ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Objective:To investigate the effect of applying the analog of miR-145(agomiR-145)to target a disintegrin and metallopro-tease 17(ADAM17)on the growth of triple-negative breast cancer(TNBC)xenograft tumors in nude mice and the underlying mecha-nism.Methods:A subcutaneous xenograft tumor model was established in nude mice with MDA-MB-231 cells(n=30).The 30 nude mice were randomly divided into agomiR group,agomiR-NC group,and control group to receive intratumoral injection of 100 μL of agomiR-145(0.33 g/L),agomiR-NC(0.33 g/L),and normal saline,respectively.We examined tumor tissue morphology with HE stain-ing;measured the expression of miR-145,ADAM17,and epidermal growth factor receptor(EGFR)in tumor tissues by real-time poly-merase chain reaction(RT-PCR);and determined the protein expression of ADAM17,EGFR,and p-EGFR in tumor tissues by immu-nohistochemistry and Western blot.Results:The tumor growth in the agomiR group was slow,with a significantly smaller tumor volume than those in the control group and the agomiR-NC group(P<0.05).The results of HE staining showed more severe necrosis and hem-orrhage within tumor tissues in the control group and the agomiR-NC group than in the agomiR group.RT-PCR results showed that the expression level of miR-145 in the agomiR group was significantly higher than those in the agomiR-NC and control groups(P<0.001);the agomiR group had a significantly lower mRNA expression level of ADAM17 than the other two groups(P<0.05);and there was no significant difference in EGFR mRNA expression between the three groups(P>0.05).Immunohistochemistry and Western blot detected significantly lower protein expression levels of ADAM17 and EGFR in the agomiR group than in the agomiR-NC group and the control group(P<0.05).Conclusion:AgomiR-145 inhibits the growth of TNBC xenografts in nude mice by targeted suppression of ADAM17-EGFR activity.

Objective:To systematically synthesize the experiences and needs of thyroid cancer patients and their stakeholders in participating in treatment decision-making, so as to provide evidence-based theoretical support for the development of localized decision aids and the implementation of shared decision-making in China.Methods:A systematic search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, VIP, Wanfang Data, and China Biomedical Literature Database for qualitative studies on the experiences and needs of thyroid cancer patients and their stakeholders in treatment decision-making. The search covered the period from the establishment of the databases to May 20, 2025. The 2020 version of the Joanna Briggs Institute (JBI) critical appraisal tool for qualitative research was used to assess study quality. Aggregative synthesis was applied to integrate the findings.Results:A total of 19 studies were included, from which 94 individual findings were extracted. These findings were categorized into 15 new categories and further synthesized into four overarching themes: role dynamics in treatment decision-making; challenging trade-offs between risks and benefits of treatment choices; multifactorial influences on treatment decisions; and multidimensional support needs.Conclusions:Treatment decision-making among thyroid cancer patients involves complex role identification, conflicting emotional experiences, and risk-benefit deliberations influenced by multiple factors. It is essential to build a "clinician-family-society" decision-support ecosystem encompassing informational, psychological, and social support. Future efforts should focus on developing culturally appropriate decision aids that integrate emotional support and innovative technologies to promote shared decision-making, enhance decision quality, and improve patient satisfaction.

Objective:To investigate effect of LncRNA C-terminal binding protein 1 antisense RNA 2(CTBP1-AS2)on malig-nant biological behavior of acute myeloid leukemia(AML)cells by regulating miR-433-3p/dipeptidyl peptidase 8(DPP8)signaling axis.Methods:AML cells HL-60 were randomly separated into si-NC group,si-CTBP1-AS2 group,si-CTBP1-AS2+anti-NC group,and si-CTBP1-AS2+anti-miR-433-3p group.CCK-8 method and EdU staining were applied to detect HL-60 cell proliferation.Flow cytometry was applied to detect HL-60 cells apoptosis.Transwell was applied to detect migration and invasion of HL-60 cells.Western blot was applied to detect expressions of PCNA,Bax,MMP-9 and DPP8 proteins in HL-60 cells.ELISA was applied to detect expres-sions of IFN-γ and IL-1β.Dual luciferase reporter gene experiment was applied to analyze interaction between LncRNA CTBP1-AS2 and miR-433-3p,and between miR-433-3p and DPP8.Results:Expressions of LncRNA CTBP1-AS2,DPP8 mRNA,A450,EdU posi-tive cells,number of migrating cells,number of invading cells,PCNA protein,MMP-9 protein,DPP8 protein and IL-1β protein ex-pressions of HL-60 cells in si-CTBP1-AS2 group were lower than si-NC group,miR-433-3p expression,apoptosis rate,Bax protein and IFN-γ protein expressions were higher than si-NC group(P<0.05).Compared with si-CTBP1-AS2 group and si-CTBP1-AS2+anti-NC group,miR-433-3p expression,apoptosis rate,and expressions of Bax protein and IFN-γ protein in si-CTBP1-AS2+anti-miR-433-3p group were decreased,DPP8 mRNA,A450,EdU positive cells,number of migrating cells,number of invading cells,PCNA protein,MMP-9 protein,DPP8 protein and IL-1β protein expressions were increased(P<0.05).LncRNA CTBP1-AS2 targeted negative regula-tion of miR-433-3p,while miR-433-3p targeted negative regulation of DPP8.Conclusion:Knocking down LncRNA CTBP1-AS2 may inhibit malignant biological behavior of AML cells,whose mechanism may be achieved by regulating miR-433-3p/DPP8 signaling axis.

