BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective:To evaluate the clinical status of long-term oral anticoagulant management in patients with atrial fibrillation, and to analyze the obstacles and promoting factors in the implementation of evidence, so as to provide evidence for clinical transformation.Methods:This study was a cross-sectional study. Through the evidence-based nursing method, guided by the Ottawa Model, the review indicators and review methods were developed based on the best evidence. The clinical status review of 100 patients who met the inclusion criteria in the Department of Cardiology, Affiliated Hospital of Jiangsu University was conducted from August to November 2022 using a convenience sampling method, and based on the results of the review, an analysis of obstacles and promoting factors was carried out to develop a clinical response.Results:This study included 100 patients with atrial fibrillation, 60 males and 40 females, aged (70.14 ± 10.39) years. Totally 26 best items were included, and 24 review indicators were developed, among which only 4 indicators had a compliance rate of 100% , 2 indicators had a compliance rate of >60% , 5 indicators had a compliance rate of <60% , and 13 indicators had a compliance rate of 0. According to the results of the review, a comprehensive and systematic analysis was conducted from the three dimensions of system, practitioners, patients and family members. For each dimension, obstacles and promoting factors were analyzed in depth from evidence-based change, potential adopters and practical environment.Conclusions:There is a gap between the best evidence and clinical status of long-term oral anticoagulant management in patients with atrial fibrillation. In-depth analysis of obstacle factors, formulate countermeasures, and promote the efficient implementation of evidence in clinical practice.

Objective:To evaluate the clinical status of long-term oral anticoagulant management in patients with atrial fibrillation, and to analyze the obstacles and promoting factors in the implementation of evidence, so as to provide evidence for clinical transformation.Methods:This study was a cross-sectional study. Through the evidence-based nursing method, guided by the Ottawa Model, the review indicators and review methods were developed based on the best evidence. The clinical status review of 100 patients who met the inclusion criteria in the Department of Cardiology, Affiliated Hospital of Jiangsu University was conducted from August to November 2022 using a convenience sampling method, and based on the results of the review, an analysis of obstacles and promoting factors was carried out to develop a clinical response.Results:This study included 100 patients with atrial fibrillation, 60 males and 40 females, aged (70.14 ± 10.39) years. Totally 26 best items were included, and 24 review indicators were developed, among which only 4 indicators had a compliance rate of 100% , 2 indicators had a compliance rate of >60% , 5 indicators had a compliance rate of <60% , and 13 indicators had a compliance rate of 0. According to the results of the review, a comprehensive and systematic analysis was conducted from the three dimensions of system, practitioners, patients and family members. For each dimension, obstacles and promoting factors were analyzed in depth from evidence-based change, potential adopters and practical environment.Conclusions:There is a gap between the best evidence and clinical status of long-term oral anticoagulant management in patients with atrial fibrillation. In-depth analysis of obstacle factors, formulate countermeasures, and promote the efficient implementation of evidence in clinical practice.

Objective To investigate the differential expression of miR-124-3p in peripheral blood and clinical sig-nificance of patients with β-thalassemia.Methods Peripheral blood samples were collected from 33 patients with β-thalassemia and 30 healthy controls in Ningde Municipal Hospital Affiliated to Ningde Normal University from June 2021 to August 2022.The expression level of miR-124-3p was detected.Luciferase reporter gene was used to verify the interaction between miR-124-3p and ERF 3'UTR.The correlation between differential expression of miR-124-3p and β-thalassemia was analyzed and the clinical diagnostic value of miR-124-3p for β-thalassemia was eval-uated.Results Compared with healthy control individuals,the expression of miR-124-3p was significantly up-reg-ulated in patients with β-thalassemia(P＜0.001).The genotype of miR-124-3p high expression group was 84.2%β0(16/19),the genotype of low expression group was 55.6%β+(10/18).ROC curve analysis showed that miR-124-3p had predictive efficacy for β-thalassemia(AUC:0.842).Luciferase reporter gene analysis showed that ERF gene was the regulatory target of miR-124-3p.Conclusions The differential expression of miR-124-3p in patients with β-thalassemia is closely related to the genotype and clinical severity of thalassemia,and ERF is negatively reg-ulated by miR-124-3p.miR-124-3p may be an effective diagnostic biomarker for β-thalassemia.

【Objective】 To measure and analyze foot development indicators of children under 3 years old, in order to provide basis for the correct clinical assessment of children foot development. 【Methods】 A total of 5 894 children under 3 years old who took physical examination in the Child Health Care Department of Xi′an People′s Hospital from August 2022 to March 2023 were randomly selected. Foot length, foot width, the ratio of foot width to length and arch index were measured by image processing system, and were compared among different age groups and sex groups. 【Results】 1) Foot length, foot width and arch index of children under 3 years old increased significantly with age, while the ratio of foot width to length decreased significantly with age(F=1 345.23, 396.21,184.65, 287.03, P<0.05). 2) There was no statistical significance in foot length, foot width and arch index between left and right foot of children under 3 years old(P>0.05). 3) Foot length and foot width of boys were greater than those of girls in all age groups, and the difference was statistically significant(tfoot length:3.45 - 10.19, tfoot width: 3.77 - 9.21, P<0.05). There was no significant difference in arch index between boys and girls in all age groups(P>0.05). 【Conclusion】 Foot shape of children under 3 years old changes with age, there are differences in foot length and width between boys and girls.

