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ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule(YTK) treats diabetic kidney disease (DKD) by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/forkhead transcription factor O1 (FoxO1) signaling pathway mediated by silent information regulator 1 (SIRT1) via advanced glycation end products (AGE)/receptor for AGE (RAGE) axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group (B), model control group, high-dose YTK (40 g·kg-1), medium-dose YTK (20 g·kg-1), low-dose YTK (10 g·kg-1), and Western medicine control (20 mg·kg-1 losartan) groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling, the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured according to the instructions of the respective assay kits. Hematoxylin and eosin (HE) staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin (α-SMA), fibronectin (FN), desmin, and nephrin. Western blot analysis was used to measure the expression levels of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), RAGE, SIRT1, Caspase-3, and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group, the model group showed significantly lower levels of SOD, GSH-Px, and CAT, and significantly higher levels of MDA (P<0.01). The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA, FN, and desmin increased significantly, while nephrin and podocin significantly decreased (P<0.01). The expression levels of PI3K, p-PI3K, Akt, p-Akt, RAGE, and Caspase-3 proteins were significantly elevated, while SIRT1 and FoxO1 protein levels were significantly reduced (P<0.01). Compared with the model control group, rats in the YTK treatment groups showed significantly higher levels of SOD, GSH-Px, and CAT, and significantly lower levels of MDA in serum (P<0.01). The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA, FN, and desmin were significantly decreased, while nephrin and podocin significantly increased (P<0.01). The expression levels of PI3K, p-PI3K, Akt, p-Akt, RAGE, and Caspase-3 in kidney tissues were significantly reduced, while SIRT1 and FoxO1 expression levels significantly increased (P<0.01). The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage, reduce proteinuria, and protect kidney function in DKD rats, thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally, a dose-response relationship was observed in the Chinese medicine groups.
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Background After working in a harsh occupational hazard environment for a long time, open-pit coal mine workers are under tremendous physical and mental pressure, which is prone to presenteeism behavior. objective To identify the relationships between presenteeism, job burnout, and social support of open-pit coal miners, and verify potential mediating effect of job burnout between social support and presenteeism. Methods In 2020—2021, a questionnaire survey was conducted among employees of 6 open-pit coal mining enterprises in Xinjiang by stratified cluster random sampling. Job Burnout Questionnaire, Job Content Questionnaire, and Presenteeism Behavior Scale were used to evaluate burnout, social support, and presenteeism behavior in the study subjects. SPSS 26.0 software was used for t test, F test, correlation analysis, and mediating effect test. Results A total of 1199 questionnaires were distributed and 1083 valid questionnaires were recovered, with an effective recovery rate of 90.3%. The M (P25, P75) scores of presenteeism behavior, social support, and job burnout were 2.0 (2.0, 5.0), 24.0 (23.0, 26.0), and 45.0 (34.0, 51.0), respectively. The Spearman correlation analysis results showed that there was a significant negative correlation between social support and job burnout (\begin{document}$ r $\end{document}=−0.200, P<0.01), a significant negative correlation between presenteeism and social support (\begin{document}$ r $\end{document}=−0.260, P<0.01), and a significant positive correlation between presenteeism and job burnout (\begin{document}$ r $\end{document}=0.304, \begin{document}$ P $\end{document}<0.01). The results of mediating effect test showed that social support had a negative effect on presenteeism (\begin{document}$ \beta $\end{document}=−0.122, \begin{document}$ P $\end{document}<0.001). Social support negatively predicted job burnout (\begin{document}$ \beta $\end{document}=−0.779, \begin{document}$ P $\end{document}<0.001). Job burnout had a partial mediating effect between social support and presenteeism, with an effect value of −0.0294 (95%CI: −0.0394, −0.0201), accounting for 24.18% of the total effect. Conclusion Social support negatively affects the presenteeism behavior of open-pit coal mine workers, and job burnout plays a partial mediating role between social support and presenteeism behavior.
