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Table of Content

      
    10 August 2023
    Volume 61 Issue 8
    基础医学
    Construction of endogenous epitope-tagged H1FX cell lines and the chromatin distribution mapping
    XU Yaning, ZHANG Xianglin, LIU Xiaoyu, GUO Haiyang
    Journal of Shandong University (Health Sciences). 2023, 61(8):  1-9.  doi:10.6040/j.issn.1671-7554.0.2022.1302
    Abstract ( 276 )   PDF (9806KB) ( 77 )   Save
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    Objective To tag endogenous H1FX with epitope sequences for chromatin immunoprecipitation sequencing(ChIP-seq)using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)genome editing technology, and to investigate the genomic binding sites and distribution of H1FX in prostate cancer 22Rv1 cells. Methods Specific guide RNA(gRNA)was designed and inserted into the plasmid pX330-U6-Chimeric_BB-CBh-hSpCas9 to construct the pX330-H1FX recombinant plasmid. Cas9 nuclease was guided to the position close to the H1FX stop codon for cleavage. With plasmid pFETCh_Donor containing the 3×FLAG epitope tag, self-cleaving peptide 2A and geneticin resistance gene sequence as the vector, the recombinant plasmid pFETCh_Donor-HOMO was constructed by adding homology arms(HOMO)that were homologous to the region on both sides of the double strand break. PX330-H1FX recombinant plasmid and pFETCh_Donor-HOMO recombinant plasmid were co-transfected into prostate cancer 22Rv1 cells. DNA was cleaved and epitope tags were integrated by homologous recombination repair. Cells were selected using medium containing geneticin after 48 hours. ChIP was performed on endogenous epitope-tagged H1FX-FLAG cell lines using FLAG antibody. ChIP-enriched DNA and input DNA libraries were constructed and sent for sequencing after the librarys were qualified. Subsequently, H1FX ChIP-seq data and gene expression data were integrated and analyzed. Results The results of Western blotting showed that the cell line only expressing H1FX-FLAG fusion protein was screened. The results of polymerase chain reaction showed that the FALG epitope tag was integrated into the correct position of the genome. Sequencing results showed that the insertion sequence and junction sequence were correct, and the H1FX-FLAG cell line tagged with endogenous epitopes was successfully constructed. The integration analysis of H1FX ChIP-seq data and gene expression data showed that the promoter regions of highly expressed genes were more likely to lack H1FX binding. Conclusion The endogenous epitope-tagged H1FX-FLAG cell lines were successfully constructed. The genomic binding sites and distribution of H1FX in 22Rv1 prostate cancer cells were preliminarily analyzed, which laid a foundation for further study on the role of H1FX in prostate cancer.
    GLP-1 inhibits oxidative stress damage through cytochrome P450 surface oxidase pathway
    HU Yanwen, ZHAO Huichen, MA Xiaoli, LIU Yuantao, ZHANG Yuchao
    Journal of Shandong University (Health Sciences). 2023, 61(8):  10-16.  doi:10.6040/j.issn.1671-7554.0.2023.0450
    Abstract ( 223 )   PDF (2032KB) ( 171 )   Save
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    Objective To explore the effects of GLP-1 against oxidative stress in vitro and the possible mechanism from cytochrome P450(CYP450)epoxygenase pathway. Methods Human umbilical vein endothelial cells(HUVECs)were treated with H2O2 to construct the oxidative stress models. The cells were divided into six groups: control group, H2O2 group, H2O2+7-36a group, H2O2+9-36a group, H2O2+7-36a+Danazol group and H2O2+9-36a+Danazol group. Cell viability was evaluated with CCK8 assay. Intracellular ROS level was determined with fluorescent probe labeling. The expressions of glucose regulatory protein 78(GRP78)and cytochrome P450 2J2(CYP2J2)were detected with Western blotting. Results Oxidative stress models were constructed after 600 μmol/L H2O2 treatment for 3 hours. Compared with the control group, the H2O2 group had decreased cell survival rate(P<0.001), increased ROS level(P<0.001)and protein expression of GRP78(P<0.05), but decreased CYP2J2 protein expression(P<0.05). Compared with the H2O2 group, the H2O2+7-36a group and H2O2+9-36a group had increased survival rate(P<0.05, P<0.01), decreased ROS level(both P<0.001)and GRP78 protein expression(both P<0.01), and increased CYP2J2 protein expression(both P<0.05). Compared with the H2O2+7-36a group, there was no statistical difference in cell survival rate in the H2O2+7-36a+Danazol group, while the ROS level increased(P<0.001), GRP protein expression incresed(P<0.001), and CYP2J2 protein expression decreased(P<0.05). Compared with the H2O2+9-36a group, there was no statistical difference in cell survival rate in the H2O2+9-36a+Danazol group, while the ROS level increased(P<0.001), GRP protein expression incresed(P<0.01), and CYP2J2 protein expression decreased(P<0.01). Conclusion GLP-1(7-36a)and its metabolite GLP-1(9-36a)can improve H2O2-induced survival decline in HUVECs and reduce the high level of oxidative stress, possibly through the CYP450 epoxygenase pathway.
