To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective To investigate the relationship between ferroptosis-related genes[heme oxygenase-1(HO-1),solute carrier family 7 member 11(SLC7A11),and long-chain acyl-coenzyme A synthetase 4(ACSL4)]expression and cardiovascular events in patients with chronic renal failure(CRF),aiming to pro-vide clinical insights for risk assessment of cardiovascular complications.Methods A total of 124 CRF pa-tients(CRF group)admitted to the hospital from January 2020 to January 2023 and 124 healthy people(con-trol group)who underwent physical examination in the hospital during the same period were selected as the research objects.The levels of ferroptosis-related gene HO-1,SLC7A11 and ACSL4 were detected and com-pared between the two groups.CRF patients were followed up for 12 months after discharge,and they were di-vided into concurrent group(n=56)and non-concurrent group(n=66)according to the occurrence of cardio-vascular events.Spearman correlation analysis was used to investigate the correlation between iron death relat-ed genes HO-1,SLC7A11,ACSL4 and cardiovascular events in CRF patients.Univariate and multivariate Lo-gistic regression analysis were used to investigate the influencing factors of cardiovascular events in CRF pa-tients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of iron death re-lated genes HO-1,SLC7A11,and ACSL4 for cardiovascular events in CRF patients.Results Serum HO-1 and SLC7A11 levels in CRF group were lower than those in control group(P＜0.05),and the ACSL4 level was higher than that in control group(P＜0.05).The serum HO-1 and SLC7A11 levels in concurrent group were lower than those in non-concurrent group(all P＜0.05),and the serum ACSL4 level was higher than that in non-concurrent group(P＜0.05).Ferroptosis-related genes HO-1 and SLC7A11 were negatively correlated with cardiovascular events(r=-0.708,—0.721,P＜0.05),while ACSL4 was positively correlated with car-diovascular events(r=0.699,P＜0.05).High serum ACSL4 expression and high cTnT level were risk fac-tors for cardiovascular events in CRF patients(P＜0.05),and high hemoglobin level and high serum HO-1 and SLC7A11 expression were protective factors for cardiovascular events in CRF patients(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of serum HO-1,SLC7A11,ACSL4,hemo-globin and cTnT alone for predicting cardiovascular events in CRF patients were 0.787,0.735,0.773,0.651 and 0.782,respectively.The AUC of the combined prediction of ferroptosis-related genes was 0.837,and the AUC of the combined application of five factors was 0.880.According to Delong's test,the AUC of both com-bined application models was significantly higher than those of individual application(P＜0.05).The nomo-gram model showed that all ferroptosis-related genes were positively expressed(HO-1＜1.5,SLC7A11＜1.15,ACSL4≥2.75),and the risk of developing concurrent cardiovascular events in CRF patients could reach over 75％.Conclusion The expression of serum HO-1 and SLC7A11 in CRF patients is decreased,and the ACSL4 expression is increased,which is closely related to cardiovascular events,and the combined detection of three indexes has high value in predicting cardiovascular events in CRF patients.

