1.Effect of Shenqi Yiliu Formula (参芪抑瘤方) Drug-Containing Serum on the Cycle of Gastric Cancer Cell AGS and Wnt/β-Catenin Pathway
Na WEI ; Chongyuan GUO ; Min BAI ; Yaorong AN ; Sichao ZHANG ; Liyang WU ; Yongqiang DUAN
Journal of Traditional Chinese Medicine 2025;66(4):399-406
ObjectiveTo investigate the potential mechanism of Shenqi Yiliu Formula (参芪抑瘤方) in treating precancerous lesions of gastric cancer (PLGC) by the Wnt/β-catenin signaling pathway. MethodsThe CCK-8 assay was used to determine the optimal intervention time for Shenqi Yiliu Formula drug-containing serum and the concentration of the Wnt/β-catenin pathway inhibitor XAV939 depends on the survival rate of AGS gastric cancer cell line. AGS cells were divided into the gastric cancer cell group (15% blank serum), inhibitor group (selected concentration of XAV939), high-dose Shenqi Yiliu Formula group (12% Shenqi Yiliu Formula drug-containing serum + 3% blank serum), medium-dose Shenqi Yiliu Formula group (6% Shenqi Yiliu Formula drug-containing serum + 9% blank serum), and low-dose Shenqi Yiliu Formula group (3% Shenqi Yiliu Formula drug-containing serum + 12% blank serum). Each group was tested in triplicate. After culturing for 24 and 48 hours, cell migration and invasion were assessed by scratch assays; after a selected intervention period (48 hours), cell cycle distribution was analyzed using flow cytometry, Ki67 protein levels were detected by immunofluorescence, the protein levels of Wnt, β-catenin, GSK-3β, and intranuclear T-cell specific factor(TCF) were measured by the protein immunoblotting assay, and the mRNA expressions of these above factors were determined by quantitative real-time PCR. ResultsThe optimal intervention time for Shenqi Yiliu Formula drug-containing serum was determined to be 48 hours, and the effective concentration of XAV939 was 20 μmol/L. Compared with the gastric cancer cell group, Shenqi Yiliu Formula at all doses reduced the cell migration rate at 24 and 48 hours (P<0.05), except for the low-dose group at 24 hours. Compared to the low-dose group at corresponding time points, high- and medium-dose Shenqi Yiliu Formula groups showed significantly reduced migration rates, particularly the high-dose group at 48 hours (P<0.05). Compared with the gastric cancer cell group, the high-dose Shenqi Yiliu Formula and inhibitor groups exhibited reduced protein and mRNA levels of Wnt, β-catenin, and TCF, along with reduced Ki67 protein levels and a decreased proportion of cells in the S and G2 phases of the cell cycle, but GSK-3β protein levels, GSK-3β mRNA expression, and the proportion of cells in the G1 phase increased (P<0.05). Compared to the inhibitor group, the high-dose Shenqi Yiliu Formula group showed a decreased proportion of G1-phase cells and an increased proportion of G2-phase cells (P<0.05), although differences in Wnt and β-catenin protein levels and mRNA expressions were not statistically significant (P>0.05). ConclusionShenqi Yiliu Formula drug-containing serum inhibits the migration and invasion of gastric cancer AGS cells and block the cell cycle at G1 phase, and its underlying mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.