    Effects of bisphenol A exposure on m6A modification level of KGN cells
    YAN Congcong, CHEN Chen, XIE Qian, WANG Yanan, ZHANG Xinlu, ZHANG Yingchun, WU Bin
    Journal of Shandong University (Health Sciences). 2023, 61(8):  17-23.  doi:10.6040/j.issn.1671-7554.0.2023.0183
    Abstract ( 209 )   PDF (2396KB) ( 263 )   Save
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    Objective To investigate the epigenetic effects of bisphenol A(BPA)exposure on the function of ovarian granulosa cells. Methods Human ovarian granuloma cells(KGN cells)were exposed to BPA(0, 0.02, 0.2, 2, 20 μg/mL)for 24 h, which were defined as vehicle group, 0.02μg/mL BPA group, 0.2 μg/mL BPA group, 2 μg/mL BPA group, and 20 μg/mL BPA group, respectively. The modification level of mRNA m6A and expression of m6A RNA methylation-related genes were measured, and the m6A modification level of antioxidant transcription factor(Nrf2)was detected with Merip-qPCR. Results BPA down-regulated the level of mRNA m6A modification(P<0.001)and changed the expression of m6A methylation-related genes(P<0.05). The expression of superoxide dismutase(SOD)and m6A modification level of Nrf2 decreased in the 2 μg/mL BPA group(both P<0.05). Conclusion BPA exposure can increase oxidative stress and damage the function of KGN cells in human ovarian granulosa tumor by down-regulating the m6A modification of Nrf2, which has an effect on the epigenetics of ovarian granulosa cells.
    Effects and mechanism of Hanjingtang on the oxidative stress induced by cold stimulation in aortic vascular smooth muscle cells
    LIU Yang, CHEN Guihai
    Journal of Shandong University (Health Sciences). 2023, 61(8):  24-30.  doi:10.6040/j.issn.1671-7554.0.2023.0017
    Abstract ( 195 )   PDF (1816KB) ( 69 )   Save
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    Objective To observe the effects and mechanism of Hanjingtang on the oxidative stress induced by cold stimulation in aortic vascular smooth muscle cells. Methods The experimental cells were divided into blank control group, model group, Hanjingtang(HJT)group and dimethyl fumarate(DMF)group. The DMF group was defined as the positive control. After vascular smooth muscle cells(A7r5)were cultured for 24 hours, they received cold stimulation at 4 ℃ for 4 hours. Cell viability was detected with CCK-8; expressions of superoxide dismutase(SOD)and malonaldehyde(MDA)were determined with immunochemistry; expression of active oxygen(ROS)was detected with DCFH-DA fluorescence; expressions of interleukin-1β(IL-1β)and nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3)were assessed with Elisa; protein expressions of cellular nuclear factor E2-associated factor 2(Nrf 2), NAD(P)H quinone oxidoreductase 1(NQO1), nuclear factor κB(NF-κB), and human nuclear factor κB inhibitor protein α(IκBα)were determined with Western blotting; mRNA expressions of NQO1 and NF-κB were detected with quantitative real-time PCR. Results Compared with the blank control group, the model group had decreased cell viability and SOD(P<0.01); increased ROS, MDA, IL-1β and NLRP3 levels; increased protein expressions of NF-κB and IκBα, but decreased protein expressions of Nrf2 and NQO1(P<0.01); increased mRNA expression of NF-κB, but decreased mRNA expression of NQO1(P<0.01). Compared with the model group, the HJT group had increased cell viability and SOD(P<0.01); decreased ROS, IL-1β, NLRP3(P<0.01), and MDA(P<0.05)levels; increased protein expressions of Nrf2 and NQO1(P<0.01), but decreased protein expressions of NF-κB and IκBα(P<0.05, P<0.01); decreased mRNA expression of NF-κB(P<0.01), but increased mRNA expression of NQO1(P<0.05). Conclusion The mechanism of enhancing cold-stimulated aortic smooth muscle cell vitality, regulating cellular ROS expression, inhibiting inflammatory factor expression, and improving oxidative stress response may be related to Nrf2/NF-κB pathway.