Objective To analyze the clinical characteristics and prognosis of patients with spon-taneous coronary artery dissection(SCAD).Methods A retrospective analysis was conducted in 40 patients with acute myocardial infarction(AMI).All patients were diagnosed with SCAD during hos-pitalization through coronary angiography(CAG)or intravascular ultrasound(IVUS).The clinical characteristics,CAG or IVUS findings,and treatment regimens of the patients were analyzed,and their prognosis was assessed through follow-up.Results Among 40 SCAD patients,there were 11 males and 29 females,with a mean age of(53.04±9.15)years.Twelve patients had identified causative factors,and seven patients presented with chest pain as the initial symptom.CAG or IVUS results showed that a total of 69 SCAD lesions were detected in 40 patients,with 15 patients having a single lesion.The primary treatment approach for the patients was medical therapy.The median fol-low-up duration was 34 months(ranging 2 to 48 months),during which 5 major adverse cardiovascu-lar and cerebrovascular events(MACCE)occurred.The patients were divided into MACCE group(5 patients)and non-MACCE group(35 patients)based on occurrence of MACCE.The mean age and the incidence of regional wall motion abnormalities on echocardiography were higher in the MACCE group than in the non-MACCE group(P＜0.05).Conclusion SCAD has distinct imaging features on CAG,and IVUS can confirm the diagnosis.Most patients are treated with medical therapy and have a generally favorable prognosis.However,patients with older age or regional wall motion abnormali-ties on echocardiography have poorer prognosis.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective Chlorination is often used to disinfect recreational water in large amusement parks;however,the health hazards of chlorination disinfection by-products(DBPs)to occupational populations are unknown.This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks. Methods Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire.Seven typical chlorinated DBPs in recreational water and spray samples were quantified by gas chromatography,and the health risks to amusement park employees exposed to chlorinated DBPs were evaluated according to the WHO's risk assessment framework. Results Trichloroacetic acid,dibromochloromethane,bromodichloromethane,and dichloroacetic acid were detected predominantly in recreational water.The carcinogenic and non-carcinogenic risks of the five DBPs did not exceed the risk thresholds.In addition,the carcinogenic and non-carcinogenic risks of mixed exposure to DBPs were within the acceptable risk limits. Conclusion Typical DBPs were widely detected in recreational water collected from three large amusement parks in Shanghai;however,the health risks of DBPs and their mixtures were within acceptable limits.

Objective This study aims to assess the clinical value of sputum and bronchoalveolar lavage fluid examination combined with acid-fast bacilli detection to provide a reference for the diagnosis and treatment of pulmonary tuberculosis.Methods We collected and analyzed relevant test data from patients who underwent smear and/or isolation of sputum and bronchoalveolar lavage fluid for acid-fast bacilli or Mycobacterium detection within the same week from January 2021 to July 2021.The test results'similarities and differences were analyzed.Results Of the 272 patients,the positive rates of sputum smear,alveolar lavage fluid smear,sputum isolation,alveolar lavage fluid isolation(hereinafter referred to as"A""B""C"and"D")were 14.71％(40/272),19.49％(53/272),25.00％(67/268)and 31.90％(74/232),respectively.The positive rate of the four tests as parallel tests was 37.50％(102/272).The result modes of A+C+,A-C+,A+C-,A-C-and A-CN(the"+""-"and"N"in the super-script stood for"positive""negative"and"undetected")accounted for 14.71％(40/272),13.97％(38/272),0,69.85％(190/272),1.47％(4/272)respectively,and the result modes of B+D+,B-D+,B+D-,B-D-and B-DN accounted for 19.12％(52/272),8.82％(24/272),0.37％(1/272),56.99％(155/272),14.71％(40/272).The percentages of these re-sult modes of A+B+,A+B-,A-B+and A-B-were 14.71％(40/272),0,4.78％(13/272),80.51％(219/272),respec-tively.The percentages of these result modes of A+D+,A+D-,A+DN,A-D+,A-D-,A-DN,AND+,AND-and ANDN were 19.12％(52/272),5.51％(15/272),4.04(11/272),8.09％(22/272),51.74％(140/272),10.29％(28/272),0.74％(2/272),0.37％(1/272),and 0.37％(1/272),respectively.Conclusion Compared with more common sputum tes-ting,for acid-fast bacteria,performing bronchoalveolar lavage fluid testing for acid-fast bacteria in alveolar lavage fluid can signifi-cantly improve etiological diagnostic performance for tuberculosis,which is worth promoting extensively in clinical practice.