2.Influencing factors and epidemic trends of lung cancer in a Hospital in Zigong Prefecture in 2019 - 2023
Xiaoyan YANG ; Liyang WEI ; Qingfeng ZHANG
Journal of Public Health and Preventive Medicine 2025;36(5):116-120
Objective To explore the trend of lung cancer prevalence and influencing factors in a Hospital of Zigong from 2019-2023. Methods Select 2 835 lung cancer patients in Zigong region admitted to the Zigong Fourth People's Hospital from January 2019 to December 2023, and analyze the changes in the clinical characteristics and age strata of patients in different time periods in this group. Three thousand non-cancer respiratory patients in the same time period were included to compare the differences in patient data and to analyze the influencing factors affecting the changes in the characteristics of lung cancer in this region. Results There was an upward trend in the number of patients with pneumonia included between 2019 and 2023, with the highest volume of patients included in 2021 (609 cases). Over the 5-year period, the percentage of patients aged 0-39 years did not change significantly and accounted for a relatively low percentage. The proportion of patients aged 40-49 years increased (APC=0.69%, t=2.990, P<0.05), and the proportion of patients over 60 years old decreased, but to a lesser extent (APC=-0.25%, t=2.210, P<0.05). There were no significant differences in male percentage, lesion site, distant metastasis, smoking history and tumor diameter among patients in different years (all P>0.05). There were significant differences in TNM stage and lymphatic metastasis among patients in different years (all P<0.05). Compared with 2019, the proportion of early stage and patients with lymph node metastasis showed an upward trend within five years (χ2early stage=9.153, Pearly stage=0.002; χ2lymph node metastasis=5.848, Plymph node metastasis=0.016). The factor associated with the change in age of lung cancer patients in different years was family history of lung cancer (P<0.01). Factors associated with histologic changes in lung cancer patients in different years were age, family history of lung cancer and smoking history (all P<0.05). Factors associated with changes in TNM distribution in lung cancer patients in different years were age, tumor diameter, family history of lung cancer and lymph node metastasis (all P<0.05). Factors associated with changes in lymph node metastasis in lung cancer patients in different years were tumor diameter and TNM stage (all P<0.05). Conclusion From 2019 to 2023, the age of patients with lung cancer in a Hospital in Zigong area showed a decreasing trend, which may be influenced by family history of lung cancer.Patients with TNM early stage and lymph node metastasis increased respectively, which influenced each other and were interfered by factors of age, tumor diameter, and family history of lung cancer.
3.A novel feedback loop: CELF1/circ-CELF1/BRPF3/KAT7 in cardiac fibrosis.
Yuan JIANG ; Bowen ZHANG ; Bo ZHANG ; Xinhua SONG ; Xiangyu WANG ; Wei ZENG ; Liyang ZUO ; Xinqi LIU ; Zheng DONG ; Wenzheng CHENG ; Yang QIAO ; Saidi JIN ; Dongni JI ; Xiaofei GUO ; Rong ZHANG ; Xieyang GONG ; Lihua SUN ; Lina XUAN ; Berezhnova Tatjana ALEXANDROVNA ; Xiaoxiang GUAN ; Mingyu ZHANG ; Baofeng YANG ; Chaoqian XU
Acta Pharmaceutica Sinica B 2025;15(10):5192-5211
Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.
4.Pancreatic Dysfunction and Influencing Factors of Glucose Metabolism in children with β-thalassemia Major After Allogeneic Hematopoietic Stem Cell Transplantation
Huilian DAI ; Shaofen LIN ; Lina ZHANG ; Hui OU ; Zulin LIU ; Honggui XU ; Ke HUANG ; Liyang LIANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(6):1071-1078
ObjectiveTo investigate and explore the characteristics and influencing factors of glucose metabolism in children with β-thalassemia major (β-TM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MethodsThe follow-up data of 41 patients with β-TM who underwent HSCT at Hematopoietic Stem Cell Transplantation Department of Children's Medical Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University were retrospectively analyzed. Their glucose metabolism characteristics were evaluated through laboratory tests and the related influencing factors were analyzed. ResultsIn the study, 41.46% (17/41) of patients developed abnormal glucose homeostasis after HSCT. Among them, 82.35% (14/17) characterized by insulin resistance, but no cases of diabetes mellitus were found. The results of insulin releasing test and oral glucose tolerance test(OGTT) showed that 45.00% (9/20) of patients had abnormal insulin releasing curve and 40.0% (8/20) had delayed serum glucose peak. The average age of HSCT in abnormal glucose homeostasis group was significantly older than that in the normal glucose homeostasis group [(8.8±3.9) years old vs (6.0±3.1) years old, P=0.015]. ConclusionsPatients with β-TM after HSCT may develop abnormal glucose homeostasis, consists largely of insulin resistance. The elder age of HSCT (≥7 years old) is a risk factor for abnormal glucose homeostasis in β-TM patients after HSCT. It is recommended to regularly monitor glucose metabolism indicators in β-TM children after HSCT, especially in elderly transplant recipients.
