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: Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research. METHODS: In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model. RESULTS: Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head. CONCLUSION This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.
Animals ; Swine ; Finite Element Analysis ; Skull/injuries* ; Craniocerebral Trauma/diagnostic imaging* ; Brain ; Biomechanical Phenomena ; Scalp

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

NG2-glia are a major type of glial cells that are widely distributed in the central nervous system (CNS). Under physiological conditions, they mainly differentiate into oligodendrocytes and contribute to the myelination of axons, so they are generally called oligodendrocyte progenitor cells. Emerging evidence suggests that NG2-glia not only act as the precursors of oligodendrocytes but also possess many other biological properties and functions. For example, NG2-glia can form synapse with neurons and participate in energy metabolism and immune regulation. Under pathological conditions, NG2-glia can also differentiate into astrocytes, Schwann cells and even neurons, which are involved in CNS injury and repair. Therefore, a deeper understanding of the biological characteristics and functions of NG2-glia under physiological and pathological conditions will be helpful for the treatment of CNS injury and disease. This article reviews the recent advances in the biological characteristics and functions of NG2-glia.
Astrocytes ; Central Nervous System ; Neuroglia ; Neurons ; Oligodendroglia

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.
Angina Pectoris ; drug therapy ; Cerebral Infarction ; drug therapy ; China ; Consensus ; Coronary Disease ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Injections ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. METHODS: Mice were immunized intranasally with PBS (negative control), or H3N2 split vaccine (3 μg/mouse) alone, or CTA1-DD (5 μg/mouse) alone, or H3N2 split vaccine (3 μg/mouse) plus CTA1-DD (5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine (3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. RESULTS: H3N2 split vaccine formulated with CTA1-DD could elicit higher IgM, IgG and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory IgA titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. CONCLUSION CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.
Adjuvants, Immunologic ; Administration, Intranasal ; Animals ; Cholera Toxin ; Female ; Immunity, Humoral ; Influenza A Virus, H3N2 Subtype ; immunology ; Influenza Vaccines ; Mice, Inbred BALB C ; Nasal Mucosa ; immunology ; Random Allocation ; Recombinant Fusion Proteins

Background: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients’ kidney function recovery. Methods: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients’ renal function recovery at discharge, fluid balance, and levels of CVP were assessed. Results: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ² = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ² = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. Conclusion Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.
China ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Spinal cord injury (SCI) is a challenging medical problem in the field of neurology, showing high incidence rate, disability rate, treatment cost and low-aged trend. Despite the clinical application of drug intervention, surgical treatment and modern rehabilitation training, no ideal curative effect has been achieved. Therefore, future study is necessary to clarify detailed pathological mechanism of SCI and identify the potential target cells for therapeutic intervention. In the central nervous system (CNS), astrocytes are the most abundant and widely distributed glial cells which play multiple key roles in maintaining homeostasis of the CNS in physiological and pathological conditions. Increasing evidence indicates that astrocytes are ideal therapeutic target cells for SCI. Here, we review current knowledge of the roles of astrocytes in the pathological reaction after SCI, astroglial transplantation and astrocyte reprogramming.