ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

Objective:To investigate the differences in prognosis between different surgical approaches in elderly patients with advanced ovarian cancer.Methods:Based on the Surveillance, Epidemiology and End Results (SEER) database, a cohort of elderly patients with advanced ovarian cancer from 2000 to 2020 was established. Through propensity score matching, 2 094 patients were selected from those who underwent two different surgical approaches to form a matched cohort (SEER database cohort), including 1 039 patients who received cytoreductive surgery and 1 055 patients who underwent local resection. Meanwhile, 148 elderly patients with advanced ovarian cancer who were treated at the First Affiliated Hospital of Shandong First Medical University from January 2012 to January 2024 were selected (hospital cohort), among whom 85 underwent cytoreductive surgery and 63 underwent local resection. The prognostic differences among patients who underwent cytoreductive surgery and local resection in two cohorts and stratified by the International Federation of Gynecology and Obstetrics (FIGO) staging were evaluated, respectively. The relationship between the causes of death and surgical approaches in elderly patients with advanced ovarian cancer was analyzed.Results:In the SEER database cohort, the median overall survival (OS) for patients who underwent cytoreductive surgery and local resection was 37 and 40 months, respectively, with 5-year OS rates of 31.47% and 33.74%, with no statistically significant difference ( χ2=0.78, P=0.378). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC who underwent cytoreductive surgery ( n=998) and local resection ( n=962) was 38 and 40 months, respectively, with no statistically significant difference ( χ2=0.20, P=0.659). For patients with stage Ⅳ, the median OS for those who underwent cytoreductive surgery ( n=41) and local resection ( n=93) was 17 and 36 months, respectively, with a statistically significant difference ( χ2=9.37, P=0.002). Among 2 094 elderly patients with advanced ovarian cancer, 1 581 had clearly identified causes of death. In patients who underwent cytoreductive surgery, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 94.52% (742/785) and 5.48% (43/785), respectively. In patients who underwent local resection, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 91.46% (728/796) and 8.54% (68/796), respectively. There was a statistically significant difference in the distribution of causes of death between the two surgical approaches ( χ2=5.69, P=0.017). In the hospital cohort, the median OS for patients undergoing cytoreductive surgery and local resection was 39 and 51 months, respectively, with 5-year OS rates of 22.85% and 23.81%, with a statistically significant difference ( χ2=6.71, P=0.010). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC undergoing cytoreductive surgery ( n=29) and local resection ( n=26) was 50 and 51 months, respectively, with no statistically significant difference ( χ2=0.15, P=0.699) ; for patients with stage Ⅳ undergoing cytoreductive surgery ( n=56) and local resection ( n=37), the median OS was 35 and 47 months, respectively, with a statistically significant difference ( χ2=6.55, P=0.011) . Conclusions:The survival outcomes of local resection in elderly patients with advanced ovarian cancer are not inferior to those of cytoreductive surgery. For FIGO stage Ⅳ patients, the survival period following local resection is superior to that of cytoreductive surgery.

Objective To compare the safety and efficacy of flow diverter with adjunctive spring coils(FAC)and simple flow diverter(FD)in the treatment of large or giant intracranial aneurysms.Methods The clinical data of 48 patients with large or giant intracranial aneurysm(55 intracranial aneurysms in total),who were treated at the First Affiliated Hospital of Zhengzhou University of China from January 2018 to September 2023,were retrospectively analyzed.According to the treatment method,the patients were divided into pure FD group and FAC group.The aneurysm occlusion rate and the incidence of procedure-related complications were compared between the two groups.Univariate and multivariate logistic regression analyses were used to identify risk factors for procedure-related complications.Results A total of 55 intracranial aneurysms detected in the 48 patients were included in this study.The median maximum diameter of aneurysms was 20.25 mm(16.45,24.62 mm).Among them,12 aneurysms were treated with FD alone,and 43 aneurysms were treated with FAC.The median follow-up time was 6.63 months(5.88,8.07 months).Compared with pure FD group,in FAC group the occlusion rate of aneurysms was significantly higher(86.1％vs.50.0％,P=0.023),while there was no statistically significant difference in the incidence of procedure-related complications between the two groups(18.18％vs.16.67％,P=1.000).Multivariate logistic regression analysis showed that the use of more than one stent(OR=6.63,95％CI=1.10-39.88,P=0.039)and the difference between the distal parent artery diameter and the stent diameter(Dd)(OR=7.00,95％CI=1.4-35.7,P=0.019)were the independent risk factors for procedure-related complications.The area under the receiver operating characteristic curve(AUC)of the receiver operating characteristic curve(ROC)for distal parent artery Dd was 0.854(95％CI=0.746-0.963).Conclusion For the treatment of large or giant intracranial aneurysms,FAC is clinically safe and effective.The mid-term follow-up aneurysm occlusion rate of FAC is higher than that of simple FD treatment.The use of more than one stent and the distal parent artery Dd are the independent risk factors for procedure-related complications in the treatment of large or giant intracranial aneurysms with FD.

