The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective:To conduct a scoping review of financial toxicity assessment tools both domestically and internationally,and to summarize their scoring methods,evaluation content,development approaches,reliability/validity,and application status,aiming to provide references for selecting or developing such tools.Methods:Following scoping review methodology,databases including CNKI,VIP,Wanfang,PubMed,Web of Science,Embase,and CINAHL were searched for studies on financial toxicity assessment tools,with the search period spanning from database inception to Oct 8,2024.Results:A total of 34 eligible studies were included,covering 14 financial toxicity assessment tools.These tools primarily focused on economic status,psychosocial responses,or coping behaviors.Tools developed by domestic scholars exhibited strong specificity but lacked generalizability.Conclusions:Existing financial toxicity assessment tools are diverse,yet their reliability and validity in Chinese patient populations require further validation.Most scales lack comprehensive dimensions,and domestically developed tools are overly specific.A universal assessment tool suitable for China's cultural and policy environment needs to be developed.

Lung cancer patients frequently experience multiple co-occurring symptoms that manifest as symptom clusters during treatment,severely compromising patients'quality of life.Sentinel symptoms,coexisting with symptom clusters,serve as predictive indicators for the emergence of these clusters.This study focuses on sentinel symptoms within symptom clusters in lung cancer patients,reviewing the current research status,identification methods,related intervention measures,and exist-ing research shortcomings.It summarizes the problems in current studies,with the goal of providing clinical nursing staff to as-sess and manage symptom clusters,as well as to conduct related nursing research.

Objective:To conduct a scoping review of financial toxicity assessment tools both domestically and internationally,and to summarize their scoring methods,evaluation content,development approaches,reliability/validity,and application status,aiming to provide references for selecting or developing such tools.Methods:Following scoping review methodology,databases including CNKI,VIP,Wanfang,PubMed,Web of Science,Embase,and CINAHL were searched for studies on financial toxicity assessment tools,with the search period spanning from database inception to Oct 8,2024.Results:A total of 34 eligible studies were included,covering 14 financial toxicity assessment tools.These tools primarily focused on economic status,psychosocial responses,or coping behaviors.Tools developed by domestic scholars exhibited strong specificity but lacked generalizability.Conclusions:Existing financial toxicity assessment tools are diverse,yet their reliability and validity in Chinese patient populations require further validation.Most scales lack comprehensive dimensions,and domestically developed tools are overly specific.A universal assessment tool suitable for China's cultural and policy environment needs to be developed.

Lung cancer patients frequently experience multiple co-occurring symptoms that manifest as symptom clusters during treatment,severely compromising patients'quality of life.Sentinel symptoms,coexisting with symptom clusters,serve as predictive indicators for the emergence of these clusters.This study focuses on sentinel symptoms within symptom clusters in lung cancer patients,reviewing the current research status,identification methods,related intervention measures,and exist-ing research shortcomings.It summarizes the problems in current studies,with the goal of providing clinical nursing staff to as-sess and manage symptom clusters,as well as to conduct related nursing research.

Objective:To analyze the effectiveness of multi-layer silicone foam dressing in preventing pressure injury of sacrococcygeal and heel by systematic evaluation.Methods:Randomized controlled studies on the effectiveness of multi-layer silicone foam dressings in preventing stress injury of sacrococcygeal and heel of hospitalized patients in CNKI, Wanfang, VIP, CBM, PubMed, Embase, The Cochrane Library and Web of Science were systematically reviewed. The retrieval time was from January 2012 to January 2023, and the Meta were screened and extracted by two researchers respectively. After evaluating the bias risk of the included studies, they were conducted by RevMan 5.4 software.Results:Eight randomized controlled studies involving 4 725 patients were included. Meta-analysis showed that multilayer silicone foam dressing could reduce the incidence of sacrococcygeal stage I pressure injury ( RR=0.18, 95% CI 0.09-0.35, P<0.01), and reduce the incidence of the first-stage heel pressure injury ( RR=0.29, 95% CI 0.13-0.66, P<0.05). It could reduce the incidence of sacrococcygeal stage Ⅱ and more serious pressure injury ( RR=0.42, 95% CI 0.31-0.58, P<0.01), but the influence on the incidence of the second-stage heel pressure injury and more serious heel pressure injury was not clear ( RR=0.52, 95% CI 0.27-0.99, P=0.05) Conclusions:Multi-layer silicone foam dressing can effectively reduce the incidence of sacrococcygeal pressure injury and reduce the incidence of first-stage pressure injury in heel, but the impact on the incidence of second-stage and more serious pressure injury in heel is still unclear.

Immune checkpoint inhibitors(ICIs)are an emerging tumor treatment approach following traditional surgery,chemoradiotherapy and targeted therapy.They have proven to be effective in a variety of cancers.However,they may induce immune-related adverse events(irAEs)during treatment,which may affect patients'quality of life and lead to treatment interruption or cessation.The key to preventing irAEs is early evaluation and identification of medical staff.Therefore,this article reviews the clinical manifestations and influencing factors of irAEs to help the early identification of high-risk groups and provide reference for clinical nursing work.

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.

ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C₁₈ column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min^-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively. ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g^-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）. ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.