1.Polygonatum Sibiricum Polysaccharides Improve Colonic Injury in a Mouse Model of Chronic Obstructive Pulmonary Disease by Regulating Bile Acid Metabolism in the Colon
Wanrong LI ; Mengting TAO ; Yuanfeng ZOU ; Dan HE ; Nengyuan TANG ; Xin TAN ; Lixia LI ; Dandan CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):431-443
ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum (PSP-NP) on colon injury in mice with chronic obstructive pulmonary disease (COPD). MethodsMale C57BL/6J mice were randomly divided into a control group, a COPD model group, and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage, while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1, Occludin, IL-6, and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content, and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing, and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid (CA), and deoxycholic acid (DCA) in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay, and the mRNA expression levels of inflammatory cytokines TNF-α, IL-6, and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice, enhanced mechanical barrier function, alleviated inflammatory response, and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota, Verrucomicrobiota, Bacteroides, and Akkermansia, while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably, in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA, with the strongest binding capacity for DCA at 58.2%. In cellular functional studies, DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α, IL-6, and NF-κB. Importantly, co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding, thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.
2.Parkin inhibits iron overload-induced cardiomyocyte ferroptosis by ubiquitinating ACSL4 and modulating PUFA-phospholipids metabolism.
Dandan XIAO ; Wenguang CHANG ; Xiang AO ; Lin YE ; Weiwei WU ; Lin SONG ; Xiaosu YUAN ; Luxin FENG ; Peiyan WANG ; Yu WANG ; Yi JIA ; Xiaopeng TANG ; Jianxun WANG
Acta Pharmaceutica Sinica B 2025;15(3):1589-1607
Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER T2 /Parkin fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.
3.CT examination big data based on the Ningbo City Medical Imaging Cloud Platform
ZHANG Qun ; ZHANG Dandan ; WANG Yong ; ZHANG Liang ; ZOU Yuanjie ; LU Beibei ; TANG Sheng
Journal of Preventive Medicine 2025;37(12):1257-1260,1265
Objective:
To evaluate the radiation dose, operational standardization, and image quality of computed tomography (CT) Ningbo City Medical Imaging Cloud Platform, so as to provide references for optimizing the quality of CT examinations.
Methods:
Six CT devices were randomly selected from the Ningbo City Medical Imaging Cloud Platform. Digital Imaging and Communication in Medicine (DICOM) image data from CT examinations of the head, neck, chest, and abdomen in males aged 36 to 60 years were collected from January 2023 to December 2024. The radiation dose levels were evaluated using the volume CT dose index (CTDIvol) and dose length product (DLP). The coefficient of variation (CV) of CTDIvol and scan length were calculated to assess scan stability. Operational standardization was evaluated using the redundancy rate of scan length and protocol matching degree. Imaging quality was assessed using the signal to noise ratio (SNR) and contrast to noise ratio (CNR).
Results:
A total of 28 897 DICOM images were collected, including 6 730 axial scans of the skull, 2 778 plain scans of the neck, 15 496 plain scans of the chest, and 3 893 plain scans of the abdomen. The typical values of CTDIvol and DLP radiation doses for the head, neck, and chest were all lower than the diagnostic reference levels. The maximum typical values of CTDIvol and DLP for the abdomen were 22.49 mGy and 941.45 mGy·cm, respectively, which were higher than the diagnostic reference levels. The CV values of CTDIvol and scan length ranged from 14.59% to 37.88% and from 8.27% to 44.96%, respectively. The scan stability of head CT was relatively poor, with CV values ranging from 21.74% to 37.88% and from 12.66% to 44.96%, respectively. The redundancy rate of scan length ranged from 6.02% to 74.40%, and the protocol matching degree ranged from 79.80% to 100.00%. The operational standardization of neck CT was relatively poor, with redundancy rates ranging from 45.70% to 74.40% and protocol matching degrees ranging from 79.80% to 95.36%. The mean SNR and mean CNR of the pulmonary arteries in the chest were relatively high, ranging from 15.81 to 17.65 and from 6.33 to 7.41, respectively.
Conclusions
The radiation doses from abdominal CT examinations on some CT devices exceed the diagnostic reference levels. The scan stability of head CT examinations and the operational standardization of neck CT examinations represent weak points in quality control. It is recommended to carry out targeted quality control training to enhance the overall quality level of CT examinations.
4.Effect of fenofibrate on the expression of miR-26a-5p/PTEN in retinal neurons of diabetic mice
Derong TANG ; Yuwen YANG ; Rui SHI ; Dandan LIU ; Rong LIN
International Eye Science 2024;24(1):24-29
AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H& E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P<0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.
