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.

Objective: To investigate the molecular mechanism of NOD-like receptor(NLR) signaling pathway induced cellular focal death in mouse kidney tissues under plateau hypoxia based on transcriptomic sequencing technology. Methods: Animal models were constructed in high-altitude kidney test group(HKT group) and plain kidney control group(PKC group),and C57/BL6 mice were bred at an altitude of 4 200 m and 400 m,respectively.Kidney tissues were aseptically taken out after 30 d and used for observation of renal histopathological changes and transcriptomics sequencing,respectively,and then differentially expressed genes(DEGs) were enriched by KEGG and GO analysis.Key gene and protein expression levels were verified by reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot analysis. Results: Hematoxylin-eosin(HE) staining showed that the renal tubules of HKT mice were disorganized,and the tubular epithelial cells were edematous with inflammatory cell aggregation.Transcriptomics sequencing analysis revealed that a total of 3 007 DEGs were identified in the HKT group,and KEGG analysis showed that DEGs were significantly enriched in the NLR signaling pathway.The mRNA expression of the key differentially expressed genes,CASP1,CASP11,GSDMD,IFI16,NAIP5,IRF9,and the downstream inflammatory factors,IL-1β and IL-18,was upregulated,and protein expression of CASP1,CASP11,and GSDMD was up-regulated. Conclusion The plateau hypoxic environment induces cellular pyroptosis by regulating the expression of NLR signaling pathway and releases downstream inflammatory factors to cause inflammatory responses.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.
Calcium ; Acupuncture Therapy ; Acupuncture ; Acupuncture Analgesia/methods* ; Acupuncture Points ; Technology

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective:To investigate the pathogen spectrum and the epidemiological characteristics of hospitalized severe acute respiratory tract infection (SARI) cases in a sentinel hospital in Tongzhou District of Beijing from 2019 to 2022, and provide reference for scientific prevention and control of SARI.Methods:This study enrolled SARI patients in the Beijing Luhe Hospital from January 2019 to December 2022. Nasopharyngeal swabs or respiratory secretions of the patients were collected and analyzed by quantitative real-time PCR to detect the pathogens and their types. The epidemiological and clinical characteristics of the cases were analyzed.Results:In this study, 1 124 SARI cases were enrolled, of which 379 were positive for respiratory pathogens with a detection rate of 33.72%. Most of the SARI cases were positive for bacteria pathogens, and the detection rates of Mycoplasma pneumoniae, Streptococcus pneumoniae, and Stenotrophomonas maltophilia were high. Influenza A virus, parainfluenza virus, and respiratory syncytial virus were the main viral pathogens detected in the cases. There were significant differences in the number of cases and the detection rate of respiratory pathogens among different age groups (χ 2=555, P=0.000 1). The predominant pathogens in different years were different. Mycoplasma pneumoniae [27.27% (51/187)] and influenza A virus [17.65% (33/187), ] were the predominant pathogens in 2019; parainfluenza virus [16.67% (10/60)], Mycoplasma pneumoniae [11.67% (7/60)], and Haemophilus influenzae [11.67% (7/60)] were the predominant pathogens in 2020; Stenotrophomonas maltophilia [24.39% (20/82)] and respiratory syncytial virus [19.51% (16/82)] were the predominant pathogens in 2021; Stenotrophomonas maltophilia [20% (10/50)] and parainfluenza virus [12% (6/50)] were the predominant pathogens in 2022. Conclusions:Most of the SARI cases in Tongzhou district of Beijing from 2019 to 2022 are caused by bacteria. More attention should be paid to the prevalence of Stenotrophomonas maltophilia and Mycoplasma pneumoniae, as well as the prevalence of respiratory syncytial virus, parainfluenza virus, and influenza A virus. The predominant pathogens change every year from 2019 to 2022. Therefore, the prevention and control strategies should be made accordingly. This study provides basis data for the national respiratory multipathogen surveillance program.

Objective To prepare injectable poly(lactic-co-glycolic)acid(PLGA)microparticle scaffolds coated with a composite of polydopamine(PDA)and carboxymethyl chitosan(CMC),and to evaluate their biocompatibility and capacity for cell loading in tissue engineering.Methods The injectable PLGA microparticles were prepared using the W/O/W double-emulsion solvent evaporation method,followed by PDA and CMC coatings to prepare the porous scaffolds that were morphologically characterized while the size distribution of particles and pores was determined.Cytotoxicity was assessed via co-incubation of the scaffolds with cells,while cell viability was evaluated using the CCK-8 assay.The morphology of cells loaded onto the scaffolds was examined using scanning electron microscopy and DAPI staining.Results The average particle size of the prepared PLGA-PDA-CMC porous scaffolds was(313.69±4.91)μm,and the average pore size was(28.99±0.74)μm.Scanning electron microscopy confirmed the success of the PDA coating while X-ray photoelectron spectroscopy proved the success of the PDA and CMC coatings.The reduced water contact angle post-PDA coating indicated enhanced hydrophilicity of the PLGA microparticles.CCK-8 assay results demonstrated the safety of the PLGA-PDA-CMC porous scaffolds.Scanning electron microscopy and fluorescence microscopy confirmed cell adhesion on the PLGA-PDA-CMC porous scaffolds.Conclusion The successful preparation of PLGA-PDA-CMC porous scaffolds,featuring PDA and CMC coatings,can enhance the hydrophilicity and cell adhesion properties of PLGA microparticles.These scaffolds can be potentially used in tissue engineering research.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Humans ; Multiple Myeloma ; Nasal Cavity

Objective: To evaluate the reliability and validity of the Chinese version of the Questionnaire of Executive Functioning (QEF) among elementary school students aged 7-12 years. Methods: A total of 841 elementary school students from four primary schools in the Pearl River Delta (Guangzhou), eastern Guangdong area (Jieyang), northern Guangdong area (Shaoguan), and western Guangdong area (Maoming) were selected for item analysis by using a stratified whole group sampling method in September 2022. A total of 377 elementary school students from the four elementary schools were selected for testing the structural validity and reliability, and 87 subjects from an elementary school in Guangzhou were selected at 15-day intervals for assessing test retest reliability test. Results: The questionnaire had good discrimination, and the correlation between the items and the total score ranged from 0.22 to 0.46 ( P <0.01). Exploratory factor analysis showed a cumulative variance contribution rate of 56.68%, with item loadings ranging from 0.41 to 0.74. Confirmatory factor analysis showed a good model fit ( χ 2/ df =3.048, CFI=0.988, TLI= 0.980 , RMSEA=0.058, SRMR =0.009). The overall Cronbach s α , split half reliability and test retest reliability of the questionnaire were 0.72 , 0.76, 0.79, respectively. Conclusion The Chinese version of the Questionnaire of Executive Functioning has good reliability and validity, and it is suitable for application to the self assessment of executive function among elementary school students.