Objective To investigate the contribution of microglia in the basolateral amygdala(BLA)to pain hypersensitivity and pain-related aversion in knee-joint monoarthritis mice.Methods A total of 61 mice were used for behavioral tests(14 mice in the control group and 47 mice in the model group),and other 6 mice were used for cell morphology(3 mice in each group).An animal model of knee-joint monoarthritis was established by injection of complete Freund's adjuvant(CFA)into the knee-joint cavity of mice.The von Frey and Hargreaves tests were used to examine mechanical allodynia and thermal hyperalgesia in mice,respectively.The place escape/avoidance paradigm test was used to examine pain-related aversion.Open field test and elevated plus maze test were used to examine anxiety-like behaviors in mice.Morphological changes of microglia in the BLA area after CFA injection were assessed by 3D reconstruction of microglia in the BLA brain region using immunofluorescence staining and Imaris software.Results Compared with the control group,CFA-arthritic mice produced significant mechanical and thermal hyperalgesia in the ipsilateral hindpaw and maintained for at least 12 and 19 days,respectively.Meanwhile,CFA injection induced pain-related aversion and anxiety-like behaviors in mice,accompanied by significant activation of BLA microglia.Inhibition of BLA microglia activation alleviated CFA-induced hyperalgesia and aversive behaviors but had no significant effects on anxiety-like behaviors.Conclusion CFA-arthritic mice produce hyperalgesia,pain-related aversion,and anxious behavior,in which hyperalgesia and pain-related aversion may be mediated by the activation of microglia in BLA.

Objective To investigate the impact of radiotherapy simulant Zeocin induced double-stranded RNA(dsRNA)on double-stranded RNA-dependent protein kinase(PKR)activation and explore its molecular mechanism in inhibiting the growth and migration of malignant gliomas.Methods We employed scratch assays,colony formation assays,and CCK8 assays to assess the impact of Zeocin on glioma growth and migration inhibition.Western blot and RT-qPCR were employed to measure the expression levels of methyl-modifying enzymes in glioma cells.The J2 antibody was used to detect endogenous dsRNA in malignant glioma cells treated with Zeocin.Western blot was used to assess the phosphorylation levels of PKR and eukaryotic initiating factor 2α(eIF2α).Results Zeocin significantly inhibited growth and migration of glioma cells;Zeocin treatment induced the production of endogenous dsRNA in malignant glioma cells;as the concentration of Zeocin increased,phosphorylated PKR and eIF2αprotein level also significantly increased;Zeocin downregulated the total m6A level of glioma cells in a dose-dependent manner;Zeocin selectively downregulated the protein level of methylase METTL14;Zeocin had no effect on mRNA levels of m6A modifying enzymes.Conclusion Zeocin probably triggered more dsRNA by downregulating the m6A level of RNA in malignant glioma cells,which in turn activated the PKR/eIF2α pathway,ultimately leading to tumor growth inhibition.

Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.

Objective To investigated vascular characteristics and clinical follow-up results of gestational trophoblastic neoplasia(GTN)with uterine arteriovenous malformation(UAVM)using contrast-enhanced magnetic resonance angiography(CE-MRA).Methods Patients clinically suspected of GTN at Obstetrics and Gynecology Hospital,Fudan University from Dec 2015 to Dec 2020 were selected.Imaging characteristics of conventional magnetic resonance imaging and CE-MRA before treatment.The International Federation of Gynecology and Obstetrics(FIGO)2000 clinical staging and prognosis scoring system was used to evaluate the severity of the condition and related risk factors,the treatment methods(chemotherapy,surgical treatment,and arterial embolization)and prognosis determined during follow-up were recorded.Results A total of 44 cases were included,including 5 cases of placental site trophoblastic tumor(PSTT)and 39 cases of the other GTN.There were 3 cases of PSTT combined with UAVM and 23 cases of the other GTN combined with UAVM.Thirty-nine cases of the other GTN were divided into two groups according to the presence or absence of UAVM.Data regarding the β-human chorionic gonadotropin(β-hCG)value(＜10 000 mIU/mL and≥10 000 mIU/mL)were evaluated using Chi-square test,and the difference was statistically significant(P=0.001).The average FIGO scores of the two groups were 4.19±3.69 and 6.70±3.39,and the difference was statistically significant(P=0.035).Conclusion When β-hCG value≥10 000 mIU/mL,the probability of UAVM occurrence increases.The higher the prognosis score is,the more possibility of formation of UAVM.The use of CE-MRA technology helps to better diagnose UAVM.

