1.Mechanism of benzoapyrene-induced mitochondrial DNA damage mediated by PDX-1/TFAM pathway
Rong CUI ; Yi CHENG ; Li WANG ; Xiaohe ZHAI
Journal of Environmental and Occupational Medicine 2026;43(5):575-581
Background Previous studies have found that exposure to benzo[a]pyrene (BaP) can lead to functional impairment of the human pancreas. Pancreatic and duodenal homeobox factor 1 (PDX-1) may play a role in regulating mitochondrial function. It is hypothesized that BaP exposure may interfere with PDX-1 expression in human pancreatic ductal epithelial cells (H6C7), thereby affecting mitochondrial transcription factor A (TFAM). This process could induce mitochondrial DNA (mtDNA) damage, disrupt pancreatic development and function, and elevate the risk of diabetes onset. Objective To investigate the mechanism of BaP-induced mtDNA damage through disruption of the PDX-1/TFAM pathway in a H6C7 cell model. Methods A H6C7 cell injury model was established using different concentrations of BaP. Cell viability was determined using cell counting kit-8 (CCK-8). After 24 h of BaP exposure (5,10, and 20 μmol·L−1), cell morphological and mitochondrial membrane potential (MMP) changes were observed via confocalmicroscopy, and PDX-1/TFAM protein expression levels were assessed. Bioinformatics analysis combined with dual-luciferase reporter assays was used to confirm PDX-1 directly targeting the TFAM promoter. Following PDX-1 overexpression or silencing in BaP treated cells, flow cytometry was used to evaluate viability and apoptosis, while Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) measured PDX-1/TFAM expression and mitochondrial DNA copy number (mtDNA-cn). Results The cell injury model demonstrated that, compared with the control group, BaP exposure reduced cell viability, disrupted membrane integrity, induced nuclear fragmentation, and decreased MMP. Protein expression levels of PDX-1 and TFAM were significantly downregulated in the 10 and 20 μmol·L−1 groups (P<0.05). Dual-luciferase reporter assays confirmed that PDX-1 overexpression upregulated TFAM levels. Flow cytometry revealed that PDX-1 overexpression significantly reduced apoptosis rate (P<0.001), whereas PDX-1 silencing increased apoptosis rate (P<0.001). Compared with the BaP-only group, BaP+PDX-1 overexpression elevated TFAM protein and mRNA expression as well as mtDNA-cn (P<0.01), while BaP+siRNA-PDX-1 suppressed these parameters (P<0.001). Conclusion BaP exposure promotes apoptosis in human pancreatic cells. PDX-1, a key gene in pancreatic development, regulates the expression of TFAM, a core regulator of mitochondrial function. This interaction triggers changes in MMP and mtDNA-cn, activates the PDX-1/TFAM/mtDNA axis, and ultimately leads to pancreatic cell injury.