Objective:To investigate the relationship between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours in primiparas using epidural analgesia.Methods:A retrospective study was conducted on the clinical data of pregnant women who delivered vaginally in the obstetrics department of the Affiliated Hospital of Jining Medical University from January 1, 2020, to December 31, 2020. The data included maternal age, pre-pregnancy body mass index (BMI), gravidity, gestational age at delivery, weight gain during pregnancy, common pregnancy complications (such as gestational hypertension, gestational diabetes, hypothyroidism, and pregnancy-related anemia), types of uterotonics, duration of each stage of labor, delivery outcomes, perineal conditions, postpartum hemorrhage within 2 hours, and neonatal birth length and weight. The exposure variable was the duration of the second stage of labor, and the outcome was the amount of postpartum hemorrhage within 2 hours. Potential risk factors were analyzed using univariate analysis. After adjusting for potential confounding factors, a generalized additive model was used for linear regression analysis, smooth curve fitting, and threshold effect analysis to observe the relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours.Results:A total of 2 067 primiparas were included in the study. The mean age of the participants was 26.5±3.6 years, the median duration of the second stage of labor was 54 min (range: 35-81 min), and the median amount of postpartum hemorrhage within 2 hours was 230 ml (range: 200-300 ml). After adjusting for factors such as maternal age, pre-pregnancy BMI, gestational age at delivery, vaginal delivery, duration of the first and third stages of labor, perineal conditions, types of uterotonics used within 2 hours postpartum, and neonatal birth length and weight, a positive relationship was found between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours ( ?=0.20, 95% CI: 0.00-0.30, P<0.05). The smooth curve fitting results showed a non-linear relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours. Threshold effect analysis indicated that the two-segment regression model (Model Ⅱ) was more suitable for fitting the correlation compared to the univariate linear regression model (Model Ⅰ), with a log-likelihood ratio test P-value of 0.001, and the inflection point was 115 min for the second stage of labor (95% CI: 99-125 min). Conclusions:In primiparas using epidural analgesia, there is a non-linear relationship and threshold effect between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours. When the second stage of labor exceeds 115 min, the extension of the second stage may increase the amount of postpartum hemorrhage within 2 hours.

Objective:To investigate the relationship between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours in primiparas using epidural analgesia.Methods:A retrospective study was conducted on the clinical data of pregnant women who delivered vaginally in the obstetrics department of the Affiliated Hospital of Jining Medical University from January 1, 2020, to December 31, 2020. The data included maternal age, pre-pregnancy body mass index (BMI), gravidity, gestational age at delivery, weight gain during pregnancy, common pregnancy complications (such as gestational hypertension, gestational diabetes, hypothyroidism, and pregnancy-related anemia), types of uterotonics, duration of each stage of labor, delivery outcomes, perineal conditions, postpartum hemorrhage within 2 hours, and neonatal birth length and weight. The exposure variable was the duration of the second stage of labor, and the outcome was the amount of postpartum hemorrhage within 2 hours. Potential risk factors were analyzed using univariate analysis. After adjusting for potential confounding factors, a generalized additive model was used for linear regression analysis, smooth curve fitting, and threshold effect analysis to observe the relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours.Results:A total of 2 067 primiparas were included in the study. The mean age of the participants was 26.5±3.6 years, the median duration of the second stage of labor was 54 min (range: 35-81 min), and the median amount of postpartum hemorrhage within 2 hours was 230 ml (range: 200-300 ml). After adjusting for factors such as maternal age, pre-pregnancy BMI, gestational age at delivery, vaginal delivery, duration of the first and third stages of labor, perineal conditions, types of uterotonics used within 2 hours postpartum, and neonatal birth length and weight, a positive relationship was found between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours ( ?=0.20, 95% CI: 0.00-0.30, P<0.05). The smooth curve fitting results showed a non-linear relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours. Threshold effect analysis indicated that the two-segment regression model (Model Ⅱ) was more suitable for fitting the correlation compared to the univariate linear regression model (Model Ⅰ), with a log-likelihood ratio test P-value of 0.001, and the inflection point was 115 min for the second stage of labor (95% CI: 99-125 min). Conclusions:In primiparas using epidural analgesia, there is a non-linear relationship and threshold effect between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours. When the second stage of labor exceeds 115 min, the extension of the second stage may increase the amount of postpartum hemorrhage within 2 hours.

