Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

Objective:To analyze the differences in emergency rescue service capacities between county-level hospitals in Zhejiang and Jiangsu provinces, and propose targeted improvement suggestions.Methods:Cluster sampling was employed, with representative county-level hospitals recommended by provincial hospital alliances in Zhejiang and Jiangsu. Emergency departments voluntarily submitted data, resulting in 24 hospitals from Zhejiang and 34 from Jiangsu. Data were collected through the China County-Level Hospital Emergency Service Capability Evaluation System. Differences between provinces were analyzed. Spearman correlation analysis explored relationships between multidimensional indicators, and multivariate logistic regression identified factors influencing hospital grade B++ and above.Results:In terms of department scale, Jiangsu had a larger emergency department area (4 853 m 2vs. 1 927 m 2, P<0.001), more beds of comprehensive inpatient wards in the emergency department (25.5 beds vs. 5.5 beds, P=0.011), and higher scores for the ratio of emergency department area to beds (4.8 vs. 3.4, P=0.005) than Zhejiang. In terms of staffing, Jiangsu had a higher proportion of doctors with master's degrees or above (13.8% vs. 0.0%, P<0.001), a higher proportion of frontline emergency medical staff with over three years of clinical experience (100.0% vs. 91.5%, P=0.001), and more doctors (19 vs. 15, P=0.039) and nurses (46 vs. 32, P=0.039). In terms of quality and safety and medical service capacity, Zhejiang had a higher severe trauma resuscitation success rate (92.9% vs. 83.75%, P=0.003), annual emergency surgery volume (1 002 vs. 428, P=0.015), and number of emergency surgery procedures (125 vs. 42, P=0.027), but Jiangsu had a shorter emergency room stay time (87.5 min vs. 136.2 min, P=0.029). In terms of informatization, Zhejiang outperformed Jiangsu in all indicators, especially in patient information interconnection and sharing (100.0% vs. 82.4%, P=0.030) and in-hospital diagnosis and treatment timeline (91.7% vs. 73.5%, P=0.043). Correlation analysis showed that the total specialty scale score was significantly positively correlated with the in-hospital emergency rescue service capacity score ( r=0.576) and the staffing score ( r=0.455). The total evaluation score was significantly positively correlated with the informatization total score ( r=0.397) and the pre-hospital emergency rescue service capacity score ( r=0.322). Binary Logistic regression analysis showed that the emergency rescue service capacity score was significantly positively correlated with hospital grade ( B=1.431, P=0.03, OR=4.185, 95% CI:1.152-15.205). For every 1-unit increase in the emergency department area ( B=0.002, P=0.05), the probability of a hospital being upgraded to B++ or above increased by 0.2% ( OR=1.002, 95% CI:1.000-1.004). Conclusions:Both provinces exhibit distinct advantages in emergency department development. Departmental scale and configuration significantly impact emergency service capabilities, while staffing and quality management constitute core elements for improvement. Informatization construction notably enhances emergency service efficiency and quality.

Objective To systematically evaluate the relationship between the intake of fruits and vegetables and the risk of prostate cancer, so as to provide relevant evidence for formulating the prevention strategies of prostate cancer. Methods Pubmed, Embase, and Web of Science databases were searched by computer for cohort studies and related literatures evaluating the relationship between vegetable and/or fruit intake and prostate cancer risk. The quality of the included literature was rated, and meta-analysis was carried out using R software (4.0. 3 version). Results A total of 20 cohort studies were included. Four studies only reported the relationship between fruit intake and the risk of prostate cancer, 4 studies only reported the relationship between vegetable intake and the risk of prostate cancer, and 12 studies reported the relationship between fruit and vegetable intake and the risk of prostate cancer. Meta-analysis results indicate that although dietary intake of vegetables in the high-intake group may reduce the risk of prostate cancer, the difference was not statistically significant (RR, 0.97; 95% CI (0.94, 1.01), P=0.11); I²=21.3%, P=0.21). There was no significant correlation between fruit intake and the risk of prostate cancer (RR, 1.00; 95% CI (0.96, 1.04) , P=0.99). Conclusion There is no significant correlation between the intake of vegetables and/or fruits and the risk of prostate cancer.

