1.Fibroblast growth factor 21 attenuates oxidative stress injury in retinal pigment epithelial cells under high glucose via FGFR1/PI3K/Akt signal pathway
Ye TIAN ; Guoheng ZHANG ; Tianhao YUAN ; Xin WANG ; Tianfang CHANG ; Yuan CHEN ; Guorui DOU
International Eye Science 2026;26(3):383-390
AIM:To investigate the effect of fibroblast growth factor 21(FGF21)on high glucose-induced oxidative stress in retinal pigment epithelial(RPE)cells and to clarify the underlying molecular mechanisms.METHODS:Single-cell sequencing data from the GEO database were analyzed to determine the expression profile of the FGF21 receptor FGFR1 in RPE cells. Human ARPE-19 cells were cultured and randomly assigned to control, high glucose(30 mmol/L), and high glucose+FGF21 analog treatment groups, with additional siFGFR1 and PI3K inhibitor groups. Cell viability in different treatment groups was assessed using CCK-8 assay, intracellular reactive oxygen species(ROS)levels were quantified using DCFH-DA fluorescent probing combined with immunofluorescence staining and flow cytometry. Transcriptome sequencing was performed on cells from the high glucose group and high glucose+FGF21 group to analyze the enrichment level of the PI3K/Akt signaling pathway. Western blotting was performed to detect phosphorylation levels of PI3K/Akt pathway components.RESULTS:Single-cell sequencing revealed specific expression of FGFR1 in RPE cells of retinal tissues from diabetic model mice. Under In vitro experiments, high glucose(30 mmol/L)exposure reduced ARPE-19 cell viability by 49.7% and increased ROS levels by approximately 2-fold. Whereas treatment with the FGF21 analog(60 ng/mL)restored cell viability and attenuated high glucose-induced ROS accumulation. Mechanistic studies demonstrated that FGFR1 knockdown inhibited the antioxidative stress of FGF21. Further validation of the molecular mechanism revealed that high glucose significantly suppressed the PI3K/Akt pathway activation(the levels of p-Akt and p-PI3K were decreased by 33.9% and 36.6%, respectively), while FGF21 effectively reversed this inhibitory effect and restored the expression of p-Akt and p-PI3K. Treatment with the PI3K inhibitor LY294002 inhibited the cytoprotective effect of FGF21 and significantly increased the ROS-positive cells, these findings confirm that PI3K/Akt signaling is indispensable downstream mechanism for FGF21 to exert its effects.CONCLUSION:FGF21 alleviates high glucose-induced oxidative stress and cellular injury in RPE cells by activating the PI3K/Akt signaling pathway through its receptor FGFR1.
2.Influencing factors for calcium salt deposition in patients with alveolar echinococcosis
Zitong XIONG ; Zhiyi LIN ; Yanxin HUANG ; Fuzhong FANG ; Zhengzhan WU ; Zirui XIN ; Chunxia HU ; Jiayu ZHOU ; Yuan YAO ; Hongwei ZHANG
Journal of Clinical Hepatology 2026;42(2):372-379
ObjectiveTo investigate the imaging features of calcium salt deposition and serological markers in patients with alveolar echinococcosis through a retrospective analysis, as well as independent risk factors for the degree of calcium salt deposition in lesions, and to provide a basis for assessing disease process. MethodsA retrospective analysis was performed for the imaging and clinical data of 107 patients with alveolar echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from December 2023 to June 2025, and according to the volume of calcium salt deposition, they were divided into non-deposition group with 16 patients, mild deposition group with 52 patients, moderate deposition group with 16 patients, and severe deposition group with 23 patients. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups, and the χ2 test or Fisher’s exact test was used for comparison of categorical data between groups. The four groups were further combined into the low deposition group (no/mild deposition) and the high deposition group (moderate/severe deposition). A binary logistic regression analysis was used to investigate the independent influencing factors for calcium salt deposition, and a predictive model was established. The receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model, and the Bootstrap method was used for internal validation. ResultsThere were significant differences between the four groups in sex distribution, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.05). The univariate analysis showed that there were significant differences between the four groups in sex, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, alanine