Objective To evaluate the clinical efficacy and safety of vericiguat combined with the new"Quadruple Therapy"for treating heart failure with reduced ejection fraction(HFrEF)and to explore its impact on left ventricular reverse remodeling(LVRR)in patients with different baseline characteristics.Methods A total of 87 patients with chronic heart failure treated with vericiguat at the Department of Cardiology,Nanjing Drum Tower Hospital from June 2022 to March 2024,were consecutively enrolled as the observation group.These patients were matched at 1:1 by age,sex,and left ventricular ejection fraction(LVEF)with 87 patients who received the standard quadruple therapy without vericiguat as the control group.Propensity score matching was used to further balance confounding factors,resulting in 64 patients in each group for final analysis.Changes in echocardiographic parameters,liver and kidney function,electrolyte levels,and blood pressure were analyzed at baseline and during the 6-month follow-up to assess the efficacy and safety of vericiguat.The primary efficacy endpoint was the occurrence of LVRR.Subgroup analyses were conducted based on baseline characteristics such as age and sex.Interaction analysis was utilized to evaluate the heterogeneity of vericiguat's efficacy.Results After 6 months of treatment,the vericiguat group showed significant improvements in cardiac structure and function compared to the control group.The left ventricular end-diastolic diameter was significantly reduced[-0.43(-1.00,-0.10)mm vs.-0.22(-0.53,0.02)mm,P=0.002],and the LVEF was significantly increased[8.45％(1.40％,16.50％)vs.2.75％(0,11.00％),P=0.002].The percentage of patients in the vericiguat group who achieved LVRR was significantly larger than in the control group(46.4％vs.27.4％,P=0.011).Multivariate logistic regression revealed that the combination of vericiguat was an independent predictor of LVRR(Model 2:OR=2.54,95％CI:1.29～5.01,P=0.007).The reverse remodeling effect remained consistent across different subgroups and was not significantly influenced by specific baseline characteristics(Pinteraction>0.05).Vericiguat did not affect blood pressure,liver and kidney function,or electrolyte levels,achieving satisfactory safety,despite its significantly higher incidence of gastrointestinal reactions(16.1％vs.5.7％,P<0.001).Conclusion The addition of vericiguat to the quadruple therapy significantly improves cardiac function and promotes left ventricular reverse remodeling in HFrEF patients while maintaining a favorable safety profile.

Objective To evaluate the clinical efficacy and safety of vericiguat combined with the new"Quadruple Therapy"for treating heart failure with reduced ejection fraction(HFrEF)and to explore its impact on left ventricular reverse remodeling(LVRR)in patients with different baseline characteristics.Methods A total of 87 patients with chronic heart failure treated with vericiguat at the Department of Cardiology,Nanjing Drum Tower Hospital from June 2022 to March 2024,were consecutively enrolled as the observation group.These patients were matched at 1:1 by age,sex,and left ventricular ejection fraction(LVEF)with 87 patients who received the standard quadruple therapy without vericiguat as the control group.Propensity score matching was used to further balance confounding factors,resulting in 64 patients in each group for final analysis.Changes in echocardiographic parameters,liver and kidney function,electrolyte levels,and blood pressure were analyzed at baseline and during the 6-month follow-up to assess the efficacy and safety of vericiguat.The primary efficacy endpoint was the occurrence of LVRR.Subgroup analyses were conducted based on baseline characteristics such as age and sex.Interaction analysis was utilized to evaluate the heterogeneity of vericiguat's efficacy.Results After 6 months of treatment,the vericiguat group showed significant improvements in cardiac structure and function compared to the control group.The left ventricular end-diastolic diameter was significantly reduced[-0.43(-1.00,-0.10)mm vs.-0.22(-0.53,0.02)mm,P=0.002],and the LVEF was significantly increased[8.45％(1.40％,16.50％)vs.2.75％(0,11.00％),P=0.002].The percentage of patients in the vericiguat group who achieved LVRR was significantly larger than in the control group(46.4％vs.27.4％,P=0.011).Multivariate logistic regression revealed that the combination of vericiguat was an independent predictor of LVRR(Model 2:OR=2.54,95％CI:1.29～5.01,P=0.007).The reverse remodeling effect remained consistent across different subgroups and was not significantly influenced by specific baseline characteristics(Pinteraction>0.05).Vericiguat did not affect blood pressure,liver and kidney function,or electrolyte levels,achieving satisfactory safety,despite its significantly higher incidence of gastrointestinal reactions(16.1％vs.5.7％,P<0.001).Conclusion The addition of vericiguat to the quadruple therapy significantly improves cardiac function and promotes left ventricular reverse remodeling in HFrEF patients while maintaining a favorable safety profile.

