BackgroundCurrently， the problem of depressed mood in college students is becoming more prominent. The experience of childhood maltreatment is a significant contributor to depression among college students. Although the association between the two has been confirmed， the specific psychosocial mechanisms underlying how childhood maltreatment affects college students' mental health remain insufficiently evidenced. ObjectiveTo explore the mediating role of emotion regulation difficulties in the relationship between childhood maltreatment and depression among college students， and to investigate the moderated effects of psychological resilience and family socioeconomic status， aiming to provide references for improving depressive symptoms in college students. MethodsOn 14 March 2024， a cluster sampling method was employed to recruit 751 college students from a university in Heilongjiang Province. Participants were assessed with Childhood Trauma Questionnaire （CTQ）， Difficulties in Emotion Regulation Scale （DERS）， Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， 10-item Connor-Davidson Resilience Scale （CD-RISC-10） and Family Socioeconomic Status Questionnaire. Pearson correlation analysis was adopted to examine the correlation between the scores of scales. Model 4 and model 7 in Process 4.2 were used to test the mediating effects of emotional regulation difficulties and the moderated effects of psychological resilience and family socioeconomic status. Results① A total of 712 （94.81%） valid questionnaires were collected. ② College students' CTQ score was positively correlated with DERS score and PHQ-9 score （r=0.296， 0.507， P<0.01）， and negatively correlated with CD-RISC-10 score and Family Socioeconomic Status Questionnaire score （r=-0.148， -0.229， P<0.01）. ③ The indirect effect value of difficulties in emotion regulation on the relationship between childhood maltreatment and depression was 0.091 （95% CI： 0.018~0.046）， accounting for 17.95% of the total effect. ④ The first half of the mediation model "childhood maltreatment → difficulties in emotion regulation → depression" （childhood maltreatment → difficulties in emotion regulation） was moderated by psychological resilience （β=-0.030， t=-6.147， 95% CI： -0.040~-0.020） and family socioeconomic status （β=-0.051， t=-3.929， 95% CI： -0.077~-0.026）. ConclusionChildhood maltreatment exerts both a direct effect on college students' depression and an indirect effect through emotion regulation difficulties. The childhood maltreatment → emotion regulation difficulties pathway in this mediation model is moderated by psychological resilience and family socioeconomic status. ［Funded by Qiqihar Medical University Graduate Student Innovation Fund Project （number， QYYCX2023-48）； Special Research Fund Project for Young Doctors of Qiqihar Academy of Medical Sciences （number， QMSI2021B-08）］

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

OBJECTIVE To mine and analyze the post-marketing adverse drug event （ADE） signals of irinotecan in adults and children populations， and to provide a reference for clinical safe medication. METHODS ADE reports of irinotecan from the first quarter of 2004 to the first quarter of 2023 in the US FDA adverse event reporting system database were extracted and the risk signals of irinotecan were detected through the reporting odds ratio and proportional reporting ratio. Statistical analysis was performed for ADE reports and signals of patients aged＜18 years （children） and ≥18 years （adults）. RESULTS A total of 8 013 ADE reports with irinotecan as the primary suspect drug were identified， including 7 656 and 357 ADE reports in adults and children， respectively. A total of 518 and 75 ADE signals were detected in the adults and children， and the mainly involved systems and organs including gastrointestinal disorders， blood and lymphatic system disorders， systemic disorders and various reactions at the administration site， etc. Most of the top 20 ADE signals in terms of frequency were documented in the drug instructions of irinotecan. New ADE signals in adults included peripheral neuropathy， oral mucosal inflammation， pulmonary embolism， epidermal nevus syndrome and reproductive toxicity， while hypertension， progressive neoplasms， tumor lysis syndromes， and embolism were new ADE signals in children. CONCLUSIONS The above new suspected high-risk signals not mentioned in the instructions should raise a high level of alertness in clinical practice of irinotecan.

