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.

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*

Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

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 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 compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle frac-tures in children.Methods A systematic search was conducted in PubMed,Embase,the Cochrane library,Web of Science,China National Knowledge Internet(CNKI),Wanfang Datebase from in ception to February 2022.Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included.Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality,their excellent and good rate of fracture healing,malunion,delayed union or nonunion,infection,limitation of elbow flexion or extension(＞10°)were ex-tracted and analyzed using software Rev Man 5.3.Results A total of 9 retrospective studies involving 647 patients were includ-ed,with 255 patients in the screw fixation group(including screw combined with Kirschner wire)and 392 patients in the Kirschner wire fixation group.Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22,95％CI(0.09,0.56),P=0.001].There were no significant differences between the 2 groups in excellent and good rate of fracture healing,malunion rate(P＞0.05).Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18,95％CI(0.05,0.65),P=0.009].Conclusion For lateral humeral condyle fractures,Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation.There were no significant differences in the excellent and good rate of fracture healing,malunion.In terms of postoperative efficacy and safety of internal fixation,orthopaedic surgeons are more like-ly to recommend screws for fixation of lateral humeral condyle fractures in children.

Objective To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL)training injuries.Methods Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed.All the cases were underwent ligament reconstruc-tion surgery.Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group,including 13 males and 1 female,aged from 22 to 31 years old with an average of(27.07±7.28)years old,autogenous hamstring tendon was used for ligament reconstruction.There were 15 patients in the enhanced reconstruction group,including 13 males and 2 females,aged from 25 to 34 years old with an average of(29.06±4.23)years old,double tunnel ligament reconstruction,the autogenous hamstring muscle was used as the anteromedial bundle,and the posterolateral bundle was replaced by a high-strength line.The difference between knee tibial anterior distance,Lysholm score,International Knee Literature Committee(IKDC)subjective score,Tegner motor level score and visual analog scale(VAS)at 6th and 12th months after the surgery,limb symmetry index(LSI)were recorded at the last follow-up and surgery-related adverse effects during follow-up.Results All patients were followed up,ranged from 13 to 15 months with an average of(13.7±0.8)months.There were no serious adverse reactions related to surgery during the period.There was no statistical difference between the preoperative general data and the observation index of the two groups(P＞0.05).The difference in tibial anterior distance at 6 and 12 months in the enhanced re-construction group(1.45±0.62)mm and(1.74±0.78)mm which were lower those that in the conventional reconstruction group(2.42±0.60)mm and(2.51±0.63)mm(P＜0.05).There was no significant difference in postoperative Lysholm score,Tegner motor level score,IKDC score,VAS,and limb symmetry index at the last follow-up(P＞0.05).Conclusion The enhanced recon-struction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique.The short-term curative effect is satisfac-tory,and it is suitable for the group with high sports demand.

ObjectiveTo observe the clinical efficacy of Maxingshigantang enema in the treatment of infant viral pneumonia by comparing related indicators， and comprehensively evaluate the effect of traditional Chinese medicine （TCM） enema on the intestinal microenvironment. MethodSixty infants with viral pneumonia were selected and randomly divided into 3 groups. The dosage of enema drugs in high- （0.117 g·mL^-1） and low-concentration （0.07 g·mL^-1） TCM enema groups was same （3.5 g per time）， and the control group received normal saline enema， once a day for 7 days. Finally， the curative effect， total symptom score， salivary secretory immunoglobulin A （sIgA）， human beta defensin 2 （hBD2） and fecal calprotectin （CALP） of each group were statistically analyzed by SPSS 21.0， and the clinical efficacy of TCM enema in treating children with pneumonia and asthma was comprehensively evaluated. ResultThe curative effect of high-concentration TCM enema group （total effective rate 100%， χ²=7.059） was equivalent to that of low-concentration TCM enema group （total effective rate 95%， χ²=4.329）， higher than that of control group （total effective rate 70%） （P<0.017）. After treatment， compared with control group and low-concentration TCM enema group， high-concentration TCM enema group had higher total symptom score of children （P<0.05， P<0.01）. The proportion of coccobacillus was reduced in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The salivary sIgA concentration was increased in three groups （P<0.05）， with high-concentration TCM enema group higher than the other groups （P<0.01）. The hBD2 concentration was decreased in three groups， with high- and low-concentration TCM enema groups lower than control group （P<0.05）. The three groups reduced the fecal CALP concentration， and high-concentration TCM enema group had the highest reduction， followed by low-concentration TCM enema group （P<0.01）. ConclusionTCM enema outweighs western medicine in improving clinical symptoms， intestinal flora， and mucosal immune function， and reducing inflammation in children， and the high-concentration TCM enema group has better curative effect. Therefore， with easiness to operate， high compliance， and significant therapeutic effect， TCM enema is worthy of clinical promotion.

OBJECTIVE: To explore the role of P2X7 receptor (P2X7R) in migration and invasion of mouse Lewis lung cancer (LLC) cells and examine the tumorigenic ability of LLC cells in P2X7R-knockout mice. METHODS: RT-PCR was used to examine P2X7R mRNA expression in LLC cells. LLC cells were treated with ATP (as a P2X7R agonist) or 2'- 3'- O- (4-benzoyl- benzoyl)-ATP (BzATP) (a P2X7R agonist) with or without pretreatment with P2X7R antagonist oxATP or A438079. The changes in migration and invasive abilities of the cells were evaluated using wound healing assay and Transwell assay; Western blotting was performed to determine the activation level of the key proteins in the AKT signaling pathway. The effects of BzATP, A438079, and LY294002 (a inhibitor of the PI3K/AKT pathway) on migration and invasion of LLC cells were also examined. In wild-type (WT) and P2X7R knockout (P2X7^-/-) C57BL/6 mice, the growth of subcutaneous LLC cell xenografts were observed by measuring tumor volume and weight. RESULTS: P2X7R expression was detected in LLC cells. Treatment with P2X7R agonist significantly enhanced migration and invasion abilities of LLC cells, and this effect was inhibited by application of P2X7R antagonists (P < 0.001). Western blotting showed that BzATP treatment of LLC cells significantly increased the expression level of p-AKT protein, which was obviously lowered by treatment with P2X7R antagonist (P < 0.01). P2X7R antagonist strongly inhibited BzATP-induced enhancement of LLC cell migration and invasion (P < 0.001). In the tumor- bearing mice, the tumor volume and weight were significantly lower in P2X7^-/- mice than in WT mice (P < 0.05). CONCLUSION P2X7R promotes migration and invasion of LLC cells by activating the AKT signaling pathway, and LLC cells show lowered tumorigenic capacity in P2X7^-/- mice.
Humans ; Mice ; Animals ; Receptors, Purinergic P2X7 ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Mice, Inbred C57BL ; Signal Transduction ; Adenosine Triphosphate/metabolism* ; Lung Neoplasms

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*