Objective: This prospective study evaluated the feasibility of chemical exchange saturation transfer (CEST) MRI for assessing disease activity in thyroid-associated ophthalmopathy (TAO). Materials and Methods: A total of 88 patients with active TAO, 76 with inactive TAO, and 30 healthy controls were enrolled. CEST MRI-derived magnetization transfer ratio (MTR) and MTR asymmetry (MTRasym) at 1 ppm, 2 ppm, and 3.5 ppm were calculated. Clinical data, MTR, and MTRasym values for the extraocular muscles (one representative muscle per eye, yielding two measurements per participant) were compared among the groups. Spearman’s correlation was used to examine associations between imaging parameters and the clinical activity score (CAS) in patients with TAO. Logistic regression analysis was used to identify independent associations between imaging parameters and disease activity in patients with TAO (active vs. inactive). Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance for discriminating active from inactive TAO. Results: Patients with active TAO showed lower MTR values (P < 0.001) and higher MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) (all P < 0.001) compared with those with inactive TAO. MTR was negatively correlated with CAS (r = -0.402; P < 0.001), while MTRasym (1 ppm), MTRasym (2 ppm), and MTRasym (3.5 ppm) were positively correlated with CAS (r = 0.369, 0.350, and 0.349, respectively;all P < 0.001). MTR and MTRasym (1 ppm) were independently associated with TAO activity. The areas under the ROC curve (AUCs) for MTR and MTRasym (1 ppm) in discriminating active from inactive TAO were 0.772 and 0.730, respectively. Combining MTR with MTRasym (1 ppm) significantly improved diagnostic performance compared with either parameter alone, achieving an AUC of 0.805 (P = 0.029 and 0.001). Conclusion MTR and MTRasym (1 ppm) were independently associated with TAO activity. Their combination further enhanced diagnostic performance in distinguishing active from inactive TAO, suggesting their potential as quantitative imaging biomarkers to guide treatment in patients with TAO.

To investigate the effect of mesenchymal stromal cells (MSCs) on the fibrosis progression and endometrial regeneration in mouse models of endometrial injury, a mouse endometrial injury model was established by physical scraping combined with lipopolysaccharide (LPS) chemical induction, and the endometrium morphology and collagen deposition were evaluated by HE and Masson staining after unilateral administration of MSCs. RT-qPCR and immunofluorescence were used to detect the expression of epithelial markers Epcam and collagen I (Col1). Primary endometrial epithelial cells were isolated to assess p21 expression. Fibrosis-related genes and signaling pathways were validated using transcriptome sequencing and RT-qPCR. The experimental results showed that MSCs increased endometrial thickness and number of glands (P<0.05), up-regulated the expression of Epcam (P<0.01), while significantly reducing uterine collagen fiber deposition (P<0.05) and the expression of p21 in primary epithelial cells (P<0.0001). Transcriptomic analysis revealed that MSCs attenuated collagen deposition by modulating genes involved in the TGF-β signaling pathway. This study elucidates that MSCs facilitate uterine repair by reversing endometrial fibrosis and promoting epithelial regeneration, and their role is related to the regulation of the TGF-β/SMAD pathway and suppression of aberrant collagen accumulation.

