Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Abstract Migraine is a widespread neurovascular disorder, the pathogenesis of which is closely linked to the release of calcitonin gene-related peptide(CGRP), leading to a significant impairment in patients′ quality of life. CGRP receptor antagonists exert their therapeutic effect by inhibiting the interaction between CGRP and its receptors, thereby preventing migraine attacks. Currently, several agents, including Rimegepant and Ubrogepant, have either received approval from the U. S. Food and Drug Administration or are in advanced stages of clinical trials.These drugs offer multiple advantages, such as the absence of vasoconstrictive effects, a rapid onset of action, and minimal interference with the immune system. Nevertheless, further investigation is necessary to assess their longterm safety, the potential emergence of drug resistance, and the development of individualized treatment protocols.Moreover, the integration of these novel therapies with existing treatment strategies remains a critical area for future research. This review aims to summarize recent national and international scientific advancements to establish a theoretical basis for the application of precision medicine in migraine management.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective: To explore the longitudinal association between only-child status and smartphone addiction among middle school students, so as to provide a basis for establishing family intervention measures for smartphone addiction in middle school students. Methods: In October 2022 and October 2023, a preliminary survey and follow-up were conducted among 8 759 middle and high school students from 30 schools in a district of Shenzhen. A self-designed questionnaire was used to determine whether the students were the only-child, and the Chinese Version of the Smartphone Addiction Scale-Short Version (C-SAS-SV) was utilized to assess the students smartphone addiction status. A multilevel mixed-effects model and subgroup analysis were applied to examine the association between only-child status and smartphone addiction among middle school students. Results: During 2022 to 2023, the prevalence of smartphone addiction in the cohort of middle school students increased from 24.1% to 25.2%. Compared with only-child, non-only child were more likely to be addicted to smartphones (adjusted model: OR =1.2, 95% CI =1.1-1.4) and also scored higher on smartphone addiction (adjusted model: β =0.9, 95% CI =0.2-1.5)( P <0.05). Subgroup analysis further revealed that compared to baseline, non-only child demonstrated an increased prevalence of smartphone addiction (adjusted model: OR = 1.2 , 95% CI =1.0-1.5) and higher addiction scores (adjusted model: β =0.8, 95% CI =0.2-1.5) after one year( P <0.05). Conclusions Non-only child face higher risk of smartphone addiction. Under the current population policy, it is crucial to address smartphone addiction among middle school students who is not only child.

Objective: To explore the potential causal association between adolescent compulsive behaviour and smartphone addiction based on longitudinal data, so as to provide reference for the establishment of adolescent smartphone addiction interventions. Methods: A preliminary survey and follow-up were conducted on 8 907 middle and high school students in a district of Shenzhen in 2022 and 2023, respectively. Compulsive behaviours were measured by using the Mental Health Inventory for Middle School Students-60 Items (MMHI-60), smartphone addiction was assessed by using the Smartphone Addiction Scale-Short Version ( SAS- SV), and the associations between compulsive behaviours and smartphone addiction were analysed by using multilevel mixed-effects models and subgroup analyses. Results: Smartphone addiction detection rates among middle school students were significantly associated with genders, father s education level, mother s education level, study load subgroups, and whether or not they were single-parent families, and there were statistical differences ( χ 2=17.21-175.34, P <0.05). Students with compulsive behaviours were 2.98 times more likely to develop smartphone addiction than those without compulsive behaviours ( OR=2.98, 95%CI=2.77-3.22, P <0.05). Subgroup analysis of middle school students without smartphone addiction in the first year found that compulsive behaviours significantly predicted smartphone addiction ( OR= 1.76 , 95%CI=1.54-2.01, P <0.05). Conclusion There is a potential causal association between obsessive-compulsive behaviours and smartphone addiction in middle school students, and obsessive-compulsive behaviours in middle school students could significantly predicted the occurrence of smartphone addiction.