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ObjectiveTo compare the therapeutic effects of oral Chinese medicines (including Chinese patent medicines) on coronary artery disease (CAD) by the Bayesian network Meta-analysis. MethodThe randomized controlled trials of treating CAD with oral Chinese medicines were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, PubMed, Web of Science, Embase, and Cochrane Library from the inception to December 1, 2022. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included articles. The direct meta-analysis was performed to compare the performance of oral Chinese medicines alone and in combination with Western medicine in the treatment of CAD in terms of intima-media thickness (IMT), vascular endothelial function, plaque score, hypersensitive C-reactive protein (hs-CRP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total response rate. Furthermore, the Bayesian network Meta-analysis was performed to compare the therapeutic effects of different Chinese medicines. ResultA total of 41 articles were included. The direct meta-analysis results showed that Chinese medicines combined with Western medicine outperformed Western medicine alone in recovering all the indicators of CAD. The Bayesian network meta-analysis yielded the following results. In terms of the total response rate, modified Huangqi Guizhi Wuwutang and Sanqi Huayu pills had obvious advantages over other Chinese medicines. In terms of IMT and plaque score, Xiaoban Huazhuo decoction, Yiqi Tongluo formula, Ruangan Jiangzhi capsules, and Guanxin Shutong capsules had obvious advantages over other Chinese medicines. In terms of blood lipid indicators, Shenqi Roumai mixture, Ruangan Jiangzhi capsules, Xiaoban Huazhuo decoction, Qiwei Sanxiong decoction, and Sanqi Huayu pills were superior to other Chinese medicines. The Chinese medicines above mainly had the functions of activating blood, resolving stasis, resolving phlegm, and dredging vessels. ConclusionThe combination of oral Chinese medicines and Western medicine is effective in treating CAD. Clinicians can use the drugs targeting abnormal indicators according to the results of this Bayesian network meta-analysis combined with the actual situation of patients to achieve better therapeutic effects.
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Objective: To explore the predictive value of serum low-density lipoprotein cholesterol/residual cholesterol (LDL-C/RC) coordination on major adverse cardiovascular events (MACE) in elderly hypertensive patients. Methods: This is a prospective cohort study. Elderly hypertensive patients hospitalized in Beijing Anzhen Hospital from June 2018 to June 2020 were prospectively enrolled. According to the coordination of baseline LDL-C/RC, patients were divided into four groups: low LDL-C and low RC (LDL-C<2.6 mmol/L, and RC<0.62 mmol/L), low LDL-C and high RC (LDL-C<2.6 mmol/L, and RC≥0.62 mmol/L), high LDL-C and low RC (LDL-C≥2.6 mmol/L, and RC<0.62 mmol/L), and high LDL-C and high RC (LDL-C≥2.6 mmol/L, and RC≥0.62 mmol/L). Patients were followed up until June 2022. The primary outcome was MACE, including non-fatal acute coronary syndrome, non-fatal acute heart failure, non-fatal stroke and death. Kaplan-Meier survival analysis was used to evaluate MACE among the four groups, and Cox regression analysis was performed to evaluate the related factors of MACE. Results: A total of 847 hypertensive patients were enrolled. There were 453 males (53.5%), mean age was (72.4±8.8) years. There were 207, 162, 263, 215 patients in the low LDL-C and low RC, low LDL-C and high RC, high LDL-C and low RC and high LDL-C and high RC group, respectively. During a median follow-up of 37 months, 196 patients (23.1%) had MACE, including 77 cases (9.1%) of ACS, 56 cases (6.6%) of acute heart failure, 34 cases (4.0%)of non-fatal stroke, 29 cases(3.4%) of all-cause mortality, and 16 cases (1.9%) of cardiovascular death. Risk of MACE of the four groups was significantly different (log-rank P<0.001). Compared with low LDL-C and low RC groups, high LDL-C and high RC groups had the highest incidence of MACE (HR=2.237, 95%CI 1.328-3.783, P=0.004), followed by low LDL-C and high RC groups (HR=1.745, 95%CI 1.220-2.527, P=0.003) and high LDL-C and low RC groups (HR=1.393, 95%CI1.048-1.774, P=0.022). In addition, the risk of nonfatal ACS among the four groups was also statistically significant (P=0.037), while the risk of nonfatal acute heart failure, nonfatal stroke, all-cause mortality and cardiovascular death were similar (all P>0.05). Multivariate Cox regression analysis showed that age (HR=1.271), duration of hypertension (HR=1.339), diabetes (HR=1.415), hyperlipidemia (HR=1.348), serum creatinine (HR=1.263), N-terminal pro-B-type natriuretic peptide (HR=1.316), LDL-C (HR=1.205), RC (HR=1.302), low LDL-C and high RC (HR=1.745), high LDL-C and low RC (HR=1.393), high LDL-C and high RC (HR=2.237) were independently associated with the occurrence of MACE. Conclusion: The coordination of LDL-C/RC affects the risk of MACE in elderly hypertensive patients, and the risk of MACE is the highest in patients with high LDL-C and high RC.
