1.Effect of Zuogui Wan and Yougui Wan on Mitochondrial Biogenesis in BMSCs Through PGC-1α/PPARγ
Ying YANG ; Xiuzhi FENG ; Yiran CHEN ; Zhimin WANG ; Xian GUO ; Yanling REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):28-36
ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form", this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells (BMSCs) by mediating peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and peroxisome proliferators-activated receptor γ (PPARγ), providing theoretical support for the prevention and treatment of postmenopausal osteoporosis (PMOP) using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group, Zuogui Wan (ZGW) group, Yougui Wan (YGW) group, and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ, CCAAT/enharcer-binding protein (C/EBP)α, C/EBPβ, lipoprotein lipase (LPL) protein, brown adipose tissue-related (BAT) proteins PGC-1α, uncoupcing protein 1 (UCP1), PR domdin-containing protein 16 (PRDM16), mitochondrial biogenesis-related PGC-1α, nuclear respiratory factor 1 (Nrf1), nuclear factor E2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). The expression of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, LPL genes, and the copy number of cytochrome B (CytoB mtDNA) gene was detected using real-time polymerase chain reaction (Real-time PCR). Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group, the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed, and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, and LPL were significantly downregulated (P<0.01), while those of the BAT-related factors PGC-1α, UCP1, PRDM16 were significantly upregulated (P<0.01). The number of mitochondria increased, accompanied by reduced swelling. The double membrane and cristae structure were clear, and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased (P<0.01). The protein expression levels of mitochondrial biogenesis-related PGC-1α, Nrf1, Nrf2, and TFAM in each treatment group were significantly increased (P<0.01). ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.
2.Study on the mechanism of Buzhong Yiqi Decoction regulating macrophage polarization in mice with autoimmune thyroiditis
Lanting WANG ; Zhaohan ZHAI ; Shouxin JU ; Liang KONG ; Jie DING ; Yao XIAO ; Yiran CHEN ; Zhimin WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):529-541
Objective:
To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice.
Methods:
Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue.
Results:
The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05).
Conclusion
Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.
3.Mechanism of Buzhong Yiqitang Intervening in Pyroptosis of AIT in NOD.H-2h4 Mice Based on NLRP3/Caspase-1/GSDMD Pathway
Zhimin WANG ; Xiao YANG ; Yiran CHEN ; Ziyu LIU ; Qingyang LIU ; Chenghan GAO ; Chen WANG ; Tianshu GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):8-15
ObjectiveTo explore the mechanism of Buzhong Yiqitang on pyroptosis in autoimmune thyroiditis (AIT) mice based on the NOD-like receptor hot protein domain related protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1(Caspase-1)/Gasdermin D (GSDMD) pathway. MethodSixty NOD.H-2h4 mice were divided into normal group, model group, low, medium, and high dose groups (4.10, 8.19, 16.38 g·kg-1)of Buzhong Yiqitang, and selenium yeast tablet group (0.26 mg·kg-1), with 10 mice in each group. Except for the normal group, all other groups were given 0.05% NaI by gavage for eight weeks to establish a model and then received the drug treatment for eight weeks. The serum levels of thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TgAb) were detected using enzyme-linked immunosorbent assay (ELISA) method. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in mouse thyroid tissue. The immunohistochemical method was used to detect the protein expression of NLRP3, Caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18. Western blot was used to detect the levels of pyroptosis-related proteins in thyroid tissue. ResultCompared with the normal group, the serum levels of TPO-Ab and TgAb in the model group were significantly increased (P<0.01). Thyroid follicles either increased in a cubic shape or were damaged and atrophied, with a large number of lymphocytes infiltrating around the follicles. Compared with the model group, the levels of TPO-Ab and TgAb in other groups were significantly reduced (P<0.01), and the morphology and structure of follicles were improved. The degree of lymphocyte infiltration was reduced. Among them, the medium dose group of Buzhong Yiqitang had the most significant reduction and improvement effect. Compared with the normal group, the positive products and mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in the thyroid tissue of the model group significantly increased (P<0.01), and the protein expression levels of NLRP3, cleaved Caspase-1, IL-1β, IL-18, and GSDMD-N were significantly increased (P<0.05, P<0.01). Compared with the model group, the positive products and mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in other groups were significantly reduced (P<0.05, P<0.01), with the most significant reduction effect in the medium dose group of Buzhong Yiqitang. The protein expression levels of NLRP3, cleaved Caspase-1, IL-1β, IL-18, and GSDMD-N were significantly reduced (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can improve AIT, and its mechanism may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit pyroptosis.