Objective To investigate how vismodegib(Vis)influences the pathogenesis of basal cell carcinoma(BCC)via a chromatin remodeling factor,bromodomain containing protein 9(BRD9),and to analyze the expression profile of BRD9 in BCC and its relationship with the immune checkpoint,programmed cell death-1 ligand 1(PD-L1)and the Hedgehog(Hh)signaling pathway.Methods ① A UVB-induced BCC model was established in SKH-1 hairless background Ptch1+/-;LacZ reporter mice.Then the mice were treated with Vis,and those without treatment served as control.X-gal staining,immunohistochemistry(IHC)staining,immunofluorescence(IF)assay,and Western blotting were used to assess the expression and localization of BRD9 and PD-L1 in tumor tissues and to evaluate immune-cell infiltration.② In vitro,mouse BCC cell line ASZ001(ASZ cells)were treated with Vis or a BRD9 degrader(dBRD9),and BRD9-overexpressing cells were generated.Cell viability and the protein and mRNA levels of BRD9,PD-L1,Gli1,and cyclin D1(Ccnd1)were measured.ChIP-qPCR was performed to examine BRD9 and H3K27ac enrichment at the PD-L1 promoter,including the promoter-proximal site(P1)and an upstream active segment(P2).Results ① At the tissue level,BRD9 was highly expressed in BCC,and co-localization of BRD9 and PD-L1 was observed within tumor regions,with evident immune-cell infiltration.Vis markedly suppressed UVB-induced BCC formation,reduced the probability of large-volume tumors(by probability-density analysis),decreased the X-gal-positive lesion area(P<0.000 1),down-regulated BRD9(P=0.024 9),and attenuated immune-cell infiltration.② At the cellular level,Vis treatment reduced cell viability and down-regulated BRD9,Gli1,and Ccnd1 in ASZ cells(P<0.000 1).dBRD9 inhibited ASZ cell viability in a dose-dependent manner and decreased PD-L1,Gli1,and Ccnd1(P<0.000 1),whereas its overexpression increased the expression of these molecules(P<0.000 1).In ASZ cells,BRD9 and H3K27ac were enriched at the PD-L1 promoter P1/P2 regions.Treatment with dBRD9 or Vis reduced BRD9 and H3K27ac enrichment at P1/P2 regions(P<0.000 1).Conclusion In BCC,BRD9 maintains chromatin activation at the proximal PD-L1 promoter and modulates Hh/Gli1 signaling,thereby promoting immune evasion.Vis remodels the tumor immune microenvironment by inhibiting the Hh-BRD9-PD-L1 axis.

Objective:To investigate the impact of the number of examined lymph nodes (ELN) on survival outcomes in gastric cancer patients with postoperative pathological stage pN3b.Methods:This retrospective cohort study included 279 pN3b gastric cancer patients who underwent D2 gastrectomy at Nanfang Hospital, Southern Medical University (September 2008 to April 2023), with 35 patients receiving combination chemotherapy and anti-PD-1 therapy (immunotherapy group) and 244 receiving adjuvant chemotherapy alone (nonimmunotherapy group). Additionally, 422 patients with pN3b from the SEER database (2005 to 2020) were collected as an external validation cohort to determine the optimal cutoff value for the number of lymph nodes examined in the nonimmunotherapy group. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) in the nonimmunotherapy group of the Nanfang Hospital cohort, stratified by whether the number of examined lymph nodes was above or below the ELN optimal cutoff value. These findings were subsequently validated in the SEER cohort.Results:The optimal ELN cutoff value (34 nodes) was determined using X-tile software and by constructing an ELN-HR fitting model with inflection point identification. In the nonimmunotherapy group, patients with ELN >34 exhibited significantly prolonged survival compared to ELN ≤34 (median OS: 25.0 (95%CI:20.5-29.5) to 17.0 (95%CI:12.7-21.3) months, P=0.004; median RFS: 19.0 (95%CI:15.6-22.4) to 13.0 (95%CI:9.5-16.5) months, P=0.048). Multivariate Cox analysis also showed ELN >34 to be an independent protective factor for both OS (HR=0.576, 95%CI: 0.397-0.836) and RFS (HR=0.701, 95%CI: 0.492-0.998). In the SEER cohort, ELN >34 was associated with a 5-month OS extension (19 to 14 months, P=0.065), with multivariate analysis supporting its independent prognostic significance (HR=0.729, 95%CI: 0.580-0.915, P=0.006). Notably, in the immunotherapy group, patients with ELN >34 ( n=30) achieved a median OS of 41 months, but the median OS had not been reached in the ELN ≤34 group ( n=5) (1 death at 48 months). Conclusion:Higher ELN (>34) correlates with improved survival in nonimmunotherapy-treated pN3b gastric cancer patients. However, in pN3b gastric cancer patients treated with immunotherapy, the optimal ELN threshold requires further exploration to determine.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Objective:To investigate the characteristics of brain functional networks alterations in patients with inflammatory bowel disease (IBD) and explore their correlations with clinical indicators and psycho-psychological scores.Methods:A cross-sectional survey study was conducted. A total of 48 IBD patients diagnosed at the Changzhou Second People′s Hospital from June 2021 to June 2023 were collected, and 32 healthy individuals matched for age, gender, and education level were selected as the healthy control group. Resting-state functional magnetic resonance imaging data were enrolled, and the topological properties of brain networks between the two groups of subjects were compared by using graph theory analysis. Pearson correlation and Spearman′s partial correlation analyses were used to explore the correlations between changes in IBD patients′ brain networks topological properties and clinical