Objective:To understand the current situation of fear of dementia among the elderly in Changsha and its related factors in order to provide empirical evidence for lowering the level of dementia fear among the elderly and formulating effective strategies.Methods:From July to September 2022, 300 elderly people living in communities in Changsha were surveyed using a random sampling method.Data were collected via a questionnaire for general information, the Fear of Dementia Scale, the Social Support Rating Scale, and the Generalized Anxiety Disorder Scale, and multiple linear regression was used to analyze related factors for fear of dementia in the elderly.Results:For elderly people in Changsha, the fear of dementia score was 46.00(33.25, 59.00), the social support score was 40.00(34.00, 44.75), and the generalized anxiety disorder score was 3.00(2.00, 4.00).According to analysis by Spearman's correlation, the level of fear of dementia among the elderly in Changsha was positively correlated to the level of generalized anxiety( r=0.232, P<0.01)and negatively correlated to the level of social support( r=-0.226, P<0.01).Multiple linear regression analysis revealed that level of education( β=-2.385, t=-3.201, P=0.002), family history of dementia( β=10.801, t=4.151, P<0.001), frequency of physical examination( β=-2.601, t=-3.497, P=0.001), and social support( β=-0.347, t=-3.093, P=0.002)were related factors for fear of dementia in the elderly in Changsha. Conclusions:Fear of dementia among the elderly in Changsha is at a moderate level, and there is no widespread generalized anxiety.Family history of dementia, education level, frequency of physical examination, and level of social support are relevant factors for fear of dementia.To lessen the level of fear of dementia, specific intervention methods should be formulated according to the relevant factors.

Objective Recurrent pregnancy loss(RPL)presents a formidable challenge for individuals undergoing in vitro fertilization-embryo transfer(IVF-ET),forming both a clinical dilemma and a focal point for scientific inquiry.This study endeavors to investigate the intricate interplay between clinical features,such as age,body mass index(BMI),and waist-to-hip ratio(WHR),and routine laboratory parameters,including sex hormones,blood composition,liver and thyroid functions,thyroid antibodies,and coagulation indicators,in RPL patients undergoing IVF-ET.By meticulously analyzing these variables,we aim to uncover the latent risk factors predisposing individuals to RPL.Identifying potential factors such as advanced maternal age,obesity,and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence.Methods This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital,Sun Yat-sen University,between January 2012 and March 2021 as the case cohort,compared with women receiving assisted reproductive treatment due to male infertility as the control cohort.The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion.The clinical characteristics and relevant laboratory indexes of the two groups were compared.Employing both univariate and multivariate logistic regression analyses,we sought to unearth potential high-risk factors underlying RPL.Additionally,a linear trend analysis was conducted to assess the linear relationship between total testosterone(TT)levels and the number of miscarriages.Results In contrast to the control cohort,the RPL cohort exhibited significant increases in age,BMI,and WHR(P<0.05).Notably,TT levels were markedly lower in the RPL cohort(P=0.022),while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone,luteinizing hormone,estradiol,progesterone,prolactin levels,and anti-Müllerian hormone levels(P>0.05).Moreover,fasting insulin(FINS)levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort(P<0.001),although no significant differences were observed in fasting blood glucose levels(P>0.05).Furthermore,the neutrophil(NEU)count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort(P<0.01).Univariate logistic regression analysis identified several factors,including age≥35 years old,BMI≥25 kg/m2,WHR>0.8,FINS>10 mU/L,HOMA-IR>2.14,NEU count>6.3×109 L-1,and an elevated NEU/lymphocyte ratio(NLR),as significantly increasing the risk of RPL(P<0.05).Although TT levels were within the normal range for both cohorts,higher TT levels were associated with a diminished RPL risk(odds ratio[OR]=0.67,95% confidence interval[CI]:0.510-0.890,P=0.005).After adjustments for confounding factors,age≥35 years old(OR=1.91,95% CI:1.06-3.43),WHR>0.8(OR=2.30,95% CI:1.26-4.19),and FINS>10 mU/L(OR=4.50,95% CI:1.30-15.56)emerged as potent risk factors for RPL(P<0.05).Conversely,higher TT levels were associated with a reduced RPL risk(OR=0.59,95% CI:0.38-0.93,P=0.023).Furthermore,the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages(Ptrend=0.003),indicating a declining trend in TT levels with escalating miscarriage occurrences.Conclusion In patients undergoing IVF-ET,advanced maternal age,lower TT levels,increased WHR,and elevated FINS levels emerged as potent risk factors for RPL.These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.