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 environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang （SYD） on the lipopolysaccharide （LPS）-induced damage of tight junction proteins in the human colorectal adenocarcinoma （Caco-2） cell model of inflammation via the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） pathway. MethodsCaco-2 cells were grouped as follows： Blank， model （LPS， 10 mg·L^-1）， SYD-containing serum （10%， 15%， and 20%）， and inhibitor （Fasudil， 25 μmol·L^-1）. After 24 hours of intervention， the cell viability in each group was examined by the cell-counting kit 8 （CCK-8） method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 （ET-1）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of RhoA， ROCK2， claudin-5， and zonula occludens-1 （ZO-1） in cells of each group. ResultsCompared with the blank group， the model group showcased a marked reduction in the cell viability （P<0.01）， elevations in the levels of ET-1， TNF-α， IL-1β， and IL-6 （P<0.01）， declines in both mRNA and protein levels of ZO-1 and claudin-5 （P<0.01）， and rises in mRNA and protein levels of RhoA and ROCK2 （P<0.01）. Compared with the model group， the Shaoyaotang-containing serum （10%， 15%， and 20%） groups had enhanced cell viability （P<0.01）， lowered levels of ET-1， TNF-α， IL-1β， and IL-6 （P<0.01）， up-regulated mRNA and protein levels of ZO-1 and claudin-5 （P<0.05， P<0.01）， and down-regulated mRNA and protein levels of RhoA and ROCK2 （P<0.01）. Moreover， the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， higher mRNA and protein levels of ZO-1 and claudin-5 （P<0.05， P<0.01）， and lower mRNA and protein levels of RhoA and ROCK2 （P<0.05， P<0.01） than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.

ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang （SYD） on the lipopolysaccharide （LPS）-induced damage of tight junction proteins in the human colorectal adenocarcinoma （Caco-2） cell model of inflammation via the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） pathway. MethodsCaco-2 cells were grouped as follows： Blank， model （LPS， 10 mg·L^-1）， SYD-containing serum （10%， 15%， and 20%）， and inhibitor （Fasudil， 25 μmol·L^-1）. After 24 hours of intervention， the cell viability in each group was examined by the cell-counting kit 8 （CCK-8） method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 （ET-1）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of RhoA， ROCK2， claudin-5， and zonula occludens-1 （ZO-1） in cells of each group. ResultsCompared with the blank group， the model group showcased a marked reduction in the cell viability （P<0.01）， elevations in the levels of ET-1， TNF-α， IL-1β， and IL-6 （P<0.01）， declines in both mRNA and protein levels of ZO-1 and claudin-5 （P<0.01）， and rises in mRNA and protein levels of RhoA and ROCK2 （P<0.01）. Compared with the model group， the Shaoyaotang-containing serum （10%， 15%， and 20%） groups had enhanced cell viability （P<0.01）， lowered levels of ET-1， TNF-α， IL-1β， and IL-6 （P<0.01）， up-regulated mRNA and protein levels of ZO-1 and claudin-5 （P<0.05， P<0.01）， and down-regulated mRNA and protein levels of RhoA and ROCK2 （P<0.01）. Moreover， the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， higher mRNA and protein levels of ZO-1 and claudin-5 （P<0.05， P<0.01）， and lower mRNA and protein levels of RhoA and ROCK2 （P<0.05， P<0.01） than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.

ObjectiveTo establish an adjusted Serfling regression model to estimate the excess cases and the excess epidemic period of hand-foot-mouth disease (HFMD) in Beijing from 2011 to 2019, so as to provide data support and decision-making basis for HFMD prevention and control. MethodsThe weekly number of HFMD cases in Beijing from 2011 to 2019 was utilized for adjusted the Serfling regression model. Then the adjusted model was used to fit the baseline and epidemic threshold of HFMD in Beijing from 2011 to 2019, calculating the excess cases and determining the excess epidemic period. ResultsA total of 279 306 cases of HFMD were reported in Beijing from 2011 to 2019, with the climax of the disease occurring in summer and autumn. After adjusting the fitting R² of the Serfling regression model to 0.773, a total of 10 excess epidemic periods totaling 92 weeks were estimated, mainly occurring in summer. The highest number of excess cases during an excess epidemic period was found in 2014 (1 272 cases, 95%CI: 990‒1 554), accounting for 65.04% of the actual cases (95%CI: 50.62%‒79.46%). ConclusionThe adjusted Serfling regression model fits well and can be utilized for early warning of HFMD and estimating the disease burden caused by HFMD.