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Mâle , Humains , Sujet âgé , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Cholestérol LDL , Études prospectives , Cholestérol , Défaillance cardiaque , Facteurs de risque , Hypertension artérielle , Accident vasculaire cérébralRésumé
Objective: To explore the predictive value of serum low-density lipoprotein cholesterol/residual cholesterol (LDL-C/RC) coordination on major adverse cardiovascular events (MACE) in elderly hypertensive patients. Methods: This is a prospective cohort study. Elderly hypertensive patients hospitalized in Beijing Anzhen Hospital from June 2018 to June 2020 were prospectively enrolled. According to the coordination of baseline LDL-C/RC, patients were divided into four groups: low LDL-C and low RC (LDL-C<2.6 mmol/L, and RC<0.62 mmol/L), low LDL-C and high RC (LDL-C<2.6 mmol/L, and RC≥0.62 mmol/L), high LDL-C and low RC (LDL-C≥2.6 mmol/L, and RC<0.62 mmol/L), and high LDL-C and high RC (LDL-C≥2.6 mmol/L, and RC≥0.62 mmol/L). Patients were followed up until June 2022. The primary outcome was MACE, including non-fatal acute coronary syndrome, non-fatal acute heart failure, non-fatal stroke and death. Kaplan-Meier survival analysis was used to evaluate MACE among the four groups, and Cox regression analysis was performed to evaluate the related factors of MACE. Results: A total of 847 hypertensive patients were enrolled. There were 453 males (53.5%), mean age was (72.4±8.8) years. There were 207, 162, 263, 215 patients in the low LDL-C and low RC, low LDL-C and high RC, high LDL-C and low RC and high LDL-C and high RC group, respectively. During a median follow-up of 37 months, 196 patients (23.1%) had MACE, including 77 cases (9.1%) of ACS, 56 cases (6.6%) of acute heart failure, 34 cases (4.0%)of non-fatal stroke, 29 cases(3.4%) of all-cause mortality, and 16 cases (1.9%) of cardiovascular death. Risk of MACE of the four groups was significantly different (log-rank P<0.001). Compared with low LDL-C and low RC groups, high LDL-C and high RC groups had the highest incidence of MACE (HR=2.237, 95%CI 1.328-3.783, P=0.004), followed by low LDL-C and high RC groups (HR=1.745, 95%CI 1.220-2.527, P=0.003) and high LDL-C and low RC groups (HR=1.393, 95%CI1.048-1.774, P=0.022). In addition, the risk of nonfatal ACS among the four groups was also statistically significant (P=0.037), while the risk of nonfatal acute heart failure, nonfatal stroke, all-cause mortality and cardiovascular death were similar (all P>0.05). Multivariate Cox regression analysis showed that age (HR=1.271), duration of hypertension (HR=1.339), diabetes (HR=1.415), hyperlipidemia (HR=1.348), serum creatinine (HR=1.263), N-terminal pro-B-type natriuretic peptide (HR=1.316), LDL-C (HR=1.205), RC (HR=1.302), low LDL-C and high RC (HR=1.745), high LDL-C and low RC (HR=1.393), high LDL-C and high RC (HR=2.237) were independently associated with the occurrence of MACE. Conclusion: The coordination of LDL-C/RC affects the risk of MACE in elderly hypertensive patients, and the risk of MACE is the highest in patients with high LDL-C and high RC.
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Mâle , Humains , Sujet âgé , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Cholestérol LDL , Études prospectives , Cholestérol , Défaillance cardiaque , Facteurs de risque , Hypertension artérielle , Accident vasculaire cérébralRésumé
ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance (IR) by inhibiting the advanced glycation end product (AGE)/receptor for the advanced glycation end product (RAGE) signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group, a model group, high-, medium-, and low-dose Yitangkang-medicated serum groups (40, 20, and 10 g·kg-1), and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted,the cell viability and glucose consumption level of each group were determined. In addition,the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), p53, cysteinyl aspartate-specific protease-3 (Caspase-3), and cysteinyl aspartate-specific protease-9 (Caspase-9)] were determined using Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group, a model group, high-,medium-,and low-dose Yitangkang groups (40, 20, and 10 g·kg-1), and a western medicine group (pioglitazone hydrochloride,1.35 mg·kg-1). The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin (STZ) in animals and verified by the hyperinsulinemic-euglycemic clamp (HEC) test. After the model was determined successfully, the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group,while Real-time polymerase chain reaction(Real-time PCR) and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2, Bax, p53, Caspase-3, and Caspase-9. Result① In vitro experiments. compared with the blank group, the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption (P<0.01). Compared with the model group, the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption (P<0.01). Compared with the blank group, the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.01). Compared with the model group, the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells (P<0.01) and decreased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.05, P<0.01). ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group (P<0.01). The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group (P<0.01). Compared with the blank group, the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.01). Compared with the model group, the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats (P<0.01) and decreased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.05, P<0.01). The medium-dose Yitangkang showed a similar effect as RAGE inhibitor, and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.
