1.Effects of resveratrol on cGAS-STING signaling pathway in fibroblast-like synoviocytes of patients with rheumatoid arthritis
Taorong Wang ; Yubao Shao ; Nannan Liu ; Wenhao Li ; Meng Li ; Xiaoyu Chen
Acta Universitatis Medicinalis Anhui 2025;60(1):73-78
Objective :
To investigate the effects of resveratrol(Res) on fibroblast-like synoviocytes(FLS) in patients with rheumatoid arthritis(RA), and to explore the possible mechanism of Res inhibiting the release of inflammatory factors from FLS.
Methods :
FLS from RA patients were culturedin vitroand treated with different concentrations of Res(0, 20, 40, 80, 160, 320 μmol/L). The viability of FLS cells was detected by CCK-8 assay after 12 and 24 h. The contents of inflammatory factor interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatant were detected by ELISA. The expression levels of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS) and stimulator of interferon gene(STING) were measured by Western blot; After lentivirus infection with FLS caused the cells to overexpress cGAS, the cells were divided into Control group(blank control), cGAS group(cGAS overexpression), Res+cGAS group(Res 160 μmol/L+cGAS overexpression) and Res group(Res 160 μmol/L). The expression level of STING protein in cells of each group was determined by Western blot, the viability of FLS cells in each group was detected by CCK-8, and the contents of inflammatory factor IL-6 and TNF-α in the supernatant of cells of each group were detected by ELISA method.
Results :
The results of CCK-8 experiment showed that under 40, 80, 160 μmol/L Res treatment, FLS viability decreased significantly after 24 h compared with blank control group(P<0.01). ELISA results showed that the contents of IL-6 and TNF-α in cell supernatant were also significantly decreased after treatment with Res of 40, 80 and 160 μmol/L(P<0.01). Meanwhile, Western blot results showed that Res could significantly decrease the protein expression levels of STING and cGAS in FLS cells after treatment of 40, 80 and 160 μmol/L(P<0.05,P<0.01). Compared with the Control group, the expression level of STING protein in FLS increased after overexpression of cGAS(P<0.05); compared with the Res group, the content of inflammatory factors in the supernatant of FLS and the expression level of STING protein in FLS significantly increased after overexpression of cGAS(P<0.01,P<0.05).
Conclusion
The appropriate concentration of Res can inhibit the release of inflammatory cytokines in FLS cells, which may be related to the blocking of cGAS-STING signaling pathway.
2.Prediction of lymph node metastasis in invasive lung adenocarcinoma based on radiomics of the primary lesion, peritumoral region, and tumor habitat: A single-center retrospective study
Hongchang WANG ; Yan GU ; Wenhao ZHANG ; Guang MU ; Wentao XUE ; Mengen WANG ; Chenghao FU ; Liang CHEN ; Mei YUAN ; Jun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1079-1085
Objective To predict the lymph node metastasis status of patients with invasive pulmonary adenocarcinoma by constructing machine learning models based on primary tumor radiomics, peritumoral radiomics, and habitat radiomics, and to evaluate the predictive performance and generalization ability of different imaging features. Methods A retrospective analysis was performed on the clinical data of 1 263 patients with invasive pulmonary adenocarcinoma who underwent surgery at the Department of Thoracic Surgery, Jiangsu Province Hospital, from 2016 to 2019. Habitat regions were delineated by applying K-means clustering (average cluster number of 2) to the grayscale values of CT images. The peritumoral region was defined as a uniformly expanded area of 3 mm around the primary tumor. The primary tumor region was automatically segmented using V-net combined with manual correction and annotation. Subsequently, radiomics features were extracted based on these regions, and stacked machine learning models were constructed. Model performance was evaluated on the training, testing, and internal validation sets using the area under the receiver operating characteristic curve (AUC), F1 score, recall, and precision. Results After excluding patients who did not meet the screening criteria, a total of 651 patients were included. The training set consisted of 468 patients (181 males, 287 females) with an average age of (58.39±11.23) years, ranging from 29 to 78 years, the testing set included 140 patients (56 males, 84 females) with an average age of (58.81±10.70) years, ranging from 34 to 82 years, and the internal validation set comprised 43 patients (14 males, 29 females) with an average age of (60.16±10.68) years, ranging from 29 to 78 years. Although the habitat radiomics model did not show the optimal performance in the training set, it exhibited superior performance in the internal validation set, with an AUC of 0.952 [95%CI (0.87, 1.00)], an F1 score of 84.62%, and a precision-recall AUC of 0.892, outperforming the models based on the primary tumor and peritumoral regions. Conclusion The model constructed based on habitat radiomics demonstrated superior performance in the internal validation set, suggesting its potential for better generalization ability and clinical application in predicting lymph node metastasis status in pulmonary adenocarcinoma.