T cell factor 1（TCF-1）is a downstream transcription factor of the Wnt/β-catenin signaling pathway，and plays an important role in the development，differentiation，and memory formation of T cells. Recent studies have shown that TCF-1 can regulate the formation and maintenance of stem-like memory T cells（Tscm），and has potential application value in evaluating the prognosis of tumor immunotherapy and as a target for tumor immunotherapy. This article reviews the regulatory effects of TCF-1 on the immune memory as well as stemness formation and maintenance of CD8 +T cells，summarizes the transcription network centered on TCF-1，and further elucidates the application and value of TCF-1 in tumor immunotherapy.

T cell factor 1（TCF-1）is a downstream transcription factor of the Wnt/β-catenin signaling pathway，and plays an important role in the development，differentiation，and memory formation of T cells. Recent studies have shown that TCF-1 can regulate the formation and maintenance of stem-like memory T cells（Tscm），and has potential application value in evaluating the prognosis of tumor immunotherapy and as a target for tumor immunotherapy. This article reviews the regulatory effects of TCF-1 on the immune memory as well as stemness formation and maintenance of CD8 +T cells，summarizes the transcription network centered on TCF-1，and further elucidates the application and value of TCF-1 in tumor immunotherapy.

Objective:To investigate the current status of scientific fitness literacy (SFL) and its influencing factors among Chinese adults aged 20-59 years.Methods:Totally 63 338 adults aged 20-59 years in the status of national fitness activities in 2020 from 1 January to 31 March 2020 were selected as the subjects, and they were divided into four age groups, namely, the 20-29 age group, the 30-39 age group, the 40-49 age group and the 50-59 age group. Data were analyzed by SPSS 29.0.Comparative analyses for age, gender, urban-rural difference were carried out by applying non-parametric tests, and multiple regression models were applied to find the influencing factors of SFL.Results:The SFL score of Chinese adults aged 20-59 years was 53.40 (41.67, 63.73), and the scores of cognition, attitude, ability and skills, behavior and habits sub-dimensions were 86.11 (72.22, 100.00), 62.96 (50.62, 75.31), 27.78 (11.11, 44.44) and 33.33 (11.11, 55.56), respectively. The SFL and the four sub-dimensions were demonstrated to have higher scores for males than females, and higher scores for adults in urban area than those in rural area(all P<0.01). The multiple regression results showed that regular exercise at a fitness facility (20-29 age group: β=0.321, t=5.940, P<0.01; 30-39 age group: β=0.187, t=2.937, P<0.01; 40-49 age group: β=0.230, t=3.988, P<0.01; 50-59 age group: β=0.415, t=5.671, P<0.01) was the Chinese adults' common influence factor on SFL.Motivation, evaluation by those around them, experience from exercising, and convenience and atmosphere of exercising were the main influence factors in the 20-29 and 30-39 age groups(all P<0.05).Comfort level of fitness venue, convenience, safety, and support of fitness place were the main influence factors in adults aged 40-59 years(all P<0.05). Conclusions:Chinese adults aged 20-59 years old have high SFL awareness scores, but low overall SFL scores. Surrounding people's evaluation, experience in exercise, comfort level of fitness place, convenience, safety and fitness policy support are the influential factors of scientific fitness literacy.

Objective The purpose of this study is to explore the effects of reminazolam and midazolam on the occurrence of deliri-um in postoperative patients with congenital heart disease.Methods A total of 131 postoperative patients with congenital heart disease were admitted to our hospital from March to August 2023,they were randomly divided into a reminazolam group(n=66)and a midazolam group(n=65).The Cornell Delirium Assessment Scale for Children was used to evaluate postoperative delirium.We analyzed and com-pared the incidence,occurrence time,and duration of the two groups.We also recorded the patient's adverse drug reactions,mechanical ventilation time,cardiac intensive care unit(CICU)stay time,and hospitalization time.Results The incidence of delirium was 51.7％in the midazolam group and 40.0％in the reminazolam group,with no statistically significant difference.However,there were significant differences in the timing of delirium occurrence between the two groups(x2=12.400,P=0.030).The duration of delirium in the remi-nazolam group was significantly shortened(x2=14.773,P=0.034).There was no statistically significant difference between the two groups in mechanical ventilation and CICU retention time.There was a difference in hospitalization time between the two groups(z=0.096,P=0.016).There were 2 cases of adverse reactions(3.08％)in the midazolam group and 5 cases(7.58％)in the reminazolam group,with no statistically significant difference.Conclusion As a benzodiazepine drug,reminazolam has a certain protective effect on postoperative delirium in patients undergoing congenital heart surgery.However,further research is needed on the application of reminazo-lam in children,including drug dosage and adverse reactions.

