Objective To explore the clinical values of non-invasive myocardial work (MW) and tissue motion annular displacement (TMAD) in evaluation of anthracycline therapy-related cardiac dysfunction in patients with non-Hodgkin lymphoma. Methods A total of 62 patients with non-Hodgkin lymphoma who received standardized chemotherapy based on doxorubicin. Two and three dimensional transthoracic echocardiography, along with two dimensional speckle tracking echocardiography, were performed one day before chemotherapy and at 3, 6, and 9 months after chemotherapy to assess left ventricular ejection fraction, global longitudinal strain (GLS), MW parameters, and TMAD. Logistic regression analysis was used to evaluate the risk factors for cancer therapy-related cardiac dysfunction (CTRCD). The receiver operating characteristic curve was used to assess the diagnostic values of MW- and TMAD-related parameters for CTRCD. Results Compared to baseline, GLS, global work index (GWI), global constructive work (GCW), global work efficiency (GWE), TMAD at midpoint (TMADmid), and TMADmid percentage of left ventricular long-axis diameter (TMADmid%) decreased at 3 months after chemotherapy, while global wasted work (GWW) increased at 6 months after chemotherapy (P＜0.05). Logistic regression analysis showed that the relative reduction in GLS and TMADmid% at 3 months after chemotherapy were independent predictors for CTRCD （P＜0.05), while MW parameters were not independent predictors for CTRCD. GLS reduction≥10.3% and TMADmid% reduction≥15.8% at 3 months after chemotherapy predicted CTRCD with 0.866 and 0.824 of area under the curve (AUC), 92% and 75% of sensitivity, and 74% and 80% of specificity, respectively. AUC of combination of two indexes improved to 0.905, with 75% of sensitivity and 90% of specificity. Conclusions In non-Hodgkin lymphoma patients, the combination of GLS and TMADmid% is helpful of predicting CTRCD early, TMAD may be a novel diagnostic index for CTRCD, and GLS has superior predictive performance than MW for CTRCD.

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

Systemic sclerosis is an autoimmune rheumatic disease that often leads to multisystem diseases,frequently resulting in pulmonary interstitial fibrosis.According to the theory of sanjiao(triple energizers)membranous channels,sanjiao connects the five zang-organs and six fu-viscera internally and the skin,muscles,and bones externally.It serves as a four-way membranous channel that connects internal organs and external structures,linking with the micromembranes of organs and blood vessels.The pathogenesis of pulmonary interstitial fibrosis secondary to systemic sclerosis involves external cold obstructing the skin and interstitial layers,impairing the defense qi and defense yang,which originate in the essence of the kidney.This leads to weak defensive qi and kidney deficiency,causing stagnation in sanjiao's energy flow and disruption of water and gasification and loss of fluid,resulting in accumulation of dampness,phlegm,and blood stasis.These obstructive factors spread along sanjiao's membranous channels,leading to multiorgan micromembrane involvement and systemic damage.The lungs,which are in direct contact with the external environment,are particularly susceptible to invasion by external pathogens.When combined with stagnation of dampness,phlegm,and blood in the lungs,this leads to secondary pulmonary fibrosis,resulting in lung dysfunction.Continuous stagnation of sanjiao exacerbates the overall condition of the patient,leading to a mixed cold-heat imbalance.Treatment focuses on"unblocking,transforming,and regulating"to restore sanjiao function,promote qi and fluid circulation,invigorate blood,and adjust the cold-heat imbalance,ultimately restoring the overall condition of the patient.