2.Mechanism of benzoapyrene-induced mitochondrial DNA damage mediated by PDX-1/TFAM pathway
Rong CUI ; Yi CHENG ; Li WANG ; Xiaohe ZHAI
Journal of Environmental and Occupational Medicine 2026;43(5):575-581
Background Previous studies have found that exposure to benzo[a]pyrene (BaP) can lead to functional impairment of the human pancreas. Pancreatic and duodenal homeobox factor 1 (PDX-1) may play a role in regulating mitochondrial function. It is hypothesized that BaP exposure may interfere with PDX-1 expression in human pancreatic ductal epithelial cells (H6C7), thereby affecting mitochondrial transcription factor A (TFAM). This process could induce mitochondrial DNA (mtDNA) damage, disrupt pancreatic development and function, and elevate the risk of diabetes onset. Objective To investigate the mechanism of BaP-induced mtDNA damage through disruption of the PDX-1/TFAM pathway in a H6C7 cell model. Methods A H6C7 cell injury model was established using different concentrations of BaP. Cell viability was determined using cell counting kit-8 (CCK-8). After 24 h of BaP exposure (5,10, and 20 μmol·L−1), cell morphological and mitochondrial membrane potential (MMP) changes were observed via confocalmicroscopy, and PDX-1/TFAM protein expression levels were assessed. Bioinformatics analysis combined with dual-luciferase reporter assays was used to confirm PDX-1 directly targeting the TFAM promoter. Following PDX-1 overexpression or silencing in BaP treated cells, flow cytometry was used to evaluate viability and apoptosis, while Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) measured PDX-1/TFAM expression and mitochondrial DNA copy number (mtDNA-cn). Results The cell injury model demonstrated that, compared with the control group, BaP exposure reduced cell viability, disrupted membrane integrity, induced nuclear fragmentation, and decreased MMP. Protein expression levels of PDX-1 and TFAM were significantly downregulated in the 10 and 20 μmol·L−1 groups (P<0.05). Dual-luciferase reporter assays confirmed that PDX-1 overexpression upregulated TFAM levels. Flow cytometry revealed that PDX-1 overexpression significantly reduced apoptosis rate (P<0.001), whereas PDX-1 silencing increased apoptosis rate (P<0.001). Compared with the BaP-only group, BaP+PDX-1 overexpression elevated TFAM protein and mRNA expression as well as mtDNA-cn (P<0.01), while BaP+siRNA-PDX-1 suppressed these parameters (P<0.001). Conclusion BaP exposure promotes apoptosis in human pancreatic cells. PDX-1, a key gene in pancreatic development, regulates the expression of TFAM, a core regulator of mitochondrial function. This interaction triggers changes in MMP and mtDNA-cn, activates the PDX-1/TFAM/mtDNA axis, and ultimately leads to pancreatic cell injury.
3.Imaging longitudinal study of coronary artery plaques in elderly men with coronary artery disease and myocardial bridges
Xue ZHENG ; Jinjin CUI ; Xinjiang WANG ; Guanzhong LIU ; Bingqi KANG ; Peng TIAN ; Hongxiang YAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):173-177
Objective To evaluate the longitudinal imaging features of coronary artery plaques in elderly male patients with CHD and myocardial bridges and explore the longitudinal changing pat-terns.Methods A total of 117 elderly male CHD patients who underwent two examinations of coronary computed tomography angiography in our medical center from January 2018 to Septem-ber 2023 were enrolled in this study.Then 216 small plaques(0.1-50 mm3 in size)were subjec-ted,and classified into the proximal myocardial bridge group(98 plaques)and other heart part group(118 plaques)according to the site of the plaques.Plaque volume,plaque composition vol-ume,FAI,and CT-derived fraction flow reserve(CT-FFR)were calculated and recorded.Results In the 2 groups of plaques,there were no statistically differences in the plaque length,plaque nec-rotic core volume,and FAI derived from the second examination than the baseline one(P>0.05).The plaque volume,intra-plaque fibers,and dense calcified volume of plaques in the second exami-nation were significantly greater than those at baseline,and CT-FFR was obviously smaller than the baseline level in both groups(P<0.05,P<0.01).In the proximal myocardial bridge group,the intra-plaque fibrofat volume in the second examination was significantly larger than that of baseline,while opposite phenomenon was observed in the plaques of the other heart part group(P<0.05).The annual changing rates of intraplaque fibrofat volume and FAI were significantly higher in the proximal myocardial bridge group than the other heart part group[0.51%(-0.32%,0.51%)vs 0.02%(-0.46%,0.20%),P=0.046;0.55%(-2.44%,1.76%)vs 0.33%(-1.36%,2.63%),P=0.044].Conclusion In elderly male patients,the intraplaque fibrofat vol-ume,FAI and CT-FFR are more likely to change in the proximal plaques of the left anterior de-scending artery myocardial bridge than the plaques of other parts of heart,so the proximal plaques of the left anterior descending artery need more clinical attention and early intervention.