Objective To analyze the occurrence status of low blood pressure (BP) in patients with refractory heart failure (RHF) and its relationship with comorbidities. Methods A retrospective analysis was conducted on the clinical data of 360 patients with RHF who were hospitalized in department of cardiology of Affiliated Nantong Hospital of Shanghai University from May 2021 to May 2025. These patients were divided into the RHF with BP group and the RHF group based on their blood pressure at admission. The general data and comorbidities were compared between both groups. Multivariate logistic regression analysis was used to identify the risk factors for coexisting BP. Results The heart rate (HR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), blood urea nitrogen, high-sensitivity cardiac troponin T, right atrial diameter, proportion of cardiac function grade IV, use rate of diuretics and prevalence rate of dilated cardiomyopathy (DCM) in the RHF with BP group were higher while the high-density lipoprotein cholesterol (HDL-C), albumin, left ventricular ejection fraction, use rate of lipid-lowering drugs and prevalence rate of coronary heart disease were lower compared to the RHF group, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis suggested that increased HR (OR=1.685, 95%CI: 1.106-2.569), increased NT-proBNP (OR=1.772, 95%CI: 1.138-2.759), decreased HDL-C (OR=0.605, 95%CI: 0.400-0.917) and DCM (OR=1.956, 95%CI: 1.176-3.255) were independent risk factors affecting BP in RHF patients (P<0.05). Conclusion The incidence rate of low blood pressure in elderly RHF patients is about 19.17%. Increased heart rate, increased NT-proBNP, decreased HDL-C and dilated cardiomyopathy are closely linked to the occurrence of low blood pressure, and they can be used as clinically related factors to identify patients at high risk of low blood pressure.

Objective: To investigate the trend in disease burden of injuries among children and adolescents in China from 1990 to 2021, so as to provide a basis for formulating prevention and control strategies and reducing this disease burden. Methods: Data on mortality, disability-adjusted life years (DALY) rate, incidence, and prevalence of injuries among children and adolescents aged <20 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. All rates were standardized using the GBD 2021 world standard population. The trend in incidence of disease burden of injuries among children and adolescents across differents genders and ages from 1990 to 2021 was evaluated using average annual percent change (AAPC). Results: From 1990 to 2021, the standardized mortality (AAPC=-5.435%), standardized DALY rate (AAPC=-5.311%), standardized incidence (AAPC=-0.466%), and standardized prevalence (AAPC=-0.810%) of injuries among children and adolescents in China showed downward trends (all P<0.05). Among these, the standardized mortality of animal contact (AAPC=-9.138%) and the standardized DALY rate of medical side effects (AAPC=-8.389%) decreased at a relatively fast pace, while the standardized incidence of falls (AAPC=0.083%) and the standardized prevalence of exposure to natural forces (AAPC=2.656%) showed upward trends (all P<0.05). The standardized mortality, standardized DALY rate, standardized incidence and standardized prevalence of injuries were higher in males than in females. The trend in males showed a downward trend (all P<0.05), consistent with the total population. The crude incidence of injuries in the group aged 15-<20 years showed an upward trend (AAPC=0.391%, P<0.05), while the trend in the group aged 10-<15 years was not statistically significant (P>0.05). The crude incidence of injuries in the groups aged 5-<10 years and <5 years showed downward trends (AAPC=-0.488% and -2.275%, both P<0.05). In 2021, the <5 years age group had the highest crude mortality and crude DALY rate of injuries, at 13.94/100 000 and 1 257.26/100 000, respectively. The 15-<20 years age group exhibited the highest crude incidence and crude prevalence, at 4 874.05/100 000and 4 050.35/100 000, respectively. Drowning and falls were major components of the disease burden across all age groups. Conclusions From 1990 to 2021, the disease burden of injuries among children and adolescents in China showed an overall downward trend. The disease burden was consistently higher in males than in females. Children aged <5 years face a high risk of fatality and disability, while adolescents aged 15-<20 years experience a high incidence and frequency of injuries. Drowning and falls were key priorities for prevention and control.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

The importance of gait assessment in the rehabilitation of cancer patients is gradually being recognized. However, quantitative analysis of balance ability in cancer patients is still limited. A total of 102 cancer patients meeting the inclusion criteria were recruited from Hefei Cancer Hospital, Chinese Academy of Sciences. Their balance ability was evaluated using the Berg Balance Scale (BBS). Gait data were collected by an electronic walkway and an IMU sensor system, including spatial-temporal and kinematic gait features such as step length, cadence, support time, and range of motion. Recursive feature elimination was used for feature selection. Ridge, Elastic Net, SVR, RF, and AdaBoost models were used to predict balance ability scores. Five-fold cross-validation was used to evaluate the performance of these models. Results show that the SVR model achieves the best performance with fifteen features (RMSE=3.22, R ²=0.91), followed by Ridge (RMSE=3.63, R ²=0.89). A method for evaluating balance ability based on gait features is proposed, providing a quantitative tool for personalized rehabilitation interventions in cancer patients.
Humans ; Postural Balance ; Neoplasms/rehabilitation* ; Gait ; Gait Analysis ; Biomechanical Phenomena ; Female

