ObjectiveTo verify the therapeutic effect of Yinqi Sanhuang Jiedu decoction （YQSH） on carbon tetrachloride （CCl₄）-induced hepatic fibrosis in mice， and to explore whether its effect was related to the inhibition of neutrophil infiltration and the formation of neutrophil extracellular traps （NETs）. MethodsThe 36 C57BL/6J mice were randomly divided into control group， model group， positive drug silybin （SF） group （55 mg·kg^-1·d^-1）， YQSH-L group， YQSH-M group， and YQSH-H group （8.325， 16.65， 33.3 g·kg^-1·d^-1， respectively），n=6 in each group. Except for the control group， mice in all other groups were intraperitoneally injected with CCl₄ to induce hepatic fibrosis. After successful modeling， each drug administration group was given the corresponding drugs by gavage for eight weeks. Hematoxylin-eosin （HE） staining， Sirius red staining and Masson staining were used to observe the pathological changes of liver tissue. Liver elasticity was detected by a color Doppler ultrasound system. Immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were performed to detect the protein expression and mRNA levels of C-X-C motif chemokine ligand 1 （CXCL1）， CXCL2 and CXCL5. Neutrophil levels were detected by flow cytometry. The expression of neutrophil elastase （NE） and myeloperoxidase （MPO） positive protein was observed by immunofluorescence. The contents of MPO， NE and CitH3 were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the control group， the liver of the model group showed obvious inflammatory cell infiltration and collagen deposition， and the liver elasticity， CXCL1， CXCL2， CXCL5 expression， neutrophil level， and MPO， NE and CitH3 levels were significantly increased （P<0.05， P<0.01）. Compared with the model group， inflammatory cell infiltration and collagen deposition in the liver tissue of mice were reduced after YQSH treatment. Moreover， the liver elasticity was reduced （P<0.01）. The protein expression （P<0.01） and mRNA level of CXCL1， CXCL2 and CXCL5 were decreased（P<0.05，P<0.01）. The neutrophil level was decreased （P<0.01）， the expression of MPO and NE positive protein was significantly decreased（P<0.05，P<0.01）， and the levels of MPO， NE and CitH3 were decreased （P<0.05， P<0.01）. ConclusionThe anti-hepatic fibrosis effect of YQSH may be related to its inhibition of chemokines （CXCL1， CXCL2， CXCL5）， reduction of neutrophil infiltration， and inhibition of NETs generation.

ObjectiveTo verify the therapeutic effect of Yinqi Sanhuang Jiedu decoction （YQSH） on carbon tetrachloride （CCl₄）-induced hepatic fibrosis in mice， and to explore whether its effect was related to the inhibition of neutrophil infiltration and the formation of neutrophil extracellular traps （NETs）. MethodsThe 36 C57BL/6J mice were randomly divided into control group， model group， positive drug silybin （SF） group （55 mg·kg^-1·d^-1）， YQSH-L group， YQSH-M group， and YQSH-H group （8.325， 16.65， 33.3 g·kg^-1·d^-1， respectively），n=6 in each group. Except for the control group， mice in all other groups were intraperitoneally injected with CCl₄ to induce hepatic fibrosis. After successful modeling， each drug administration group was given the corresponding drugs by gavage for eight weeks. Hematoxylin-eosin （HE） staining， Sirius red staining and Masson staining were used to observe the pathological changes of liver tissue. Liver elasticity was detected by a color Doppler ultrasound system. Immunohistochemistry and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were performed to detect the protein expression and mRNA levels of C-X-C motif chemokine ligand 1 （CXCL1）， CXCL2 and CXCL5. Neutrophil levels were detected by flow cytometry. The expression of neutrophil elastase （NE） and myeloperoxidase （MPO） positive protein was observed by immunofluorescence. The contents of MPO， NE and CitH3 were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the control group， the liver of the model group showed obvious inflammatory cell infiltration and collagen deposition， and the liver elasticity， CXCL1， CXCL2， CXCL5 expression， neutrophil level， and MPO， NE and CitH3 levels were significantly increased （P<0.05， P<0.01）. Compared with the model group， inflammatory cell infiltration and collagen deposition in the liver tissue of mice were reduced after YQSH treatment. Moreover， the liver elasticity was reduced （P<0.01）. The protein expression （P<0.01） and mRNA level of CXCL1， CXCL2 and CXCL5 were decreased（P<0.05，P<0.01）. The neutrophil level was decreased （P<0.01）， the expression of MPO and NE positive protein was significantly decreased（P<0.05，P<0.01）， and the levels of MPO， NE and CitH3 were decreased （P<0.05， P<0.01）. ConclusionThe anti-hepatic fibrosis effect of YQSH may be related to its inhibition of chemokines （CXCL1， CXCL2， CXCL5）， reduction of neutrophil infiltration， and inhibition of NETs generation.

