1.Graphene-mediated Far-infrared Therapy Enhances Anti-non-small Cell Lung Cancer Effects of Panax quinquefolium Saponins via cGAS/STING Signaling Pathway
Huifang ZANG ; Zikai GENG ; Yan GAO ; Lu LIU ; Yifei WANG ; Bonian ZHAO ; Jing LYU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):131-145
ObjectiveTo investigate whether the inhibitory effect of Panax quinquefolium saponins (PQS) on non-small cell lung cancer (NSCLC) is enhanced under graphene-mediated far-infrared therapy (GFIR), and to analyze its relationships with mitochondrial dysfunction, mitochondrial DNA (mtDNA) leakage, and the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathways. MethodsIn the cell experiments, the cell-counting kit 8 (CCK-8) was employed to assess the inhibitory effects of PQS alone or in combination with GFIR (PQS+GFIR) on A549 cell viability. The scratch assay and the colony formation assay were adopted to evaluate cell migration and colony formation capabilities, respectively. Flow cytometry was employed to assess apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) levels. Immunofluorescence (IF) assay was performed to assess mitochondrial localization. Real-time polymerase China reaction(PCR) was used to detect mitochondrial DNA (mtDNA) leakage. A STING knockdown cell model was established by transfecting cells with small interfering RNA (siRNA), and the knockdown efficiency was assessed by Real-time PCR and Western blot. The cell viability and apoptosis following gene knockdown were assessed through the CCK-8 assay and flow cytometry. In the animal experiments, an allogeneic xenograft mouse model was established with Lewis lung cancer cells. Mice were randomized into a control group, a model group, a cisplatin group, a low-dose PQS (PQS-Low, 90 mg·kg-1) group, a high-dose PQS (PQS-High, 180 mg·kg-1) group, a low-dose PQS combined with GFIR (PQS-Low+GFIR, 90 mg·kg-1) group, and a high-dose PQS combined with GFIR (PQS-High+GFIR, 180 mg·kg-1) group. Treatment lasted for 14 days, and the fluorescence intensity was monitored at the tumor site by small-animal in vivo imaging during the treatment period. Flow cytometry was utilized to determine the proportions of T-lymphocyte subsets, B-lymphocyte levels, and peripheral blood NK cell levels in the spleens of mice. Immunohistochemical (IHC) staining was performed to assess the infiltration of CD3+, CD4+, and CD8+ T-lymphocytes in the tumor tissue. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of interferon-α (IFN-α), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in mouse tumors. The mRNA levels of cGAS, STING, TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), interferon beta 1 (IFNB1), and nuclear factor κB p65 (NF-κB p65) were determined by Real-time PCR. The protein levels of cGAS, STING, p-STING, TBK1, p-TBK1, IRF3, p-IRF3, NF-κB p65, and p-NF-κB p65 were quantified via Western blot. ResultsThe cell experiment results showed that compared with the control group, PQS inhibited the viability and migration of A549 cells, promoted apoptosis, affected mitochondrial localization, reduced mitochondrial membrane potential, increased the ROS level, and promoted mtDNA leakage. Following STING knockdown, the reductions in cell viability and the apoptosis-inducing effects caused by PQS were partially reversed (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group showed inhibited A549 cell migration and colony formation, exacerbated apoptosis, downregulated mitochondrial membrane potential, elevated ROS levels, and promoted mtDNA leakage. After STING knockdown, the reduced A549 cell viability and abnormal apoptosis phenotype were further reversed (P<0.05, P<0.01). The animal experiment results showed that compared with the control group, the model group mice exhibited reduced proportions of T-lymphocyte subsets, CD19+ B-lymphocyte levels, and peripheral blood NK1.1+ cell levels in the spleen (P<0.01). Compared with the model group, the PQS group showed increased immune cell parameters in mice (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group exhibited enhanced levels of the aforementioned indicators (P<0.01). Compared with the model group, the PQS group showed significantly reduced fluorescence intensity in transplanted tumors, significantly upregulated expression of CD3 and CD4 in the tumor tissue, elevated levels of IFN-α and IL-6 in tumors, and upregulated mRNA levels of cGAS, STING, TBK1, IRF3, IFNB1, and NF-κB p65 as well as upregulated protein level of cGAS and phosphorylation level of STING in tumors (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group demonstrated further reduced tumor fluorescence intensity, elevated levels of CD3, CD4, and CD8 as well as cytokine levels in tumor tissue, and upregulated mRNA levels of genes related to the cGAS/STING pathway as well as upregulated protein level of cGAS and phosphorylation levels of STING, TBK1, IRF3, and NF-κB p65 (P<0.05, P<0.01) ConclusionGFIR enhances the inhibitory effect of PQS on NSCLC, potentially through mitochondrial dysfunction, mtDNA leakage, and activation of the cGAS/STING signaling pathway.