4.Study on the mechanism of herb cake-partitioned moxibustion inhibiting tumor growth in colitis-associated colorectal cancer based on KDM4D receptor
Hongxiao XU ; Yiran WANG ; Jing XU ; Yan HUANG ; Yu QIAO ; Feifei LI ; Guona LI ; Jimen ZHAO ; Feng LI ; Ziyi CHEN ; Kunshan LI ; Mu'en GU ; Huangan WU ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(1):1-11
Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.
5.Improvement of Thyroid Injury in AIT Mice by Inhibiting Ferroptosis Through Regulation of Nrf2/PPARγ/GPX4 Pathway by Buzhong Yiqitang
Ziyu LIU ; Zhuo ZHAO ; Yiran CHEN ; Huimin CAO ; Si CHEN ; Zhimin WANG ; Tianshu GAO ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):10-18
ObjectiveTo investigate the mechanism of Buzhong Yiqitang in ameliorating ferroptosis in autoimmune thyroiditis (AIT) mice based on the nuclear factor erythroid 2-related factor 2 (Nrf2)/peroxisome proliferator-activated receptor γ (PPARγ)/glutathione peroxidase 4 (GPX4) pathway. Method120 SPF-grade 7-8-week-old NOD.H-2h4 mice were randomly divided into control group, model group, low-, medium-, and high-dose Buzhong Yiqitang groups, and western medicine group, with 20 mice in each group. Except for the control group, all mice were fed with classic high-iodine water (0.05% NaI) to induce AIT models after 8 weeks. The low-, medium-, and high-dose Buzhong Yiqitang groups were administered 4.78, 9.56, 19.12 g·kg-1 of Buzhong Yiqitang, respectively, via gavage. The western medicine group was given 3.033×10-5 g·kg-1 selenium yeast tablet suspension via gavage, while the control and model groups were given an equal volume of distilled water via gavage. After 8 weeks of continuous treatment, samples were collected. The pathological morphology of mouse thyroid tissue was observed through hematoxylin-eosin (HE) staining,the content of serumantithyroid peroxidase autoantibody(TPOAb)and anti-thyroglobulin antibodies(TGAb)was measured by enzyme-linked immunosorbent assay (ELISA),the kit was used to detect the levels of superoxide dismutase (SOD), and malondialdehyde (MDA) in mouse serum. Immunofluorescence was used to detect the localized expression of GPX4 in thyroid tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of Nrf2, PPARγ, solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), lysolipid lecithin acyltransferase 3 (LPCAT3), and GPX4 mRNA in thyroid tissue. Western blot was used to detect the expression of Nrf2, PPARγ, SLC7A11, SLC3A2, LPCAT3, and GPX4 proteins in thyroid tissue. ResultCompared with control group, model group under light microscopy showed significant lymphocyte infiltration in the thyroid tissue, significantly increased levels of TGAb and TPOAb in serum (P<0.01), significantly increased MDA levels and decreased SOD levels in serum (P<0.01), significantly decreased expression of Nrf2, PPARγ, SLC7A11, SLC3A2, and GPX4 (P<0.01) in thyroid tissue, while the expression of LPCAT3 was significantly increased (P<0.01). Compared with model group, the Buzhong Yiqitang groups and the western medication group under light microscopy showed lymphocyte infiltration in the thyroid tissue of was decreased, significantly decreased levels of TPOAb and TGAb in serum (P<0.05,P<0.01), decreased MDA levels and increased SOD levels in serum(P<0.05,P<0.01),significantly increased expression of Nrf2, PPARγ, SLC7A11, SLC3A2, and GPX4, while the expression of LPCAT3 was significantly decreased (P<0.05,P<0.01) in the thyroid tissue. Compared with western medication group, Buzhong Yiqitang groups showed significant overall trends in the expression of Nrf2, PPARγ, SLC7A11, SLC3A2, GPX4, and LPCAT3 (P<0.05,P<0.01). ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT, and its mechanism of action may be related to the regulation of Nrf2/PPARγ/GPX4 to inhibit ferroptosis.
