ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

Objective:To investigate the association between albumin-corrected anion gap(ACAG)and short-to long-term death out-comes in patients with acute pancreatitis(AP).Methods:This retrospective study was based on the Medical Information Mart for Inten-sive Care-IV database,and the adult patients who were diagnosed with AP and were admitted to the intensive care unit were enrolled in this study.Cox regression risk analysis,receiver operating charac-teristic(ROC)curve analysis,Kaplan-Meier survival curve analy-sis,restricted cubic spline,and subgroup analysis were used to in-vestigate the value of ACAG in predicting the death outcome of AP patients.Results:A total of 444 patients were enrolled in this study,and according to the death status of the patients on day 28 after ad-mission,the patients were divided into survival group with 412 pa-tients and death group with 32 patients,with a mortality rate of 7.2%on day 28 after admission.The multivariate Cox regression analysis showed that ACAG was an independent predictive factor for all-cause mortality rate on day 28 after admission in AP patients(hazard ratio[HR]=1.18,95%CI=1.05-1.32),while it was not an in-dependent predictive factor for death outcome on days 90(HR=1.05,95%CI=0.97-1.14)and 180(HR=1.01,95%CI=0.94-1.09)and at 1 year(HR=1.02,95%CI=0.95-1.10).The ROC curve analysis showed that ACAG had an area under the ROC curve(AUC)of 0.732(95%CI=0.632-0.832)in predicting 28-day death outcome,which was better than that of AG(AUC=0.665,95%CI=0.550-0.781)and serum albumin(Alb)(AUC=0.655,95%CI=0.550-0.761)and was similar to that of Sequential Organ Failure Assessment(SOFA)score(AUC=0.745,95%CI=0.651-0.838).The ROC curve showed that the optimal cut-off value of ACAG was 21.375.Based on the cut-off value of ACAG of 21.375,the patients were divided into high-value group and normal-value group,and the Kaplan-Meier curve analysis showed that the patients with a high level of ACAG had a significantly higher mortality rate than those with normal ACAG(P<0.001).The subgroup analysis showed that the results were stable.Conclusion:ACAG can be used as an independent pre-dictive factor for all-cause mortality rate on day 28 after admission in AP patients,with a better efficacy than AG and Alb and a similar efficacy to SOFA.However,it is not significantly associated with 90-day,180-day,and 1-year death outcomes in AP patients.

Objective:To investigate the protective mechanism of cerium oxide nanoparticles(CeO2 NPs)against acute pancreatitis(AP),with a focus on their antioxidant and anti-inflammatory properties.Methods:CeO2 NPs were characterized by transmission elec-tron microscopy(TEM)and dynamic light scattering.In in vitro experiments,cell counting Kit-8(CCK-8)assay,flow cytometry,and Western blotting were used to validate the role of CeO2 NPs in preventing the apoptosis of pancreatic acinar cells.In in vivo experi-ments,C57BL/6 mice were divided into control group,AP group,AP+CeO2 group,SAP group,and SAP+CeO2 group to investigate the mechanism of action of CeO2 NPs in alleviating inflammation and oxidative stress in AP mice.Results:CeO2 NPs demonstrated rela-tively good stability and biocompatibility,with a particle size of(50±4)nm on TEM.In vitro experiments showed that CeO2 NPs sig-nificantly reduced the apoptosis of pancreatic acinar cells by alleviating lipid peroxidation and maintaining mitochondrial membrane potential.In vivo experiments showed that CeO2 NPs could reduce the serum levels of amylase,lipase,and inflammatory cytokines(in-terleukin-6 and tumor necrosis factor-α).This result might be related to the regulation of the IKK/P53/Bcl-2 pathway.CeO2 NPs re-duced the production of reactive oxygen species and enhanced anti-oxidant response by regulating the Nrf-2 signaling pathway.Con-clusion:CeO2 NPs exert anti-inflammatory and antioxidant effects by regulating the IκB kinase/tumor protein p53/B-cell lymphoma 2(IKK/P53/bcl-2)and nuclear factor erythroid 2-related(Nrf-2)signaling pathways,thereby showing promising potential for the treatment of AP.