Objective:To explore the effects of adenoid hypertrophy on the growth and development of cranio-maxillofacial hard tis-sues in children at different growth stages.Methods:The cephalic lateral images of 232 children aged 4 to 16 years were measured and analyzed by Bjork-Jarabak cephalometric analysis.The patients were divided into 3 groups:CVM 1-2(A),CVM 3-4(B)and CVM 5-6(C)according to cervical vertebral maturation(CVM).Adenoid hypertrophy group and normal group were set up by Adenoi-dal-Nasopharyngeal Ratio(A/N Ratio)of 0.61.A,B and C groups included 28,55 and 23 cases in the subjects with adenoid hyper-trophy,and 12,65 and 49 cases in those of normal controls respectively.T-test was used to explore the difference of growth and devel-opment measurements among different subgroups of the same CVM stage and the change trend of the difference in different CVM sta-ges.Results:Hypertrophic adenoid children's S-Ar,N-Me and S-Ar/Ar-Go were significantly larger in CVM 1-2 subjects(P＜0.05);Ar-Go-Me,N-S-Ar and Ar-Go-N were significantly larger in CVM 5-6 subjects(P＜0.05),while S-Ar-Go decreased significantly(P＜0.05);S-N,Go-Me,S-Go,S-N/Go-Me and Ar-Go/N-Me had no significant differences in the whole stages(P＜0.05).Conclu-sion:Adenoid hypertrophy has great effect on the cranio-maxillofacial growth trend.It induces more posterior position of condyle,tilt-ing back of mandibular ramus,vertical growth and clockwise rotation of the mandible and incline to form class Ⅱ malocclusion.The effects are more prominant in early and late growth and development stages of the children.

Objective To investigate the changes in microglia phenotype after cerebral ischemia reperfusion(1R)injury and the effects of adenosine on nerve injury of cerebral IR injured rats.Methods Thirty-six healthy male Sprague Dawley rats were randomly divided into the sham operation(Sham)group,IR group,and adenosine pretreatment(AP)group,with 12 rats in each group.Before modeling,rats in the AP group were intraperitoneally injected with 2 mL of adenosine injection daily for 3 consecutive days,and rats in the Sham group and IR group were intraperitoneally injected with 2 mL of normal saline daily for 3 consecutive days.The middle cerebral artery occlusion models of rats in the IR group and AP group were constructed by using the suture-occluded method,and only the carotid artery of rats was isolated in the Sham group without ligation of blood vessels.At 2 hours after modeling,the neuroethology of rats in each group were evaluated according to a 5-point neurobehavioral scale.At 24 hours after restoring the blood perfusion in the middle cerebral artery,the rats in each group were executed,and their brain tissues were removed.The morphological changes of the brain tissues in the ischemic penumbra region were observed after hematoxylin-eosin(HE)staining.The co-expression of M1-type microglia markers and M2-type microglia markers was detected by immunofluorescence staining.The relative expression levels of pro-inflammatory factors inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α)and interleukin(IL)-1β released by M1-type microglia,and anti-inflammatory factors IL-4,IL-10 and transforming growth factor-β(TGF-β)released by M2-type microglia were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Results The neurobehavioral scores of rats in the IR group and AP group were significantly higher than those in the Sham group,and the neurobehavioral score of rats in the IR group was significantly higher than that in the AP group(P＜0.05).HE staining results showed that the brain cells of rats in the Sham group were structurally complete and tightly arranged,with visible nuclei and no interstitial edema;the brain cells of rats in the IR group were structurally damaged and irregularly arranged,with loose cytoplasm and vacuoles in the cytosome;the structure of brain cells of rat in the AP group was better than that in the IR group,and there were many regularly-arranged normal cells,with complete nuclei.Immunofluorescence staining results showed that the number of M1-type and M2-type microglia in the ischemic penumbra region of rats in the IR group and AP group was significantly higher than that in the Sham group;the number of M1-type microglia in the IR group was significantly higher than that in the AP group,and the number of M2-type microglia was significantly lower than that in the AP group(P＜0.05).qRT-PCR results showed that the relative expression levels of pro-inflammatory cytokines TNF-α,IL-1β,iNOS and anti-inflammatory cytokines IL-4,IL-10,TGF-β in the IR group and AP group were significantly higher than those in the Sham group(P＜0.05);the relative expression levels of pro-inflammatory factors TNF-α,IL-1β and iNOS in the AP group were significantly lower than those in the IR group(P＜0.05),while the relative expression levels of anti-inflammatory factors IL-4,IL-10 and TGF-β were significantly higher than those in the IR group(P＜0.05).Conclusion AP can promote the polarization of microglia from M1 type to M2 type,inhibit the release of pro-inflammatory factors,increases the expression of anti-inflammatory factors,and thus has a neuroprotective effect on rats after cerebral IR injury.

Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying the progression of this disease remain elusive.Presently,clinically employed drugs are scarce for the treatment of PF.Hence,there is an urgent need for developing novel drugs to address such diseases.Our study found for the first time that a natural source of Prismatomeris connata Y.Z.Ruan(Huang Gen,HG)ethyl acetate extract(HG-2)had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic(TGF-β1/Smad)pathway.Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation,cellular response to reactive oxygen species,and extracellular matrix(ECM)disassembly.Moreover,mass spec-trometry imaging(MSI)was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2,which was related to arginine biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,and the upregulation of glycerophospholipid metabolism.In conclusion,we elaborated on the relationship between metabolite distribution and the progression of PF,constructed the regulatory metabolic network of HG-2,and discovered the multi-target therapeutic effect of HG-2,which might be conducive to the development of new drugs for PF.

Objective:To explore the value of deep learning technology based on mammography in differentiating for breast imaging reporting and data system (BI-RADS) category 3 and 4 lesions.Methods:The clinical and imaging data of 305 patients with 314 lesions assessed as BI-RADS category 3 and 4 by mammography were analyzed retrospectively in Shenzhen People′s Hospital and Shenzhen Luohu People′s Hospital from January to December 2020. All 305 patients were female, aged 21 to 83 (47±12) years. Two general radiologists (general radiologist A and general radiologist B) with 5 and 6 years of work experience and two professional breast imaging diagnostic radiologists (professional radiologist A and professional radiologist B) with 21 years of work experience and specialized breast imaging training were randomly assigned to read the imaging independently at a 1∶1 ratio, and then to read the imaging again in combination with the deep learning system. Finally, breast lesions were reclassified into BI-RADS category 3 or 4. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the diagnostic performance, and the differences of AUCs were compared by DeLong method.Results:The AUC of general radiologist A combined with deep learning system to reclassify BI-RADS category 3 and 4 breast lesions was significantly higher than that of general radiologist A alone (AUC=0.79, 0.63, Z=2.82, P=0.005, respectively). The AUC of general radiologist B combined with deep learning system to reclassify BI-RADS category 3 and 4 breast lesions was significantly higher than that of general radiologist B (AUC=0.83, 0.64, Z=3.32, P=0.001, respectively). There was no significant difference in the AUCs between professional radiologist A combined with deep learning system and professional radiologist A, and professional radiologist B combined with deep learning system and professional radiologist B in reclassifying BI-RADS category 3 and 4 breast lesions ( P>0.05). Conclusion:The deep learning system based on mammography is more effective in assisting general radiologists to differentiate between BI-RADS category 3 and 4 lesions.

