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.

ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

OBJECTIVE: To investigate the surgical technique and effectiveness of tension band-assisted plate fixation combined with external fixator for volar marginal fractures of the distal radius. METHODS: A retrospective analysis was performed on the clinical data of 12 patients with volar marginal fractures of the distal radius treated by Kirschner wire tension band-assisted anatomical plate fixation combined with external fixator between October 2018 and July 2023. The cohort included 9 males and 3 females, aged from 20 to 52 years (mean, 35.5 years). The injury causes included traffic accidents in 6 cases, falls from height in 3 cases, and fall in 3 cases. According to AO/Orthopaedic Trauma Association (AO/OTA), there were 1 case of type B2, 4 cases of type B3, 2 cases of type C1, 3 cases of type C2, and 2 cases of type C3. According to Fernandez classification, there were 2 cases of type Ⅲ, 5 cases of type Ⅳ, and 5 cases of type Ⅴ. Associated injuries included radiocarpal joint dislocation or subluxation in 7 cases and median nerve injury in 2 cases. The time from injury to operation was 2-7 days (mean, 3.2 days). Postoperatively, functional outcomes were evaluated using the modified Mayo wrist score and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Grip strength was measured as the ratio to the unaffected side, and wrist range of motion (ROM) including dorsiflexion, palmar flexion, ulnar deviation, and radial deviation was assessed. RESULTS: All procedures were successfully completed, with an operation time of 55-110 minutes (mean, 65 minutes). All patients were followed up 6-36 months (mean, 13.7 months). Surgical incisions healed by first intention, without complications such as vascular-nerve injury or infection. Bony union and articular congruency were attained in all patients, with a healing time of 3-5 months (mean, 3.8 months). During follow-up, 1 case of Kirschner wire migration occurred with no instances of infections, radiocarpal dislocations, internal fixation failures, or extensor pollicis longus tendon ruptures. At last follow-up, the modified Mayo wrist score ranged from 65 to 92 (mean, 80.8), the DASH score ranged from 7 to 15 (mean, 11.6), the grip strength was 65%-90% (mean, 78.2%) of the unaffected side; and wrist ROM was palmar flexion 60°-85° (mean, 77.4°), dorsiflexion 55°-80° (mean, 74.8°), radial deviation 10°-25° (mean, 18.8°), and ulnar deviation 15°-30° (mean, 24.5°). CONCLUSION Kirschner wire tension band-assisted anatomical plate fixation combined with external fixator for volar marginal fractures of the distal radius is a simple method with reliable fixation, which can achieve satisfactory effectiveness.
Humans ; Male ; Adult ; Female ; Radius Fractures/diagnostic imaging* ; Retrospective Studies ; Middle Aged ; Bone Plates ; Bone Wires ; External Fixators ; Young Adult ; Fracture Fixation, Internal/instrumentation* ; Treatment Outcome ; Range of Motion, Articular ; Hand Strength ; Wrist Injuries/surgery*

OBJECTIVE: To investigate the feasibility and effectiveness of precise-guided temporary fixation assistive devices in assisting the main nail guide pin placement and precise temporary fixation in proximal femoral nail antirotation (PFNA) internal fixation of femoral intertrochanteric fractures. METHODS: A prospective randomized controlled study was conducted to analyze the clinical data of 60 patients with femoral intertrochanteric fractures over 65 years old who met the selection criteria between January 2020 and June 2022 and were treated with PFNA internal fixation. The patients were randomly divided into the trial group (auxiliary device guided main nail guide pin placement and temporary fixation) and the control group (conventional treatment), with 30 cases in each group. There was no significant difference in baseline data such as gender, age, cause of injury, time from injury to operation, fracture side, AO/Orthopaedic Trauma Association (AO/OTA) classification, and combined medical diseases between the two groups ( P>0.05). The operation time, times of main nail guide pin placement, intraoperative fluoroscopy frequency, intraoperative blood loss, and perioperative blood transfusion were recorded and compared between the two groups. The quality of fracture reduction was evaluated by CHANG Shimin et al criteria. Harris score was used to evaluate the hip function at 1 year after operation. RESULTS: In the trial group, 2 temporary fixation needles were successfully placed 2-5 times, including 2 times in 13 cases (43.3%), 3 times in 8 cases (26.7%), 4 times in 7 cases (23.3%), and 5 times in 2 cases (6.7%). The operation time, times of main nail guide pin placement, intraoperative fluoroscopy frequency, and intraoperative blood loss in the trial group were significantly less than those in the control group, and the reduction quality score was significantly better than that in the control group ( P<0.05). There was no significant difference in perioperative blood transfusion between the two groups ( P>0.05). All patients were followed up 12-19 months (mean, 15 months). There was no complication such as incision infection, deep vein thrombosis, or internal fixation loosening. At 1 year after operation, the Harris score of the affected hip joint in the trial group was significantly higher than that in the control group ( P<0.05). CONCLUSION The technique of main nail guide pin placement and temporary fixation under the guidance of auxiliary devices in PFNA internal fixation can achieve faster insertion of the main nail guide pin, accurate temporary fixation to maintain reduction, and avoid the subsequent operation space, so as to improve the effectiveness.
Humans ; Bone Nails ; Male ; Female ; Hip Fractures/surgery* ; Fracture Fixation, Intramedullary/instrumentation* ; Aged ; Prospective Studies ; Operative Time ; Treatment Outcome ; Fracture Fixation, Internal/instrumentation* ; Aged, 80 and over