2.Graphene-mediated Far-infrared Therapy Enhances Anti-non-small Cell Lung Cancer Effects of Panax quinquefolium Saponins via cGAS/STING Signaling Pathway
Huifang ZANG ; Zikai GENG ; Yan GAO ; Lu LIU ; Yifei WANG ; Bonian ZHAO ; Jing LYU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):131-145
ObjectiveTo investigate whether the inhibitory effect of Panax quinquefolium saponins (PQS) on non-small cell lung cancer (NSCLC) is enhanced under graphene-mediated far-infrared therapy (GFIR), and to analyze its relationships with mitochondrial dysfunction, mitochondrial DNA (mtDNA) leakage, and the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathways. MethodsIn the cell experiments, the cell-counting kit 8 (CCK-8) was employed to assess the inhibitory effects of PQS alone or in combination with GFIR (PQS+GFIR) on A549 cell viability. The scratch assay and the colony formation assay were adopted to evaluate cell migration and colony formation capabilities, respectively. Flow cytometry was employed to assess apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) levels. Immunofluorescence (IF) assay was performed to assess mitochondrial localization. Real-time polymerase China reaction(PCR) was used to detect mitochondrial DNA (mtDNA) leakage. A STING knockdown cell model was established by transfecting cells with small interfering RNA (siRNA), and the knockdown efficiency was assessed by Real-time PCR and Western blot. The cell viability and apoptosis following gene knockdown were assessed through the CCK-8 assay and flow cytometry. In the animal experiments, an allogeneic xenograft mouse model was established with Lewis lung cancer cells. Mice were randomized into a control group, a model group, a cisplatin group, a low-dose PQS (PQS-Low, 90 mg·kg-1) group, a high-dose PQS (PQS-High, 180 mg·kg-1) group, a low-dose PQS combined with GFIR (PQS-Low+GFIR, 90 mg·kg-1) group, and a high-dose PQS combined with GFIR (PQS-High+GFIR, 180 mg·kg-1) group. Treatment lasted for 14 days, and the fluorescence intensity was monitored at the tumor site by small-animal in vivo imaging during the treatment period. Flow cytometry was utilized to determine the proportions of T-lymphocyte subsets, B-lymphocyte levels, and peripheral blood NK cell levels in the spleens of mice. Immunohistochemical (IHC) staining was performed to assess the infiltration of CD3+, CD4+, and CD8+ T-lymphocytes in the tumor tissue. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of interferon-α (IFN-α), interferon-β (IFN-β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in mouse tumors. The mRNA levels of cGAS, STING, TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), interferon beta 1 (IFNB1), and nuclear factor κB p65 (NF-κB p65) were determined by Real-time PCR. The protein levels of cGAS, STING, p-STING, TBK1, p-TBK1, IRF3, p-IRF3, NF-κB p65, and p-NF-κB p65 were quantified via Western blot. ResultsThe cell experiment results showed that compared with the control group, PQS inhibited the viability and migration of A549 cells, promoted apoptosis, affected mitochondrial localization, reduced mitochondrial membrane potential, increased the ROS level, and promoted mtDNA leakage. Following STING knockdown, the reductions in cell viability and the apoptosis-inducing effects caused by PQS were partially reversed (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group showed inhibited A549 cell migration and colony formation, exacerbated apoptosis, downregulated mitochondrial membrane potential, elevated ROS levels, and promoted mtDNA leakage. After STING knockdown, the reduced A549 cell viability and abnormal apoptosis phenotype were further reversed (P<0.05, P<0.01). The animal experiment results showed that compared with the control group, the model group mice exhibited reduced proportions of T-lymphocyte subsets, CD19+ B-lymphocyte levels, and peripheral blood NK1.1+ cell levels in the spleen (P<0.01). Compared with the model group, the PQS group showed increased immune cell parameters in mice (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group exhibited enhanced levels of the aforementioned indicators (P<0.01). Compared with the model group, the PQS group showed significantly reduced fluorescence intensity in transplanted tumors, significantly upregulated expression of CD3 and CD4 in the tumor tissue, elevated levels of IFN-α and IL-6 in tumors, and upregulated mRNA levels of cGAS, STING, TBK1, IRF3, IFNB1, and NF-κB p65 as well as upregulated protein level of cGAS and phosphorylation level of STING in tumors (P<0.05, P<0.01). Compared with the PQS group, the PQS+GFIR group demonstrated further reduced tumor fluorescence intensity, elevated levels of CD3, CD4, and CD8 as well as cytokine levels in tumor tissue, and upregulated mRNA levels of genes related to the cGAS/STING pathway as well as upregulated protein level of cGAS and phosphorylation levels of STING, TBK1, IRF3, and NF-κB p65 (P<0.05, P<0.01) ConclusionGFIR enhances the inhibitory effect of PQS on NSCLC, potentially through mitochondrial dysfunction, mtDNA leakage, and activation of the cGAS/STING signaling pathway.