4.Imaging longitudinal study of coronary artery plaques in elderly men with coronary artery disease and myocardial bridges
Xue ZHENG ; Jinjin CUI ; Xinjiang WANG ; Guanzhong LIU ; Bingqi KANG ; Peng TIAN ; Hongxiang YAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):173-177
Objective To evaluate the longitudinal imaging features of coronary artery plaques in elderly male patients with CHD and myocardial bridges and explore the longitudinal changing pat-terns.Methods A total of 117 elderly male CHD patients who underwent two examinations of coronary computed tomography angiography in our medical center from January 2018 to Septem-ber 2023 were enrolled in this study.Then 216 small plaques(0.1-50 mm3 in size)were subjec-ted,and classified into the proximal myocardial bridge group(98 plaques)and other heart part group(118 plaques)according to the site of the plaques.Plaque volume,plaque composition vol-ume,FAI,and CT-derived fraction flow reserve(CT-FFR)were calculated and recorded.Results In the 2 groups of plaques,there were no statistically differences in the plaque length,plaque nec-rotic core volume,and FAI derived from the second examination than the baseline one(P>0.05).The plaque volume,intra-plaque fibers,and dense calcified volume of plaques in the second exami-nation were significantly greater than those at baseline,and CT-FFR was obviously smaller than the baseline level in both groups(P<0.05,P<0.01).In the proximal myocardial bridge group,the intra-plaque fibrofat volume in the second examination was significantly larger than that of baseline,while opposite phenomenon was observed in the plaques of the other heart part group(P<0.05).The annual changing rates of intraplaque fibrofat volume and FAI were significantly higher in the proximal myocardial bridge group than the other heart part group[0.51%(-0.32%,0.51%)vs 0.02%(-0.46%,0.20%),P=0.046;0.55%(-2.44%,1.76%)vs 0.33%(-1.36%,2.63%),P=0.044].Conclusion In elderly male patients,the intraplaque fibrofat vol-ume,FAI and CT-FFR are more likely to change in the proximal plaques of the left anterior de-scending artery myocardial bridge than the plaques of other parts of heart,so the proximal plaques of the left anterior descending artery need more clinical attention and early intervention.
5.Predictive value of serum Lp-PLA2 level for high-risk coronary plaques in elderly males
Jinjin CUI ; Keyu WANG ; Xinwei CHANG ; Fang LI ; Hongxiang YAO ; Xue ZHENG ; Jian ZHAO ; Guanzhong LIU ; Xinjiang WANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(7):836-840
Objective To investigate the value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)for predicting high-risk coronary plaques in elderly males.Methods A retrospective study was conducted on 46 elderly males aged ≥60 years undergoing health check-ups and coro-nary computed tomography angiography in our hospital between May and July 2024.Their general clinical data were collected.Artificial intelligence software was used to analyze coronary calcium scores and plaque characteristics.The participants were divided into a high-risk plaque group(n=15)and a non-high-risk plaque group(n=31).The differences were compared between the two groups.Multivariate logistic regression analysis was used to identify the influencing factors for high-risk coronary plaques.ROC curve was plotted to determine the predictive value of serum Lp-PLA2 for high-risk plaques,and its AUC value was calculated.Results The high-risk plaque group had significantly larger proportions of smoking history and hyperlipidemia,and higher level of homocysteine and Lp-PLA2 than the non-high-risk plaque group(P<0.05,P<0.01).Multiva-riate logistic regression analysis indicated that Lp-PLA2 was an independent risk factor for high-risk coronary plaques(HR=1.030,95%CI:1.008-1.053,P<0.05).ROC curve analysis revealed that the AUC value of Lp-PLA2 in predicting high-risk coronary plaques was 0.833(95%CI:0.694-0.927,P<0.01),with a sensitivity of 93.3%,a specificity of 71.0%,a positive predictive value of 62.5%,and a negative predictive value of 100%.Conclusion Serum Lp-PLA2 is of signif-icant value in predicting high-risk coronary plaques in elderly men.
