Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*

Objective To investigate the inhibitory effect of mannose on proliferation and apoptosis of HeLa cells of cervical cancer and its effect on Wnt/β-catenin pathway.Methods Cervical cancer HeLa cells were cultured in vitro and divided into control group(without any treatment)and low,medium and high dose experimental groups(cells treated with 5,10 and 25 mmol·L-1 mannose).Cell counting kit 8(CCK-8)and flow cytometry were used to detect cell proliferation and apoptosis.The B cell lymphoma-2(Bcl-2),p21,Bcl-2 associated X protein(Bax)and Wnt/β-catenin pathway-related proteins were detected by Western blot.Results The cell inhibition rates of control group and low,medium,high dose experimental groups were(0.00±0.13)％,(11.25±3.42)％,(23.78±3.41)％and(35.98±4.52)％;apoptosis rates were(4.59±0.35)％,(11.45±1.32)％,(18.47±2.01)％and(25.69±2.43)％;p21 protein expression were 0.21±0.03,0.34±0.04,0.51±0.06 and 0.69±0.05;the Bcl-2 protein expression were 0.89±0.06,0.67±0.04,0.52±0.05 and 0.35±0.06;Bax protein expression were 0.34±0.05,0.49±0.06,0.65±0.07 and 0.81±0.06;Wnt1 protein expression were 0.74±0.07,0.60±0.05,0.46±0.05 and 0.32±0.04;β-catenin protein expression were 0.80±0.06,0.65±0.05,0.47±0.06 and 0.29±0.05.The above indexes showed statistically significant differences between control group and low,medium and high dose experimental groups(all P＜0.05).Conclusion Mannose inhibits proliferation and induces apoptosis of HeLa cells of cervical cancer,and the mechanism may be related to the inhibition of Wnt/β-catenin pathway.

Objective To analyze the incidence of venous thromboembolism(VTE)in pulmonary patients and explore the assessment and prevention of the risk of pneumonia accompanied VTE.Methods The patients with pneumonia were divided into control group(simple pneumonia)and treatment group(with VTE)according to the condition of VTE.Demographic data,blood routine,coagulation index,liver and kidney function index and blood gas index were collected.Statistical methods like chi square test,t-test and nonparametric rank sum test were applied to compare the differences between the two groups.Finally,the nomogram was established according to the logistic regression results and the receiver operating characteristic(ROC)curve was calculated.Results 106 cases in control group and 29 cases in treatment group.Univariate analysis showed that age,D-dimer,fibrinogen degradation products,white blood cell count,neutrophil count,albumin-globulin ratio were statistically significant(P＜0.05).Multivariate logistic regression analysis suggests that age[odds ratio(OR)=1.052],D-dimer(OR=2.339),and albumin/globulin(OR=0.042)are independent affecting factors for VTE in pneumonia patients.A nomogram was developed and ROC was calculated,the area under curve(AUC)was 0.754.Conclusion High age,elevated D-dimer and decreased albumin/globulin are independent risk factors for VTE in pneumonia patients.More over,the established prediction model has good accuracy.

Objective To establish an evaluation criterion for high-quality nursing services in comprehensive hospitals of Grade Three in Guangdong Province and provide references for promoting the evaluation of high quality nursing services and standardising high quality nursing services.Methods Based on literature review,brainstorming and references of relevant domestic systems,standards and policies,a pool of evaluation index items and a preliminary questionnaire were constructed.Delphi method was used for two rounds of expert consultations on evaluation indicators.Results The positive coefficients of the two rounds of expert consultations were of 80.00%and 91.67%,respectively,with the authority coefficients both at 0.93.The Kendall coordination coefficients for hospital part were 0.128 and 0.116 respectively,for ward part were 0.193 and 0.107 with statistical differences(both P＜0.001).The evaluation criteria for high-quality nursing services in general hospitals above the third level in Guangdong Province involved in nursing services of hospitals and wards.There were 8 primary indicators,22 secondary indicators and 65 tertiary indicators in the nursing services at hospital part,and 9 primary indicators,23 secondary indicators and 50 tertiary indicators in the nursing services at ward part.Conclusions The evaluation criteria for high-quality nursing services in comprehensive hospitals above the third level in Guangdong Province,established in this study,are scientifically valid and reliable.They allow improvement of management system for the high-quality nursing services as well as guide the healthy development of high-quality nursing services.