    临床医学
    Role of protein disulfide isomerase TMX1 in promoting chemotherapy resistance in lung cancer
    WANG Yanan, LIANG Chuanjie, JIA Mengqi, YUAN Huiqing
    Journal of Shandong University (Health Sciences). 2023, 61(8):  31-39.  doi:10.6040/j.issn.1671-7554.0.2023.0169
    Abstract ( 249 )   PDF (7625KB) ( 109 )   Save
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    Objective To investigate the role of protein disulfide isomerase(PDI)in lung cancer development and chemotherapy treatment. Methods PDI family members expressed in lung tissue were screened using the Human Protein Atlas. The mRNA levels of some PDI family members in lung cancer and adjacent tissues of 10 patients were analyzed with qRT-PCR. The protein expressions of some PDI family members in cancer tissues and adjacent tissues of 4 to 6 patients were determined with Western blotting and verified with immunohistochemistry, in order to explore the relationship between the significantly changed differential genes and the prognosis of patients, especially the role of TMX1 in the occurrence and development of lung cancer. The transcription and protein levels of TMX1 in lung cancer cells, lung cancer multi-drug resistant cells and non-tumor epithelial cells were detected with qRT-PCR and Western blotting. After cells with overexpression and knockdown of TMX1 were constructed with liposome transfection, the effects of TMX1 on the survival of lung cancer cells were detected with MTT assay, and the effects of TMX1 on the efficacy of cisplatin and docetaxel were analyzed. Results Compared with the adjacent tissues, cancer tissues exhibited significantly reduced mRNA and protein levels of PDIA2, significantly increased mRNA levels of PDIA3, PDIA6, TMX1 and TMX3. Analysis of TCGA database showed that lower expressions of PDIA2 and TMX1 were associated with better prognosis, higher expression of PDIA6 was associated with slightly prolonged survival, and higher expressions of PDIA3 and TMX3 were associated with significantly prolonged survival. The transcription level of TMX1 was higher in different types of lung cancer cells than in non-tumor epithelial cells; its protein expression was significantly increased in lung adenocarcinoma A549 cells and small cell lung cancer H446 cells. TMX1 was highly expressed in drug-resistant cells of lung cancer, and its expression in sensitive cells was upregulated after cisplatin and docetaxel treatment. After knockdown of TMX1, the survival of lung cancer A549 cells was reduced and the sensitivity to cisplatin and docetaxel was increased. Overexpression of TMX1 in low-expression H1688 cells resulted in increased cell survival and greater tolerance to cisplatin and docetaxel. Conclusion TMX1 promotes survival of lung cancer cells and resistance to cisplatin and docetaxel.
    Expression and potential mechanism of VPS72 in lung adenocarcinoma/ squamous cell carcinoma by integrated bioinformatics analysis
    MENG Jianli, WANG Qinggang
    Journal of Shandong University (Health Sciences). 2023, 61(8):  40-49.  doi:10.6040/j.issn.1671-7554.0.2022.1243
    Abstract ( 241 )   PDF (15372KB) ( 48 )   Save
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    Objective To explore the expression, prognostic relationship and potential mechanism of vacuolar protein sorting 72 homolog(VPS72)in lung adenocarcinoma/squamous cell carcinoma using multiple databases. Methods The expression level of VPS72 in lung adenocarcinoma/squamous cell carcinoma was analyzed based on TCGA data set, TIMER database and R language data package. The prognostic relationship and diagnostic value of VPS72 were evaluated with Kaplan-Meier Plotter and ROC curve online software. The interacting proteins and co-expressed genes of VPS72 were screened with STRING and LinkedOmics, and GO/KEGG functional enrichment analysis was performed with LinkedOmics. The correlation between the expression of VPS72 and immune cell infiltration was analyzed with TIMER. The correlation between VPS72 expression and different immune subtypes was analyzed in TISIDB database. Results VPS72 was highly expressed in lung adenocarcinoma/squamous cell carcinoma. Lung adenocarcinoma patients with high expression of VPS72 had significantly shorter overall survival(P=0.01), but there was no significant difference in the overall survival of lung squamous cell carcinoma patients with high expression of VPS72(P=0.17). PPI analysis showed that VPS72 interacted with 10 proteins, including H2AFZ, RUVBL1, DMAP1, and so on. GO/KEGG functional enrichment analysis showed that VPS72 was mainly involved in spliceosome and ribosome synthesis. The expression of VPS72 in lung adenocarcinoma was negatively correlated with the infiltration of a variety of immune cells, including B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils and dendritic cells. In lung squamous cell carcinoma, VPS72 expression was negatively correlated with macrophages and neutrophils. In lung adenocarcinoma/squamous cell carcinoma, VPS72 expression was correlated with 6 immune subtypes. Conclusion The expression of VPS72 is significantly increased in lung adenocarcinoma/squamous cell carcinoma, which is related to the prognosis of lung adenocarcinoma and involved in a variety of pathways and immune cells. VPS72 may become a new target for prognosis prediction and treatment of lung adenocarcinoma/squamous cell carcinoma.