3.Primary regional disparities in clinical characteristics, treatments, and outcomes of a typically designed study of valvular heart disease at 46 tertiary hospitals in China: Insights from the China-VHD Study.
Xiangming HU ; Yunqing YE ; Zhe LI ; Qingrong LIU ; Zhenyan ZHAO ; Zheng ZHOU ; Weiwei WANG ; Zikai YU ; Haitong ZHANG ; Zhenya DUAN ; Bincheng WANG ; Bin ZHANG ; Junxing LV ; Shuai GUO ; Yanyan ZHAO ; Runlin GAO ; Haiyan XU ; Yongjian WU
Chinese Medical Journal 2025;138(8):937-946
BACKGROUND:
Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China.
METHODS:
Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.
RESULTS:
Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P <0.05).
CONCLUSIONS:
This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics.
REGISTRATION
ClinicalTrials.gov , NCT03484806.
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
China/epidemiology*
;
Heart Valve Diseases/therapy*
;
Kaplan-Meier Estimate
;
Tertiary Care Centers
;
Treatment Outcome
4.Mucosal Immunity of IgA Nephropathy and Treatment from Pharynx
Mingming ZHAO ; Yu ZHANG ; Liusheng LI ; Zikai YU
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(7):15-18
IgA nephropathy is a common primary glomerulopathy; the main clinical manifestation is hematuria, with or without proteinuria. However, the pathogenesis associated with mucosal immunity is not completely clear. At present, modern medical treatment delays the progression of IgA nephropathy mainly by controlling blood pressure, reducing proteinuria and delaying renal function failure. The method of combination of disease and syndrome of TCM has received satisfactory efficacy in the treatment of IgA nephropathy. Based on the relationship between mucosal immune and treated from pharynx, this article investigated the occurrence, development and treatment of IgA nephropathy.
5.Study of biometric identification of heart sound base on Mel-Frequency cepstrum coefficient.
Wei CHEN ; Yihua ZHAO ; Sheng LEI ; Zikai ZHAO ; Min PAN
Journal of Biomedical Engineering 2012;29(6):1015-1020
Heart sound is a physiological parameter with individual characteristics generated by heart beat. To do the individual classification and recognition, in this paper, we present our study of using wavelet transform in the signal denoising, with the Mel-Frequency cepstrum coefficients (MFCC) as the feature parameters, and propose a research of reducing the dimensionality through principal components analysis (PCA). We have done the preliminary study to test the feasibility of biometric identification method using heart sound. The results showed that under the selected experimental conditions, the system could reach a 90% recognition rate. This study can provide a reference for further research.
Algorithms
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Artificial Intelligence
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Heart Sounds
;
physiology
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Humans
;
Individuality
;
Pattern Recognition, Physiological
;
physiology
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Principal Component Analysis
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Signal Processing, Computer-Assisted
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Wavelet Analysis
6.Progress in research on LiquiChip technology in biomedical engineering.
Journal of Biomedical Engineering 2010;27(6):1406-1409
As a novel BioChip technique, LiquiChip technique uses fluorescent polystyrene beads as the carrriers of various probes, thus the related reactions of bio-molecules are in liquid system. LiquiChip technique is of use in the methods to detect bio-macromolecules, e. g. DNA detection, immunoassay, cytokine assay, hormone assay, environmental survey and analysis. In comparison to conventional biochip, LiquiChip presents the advantages of high-throughput, high sensitivity, high accuracy, fine repeatability, wide linear range, etc. Now LiquiChip technique is widely used in biomedical engineering field.
Animals
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Biomedical Engineering
;
trends
;
Biosensing Techniques
;
methods
;
Humans
;
Microfluidic Analytical Techniques
;
methods
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Molecular Imprinting
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Protein Array Analysis
;
methods
7.Progress in megnetic nanobead preparation and application in bio-mediacal engineering
Zikai ZHAO ; Guohua HUI ; Yuquan CHEN
International Journal of Biomedical Engineering 2009;32(3):183-185,189
As a novel functional material with great application values, magnetic nanobead has been in fast development in recent years. Magnetic nanobead is provided with characteristics of beth polymeric and mag-netic particles, so it can be detected easily fi'om the medium and can be easily located since they can move di-rectionally when motivated by external electric field. The magnetic nanobead is widely used in biomedical engi-neering research due to its unique physical and chemical properties which simplify the complex experiments op-erations and shorten the testing period.

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