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.

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.

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.

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.

The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr⁺ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat⁺Oxtr⁺ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.
Animals ; Receptors, Oxytocin/metabolism* ; Male ; Brain/growth & development* ; Mice ; Mice, Inbred C57BL ; Neurons/metabolism* ; Single-Cell Analysis ; Gene Expression Regulation, Developmental ; RNA, Messenger/metabolism* ; Animals, Newborn

BACKGROUND: Physical activity, sedentary behavior (SB), and sleep duration are associated with brain health. Effects of those on developing Parkinson's disease (PD) are poorly investigated. This study aimed to examine the independent and joint associations of physical activity, SB, sleep with PD risk. METHODS: We analyzed data on 401,697 participants from the UK Biobank cohort, which was enrolled in 2006-2010. Physical activities were measured based on a questionnaire. Sleep and SB time were defined through self-reported total number of hours. Models fitted with restricted cubic spline were conducted to test for linear and non-linear shapes of each association. Cox proportional hazards regression models were used to estimate the association of three modifiable behaviors. RESULTS: Our analytic sample included 401,697 participants with 3030 identified cases of PD (mean age, 63 years; 62.9% male). PD risk was 18% lower in the high total physical activity group (95% CI, 0.75-0.90), 22% lower in the high leisure-time physical activity (LTPA) group (95% CI, 0.71-0.86) compared with the low level and 14% higher in the high sleep duration group (95% CI, 1.05-1.24) compared to moderate group. Total SB time was irrelevant with PD risk, while high TV viewing showed a 12% increase of PD risk compared to the low group (95% CI, 1.02-1.22). Low computer use (0 h/day) was associated with a 14% higher risk compared to 1 h/day use (95% CI, 1.04-1.26). Those associations were independent. A combination of 7 h/day sleep, moderate-to-high computer use, and moderate-to-vigorous intensity of LTPA showed lowest PD risk (HR, 0.70; 95% CI, 0.57-0.85). CONCLUSIONS Physical activity, SB, and sleep were associated with PD risks separately. Our findings emphasize the possibility for changing these three daily activities concurrently to lower the risk of PD. These findings may promote an active lifestyle for PD prevention.
Humans ; Parkinson Disease/physiopathology* ; Male ; Sedentary Behavior ; Female ; Middle Aged ; Exercise/physiology* ; Prospective Studies ; Sleep/physiology* ; Aged ; Surveys and Questionnaires ; Proportional Hazards Models ; Risk Factors

BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

Objective To study the accuracy and safety of oral mucosal exfoliated cell specimens used in the bedside rapid detection of MTHFR C677T genotype by using the fluorescent probe method.Methods The outpatients and inpatients with hypertension visited and admitted in the department of cardiovascular medicine of this hospital from January 2019 to September 2020 were selected.The plasma homocysteine (Hcy) level in all patients was detected in the laboratory,a total of 482 hypertensive patients with Hcy≥10 μmol/L were se-lected,and the oral mucosal cells and whole blood sample were collected in all patients,and the genotypes of the above specimens were detected by the oral mucosal exfoliative cell fluorescent probe method and whole blood sample contrast reagents.If the two test results were inconsistent,the "gold standard" Sanger sequen-cing method was used to detect the whole blood sample for the final determination of MTHFR C677T geno-type.The coincidence rate was compared between the two detection methods,and the probability of adverse e-vents during the samples collection was observed and recorded.The accuracy and safety of fluorescence probe method for detecting MTHFR C677T genotype in the patients with oral mucosa exfoliation was evaluated.Re-sults The oral mucosal exfoliated cell samples and whole blood samples from 482 hypertensive patients were successfully collected,and no obvious adverse reactions occurred during the sampling process.The incidence rate of total mutation of MTHFR C677T gene detected by the fluorescence probe method and contrast reagent all were 73.23％ (353/482),the coincidence rate of homozygous wild type (CC type) in MTHFR C677T gene detected by the two methods was 100.00％ (95％CI:97.11-100.00),which of heterozygous mutant type (CT type) was 99.14％ (95％CI:96.91-99.76),which of homozygous mutant type (TT type) was 99.17％(95％CI:95.47-99.85),the total coincident rate of MTHFR C677T genotype was 99.38％ (95％CI:98.19-99.79)and the detection results consistency Kappa value was 0.9902.Conclusion The detection of MTHFR C677T gene mutation in oral mucosal exfoliated cells by fluorescent probe method is simple with less invasion,moreover which is rapid,safe and accurate.

Objective To review the research of self-management intervention in patients with hematopoietic stem cell transplantation,clarify the intervention elements,so as to provide references for clinical practice and future related research.Methods According to the scoping review framework,a literature search was performed in the PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,Wan fang Database,VIP,CBMdisc for all the studies on self-management intervention of patients with hematopoietic stem cell transplantation.The retrieval time was from the establishment of the database to December,2022.There were 2 researchers who extracted and analyzed the data of the included literature.Results A total of 12 articles were included,including 3 randomized controlled trials,8 quasi-experimental studies,and 1 mixed study.6 studies were conducted with interventions based on the theoretical basis or nursing model such as self-management oriented 5A nursing model,continuous nursing model,problem-based learning theory.The intervention methods of 12 studies included nurse-led self-management guidance,mobile applications,multidisciplinary collaboration,and graphic cards.The intervention time was mostly 1～3 months.The outcome indicators included feasibility evaluation indicators such as operability,ease of use,and user satisfaction of the application,and effect evaluation indicators such as self-management ability,quality of life,and medication compliance of patients.The results showed that self-management interventions could improve patient self-management ability,quality of life,medication compliance,and improve their psychological and nutritional status.Conclusion The research on self-management intervention in patients with hematopoietic stem cell transplantation is still in the development stage,and its positive effect has been preliminarily verified.Medical staff should strengthen the self-management evaluation of patients with hematopoietic stem cell transplantation,play the role of multidisciplinary team,use electronic health intervention methods,and formulate multi-level,scientific and effective self-management intervention programs.

Humans ; Stroke Volume ; Incidence ; Goals ; Meningioma/complications* ; Postoperative Complications/epidemiology* ; Fluid Therapy/adverse effects* ; Meningeal Neoplasms/complications*