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Objective:To investigate the relationship between transcription factors (TFs) and the prognosis of colon cancer, and to construct a prognosis model through TCGA and GEO dual databases, so as to quantify the risk of patients and guide clinical treatment decisions.Methods:The transcriptome and clinical data of colon cancer in TCGA and GEO databases were used in this study. The transcriptome data were annotated and the gene expression was calculated. The difference analysis of TFs in TCGA and GEO (log2FC > 1, P-value (Fdr) < 0.05) was performed. The difference TFs of double data intersection were used for correlation prognosis analysis ( P<0.01). The risk coefficient and risk value of prognosis-related TFs were calculated by COX multivariate analysis, and the prognosis model of TFs was constructed by COX model with "survival" and "glmnet" package. The survival curve ( P<0.001) and ROC curve (AUC>0.75) of the sequence set and verification set were drawn, and the distribution of risk value was visualized. After grouping according to risk value, GSEA enrichment analysis was calculated, gene set grid was constructed, target genes were predicted, and finally, pathway enrichment analysis of GO and KEGG was carried out. Results:387 TFs with different expressions in TCGA and GEO databases were used to draw heat map, volcanic map and TFs-related forest map, and the prognosis model of colon cancer was constructed according to COX multivariate analysis=0.310×HSF4+0.137×IRX3-0.127×ATOH1+0.290×OVOL3+0.137×HOXC6+0.155×SIX2+0.092×ZNF556-0.444×CXXC5+0.429×TIGD1+0.413×TCF7L1. Through enrichment analysis, our results showed that these prognostic factors may directly or indirectly act on cancer pathways, such as basic cell carcinoma and cancer signaling pathway, local tissue-cell adhesion, and extracellular matrix.Conclusions:The constructed TFs prognosis model of colon cancer can quantify the prognostic risk of colon cancer, and its high-risk group is an independent risk factor of colon cancer prognosis. This model is a new way to evaluate the prognosis of colon cancer.
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Objective To investigate the effects of dams-offspring separation on anxiety-like behaviors of dams, and if these anxiety-like behaviors of dams are associated with estrogen receptorα(ERα) and β( ERβ)in some brain regions. Methods Thirty C57BL/6 J female mice were divided into three groups, control group (CG, n= 10,non-isolated group), short-term separation group( SG,/i= 10, dams were separated from their offspring for 15 minuts per day from the second day to the tenth day after childbirth ) and long-term separation group ( LG, n = 10, dams were separated from their offspring for 3 hours per day from the second day to the tenth day after childbirth ). Anxiety-like behaviors of dams were evaluated in an open-field (OF) and elevated plus-maze test ( EPM ). The level of ERα- immunoreactive neurons (ERα-IRs) and ERβ-immunoreactive neurons (ERβ-IRs) in three brain regions including medial preoptic area (mPOA), hypothalamic ventromedial nucleus (VMH) and medial amygdaloid nucleus ( MeA) were analyzed. Results In OF, compared to CG group and SG group, LG group had significantly less time in center area, crossing number and total distance(P0.05 ). In EPM, compared to CG group and SG group, LG group had significantly less percentage of time, distance in open arms and total distance(P<0.001 ). Compared to CG group and SG group, LG group had significantly less ERa-IRs and ERβ-IRs in mPOA, VMH, and MeA(P<0.01). Conclusion Dams that are long-termly separated from their offspring may have anxiety-like behavior, and this behavior may be related to the significant reduction of ERa and ERβ in these brain regions.