3.Association of Estimated Glucose Disposal Rate With the Stenosis Severity of Coronary Artery Disease: A Cross-sectional Study
Yubin WU ; Zhiteng CHEN ; Maoxiong WU ; Wenhao LIU ; Qian CHEN ; Shiyi ZHOU ; Yan-xin CHEN ; Min XIA
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):136-145
ObjectiveTo investigate the association between estimated glucose disposal rate (eGDR) and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients (mean age: 62(53-68) years) who underwent coronary angiography for suspected coronary artery disease (53.9% were male). Insulin resistance level (IR) was calculated according to eGDR formula: eGDR = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [hypertension (yes = 1 / no = 0), HbA1c = HbA1c (%)]. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels: no-obstructive CAD group (all coronary stenosis were<50%, n=704), Single-vessel CAD group (only one involved major coronary artery stenosis≥50%, n=205), Multi-vessel CAD group (two or more involved major coronary arteries stenosis≥50%, n=349); Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic (ROC) curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). In multivariate logistic regression models, individuals with the lowest quantile of eGDR (T1) were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR (T3) (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD (P-nonlinear>0.05). In non-diabetic patients, compared with the reference group (T3), the T1 group had a significantly increased risk of CAD (OR: 1.42; 95% CI: 1.00~2.01; P<0.05) and multi-vessel CAD (OR: 1.86; 95%CI: 1.21~2.86; P<0.05). No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis, when eGDR was added to traditional model for CAD, significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR, as a non-insulin measure to assess IR, could be a valuable indicator of CAD severity for population.
4.The Correlation between Tooth Brushing Frequency and Blood Indicators in Adolescents: A Cross-sectional Observational Study
Xu ZHANG ; Hanze DU ; Wenhao ZHAI ; Shuaihua SONG ; Xiaoyuan GUO ; Linlin WEN ; Lei HUANG ; Shi CHEN ; Daowei LI ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2024;15(4):960-967
To analyze the effects of tooth brushing frequency on blood indicators among adolescents and to preliminarily explore the effects of tooth brushing frequency on general health. Using convenience sampling method, the study included the students of class 2021 of Jining No. 7 Middle School and student athletes from the Jining Sports Training Center. Univariate and multivariate linear regression analyses were used to investigate the correlation between tooth brushing frequency and blood indicators such as eosinophil percentage (EOS%), eosinophil count (EOS#), basophil percentage (BAS%), basophil count (BAS#), superoxide dismutase (SOD), insulin-like growth factor 1 (IGF-1) and uric acid (UA). A total of 305 students were included (167 from Jining No. 7 Middle School, 138 from Jining Sports Training Centre), with 192 (62.95%) males and 113 (37.05%) females. They were divided into three groups based on daily teeth brushing frequency: ≤1 time (40.33%, 123/305), 2 times (53.77%, 164/305), and ≥3 times (5.90%, 18/305).Univariate linear regression analysis showed that brushing twice daily was negatively correlated with EOS%, EOS#, BAS%, and BAS#(all The adolescent tooth brushing frequency correlates with several blood indicators affecting general health, suggesting that there may be a potential association between oral health and general health.
5.Effect of Gualou Xiebai Banxiatang on Myocardial Microangiogenesis and HIF-1α/VEGF-related Pathways in Myocardial Ischemia Model Rats
Wenhao CHEN ; Weishan MENG ; Hong LI ; Weiwei TIAN ; Qi ZHANG ; Yingying TAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):1-9
ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury, and to observe the effect of myocardial microvascular density (MVD), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected, with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride (ISO,80 mg·kg-1·d-1, 2 d) to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling, the rats were randomly divided into the model group, high, medium, and low dose groups of Gualou Xiebai Banxiatang, and the metoprolol group. The high, medium, and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42, 5.21, 2.61 g·kg-1·d-1, respectively, while the metoprolol group was given metoprolol at 2.6 mg·kg-1·d-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention, relevant tests were conducted, and serum was collected to measure heart function-related indicators. Hematoxylin-eosin (HE) and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry (IHC) was used to detect the positive expression of platelet endothelial cell adhesion molecule (CD31). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of N-terminal pro-brain natriuretic peptide (NT-proBNP) and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group, the model group showed significantly increased serum levels of LDH, CK, CK-MB, NT-proBNP, and VEGF (P<0.01), significantly increased collagen volume fraction (CVF) (P<0.01), significantly decreased MVD (P<0.01), and elevated protein expression levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.05, P<0.01). Compared with the model group, the metoprolol group had significantly lower serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.01), significantly higher VEGF levels (P<0.01), significantly decreased CVF (P<0.01), significantly increased MVD (P<0.01), and significantly increased protein expression levels of PI3K, mTOR, and VEGF (P<0.01), with no statistically significant change in HIF-1α protein expression. Compared with the model group, the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.05, P<0.01), increased VEGF levels (P<0.05, P<0.01), significantly reduced CVF (P<0.01), increased MVD (P<0.05, P<0.01), and significantly increased protein levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.01). In the low dose group of Gualou Xiebai Banxiatang, compared with the model group, serum levels of LDH and NT-proBNP were decreased (P<0.05), VEGF was increased (P<0.05). Moreover, CVF was decreased (P<0.05), and the protein expression levels of PI3K, mTOR, HIF-1α, and VEGF were significantly increased (P<0.01). ConclusionGualou Xiebai Banxiatang can improve cardiac function, reduce myocardial pathological damage, enhance endothelial cell function, promote myocardial microvascular formation, and upregulate the expression of PI3K, mTOR, HIF-1α, and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.