Objective To investigate the role of heme oxygenase-1(HO-1)on HBV replication and the antiviral effect of HO-1 combined with α-interferon(IFN-α).Methods HepG2.2.15 cells and HBV1.3-transfected HepG2 cells(HepG2-HBV1.3)were used as HBV replicating cell models;Hemin treated HepG2.2.15 and HepG2-HBV1.3 cells,to induce the expression of HO-1 molecules.CCK-8 method was used to assess the toxic effects of Hemin on HepG2 and HepG2.2.15;chemiluminescence method was used to analyze HBsAg and HBeAg in the supernatants of Hemin-treated group and si-HO-1 and other experimental groups;RT-qPCR was used to ana-lyze HO-1,IFN-β and HBV-DNA;Western blot was used to analyze the expression of IRF-3 and the expression of related molecules in the JAK/STAT signaling pathway;Hemin combined with IFN-α treated HepG2.2.15 to moni-tor whether HO-1 had synergistic IFN-α antiviral effect.Results Hemin dose-dependently induced HO-1,and HO-1 was induced to exert a significant anti-HBV effect,while the expression of IFN-β,IRF-3,and IRF-9 and MxA,downstream molecules of the JAK/STAT signaling pathway,were all increased.Silencing HO-1 expression reversed the antiviral effect in the Hemin-induced group,and at the same time,type Ⅰ interferon IFN-β showed low expression,and the expression of IRF-9 and MxA in the JAK/STAT signaling pathway was inhibited as well.He-min combined with IFN-α exerted stronger antiviral effects.Conclusion HO-1 can exert an anti-HBV effect,which may be due to increased phosphorylation of IRF-3 to induce type Ⅰ interferon expression and thus activate the JAK/STAT signaling pathway to exert an antiviral effect;HO-1 can synergize with IFN-α to exert an antiviral effect.

Band 3 protein is an important channel protein in the erythrocyte membrane which mediates the anion transport process inside and outside the cell membrane,as well as contributes to the maintenance of erythrocyte morphology,and has important physiological functions.However,the distribution state of this protein in the primary cell membrane is not known.Cryo-scanning electron microscopy enables imaging of the surface morphology of biological samples in a near-physiological state.In order to investigate the distribution of band 3 protein on erythrocyte membranes under physiological conditions,the present study utilized 5-nm gold nanoparticles modified with the antibodies to specifically bind to the band 3 protein on human blood erythrocyte membranes and imaged them by cryo-scanning electron microscopy,to obtain distribution of band 3 protein on human blood erythrocyte membranes.The results showed that the membrane proteins on the erythrocyte membranes tended to be clustered and distributed to form ″protein islands″,and band 3 proteins were mainly distributed in these protein islands,which were tightly connected with each other to form several functional microregions to play their respective roles.

Objective:To evaluate the effect of venous excess ultrasound score (VExUS Score) in the acute kidney injury(AKI) in Patients with sepsis, so as to reduce the risk of disease and improve the prognosis of patients.Methods:This experiment was a single-center prospective cohort study. Include septic patients with AKI who were admitted to the Department of Emergency Intensive Care Unit of the First Affiliated Hospital of Anhui Medical University from February 2022 to February 2023, Those with inadequate window, inferior vena cava (IVC) thrombus, age<18 years and known case of cirrhosis with portal hypertension were excluded from the study. Patients underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis.Results:Totally 86 patients were enrolled for the study. The mean age was (60.43±15.48) with 50 (58.1%) males. Mean sequential organ failure assessment (SOFA) score was (6.23±1.87). 38 patients (44.2%) were in AKI stage 1, while 24 patients (27.9%) were in AKI stage 2 and stage 3 each. 52 patients (60.5%) had VExUS grade Ⅲ. Resolution of AKI injury showed significant correlation with improvement in VExUS grade ( p value 0.003). Similarly, there was significant association between changes in VExUS grade and fluid balance ( p value 0.005). There was no correlation between central venous pressure (CVP), left ventricular function, and right ventricular function with change in VExUS grade. Conclusions:The study shows a significant correlation between the VExUS Score and AKI staging, With improvement in kidney function, there is decline in the VExUS grade as well. Moreover VExUS Score might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal.

