Objective:To study the characteristics of thyroid-associated ophthalmopathy (TAO) clinical trials based on WHO International Clinical Trials Registry Platform (ICTRP).Methods:The WHO ICTRP database was searched from their inception to October 25, 2024.Data including the basic registration information, study type, study design, study stage, intervention measures and outcomes were extracted, and a descriptive analysis of the included trials was performed using bibliometric method.Results:A total of 288 trials were identified, the number of registrations for TAO interventional clinical trials was on the rise.Among them, 13 trials without key registration information, 93 without intervention, 2 with non-TAO subjects, 28 without control group, and 4 with duplicate study registration numbers or extension studies were excluded.Finally, 142 intervention trials were included in this study.The top three in registration numbers were China (44 trials), the United States (40 trials), and Europe (31 trials), and most of them were single-center studies (99 trials, accounting for 69.7%). For study design, 131 trials were randomized controlled trials, and 122 trials reported its masking method.Main stage of the trials was phase Ⅲ (31 trials, accounting for 21.8%). Drug treatments (121 trials, accounting for 85.2%) were the main intervention measures, and most of them were monoclonal antibody drugs (55 trials). Clinical activity score (81 trials) and exophthalmia (80 trials) were the commonly used outcome measures.Conclusions:The number of registrations for TAO interventional clinical trials is on the rise, with monoclonal antibody drugs as the main intervention measures.However, issues such as the limited registration number, uneven distribution of countries/regions, incomplete information, and low quality of study design remain to be addressed.Researchers should raise the awareness of registration and design of clinical trials, deepen international and interregional cooperation, improve the review and tracking mechanism of clinical trial registration platforms, and promote the high-quality development of TAO clinical trials.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

Objective:To analyze the population structure, quantity of rodents, fleas and epidemiological characteristics of animal plague in the plague foci of Erenhot in Inner Mongolia Autonomous Region, and to provide a basis for scientific prevention and control of plague.Methods:The descriptive epidemiological method was used to analyze the surveillance and epidemic data of plague in Erenhot from 2013 to 2023 (from the plague prevention and control management information system of the Chinese Center for Disease Control and Prevention, and the summary of plague surveillance data in Inner Mongolia Autonomous Region from 2013 to 2023), including rat density, nocturnal rat capture, flea infection of rodents, bacteriological and serological detection, etc.Results:From 2013 to 2023, a total of 418 hm 2 of plague foci were investigated in Erenhot, 1 054 rats were caught, and the density of rats was 2.52/hm 2, among which Meriones unguiculatus was the dominant species ( n = 480), and the density was 1.15/hm 2. The capture rate of nocturnal rodents was 6.38% (1 291/20 250). The flea infestation rate of rodents was 35.53% (1 491/4 197), with a flea index of 1.25. Xenopsylla conformity is the dominant flea species ( n = 1 886). Animal plague outbreaks occurred in 7 years, with 11 positive rodents and 10 groups of positive fleas identified by the bacteriology tests, and a total of 21 strains of Yersinia pestis isolated. Eleven positive sera samples were detected by serology. Conclusion:The rodent density in the plague foci of Erenhot is relatively low, but the flea index is high, the animal epidemic is active, facing a significant risk of imported human and animal plague epidemics.

