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.

Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) represent a diverse family of secreted metalloproteinases, comprising 19 distinct members categorized into five groups based on their substrate specificity: proteoglycanases, procollagen N-peptidases, von Willebrand factor-cleaving protease, cartilage oligomeric matrix proteases and other proteases. Among these, ADAMTS proteoglycanases predominantly target hyalectans, pivotal components in extracellular matrix (ECM) remodeling and inflammation. Dysfunction of ADAMTS proteoglycanases disrupts the structure and function of hyalectans, thereby perturbing ECM homeostasis, resulting in reproduction disorders, including abnormal follicular development, ovulation dysfunction, impaired implantation, placentation and preterm labor. Hence, investigation of the role of ADAMTS proteoglycanases offers valuable insights into the molecular mechanisms underlying the physiological or pathological processes within the female reproductive system, thereby paving the way for innovative strategies in predicting, preventing and treating reproductive system diseases. This review summarizes the recent research advances in the structure and regulation of ADAMTS proteoglycanases and their role in female reproductive system.
Humans ; Female ; ADAMTS Proteins/physiology* ; ADAM Proteins/physiology* ; Pregnancy ; Animals ; Genitalia, Female/enzymology* ; Extracellular Matrix/metabolism*

This study explored the prescription pattern of traditional Chinese medicine(TCM) in the treatment of hypertensive left ventricular hypertrophy(LVH), so as to provide a relevant theoretical basis for the clinical diagnosis and treatment of hypertensive LVH. The study systematically searched the databases of CNKI, Wanfang, VIP, and SinoMed to screen out the qualified literature on TCM treatment of hypertensive LVH and used Microsoft Excel 2021 to establish the relevant prescription database. It also counted the frequency, property, flavor, and meridian affiliation of TCM in the prescriptions and classified their efficacy. The study used Lantern 5.0 and Rstudio software to analyze the hidden structural models and association rules of the high-frequency TCM with a frequency of >3.50% and adopted Origin 2024 software to visualize the data, so as to explore the prescription pattern of TCM in treating hypertensive LVH. The results showed that a total of 128 TCM prescriptions were included, involving 163 TCM with a total frequency of 1 242. The high-frequency TCM included Salviae Miltiorrhizae Radix et Rhizoma, Uncariae Ramulus Cum Uncis, Gastrodiae Rhizoma, Poria, and Chuanxiong Rhizoma, with the main efficacy from blood-activating and stasis-resolving herbs, tonic herbs, and liver-calming and wind-extinguishing herbs. The latent structure analysis(LSA) identified 10 latent variables, 20 latent classes, 7 comprehensive clustering models, and 23 core prescriptions. It was speculated that the common syndromes of hypertensive LVH included blood stasis obstructing the collaterals, ascending hyperactivity of liver Yang, Yin deficiency with Yang hyperactivity, and intermingled phlegm and blood stasis. The association rule analysis yielded 33 strong association rules, with the highest comprehensive association rule being Gastrodiae Rhizoma→Uncariae Ramulus Cum Uncis. Hypertensive LVH is characterized by asthenia in origin and asthenia in superficiality, with Yin deficiency and Qi deficiency as the origin and blood stasis and phlegm as the superficiality. Clinical treatment focuses on activating blood circulation, resolving stasis, tonifying Qi, and nourishing Yin, combined with syndrome-specific therapies such as calming wind and stopping convulsions, clearing heat, eliminating dampness and resolving phlegm, and promoting diuresis and reducing swelling.
Drugs, Chinese Herbal/therapeutic use* ; Data Mining ; Humans ; Hypertension/complications* ; Hypertrophy, Left Ventricular/physiopathology* ; Medicine, Chinese Traditional ; Drug Prescriptions

OBJECTIVE: To investigate the clinicopathological features and differential diagnosis of male genital system lymphoma (MGSL). METHODS: We retrospectively analyzed the clinicopathological and immunophenotypic features and prognosis of 80 cases of MGSL. RESULTS: The onset age of the MGSL patients ranged from 4 to 85 (median 62) years old. All the cases showed non-specificity of the imaging features and clinical manifestations. MGSL was located mainly in the testis (n = 66), followed by the prostate (n = 7), epididymis (n = 3), scrotum (n = 3) and penile glans (n = 1). Diffused large B cell lymphoma (DLBCL) was the most common pathological type (n = 62), next came extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (n = 7) and other rare types (n = 12). During the 1－112-month follow-up of 10 of the 19 patients, 1 died at 1 month after diagnosed with prostatic B-lymphoblastic lymphoma (B-LBL) and another 1 died at 50 months after diagnosed with testicular DLBCL. CONCLUSION MGSL is rare clinically, mainly of the DLBCL type pathologically, lacking specificity in clinical symptoms and imaging manifestation. The definite diagnosis of the malignancy depends on histopathology combined with related molecular examination and immunohistochemical labeling, and R-CHOP chemotherapy is the first choice for its treatment.
Humans ; Male ; Middle Aged ; Aged ; Retrospective Studies ; Adult ; Aged, 80 and over ; Young Adult ; Adolescent ; Child ; Child, Preschool ; Genital Neoplasms, Male/diagnosis* ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Lymphoma/diagnosis*