Objective To explore the correlation between the urinary neutrophil gelatinase-associated lipid carrier protein(NGAL)and Brachial artery flow-mediated vasodilation(FMD)in Prehypertension.Methods 156 patients with Prehypertension found to have the normal high blood pressure during a health examination at the Luo Shi Road Community Health Service Center of Wuchang Hospital in Wuhan from September 2022 to September 2023 were included and divided into the normal endothelial function group and the endothelial dysfunction group with 89 cases and 67 cases respectively in each group according to whether the FMD was above 10% .The sex,age,smoking history,height,weight,SBP,DBP,FBG,Scr,eGFR,BUN,UA,Hcy,urine NGAL,FMD and other indicators were collected.The correlation between FMD and NGAL in prehypertension was analyzed by using independent samples t-test,Pearson linear correlation,multiple linear regression,binary logistic regression,and receiver operator characteristic(ROC)curves.Results There were no significant differences in gender,smoking history,SBP,FBG,TG,LDL-c,TC,BUN,Scr,UA,eGFR and Hcy(all P>0.05).The age,BMI,DBP,HDL-c,and urine NGAL levels in the endothelial dysfunction group were significantly higher than those in the normal endothelial function group(P<0.05).Pearson linear correlation analysis showed that urine NGAL levels were negative correlated with FMD(r =-0.632 P<0.05).Multiple linear regression analysis:NGAL,DBP significantly affected FMD(all P<0.05).NGAL and diastolic blood pressure were independent risk factors for FMD.The area under the curve of ROC curve analysis was 0.813,0.895 and 0.906 respectively for urinary NGAL,DBP and urinary NGAL combined with DBP.DBP combined with urinary NGAL had the higher diagnostic efficacy.Conclusion Urinary NGAL and DBP are associated with the endothelial dysfunction,and urinary NGAL is expected to be a new biomarker for evaluating the vascular endothelial function loss and a target for the intervention of prehypertension

Objective To explore the relationship between the types of bicuspid aortic valves(BAV)and the outcome of functional mitral regurgitation(FMR)and the affecting factors of FMR.Methods From Jun 2018 to Sep 2022,patients with severe BAV aortic valve stenosis(AS)complicated with FMR underwent post transcatheter aortic valve replacement(TAVR)in Zhongshan Hospital,Fudan University were retrospectively analyzed.The baseline information and imaging data of different BAV patients were collected.Logistic regression was used to analyze the factors affecting the outcome of FMR(improvement and non-improvement).Result A total of 100 patients with TAVR were included,including 49 patients with type 0 of BAV and 51 patients with type 1 of BAV.Compared with patients of type 1,patients of type 0 had younger age[(72.78±6.09)y vs.(77.00±8.35)y,P=0.050],lower male ratio(47%vs.73%,P= 0.009)higher BMI[(23.19±2.62)kg/m2 vs.(21.99±3.13)kg/m2,P=0.041],and lower incidence of aortic regurgitation(69%vs.92%,P=0.040).Compared with the non-improvement group,the improvement group had a lower incidence of coronary heart disease(5%vs.18%,P=0.042),higher incidence of pulmonary hypertension(20%vs.2%,P=0.007),larger left ventricular diastolic diameter[(51.98±6.74)mm vs.(48.04±7.72)mm,P=0.009]and higher maximum flow velocity[(4.86±0.95)cm/s vs.(4.47±0.75)cm/s,P= 0.023]of the aortic valve.The results of Logistic regression analysis showed that preoperative pulmonary hypertension,left ventricular end-diastolic diameter and maximum valvular flow velocity of BAV patients were the potential affecting factors of FMR improvement after TAVR.Conclusion No significant difference was found in FMR improvement between BAV patients of type 0 and type 1 after TAVR.For BAV patients with AS,preoperative pulmonary hypertension,larger left ventricular end-diastolic diameter,and faster aortic valve flow velocity were associated with higher FMR improvement rate.