Objective:To evaluate the application method and effect of standardized scenario simulation teaching based on Kirkpatrick model in vocational protection education for nursing students.Methods:A historical controlled trial study was designed. Practical nursing students enrolled in 2018-2019 and 2017-2018 were selected into the experimental group ( n=203) and control group ( n=196), respectively. The experimental group adopted standardized scenario simulation teaching in the prevention and control education of needlestick injuries, and the control group adopted traditional classroom lecture. Using the Kirkpatrick model, the teaching effect of needlestick injuries protection for nursing students were compared between the 2 groups from such 4 levels as in reaction level, learning level, behavior level and results level. Results:There was no significant difference in the baseline data between the two groups in terms of age, gender, educational background and test scores of nursing professional knowledge as compared to that before practice. In reaction level: the nursing students' satisfaction of experimental group in teaching methods ( t=25.149, P<0.001) and teaching environment ( t=12.827, P<0.001) are higher than that of the control group, with statistical significance. In learning level: the test scores of needlestick injury knowledge in experimental group were significantly higher than those in control group ( t=8.221, P<0.001). In behavior level: the level of needlestick injury protection behavior in the experimental group was significantly higher than that in the control group ( t=9.250, P<0.001), and the knowledge conversion rate in the experimental group was higher than that in the control group ( t=6.054, P<0.001). In results level: the needlestick injuries incidence of experimental group was significantly lower than that of the control group ( χ2=15.815, P<0.001), the reported rate of needlestick injuries of experimental group was significantly lower than that of the control group ( χ2=14.185, P<0.001). Conclusion:The implementation of standardized scenario simulation teaching can effectively improve the effectiveness of vocational protection learning and reduce the incidence of needlestick injuries.

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Objective: To observe the evaluation function of gated equilibration ventriculography for the changes of left ventricular function in breast cancer with targeted therapy. Methods: From February 2016 to December 2017, a total of 60 female breast cancer patients (age: 28-65 (48.7±9.4) years) were included prospectively. Patients were divided into 2 groups: lapatinib combined with taxeme-based chemotherapy group (group A; n=25, age: 29-65 (47.8±11.3) years) and lapatinib monotherapy group (group B; n=35, age: 31-62 (51.1±8.5) years). All patients underwent gated equilibration ventriculography before treatment and 6/12 months after treatment. The parameters of left ventricular function including left ventricle ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), 1/3 ejection fraction (EF), 1/3 filling fraction (FF), time to peak ejection rate (TPER) and time of peak filling rate (TPFR) were observed. Repeated measurement analysis of variance, independent-samples t test and Wilcoxon rank sum test were performed. Results: In group A, the PER at 12 months after treatment ((3.11±0.48) end-diastolic volume (EDV)/s) was lower than that before treatment ((3.60±0.62) EDV/s; F=3.447, t=0.60, P<0.05), while there was no statistical difference between PER at 6 months after treatment ((3.34±0.57) EDV/s) and that before treatment (t=0.51, P>0.05); the PFR at 6 months ((3.07±0.71) EDV/s) and 12 months after treatment ((2.84±0.54) EDV/s) declined significantly compared with that before treatment ((3.57±0.81) EDV/s; F=5.345, t=0.82 and 0.75, both P<0.05). In group B, the PFR at 12 months after treatment ((2.86±0.55) EDV/s) declined significantly compared with that before treatment ((3.23±0.87) EDV/s; F=3.214, t=0.84, P<0.05). The decrease of PFR at 6 months and 12 months after treatment in group A was greater than that in group B (-0.37(-0.78, 0.15) vs -0.13(-0.44, 0.17) EDV/s; z=-1.569, P<0.05). Conclusions The gated equilibration ventriculography can effectively monitor the left ventricular function of breast cancer patients after targeted therapy. PER and PFR may be more sensitive than other parameters to assess heart function changes. The lapatinib combined with taxeme-based chemotherapy can affect diastolic function more and earlier than lapatinib monotherapy.

