Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective: This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively. Methods: The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model. Results: Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group. Conclusion This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.

Objective To assess the impact of statins combined with sorafenib(SRF)therapy on survival outcomes in patients with metastatic renal cell carcinoma(mRCC).Methods Clinical data of mRCC patients treated in the 908th Hospital of the Joint Security Force from November 2019 to November 2023 were retrospectively analyzed.They were categorized into statin group and non-statin group according to whether they used statins or not,and the differences in the primary endpoint of overall survival(OS),secondary endpoints of progression-free survival(PFS),objective response rate(ORR),and disease control rate(DCR)were compared between the two groups.Results A total of 80 patients were included in the study,with 27 in the statin group and 53 in the non-statin group.There were no statistically significant differences in partial remission,stable disease,disease progression,and DCR between the two groups(P＞0.05);complete remission and ORR were significantly higher in the statin group than in the non-statin group(P＜0.05).Kaplan-Meier analysis showed that,compared with the non-statin group,the median PFS and OS of the statin group were prolonged,and the difference in median PFS between the two groups was statistically significant(P＜0.05).In terms of safety,the incidence of other adverse events was similar in both groups(P＞0.05).Conclusion Statins combined with SRF treatment regimen can improve ORR and DCR and prolong median PFS and OS in patients with mRCC.

Objective:To investigate the implementation status of peripherally inserted central catheter (PICC) tip intracardiac electrocardiogram positioning technology in the hospitals, so as to provide reference for promoting the development of intracardiac electrocardiogram positioning technology.Methods:This study was a cross-sectional survey. Using the convenient sampling method, members of Intravenous Infusion Committee of Chinese Nursing Association selected PICC/ intravenous therapy leaders meeting the inclusion criteria from 5 to 10 hospitals in their work area as the research objects from December 2022 to January 2023. The self-made PICC Tip Intracardiac Electrocardiogram Positioning Technology Implementation Status Questionnaire was used to investigate the PICC/intravenous therapy leaders. A total of 205 questionnaires were distributed in 28 provinces/autonomous regions/municipalities directly under the Central Government, and 199 valid questionnaires were collected, with an effective recovery rate of 97.1%. Results:Among 199 hospitals, 63.3% (126/199) of them successfully implemented PICC tip intracardiac electrocardiogram positioning technology. Among the 126 hospitals that implemented PICC tip intracardiac electrocardiogram positioning technology, only 20 hospitals included it in their charging items. A total of 50.3% (100/199) of hospitals established a unified intracardiac electrocardiogram guided PICC catheterization procedure; 47.7% (95/199) of hospitals organized/participated in training programs on PICC tip intracardiac electrocardiogram positioning technology, and 57.3% (114/199) of hospital PICC/intravenous therapy leaders participated in training programs related to PICC tip intracardiac electrocardiogram positioning technology. In terms of the relevant achievements of 199 research hospitals, 56 papers, seven utility model patents and 28 awards were issued.Conclusions:The application, training and achievement output of PICC tip intracardiac electrocardiogram positioning technology need to be further improved. It is suggested to sink high-quality resources, formulate implementation procedures and evaluation standards, standardize nursing service project management, increase training efforts, and improve scientific research thinking of intravenous therapy nurses, so as to promote the standardization development of new technologies.

Objective:To explore the training needs of peripherally inserted central catheter (PICC) specialist nurses in Shandong Province for subcutaneous tunnel technique, so as to provide reference for conducting systematic and standardized training.Methods:This study was a cross-sectional survey. From October to December 2022, convenience sampling was used to select 922 PICC specialist nurses in Shandong Province as the research subject. A self-made questionnaire was used to investigate the training needs of PICC specialist nurses for subcutaneous tunnel technique.Results:A total of 922 questionnaires were distributed, and 922 valid questionnaires were collected, with an effective response rate of 100.00%. 22.78% (210/922) of PICC specialist nurses used subcutaneous tunnel technique. In terms of training willingness, 92.08% (849/922) of PICC specialist nurses had a training need for subcutaneous tunnel technique. In terms of training content needs, the total score of PICC specialist nurses for subcutaneous tunnel technique training content needs was (62.26±11.06), and the average score for each item was >4.15, and the highest scoring item was the sharing of special cases in tunnel PICC (4.60±0.77), and the lowest scoring item was PICC maintenance knowledge (4.15±1.15) .Conclusions:The application rate of subcutaneous tunnel technique is low, and PICC specialist nurses have a high training need. Managers should increase training efforts for this technique, improve training content, innovate training models, develop targeted training programs, so as to promote the application and promotion of this technique.

Objective:To systematically review thrombosis risk prediction models associated with peripherally inserted central venous catheter (PICC) in adults and provide a basis for the clinical application of these models and the development of subsequent models.Methods:Databases such as CNKI, Wanfang, VIP, PubMed, CINAHL, Web of Science, and Ovid were searched to collect studies on thrombosis risk prediction models related to adult PICC, covering all entries from the inception of the databases until December 31, 2022. Two researchers independently screened the literature, extracted data, and assessed the risk of bias.Results:Nineteen studies were included. D-dimer was the most common predictive factor; only five studies underwent external validation, and six studies evaluated model calibration. All included studies exhibited high risk of bias, primarily due to methodological deficiencies in model development and validation processes; the combined area under the receiver operating characteristic curve for nine models was 0.80 (95% Confidence Interval: 0.75-0.85) .Conclusions:Research on thrombosis risk prediction models related to adult PICC is still in its developmental stage. Most of the known models perform well with comprehensive and easily obtainable predictive factors, yet they exhibit methodological shortcomings. Future research should focus on improving the methodological quality and external validation during model development and validation processes.