Objective To analyze the effect of endoscopic tumor resection by submucosal tunnel(STER)on recurrence in patients with submucosal tumors(SMT)around cardia.Methods A total of 92 patients with SMT around cardia were selected and divided into the treatment group(n=46)and the control group(n=46)using random number table method.The treatment group and the control group were treated with STER and endoscopic submucosal dissection(ESD),respectively,and both groups were followed up for 12 months after surgery.Periop-erative indexes,therapeutic effects,quality of life,sleep,inflammatory indexes,immune indexes before and 1 week after surgery,complications 1 week after surgery,recurrence 12 months after surgery were compared between the two groups.Results Compared with the control group,the surgery time of the treatment group was longer,the hospital stay was shorter and treatment cost were lower,and the stripping speed was faster(P＜0.05).Compared with before surgery,scores of Pittsburgh sleep Quality index(PSQI),serum levels of interleukin-8(IL-8),inter-leukin-6(IL-6),high-sensitive C-reactive protein(hs-CRP)and whole blood levels of CD8+decreased in the two groups 1 week after surgery,and the levels were lower in the treatment group(P＜0.05).Compared with the preoperative results,the levels of whole blood CD4+and CD4+/CD8+,scores of Quality of Life Core 46 Questionnaire(QLQ-C46),Karnofsky Score(KPS)were higher in the two groups 1 week after surgery,those in the treatment group was higher(P＜0.05).1 week after surgery,the complication rate of the two groups was lower in the treat-ment group(P＜0.05),and 12 months after surgery,the recurrence rate of the two groups was not statistically significant(P＞0.05).Conclusion STER treatment for SMT around cardia was highly effective,resulting in superior perioperative outcomes,enhanced life and sleep quality,reduced systemic inflammation,and bolstered immune function.Moreover,it significantly lowered the risk of complications without raising the rates of recurrence.

Objective:To investigate the clinical efficacy of extracorporeal shock wave (ESWT) combined with stretching training in the treatment of chronic plantar fasciitis.Methods:A prospective case-control study was conducted to include the patients with chronic plantar fasciitis who had been admitted to Department of Orthopaedic Trauma, Nanfang Hospital, Southern Medical University from June 2021 to June 2022. A SPSS random number generator was used to randomize the patients into an experimental group (receiving treatment with ESWT combined with stretching training) and a control group (receiving stretching training only). Shear wave elastography (SWE) was used to quantitatively evaluate the elastic modulus of the plantar fascia. The 2 groups were compared in terms of visual analogue scale (VAS) pain score, plantar fascia thickness, and elastic modulus of the plantar fascia in the patients at 12 weeks after treatment; the correlation between VAS pain score and elastic modulus of the plantar fascia was examined using Spearman analysis in the patients at 12 weeks after treatment.Results:This study included a total of 41 patients (52 feet), 20 males and 21 females with an age of (49.9±8.2) years. There were 16 left sides, 14 right sides and 11 bilateral sides affected. The course of the disease was 7.0 (6.0, 12.0) months. The 2 groups were comparable because there were no significant differences in the general data before treatment between them ( P>0.05). The VAS pain score at 12 weeks after treatment for the experimental group was 1.0 (1.0, 2.0) points, significantly lower than that for the control group [3.0 (2.0, 3.0) points] ( P<0.05). The elastic modulus of the plantar fascia at 12 weeks after treatment for the experimental group was (79.48 ± 17.65) kPa, significantly higher than that for the control group [(57.08 ± 14.16) kPa] ( P<0.05). However, there was no statistically significant difference between the 2 groups in the thickness of the plantar fascia at 12 weeks after treatment ( P>0.05). There was a significant correlation between VAS pain score and elastic modulus of the plantar fascia after 12 weeks of treatment ( r = -0.708, P<0.001). Conclusion:In the treatment of chronic plantar fasciitis, combination of ESWT and stretching training is more effective than stretching training only.