5.Expression of long-chain non-coding RNA-P21 in hydrogen peroxide induced human lens epithelial cells damage
Xiaoming DONG ; Yuxuan LIU ; Liyang JI ; Jing WANG ; Jinsong ZHANG
Chinese Journal of Experimental Ophthalmology 2024;42(3):232-239
Objective:To detect the changes in the biological activity and expression of long-chain non-coding RNA-p21 (lncRNA-p21) in human lens epithelial cells HLE-B3 damage induced by hydrogen peroxide.Methods:HLE-B3 cells were divided into normal control group and hydrogen peroxide group, which were cultured in normal culture medium and culture medium containing 200 μmol/L hydrogen peroxide for 24 hours, respectively.Cell viability was determined by MTS colorimetric method.Cellular reactive oxygen species (ROS) level was detected using ROS assay kits.Cell apoptosis was tested by flow cytometry.Cell Caspase-3 activity was detected using Caspase-3 assay kit.Expressions of Bax and Bcl-2 proteins related to cell apoptosis were determined by Western Blot.Cell cycle distribution was determined by flow cytometry.Cell proliferation ability was detected by EDU proliferation assay kit.The expression of lncRNA-p21 in cells was detected by real time fluorescence quantitative polymerase chain reaction (PCR).The localization of lncRNA-p21 in cells was detected by fluorescence in situ hybridization.Results:The ROS content of cells in hydrogen peroxide group was (4.65±0.38), significantly higher than (1.00±0.01) of normal control group, and the difference was statistically significant ( t=16.66, P<0.05).Compared with the normal control group, the cell apoptosis rate was significantly increased, the activity of Caspase-3 was enhanced, and the relative expression of Bax was significantly increased in the hydrogen peroxide group, with statistically significant differences ( t=20.69, 39.80, 12.73, all at P<0.05).Compared with the normal control group, the proportion of G2 phase cells in the hydrogen peroxide group significantly increased, showing a statistically significant difference ( t=23.10, P<0.05).The EDU-positive cell rate of hydrogen peroxide group was (25.41±6.99)%, significantly lower than (50.58±9.15)% of normal control group ( t=6.559, P<0.05).The relative expression level of lncRNA-p21 in the hydrogen peroxide group was 2.36±0.29, significantly higher than 1.02±0.02 in the normal control group ( t=7.893, P<0.05).The fluorescence in situ hybridization experiments indicate that lncRNA-p21 was localized in the cytoplasm. Conclusions:In the oxidative stress model induced by hydrogen peroxide, the proliferation ability of lens epithelial cells significantly decreases, the apoptosis level significantly increases, and the expression levels of ROS and lncRNA-p21 enhances.lncRNA-p21 may be involved in the oxidative stress injury process of lens epithelial cells.
