Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations, leading to enhanced lipid peroxidation. In neurological disorders, both oxidative stress and mitochondrial damage can contribute to ferroptosis, resulting in nerve cell dysfunction and death. The ubiquitin-proteasome system (UPS) refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome. In neurological conditions, the UPS plays a significant role in regulating ferroptosis. In this review, we outline how the UPS regulates iron metabolism, ferroptosis, and their interplay in neurological diseases. In addition, we discuss the future application of small-molecule inhibitors and identify potential drug targets. Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applications in neurological diseases.
Ferroptosis/physiology* ; Humans ; Proteasome Endopeptidase Complex/metabolism* ; Nervous System Diseases/metabolism* ; Animals ; Ubiquitin/metabolism* ; Iron/metabolism*

OBJECTIVE: To investigate the mechanism of autophagy in regulating bacterial translocation in intestinal infection caused by hypervirulent Klebsiella pneumonia (hvKp) and explore the method of reducing translocation infection of intestinal bacteria. METHODS: Fifty C57BL/6J mice were divided into gavage group (n = 40) and control group (CO group, n = 10). The gavage group was orally administered with 200 μL/d of hvKp (colony count of 10⁹ CFU/mL) continuously for 5 days to establish a hvKp intestinal infection model. CO group was given an equal amount of normal saline. After the experiment, the mice were anesthetized with lsofluraneand euthanized with cervical dislocation under anesthesia. Peripheral venous blood of mice was collected to detect bacterial translocation by 16S rDNA sequencing, then divided into translocation group (BT+ group) and non-translocation group (BT- group). Hematoxylin-eosin (HE) staining was used to evaluate intestinal morphology. The ultrastructural changes of intestinal tissues were observed by electron microscope. The levels of intestinal oxidative stress indicators such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GPx) were measured. Translocation was detected by in situ hybridization. The expression of tight junction protein microtubule-associated protein 1 light chain 3-II (LC3-II) and autophagy protein Beclin-1 were measured by Western blotting. The mRNA expression of tight junction proteins ZO-1 and Claudin-2 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of autophagy protein and tight junction protein were observed by immunofluorescence. RESULTS: Two out of 40 mice in the gavage group died after developing aspiration pneumonia. All mice in the CO group survived. The 16S rDNA sequencing results showed that no bacteria were detected in the peripheral blood of the CO group, but bacteria were detected in the peripheral blood of 18 mice in the gavage group, with a bacterial translocation rate of 47.4%. The BT- and BT+ groups showed intestinal mucosal tissue damage, with severe damage in the BT+ group. Compared with the CO group, the level of MDA in the BT- and BT+ groups were significantly increased, while the activities of SOD and GPx were significantly decreased. Compared with the BT- group, the MDA level in the BT+ group further increased, while the SOD and GPx activities further decreased [MDA (mmol/mg): 2.98±0.11 vs. 2.48±0.11, SOD (U/mg): 62.40±5.45 vs. 73.40±4.08, GPx (U/mg): 254.72±10.80 vs. 303.55±8.57, all P < 0.01]. The results of in situ hybridization detection showed that after continuous gastric lavage for 5 days, displaced hvKp was detected in the intestinal mucosal lamina propria and liver tissue of the BT+ group. Compared with the CO group, the protein expressions of LC3-II and Beclin-1 in the BT- and BT+ groups were significantly increased. The protein expressions of LC3-II and Beclin-1 in the BT+ group were obviously lower than those in the BT- group (LC3-II/β-actin: 0.38±0.04 vs. 0.70±0.09, Beclin-1/β-actin: 0.62±0.05 vs. 0.86±0.05, both P < 0.01), and there were autophagosomes in the intestinal mucosa. These results indicated that intestinal mucosal autophagy was activated after hvKp continuous gavage. Compared with CO group, the mRNA expressions of ZO-1 and Claudin-2 in the BT- and BT+ groups were significantly decreased. Compared with the BT- group, the mRNA expressions of ZO-1 and Claudin-2 in the BT+ group was further reduced [ZO-1 mRNA (2^-ΔΔCT): 0.78±0.06 vs. 0.88±0.06, Claudin-2 mRNA (2^-ΔΔCT): 0.40±0.04 vs. 0.70±0.06, both P < 0.01]. The immunofluorescence results showed that the fluorescence intensity of LC3-II, Beclin-1, ZO-1, and Claudin-2 in the BT+ group was significantly lower than that in the BT- group. CONCLUSION HvKp can activate intestinal mucosal autophagy and reduce the damage to intestinal mucosal barrier function by down-regulating oxidative stress level, reduce the occurrence of bacterial translocation.
Animals ; Oxidative Stress ; Mice, Inbred C57BL ; Autophagy ; Intestinal Mucosa/microbiology* ; Bacterial Translocation ; Mice ; Klebsiella Infections/microbiology* ; Superoxide Dismutase/metabolism* ; Beclin-1