Alcoholic liver disease （ALD） poses a serious threat to the health of drinkers worldwide， and establishing appropriate animal models of ALD is an important foundation for conducting disease-related research. Due to the physiological and pathophysiological differences between rodents and humans， alcohol feeding alone is difficult to induce a model that closely matches the disease manifestations in humans， and therefore， the “two-hit” hypothesis （ combining alcohol with another liver injury factor to induce the expected state of liver injury） has been widely used. This article classifies the more commonly used and effective “two-hit” regimens into three major categories of special diets， chemical substances， and genetic engineering， which are divided into high-fat diet， high-iron diet， carbon tetrachloride， lipopolysaccharide， and genetic engineering for further analysis. Although these five “two-hit” models have their own advantages and disadvantages， they can nearly cover the disease spectrum of ALD. In the future， the development of ALD animal models can focus on narrowing the pathophysiological differences in alcohol-induced liver injury between animals and humans and simulating more complex drinking patterns in humans.

Objective:To evaluated the efficacy and safety of eltrombopag in patients with systemic lupus erythematosus (SLE)-related refractory immune thrombocytopenia (ITP).Methods:Nine patients with severe SLE-associated refractory ITP were recruited the People's Hospital of Xinjiang Uygur Automomous Region from Septermber 2021 to February 2024 and received eltrombopag 50 mg orally daily for 1 month; basic patient information, platelet counts, other laboratory parameters and adverse events were recorded. Normally distributed continuous data were expressed as mean±standard deviation ( Mean±SD) and compared using paried samples t-test; non-normally distributed data were presented as median (interquartile range) [ M( Q1, Q3)]; categorical variables were described as n (%). Results:Eight participants (88.9%) completed the study, and at 1 month, five patients showed significant improvement in subcutaneous bleeding and erythema of the skin and mucous membranes, and three patients showed significant relief of joint and muscle involvement, and the patients′ platelet counts were (16.9±9.6)×10 9/L before treatment and increased to (114.0±53.9)×10 9/L. Differences in platelet levels before and after treatment in intergroup comparisons ( t=-4.881 , P=0.002), of which 4 patients achieved complete remission of platelet involvement, 3 patients achieved partial remission of platelet involvement, 4 cases were significantly efficacious and 3 cases efficacious. Follow-up data showed that platelet counts remained normal with no significant adverse events and one patient discontinued the study after 2 weeks of eltrombopag due to abnormal blood counts. Conclusion:Eltrombopag may be a promising new option for patients with SLE-associated refractory ITP with satisfactory remission rates, but large sample studies are needed for validation.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.

Decreased exercise tolerance is a common clinical issue in children with congenital heart disease (CHD), significantly impacting their long-term quality of life and increasing the risk of adverse cardiovascular events.However, due to the complexity of CHD, the diversity of assessment methods, and the limitations in equipment accessibility, standardized protocols for evaluating and intervening in exercise tolerance are still lacking.In order to provide a basis for improving exercise tolerance in children with CHD, the latest domestic and international research on the assessment and intervention of exercise tolerance in children with CHD was systematically summarized.The applicability, advantages, and limitations of existing methods, including cardiopulmonary exercise testing, the 6-minute walk test, and smart wearable devices in clinical practice were discussed.Furthermore, the effectiveness of various intervention strategies (such as exercise training, nutritional management, surgical correction, and pharmacological treatment) in improving exercise tolerance was analyzed.

Objective:To analyze the research hotspots and trends in the stigmatization of adolescents living with HIV/AIDS.Methods:Relevant literature was retrieved from the Web of Science Core Collection database, with the search covering from database inception to May 1, 2024. CiteSpace software was used to conduct bibliometric analysis, including the distribution of countries, institutions, authors, keywords, and cited references. Knowledge maps were generated to visualize the findings.Results:A total of 414 articles were included in the analysis. The number of publications has shown an overall upward trend. The United States had the highest number of publications (244 articles), the most productive institution was University of Cape Town (31 articles), and the most productive author was Linda-Gail Bekker (9 articles). Research hotspots mainly focused on stigmatization, behavioral patterns, mental health, treatment adherence, social support, and intervention models.Conclusions:Research on the stigmatization of adolescents living with HIV/AIDS is currently at a critical stage. Future studies should continue to explore the multidimensional impact of stigma and focus on the development of region-specific and individualized intervention models, while actively constructing a comprehensive support system within the field of public health.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.