Objective To compare the efficacy and safety between thermal ablation combined with synchronous transcatheter arterial chemoembolization(TACE)and TACE in patients with liver metastasis of neuroendocrine tumors of different pathologic grades.Methods A retrospective analysis was performed on patients with liver metastases of neuroendocrine tumors admitted to Department of Interventional Radiology,Zhongshan Hospital,Fudan University from Nov 1,2006 to Jul 31,2022.The patients were divided into synchronous ablation group and TACE group according to treatment mode and subgroups according to pathological grade.The lesions were evaluated by postoperative imaging examination.The patients were followed up until Jul 31,2023,and surgery-related complications were recorded.The endpoint of prognosis were progression-free survival(PFS)and overall survival(OS).Results A total of 86 patients with neuroendocrine tumor were collected,including 34 patients in simultaneous ablation group and 52 patients in TACE group.According to WHO classification,21 patients at G1 stage,45 patients at G2 stage and 20 patients at G3 stage were included.No serious postoperative complications occurred in all patients.The median OS was 47.0(95%CI:31.2-62.8)months in the TACE group and 56.0(95%CI:8.3-73.4)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.50).The median PFS was 18.0(95%CI:6.0-30.0)months in the TACE group and 29.0(95%CI:10.0-48.0)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.22).Of the 45 patients at G2 stage,27 received TACE with a median OS of 47.0 months,and 18 received synchronous ablation with a median OS of 59.0 months,and there was no statistical difference between the two groups(P=0.45).The median PFS was 12.0 months in the TACE group and 32.0 months in the synchronous ablation group,and the difference between the two groups was statistically significant(P=0.03).Conclusion Comparing with TACE,simultaneous ablation can delay disease progression in patients with liver metastasis of neuroendocrine tumors to a certain extent and has good safety,especially for patients with liver metastases of neuroendocrine tumors with intermediate or low grade.

Objective To explore the experience of migraine in patients undergoing closure of patent foramen ovale,so as to develop targeted interventions for relieving patients'migraine and improving quality of life.Methods It was a qualitative study.A total of 11 patients who experienced migraine,underwent closure of patent foramen ovale,and admitted to the Department of Cardiology,Zhongshan Hospital,Fudan University from Oct 2022 to Apr 2023 were selected.One-to-one,in-depth semi-structured interviews were conducted.The conventional content analysis was used for data analysis.Results The migraine experience of patients undergoing closure of foramen ovale could be shown in 5 themes:migraines attacked varied;migraines brought serious physical and mental effects;migraines were dealt with in a variety of ways;patients had expectations for closure;professional support was needed.Conclusion The experience of migraine in patients undergoing closure of patent foramen ovale varied and was long-lasting.Patients were unable to effectively deal with migraine which had great negative effects.Multidisciplinary pain clinics could be established.Health care professionals should provide patients with professional and personalized pain management,pay attention to the accompanying symptoms and the negative mood,and improve patients'awareness and management level of migraine.

Objective To investigate the incidence of malignant tumors in type 2 diabetes mellitus(T2DM)patients and the effect of fasting blood glucose(FBG)on the incidence.Methods A record linkage was carried out between Cancer Registry System in Shanghai and the electronic health record(EHR)of residents in Minhang District during 2004-2020,then a retrospective cohort study was conducted for analysis.Fasting blood glucose classification was conducted with Q1 group(＜7.0 mmol/L),Q2 group(7.0-7.9 mmol/L),Q3 group(8.0-9.7 mmol/L),and Q4 group(≥9.8 mmol/L).To quantify the hazard and effect on the risk of cancer incidence in diabetic patients,the Cox regression model and restricted cubic splines(RCS)were used.Results The study included 70 361 subjects in total,with a male to female ratio of 49.03%to 50.97%,an average age of(63.15±10.56)years,and an average follow-up time of(9.25±4.38)years.Malignant tumor incidence rate was 868.14/100 000 person years,while male 939.87/100 000 person years,female 801.85/100 000 person years,respectively.And the incidence of malignant tumor decreased with the duration of the disease(P＜0.05).With an OR of 1.44(95%CI:1.33-1.56),Q3 group had the highest influence on the incidence of malignant tumors in multivariate analysis when compared to Q1 group.After adjusted the impact of age,the RCS graphs revealed a nonlinear trend in which the incidence of malignant tumors increased initially,then slowed down or decreased with an increase in mean glucose fasting,and the difference was statistically significant(Pnonlinear＜0.05).Conclusion With high incidence of malignant tumors in T2DM patients,the impact of glucose fasting on the incidence of malignant tumors does not depend entirely on the concentration.