aminotransferase, albumin, creatinine, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.1). The multi-collinearity diagnosis showed that the VIF values for all continuous variables ranged from 1.104 to 1.760, suggesting that collinearity did not affect modeling. An ordinal logistic regression model was established based on sex, involvement of other sites, calcium ion, lymphocyte percentage, and uric acid. The multivariate analysis showed that lymphocyte percentage (odds ratio [OR]=1.106, 95% confidence interval [CI]: 1.041 — 1.174, P=0.001) and blood calcium level (OR=0.005, 95%CI: 0.000 —0.230, P=0.007) were independent influencing factors for the degree of calcium salt deposition. The regression equation was established as Logit(P)=8.231 + 0.100 × lymphocyte percentage -5.344 × calcium ion. The ROC curve analysis showed that the model had an area under the ROC curve of 0.716, with a Youden index of 0.353, a sensitivity of 1.000, and a specificity of 0.353. The Hosmer-Lemeshow test showed that the model had poor calibration (χ2=20.688, P=0.008). The Bootstrap method with 1000 repeated samples showed that the estimated values of lymphocyte percentage (OR=1.106, 95%CI: 1.049 — 1.186, P=0.002) and calcium ion (OR=0.005, 95%CI: 0.000 — 0.214, P=0.010) were consistent with the original model, and the confidence intervals did not include 1, which further supported the reliability of the model. ConclusionBoth lymphocyte percentage and blood calcium level are independent influencing factors for calcium salt deposition in alveolar echinococcosis, and the degree of calcium salt deposition in alveolar echinococcosis lesions increases with the reduction in blood calcium level and the increase in lymphocyte percentage.
3.Clinical efficacy of Huangkui capsules in the treatment of targeted drug-related proteinuria in patients with hepatocellular carcinoma
Miao LI ; Jia YUAN ; Chu LIU ; Maopei CHEN ; Xin XU ; Ningling GE ; Yi CHEN ; Lan ZHANG ; Rongxin CHEN ; Yan WANG
Chinese Journal of Clinical Medicine 2026;33(1):88-94
Objective To investigate the therapeutic effect of Huangkui capsules on targeted drug-related proteinuria in patients with hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on clinical data of HCC patients with targeted drug-related proteinuria from June 2023 to December 2024 at Zhongshan Hospital, Fudan University. According to the treatment plan, patients were divided into the conventional treatment group and the Huangkui combination treatment group (Huangkui capsules combined with conventional treatment), and the clinical efficacy between the two groups was compared. The logistic regression analysis was used to identify the main factors affecting treatment efficacy. Results The Huangkui combination treatment group (n=29) showed a significantly higher overall effective rate (79.3% vs 42.3%, P=0.005), and an earlier proteinuria improvement (median time: 3 months vs 6 months, P=0.008) than the conventional treatment group (n=26) . The multivariate logistic regression analysis showed angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker (ARB) using (OR=0.190, 95%CI 0.045-0.808, P=0.025), targeted drug adjustment (OR=0.132, 95%CI 0.030-0.581, P=0.007), and Huangkui capsules using (OR=0.168, 95%CI 0.039-0.730, P=0.017) were protective factors for treatment efficacy of targeted drug-related proteinuria. Conclusions On the basis of conventional treatment, additive treatment with Huangkui capsules can alleviate targeted drug-related proteinuria faster and more effectively in HCC patients.
4.Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma
Shan LI ; Jie HU ; Yihan YAN ; Xinrui LIU ; Xiao DONG ; Huijun LIANG ; Xin TANG ; Junji TAO ; Rong ZHANG ; Yuan HU ; Ailong HUANG ; Kai WANG ; Ni TANG
Clinical and Molecular Hepatology 2026;32(2):661-682
Background/Aims:
Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial.
Methods:
A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining.
Results:
Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth.
Conclusions
These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.
5.Application effect of oral health management program based on behavior change wheel theory for children aged 5-6 years
YUAN Meng, ZHANG Xin, DUAN Xiaoyan
Chinese Journal of School Health 2025;46(2):210-214
Objective:
To evaluate the application effect of oral health management program based on behavior change wheel (BCW) theory, so as to provide a reference for improving children s awareness of oral self management and the development of healthy oral behaviors.