Objective To observe the efficacy and safety of Yifei Sanjie Decoction in the treatment of multiple pulmonary nodules.Methods A prospective randomized controlled clinical study was conducted to select 189 patients with multiple pulmonary nodules who saught medical attention at the Pulmonary Nodule Diagnosis and Treatment Center of Dongfang Hospital,Beijing University of Chinese Medicine and the Department of Thoracic Surgery of Beijing Shijitan Hospital Affiliated to Capital Medical University from January 2023 to March 2025.According to the random number table method,126 cases were randomly divided into the trial group and 63 cases in the blank control group at a ratio of 2∶1.The trial group was treated with modified Yifei Sanjie Decoction,and the blank control group was only followed up without intervention.The course of treatment was 3 months.The patients in the two groups were reexamined with lung CT after 3 months.The efficacy was evaluated by the area reduction rate of the major pulmonary nodules and the cumulative multiple pulmonary nodules in patients with multiple pulmonary nodules combined with the average diameter and malignant signs.According to the property of the major pulmonary nodules,we divided the patients into ground glass,solid,and mixed ground glass subgroups to evaluate the efficacy of different types of pulmonary nodules.We evaluated the change of malignant risk of pulmonary nodules according to the change of Mayo score.We evaluated the safety of the treatment medicine by blood routine,urine routine,and liver and kidney function.Results A total of 175 patients completed the study,117 in the trial group and 58 in the blank control group.The total effective rates of the major pulmonary nodules and the cumulative multiple pulmonary nodules in the trial group were 41.03%and 42.74%,respectively,the total effective rate of nodule number change was 29.91%which were significantly higher than those in the blank control group(P<0.05).In the trial group,the total effective rates of the major pulmonary nodules in the ground glass(72 cases),solid(28 cases),and mixed ground glass(17 cases)subgroups were 40.28%,32.14%,and 58.82%,respectively,the total effective rates of the cumulative multiple pulmonary nodules were 38.89%,42.86%,and 58.82%,respectively,which were significantly higher than those in corresponding subgroups of ground glass(37 cases),solid(14 cases),and mixed ground glass(7 cases)of the blank control(P<0.05).After treatment,the average diameter,area,and Mayo score of the major pulmonary nodules and the cumulative multiple pulmonary nodules in the trial group were significantly lower than those in the blank control group and before treatment(P<0.05),the average diameter,area,and Mayo score of the major pulmonary nodules and the cumulative multiple pulmonary nodules in the ground glass,solid,and mixed ground glass subgroups were lower than those in corresponding subgroups of the blank control group,and significantly lower than those before treatment(P<0.05).The number of nodules and malignant signs in the trial group were lower than before,while those in the blank control group were higher than before.There were no serious adverse events in the two groups during the study.Conclusion Yifei Sanjie Decoction can effectively treat the major pulmonary nodules and the cumulative multiple pulmonary nodules in patients with multiple pulmonary nodules,reduce the average diameter and area of nodules,reduce the Mayo score,and reduce the malignant signs and number of nodules.In the ground glass,solid,and mixed ground glass groups,the curative effect is well,and the safety is high,it can be used for the clinical treatment of multiple pulmonary nodules.

Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.

Objectives:To explore the value of non-invasive myocardial work combined with myocardial contrast echocardiography(MCE)in the early diagnosis of coronary artery disease and its efficacy in stratifying the severity of coronary vessel lesions.Methods:A total of 130 patients with suspected coronary artery disease admitted to the First Affiliated Hospital of Dalian Medical University from June 2024 to January 2025 were enrolled in this study.All patients underwent echocardiography and MCE after admission,and coronary angiography(CAG).Based on CAG results,patients were divided into non-CAD group(n=45,coronary artery stenosis<50%)and CAD group(n=85,coronary artery stenosis≥50%).Patients in CAD group were further divided into low-score CAD group(≤49 points,n=43)and high-score CAD group(>49 points,n=42)according to the median of Gensini score(49 points).Non-invasive MW indices and quantitative MCE parameters were assessed.A binary logistic regression model was used to construct a combined diagnostic model,and the value of each parameter in diagnosing CAD and evaluating the severity of coronary lesions was calculated.The receiver operating characteristic(ROC)curve of subjects was estimated,and the area under the curve(AUC)was calculated to evaluate its sensitivity and specificity for early diagnosis of coronary heart disease.Results:Compared with the non-CAD group,the global longitudinal strain,global work index(GWI),and global constructive work(GCW)in both low-score and high-score CAD groups were significantly lower(all P<0.05),and the global work efficiency in the high-score CAD group was significantly reduced(P<0.05).MCE indices in both low-score and high-score CAD groups were significantly lower than those in the non-CAD group(all P<0.05).The multivariate logistic stepwise regression analysis and ROC curve showed that GWI(OR=0.997,95%CI:0.995-0.999,P=0.003)and A value(representing the peak intensity of the curve,reflecting myocardial blood volume(OR=0.415,95%CI:0.246-0.698,P=0.001)were independent predictors of low-score CAD.The combined diagnostic sensitivity and specificity for low-score coronary artery disease were 72.1%and 88.9%respectively,with an AUC of 0.851.GCW(OR=0.997,95%CI:0.995-1.000,P=0.019)and β-value(OR=0.000,95%CI:0.000-0.003,P<0.001)were independent predictors of high-score CAD.The combined diagnostic sensitivity and specificity for high-score coronary artery disease were 88.1%and 88.9%respectively,with an AUC of 0.934.Conclusions:Both non-invasive myocardial work parameters and MCE parameters have high diagnostic efficacy for coronary artery lesions of various degrees.The combined application of the two methods significantly improves the accuracy of coronary artery disease diagnosis,with improved sensitivity and specificity than single technique.Our results provide a new non-invasive comprehensive diagnostic model for clinical early diagnosis and risk stratification of coronary artery disease.