Pancreatic cancer is currently recognized as one of the most malignant solid tumors， with a 5-year survival rate of 13% over a long period of time， and 80% of the patients have lost the opportunity for surgery at the time of confirmed diagnosis. In addition， the efficacy of conventional radiochemotherapy and targeted therapy is limited by high tumor heterogeneity and the complex immunosuppressive microenvironment. In recent years， mRNA vaccines have become a new focus of tumor immunotherapy due to their unique technical advantages. Based on non-integrating mRNA templates， mRNA vaccines enable precise encoding of tumor neoantigens， which are efficiently expressed in the host and can induce multifaceted immune responses. As for pancreatic cancer， current studies mainly focus on the development and optimization of tumor-associated antigen vaccines and tumor-specific antigen vaccines， as well as next-generation sequencing-guided neoantigen epitope optimization， innovative targeted delivery systems， and artificial intelligence-powered predictive models for immune response， thereby promoting the application of mRNA vaccines in the precise treatment of pancreatic cancer. Further studies should make breakthroughs in the targeted blockade of critical immunosuppressive molecules within the tumor microenvironment， the precise identification of tumor-specific antigenic epitopes， and the development of highly efficient vaccines， so as to bring new hopes for patients with pancreatic cancer.

Objective:To develop and validate clinical predictive models for identifying poor short-term response to recombinant human growth hormone(rhGH) treatment in children with short stature.Methods:A retrospective analysis was conducted on 118 children diagnosed with growth hormone deficiency or idiopathic short stature who were treated at the First Affiliated Hospital of Zhengzhou University and two other hospitals between January 1, 2020, and January 1, 2024. A poor response to rhGH was defined as a height increase of less than 0.2 standard deviation score(SDS) after 6 months of rhGH treatment. LASSO regression was used to identify predictive variables from baseline and follow-up data. Two logistic regression models were conducted: Model A(incorporating baseline variables only) and model B(incorporating both baseline and follow-up variables), and nomograms were created for visualization. External data and internal resampling were used for dual validation of the models, and their performance was compared.Results:A total of 118 children with short stature were included. Six baseline predictive variables(diagnosis, initial height SDS, bone age, bone age-chronological age difference, rhGH dose, and gender) and one follow-up variable(height SDS after 3 months of rhGH treatment) were identified. Area under the curve values for Model A and Model B were 0.753(95% CI 0.696-0.811) and 0.930(95% CI 0.891-0.975), respectively. Calibration curves, decision curve analysis, and other evaluation metrics demonstrated good discrimination and clinical utility for both models. Model B, incorporating the 3-month follow-up variable, showed superior predictive performance compared to Model A. Conclusions:The clinical prediction models developed in this study(Model A and Model B) are practical and reliable tools for quantitatively, conveniently, and intuitively identifying children with short stature at risk of poor response to rhGH treatment.