5.Effects of miR-26a-5p on high glucose-induced retina Müller activation and apoptosis by regulating PTEN/PI3K/Akt signaling pathway
Derong TANG ; Yuwen YANG ; Rui SHI ; Dandan LIU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):705-711
Objective To investigate the effects of microRNA-26a-5p(miR-26a-5p)on high glucose-induced retina Müller activation and apoptosis by regulating PTEN/PI3K/Akt signaling pathway,and the potential mechanism of diabetic retinal neurodegeneration.Methods Various concentrations of high glucose were added into rMC-1 culture.CCK-8 and flow cytometry was used to examine cell proliferation and apoptosis respectively.The regulatory effects of miR-26a-5p on the expressions of PTEN,PI3K and Akt were observed by real-time PCR;the expression levels of IL-1β and IL-6 in Müller cells were examined by ELISA.The data were processed by Graphpad 8.0 software.Results Müller cells grew actively in high-glucose stimulation culture.Compared with the control group,the activity of Müller cells stimulated by 50 mmol/L glucose increased gradually at 12 h and 24 h,but decreased at 48 h after stimulation,when Müller cells apoptosis increased.The difference between the groups was statistically significant(P<0.05).The expression of miRNA-26a-5p decreased,that of PTEN increased,and those of PI3K and Akt decreased.Meanwhile,IL-1β and IL-6 levels were significantly increased in Müller cells.miR-26a-5p over-expression alleviated injuries to high glucose stimulated retinal Müller cells by inhibiting PTEN,which upregulated the expression of PI3K/Akt and downregulation of IL-1β and IL-6(P<0.01).Conclusion Upregulating miR-26a-5p protects Müller cells against apoptosis,probably through regulation of PTEN/PI3K/Akt and affecting the production of inflammatory factors.
6.Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai
Jing WU ; Lei ZHANG ; Yu JIANG ; Dandan TANG ; Yuxuan XIAO ; Yun ZHANG ; Honglan LI ; Wensui ZHAO ; Qinghua XIA ; Yongbing XIANG
Chinese Journal of Oncology 2024;46(2):168-176
Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P<0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P>0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P<0.05) and females showing a downward trend (AAPC=-1.67%, P<0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.
7.Long-Term Survival Trend of Gynecological Cancer:A Systematic Review of Population-Based Cancer Registration Data
Zhou XIAOHUI ; Yang DANNI ; Zou YIXIN ; Tang DANDAN ; Chen JUN ; Li ZHUOYING ; Shen QIUMING ; Xu QUN ; Xiang YONGBING
Biomedical and Environmental Sciences 2024;37(8):897-921
Gynecological cancer significantly affect the health of women.This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers.We searched PubMed,Embase,Web of Science,SinoMed,and SEER for survival analyses of cancer registration data of cervical,endometrial,and ovarian cancers published between 1980 and 2022.Globally,the highest 5-year observed survival rate for cervical cancer was 76.5%in Anshan,Liaoning,China(2008-2017).The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland(1995-1999,82.5%)and Singapore(1988-1992,62.0%).The 5-year relative survival rate of cervical cancer patients was higher in Haining,Zhejiang,China(2011-2014,85.8%).Korea ranked first at 89.0%and 64.5%for endometrial and ovarian cancers,respectively.Survival rates have improved for cervical,endometrial,and ovarian cancers.Patients aged≥75 years and those with advanced-stage disease had the worst 5-year survival rates.Survival rates were better for squamous cell carcinoma in cervical cancer,for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer,and for germ cell and sex-cord stromal tumors in ovarian cancer.Over the past four decades,the survival rates of gynecological cancers have increased globally,with notable increases in cervical and endometrial cancers.Survival rates are higher in developed countries,with a slow-growing trend.Future studies should focus on improving survival,especially in ovarian cancer patients.
8.Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai
Jing WU ; Lei ZHANG ; Yu JIANG ; Dandan TANG ; Yuxuan XIAO ; Yun ZHANG ; Honglan LI ; Wensui ZHAO ; Qinghua XIA ; Yongbing XIANG
Chinese Journal of Oncology 2024;46(2):168-176
Objectives:To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district.Methods:Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods.Results:The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/10 5 and 597.51/10 5, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P<0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P>0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P<0.05) and females showing a downward trend (AAPC=-1.67%, P<0.05). Conclusions:The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.