Objective:To establish the predictive models for the prognosis of ductal carcinoma in situ (DCIS) at different pathological stages, and to evaluate the predictive performance of the models.Methods:Complete data of 273 patients with confirmed DCIS at different pathological stages who underwent mammography examination in Shenzhen People′s Hospital, Peking University Shenzhen Hospital and Shenzhen Luohu People′s Hospital from November 2014 to December 2020 were retrospectively collected, including 110 cases in the DCIS+ductal carcinoma in situ with microinvasion (DCIS-MI) group and 163 cases in the invasive ductal carcinoma (IDC)-DCIS group. The clinical, imaging and pathological features were analyzed. Mammary Mammo AI fusion model and deep learning-based natural language processing (NLP) structured diagnostic report model were used for image feature extraction. Patients in each group were randomly divided into training set and validation set with a ratio of 6∶4, and the predictors were screened by univariate and multivariate logistic regression analysis. The lowest Akaike information criterion value of each group was selected to construct the final predictive model. The receiver operating characteristic (ROC) curve was drawn to evaluate the performance of each model.Results:Taking estrogen receptor (-) or human epidermal growth factor receptor 2 (3+) as the poor prognostic reference, there were 62 cases considered with poor prognosis and 48 cases with good prognosis in DCIS+DCIS-MI group; while in the IDC-DCIS group, taking the Nottingham prognostic index as the reference, 33 cases were considered with poor prognosis, 73 cases with moderate prognosis, and 57 cases with good prognosis. Four predictive factors were screened to construct the DCIS+DCIS-MI-group predictive model, including DCIS nuclear grade, calcification with suspicious morphology in mammography, DCIS pathologic subtype and DCIS with microinvasion. Five predictive factors were screened to construct the IDC-DCIS-group predictive model, including neural or vascular invasion, Ki67 level, DCIS subtype, DCIS component proportion and associated features in mammography. The area under curve (AUC) for predicting poor prognosis of DCIS+DCIS-MI was 0.92 (95%CI 0.84-1.00) in the training set and 0.90 (95%CI 0.82-0.99) in the validation set; while the AUC for predicting poor prognosis of IDC-DCIS was 0.84 (95%CI 0.76-0.93) in the training set and 0.78 (95%CI 0.64-0.91) in the validation set.Conclusion:The developed models based on deep learning combined with NLP can effectively predict the prognosis of DCIS at different pathological stages, which are beneficial to the risk stratification of patients with DCIS, providing a reference for clinical decision.

Objective To detect the expression levels of miR-7-5p and POLE4 in non-small cell lung cancer cells and their effect on cells proliferation, migration and invasion. Methods qRT-PCR was used to detect the relative expression levels of miR-7-5p and POLE4 mRNA in NSCLC tissues, adjacent tissues, tumor cells and human normal bronchial epithelial cells. Luciferase reporter gene was used for analyzing of the targeting relation between POLE4 and miR-7-5p in NSCLC cells. si-NC and si-POLE4 were transfected into SPC-A-1 cells as the si-NC group and si-POLE4 group, and the control group was set at the same time. MTT method, scratch test and Transwell test were used to detect cell proliferation, migration and invasion. Results The expression levels of miR-7-5p in NSCLC tissues and cells were reduced, and the expression levels of POLE4 were increased. miR-7-5p could target to combine with POLE4. After 72 hours of culture, the OD value in si-POLE4 group was significantly lower than those in the control group and si-NC group (P < 0.05). The migration rate and the number of transmembrane cells in the si-POLE4 group cultured for 48 hours were lower than those in the control group and the si-NC group (P < 0.05). Conclusion miR-7-5p may inhibit the proliferation, migration and invasion of non-small cell lung cancer cells by targeting POLE4.

Objective To investigate the expressions of AGGF1 in esophageal squamous cell carcinoma (ESCC) and their relationships with clinical features and prognosis of ESCC. Methods The expressions of AGGF1 in 70 cases of ESCC and 30 cases of normal esophageal tissue were examined using SP immunohistochemical staining and were analyzed according to the clinical features and follow-up data. Results The expressions of AGGF1 in 70 cases of ESCC was significantly higher than those in 30 cases of normal esophageal tissue [54.29%(38/70) vs. 23.33%(7/30)](P=0.004). The expressions of AGGF1 in ESCC were significantly related to the TNM stage, clinical stage and prognosis (P all<0.05). The OS was shorter in the positive teams of AGGF1 than that in the negative teams [(19.7 ± 3.5) months vs. (33.2 ± 4.0) months] (P=0.015). Cox- proportional multivariate analysis showed that positive expressions of AGGF1 and VEGF (P=0.043, 0.024) and clinical stage (P=0.035) were significant prognostic factors in overall survival. Conclusions AGGF1 has high expressions in ESCC, and it is closely related to the clinical features and prognosis of ESCC.