practical guidance for the development of localized bibliotherapy intervention programs.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca²⁺ level, but the intake and effects of the intracellular Ca²⁺ remain unclear. The Ca²⁺ influx is controlled by members of Ca²⁺ channels, among which calcium voltage-gated channel subunit alpha1 C (Ca_V1.2) is the most robust. This study aimed to reveal the role and underlying mechanism of MC Ca_V1.2 in allergic inflammation. We found that Ca_V1.2 participated in MC activation and allergic inflammation. Nimodipine (Nim), as a strong Ca_V1.2-specific antagonist, ameliorated allergic inflammation in mice. Further, Ca_V1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C (PKC), which calcium/calmodulin-dependent protein kinase II (CaMKII) catalyzed. Overexpression or knockdown of MC Ca_V1.2 influenced MC activation. Importantly, Ca_V1.2 expression in MC had detrimental effects, while its deficiency ameliorated allergic pulmonary inflammation. Results provide novel insights into Ca_V1.2 function and a potential drug target for controlling allergic inflammation.

Allergic inflammation is closely related to the activation of mast cells(MCs),which is regulated by its intracellular Ca2+level,but the intake and effects of the intracellular Ca2+remain unclear.The Ca2+influx is controlled by members of Ca2+channels,among which calcium voltage-gated channel subunit alpha1 C(Cav1.2)is the most robust.This study aimed to reveal the role and underlying mechanism of MC Cav1.2 in allergic inflammation.We found that Cav1.2 participated in MC activation and allergic inflammation.Nimodipine(Nim),as a strong Cav1.2-specific antagonist,ameliorated allergic inflammation in mice.Further,Cav1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C(PKC),which calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)catalyzed.Overexpression or knockdown of MC Cav1.2 influenced MC activation.Importantly,Cav1.2 expression in MC had detrimental effects,while its deficiency ameliorated allergic pulmonary inflammation.Results provide novel insights into Cav1.2 function and a potential drug target for controlling allergic inflammation.

Objective: To explore the association between interaction effects of dietary behaviors and caregivers s type on overweight or obesity among left-behind children, and to provide a reference for overweight or obesity prevention among the left-behind children. Methods: From October to December 2018, 877 left-behind children aged 7-18 years were randomly selected from a stratified cluster in county, Shangrao City, Jiangxi Province.Type of caregives, dietary behavior, health status were collected from questionnaires, height, weight were examined. Results: The detection rate of overweight and obesity in left-behind children was 21.7%(190/877), and the rate of overweight and obese left-behind children with other foster parents was 29.8%(158/530), higher than the rate of 16.2%(32/198). The detection rate of overweight and obesity of left-behind children who consumed high level of western fast food was 59.0%(59/100). There were significant differences in rate of overweight and obesity by type of caregiver and western food consumption. Regression analysis showed that the detection rate of overweight and obesity of left-behind children who often ate western fast food was 5.70 times(95%CI=3.62-8.99) high than that of those who seldom ate western fast food. Interaction analysis showed that the interaction(synergistic effect) of the type of adopter × whether the adopter often ate western fast food(father or mother × yes) presents a positive multiplying interaction(synergistic effect). Left-behind children under paternal or maternal care together with high western fast food consumption greatly increased the risk of overweight and obesity(OR=6.94, 95%CI=2.76-17.44). Conclusion Frequent consumption of western fast food together with one parent stay at home is associated with overweight and obesity of left-behind children. These two factors have a synergistic effect, which greatly increases the risk of overweight and obesity of left-behind children. In other words, their interaction is a major risk factor.

Objective To investigate the relationship between leptin level of IGR patients and intima-media thickness (IMT) of carotid arterial. Methods One hundred and eighteen IGR patents were enrolled into the following three groups according to the result of oral glucose tolerance test (OGTT): 38 cases of the purely impaired fasting glucose (IFG) group, 42 cases of the purely impaired glucose tolerance (IGT) group and 42 cases of the IFG combining with IGT (IFG + IGT) group. Thirty-eight cases with normol glucose tolerance (NGR) were enrolled in the NGR group. The blood fat, fasting blood-glucose (FBG), fasting insulin (insulin), fasting C peptide , 2 h-postprandial blood glucose , 2 h-insulin , 2 h-C peptide , glycosylated hemoglobin (HbA1C), C-reactive protein (CRP), body mass index (BMI), leptin and IMT were determined in patients of the three groups and the healthy controls. The multiple linear regression was used to analyze the relationship between leptin level and IMT , and person correlation was further used to analyze the affinity degree between leptin level and IMT. Results Compared with the NGT group, the inter-group comparison showed that leptin level was significantly increased in the IFG, IGT and (IFG + IGT) groups (P < 0.05, respectively). Compared with the IFG and IGT groups, IMT and the leptin level were increased in the (IFG + IGT) group (P < 0.05, respectively). The multiple linear regression analysis showed that leptin level was correlated with the increase of IMT in the (IFG + IGT) group (P < 0.05), but not in the IFT group and the IGT group. Conclusion The leptin level in the IGR group and the IMT in the IFG + IGT ) group were significantly increased , the leptin level was closely associated with IMT.

Comorbid depression and chronic pain are highly prevalent in individuals suffering from physical illness .Here, we critically examine that inflammation is the possible mechanism of comorbidity of pain and depression .These mechanisms include direct effects of cytokines on the neuronal environment or indirect effects via downregulation of G protein -coupled receptor kinase 2, activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase that generates toxic kynurenine metabolites .We review the role of in-flammation in the mechanism of the commorbidity of depression and pain .