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Objective:To analyze the effects of β-receptor blockers on all-cause mortality in elderly patients with mild-moderate chronic heart failure(CHF)and chronic obstructive pulmonary disease(COPD), and to analyze risk factors relevant to death.Methods:This was a multicenter retrospective cohort study from January 2013 to December 2017.The 400 elderly patients with CHF and COPD treated in Rizhao People's Hospital(187 cases), Shandong Provincial Hospital(122 cases)and Beijing Anzhen Hospital(91 cases)were enrolled.The patients receiving β-receptor blockers were included as β-receptor blockers group(n=200), and the patients matching for similar age and cardio-pulmonary function, not receiving β-receptor blockers were selected as the control group(n=200). All patients were followed up until December 31, 2019.The primary endpoints were all-cause mortality.The risk factors for all-cause death were compared and analyzed.Results:Among 400 patients, the average age was(72.2±11.7)years with 226 males(56.5%). There was no significant difference in baseline data such as age, gender ratio, body mass index, heart function, lung function, and treatment regimen after matching between the two groups(all P>0.05). At end of 3-years follow-up, risks of all-cause mortality( χ2=7.284, P<0.01), and re-hospitalization risk due to worsening heart failure( χ2=6.782, P<0.01), acute exacerbation of COPD( χ2=6.921, P<0.01)were significantly reduced in β-receptor blockers group versus control group.Multivariate Cox regression analysis showed that age ≥75 years( HR=2.142), diabetes( HR=1.929), ratio of baseline forced expiratory volume in the first second / forced vital capacity <66.8%( HR=1.114), baseline glomerular filtration rate <72.0 ml/min( HR=3.572)and left ventricular ejection fraction <46.4%( HR=2.294)at end of 3-year follow-up were risk factors for mortality, whileβ-receptor blockers( HR=0.745)was a protective factor(all P<0.05). Conclusions:β-receptor blockers can significantly reduce the mortality and re-hospitalization rate in elderly patients with CHF and COPD.
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Objective:To compare the efficacy and safety of different treatment methods for thoracoabdominal aortic aneurysm(TAAA).Methods:The clinical data of 39 TAAA patients admitted to our department from Jan 2010 to Feb 2018 were retrospectively analyzed.Results:There were 25 patients in endovascular group, 11 in open group and 3 in hybrid group. The mean age in the endovascular group was significantly higher than that in the open group ( P<0.05). The blood loss and operation time in the endovascular group were significantly lower than those in the open group and the hybrid group ( P<0.05). There was no significant difference in the operation success rate, the complication rate in post-operative 30 days and the rate of re-intervention ( P>0.05) among the three groups. The post-operative 30 days mortality was significantly higher in the hybrid group than that in the endovascular group and open group ( P<0.05). During the follow-up period, the complication rate in the endovascular group was significantly higher than that in the open group ( P<0.05). Conclusion:Endovascular surgery is more suitable for elderly patients because of shorter operation time, less trauma and bleeding.
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Objective:To analyze the difference of positioning accuracy by cone beam CT(CBCT) between modified head neck shoulder thermoplastic mask and breast bracket in intensity modulated radiotherapy for breast cancer patients after modified radical mastectomy.Methods:A total of 68 cases of breast cancer treated with IMRT after modified radical mastectomy were selected from August 2015 to December 2018. According to the different immobalization methods, the patients were divided into two groups: modified head neck shoulder thermoplastic mask group (body mask group, 42 cases) and breast bracket group (bracket group, 26 cases). After the first, sixth, 11th, 16th and 21st treatment, the patients were scanned by CBCT. The positioning errors in left and right (RL), anterior and posterior (AP) and head and foot (SI) directions were obtained, and the duration of radiotherapy positioning was recorded. The positioning error, distribution ratio and positioning duration were compared between two groups, and the respective MPTV margin were calculated. The influence of various factors on the setup error of patients was analyzed in the mask group. Results:There were 210 scans in the body mask group and 130 in the bracket group. The setup errors of the body mask group and bracket group in RL, AP and SI directions were (2.12±2.01) and (2.38±1.92) mm, (3.29±2.46) and (3.88±2.76) mm, (3.47±2.29) and (4.11±3.15) mm, respectively, and the differences in AP and SI directions were statistically significant ( t=-2.05, -2.16, P<0.05). The proportion of setup errors less than or equal to 3 mm in the direction for body mask group was higher than that of bracket group ( χ2=4.97, P<0.05). The proportion of setup errors more than 5 mm in AP and SI directions for body mask group was lower than that of bracket group ( χ2=5.21, 9.29, P<0.05). The positioning duration of mask group was