In the current process of talent cultivation in biology majors,some challenges like teaching content that lags behind the forefront of scientific research,instructional models that deviate from the principles of effective knowledge transmission,and evaluation systems that lack dimensions reflecting scientific innovation.As a strategy of tackling challenges,the Genetic Engineering teaching team,drawing on theoretical analysis and extensive teaching practice,has explored a reform of the instructional model from the perspective of integrating theory with practice.This effort led to the development of a research-oriented teaching model characterized by four iterative stages:knowledge instruction,thinking exercises,practical operation,and feedback evaluation.This model is ground-ed in five core elements of scientific thinking:criticality,coherence,simplicity,logic,and integrity.Imple-mentation follows the four-step framework,emphasizing structured knowledge delivery,cultivation of analytical thinking,hands-on experimentation,and comprehensive feedback.After one semester of application,it was found that through reconstructed knowledge systems,immersive simulations of research contexts,realistic problem-solving of technical bottlenecks and all-round feedback,this teaching model effectively fosters scientific thinking among both instructors and students,significantly enhances students'scientific research ca-pabilities and improves overall teaching effectiveness.

Taste is an important aspect that affects the application and development of oral liquid preparations of tradi-tional Chinese medicine,and bitterness is the main adverse taste of such preparations.In January 2024,the Chinese Society of Tra-ditional Chinese Medicine released the social organization standard"Technical Specification for Sensory Evaluation of Bitterness of Oral Liquid Preparation of Traditional Chinese Medicine"(standard number:T/CACM 1574-2024),led by the Chinese Medi-cine Preparation Branch of the Chinese Society of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,and Beijing University of Traditional Chinese Medicine,with the participation of 22 units nation-wide.It provided scientific guidance and good tools for the evaluation of bitterness of such preparations and lays a technical foun-dation for the subsequent implementation of taste improvement.This article provided a detailed introduction to the background and significance,formulation process,and main content of the standard development,which is beneficial for traditional Chinese medi-cine pharmacists to understand the standard better,apply,promote,and improve the group's standard,thereby promoting the im-provement of the taste quality and patient acceptance of such preparations,and promoting the development of the modernization of traditional Chinese medicine.

Objective To explore the predictive value of MRI parameters of carotid artery plaque combined with low density lipoprotein cholesterol/high density lipoprotein cholesterol(LDL-C/HDL-C)ratio for predicting ischemic stroke in young patients with carotid atherosclerosis.Methods Totally 125 young patients with carotid atherosclerosis were prospectively included and divided into stroke group and non-stroke group based on whether ischemic stroke occurred within 3 months.Clinical data,laboratory indicators and carotid plaque-related MRI parameters were compared between groups.Based on carotid plaque-related MRI parameters being statistically different between groups,combined model 1 was constructed using multivariable logistic regression analysis,while combined model 2 was constructed combined with LDL-C/HDL-C ratio.The efficacy of each parameter and model for predicting ischemic stroke in young adults was analyzed.Results There were 48 cases in stroke group and 77 cases in non-stroke group.The levels of glycosylated hemoglobin,LDL-C,LDL-C/HDL-C ratio,carotid artery stenosis rate,plaque eccentricity index and plaque enhancement rate in stroke group were all higher than those in non-stroke group(all P＜0.05).The area under the curve(AUC)of LDL-C/HDL-C ratio,carotid artery stenosis rate,plaque eccentricity index,plaque enhancement rate,combined model 1 and 2 for predicting ischemic stroke in young adults was 0.816,0.757,0.768,0.805,0.883 and 0.936,respectively,of combined model 1 was higher than those of single parameter(all P＜0.05),while of combined model 2 was higher than that of combined model 1(Z=2.336,P=0.020).Conclusion MRI parameters of carotid artery plaque combined with LDL-C/HDL-C ratio could effectively predict ischemic stroke in young patients with carotid atherosclerosis.