    Clinical efficacy of Budesonide/Formoterol in the treatment of SARS-CoV-2-associated cough
    WANG Junren, LI Daowei, WANG Xingguang, JIANG Shujuan
    Journal of Shandong University (Health Sciences). 2023, 61(8):  50-53.  doi:10.6040/j.issn.1671-7554.0.2023.0280
    Abstract ( 493 )   PDF (377KB) ( 172 )   Save
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    Objective To observe the efficacy and safety of Budesonide/Formoterol in the treatment of SARS-CoV-2-associated cough. Methods Clinical data of patients with acute or subacute cough after SARS-CoV-2 infection who received Budesonide/Formoterol(160 μg∶ 4.5 μg)during Dec. 1, 2022 and Jan. 30, 2023 were retrospectively analyzed. Severity of cough was evaluated with visual analogue scale(VAS). Results A total of 168 patients were involved, including 73 males and 95 females. The patients aged 18 to 80 years, average(47.02±15.13)years. Cough duration ranged from 5 to 60 days, average(26.18±12.62)days. The total effective rate of treatment was 84.51%, and the cough symptoms significantly improved after an average of(5.29±2.45)days of treatment. After treatment, the VAS score decreased from(5.91±1.77)to(1.35±2.12),(P<0.001). Mild adverse reactions such as voice hoarse, headache and palpitation occurred in 5 cases, with an adverse reaction rate of 2.98%. No serious adverse reactions occurred. Conclusion Budesonide/Formoterol has a significant clinical effect in the treatment of cough after SARS-CoV-2 infection and can quickly relieve cough symptoms, which has clinical application value.
    Clinical value of CD38 expression in endometrium for anti-inflammatory therapy before embryo transfer
    LI Junxiu, YUAN Yingying, HUANG Lingyan, ZHAO Junli
    Journal of Shandong University (Health Sciences). 2023, 61(8):  54-60.  doi:10.6040/j.issn.1671-7554.0.2023.0219
    Abstract ( 413 )   PDF (631KB) ( 92 )   Save
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    Objective To investigate the clinical value of CD38 expression in endometrium in patients with infertility or embryo implantation failure before embryo transfer. Methods A total of 145 cases of CD138 and CD38 positive endometrium patients were selected from in vitro fertilization or intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET)in the Reproductive Medicine Center of General Hospital of Ningxia Medical University during Sep. 2019 and May 2022. The patients were divided into treatment group and control group according to whether they received anti-inflammatory treatment. The positive rate of CD138 and CD38 was fitted by smooth curve with continuous pregnancy rate as index. According to CD38=10%/HPF value to cut-off, the patients were divided into mild chronic inflammation group(CD38<10%/HPF)and severe chronic inflammation group(CD38≥10%/HPF). The effects of anti-inflammatory therapy on the pregnancy outcomes in patients with different levels of inflammation were compared. With continuous pregnancy as the primary endpoint, relevant factors were analyzed with multiple Logistic regression. Results In the mild chronic inflammation group, there were no significant differences in age, body mass index(BMI), anti-Mullerian hormone(AMH), basal follicle-stimulating hormone(bFSH), infertility duration, embryo transfer type, intimal thickness on the day of transfer and embryo age between the treatment group(n=77)and control group(n=17)(P>0.05), but there was significant difference in the number of transferred embryos between the two groups(P<0.05). Single embryo transfer was adopted in the treatment group. There were no significant differences in embryo