6.Outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network
Siyuan JIANG ; Chuanzhong YANG ; Xiuying TIAN ; Dongmei CHEN ; Zuming YANG ; Jingyun SHI ; Falin XU ; Yan MO ; Xinyue GU ; K. Shoo LEE ; Wenhao ZHOU ; Yun CAO
Chinese Journal of Pediatrics 2024;62(1):22-28
Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.
7.CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar Ⅰ disorder
Xiaofei ZHANG ; Xiaoyu LIANG ; Xiaofang CHENG ; Jianshan CHEN ; Wenhao DENG ; Yizhi ZHANG ; Liqian CUI ; Xiongchao CHENG ; Xuan LI ; Chanjuan YANG ; Biyu YE ; Liping CAO
Chinese Journal of Medical Genetics 2024;41(9):1045-1052
Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.
8.Expression of FAT1 in Lung Adenocarcinoma and Its Relationship with Immune Cell Infiltration
DING CHEN ; ZHAO WENHAO ; HUANG HUA ; LI YONGWEN ; ZHANG ZHANRUI ; ZHANG RUIHAO ; WANG YANAN ; WU DI ; CHEN CHEN ; LIU HONGYU ; CHEN JUN
Chinese Journal of Lung Cancer 2024;27(2):109-117
Background and objective Lung cancer is a leading cause of cancer-related deaths.Non-small cell lung cancer(NSCLC)is the most common pathological subtype,with adenocarcinoma being the predominant type.FAT atypical cadherin 1(FAT1)is a receptor-like protein with a high frequency of mutations in lung adenocarcinoma.The protein encoded by FAT1 plays a crucial role in processes such as cell adhesion,proliferation,and differentiation.This study aims to investigate the expression of FAT1 in lung adenocarcinoma and its relationship with immune infiltration.Methods Gene expression levels and relevant clinical information of 513 lung adenocarcinoma samples and 397 adjacent lung samples were obtained through The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)data.The mRNA expression levels of the FAT1 gene in lung adenocarcinoma tissues were analyzed,along with its association with the prognosis of lung adenocarcinoma patients.Pathway enrichment analysis was conducted to explore the signaling pathways regulated by the FAT1 gene.Immu-noblotting was used to detect the differential expression of FAT1 in lung epithelial cells and various lung cancer cell lines,while immunohistochemistry was employed to assess FAT1 expression in lung cancer and adjacent tissues.Results FAT1 gene muta-tions were identified in 14%of lung adenocarcinoma patients.TCGA database data revealed significantly higher FAT1 mRNA expression in lung adenocarcinoma tissues compared to adjacent lung tissues.Kaplan-Meier analysis indicated lower survival rates in lung adenocarcinoma patients with higher FAT gene expression.Pathway enrichment analysis suggested the involve-ment of FAT1 in tumor development pathways,and its expression was closely associated with immune cell infiltration.Immu-nohistochemical validation demonstrated significantly higher expression of FAT1 in cancer tissues compared to adjacent lung tissues.Conclusion FAT1 mRNA is highly expressed in lung adenocarcinoma tissues,and elevated FAT1 mRNA expression is associated with poor prognosis in lung adenocarcinoma patients.FAT1 may serve as a potential biomarker for lung cancer.
9.Standardized specialist training for developmental and behavioral pediatrics in China and the United States: current status and thoughts
Xiaoyang CHEN ; Lingling WU ; Wenhao LI ; Wenyuan JIN ; Yanyan WANG ; Xiaolin LIU ; Zhiwei ZHU
Chinese Journal of Medical Education Research 2024;23(3):314-320
The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.
10.Advances in application of EEG-fNIRS technology in researches on neuropsychiatric disorders
Chenyang GAO ; Kai WU ; Wenhao LI ; Yi LI ; Zhile JIANG ; Yuxin WANG ; Wenrui CHEN ; Jing ZHOU
Chinese Journal of Medical Physics 2024;41(3):348-355
Currently,electroencephalogram(EEG),functional near-infrared spectroscopy(fNIRS),and functional magnetic resonance imaging have been widely studied and applied to neuropsychiatric disorders.In recent years,the devices which can realize the simultaneous acquisition of EEG and fNIRS has been developed and gradually applied in the studies on neuropsychiatric disorders.The review provides an introduction of the techniques of synchronized detection and data analysis for EEG-fNIRS,summarizes the analysis methods and new findings of the recent studies of stroke,epilepsy,and other neuropsychiatric disorders using EEG-fNIRS,and also discusses the future research directions.


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