6.Clinical and Genetic Study on 48 Children with Short Stature of Unknown Etiology
Lele HOU ; Shaofen LIN ; Xiaojuan LI ; Zulin LIU ; Hui OU ; Lina ZHANG ; Zhe MENG ; Liyang LIANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):127-135
ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology, providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations, laboratory test and whole exome sequencing (WES) results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children (30 boys and 18 girls) were enrolled, aged 7.73 ± 3.97 years, with a height standard deviation score ( HtSDS) of -3.63 ± 1.67. Of the patients, 33 (68.8%) suffered from facial anomalies, 31 (64.6%) from skeletal abnormalities, 26 [54.2%, 61.5% of whom born small for gestational age (SGA)] from perinatal abnormalities, 24 [50.0%, 87.5% of whom with growth hormone (GH) peak concentration below normal] from endocrine disorders and 21(43.8%) had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was (9.72 ± 7.25) ng/mL, IGF-1 standard deviation score was -0.82 ± 1.42, the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES, 14 (56.0%) had pathogenic mutation, 6 (24.0%) likely pathogenic mutation, and 5 (20.0%) mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes, including 10 affecting intracellular signaling pathways (PTPN11, RAF1, RIT1, ARID1B, ANKRD11, CSNK2A1, SRCAP, CUL7, SMAD4 and FAM111A) and 4 affecting extracellular matrix (ECM) components or functions (ACAN, FBN1, COL10A1 and COMP). ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies, disproportionate body types, skeletal abnormalities, SGA, GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.
7.Comparison of the control effect of corneal refractive therapy with vision shaping treatment designed orthokeratology on corneal morphology myopia at low E-values
Xia JIN ; Xiaohong GUO ; Liyang TONG ; Ying WANG ; Xiaojin ZHANG ; Lu ZHANG ; Feng'e XU
International Eye Science 2024;24(3):441-447
AIM: To observe and analyze the effectiveness and safety of wearing corneal refractive therapy(CRT)and vision shaping treatment(VST)designed orthokeratology in controlling myopic progression in adolescents with low E-value corneal morphology.METHODS: This prospective study involved 100 cases(100 eyes)of adolescent myopia patients fitted with orthokeratology at our optometry clinic from January 2020 to December 2021. The data of right eye were collected for research, and they were divided into low myopia group(-1.00 to -3.00 D)and moderate myopia group(-3.25 to -5.00 D)according to spherical equivalent, with 50 cases in each group. Each group of patients was further randomly divided into the CRT group and the VST group, with 25 cases in each group. Uncorrected visual acuity, refractive error, axial length(AL), tear film break-up time(BUT), corneal endothelial cell density, corneal staining grading, lens decentration, and refractive power at 15°-30° were measured before and after wearing orthokeratology, with a follow-up duration of 1.5 a.RESULTS: The uncorrected visual acuity of CRT and VST subgroups in the low myopia group showed no statistical significance at any time point after wearing orthokeratology. However, in the moderate myopia group, CRT subgroup showed better uncorrected visual acuity than the VST subgroup, with significant differences at 1 d and 1 wk(t=-9.474, -12.067, both P<0.01); no significant differences were noted at other time points. After wearing lens for 6 mo and 1.5 a, the AL growth for the CRT subgroup in low and moderate myopia was less than the VST subgroup, with no statistically significant differences. There were no statistically significant differences in binocular BUT and corneal endothelial cell density after wearing lens for 6 mo and 1.5 a. Corneal injury was lower in the CRT subgroup than that in the VST subgroup, but the difference was not statistically significant(Z=-1.803, P=0.071). Lens decentration was significantly better in the CRT subgroup than in the VST subgroup(Z=-4.629, P<0.001). In the periphery of the retina at 15°-30°, there were no significant differences in the amount of myopic defocus between the two groups, while it was statistically significant at 1, 3, and 6 mo in the moderate myopia subgroup(t=-3.949, P=0.008; t=-5.833, P<0.001; t=-6.231, P<0.001), indicating that CRT subgroup could produce a greater amount of myopic defocus.CONCLUSION: For patients with low E-value corneal morphology, CRT, using the vector height at 8 mm on the cornea for fitting, is not limited to the corneal E-value. It shapes faster and improves uncorrected visual acuity after shaping, especially for moderate myopia, achieving better daytime vision. In terms of controlling myopia, CRT fitting elevates return zone depth(RZD), creating a small central optical zone to produce more peripheral myopic defocus. However, there was no significant difference between the two groups in controlling AL growth. Both groups showed minimal corneal damage, indicating consistent safety in myopia control.