shorter than of bracket group ( t=-2.16, P<0.05). The MPTV margins of the mask group in RL, AP and SI directions were smaller than those of the bracket group. The modified head, neck and shoulder thermoplastic mask immobalization method led to large setup errors in AP and / or SI directions for the elderly (≥ 60 years old), the patients with body mass index (BMI) ≥ 24 kg/m 2 and the patients who were relatively unfamiliar with the radiotherapy process (treatment time≤ 2 weeks). The setup error for patients aged < 60 years old in SI direction was smaller than that for the elderly (≥ 60 years old) patients ( t=-2.43, P<0.05). The setup error for patients with BMI <24 kg/m 2 in AP and Si directions was smaller than that with BMI ≥24 kg/m 2 ( t=-2.21, -2.04, P<0.05). The setup error for treatment time > 2 weeks in AP direction was smaller than that for treatment time ≤ 2 weeks ( t=2.23, P<0.05). Conclusions:In IMRT radiotherapy for breast cancer patients after modified radical mastectomy, the application of modified head neck shoulder thermoplastic mask can reduce the setup error in the anterior-posterior and superior-inferior directions, and shorten the positioning duration. For the elderly (≥ 60 years old), BMI ≥ 24 kg/m 2 and the patients who are not familiar with the radiotherapy process (treatment time ≤ 2 weeks), attention should be paid to the setup of anterior-posterior and superior-inferior directions to ensure the treatment effect of radiotherapy.
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OBJECTIVE@#To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS).@*WETHODS@#Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein.@*RESULTS@#Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein.@*CONCLUSION@#The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.
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Humains , Analyse de mutations d'ADN , Exons , Fibrilline-1 , Génétique , Fibrillines , Syndrome de Marfan , Génétique , Mutation , PedigreeRésumé
[Abstracts] Objective To investigate the effect and mechanism of acidizing pretreatment in respiratory acidosis on ischemia-reperfusion (IR) lung injury in rats. Methods Forty-eight male Sprague-Dawley rats, weighted 250-300 g, were randomly divided into 6 groups (8 each). Rats in control group: the left pulmonary hilum was dissociated without occlusion; in sham group: the respiratory rate was adjusted to maintain the partial pressure of end-tidal carbon dioxide reached 56-65 mmHg for 5 min, the left hilar not blocked; in IR group: the left pulmonary hilum was occluded for 45 min followed by reperfusion for 180 min; in group APC: done as in sham group and blocked the left hilar as in group IR; in group SB+IR: MMP-9 inhibitor SB-3CT 5 mg/kg was intraperitoneally injected, and then treated as in group IR 30 min after; in group SB+APC: done as in group APC, and then SB-3CT 5 mg/kg was injected 30 min after. Rats in all the 6 groups were sacrificed by arterial bleeding when the experiments ended, and lung tissues were taken. HE staining was performed to observe the pathological changes of lung tissues, and immunohistochemistry was used to detect the infiltration of neutrophils (PMN) in lung tissue. Western blotting was used to detect the expression of NF-κB and MMP-9 proteins. Immunofluorescence staining was used to detect the co-expression of NF-κB and MMP-9 proteins. Results Statistically significant differences existed in each group (P0.05). The above indicators were significantly higher in group IR, group APC, group SB+IR and group SB+APC than those in control group and sham group (P0.05). Conclusions In the IR rat model, acidizing pretreatment in respiratory acidosis can alleviate PMN infiltration and IR lung injury. The mechanism may be related to inhibition of NF-κB/MMP-9 protein expression.
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Aberrant oxidative metabolism in cells is one of the hallmarks of cancer. Overproduction of reactive species promotes carcinogenesis by inducing genetic mutations and activating oncogenic pathways, and thus, antioxidant therapy is considered as an important strategy for cancer prevention and treatment. Caveolin-1 (Cav-1), a constituent protein of caveolae, is involved in not only the formation of the caveolae, vesicular transport, maintaining cholesterol homeostasis directly, but also many cellular physiological and pathological processes including growth, regulation of mitochondrial antioxidant level, apoptosis and carcinomas by interacting with a lot of signaling molecules through caveolin scaffolding domain. Cav-1 has also been shown to mediate tumor genesis and progression through oxidative stress modulation, while Cav-1-targeted treatment could scavenge the reactive species. Intracellular reactive species could modulate the expression, degradation, post-translational modifications and membrane trafficking of Cav-1. More importantly, emerging evidence has indicated that multiple antioxidants could exert antitumor activities in cancer cells by modulating the signaling of Cav-1. This paper reviewed the research progresses on the roles of Cav-1 and oxidative stress in tumorigenesis and development, and would provide new insights on designing strategies for cancer prevention or treatment.