indicators and psycho-psychological scores.Results:In the IBD group, 29 patients were males (60.4%) and 19 were females (39.6%) ; the total disease course was 1.0 (0.3, 5.0) years; 34 patients were Crohn′s disease and 14 ulcerative colitis; they were mainly in the active phase (58.84%, 28/48) . The scores of the hospital anxiety and depression scale (HADS-A and HADS-D) in IBD patients were higher than those in the healthy control group (both P<0.01) . In terms of global properties, both the IBD group and the healthy control group had "small-world" properties (both σ>1.1) . Compared with the healthy control group, the IBD group had lower clustering coefficients, global efficiency, and local efficiency, and longer characteristic path lengths, with all differences being statistically significant (all P<0.05) . In terms of local properties, compared with the healthy control group, the IBD group had higher degree centrality and nodal efficiency in the left middle frontal gyrus, higher betweenness centrality in the left thalamus, lower betweenness centrality and degree centrality in the right parahippocampal gyrus, lower nodal clustering coefficients in the bilateral middle temporal gyrus, right anterior cingulate gyrus and paracingulate gyrus, and lower nodal local efficiency in the bilateral caudate nuclei and left middle temporal gyrus, with all differences being statistically significant (all P<0.05) . The degree centrality of the right parahippocampal gyrus in the IBD group was negatively correlated with the HADS-A score ( r = -0.401, P = 0.005) , and the betweenness centrality was also negatively correlated with the HADS-A score ( r = -0.343, P = 0.017) . The nodal clustering coefficient of the right middle temporal gyrus in the IBD group was positively correlated with the total disease course ( rs = 0.589, P<0.001) . Conclusion:IBD patients have decreased overall information transmission capacity in brain networks, reduced limbic system function, and abnormal functions in brain areas related to pain perception, which are correlated to some extent with the disease course and psycho-psychological state.

Objective:To investigate the changes of brain microstructure in active Crohn's disease (CD) patients with or without anxiety by diffusion kurtosis imaging (DKI), and to explore the relationship between brain microstructure and anxiety in patients with CD.Methods:Thirty-seven patients with CD who were treated in Changzhou Second People's Hospital Affiliated to Nanjing Medical University from January 2022 to January 2023 were included as the CD group, and 20 healthy subjects were included as the healthy control group during the same period. All subjects were assessed with hospital anxiety and depression scale-anxiety (HADS-A) before magnetic resonance imaging(MRI) scan. According to the HADS-A score, CD patients were divided into the CD group with anxiety (16 cases) and the CD group without anxiety (21 cases). After MRI scan, DKI parameters were obtained by DKE software. One-way analysis of variance was used to compare DKI parameters between the two groups of CD patients and the healthy control group. Pearson correlation was used to analyze the correlation between DKI parameters in different brain areas and psychological scale scores in the two groups of CD patients.Results:The axial diffusion kurtosis(AK)values in the right insula, the left superior temporal gyrus, the right thalamus, the left middle temporal gyrus, the right inferior temporal gyrus, the left lingual gyrus and the right anterior cuneus were significantly different among the three groups ( F=3.060-9.627, all P<0.05).There were significant differences in the radial diffusion kurtosis(RK) values in the right cerebellar region 6 and the left hippocampus among the three groups ( F=4.124, 3.536, 4.200, all P<0.05). Further multiple comparison results showed that the AK values of the right insula (0.701±0.028)( P=0.019), the left superior temporal gyrus (0.764±0.016)( P=0.002) and the right thalamus (0.728±0.016)( P=0.001) in the CD group without anxiety were lower than those of the healthy control group(0.726±0.010, 0.780±0.015, 0.771±0.082), and the RK value of the right cerebellar region 6 ( P=0.021) was lower than that of the healthy control group. The AK values of the right insula ( P=0.023), the left superior temporal gyrus ( P=0.015), the right thalamus ( P=0.031), the left middle temporal gyrus ( P=0.006), the right inferior temporal gyrus ( P=0.001) and the left lingual gyrus ( P=0.007) in the CD group with anxiety were lower than those in the healthy control group. The RK values of right cerebellar region 6 ( P=0.012) and left hippocampus ( P=0.004) were lower than those of healthy control group. The AK values of the right insula ( P=0.002) and the right anterior cuneus ( P=0.017) in the group with anxiety were lower than those in the CD group without anxiety. In the CD group with anxiety, the AK value of the right insula was correlated with erythrocyte sedimentation rate(ESR)( r=-0.47, P=0.048), HADS-A score ( r=-0.68, P=0.002), SES-CD( r=-0.84, P<0.001) and duration of disease ( r=-0.61, P=0.008) were negatively correlated. AK values in the left superior temporal gyrus with anxiety CD group were negatively correlated with HADS-A score ( r=-0.51, P=0.030) and SES-CD score ( r=-0.48, P=0.046). Conclusion:The microstructure of some brain regions was damaged in CD patients with or without anxiety, which was manifested as decreased RK and AK values in DKI parameter values, which may be related to the anxiety state in active CD patients.