6.Mechanism of Buzhong Yiqitang in Improving Autoimmune Thyroiditis by Regulating Th17 Cells Through miR-155/Ndfip1/Pten Axis
Xiaohui LI ; Zhuo ZHAO ; Yiran CHEN ; Huimin CAO ; Si CHEN ; Zhimin WANG ; Tianshu GAO ; Ziyu LIU ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):19-26
ObjectiveTo explore the mechanism of Buzhong Yiqitang in improving autoimmune thyroiditis (AIT) by regulating helper T cell 17(Th17) cells through microRNA-155 (miR-155)/Nedd4 family interaction protein 1 (Ndfip1)/phosphatase and tensin homology (Pten) axis. MethodThe 100 SPF grade 8 week-old NOD.H-2h4 mice were fed with high iodine water (0.05% NaI) for 8 weeks, and AIT model was made. They were divided into model group, Buzhong Yiqitang low-,medium-,and high-dose groups (4.78,9.56,19.12 g·kg-1·d-1) and selenium yeast tablet group (3.033×10-5 g·kg-1) according to random number table method. There were 20 mice in each group and 20 mice in the control group. The control group and the model group were given the same amount of distilled water. After 8 weeks of continuous administration, Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of miR-155-5p, Ndfip1, Pten, protein tyrosine kinase 1 (Jak1), signaling and transcriptional activator 3 (Stat3) retinoic acid-associated orphan receptor γt (RORγt), and interleukin-17 (IL-17) mRNA in mouse thyroid tissue. Western blot was used to detect the expression of Ndfip1, Pten, Jak1, Stat3, RORγt, and IL-17 proteins in mouse thyroid tissue, immunohistochemical method was used to detect the expression of Ndfip1 and Pten proteins in mouse thyroid tissue; flow cytometry was used to detect the proportion of Th17 cells in mouse spleen. ResultCompared with the control group, the proportion of Th17 cells was increased (P<0.01). The expressions of miR-155-5p, Jak1, Stat3, RORγt and IL-17 were increased (P<0.01), while the expressions of Ndfip1 and Pten were decreased (P<0.01). Compared with model group, the proportion of Th17 cells was decreased (P<0.05,P<0.01). The expressions of miR-155-5p, Jak1, Stat3, RORγt and IL-17 were decreased (P<0.05,P<0.01), while the expressions of Ndfip1 and Pten were increased (P<0.05,P<0.01). ConclusionThe application of Buzhong Yiqitang can improve the autoimmune disorder of AIT mice, the mechanism of which may be related to the regulation of Ndfip1/Pten axis by miR-155 and then the regulation of Th17 cell differentiation.