9.Effects of sitagliptin activation of the stromal cell-derived factor-1/CXC chemokine receptor 4 signaling pathway on the proliferation,apoptosis,inflammation,and osteogenic differentiation of human periodontal ligament stem cells induced by lipopolysaccharide
Xiaoxue TANG ; Zheng ZHOU ; Qiqi LI ; Dandan JIANG
West China Journal of Stomatology 2024;42(1):37-45
Objective This study aimed to investigate the effects of sitagliptin on the proliferation,apoptosis,in-flammation,and osteogenic differentiation of human periodontal ligament stem cells(hPDLSCs)in lipopolysaccharide(LPS)-induced inflammatory microenvironment and its molecular mechanism.Methods hPDLSCs were cultured in vitro and treated with different concentrations of sitagliptin to detect cell viability and subsequently determine the exper-imental concentration of sitagliptin.An hPDLSCs inflammation model was established after 24 h of stimulation with 1 μg/mL LPS and divided into blank,control,low-concentration sitagliptin(0.5 μmol/L),medium-concentration sita-gliptin(1 μmol/L),and high-concentration sitagliptin(2 μmol/L),high-concentrationsitagliptin+stromal cell derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway inhibitor(AMD3100)(2 μmol/L+10 μg/mL)groups.A cell-counting kit-8 was used to detect the proliferation activity of hPDLSCs after 24,48,and 72 h culture.The apoptosis of hPDLSCs cultured for 72 h was detected by flow cytometry.After inducing osteogenic differentiation for 21 days,alizarin red staining was used to detect the osteogenic differentiation ability of hPDLSCs.The alkaline phosphatase(ALP)activity in hPDLSCs was determined using a kit.The levels of inflammatory factors[tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-6]in the supernatant of hPDLSCs culture were detected by enzyme-linked immu-nosorbent assay.The mRNA expressions of osteogenic differentiation genes[Runt-associated transcription factor 2(RUNX2),osteocalcin(OCN),osteopontin(OPN)],SDF-1 and CXCR4 in hPDLSCs were detected by real-time fluores-cence quantitative polymerase chain reaction(RT-qPCR).Western blot analysis was used to determine SDF-1 and CX-CR4 protein expression in hPDLSCs.Results Compared with the blank group,the proliferative activity,number of mineralized nodules,staining intensity,ALP activity,and RUNX2,OCN,OPN mRNA,SDF-1,and CXCR4 mRNA and protein expression levels of hPDLSCs in the control group significantly decreased.The apoptosis rate and levels of TNF-α,IL-1β,and IL-6 significantly increased(P<0.05).Compared with the control group,the proliferative activity,number of mineralized nodule,staining intensity,ALP activity,and RUNX2,OCN,OPN mRNA,SDF-1,and CXCR4 mRNA and protein expression levels of hPDLSCs in low-,medium-,and high-concentration sitagliptin groups in-creased.The apoptosis rate and levels of TNF-α,IL-1β,and IL-6 decreased(P<0.05).AMD3100 partially reversed the effect of high-concentration sitagliptin on LPS-induced hPDLSCs(P<0.05).Conclusion Sitagliptin may promote the proliferation and osteogenic differentiation of hPDLSCs in LPS-induced inflammatory microenvironment by activating the SDF-1/CXCR4 signaling pathway.Furthermore,it inhibited the apoptosis and inflammatory response of hPDLSCs.
10.Current situation and influencing factors of fertility intention to have a third child among childbearing age women in Heilongjiang Province under three-child policy
Yue DONG ; Qiang LI ; Lin CAO ; Dandan YU ; Meiling TANG ; Yingyan ZHANG
Chinese Journal of Modern Nursing 2024;30(24):3309-3313
Objective:To explore the current status and influencing factors of fertility intention to have a third child among childbearing age women in Heilongjiang Province under three-child policy.Methods:From January to April 2023, convenience sampling was used to select 10 600 women of childbearing age from ten districts and counties in five cities in Heilongjiang Province (Jiamusi, Qiqihar, Harbin, Heihe, Suihua) as research subjects. The Fertility Intention to Have a Third Child Questionnaire among Childbearing Age Women in Heilongjiang Province was used to investigate women of childbearing age. Multi-class Logistic regression was used to explore the influencing factors of fertility intention of childbearing age women to have a third child.Results:A total of 10 600 questionnaires were distributed, and 9 554 valid questionnaires were collected, with a valid response rate of 90.13% (9 554/10 600). Among 9 554 women of childbearing age, 2 248 had the intention to have a third child, 5 036 had no intention, and 2 270 were uncertain. Multi-class Logistic regression analysis showed that age, education level, per capita monthly income of the family, occupation, fertility status, pregnancy complications, economic pressure to have a third child, parents' attitudes towards having a third child, and satisfaction with childcare services were the influencing factors of the fertility intention of childbearing age women in Heilongjiang Province to have a third child ( P<0.05) . Conclusions:Under the three-child policy, women of childbearing age in Heilongjiang Province have a low intention to have a third child. Relevant departments should formulate policies based on the influencing factors.


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