6.Application of cardiac magnetic resonance myocardial strain technology in elderly men with hypertrophic cardiomyopathy
Xue ZHENG ; Bingqi KANG ; Jinjin CUI ; Guanzhong LIU ; Xinjiang WANG ; Xue YANG ; Shuxia WANG ; Ping ZHU ; Hongxiang YAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(5):548-553
Objective To explore the application value of CMR myocardial strain technique in eld-erly males with HCM.Methods A retrospective analysis was conducted on 50 elderly male pa-tients who underwent CMR examination at the Second Medical Center of Chinese PLA General Hospital from April 2020 to December 2024.According to being diagnosed with HCM or not,they were divided into a HCM group(24 cases)and a control group(26 cases).Post-processing soft-ware CVI42 was used to obtain two sets of basic functional and strain parameters of the left ven-tricle(LV)and left atrium(LA).The parameters of LV included LV mass,LV mass index(LV massi),global longitudinal strain(GLS),and so on,while the parameters of LA included minimum LA volume(LAV),minimum LA volume index(LA VI),LA passive strain(εe),LA peak early negative strain rate(SRe)and LA peak late negative strain rate(SRa),etc.The two sets of LV and LA parameters of basic functional and strain were compared between the two groups.Results The HCM group had significant higher LV mass and LV massi and minimum LAV and LAVI,but lower GLS,εe,SRe and SRa in 2D and 3D speckle-tracking echocardiography than the control group(P<0.05,P<0.01).The AUC value of 2D GLS,SRa,and logistic regres-sion model in predicting HCM was 0.887(95%CI:0.766-0.959),0.740(95%CI:0.597-0.854),and 0.929(95%CI:0.820-0.983),respectively,with a sensitivity of 76.92%,57.69%,and 84.62%,and a specificity of 70.83%,83.33%,and 91.67%,respectively.The logistic regression model demonstrated higher AUC value,sensitivity,and specificity than 2D GLS and SRa.Conclusion CMR myocardial strain technology is of significant diagnostic value for elderly male patients with HCM.
7.Effect of healthy side tilt training on balance function in patients with Pusher syndrome after stroke
Wenwen MA ; Yanzheng WEN ; Manripati ROZI ; Boya CUI ; Qimei SUYIN
Chinese Journal of Rehabilitation Theory and Practice 2025;31(2):225-230
ObjectiveTo observe the effect of healthy side tilt training on balance function in patients with Pusher syndrome (PS) after stroke. MethodsFrom February, 2021 to November, 2023, 40 patients with PS after stroke in People's Hospital of Bayingolin Mongolian Autonomous Prefecture were selected. They were divided into control group (n = 20) and experimental group (n = 20) in accordance with the order of the patients' admission. The control group received comprehensive training for paralyzed limbs combined with sitting balance training, and the experimental group received comprehensive training for paralyzed limbs combined with healthy side tilt training, for three weeks. They were assessed with Burke Lateropulsion Scale (BLS), Fugl-Meyer Assessment-Balance (FMA-B) and modified Barthel Index (MBI) before and after treatment. ResultsAfter treatment, BLS score significantly decreased in both groups (t > 12.603, P < 0.001), and was lower in the experimental group than in the control group (t = -2.559, P < 0.05). The scores of FMA-B and MBI were significantly increased in both groups (|Z| > 3.941, |t| > 12.082, P < 0.001), and FMA-B score was higher in experimental group than in the control group (Z = -2.538, P < 0.05). ConclusionComprehensive training for paralyzed limbs combined with healthy side tilt training can effectively improve the balance function and postural control of patients with PS after stroke, and improve the activities of daily living.