Objective:To study the characteristics of thyroid-associated ophthalmopathy (TAO) clinical trials based on WHO International Clinical Trials Registry Platform (ICTRP).Methods:The WHO ICTRP database was searched from their inception to October 25, 2024.Data including the basic registration information, study type, study design, study stage, intervention measures and outcomes were extracted, and a descriptive analysis of the included trials was performed using bibliometric method.Results:A total of 288 trials were identified, the number of registrations for TAO interventional clinical trials was on the rise.Among them, 13 trials without key registration information, 93 without intervention, 2 with non-TAO subjects, 28 without control group, and 4 with duplicate study registration numbers or extension studies were excluded.Finally, 142 intervention trials were included in this study.The top three in registration numbers were China (44 trials), the United States (40 trials), and Europe (31 trials), and most of them were single-center studies (99 trials, accounting for 69.7%). For study design, 131 trials were randomized controlled trials, and 122 trials reported its masking method.Main stage of the trials was phase Ⅲ (31 trials, accounting for 21.8%). Drug treatments (121 trials, accounting for 85.2%) were the main intervention measures, and most of them were monoclonal antibody drugs (55 trials). Clinical activity score (81 trials) and exophthalmia (80 trials) were the commonly used outcome measures.Conclusions:The number of registrations for TAO interventional clinical trials is on the rise, with monoclonal antibody drugs as the main intervention measures.However, issues such as the limited registration number, uneven distribution of countries/regions, incomplete information, and low quality of study design remain to be addressed.Researchers should raise the awareness of registration and design of clinical trials, deepen international and interregional cooperation, improve the review and tracking mechanism of clinical trial registration platforms, and promote the high-quality development of TAO clinical trials.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Objective:To measure the distance between the fetal bladder neck and the rectal end using prenatal MRI and analyze the developmental patterns of this distance and the gender differences in the second and third trimesters of pregnancy.Methods:This retrospective cohort study involved fetuses born at Guangzhou Women and Children's Medical Center, Guangzhou Medical University after regular prenatal examinations from January 2019 to December 2022 and confirmed to have typical anorectal structures after birth. These fetuses had undergone prenatal MRI examinations for reasons other than abdominal issues. The morphology of the fetuses' colons, rectums, and bladders was observed, and the vertical distance between the bladder neck and the rectal end was measured on sagittal T1weighted imaging. Differences in the distance between male and female fetuses were analyzed. The fetuses were divided into five groups based on their gestational age at the time of MRI examination (23-24 weeks, >24-26 weeks, >26-28 weeks, >28- 30 weeks, and >30-32 weeks), and the changes in the distance with gestational age were analyzed. Statistical analysis was performed using t-test, Kruskal-Wallis test, and Spearman correlation analysis. Pairwise comparisons among multiple groups were conducted using the Bonferroni method. Results:(1) A total of 142 fetuses were included in this study, all of which were singletons, with 73 males (51.4%) and 69 females (48.6%). The gestational age at the MRI examination was 28 weeks (26-30 weeks). (2) All fetuses had meconium filling the entire rectum and colon, with the rectal end located 0.570-2.610 cm below the bladder neck. (3) The distance between the bladder neck and the rectal end was shorter in male fetuses than in female fetuses [(1.140±0.261) vs. (1.519±0.405) cm, t=－6.58, P<0.001]. (4) In female fetuses, four pairs of groups showed statistically significant differences in the distance (23-24 weeks group vs. >26-28 weeks, >28- 30 weeks, and >30-32 weeks groups, and >24-26 weeks group vs. >30-32 weeks group). However, only two groups of male fetuses (23-24 weeks group vs. >28-30 weeks group) had statistically significant differences in the distance (all P<0.005). (5) The distance was moderately correlated with gestational age in male fetuses ( r=0.42, P<0.001), but they were strongly correlated in female fetuses ( r=0.66, P<0.001). Conclusions:The distance between the bladder neck and the rectal end in fetuses shows certain developmental patterns and gender differences in pregnancy's second and third trimesters. The correlation between the value and gestational age is stronger in female fetuses.

Objective To investigate the potential beneficial predictors for endovascular treatment(EVT)in case of acute anterior circulation large vessel occlusion with large-core infarction.Methods We made a retrospective inclusion of 92 patients with anterior circulation large vessel occlusion and core infarct volume ranging from 50 to 100 mL,who underwent EVT at Zhangzhou Municipal Hospital of Fujian Province from March 2018 to February 2021.All the patients were confirmed as anterior circulation large infarction and large infarct volume using computed tomography(CT),computed tomography angiography(CTA),and computed tomography perfusion(CTP)before EVT.All clinical and imaging data were collected to observe the postoperative recurrence rate,incidence of symptomatic intracranial hemorrhage(sICH),and functional prognosis 90 days.Then the patients were divided into favorable outcomes group(mRS≤3)and unfavorable outcomes group(mRS＞3)based on Rankin scores 90 days post-stroke.Univariate and multivariate Logistic analysis were conducted to analyze factors influencing the patients'prognosis.By combining the results of multivariate analysis,we constructed receiver operating characteristic(ROC)curves and identified the cut-off value to evaluate the predictive value of age for post-vascular treatment prognosis.Results Among the included patients,the postoperative revascularization rate(mTIICI≥2b)was 95％(88 cases),the rate of favorable outcomes at 90 days postoperatively(mRS≤3)was 32.61％(30 cases),the incidence of sICH was 13％,and the mortality rate was 31.5％.Compared with the unfavorable outcomes group,the favorable outcomes group had a younger age and a higher proportion of males.Multivariate analysis indicated that older age was an independent risk factor for adverse outcomes following endovascular treatment(OR=4.97,95％CI:1.78-13.90,P=0.002).The ROC curve indicated that the area under the curve was maximized at the age of 72.5 years(AUC=0.763,95％CI:0.661-0.864,P＜0.001).Its sensitivity and specificity was 0.565 and 0.833,respectively.Conclusion Age is an independent predictor of the prognosis of acute procirculatory large core stroke.Patients with large core infarction older than 72.5 years may not benefit from endovascular therapy,which needs to be confirmed by a multicenter large sample prospective randomized controlled trial.