Background The moderation role of environmental factors in the spread of hand-foot-and-mouth disease (HFMD) has attracted much attention, but the existing conclusions are inconsistent. For example, some scholars believe that high temperature, high humidity, and high concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) increase the risk of HFMD, but other scholars have reached the opposite conclusion, or believe that there is no significant relationship. Objective Based on distributed lag nonlinear model (DLNM), to investigate the relationship between the incidence of HFMD and meteorological and air pollutant variables in Lianyungang City, and to provide scientific basis for early warning. Methods Daily data of meteorological factors and air pollutants in Lianyungang City from 2021 to 2024 were retrieved. Meteorological factors included average daily temperature, average wind speed, average air pressure, and relative humidity. Air pollutant indicators included PM_2.5, inhalable particulate matter (PM₁₀), carbon monoxide (CO), sulfur dioxide (SO₂), NO₂, and ozone (O₃). Spearman correlation analysis was used to analyze their correlations with HFMD, and the R package (version 4.3.1) dlnm was used to construct a DLNM model. Results During the study period, a total of 10503 cases were reported, with a male to female ratio of 1.47∶1 and the highest proportion of scattered children (49.97%). The Spearman correlation analysis results showed that daily average temperature (r=0.40), relative humidity (r=0.17) and O₃ (r=0.14) were positively correlated with the incidence of HFMD (all Ps<0.01), while average air pressure (r=−0.34), PM_2.5 (r=−0.24), PM₁₀ (r=−0.24), CO (r=−0.22), and NO₂ (r=−0.06) were negatively correlated with it (all Ps<0.05). There was no statistical relationship of SO₂ and average wind speed with the incidence of HFMD (both Ps>0.05). The cumulative risk effect was greatest when the daily average temperature was 28.50 ℃ (CRR=4.63, 95%CI: 2.68, 8.01). The average wind speed below 0.50 m·s⁻¹ and in the range of 2.50-3.50 m·s⁻¹ showed an acute risk effect, and low pressure (below 1016.00 hPa) could immediately increase the risk of the disease. The cumulative risk effect was greatest when the relative humidity was 100% (CRR=3.16, 95%CI: 1.77, 5.65). The greatest cumulative protective effects of PM_2.5 and PM₁₀ were present at concentrations of 158.00 μg·m⁻³ (CRR=0.12, 95%CI: 0.01, 0.99) and 561.50 μg·m⁻³ (CRR=0.01, 95%CI: 0.01, 0.99) respectively. The protective effect of CO was the strongest at the highest concentration (67.00 μg·m⁻³) (RR=0.67, 95%CI: 0.34, 0.64). The cumulative protective effects of SO₂ and NO₂ were both most significant at the concentration of 0.50 μg·m⁻³. Low concentrations of O₃ (below 48.00 μg·m⁻³) showed a risk effect, and the single-day protective effect was significant when the concentration was 141.00 μg·m⁻³. Conclusion There is a nonlinear and hysteretic relationship between environmental factors and the incidence of HFMD. A rational and efficient early warning and prevention and control system can be constructed accordingly.

Cavernous transformation of the portal vein （CTPV） is a significant challenge in clinical practice. In recent years， transjugular intrahepatic portosystemic shunt has gradually been applied in the treatment of CTPV patients， but it had a technical success rate and a relatively high surgical risk. The scholars have adopted various modified techniques of portosystemic shunt to improve success rate and safety. However， for CTPV patients with extensive occlusion of the main portal vein， this surgery remains difficult， and individualized strategies for portosystemic shunt should be formulated. This article reports a case of CTPV treated by transjugular extrahepatic portosystemic shunt assisted by endoscopic ultrasound-guided portal vein localization， in order to explore a new pathway for the clinical management of patients with CTPV.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective:With the help of the advanced ACD Labs/AutoChrom method development software,param-eter simulation design was carried out.Based on the results of software simulation and actual investigation,an HPLC method for the determination of related impurities in safinamide mesylate raw material drug was established.Methods:A Waters Atlantis T3 column(4.6 mm ×250 mm,5 μm)was used.The phosphate buffer with a pH of 7.0 was used as mobile phase A,and acetonitrile was used as mobile phase B.Gradient elution was performed at a flow rate of 1.3 mL·min-1,the detection wavelength was 228 nm,the column temperature was 35 ℃,and the injection volume was 10 μL.Results:Impurities 1-12 in safinamide mesylate could be effectively separated from the main component.The linear ranges were 0.102 1-5.329,0.102 9-5.379 7,0.106 8-4.972 9,0.102 1-5.135,0.103 8-5.314 7,0.097 7-4.869 8,0.095 2-4.760 5,0.095 3-5.109 5,0.050 5-5.287 5,0.098 7-4.885 6,0.102 4-4.997 5,0.050 8-5.134 7 μg·mL-1,respectively.The limits of detection(LOD)were 0.051,0.051 4,0.053 4,0.051 1,0.051 9,0.048 8,0.047 6,0.047 7,0.025 3,0.049 3,0.051 2,0.025 4 μg·mL-1,and the limits of quantification(LOQ)were 0.102 1,0.102 9,0.106 8,0.102 1,0.103 8,0.097 7,0.095 2,0.095 3,0.050 5,0.098 7,0.102 4,0.050 8 μg·mL-1.The accuracy,preci-sion and durability all met the requirements.Conclusion:This method is suitable for the determination and quality control of the related substances of 12 impurities in safinamide mesylate raw materials.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

The International Society for Heart and Lung Transplantation released 2025 guidelines for the management of heart failure in children, which is an update of the 2014 edition.The new guidelines deeply integrate major advancements in the field of adult heart failure (such as the application of angiotensin receptor-neprilysin inhibitors and sodium-dependent glucose transporters 2 inhibitor) with the uniqueness and complexity of pediatric heart failure.They propose more refined heart failure staging, classification, diagnostic evaluation processes, and treatment strategies while systematically emphasizing, for the first time, the importance of complication management and palliative care.This article aims to provide an in-depth interpretation of the core updates and highlights of 2025 guidelines and offer insights and recommendations for clinical practice, research directions, and the revision of guidelines/consensus in the field of pediatric heart failure in China based on China′s national conditions.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*