Mast cells, autoantibodies, inflammatory cells, coagulation cascade, complement system and nervous system are all involved in the complex pathogenesis of chronic spontaneous urticaria (CSU) , while mast cells play a pivotal role in it. With deeper understanding of the pathogenesis of CSU, cutting-edge therapeutic methods are gradually being used in clinical practice. Nowadays, pharmacotherapyeutic studies are more focused on accurately modulating the pathological state of mast cells. This review summarizes recent advances in the pathogenesis of and medicines for CSU.

Objective:To develop a prone position management program and evaluate its effectiveness in preventing ventilator-associated pneumonia (VAP) in children with congenital heart disease combined with acute respiratory distress syndrome, in order to provide experience for clinical application.Methods:This was a quasi-experimental study. Convenient sampling method was used to select children with congenital heart defect who underwent mechanical ventilation in the Cardiothoracic Surgical Care Unit of Shanghai Children′s Medical Center, Shanghai Jiao Tong University, School of Medicine from June 2018 to December 2021 as the study subjects. The control group consisted of 80 hospitalized children from June 2018 to December 2019. They were used general nursing interventions to prevent VAP. The 42 hospitalized children from January 2020 to December 2021 were the intervention group, who usd the prone position management program on the basis of the control group. The differences in the incidence of VAP, duration of mechanical ventilation, duration of ICU stay, oxygenation index and the incidence of adverse events between the two groups were compared.Results:The incidence of VAP and mechanical ventilation duration in the intervention group were 4.8% (2/42) and 67.50 (55.00/101.50), which were lower than 35.0% (28/80) and 92.50 (68.00/142.00) of the control group, and the differences were statistically significant ( χ2=11.98, Z=3.40, both P<0.01). And the trend of increasing oxygenation index with the intervention group was better than the control group ( F=8.38, P<0.05). There was no statistical difference in the incidence of adverse events between the two groups (all P>0.05). Conclusions:The application of prone ventilation program with congenital heart disease children complicated with acute respiratory distress syndrome is safe and can significantly improve the oxygenation index, shorten the duration of mechanical ventilation and reduce the incidence of VAP.

Objective:To explore the situation and characteristics of the practice of severe cardiac analgesia, sedation and delirium in children in China, so as to lay a research foundation for standardizing the prevention process of severe cardiac analgesia, sedation and delirium in children.Methods:This study was a cross-sectional study, using questionnaire survey. The Analgesia, Sedation and Delirium Practice Questionnairewas designed according to consensus, clinical suggestions and clinical practice. In August 2021, the electronic questionnaire was issued to the Children's Cardiac Intensive Care Unit (ICU) in children's hospitals through the Pediatric Nursing Alliance Pediatric Congenital Nursing Group of the National Children's Medical Center. A total of 15 ICUs were included, all of which completed the survey, and the effective recovery rate of the questionnaire was 100%.Results:The 15 ICUs all had pain assessment system, including 11 with pain assessment standard operating procedures, 8 with sedation assessment standard operating procedures, and 4 with delirium assessment. However, there was no specific process or system for delirium assessment in ICU. All 15 ICUs used analgesics, 8 of them used opioids for analgesia immediately after cardiac surgery, 5 of them used analgesics according to the patient's condition, 2 of them used analgesics according to the pain score. Non-steroidal paracetamol was the first choice for non-postoperative children, and 6 of 15 ICUs used analgesics according to the pain score. All 15 ICUs used sedative drugs, 6 of which used sedative drugs within 1 hour after admission, 6 of which were decided by the doctor according to the situation of the child, 3 of which used sedative drugs according to the sedation score, and 7 of which used midazolam as the first choice. A total of 6 the 15 ICUs carried out some projects in the "ABCDEF" delirium prevention program.Conclusions:In this investigation, the use of analgesic and sedative drugs in ICU is heterogeneous, the evaluation process of analgesia and sedation has not been established, and delirium has not attracted enough attention. Rational sedation and analgesia need to develop standardized sedation and analgesia evaluation procedures. At present, high-quality clinical studies are still needed to provide data support for the construction of standardized processes.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.