Objective:To conduct a scoping review on the literature related to the core competencies of clinical nursing specialists and clarify the contents and applicable scenarios of the core competency elements of clinical nursing specialists.Methods:Guided by the methodological framework of PRISMA-ScR, this study focused on the capabilities, competencies, roles, and responsibilities of clinical nursing specialists in the context of medical institutions. A systematic search was conducted in 6 English databases (Web of Science, PubMed, Embase, CINAHL, ProQuest, Cochrane Library) and 4 Chinese databases (Chinese National Knowledge Infrastructure, Wanfang, VIP, SinoMed) to extract relevant studies on categories of clinical nursing specialist positions, research types, authors, countries, publication years, core competency elements. The search time range was from January 1, 2013, to June 1, 2023.Results:A total of 1 406 relevant articles were retrieved, with 15 articles finally included. Six primary indicators (clinical nursing practice capability, public health management ability, nursing management ability, nursing research ability, nursing education ability, ethics/morality/law), 16 secondary indicators, and 57 tertiary indicators were summarized.Conclusions:China can reference the establishment of core competency elements for clinical nursing specialists from other countries, integrate them with Chinese clinical practice to improve the competency requirements for clinical nursing specialists, and further refine the nursing management system for various positions.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and current therapeutic strategies are limited in their effectiveness.The expressions of Rab5 and the M2 tumor-associated macrophage marker CD163 in tissues were detected by Western blot. The migration and invasion of cells were determined using a Transwell assay. The expressions of the exosome markers were evaluated by Western blot. The polarization of human macrophages (THP-1) was determined by incubation of THP-1 cells with conditioned medium or exosomes collected from MDA-MB-231 cells with indicated transfections or by a coculture system of THP-1 and MDA-MB-231 cells. The M1 and M2 macrophage markers were evaluated by qRT-PCR. The expression of Rab5 in TNBC was significantly higher than that in normal breast tissue. Rab5 expressions in triple-negative and luminal A breast cancer were higher than those in other molecular subtypes. Higher CD163 expression was observed in triple-negative breast cancer and in triple-negative and luminal B subtypes. Rab5 knockdown suppressed but Rab5 overexpression promoted the migration and invasion capacity of MDA-MB-231 cells. The levels of CD63 and CD9 in the medium of Rab5 knockdown cells were lower than those in control cells, whereas higher levels of CD63 and CD9 were observed in Rab5 overexpression cells. Rab5 knockdown decreased the excretion but did not alter the diameter of the exosomes. Knockdown of Rab5 facilitated the anti-tumor polarization of macrophages, which was partially reversed by Rab5 overexpression. Therefore, Rab5 is expected to be a potential therapeutic target for triple-negative breast cancer.

Objective:To investigate the distribution characteristics of virulence-related phenotypes/genotype, capsular serotype, drug resistance phenotypes, and sequence typing (ST) of Klebsiella pneumoniae in patients living in Zhongjiang county, improve clinical understanding, and provide evidence for the prevention and control of bacterial drug resistance and clinical rational drug use. Methods:The data of 135 strains of Klebsiella pneumoniae isolated from patients who received treatment in Zhongjiang County People's Hospital from July to December 2019 were retrospectively analyzed. Bacterial identification and drug sensitivity testing were performed using the WalkAway-40Plus automated microbiology system. Strains with a high viscosity phenotype were identified using wire drawing experiments. Hypervirulence-associated capsular serotype and virulence genes were verified by polymerase chain reaction. ST of Klebsiella pneumoniae strain was identified using multilocus sequence typing. Results:Strains with a high viscosity phenotype were identified in 50.4% of the 135 strains. 54.1%, 54.8%, and 54.1% of the strains were positive for virulence genes iucA, iroN, rmpA. The proportion of strains with capsular Serotype K1 or K2 was 11.9% and 15.6%, respectively. A total of 65 kinds of ST were identified, with ST23 and ST37 being the most common, accounting for 11.1% and 6.7%, respectively. The resistance rate of the strains to 16 kinds of antibiotics was 0.0%-25.2%, and the resistance rate to Carbapenem antibiotics, Amikacin, and Tigecycline was less than 1%. The positive rate of virulence gene of strains with a high viscosity phenotype was significantly higher than that of strains without a high viscosity phenotype ( P < 0.001), and its resistance rate to Cephalosporin was significantly lower in strains with a high viscosity phenotype than that in strains without a high viscosity phenotype ( P < 0.001). Conclusion:Klebsiella pneumoniae in Zhongjiang County is characterized by "high virulence and low drug resistance". It is necessary to continuously monitor the changes in the virulence and drug resistance of Klebsiella pneumoniae in Zhongjiang County, Sichuan Province, and be alert to the rapid dissemination of highly virulent strains.