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

Objective:In critical care medicine, extubation is a pivotal step in the management of mechanically ventilated patients. Accurately determining the optimal timing for extubation is essential for minimizing complications and improving patient survival rates. However, reliable indicators to predict clinical outcomes following extubation remain scarce. This study aims to identify a novel and robust predictor of extubation success in critically ill patients, thereby providing clinicians with more precise decision-making support.Methods:This retrospective study analyzed data from adult patients who underwent mechanical ventilation and were evaluated for extubation across six intensive care units (ICUs) at Xiangya Third Hospital of Central South University between January 2019 and December 2021. Patients with a history of difficult airway, upper airway obstruction, or neuromuscular disorders affecting respiratory function were excluded. The primary outcome was the reintubation rate within 24 hours post-extubation. Categorical variables were analyzed using the chi-square test or Fisher’s exact test, while between-group differences were assessed with the Mann-Whitney U test. Significant predictors identified in univariate analysis were further evaluated via multivariate logistic regression. The diagnostic accuracy of the maximum inspiratory pressure/body mass index (MIP/BMI) ratio was determined using receiver operating characteristic (ROC) curve analysis, with the Youden index employed to establish the optimal cutoff value. Kaplan-Meier analysis and log-rank tests were used to compare extubation success rates between groups. Statistical analyses were performed using SPSS V28.0 and Stata v.16.0. Results:Diabetes comorbidity ( OR: 8.181, 95% CI: 1.659–40.338) and MIP/BMI ( OR: 0.140, 95% CI: 0.042–0.469) were identified as independent predictors of reintubation. The area under the ROC curve (AUROC) for MIP/BMI was 0.753, demonstrating good predictive accuracy. The optimal cutoff value for MIP/BMI was 1.26 cmH 2O/(kg·m 2), with a sensitivity of 55.3% and specificity of 92.3%. Kaplan-Meier analysis revealed a significantly higher reintubation rate in the low MIP/BMI group compared to the high MIP/BMI group ( P = 0.009), further validating its predictive utility. Conclusions:This study establishes MIP/BMI as a novel and clinically valuable predictor of extubation outcomes in critically ill patients. A cutoff value of 1.26 cmH 2O/(kg·m 2) was found to best predict successful extubation.

Objective     To investigate the effects of different types of tricuspid regurgitation, implantation positions, and device models on the treatment outcomes of K-Clip for tricuspid regurgitation using numerical simulations. Methods     Three-dimensional reconstruction of the heart model was performed based on CT images. Two different regurgitation orifices were obtained by modifying the standard parameterized tricuspid valve leaflets and chordae tendineae. The effects of different K-Clip models at different implantation positions (posterior leaflet midpoint, anterior-posterior commissure, anterior leaflet midpoint, posterior septal commissure) were simulated using commercial explicit dynamics software Ls-Dyna. Conclusion     For the two types of regurgitation in this study, clipping at the posterior leaflet midpoint resulted in a better reduction of the regurgitation orifice (up to 75% reduction in area). Higher clamping forces were required for implantation at the anterior leaflet midpoint and posterior septal commissure, which was unfavorable for the smooth closure of the clipping components. There was no statistical difference in the treatment outcomes between the 18T and 16T K-Clip components, and the 16T component required less clamping force. Therefore, the use of the 16T K-Clip component is recommended.

The study explored the pathological mechanism of doxorubicin chemotherapy-induced neurotoxicity and the intervention methods of traditional Chinese medicine. BALB/c mice were selected to establish tumor-bearing mouse models by orthotopic injection of 4T1 triple-negative breast cancer cells. After randomization, the mice were treated with doxorubicin chemotherapy or doxorubicin chemotherapy + Kaixin San(KXS). The lesions in the prefrontal cortex of mice were observed by pathological examination, and the lesion information was obtained by long non-coding RNA sequencing. The occurrence of lesions was determined by Western blot and biochemical indicators. In addition, neuroblastoma cells and microglia cells were used to construct in vitro models, and drug-containing serum and p-AMPK dephosphorylation inhibitors were used to further verify the accuracy of animal experiments. Pathological results showed that KXS could alleviate doxorubicin-induced neuronal degeneration in the prefrontal cortex. The long non-coding RNA sequencing suggested that neuronal degeneration and the intervention process of KXS were related to ferroptosis, immune diseases, AMPK signaling pathway, etc. Western blot and biochemical indicators confirmed that this process was directly related to the activation of the AMPK/HIF-1α/ACSL4 signaling pathway to alleviate ferroptosis of neurons and immune response of glial cells. In conclusion, KXS could alleviate doxorubicin-induced neurotoxicity by activating the AMPK signaling pathway and reducing the ferroptosis of neurons and immune response of glial cells.
Animals ; Doxorubicin/toxicity* ; Mice ; AMP-Activated Protein Kinases/genetics* ; Signal Transduction/drug effects* ; Mice, Inbred BALB C ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Humans ; Cell Line, Tumor ; Neurotoxicity Syndromes/genetics*