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Humains , Antioxydants , Apoptose , Carcinogenèse , Carcinomes , Anatomopathologie , Cavéoline-1 , Mitochondries , Tumeurs , Anatomopathologie , Stress oxydatif , Transduction du signalRésumé
Objective To observe the effects of resveratrol on human retinal pigment epithelium cells against H2O2-induced cell apoptosis and cell cycle. Methods Human RPE cells were divided into 3 groups ran-domly including normal control group,H2O2injury group and resveratrol protected group. H2O2injury group was treated with 200 μmol/L H2O2,and resveratrol protected group were treated with 50 mg/L resveratrol and then treat-ed with 200 μmol/L H2O2.CCK-8 was used to observe inhibitory rate of cell,and the flow cytometry was applied to detect the apoptosis and cell cycle distribution. Results CCK-8 assay showed that the inhibitory rate of cell treat-ed with resveratrol(50 mg/L)were obviously decreased,which was significantly different with H2O2injury group (P < 0.05),the apoptosis levels of cell treated with resveratrol for 2,8,24 h were significantly decreased(P <0.01).Moreover,the cell cycle distribution in the G0/G1 phases was also significantly decreased(P<0.01),the cell cycle distribution in the S phases was significantly increased(P<0.01).Conclusion Resveratrol can inhibit the cell apoptosis on human retinal pigment epithelium cells induced by H2O2,which is related to cell cycle regula-tion.
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Objective To investigate the clinical value of negative pressure vacuum cushion combined with thermoplastic body membrane in radiotherapy for Wilms tumor in children.Methods A total of 42 pediatric patients with Wilms tumor who received radiotherapy after surgery were enrolled in the study and were randomly divided into two groups according to the fixation positions:group A and group B.During radiotherapy, the patients in group A were fixed with negative pressure vacuum cushion, and those in group B were fixed by negative pressure vacuum cushion combined with thermoplastic body membrane.The setup errors, short-term effects, adverse reactions, and prognosis were compared between the two groups.ResultsGroup B showed significantly lower translational errors and rotational errors, as well as significantly higher rates of ≤3 mm and ≤5 mm errors, compared with the group A (P=0.04,0.04,0.04,0.03,0.00,0.04,0.04,0.00,0.04).Group B also showed significantly higher complete remission rates and response rates than group A (P=0.02,0.04).There were no significant differences in the adverse reaction rates (P=0.75) and the overall survival (OS) rates at 2 and 3 years (P=0.68,0.74) between the two groups.Group A had the MPTV values in left-right (LR) direction (x-axis), superior-inferior (SI) direction (y-axis), and anterior-posterior (AP) direction (z-axis) being 5.74 mm, 5.93 mm, and 5.94 mm, respectively, and group B had the MPTV values at LR, SI, and AP directions being 4.21 mm, 5.71 mm, and 4.61 mm, respectively.Conclusions In the radiotherapy positioning for Wilms tumor in children, fixation limbs with negative pressure vacuum cushion combined with thermoplastic body membrane effectively reduces the setup errors and improves the effect of radiotherapy, so it holds promise for clinical application.
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Caveolin-1 (Cav-1), as an important structural protein of caveolae, has been proven to be correlated with several signal transduction pathways. Recent studies have shown that Cav-1 may play a critical role in response to DNA damage in irradiated pancreatic cancer cells. However, it is not known whether down-regulation of Cav-1 is required to enhance the damage of other kinds of human cells exposed to X-radiation. In this study, the role of Cav-1 in Chang liver cell line (CHL) exposed to X-radiation was investigated. Cav-1 knockdown cell line (CHL-CAV7) was stably established by the siRNA plasmids transfection, and Cav-1 expression was suppressed by 60%, compared with that of control group (CHL-C) which was transfected with non-targeting plasmids. Cellular survival ability and the expressions of proteins related to DNA damage and repair were examined by colony formation assay and Western blot, respectively. Down-regulation of Cav-1 expression induced a significant decrease of the survival rate in CHL-CAV7 cells exposed to 8 and 10 Gy X-radiation. Compared with CHL-C cells, CHL-CAV7 cells showed increased γH2AX expression, as well as decreased p-ATM, DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and p53 protein expressions when treated with X-radiation. Meanwhile, the colocalization of Mdm2 and Cav-1 was decreased in CHL-CAV7 cells compared with that in CHL-C cells. These results suggest that the down-regulation of Cav-1 may aggravate DNA damage of CHL cells through reducing the interaction of Cav-1 and Mdm2, which results in the promotion of p53 degradation.