[摘 要] 目的：探讨肝细胞癌（HCC）患者血清及癌组织中miR-203a和其靶基因的表达及其与患者临床病理特征和预后的关系。方法：利用生物信息学方法从TargetScan、miRDB和PicTar网站预测HCC组织中miR-203a的靶基因，通过双荧光素酶报告基因实验进行验证。选取2018年1月至2019年6月在常州市金坛区第二人民医院手术切除的96例HCC患者的癌和癌旁组织标本、血清和临床资料，以及90例健康体检者的血清作为对照。qPCR法检测血清miR-203a水平，以及HCC组织和癌旁组织中miR-203a及其靶基因表达，比较分析不同临床病理特征HCC患者miR-203a及其靶基因表达。随访3年，采用Kaplan-Meier法进行生存（OS）分析。结果：从数据库筛选出HCC中miR-203a相关的靶基因共10个，包括APC、CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PAQR3、PRMT5和SOSC3。HCC组织中miR-203a和APC、PAQR3 mRNA表达水平均显著低于癌旁组织（均P<0.01），CDK6、GATA6、HOXD3、IGF1R、IGFBP5、KCNE2、PRMT5和SOSC3 mRNA表达水平均显著高于癌旁组织（均P<0.01）；血清miR-203a、HCC组织miR-203a及其靶基因表达均与患者肿瘤临床分期、分化程度、肝功能分级、OS率有关（均P<0.01）。结论：HCC组织中miR-203a呈低表达，miR-203a及靶基因表达均与患者肿瘤临床分期、分化程度、肝功能及远期OS率有关。

BACKGROUND: Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown. METHODS: Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance. RESULTS: Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments. CONCLUSIONS Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.
Animals ; Humans ; Mice ; Apoptosis ; Bone Marrow Cells ; Cell Communication ; Connexin 43/genetics* ; Gap Junctions/metabolism* ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology* ; Mesenchymal Stem Cells/metabolism* ; Tumor Microenvironment ; Calcium/metabolism*

In recent years, peripherally inserted central catheter (PICC) plays an important role in tumor chemotherapy, parenteral nutrition, long-term intravenous infusion, and is an indispensable lifeline for critically ill patients and cancer patients. This article reviews the application of new tool technology in PICC catheterization, the management of PICC catheter-associated complications, the training status and development prospects of PICC specialist nurses, and discusses the current practice status and research prospects of PICC technology in China, with a view to providing a reference basis for promoting the development of PICC technology in China.

Objective: To observe the effects of electroacupuncture (EA) with three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) on the apoptosis of neurons and c-Jun N-terminal kinase (JNK) signaling pathway in the hippocampus of rats with vascular dementia (VD), and explore the mechanism of EA intervention for VD. Methods: Fifty male Sprague-Dawley rats were randomly divided into a model group, a sham operation group, a 100 Hz EA group, a 2 Hz EA group, and a 2 Hz/100 Hz EA group, with ten rats in each group. The VD model rats were established by repeated ischemia-reperfusion of bilateral common carotid arteries. The rats in the EA groups received EA intervention at Baihui (GV20), Dazhui (GV14), Geshu (BL17) and Zusanli (ST36), once a day for 14 d. Afterward, Morris water maze was used to examine the learning and memory performances of the rats in each group, hematoxylin-eosin staining to observe the histomorphological changes in the hippocampal CA1 region, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling to test the apoptosis of neurons in the hippocampal CA1 region, and Western blot to detect the protein expression levels of JNK, phosphorylated JNK (p-JNK), Caspase-8, and Caspase-3 in the hippocampus tissue. Results: Compared with the sham operation group, the escape latency of the model group in water maze test was prolonged; the number of crossing the original platform was decreased (P<0.01); the hippocampal neurons were severely damaged and the number of surviving neurons was decreased (P<0.01), whereas the number of apoptotic neurons was increased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were significantly increased (P<0.01). Compared with the model group, the escape latency of each EA group was significantly shortened; the number of crossing the original platform was significantly increased (P<0.01); the damage of hippocampal neurons was alleviated, the number of surviving neurons was increased (P<0.01), and the number of apoptotic neurons was decreased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were decreased (P<0.01). The results in the 2 Hz EA group and the 2 Hz/100 Hz EA group were superior to those in the 100 Hz EA group. Conclusion: EA with the three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) can improve the learning and memory performances in VD rats subjected to ischemia-reperfusion, its mechanism may be related to the inhibition of neuronal apoptosis and the regulation of the related protein expression of JNK signaling pathway, and the intervention effects of EA with 2 Hz and 2 Hz/100 Hz are more significant.