implantation rate, biochemical pregnancy rate, clinical pregnancy rate, early abortion rate and continuous pregnancy rate between the two groups(P>0.05). In the severe chronic inflammation group, there were no significant differences in age, BMI, AMH, bFSH, duration of infertility, type of embryo transfer, intimal thickness on the day of transfer, embryonic age of transferred embryos and number of transferred embryos between the treatment group(n=33)and control group(n=18)(P>0.05). The embryo implantation rate(50% vs 22.22%, P=0.021)and sustained pregnancy rate(54.54% vs 22.22%, P=0.039)in the treatment group were significantly higher than those in the control group. The clinical pregnancy rate of the treatment group was higher than that of the control group(60.6% vs 33.33%, P=0.083), and the early abortion rate was lower(5% vs 33.33%, P=0.123), but the differences were not statistically significant(P>0.05). Multivariate Logistic regression analysis showed that anti-inflammatory therapy before transplantation had no significant effects on the duration of pregnancy in mild chronic inflammation patients, but was a protective factor for the duration of pregnancy in severe chronic inflammation patients(P=0.020, OR=4.705, 95%CI=1.284-17.572). Conclusion It may be more reasonable to use endometrial CD38 positive 10%/HPF to distinguish the degrees of chronic endometritis and to guide pre-transfer anti-inflammatory therapy. When chronic endometritis is mild, anti-inflammatory treatment has no significant effects on the pregnancy outcomes; when chronic endometritis is severe, the pregnancy rate shows a downward trend. Anti-inflammatory therapy may reverse the adverse pregnancy outcomes and improve pregnancy outcomes after embryo transfer.
    Prognosis and fertility outcomes of patients with borderline ovarian tumors undergoing fertility-sparing surgery
    LIU Chang, WANG Qiannan, ZHANG Yue, CHEN Zhongshao, CHU Ran, YAO Shu
    Journal of Shandong University (Health Sciences). 2023, 61(8):  61-66.  doi:10.6040/j.issn.1671-7554.0.2023.0343
    Abstract ( 256 )   PDF (527KB) ( 144 )   Save
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    Objective To explore the clinical prognosis and fertility outcomes in patients with borderline ovarian tumors(BOT)who underwent fertility-sparing surgery(FSS). Methods A retrospective analysis was conducted on BOT patients who received FSS in Qilu Hospital of Shandong University during Jan. 2009 and Dec. 2019. Risk factors associated with disease free survival(DFS)were determined with univariate and multivariate Cox proportional hazard regression analysis. Risk factors related to postoperative fertility outcomes were assessed with univariate and multivariate binary Logistic regression analysis. Results A total of 167 BOT patients were included and followed up for a median of 56(range 2-143)months, during which 25 patients(15.0%)had recurrence. Multivariate Cox proportional hazard regression analysis showed bilateral tumor(HR=3.908, 95%CI: 1.751-8.721, P=0.001)was related to DFS. Among the 72 patients with pregnancy intention, 39(54.2%)had pregnancy, 37 gave birth successfully, and 2 terminated pregnancy. Multivariate binary Logistic regression analysis showed that mucinous tumor(OR=3.279, 95%CI: 1.104-9.739, P=0.032)and laparoscopic surgery(OR=4.199, 95%CI: 1.462-12.058, P=0.008)were associated with successful pregnancy after FSS. Conclusion BOT patients undergoing FSS have a favorable prognosis outcome; bilateral tumors are correlated with poorer DFS; the pathological type and surgical approach may affect the postoperative fertility outcomes.