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Potassium channels have multitudinous subtypes, which are widely distributed on cell membranes. They affect various cellular physiological functions through participating in processes such as resting potential formation, substance transportation, enzyme activity and cellular communication. Autophagy is a significant mechanism to maintain intracellular metabolic homeostasis. The abnormity of autophagy may lead to the occurrence and development of multiple diseases. Recently, it has been reported that Kchannels and cell autophagy are closely related. Here, we reviewed the recent research progresses on regulation of autophagy signaling, autophagy flux or autophagolysosome formation by Kchannel, and discussed the physiological significance of autophagy regulation by Kchannel.
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To study the correlation between the spatial cognitive impairment and different subtypes of estrogen receptor α (ERα) of hippocampus in diabetic mice, we used alloxan (intraperitoneal injection) to induce type 1 diabetes in male Kunming mice and compared the spatial cognitive ability of the model mice with that of control mice through Morris water maze test. Meanwhile, using Western blot, we detected the protein expressions of ER-α36, ER-α66, caveolin-1, PKCα, cAMP-response element binding protein 2 (CREB2), and synaptophysin (Syn) in the hippocampus of the mice. The results showed that on the 3rd and 5th days of training, the ability of spatial learning and memory in the diabetic mice was significantly inferior to that of the control mice (P < 0.05). In the diabetic mice, the protein expressions of caveolin-1 and PKCα were decreased (P < 0.05), but ER-α66 expression was unaffected, while ER-α36 and CREB2 expressions were significantly increased (P < 0.05) compared with those of the control mice. The results suggest that abnormal expression of ER-α36 and related signal molecules may be important factors for diabetes-induced spatial cognitive impairment.
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Animaux , Mâle , Souris , Cavéoline-1 , Métabolisme , Dysfonctionnement cognitif , Protéine de liaison à l'élément de réponse à l'AMP cyclique , Métabolisme , Diabète expérimental , Récepteur alpha des oestrogènes , Métabolisme , Hippocampe , Métabolisme , Apprentissage du labyrinthe , Mémoire , Protein kinase C-alpha , Métabolisme , Synaptophysine , MétabolismeRésumé
Objective To analyze the characteristics and prognosis of intra-aortic balloown pump (IABP) supported percutaneous coronary intervention (PCI) in patients with Acute Coronary Syndrome (ACS) complicated with cardiogenic shock (CS).Methods 197 ACS patients complicated with CS patients received IABP supported PCI in Beijing Anzhen hospital from January 2014 to December 2015 were involved.According to the clinical results, all patients were divided into survival group and non-survival group.The clinical and laboratory parameters were compared between groups.Results Among the 197 patients enrolled, there were 162 patients in the survival group and 35 patients in the non-survival group.The mean age was (57.3±14.7) year-old, mean arterial blood pressure (MAP) on admission was (53.3±14.6) mmHg (1 mmHg=0.133 kPa).Percentage of diabetes comorbidity, cTnI level, oxygen index and MAP were significantly different between the survival and the non-survival groups (P<0.05).The symptom onset to balloon time and door-to-balloon time intervals were found delayed with significant difference in the non-survival group compared to the survival group (P<0.05).IABP improved hemodynamic parameters including blood pressure, cardiac function and oxygen index (P<0.05) in both groups.Duration of vasopressor usage, IABP implantation, percentage of invasive mechanical ventilation, length of stay in intensive care unit, acute kidney injury (AKI) and re-infarction were also significantly different between the two groups (P<0.05).Conclusions Adverse events risk is higher in ACS patients complicated with cordiogenic shock requiring IABP support for PCI.Patients with mortal outcomes are older, comorbid with diabetes mellitus and history of myocardial infarction and higher event rates of re-infarction and acute kidney injury during hospitalization.Intensive care should be implemented to reduce the incidence of adverse events.