OBJECTIVE To offer references and implementation paths for updating and enhancing the China’s current essential medicines list system， formulating a specific list of essential medicines for children in China， promoting the research and development of pediatric medications， and improving the accessibility and safety of pediatric medications for children. METHODS Comparative and descriptive analysis was utilized to statistically analyze the classification， dosage forms， specifications， disease spectrum， and symbolic annotations of the 9th edition of the WHO Model List of Essential Medicines for Children （WHO EMLc）. Differences were compared among WHO EMLc， the 2018 National Essential Medicines List （NEML）， and five batches of the List of Encouraged R&D and Declaration of Pediatric Drugs issued by the National Health Commission from 2016 to 2024. The availability of drugs in the 9th edition of WHO EMLc in China was discussed. RESULTS & CONCLUSIONS The differences between the two lists were relatively substantial. A total of 101 drugs overlapped， accounting for 27.98% of the total number of drugs in the 9th edition of the WHO EMLc. Compared with the 2018 NEML， the 9th edition of the WHO EMLc showed notable advantages in the diversity of pediatric-appropriate drug types， dosage form adaptability， and specification precision. The List of Encouraged R&D and Declaration of Pediatric Drugs， to some extent， had filled the gap in China’s pediatric medications， enriching the variety of drug types and dosage forms for children. However， nearly 80% of the drugs on the list were not yet marketed， still facing problems such as a low R&D conversion rate and insufficient policy incentive effects. It is recommended to establish a tiered and classified pediatric essential medicines list based on China’s national conditions， drawing on the selection experience of the WHO and developed countries/regions； strengthen support for the R&D of appropriate pediatric dosage forms and specifications； implement policy preferences throughout the entire cycle of application， review and procurement； encourage evidence-based pediatric practices， accelerate the R&D， market launch， and selection processes of pediatric essential medicines， and ensure the accessibility of pediatric medicines.

Secondary organizing pneumonia after infection is a pathological condition characterized by connective tissue filling and obstructing the alveoli and bronchioles, in which following an infection in the lung, the inflammatory response is not controlled in a timely and effective manner. The pathogenesis and treatment of this condition can be interpreted through the Sanjiao membranous tube theory and the concept of stagnation within the pulmonary micro-membrane. Sanjiao is conceptualized as a four-way membranous tube that internally connects with the zangfu organs and externally with the skin and muscles, enabling the circulation of energy and fluids throughout the body. It also maintains communication with the zangfu micro-membranes. Within the lungs, the pulmonary micro-membrane is distributed and connected to the upper jiao membranous tube, facilitating the movement of qi and fluids and supporting nutrient distribution. External pathogens may invade the Sanjiao membranous system through the external membranous tube, travel internally along this system, and transform into latent pathogens that settle within the pulmonary micro-membrane. These latent pathogens can subsequently transform into heat or dampness, leading to the depletion of lung qi and impairing the lung′s ability to regulate and transport body fluids. Consequently, fluids may seep into the pulmonary micro-membrane, where they are transformed into dampness, turbidity, and phlegm. The accumulation of damp-turbidity and phlegm obstructs the flow of qi and blood, resulting in blood stasis in the pulmonary collaterals. This stagnation occurring within both the pulmonary micro-membrane and its associated collaterals underlies the development of secondary organizing pneumonia after infection. In severe cases, this condition may progress to pulmonary interstitial fibrosis. The therapeutic approach emphasizes expelling latent pathogens, regulating and dredging the pulmonary micro-membrane, tonifying the healthy qi, and supporting health. Regulating and dredging the pulmonary micro-membrane is a crucial step, with a focus on promoting the flow of lung qi, resolving dampness and phlegm, and activating blood circulation to remove stasis.

The vasculature plays a critical role in homeostasis and health as well as in the development and progression of a wide range of diseases, including cancer, cardiovascular diseases, metabolic diseases (and their complications), chronic inflammatory diseases, ophthalmic diseases, and neurodegenerative diseases. As such, the growth of the vasculature mediates normal development and physiology, as well as disease, when pathologically induced vessels are morphologically and functionally altered owing to an imbalance of angiogenesis-stimulating and angiogenesis-inhibiting factors. This review offers an overview of the angiogenic process and discusses recent findings that provide additional interesting nuances to this process, including the roles of intussusception and angiovasculogenesis, which may hold promise for future therapeutic interventions. In addition, we review the methodology, including those of in vitro and in vivo assays, which has helped build the vast amount of knowledge on angiogenesis available today and identify important remaining knowledge gaps that should be bridged through future research.
Animals ; Signal Transduction/physiology* ; Humans ; Neovascularization, Pathologic/physiopathology* ; Neovascularization, Physiologic/physiology* ; Models, Animal ; Angiogenesis