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective:To analyze the status quo of medical resources allocation of midwifery institutions in Shenzhen,to measure the spatial accessibility of the midwifery institutions,to give the optimal location of new midwifery institutions,and to optimize the allocation of midwifery medical resources.Methods:The spatial accessibility of midwifery institutions was accurately measured using the two-step moving search method,and the spatial layout optimization analysis was carried out using the model of maximum coverage site selection problem.Results:(1)There is obvious spatial heterogeneity in the accessibility of midwifery institutions in Shenzhen,with the accessibility of the western region higher than that of the eastern region,and that of the urban center higher than the peripheral region;(2)the accessibility of midwifery institutions in Shenzhen is obviously affected by factors such as demography,economy,topography,and road network;(3)after simulating the addition of new midwifery institutions by using the maximal-coverage siting model,the accessibility of midwifery institutions in various districts of Shenzhen rises significantly.Conclusion:(1)to formulate urban maternal and child health care resource plans based on accurate portraits of regional populations;(2)to use the advantages of digital intelligence technology to drive the optimization of the layout and radiation of high-quality maternal and child health care resources;(3)and to give priority to establish maternal and child medical institutions in low-accessibility areas and special medical bus lines.

Fatty liver is common disease of nutritional metabolism in the perinatal period,character-ized by elevated levels of NEFA in the blood and disorders of lipid metabolism.High concentra-tions of NEFA damage mitochondria and promote the release of reactive oxygen species(ROS).At the same time,lipid peroxidation occurs in lipid accumulation in hepatocytes,producing free radi-cals such as ROS,which leads to oxidative stress in the liver.When the level of intracellular ROS increases,thioredoxin-interacting protein(TXNIP)activates nucleotide-binding oligomerization structure-like protein 3(NLRP3)inflammasomes,and oxidative stress can regulate pyroptosis,but it is unclear whether reactive oxygen species(ROS)produced by oxidative stress in hepatocytes can mediate pyroptosis and induce liver injury in dairy cows through the TXNIP/NLRP3 pathway.In this study,liver tissue samples from healthy dairy cows and fatty liver cows were collected,and NEFA was used to construct a fatty liver cell model,and triglyceride(TG)content and oxidative stress related indicators were detected by kit.Western blot was used to detect the activation of NL-RP3 inflammasomes,the inflammatory pathway of NF-κB and the expression levels of pyroptosis-related proteins.Fluorescence quantitative PCR was used to detect the relative expression level of inflammatory factor mRNA.The results showed that compared with the healthy(control)group,the TG content of fatty liver tissue and fatty liver cells was significantly increased(P＜0.05),the activities of SOD and GSH-Px were significantly decreased(P＜0.05),and the protein expression levels of TXNIP,NLRP3,GSDMD-N and Caspase-1 were significantly up-regulated(P＜0.05).The results of the antioxidant model of fatty hepatocytes using NEFA and antioxidants(NAC)showed that compared with the fatty hepatocyte model,the content of ROS in hepatocytes was sig-nificantly reduced,and oxidative stress,NLRP3 inflammasome activation and pyroptosis were alle-viated.In summary,this study found that when fatty liver disease occurs in dairy cows,ROS pro-duced by oxidative stress in the liver can mediate pyroptosis through the TXNIP/NLRP3 path-way,which can lead to liver injury in fatty liver cows.