8.Blood management strategy for massive transfusion patients in frigid plateau region
Haiying WANG ; Jinjin ZHANG ; Lili CHEN ; Xiaoli SUN ; Cui WEI ; Yongli HUANG ; Yingchun ZHU ; Chong CHEN ; Yanchao XING
Chinese Journal of Blood Transfusion 2025;38(2):268-273
[Objective] To explore the strategy of blood management in patients with massive transfusion in the frigid plateau region. [Methods] The treatment process of a patient with liver rupture in the frigid plateau region was analyzed, and the blood management strategy of the frigid plateau region was discussed in combination with the difficulties of blood transfusion and literature review. [Results] The preoperative complete blood count (CBC) test results of the patient were as follows: RBC 3.14×1012/L, Hb 106 g/L, HCT 30.40%, PLT 115.00×109/L; coagulation function: PT 18.9 s, FiB 1.31 g/L, DD > 6 μg/mL, FDP 25.86 μg/mL; ultrasound examination and imaging manifestations suggested liver contusion and laceration / intraparenchymal hematoma, splenic contusion and laceration, and massive blood accumulation in the abdominal cavity; it was estimated that the patient's blood loss was ≥ 2 000 mL, and massive blood transfusion was required during the operation; red blood cell components were timely transfused during the operation, and the blood component transfusion was guided according to the patient's CBC and coagulation function test results, providing strong support and guarantee for the successful treatment of the patient. The patient recovered well after the operation, and the CBC test results were as follows: RBC 4.32×1012/L, Hb 144 g/L, HCT 39.50%, PLT 329.00×109/L; coagulation function: APTT 29.3 s, PT 12.1 s, FiB 2.728 g/L, DD>6 μg/mL, FDP 25.86 μg/mL. The patient was discharged after 20 days, and regular follow-up reexamination showed no abnormal results. [Conclusion] Individualized blood management strategy should comprehensively consider the patient’s clinical symptoms, the degree of hemoglobin decline, dynamic coagulation test results and existing treatment conditions. Efficient and reasonable patient blood management strategies can effectively improve the clinical outcomes of massive transfusion patients in the frigid plateau region.
9.Bronchial arterial chemoembolization combined with tislelizumab for the treatment of locally advanced non-small cell lung cancer:analysis of its clinical effect
Rong LIU ; Houfa NING ; Xinjiang CUI
Journal of Interventional Radiology 2025;34(5):477-481
Objective To discuss the clinical efficacy of bronchial arterial chemoembolization(BACE)combined with tislelizumab in treating unresectable locally advanced non-small cell lung cancer(NSCLC)with negative driver gene.Methods The clinical data of 54 patients of locally advanced NSCLC with negative driver gene,who were admitted to the Affiliated Hospital of Shandong Second Medical University of China from April 2020 to April 2021,were retrospectively analyzed.Of the 54 patients,27 received BACE combined with Tislelizumab(combination group)and 27 received BACE alone(control group).After three cycles of BACE treatment,the patients were followed up for 20 months.The clinical short-term efficacy,the preoperative and postoperative karnofsky performance status(KPS)score,surgical complications and adverse event(AE)in both groups were statistically analyzed.The number of patients who obtained successful transformation after treatment and the median progression-free survival(mPFS)in both groups were calculated.Results The objective response rate(ORR)and disease control rate(DCR)of the combination group were higher than those of the control group(ORR:81.48%vs 55.56%and DCR:96.29%vs 77.78%).A total of 4 patients in the combination group met the requirements of R0 resection,and the transformation success rate was 14.81%,while no patient in the control group met the requirements of R0 resection,the difference between the two groups was statistically significant(P<0.05).The mPFS of the combination group was 13.3 months,which was strikingly longer than 9.2 months of the control group(P<0.05).The postoperative improvement rate of KPS score in the combination group was remarkably higher than that in the control group(77.78%vs 48.15%,P<0.05).Conclusion For unresectable locally advanced NSCLC with negative driver gene,BACE combined with Tislelizumab can effectively kill tumor cells,thus the original unresectable tumor may be,in some extent,surgically treated with R0 resection,and a higher ORR as well as a higher DCR can be well expected,the patient's quality of life can be improved,and the patient's mPFS can be prolonged.
10.Three new gallic acid sugaresters from Elaeagnus oxycarpa Schlechtend leaves and their antioxidant and tyrosinase inhibitory activities
Feng-zhen CUI ; Jian-hong FU ; Guo-yan XU ; AYEKABAYR·EKBAYR ; Chang-da MA
Acta Pharmaceutica Sinica 2025;60(2):434-441
Five compounds were isolated and purified from the water extract of

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