Methods:
A total of 120 children aged 5-6 from 2 kindergartens in Yubei District in Chongqing City, selected by convenience sampling method from September 2023 to March 2024, were divided into a experimental group and a control group (60 each). Children in the experimental group were given an oral health education programme based on BCW theory (promoted health awareness, cultivated healthy behavior ability, strengthened awareness and ability, and provided opportunitiess) on the basis of conventional oral health education, and children in the control group were given conventional oral health education; data were collected before and 3 months after the intervention, respectively. Comparisons between groups were made using the Mann-Whitney U test and χ 2 test.
Results:
Before intervention, there were no significant differences in plaque index [2.00(1.00,2.00), 2.00(1.00,2.00)] and the number of filled teeth [0.00(0.00,1.00), 0.00( 0.00 ,1.00)] between the experimental group and the control group ( Z=-0.88, -0.42, P >0.05). After intervention, the plaque index of the experimental group [1.00(0.00,1.00)] was lower than that of the control group [1.00(0.25,2.00)] and before intervention, and the number of filling teeth in the experimental group [1.00(0.00,2.00)] was higher than that of the control group [1.00(0.00,1.00)] and before intervention, the differences were statistically significant ( Z =-3.14, -5.48; -2.08, -3.02, P <0.05). Before intervention, there were no significant differences in oral health behavior report rate and oral health knowledge mastery rate between the two groups ( χ 2=0.30-0.91, 0.15-1.43, P > 0.05 ). After intervention, the report rates of health tooth brushing (method, frequency and duration) and preventive behavior (using fluoride toothpaste, pit and fissure sealing prevention and fluoride application prevention) in the experimental group were better than those in the control group and before intervention, and the differences were statistically significant ( χ 2=4.88-9.38, 9.13- 22.63 , P <0.05). The mastery rates of oral health knowledge in the experimental group were better than that in the control group, and the differences were statistically significant ( χ 2=4.62-8.54, P <0.05).
Conclusion
Oral health management programs based on the BCW theory are more conducive to improving children s oral hygiene, as well as enhancing children s basic oral knowledge and promoting the development of oral health behaviors.
6.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
7.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
8.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
9.Molecular mechanism of programmed cell death in lung cancer and progress in traditional Chinese medicine intervention.
Cheng LUO ; Bo NING ; Xin-Yue ZHANG ; Yu-Zhi HUO ; Xin-Hui WU ; Yuan-Hang YE ; Fei WANG
China Journal of Chinese Materia Medica 2025;50(3):632-643
Lung cancer is one of the most common and deadliest cancers globally, with its incidence and mortality rates rising each year. Therefore, finding new, safe, and effective alternative therapies poses a significant research challenge in this field. Programmed cell death refers to the process by which cells actively self-destruct in response to specific stimuli, regulated by genetic mechanisms. Modern research indicates that dysregulation of programmed cell death is widespread in the occurrence and progression of lung cancer, allowing cancer cells to evade death while continuing to proliferate and metastasize. Thus, inducing the death of lung cancer cells can be considered a novel therapeutic strategy for treating the disease. In recent years, research on traditional Chinese medicine(TCM) in the field of oncology has gained widespread attention, becoming a focal point. An increasing number of studies have demonstrated that TCM can inhibit the progression of lung cancer and exert anti-cancer effects by inducing apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis. This paper provided a comprehensive review of the molecular mechanisms of programmed cell death in lung cancer, along with the potential mechanisms and research advancements related to the regulation of these processes by TCM, so as to establish a theoretical foundation and direction for future basic and clinical research on lung cancer.
Humans
;
Lung Neoplasms/pathology*
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/therapeutic use*
;
Apoptosis/drug effects*
;
Animals
;
Autophagy/drug effects*
10.Research progress on natural small molecule compound inhibitors of NLRP3 inflammasome.
Tian-Yuan ZHANG ; Xi-Yu CHEN ; Xin-Yu DUAN ; Qian-Ru ZHAO ; Lin MA ; Yi-Qi YAN ; Yu WANG ; Tao LIU ; Shao-Xia WANG
China Journal of Chinese Materia Medica 2025;50(3):644-657
In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Inflammasomes/metabolism*
;
Inflammation/drug therapy*
;
Anti-Inflammatory Agents/therapeutic use*
;
Humans
;
Animals
;
Disease Models, Animal
;
Biological Products/therapeutic use*
;
Drug Discovery
;
Medicine, Chinese Traditional/methods*


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