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.

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Traditionally, platelets, which are anucleate cell fragments derived from blood cells, have been primarily associated with their pivotal functions in hemostasis and thrombosis. However, recent research has elucidated their significant role in immune regulation, highlighting their expression of various immune receptors, involvement in numerous immune-related signaling pathways, and activation of diverse effector functions. This paper elaborates on the fundamental biological characteristics and immune functions of platelets, the involvement of activated platelets in immune regulation, and their prospective applications in clinical therapy. Furthermore, the paper discusses future directions in platelet immune research, as well as the prospects and developmental trends in immunotherapy, aiming to furnish a thorough reference for the investigation and clinical utilization of platelets within the domain of immune regulation.

Objective:To elucidate the inhibitory effect of interferon-γ(IFN-γ)on the proliferation of neuroblastoma cells and the protentral gene signature of IFN-γ and the relationship between the expression of gene signature of IFN-γ in the neuroblastoma cells and its adverse prognosis,and to clarify the effect of IFN-γ and its gene signture in the neuroblastoma.Methods:The SK-N-BE(2)(proto-oncogene N-MYC amplification type)and SH-SY5Y(proto-oncogene N-MYC non-amplification type)neuroblastoma cells were selected and treated with different concentrations(0,500,750,1 000 and 1 500 μg·L-1)of IFN-γ for 24 h,followed by cell proliferation assays using cell counting kit-8(CCK-8).Transcriptome sequencing was then performed to identify the gene signature of IFN-γ.Additionally,the tissue microarrays from 23 cases of neuroblastoma and 6 cases of normal adrenal gland samples were collected,immunohistochemistry(IHC)analysis was used to to detect the expression of gene signature of IFN-γ.Based on the expression levels of gene signature of IFN-γ,the samples were divided into SULT2B1 low and high expression groups.The correlation between the expression of gene signature of IFN-γ and poor prognosis of the patients was analyzed.Results:The CCK-8 assay results showed that as IFN-γconcentration increased,the proliferation of SK-N-BE(2)cells was significantly inhibited(P＜0.01),with inhibitory rates of SK-N-BE(2)cells in four groups were 6.73％,6.77％,7.67％,and 9.19％,respectively.In contrast,the proliferation rate of SH-SY5Y cells were significantly increased with the increase of IFN-γ concentrations(P＜0.01),and the proliferation rates of SH-SY5Y cells in four groups were 46.80％,79.19％,70.30％,and 72.33％,respectively.Transcrip tome sequencing identified hydroxysteroid sulfotransferase 2B1(SULT2B1)as a potential gene signature of IFN-γ.The IHC analysis results showed the expression amount of SULT2B1 protein in neuroblastoma tissues was increased.The clinical data analysis results revealed significant differences in age(Z=-2.618,P=0.018),lymphnode metastasis(x2=4.439,P=0.035),and distant metastasis(x2=5.856,P=0.016)between low and high SULT2B1 expression groups.Conclusion:IFN-γ can inhibit the proliferation of SK-N-BE(2)cells while promoting the proliferation of SH-SY5Y cells.SULT2B1 is a potential gene signature of IFN-γ,and its expression is upregulated in neuroblastoma tissue.SULT2B1 high expression is significantly associated with poor prognosis in the neuroblastoma patients.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective To investigate the HPV vaccination status of children aged 9-14 years, parents’ vaccine-related cognition, willingness to vaccinate children and their influencing factors. Methods From January to April 2021, the convenience sampling method was used to collect data based on the online platform and the Department of Pediatrics and Adolescent Gynecology of the Children's Hospital of Zhejiang University School of Medicine. The data were analyzed by descriptive analysis, Chi-square test, and logistic regression. Results A total of 864 questionnaires were collected, and 846 valid questionnaires were obtained after screening, with an effective rate of 97.9%. 13.57% of mothers and 3.09% of girls were vaccinated, and the vaccine awareness rate was 68.43%. 87.22% of parents were willing to bring their children for vaccination. Risk perception (OR=4.79, 95% CI: 2.22-10.35), willingness to vaccinate themselves (OR =29.01, 95% CI: 12.62-66.69), awareness of sex education (OR =3.73, 95% CI: 1.08-12.83) and whether the vaccines were free (P<0.001) were related to whether parents were willing to vaccinate their children. Conclusion Parents of children aged 9-14 have high awareness of HPV and HPV vaccine and are willing to vaccinate their children with HPV vaccine , but the vaccination rate in children is low. Disease perception, willingness to vaccinate, awareness of sex education, and whether vaccines are free are all the factors influencing parents' willingness to vaccinate children.

Objective To analyze the residents' satisfaction with the enforcement of The Regulations of Tianjin Municipality on Smoking Control in Public Places (hereinafter referred to as The Regulations) and its influencing factors. Methods From November to December 2020, 16 districts of Tianjin were selected as the research site, and one street was randomly selected from each district. The accidental sampling was used to conduct a questionnaire survey on 4,160 permanent residents in Tianjin. χ² test was used in univariate analysis and multivariate logistic regression model was used to analyze and adjust the confounding factors. The public satisfaction and its influencing factors were analyzed. Results A total of 4 022 questionnaires were collected and 2 730 were included in the study. In 2020, 89.3 percent of Tianjin residents were satisfied with the enforcement of the Regulations. Compared with residents aged 15-24, residents in other age groups were less satisfied with the enforcement of the Regulations. Compared with residents with primary school education or below, residents with high school education or bachelor's degree or the same educational level were less satisfied with the enforcement of the Regulations. Residents with chronic diseases (OR=1.885 , P<0.01) and exposure to second-hand smoke in the last 30 days (OR=1.903, P<0.01) were less satisfied with the enforcement of the Regulations, while those who supported the Regulations (OR=0.511, P<0.01) and residents who had been exposed to public service advertisements on tobacco control in the last 30 days (OR=0.043, P<0.01) were more satisfied with the enforcement of the Regulations. Conclusion The residents of Tianjin are highly satisfied with the enforcement of the Regulations. Age, education background, support for the Regulations, chronic disease, exposure to secondhand smoke in the last 30 days and exposure to public service advertisements in the last 30 days are the main influencing factors of satisfaction with the enforcement of tobacco control regulations.