Objective To explore the relationship between community health follow-up management and the quality of life of residents receiving home care from long-term care insurance(LTCI),and provide a basis for the construction of an integrated community home care service model centered on disabled residents.Methods According to the inclusion and exclusion criteria,and the principle of convenience,a sample was selected consisting of residents who participated in LTCI home care from Jan 1 to Dec 31,2021,in Meilong Community of Minhang District,Shanghai.After a year of participation,the subjects'quality of life was assessed face-to-face by trained community doctors using the 36-item short form health survey(SF-36).Based on the electronic health records of residents,the community chronic disease management system,the LTCI management system,and combined with on-site questionnaire survey,community doctors collected the demographic information,lifestyle,types of diseases,chronic disease comorbidity status,and health follow-up management provided by primary medical and health institutions.To assess the association between community health follow-up management and residents'quality of life with home care insurance for elderly care through cross-sectional analysis.Results The survey revealed that 230(57.64%)individuals had indeed received health follow-up management provided by the community health service center.The scores of the general health,physiological function,physical pain,mental health,vitality,and emotional function dimensions on the SF-36 scale were found to be higher compared to those of no follow-up population.The difference between the two groups exhibited statistical significance(all P＜0.05).Furthermore,individuals who actively engaged in the health follow-up management provided by community health service centers exhibited significantly higher scores in terms of health change(P=0.003),indicating a relatively favorable overall health status.After adjusting for demographic and confounding variables,further analysis revealed a significant positive association between health follow-up management provided by community health service centers and the overall health,physiological function,physical pain,mental health,and vitality dimensions of the SF-36 scale among LTCI beneficiaries(all P＜0.05).Conclusion The provision of health follow-up management by community health service centers exerts a significant positive impact on the quality of life among disabled residents covered by LTCI.It is an effective way to improve the quality of LTCI home care services.

Objective To investigate the relationship between triglyceride-gluscose(TyG)index in early pregnancy and the delivery of small for gestational age infant(SGA)in patients with gestational diabetes mellitus(GDM).Methods A total of 1 532 pregnant women from Shanghai Fifth People's Hospital and the Second People's Hospital of Kashgar Region,who were enrolled in the study between Jan 2018 and Jun 2023 and met the inclusion criteria,were categorized into the group with GDM(754 cases)and the group without GDM(778 cases)based on the results of the oral glucose tolerance test(OGTT)conducted at 24-28 weeks of pregnancy.Within the GDM group,patients were further categorized into 3 groups based on neonatal weight:SGA group,large for gestational age infant(LGA)group,and appropriate for gestational age infant(AGA)group.A Logistic regression model was used to analyze the independent influences on SGA delivery in patients with GDM to analyze the correlation between the TyG index and the occurrence of SGA.The predictive value of the TyG index in early pregnancy for SGA delivery in GDM patients was analyzed using ROC curves.Results The TyG index in the SGA group of GDM patients was significantly lower than that in the LGA,AGA and control without GDM group(P＜0.05).Multifactorial logistic regression analysis revealed that the TyG index was independently correlated with the SGA in GDM patients(P＜0.05).The ROC curve analysis demonstrated a good predictive value of the TyG index in early gestation for SGA delivery in GDM patients(AUC=0.821,95%CI:0.763-0.879,P＜0.001).Conclusion The TyG index in early pregnancy among GDM patients is independently correlated with the occurrence of SGA infants and has a good predictive value for SGA delivery in GDM patients.

Objective To study and verify the function of de novo interferon regulatory factor(IRF8)frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level.Methods The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells,or packed into lentivirus to infect two kinds of immune cell lines.Q-PCR,Western blot,immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation.Results The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully,and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well.Compared with wildtype,the molecular weight of IRF8 variant was slightly increased,while the expression level presents in opposition,even if on transcription level.Moreover,the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm,and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein.Conclusion The de novo frameshift mutation was presumed as gain-of-function(GOF)mutation.