    Renal transplantation in 12 pairs of ABO incompatible relatives and literature review
    DING Handong, ZHONG Jinbiao, WANG Qin, LIAO Guiyi
    Journal of Shandong University (Health Sciences). 2023, 61(8):  67-73.  doi:10.6040/j.issn.1671-7554.0.2022.1341
    Abstract ( 233 )   PDF (2672KB) ( 158 )   Save
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    Objective To explore the perioperative management, prevention and treatment of complications of ABO incompatible relatives who underwent kidney transplantation. Methods Data of 12 pairs of donors and recipients of ABO incompatible renal transplantation completed during July 2020 and April 2021 were collected, including 2 type A donors to type O recipients and 1 type A donor to type B recipients; 6 type B donors to type O recipients and 1 type B donor to type A recipient; 2 type AB donors to type B recipients. According to the titer of blood group antibody in the first test, different desensitization treatment schemes of rituximab(rituximab), plasma exchange and immunosuppressant were adopted. The changes of perioperative blood group antibody titer, renal function and lymphocyte count were monitored. Results The blood group antibody titers of 12 recipients treated with simplified desensitization schemes reached the preoperative target. The titer of blood group antibody increased in 4 recipients within half a month after transplantation, and plasma treatment intervention was conducted. Postoperative complications such as rebound after normal creatinine, severe anemia, recurrent diarrhea, arrhythmia, heart failure and positive urinary BK virus occurred in 1 case, respectively. After treatment, the renal function recovered well. Conclusion The simplified pretreatment schemes can achieve ideal blood group antibody titer, individualized and accurate prevention and treatment of complications, and achieve satisfactory short-term curative effects.
    New BTK gene deletion mutation: a case report and literature review
    WEI Junjie, YUE Qiangwei, SUN Lifeng
    Journal of Shandong University (Health Sciences). 2023, 61(8):  74-78.  doi:10.6040/j.issn.1671-7554.0.2022.0841
    Abstract ( 306 )   PDF (3393KB) ( 223 )   Save
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    Objective To investigate the clinical manifestations, laboratory examinations and gene characteristics of a child with X-linked agammaglobulinemia(XLA)caused by a new BTK gene deletion. Methods The clinical manifestations, laboratory examinations and genetic characteristics of a child with XLA admitted to Shandong Provincial Hospital Affiliated to Shandong First Medical University in August 2016 were analyzed, and relevant literature was reviewed in Wanfang, CNKI and PubMed databases. Results The child, male, 7 years and 7 months old, had a history of repeated bacterial infection since the age of 3. Peripheral blood immune function showed CD19+ 0.06%, IgG <1.42 g/L, IgA <0.23 g/L, IgM 0.44 g/L, with significantly reduced immune function. Chest CT showed bronchiectasis and bronchopneumonia. Gene test report suggested deletion of exon 2-5 of BTK gene, and the mother of the child was suspect of heterozygous deletion. There are no reports in the Human Gene Mutation Database(HGMD)of X-linked gammaglobulinemia due to a deletion mutation in exons 2-5. In 5 years of follow-up, the patient received 7.5-10 g of human immunoglobulin every 1-2 months, and no repeated bacterial infection occurred. Chest CT showed mild bronchiectasis. The childs mother was pregnant again and genetic testing by amniocentesis revealed no fetal BTK gene abnormality, and the childs brother was born with normal immune function. Conclusion Children with recurrent bacterial infections and bronchiectasis should be routinely screened for immune function, and those with abnormalities should be genetically tested for a definitive diagnosis. Children with confirmed XLA should be treated regularly with intravenous gamma globulin replacement therapy. Genetic testing of amniotic fluid for BTK is required if the mother becomes pregnant again.
    公共卫生与管理学
    Mediation effects of hypertension on the association between exposure to non-steroidal anti-inflammatory drugs and risk of cardio-cerebrovascular diseases in middle-aged and elderly people
    YU Qingqing, CHANG Kaifeng, LI Jiqing, ZHANG Kai, FU Ping,LIU Xiaowen, ZHAO Yingqi, XUE Fuzhong
    Journal of Shandong University (Health Sciences). 2023, 61(8):  79-85.  doi:10.6040/j.issn.1671-7554.0.2023.0224
    Abstract ( 262 )   PDF (872KB) ( 272 )   Save
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    Objective To explore the mediation effects of hypertension on the association between exposure to non-steroidal anti-inflammatory drugs(NSAIDs)and the risk of cardio-cerebrovascular diseases. Methods A follow-up cohort was constructed based on Pingyi Collaboration Center of National Institute of Health and Medical Big Data. NSAIDs exposure was defined as annual cumulative dose ≥30 cDDDs. The association between NSAIDs and blood pressure and cardio-cerebrovascular diseases were assessed with generalized estimation equation model(GEE)and Cox proportional risk regression model. The mediating effects of hypertension were evaluated with Baron-Kenny method. Results A total of 81,791 subjects were involved. The median follow-up time was 4.25(IQR: 3.22-4.46)years, with 26,514 cardio-cerebrovascular disease outcomes. Multivariate GEE results showed that NSAIDs exposure was significantly associated with increased systolic blood pressure(β=0.98, 95%CI: 0.67-1.29), decreased diastolic blood pressure(β=-0.19, 95%CI: -0.37 - 0.01), and increased risk of hypertension(OR=1.13, 95%CI: 1.08-1.18). Multivariate Cox model showed that the HR of NSAIDs associated with cardio-cerebrovascular diseases, cerebrovascular diseases and cardiovascular diseases were 1.13(95%CI: 1.10-1.16), 1.13(95%CI: 1.09-1.17)and 1.17(95%CI: 1.13-1.21), respectively. Mediation analysis showed that hypertension played a partial mediating role in the relationship between NSAIDs exposure and cardio-cerebrovascular diseases, with a mediating proportion of 9.27%. Conclusion NSAIDs, which can increase systolic blood pressure and decrease diastolic blood pressure, is a risk factor for cardio-cerebrovascular diseases. Hypertension is a mediating factor between NSAIDs and cardio-cerebrovascular diseases.