Purpose To explore the key molecules mechanisms underlying the selective activation of macrophage and the regulation of Dicer expression induced by glioblastoma(GBM)cells,as well as its prognostic significance.Methods Glioblastoma conditional medium(GCM)was fractionated by molecular weight using ultrafiltration.Specif-ic molecular weight components of GCM that upregulate Dicer expression in mouse bone marrow derived macrophages(BMDMs)were identified.Secreted proteins were identified by mass spectrometry(MS).The correlation between candidate proteins and GBM prognosis was analyzed using the TCGA and CGGA database.In vitro experiments of the candidate proteins on Dicer expression in BMDMs were further carried out.Results GCM components with a molecu-lar weight of＞50 kDa significantly upregulated Dicer expression in BMDMs.MS identified five key secreted proteins:Prg4,Psap,Hexa,Aebp1,and Itih2.High expression of Prg4 was significantly positively correlated with poor progno-sis in GBM patients(P＜0.001)and was associated with the expression of selective macrophage activation markers.Recombinant Prg4 protein stimulated BMDMs and induced Dicer expression in mouse BMDMs.Conclusion This study reveals that glioma cells induce Dicer expression in macrophages by secreting Prg4,providing a theoretical basis for GBM therapeutic strategies targeting the Prg4-Dicer axis.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Purpose To summarize the clinicopathological features of pheochromocytoma and paraganglioma(PPGL)and discuss the potential correlation between SDHB immunophenotype and prognosis in PPGLs.Methods A retrospective analysis was conducted on 30 samples of PPGL along with their corresponding clinicopathological informa-tion,SDHB immunophenotype characteristics,and the risk of recurrence and metastasis.Results The study included 20 extra-adrenal paragangliomas and 10 pheochromocytoma cases.The male-to-female ratio was 13∶17,with a mean age of 56(range from 21 to 79).Four cases recurred,one case resulted in death and five cases failed to follow-up.All recurrent or fatal cases were paraganglioma patients.Among the 30 cases,3 had multiple nodular lesions,and the re-maining cases were single nodule.The neck was the most frequent site for paraganglioma(6/20),followed by retroper-itoneum(5/20).Histologically,the tumors displayed a variable"zellballen"architecture with a highly vascularized stroma.The chief cells had abundant pale eosinophilic cytoplasm and slightly to moderately atypical nuclei,and pe-ripherally located sustentacular cells.Positive immunoreactivity with markers of neuroendocrine cells,including Syn,CgA,and GATA3,was found in tumor chief cells,which were nonreactive for CK.The sustentacular cells exhibited positive immunoreactivity for the S-100 protein.SDHB deficiency was demonstrated in 12 of 30 cases,with only one case being pheochromocytoma.The recurrence rate in SDHB-deficient group was higher than that in the positive group(33.3％vs 6.7％).Only one case of paraganglioma developed distant metastasis and death.Conclusion SDHB de-ficiency was predominantly observed in paragangliomas and serverd as an indipentent factor for metastatic risk in PPGLs.It was closely associated with younger age at onset,invasiveness,extra-adrenal tumorgenesis,and a high rate of tumor recurrence.