8.Advances in research on the role of biliary tract microecology in gallstone formation
Liyang CUI ; Lina YING ; Ruifang LI ; Yan SUN ; Zhenyu ZHANG ; Jun ZHANG
Chinese Journal of Primary Medicine and Pharmacy 2024;31(4):636-640
Cholelithiasis, a prevalent disease of the digestive system, is characterized by its intricate and diverse mechanisms, which are influenced by a complex interplay of genetic, environmental, lifestyle, and other factors. Recently, with the widespread application of molecular biology techniques, the role of the biliary tract microecological environment in the pathogenesis of gallstones has garnered increasing attention. This review includes the most recent and pertinent literature on the association between biliary tract microecology and gallstones, summarizing the latest research advancements in this field. Furthermore, it delves into the role of the biliary tract microecology in the formation of both cholesterol and pigment gallstones.
9.Impact of therapeutic plasma exchange intervention timing and liver injury periodization on the prognosis of pa-tients with exertional heat stroke
Zongzhong HE ; Min WANG ; Yuan ZHUANG ; Jie LIN ; Leiying ZHANG ; Liyang ZOU ; Lingling LI ; Chunya MA ; Xiaomin LIU ; Xiang QUAN ; Ying JIANG ; Mou ZHOU ; Hongjun KANG ; Yang YU
Chinese Journal of Blood Transfusion 2024;37(7):728-733
Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P<0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P<0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.
10.Detection of colorectal advanced neoplasms among the cancer screening population in urban areas of Henan Province and analysis on its influencing factors
Lanwei GUO ; Liyang ZHENG ; Qiong CHEN ; Yin LIU ; Huifang XU ; Ruihua KANG ; Hong WANG ; Xiaoyang WANG ; Shuzheng LIU ; Shaokai ZHANG
Chinese Journal of Oncology 2024;46(8):794-800
Objective:To analyze the detection of colorectal advanced neoplasms in the population who underwent colonoscopy screening in Henan Province as part of the Urban China Cancer Screening Program and its influencing factors.Methods:A cross-sectional study design was employed. Based on the Cancer Screening Program conducted in Henan Province, the study enrolled 7 454 urban residents who manifested no symptoms and were recruited from eight cities in the province, including Zhengzhou, Zhumadian, Anyang, Luoyang, Nanyang, Jiaozuo, Xinxiang, and Puyang from October 2013 to October 2019, and participated in colonoscopy screening. The χ 2 test was used to compare the detection rates of colorectal advanced neoplasms among participants with different characteristics, and a multivariate logistic stepwise regression model was used to analyze the factors affecting the detection rates. Results:A total of 7 454 subjects underwent colonoscopy screening, and 112 cases of colorectal advanced neoplasms were detected. Multivariate logistic regression analysis suggested that older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative were risk factors for colorectal advanced neoplasms. The detection rate was significantly higher in people aged 60-74 years compared with those aged 40-49 years, with an odds ratio ( OR) of 2.04 (95% CI: 1.23-3.38).The rates were higher in people who smoked than those who did not smoke, with an OR of 2.21 (95% CI: 1.48-3.31), and in people who consumed more meat than those who consumed less, with an OR of 1.53 (95% CI: 1.04-2.26). Those with diabetes had a higher detection rate compared with those without, with an OR of 1.69 (95% CI: 1.07-2.69), and those with a first-degree family history of colorectal cancer had a higher detection rate than those without, with an OR of 1.64 (95% CI: 1.09-2.46). Conclusion:The detection rate of colorectal advanced neoplasms through colonoscopy screening in Henan Province covered by the Urban China Cancer Screening Program is 1.50%. Older age, smoking, higher meat intake, history of diabetes, and family history of colorectal cancer in a first-degree relative are identified as risk factors for colorectal advanced neoplasms.


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