    Causal relationship between uterine leiomyomas and breast cancer: a two-sample Mendelian randomization study
    ZHANG Nana, ZHAO Yiming, LIU Xinmin
    Journal of Shandong University (Health Sciences). 2023, 61(8):  86-93.  doi:10.6040/j.issn.1671-7554.0.2022.1021
    Abstract ( 461 )   PDF (1180KB) ( 207 )   Save
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    Objective To investigate the causal relationship between uterine leiomyomas(ULs)and breast cancer(BC). Methods The study employed a two-sample Mendelian randomization(MR)method, the European genetic data from published genome-wide association study, and ULs as exposure, single nucleotide polymorphisms(SNPs)of ULs as instrumental variables, and BC as outcome variable. In addition, 5 molecular subtypes of BC were analyzed as outcome variables. The heterogeneity of SNPs was determined with Cochrans Q test, and the pleiotropy was determined with MR-egger. Inverse variance weighted(IVW), MR-Egger, weighted median and MR-PRESSO were used to evaluate the causal relationship of ULs with BC. The R software was used for data analysis and visualization processing. Results A total of 25 SNPs of ULs were finally extracted. Cochrans Q test suggested that heterogeneity existed among some subgroups(P<0.01). No pleiotropy was observed(P>0.05). MR analysis showed that there was no causal relationship between ULs predicted by gene and overall BC(IVW: OR=0.98, 95%CI: 0.86-1.12, P=0.79), and there was no causal relationship with 5 molecular subtypes of BC(P>0.01). Conclusion There is no causal relationship between ULs and increased risk of overall BC in Europeans, and no causal relationship between ULs and any molecular subtype of BC.
    Correlation between vegetation cover and death risk of respiratory cancers
    LU Wei, LIU Huan, JIA Xianjie, SU Ping, SHI Jie, WANG Yaqian, CHI Weiwei
    Journal of Shandong University (Health Sciences). 2023, 61(8):  94-100.  doi:10.6040/j.issn.1671-7554.0.2022.1153
    Abstract ( 190 )   PDF (1113KB) ( 130 )   Save
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    Objective To evaluate the relationship between vegetation cover and death risk of respiratory cancers. Methods Patients with respiratory cancers in Pingyi County were involved. Normalized difference vegetation index(NDVI), enhanced vegetation index(EVI), and soil-adjusted vegetation index(SAVI)were taken as indicators of vegetation cover. Extended time-dependent Cox proportional risk regression model was applied to calculate the hazard ratios(HR)and 95%CI for NDVI, EVI, and SAVI and death from respiratory cancers. Stratified analyses were conducted according to age, sex, and air quality. Results A total of 5,314 subjects were involved, including 3,594 deaths from respiratory cancers during 2014 and 2020. T2 levels of EVI and SAVI were negatively correlated with the risk of death of respiratory cancers(HR=0.871, 95%CI: 0.793-0.956, P=0.004; HR=0.885, 95%CI: 0.810-0.967, P=0.007). Stratified analysis showed negative association between vegetation cover and death risk of respiratory cancers in patients aged ≥60 years, female, and those living with PM2.5 concentrations below 70 μg/m3(all P<0.05). Conclusion Higher vegetation coverage may be protective for elderly female patients with respiratory cancers living in areas with good air quality.