7.Effect of Buzhong Yiqitang on Fas/FADD/Caspase-8 Cell Apoptotic Signaling Pathway in Mice with Autoimmune Thyroiditis
Xiaohui LI ; Zhuo ZHAO ; Yiran CHEN ; Huimin CAO ; Si CHEN ; Zhimin WANG ; Tianshu GAO ; Ziyu LIU ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):27-34
ObjectiveTo investigate the effects of Buzhong Yiqitang on the tumor necrosis factor receptor superfamily member 6 (Fas)/Fas related death domain protein (FADD)/Caspase-8 cell apoptotic signaling pathway in mice model with autoimmune thyroiditis (AIT). MethodThere were 120 SPF grade NOD.H-2h4 mice aged 8 weeks, 100 of which were fed with high iodine water (0.05% NaI), and the AIT model was made after 8 weeks. According to random number table method, they were divided into model group, Buzhong Yiqitang low-dose, medium-dose and high-dose groups (4.78, 9.56, 19.12 g·kg-1), selenium yeast tablet group (3.033×10-5 g·kg-1), with 20 mice in each group and 20 control group. The apoptosis of thyroid cells was detected by in situ end labeling (TUNEL) after 8 weeks of administration. The real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of Fas, FADD, Caspase-8, and Caspase-3 in thyroid tissue. Western blot was used to detect the protein expression of Fas, FADD, Caspase-8, Caspase-3, cleaved Caspase-8, and cleaved Caspase-3 in thyroid tissue, and the immunohistochemical method was used to detect the protein expression of Fas and Caspase-3 in thyroid tissue. ResultCompared with control group, there were more positive expressions of apoptotic cells in model group under fluorescence microscope, and the expressions of Fas, FADD, Caspase-8, Caspase-3, cleaved Caspase-8 and cleaved Caspase-3 were significantly increased (P<0.05, P<0.01). Compared with model group, the positive expression of thyroid apoptotic cells in each administration group was decreased under fluorescence microscope, and the expressions of Fas, FADD, Caspase-8, Caspase-3, cleaved Caspase-8, cleaved Caspase-3 were significantly decreased (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can effectively improve thyroid cell apoptosis and inflammatory injury in AIT mice. The mechanism may be related to the inhibition of Fas/FADD/Caspase-8 signaling pathway.
8.Research progress of acute idiopathic maculopathy
Yiran JIA ; Libin JIANG ; Chaoyang WANG ; Chunli CHEN
International Eye Science 2024;24(11):1738-1742
Acute idiopathic maculopathy(AIM)is an inflammatory lesion of unknown cause that primarily affects the macula. It follows a unique natural course, distinct from other maculopathy, often manifesting as a sudden loss of visual acuity followed by flu-like symptoms that gradually resolve as the disease subsides. A comprehensive understanding of the unique history, multimodal imaging, and a thorough systematic examination are crucial in determining the final diagnosis of AIM. The treatment and prognosis of AIM remain controversial. Meanwhile, it presents similar clinical manifestations and pathological changes to various chorioretinopathy, posing challenges for clinical differentiation. This article provides a review of its pathogenesis, clinical symptoms, multimodal imaging features, diagnosis and differential diagnosis, treatment and prognosis, in order to reduce misdiagnosis and mistreatment while enhancing comprehension of AIM.
9.Death characteristics and trend analysis of malignant tumors in Danjiangkou City in 2015 - 2022
Jianxin WANG ; Yaxue ZHU ; Jing ZHU ; Zhe ZHANG ; Yiran JI ; Yanyan CHEN
Journal of Public Health and Preventive Medicine 2024;35(6):55-58
Objective To investigate the epidemiological characteristics and changing trend of malignant tumor death in Danjiangkou City, the water source area along the middle route of South-to-North Water Diversion Project. Methods The surveillance data of cancer death cases in Danjiangkou City from 2015 to 2022 were collected, and the mortality rate, gender mortality rate, age-specific mortality rate and the rank of cancer cause of death were calculated. Joinpoint regression model was used to analyze the trend of malignant tumor mortality and standardized mortality. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated to analyze the trend changes. Results From 2015 to 2022, a total of 6 254 deaths from malignant tumors were reported in Danjiangkou City, with a crude mortality rate of 178.57/100 000 and a standardized mortality rate of 152.77/100 000. There were 4 366 male deaths, and the crude mortality and standardized mortality were 244.70/100 000 and 212.87/100 000 , respectively. There were 1 888 female deaths, and the crude mortality rate and the standardized mortality rate were 109.89/100 000 and 92.69/100 000, respectively. The crude death rate of malignant tumors in the whole population in Danjiangkou City showed an increasing trend from 2015 to 2022, and the difference was statistically significant (AAPC=5.18%, t=4.07, P<0.05). The crude mortality rates of malignant tumors in both men and women showed an upward trend, and the differences were statistically significant (AAPC =5.56% and 4.35%, both P<0.05). The standardized mortality rates of malignant tumors in the whole population, women and men remained stable, and the differences were not statistically significant (AAPC=0.68, 1.59 and -0.74, all P>0.05). The trend analysis of age-specific mortality of malignant tumors showed that the age-specific mortality of malignant tumors in the whole population, men and women showed an increasing trend with age, and the differences were statistically significant (AAPC =9.22%, 9.40% and 8.53%, P<0.05). The mortality rate of malignant tumors in 0-, 1-, 10-, 45- and 70- age groups decreased year by year (AAPC =-79.62%, -7.19%, -65.99%, -8.88%, and -5.83%, all P<0.05). The mortality rate in the age group of over 75 years old showed an increasing trend (AAPC =12.24%, P<0.05), and the differences were statistically significant. The top 10 malignant tumor deaths in the whole population were lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal cancer , leukemia , pancreatic cancer , breast cancer , brain malignant tumor and cervical cancer, accounting for 88.49% of all malignant tumor deaths. Mortality rates in lung cancer (AAPC =6.75%), esophageal cancer (AAPC=11.24%), colorectal cancer (AAPC =12.95%), leukemia (AAPC=8.10%), pancreatic cancer (AAPC=15.11%), breast cancer (AAPC=13.11%) and brain malignancies (AAPC=11.16%) showed an increasing trend, and the differences were statistical significant (P<0.05). Conclusion Malignant tumor is the main cause of death in Danjiangkou City. The death rate increases year by year and increases with age. Lung cancer, stomach cancer and liver cancer are the main causes of death. Men and the elderly are high-risk groups of malignant tumors. Early detection and treatment of malignant tumors should be strengthened to reduce the incidence and death.
10.Pristimerin enhances cisplatin-induced apoptosis in nasopharyngeal carcinoma cells via ROS-mediated deactivation of the PI3K/AKT signaling pathway
Yuanyuan WANG ; Teng CHEN ; Xiaofan CONG ; Yiran LI ; Rui CHEN ; Pei ZHANG ; Xiaojin SUN ; Surong ZHAO
Journal of Southern Medical University 2024;44(5):904-912
Objective To explore the effect of pristimerin combined with cisplatin on proliferation and apoptosis of nasopharyngeal carcinoma cells.Methods CCK-8 assay was used to examine the survival rate of HNE-1 and CNE-2Z cells following treatment for 24 h with different concentrations of pristimerin,cisplatin or their combination.The changes in colony formation ability,apoptosis,and intracellular reactive oxygen species(ROS)levels of the treated cells were analyzed using colony formation assay and flow cytometry.Western blotting was performed to detect the changes in protein expressions in the cells.The effects of pre-treatment with NAC on proliferation,apoptosis,and PI3K/AKT signaling pathway were observed in pristimerin-and/or cisplatin-treated cells.Results Both pristimerin and cisplatin significantly lowered the survival rate of HNE-1 and CNE-2Z cells(P<0.05).Compared with pristimerin or cisplatin alone,their combination more strongly inhibited survival and colony formation ability of the cells,increased cell apoptosis rate and intracellular ROS levels,upregulated the protein expressions of Bax,cleaved caspase-3,and cleaved PARP,and downregulated the protein expressions of Bcl-2,Mcl-1,PARP and p-PI3K and p-AKT(P<0.05).NAC pretreatment significantly attenuated proliferation inhibition and apoptosis-promoting effects of pristimerin combined with cisplatin,and partially restored the downregulated protein expressions of p-PI3K and p-AKT in HNE-1 and CNE-2Z cells with the combined treatment(P<0.05).Conclusion Pristimerin can enhance cisplatin-induced proliferation inhibition and apoptosis in nasopharyngeal carcinoma cells,the mechanism of which may involve ROS-mediated deactivation of the PI3K/AKT signaling pathway.


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