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Objective To study the antioxidant activity and organ protection of different components of Panax notoginseng polysaccharide(PNPS)in D-galactose-induced oxidative damage aging model mice.Methods KM mice were randomly divided into normal group,model group,vitamin C(VC)group(given 200 mg·kg-1 VC),crude polysaccharide from Panax notoginseng(CPPN)group,neutral polysaccharide from Panax notoginseng(NPPN)group and acidic polysaccharide from Panax notoginseng(APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ)group(given 400 mg·kg-1 CPPN,NPPN,APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ,respectively).Except for the normal group,oxidative injury aging mouse models were established by intraperitoneal injection of 1 g·kg-1 D-galactose.The mice were sacrificed after continuous administration for 42 days,and serum and liver homogenate were prepared.Malondialdehyde(MDA)was determined by thiobarbituric acid method;superoxide dismutase(SOD)was determined by tetrazole salt method;glutathione peroxidase(GSH-Px)was determined by double antibody sandwich method.Results Serum SOD in the normal group,model group,VC group,CPPN group,NPPN group and APPN-Ⅰ,APPN-Ⅱ,APPN-Ⅲ groups were(15.07±0.69),(12.79±1.51),(15.56±1.01),(13.69±0.96),(14.27±0.64),(14.31±0.99),(14.18±0.79)and(15.85±0.89)U·mL-1;serum GSH-Px were(105.35±4.97),(90.36±4.31),(111.51±7.00),(113.03±8.06),(118.77±5.19),(123.60±8.08),(131.65±3.60)and(149.22±13.32)ng·L-1;serum MDA were(1.72±0.26),(4.16±0.92),(2.26±0.59),(2.82±0.47),(2.46±0.50),(1.98±0.41),(2.39±0.39)and(2.07±0.24)nmol·mL-1;the liver SOD were(234.22±3.84),(205.04±7.28),(234.63±6.37),(214.99±17.66),(234.13±3.63),(234.63±3.44),(233.87±5.63)and(235.42±2.33)U·mgprot-1;liver GSH-Px were(274.27±23.72),(207.00±15.22),(257.68±16.39),(249.79±18.78),(252.62±10.92),(256.25±21.83),(261.20±17.52)and(263.16±17.98)ng·L-1;liver MDA were(35.70±3.52),(49.65±6.32),(36.15±2.48),(39.17±4.29),(37.40±6.19),(35.34±4.06)and(35.90±5.36),(33.31±7.64)nmol·mgprot-1.Compared with the normal group,SOD,GSH-Px in serum and liver of mice in the model group were significantly reduced,and the content of MDA was significantly increased(all P＜0.01).After treatment with different components of Panax notoginseng polysaccharide,the oxidative indicators in mice were significantly improved,among which APPN-Ⅲ have the best antioxidant activity,which could significantly increase the activities of SOD,GSH-Px in serum and liver,and reduce the content of MDA(all P＜0.01).Conclusion Different components of Panax notoginseng polysaccharide have antioxidant activity and organ protection in vivo,among which APPN-Ⅲ has the best antioxidant activity and has a good organ protection effect.

Objective To establish a simple model for arteriosclerosis(AS)screening to provide a viable tool for the timely identification of AS risk among residents aged 40～65 years.Methods Data were obtained from the Sleep and Chronic Diseases Program in Fuquan City.The original dataset was divided into a training subset and a validation subset(80%:20%).LASSO and logistic regression models were used to screen variables,perform multivariate regression analyses.Internal validation was performed using the Bootstrap method.Nomogram Plot was constructed,and risk score thresholds were determined based on ROC curves to classify high-risk populations.Results RS Model was established to include age,gender,napping,sleep efficiency,sleep disorders,hyperten-sion and diabetes,with AUC=74.80%and a model risk score threshold=84.20.PHC Model was established to include age,gender,napping,sleep efficiency,systolic blood pressure,fasting blood glucose,and pulse variables,with AUC=82.80%and a risk score threshold of 78.00.Decision curves showed that both models performed well in terms of calibration and actual benefits for health management.Conclusion The two AS screening models exhibit acceptable accuracy and differentiation.Therefore,it can be applied in residents'self-health management and in primary care organizations'screening work in a large scale.

Objective To investigate the influence of peripheral blood neutrophil-to-lymphocyte ratio (NLR),monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis in the patients with multiple myeloma (MM).Methods A total of 159 newly diagnosed MM admitted and treated in the Affiliated Hospital of Guizhou Medical University from January 2019 to May 2023 were selected as the study subjects.The general clinical data,blood biochemical and marrow routine detection results before the in-itial treatment were collected.NLR,MLR and PLR were calculated.The univariate and multivariate Cox-re-gression model was adopted to analyze the influencing factors.The receiver operating characteristic (ROC) curve was used to analyze the predictive value.The Kaplan-Meier survival curve and Log-Rank test were used to conduct the survival analysis.Results The ROC curve showed that the critical values of NLR,MLR and PLR were 2.682,0.317 and 147.786 respectively.The patients were divided into the high/low NLR groups (n=61,n=98),high/low MLR group (n=76,n=83) and high/low PLR groups (n=59,n=100).The pro-portions of blood calcium<2.5 mmol/L and creatinine<177 μmmol/L in the low NLR group in the low NLR group were higher compared with the high NLR group (P<0.05);the blood calcium,creatinine and DS stage had statistical differences between the low MLR group and high MLR group (P<0.05);blood calcium had statistical difference between the low PLR group and high PLR group (P<0.05).After 3 treatment courses,the complete remission rate in the high NLR group,high MLR group and high PLR group was significantly lower than that in the corresponding low group (P<0.05).The multivariate Cox-regression analysis results showed that hemoglobin<100 g/L and high PLR were the independent risk factors affecting the progress free survival (PFS) stage in the patients with MM (P<0.05).The age>60 years old was the independent risk factors affecting the overall survival (OS) in the patients with MM (P<0.05).Conclusion NLR,MLR and PLR could serve as the assisted tool to evaluate the prognosis in the patients with MM.