BACKGROUND: Lung cancer is one of the malignant cancers with the highest incidence rate, and it is important to identify the factors contributing to lung cancer carcinogenesis for prevention. Lifestyle and genetic factors play important roles in cancer development, however the impact of dietary factors, such as soy product intake, on lung cancer risk remains inadequately understood. This study aims to explore the associations between soy product intake, genetic risk, and lung cancer incidence, and validate the consistent effects of soy product intake in European populations, thereby providing new insights for lung cancer prevention. METHODS: Utilizing the Shanghai Suburban Adult Cohort and Biobank (SSACB) (n=66,311), Cox proportional hazards model was adopted to assess the association between soy product intake and lung cancer incidents, followed by subgroup analyses stratified by gender, smoking status, and pathological types of lung cancer. The UK Biobank (UKB) was used for validation of the effect of soy product intake on lung cancer. To investigate the association between genetic factors and lung cancer, in addition to previously reported loci, we incorporated newly identified loci from two independent studies in Southeast China: a nested case-control population from the SSACB cohort (433 cases/650 controls) and a case-control study from the Shanghai Cancer Center-Taizhou cohort (1359 cases/1359 controls). Meta-analysis and Linkage disequilibrium clumping (LD clumping) of the association results identified 23 loci for polygenic risk score (PRS) construction. Subsequently, conditional Logistic regression model was used to assess the association between genetic risk and lung cancer. RESULTS: In SSACB cohort, after adjusting for age, gender, smoking, chronic bronchitis, body mass index (BMI), vegetable intake and red meat intake, sufficient soy product intake was significantly associated with a reduced risk of lung cancer [hazard ratio (HR)=0.60, 95%CI: 0.47-0.77, Padj=6.69E-05], an effect that was consistent in males and females, smokers and non-smokers. In UKB, although the association did not reach statistical significance, a protective trend against lung cancer was also observed (HR=0.76, 95%CI: 0.55-1.06, Padj=0.10). In the nested case-control population within SSACB, a PRS score generated in the Chinese population was significantly correlated with lung cancer risk. After adjustment of age, gender, smoking, chronic bronchitis, and soy product intake, the high-PRS group had a 1.88 times higher risk of lung cancer compared to the low-PRS group (Padj=1.84E-03). CONCLUSIONS The prospective cohort study found that adequate intake of soy products was significantly associated with a reduced risk of lung cancer, while a high PRS is a risk factor for lung cancer development. Integrating soy product intake and PRS into traditional epidemiological risk factor prediction will guide personalized lung cancer prevention and high-risk population stratification.
Humans ; Lung Neoplasms/etiology* ; Male ; Female ; China/epidemiology* ; Middle Aged ; Adult ; Aged ; Prospective Studies ; Biological Specimen Banks ; Risk Factors ; Case-Control Studies ; Cohort Studies

Objective:Ménière's disease（MD） is a common disorder of the inner ear. The fluctuating clinical symptoms and the absence of gold standards for diagnosis have posed serious problems for clinical diagnosis and treatment over the years. With the development of science and technology, artificial intelligence （AI） has been widely used in the field of medicine, and the potential of AI application to MD is demonstrated. The purpose of this review is to outline the use of AI in MD. Initially, specific instances where AI aids in differentiating MD from other causes of vertigo are presented. Furthermore, the role of AI in the evaluation of Endolymphatic Hydrops （EH）, particularly through imaging and biochemical assays, is highlighted due to its correlation with MD. Additionally, the effectiveness of AI in managing MD patients and forecasting disease progression is examined. In conclusion, the prevalent challenges hindering the clinical integration of AI in MD treatment are discussed, alongside potential strategies to surmount these barriers.
Humans ; Meniere Disease/diagnosis* ; Artificial Intelligence ; Endolymphatic Hydrops/diagnosis*