Background and purpose:Prostate-speciifc membrane antigen (PSMA), a cell surface protein with high expression in prostate carcinoma (PC) cells, is an attractive target for PC imaging and therapy. Small-molecule radiopharmaceuticals targeting PSMA can detect the location and extent of disease with high sensitivity and speciifcity. The aim of this study was to evaluate the value of technetium-99m-labelled small molecule against PSMA (HYNIC-Glu-Urea-A,99mTc-PSMA) for the detection of primary and metastatic prostate cancers.Methods:Twenty-four prostate cancer patients and 1 patient with benign prostate hyperplasia received whole-body scan followed by abdominopelvic SPECT/CT 2 h after intravenous injection of99mTc-PSMA. Tumor to muscle uptake ratio of99mTc-PSMA was calcu-lated using region of interest (ROI) technology. The sensitivity and specificity of99mTc-PSMA were evaluated. The relationships between positive99mTc-PSMA and prostate speciifc antigen (PSA) level and Gleason Score were analyzed. Results:Based on per patient, the sensitivity and speciifcity of99mTc-PSMA were 72.7% (16/22) and 100% (3/3), re-spectively. The level of PSA in patients with positive99mTc-PSMA imaging was signiifcantly higher than that in patients with negative99mTc-PSMA imaging [(PSA median 17.31 ng/mL, range: 2.26-3 239.0 ng/mL)vs(PSA median 0.49 ng/mL, range: 0.07-9.28 ng/mL)] (Z=-3.51,P<0.001). Among newly diagnosed patients and recurrent patients with PSA more than 2.0 nm/mL, it was apparent that99mTc-PSMA imaging was able to detect lesions with improved sensitivity of 94.1% (16/17). Gleason Scores between positive99mTc-PSMA patients and negative99mTc-PSMA patients were not significantly different (Z=-0.69,P=0.52).Conclusion:With the combination of whole-body scan and tomography, 99mTc-PSMA SPECT/CT can be an excellent and speciifc molecular imaging strategy to detect prostate cancer and its metastases.

The specific human immunoglobulin is a hyperimmune globulin against a particular pathogen or biotoxin .It′s an important variety in plasma derivatives .Specific human immunoglobulin is usually used to prevent and treat pathogen in -fections with high morbidity , severe outcomes and no efficient treatment available .Thus it has unique advantages in preven-tion and management of infectious diseases .A variety of specific human immunoglobulins have been licensed abroad , but the development of new specific human immunoglobulins is slow in China due to technical constraints , limited economic benefits or for other reasons .Here we reviewed some specific human immunoglobulins and their preventive and therapeutic effect on infectious diseases .

Objective To evaluate the volume of left ventricle (LV) based on PET-CT in left-sided breast cancer patients treated with adjuvant radiotherapy. To assess the impact of dose and volume in interrelations for heart and cardiac sub-structures using dose-volume histograms. Methods From October 2008 to February 2009, 14 patients with post-operatively confirmed left-sided breast cancer were enrolled in this study. Patients were scanned using contrast enhanced CT for simulation and FDG PET-CT have been applied to display the structure of left ventricle in each patient before radiotherapy (RT). The LV has been delineated based on PET-CT. Other critical sub-structures, such as left anterior descending coronary artery (LAD) have been contoured in each patient. The six-field simple intensity modulated radiotherapy (slMRT)technique has been created in all patients. Results The mean volumes of left ventricle based on PET-CT (LV-PET) were 112. 931 cm3. The volume of LV receiving ≥50% prescription dose highly correlated with the volume of heart receiving ≥50% prescription dose (R = 0. 869, P = 0. 000). There was less correlation between the volume of LAD and the volume of heart receiving ≥ 50% prescription dose ( R = 0. 220, P =0. 440). Conclusions The left ventricle could be delineated efficiently based on imaging of PET-CT. The volume of LV receiving higher dose in RT has high correlation with the volume of heart using sIMRT technique. It may pave the way for further exploring radiation induced cardiac injury in patients with breast cancer.