Objective To establish a risk factor model for intracranial artery stenosis in young patients with acute ischemic stroke(AIS)based on high-resolution magnetic resonance vascular wall imaging(HR-VWI).Methods Young patients with AIS(n=290)treated at Hengshui People's Hospital between January 2021 and January 2023 were retrospectively analyzed and randomly divided into a modeling set(203 cases)and a validation set(n=87)at a ratio of 7∶3.Patients in the modeling set were divided into the stenosis and non-ste-nosis groups according to whether they had intracranial artery stenosis.Multivariate logistic regression was used to analyze the clinical data and HR-VWI characteristics of the patients in the modeling set to screen for factors influencing intracranial artery stenosis in young patients with AIS.R software was used to construct and verify the risk factor model.Results Among the 290 patients,88 had intracranial artery stenosis(30.34％).The proportions of low-density lipoprotein cholesterol(LDL-C),plaque load,smoking history,hypertension,and eccentric plaques were higher in the stenosis group than in the non-stenosis group(P＜0.05),and the minimum lumen area and remode-ling index were lower in the stenosis group than in the non-stenosis group(P＜0.05).Multivariate logistic regression analysis showed that smoking history,hypertension,LDL-C level,plaque load,plaque morphology,and remodeling index were all factors influencing intracra-nial artery stenosis in young patients with AIS(P＜0.05).Based on the above risk factors,R was used to build a nomogram early warning model.The ROC results showed that the AUC of the nomogram model for predicting intracranial artery stenosis in the modelling and vali-dation sets were 0.872(95％CI:0.815-0.902)and 0.850(95％CI:0.789-0.891),respectively.The Hosmer-Lemeshow test results of the modeling and validation sets were x2=0.589,P=0.571 and x2=0.602,P=0.558,respectively.The calibration curves of the two groups were consistent with the standard curves.Conclusion The risk factor model for intracranial artery stenosis in young patients built in this study based on HR-VWI features exhibits good predictive efficacy,providing a new method for clinical prevention and treatment.

Taste is an important aspect that affects the application and development of oral liquid preparations of tradi-tional Chinese medicine,and bitterness is the main adverse taste of such preparations.In January 2024,the Chinese Society of Tra-ditional Chinese Medicine released the social organization standard"Technical Specification for Sensory Evaluation of Bitterness of Oral Liquid Preparation of Traditional Chinese Medicine"(standard number:T/CACM 1574-2024),led by the Chinese Medi-cine Preparation Branch of the Chinese Society of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,and Beijing University of Traditional Chinese Medicine,with the participation of 22 units nation-wide.It provided scientific guidance and good tools for the evaluation of bitterness of such preparations and lays a technical foun-dation for the subsequent implementation of taste improvement.This article provided a detailed introduction to the background and significance,formulation process,and main content of the standard development,which is beneficial for traditional Chinese medi-cine pharmacists to understand the standard better,apply,promote,and improve the group's standard,thereby promoting the im-provement of the taste quality and patient acceptance of such preparations,and promoting the development of the modernization of traditional Chinese medicine.

Objective To explore the predictive value of MRI parameters of carotid artery plaque combined with low density lipoprotein cholesterol/high density lipoprotein cholesterol(LDL-C/HDL-C)ratio for predicting ischemic stroke in young patients with carotid atherosclerosis.Methods Totally 125 young patients with carotid atherosclerosis were prospectively included and divided into stroke group and non-stroke group based on whether ischemic stroke occurred within 3 months.Clinical data,laboratory indicators and carotid plaque-related MRI parameters were compared between groups.Based on carotid plaque-related MRI parameters being statistically different between groups,combined model 1 was constructed using multivariable logistic regression analysis,while combined model 2 was constructed combined with LDL-C/HDL-C ratio.The efficacy of each parameter and model for predicting ischemic stroke in young adults was analyzed.Results There were 48 cases in stroke group and 77 cases in non-stroke group.The levels of glycosylated hemoglobin,LDL-C,LDL-C/HDL-C ratio,carotid artery stenosis rate,plaque eccentricity index and plaque enhancement rate in stroke group were all higher than those in non-stroke group(all P＜0.05).The area under the curve(AUC)of LDL-C/HDL-C ratio,carotid artery stenosis rate,plaque eccentricity index,plaque enhancement rate,combined model 1 and 2 for predicting ischemic stroke in young adults was 0.816,0.757,0.768,0.805,0.883 and 0.936,respectively,of combined model 1 was higher than those of single parameter(all P＜0.05),while of combined model 2 was higher than that of combined model 1(Z=2.336,P=0.020).Conclusion MRI parameters of carotid artery plaque combined with LDL-C/HDL-C ratio could effectively predict ischemic stroke in young patients with carotid atherosclerosis.