Objective:To systematically synthesize the experiences and needs of thyroid cancer patients and their stakeholders in participating in treatment decision-making, so as to provide evidence-based theoretical support for the development of localized decision aids and the implementation of shared decision-making in China.Methods:A systematic search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, VIP, Wanfang Data, and China Biomedical Literature Database for qualitative studies on the experiences and needs of thyroid cancer patients and their stakeholders in treatment decision-making. The search covered the period from the establishment of the databases to May 20, 2025. The 2020 version of the Joanna Briggs Institute (JBI) critical appraisal tool for qualitative research was used to assess study quality. Aggregative synthesis was applied to integrate the findings.Results:A total of 19 studies were included, from which 94 individual findings were extracted. These findings were categorized into 15 new categories and further synthesized into four overarching themes: role dynamics in treatment decision-making; challenging trade-offs between risks and benefits of treatment choices; multifactorial influences on treatment decisions; and multidimensional support needs.Conclusions:Treatment decision-making among thyroid cancer patients involves complex role identification, conflicting emotional experiences, and risk-benefit deliberations influenced by multiple factors. It is essential to build a "clinician-family-society" decision-support ecosystem encompassing informational, psychological, and social support. Future efforts should focus on developing culturally appropriate decision aids that integrate emotional support and innovative technologies to promote shared decision-making, enhance decision quality, and improve patient satisfaction.

Objective:To identify the classification of neck and shoulder dysfunction in patients after neck lymph node dissection for head and neck tumors and analyze the characteristics of these dysfunctions.Methods:A convenience sampling method was used to select patients who underwent neck lymph node dissection and visited the Head and Neck Cancer Rehabilitation Nursing Clinic at Beijing Tongren Hospital, Capital Medical University, from March to May 2024. General data questionnaires, neck function indicators, and shoulder function symptom questionnaires were used for investigation.Results:A total of 113 patients who underwent neck lymph node dissection for head and neck tumors were included in the study. The top three neck dysfunction indicators with the highest occurrence rates were abnormal neck extension (87.6%, 99/113) , abnormal neck bending on the affected side (84.1%, 95/113) , and abnormal neck rotation on the affected side (84.1%, 95/113) . The top three shoulder dysfunction indicators with the highest occurrence rates were: abnormal shoulder flexion on the affected side (83.2%, 94/113) , abnormal shoulder abduction on the affected side (81.4%, 92/113) , and abnormal horizontal shoulder abduction on the affected side (80.5%, 91/113) . Using 18 indicators of neck and shoulder dysfunction as clustering variables, patients were classified into three groups: severe dysfunction group (53.1%, 60/113) , moderate dysfunction group (35.4%, 40/113) , and mild dysfunction group (11.5%, 13/113) . The differences in disease type and neck and shoulder function indicators between the three groups were statistically significant ( P<0.05) . Conclusions:Neck and shoulder dysfunction in patients after neck lymph node dissection for head and neck tumors is relatively severe, primarily manifesting as an abnormal range of motion. Healthcare providers should strengthen neck and shoulder function assessments in these patients and consider a range of motion exercises as a key rehabilitation program.

Objective:To investigate effect of LncRNA C-terminal binding protein 1 antisense RNA 2(CTBP1-AS2)on malig-nant biological behavior of acute myeloid leukemia(AML)cells by regulating miR-433-3p/dipeptidyl peptidase 8(DPP8)signaling axis.Methods:AML cells HL-60 were randomly separated into si-NC group,si-CTBP1-AS2 group,si-CTBP1-AS2+anti-NC group,and si-CTBP1-AS2+anti-miR-433-3p group.CCK-8 method and EdU staining were applied to detect HL-60 cell proliferation.Flow cytometry was applied to detect HL-60 cells apoptosis.Transwell was applied to detect migration and invasion of HL-60 cells.Western blot was applied to detect expressions of PCNA,Bax,MMP-9 and DPP8 proteins in HL-60 cells.ELISA was applied to detect expres-sions of IFN-γ and IL-1β.Dual luciferase reporter gene experiment was applied to analyze interaction between LncRNA CTBP1-AS2 and miR-433-3p,and between miR-433-3p and DPP8.Results:Expressions of LncRNA CTBP1-AS2,DPP8 mRNA,A450,EdU posi-tive cells,number of migrating cells,number of invading cells,PCNA protein,MMP-9 protein,DPP8 protein and IL-1β protein ex-pressions of HL-60 cells in si-CTBP1-AS2 group were lower than si-NC group,miR-433-3p expression,apoptosis rate,Bax protein and IFN-γ protein expressions were higher than si-NC group(P<0.05).Compared with si-CTBP1-AS2 group and si-CTBP1-AS2+anti-NC group,miR-433-3p expression,apoptosis rate,and expressions of Bax protein and IFN-γ protein in si-CTBP1-AS2+anti-miR-433-3p group were decreased,DPP8 mRNA,A450,EdU positive cells,number of migrating cells,number of invading cells,PCNA protein,MMP-9 protein,DPP8 protein and IL-1β protein expressions were increased(P<0.05).LncRNA CTBP1-AS2 targeted negative regula-tion of miR-433-3p,while miR-433-3p targeted negative regulation of DPP8.Conclusion:Knocking down LncRNA CTBP1-AS2 may inhibit malignant biological behavior of AML cells,whose mechanism may be achieved by regulating miR-433-3p/DPP8 signaling axis.