Sepsis,a syndrome characterized by organ dysfunction caused by infection,exhibits high incidence and mortality.The pathogenesis of sepsis is complex and involves a cascade of immune reactions,with no specific drugs currently available.Sepsis is mainly treated with Western medical supportive therapies such as antibiotics,hemodynamic management,and mechanical ventilation.However,the occurrence of immune cas-cades significantly increases patients'vulnerability to secondary infections,leading to septic shock and unfavor-able prognoses.International consensus indicates that initiating dynamic monitoring of patients'immune function within 48 h post-sepsis diagnosis can effectively decelerate sepsis progression.Extensive studies have indicated that macrophages,serving as the first line of defense in the innate immune system against pathogens,play a vital role in treating immune system disorders by regulating macrophage polarization and the ratio of cytokines activated.Mitophagy,a hot topic in recent years,has increasingly been shown to play a crucial role in regulating inflammatory signal transduction.Promoting mitophagy during the stage of cytokine storm can mitigate uncontrolled infection and excessive inflammation in sepsis,and inhibiting mitophagy during immunosuppression can enhance host immunity,facilitate bacterial clearance,and improve the survival rate of patients.The idea of treating dis-ease before its onset in traditional Chinese medicine(TCM)coincides with the current consensus among sepsis experts on prevention and interception.The TCM therapies such as extracts of Chinese medicine decoction pieces,TCM compound prescriptions,and acupuncture and moxibustion have the effects of clearing heat and detoxifying,activating blood and resolving stasis,reinforcing healthy qi and consolidating root,and purging.These approa-ches dynamically regulate the levels of mitophagy-related proteins,such as phosphatase and tension homology-induced putative kinase 1,Parkin-E3 ubiquitin protein ligase,light chain 3,and p62,while maintaining a suitable ratio between M1 and M2 macrophages.Consequently,they effectively prevent,halt,or even reverse the progression of sepsis,offering a novel perspective on sepsis management by emphasizing prevention before disease onset and controlling development of existing disease.

Purpose To explore the CT features of solid components between benign and malignant mixed ground-glass nodules(mGGO),and between minimally invasive adenocarcinoma(MIA)and invasive adenocarcinoma(IAC),and to improve the accuracy of preoperative diagnosis of mGGO.Materials and Methods The clinical and imaging data of 313 patients with mGGO admitted to the First Affiliated Hospital of Chongqing Medical University from January 2016 to July 2022 were retrospectively analyzed,and all patients were divided into benign group(95 cases)and malignant group(218 cases)according to follow-up or pathological results.All patients in malignant group were further divided into MIA(118 cases)and IAC(100 cases)groups.Logistic regression analysis models were established using the statistically significant CT features above,and the area under the curve(AUC)was calculated to evaluate the effectiveness of the model.Results ① Comparison of clinical characteristics between benign and malignant groups:malignant mGGO were more common in older people,females and nonsmokers,without smoking history,and the differences between two groups were significantly different(Z=-3.776,χ2=13.587,19.257;all P<0.001).②Comparison of CT features between benign and malignant groups:benign group existed a higher proportion of single solid component(84.21%vs.55.50%),while malignant group existed a higher proportion of multiple solid components(44.50%vs.15.79%),and the difference between two groups was significantly different(χ2=23.728,P<0.001).As for patients with single solid component,the solid components in malignant group were more likely to be irregular,mostly with eccentric distribution,and the proportion of solid components connected with blood vessels and pleura were higher than the benign group,the differences between two groups were significant(χ2=23.785,5.025,7.264;all P<0.05).Meanwhile,the benign group also had higher CT value[-153.00(-254.00,-80.50)Hu vs.-265.00(-363.25,-122.00)Hu],while lower relative CT value(0.30±0.16 vs.0.41±0.22),the differences between two groups were significant(all P<0.001).Logistic regression analysis:irregular morphology of the solid component(OR=0.236,P<0.001)and higher CT value(OR=1.009,P<0.05)were independent predictors of malignant mGGO.Receiver operator characteristic(ROC)curve analysis showed that the AUC was 0.772,and its accuracy,sensitivity and specificity was 70.65%,74.40%and 65.00%,respectively.③Comparison of CT features between MIA and IAC groups:MIA group existed a higher proportion of single solid component(74.58%vs.33.00%),while IAC group existed a higher proportion of multiple solid components(67.00%vs.25.42%),and the difference between two groups was significantly different(χ2=37.885,P<0.001).As for patients with single solid component,the solid components in IAC group were more likely to be irregular,it also had higher area,area proportion,and CT value,while lower relative CT value than the MIA group,the differences between two groups were significant(χ2=7.563,Z=-4.388,-3.923,-3.996;all P<0.05).Logistic regression analysis:eccentric distribution of the solid component(OR=0.083,P<0.05)and large area(OR=1.063,P<0.05)were independent predictors of IAC.ROC curve analysis showed that the AUC was 0.865,and its accuracy,sensitivity and specificity was 83.47%,87.90%and 68.20%,respectively.Conclusion The solid components between benign and malignant nodules as well as between MIA and IAC show different CT features.Based on these different features,it's helpful to improve the preoperative diagnostic accuracy of mGGO and guide the clinical treatment plans.