Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To explore the feasibility and accuracy of three-dimensional (3D) modeling methods based on ultrasound imaging data for normal and abnormal fetal cardiac structures, and to construct a methodology system for 3D printing of fetal heart based on ultrasound.Methods:A total of 93 fetuses examined in Tangdu Hospital of Air Force Military Medical University from January to December 2019 were selected. Fetal echocardiography was obtained using spatio-temporal image correlation (STIC). Ninety-three hearts were 3D modeled by blood flow modeling, blood pool modeling and cavity modeling, and printed by stereolithography technique. The data measured on the 3D digital models and 3D printed solid models were compared with the corresponding fetal echocardiographic images respectively in order to evaluate the accuracy of the modeling methods.Results:The fetal cardiac blood flow models based on Doppler flow image data showed the malformation and trend of small blood vessels. The fetal cardiac structure models printed based on blood pool modeling displayed the malformation of heart and large blood vessels. Models printed based on cavity modeling method accurately displayed valve and structural defects.For 83 normal fetal hearts, the long diameters of left and right ventricles measured on echocardiography [(15.3±1.9)mm, (13.2±1.9)mm] were compared with those measured on digital models [(15.1±1.9)mm, (12.9±1.9)mm] and 3D printed models[(15.1±1.9)mm, (13.0±1.9)mm], respectively, and there were no significant differences between any two groups of them ( P>0.05). Bland-Altman showed good consistency for all measurements within and between operators. Conclusions:The three modeling methods, including blood flow modeling, blood pool modeling and cavity modeling, have their own advantages in displaying different types of fetal heart malformations. Appropriate modeling methods should be selected for 3D modeling and printing to make up for the limitations of single modeling method. The consistency between measurements on 3D models and those on echocardiography is high, and the repeatability between operators is good.

Objective:To investigate the postoperative changes in levels of 25-hydroxy vitamin D (25-[OH]D], parathyroid hormone (PTH) and other relevant biomarkers in obese patients receiving metabolic surgery and analyze the dynamic changes in relevant biomarkers in the short term (after 3-6 months) and the long term (after 12-24 months).Methods:A total of 96 obese patients who underwent metabolic surgery and received follow-up examinations from January 2018 to January 2020 were included. Baseline and postoperative data were collected, including anthropometric data (height, weight, neck circumference, waistline and hipline) and laboratory test results (fasting glucose, glycated hemoglobin, 25-[OH)D, PTH, serum calcium and serum phosphorus). Body mass index (BMI) and waist-hip ratio were calculated. The anthropometric data were analyzed by repeated measures analysis of variance and laboratory data were compared between groups using t test and Kruskal-Wallis test. Results:96 patients (33 males and 63 females) were included, of whom 49 were complicated with diabetes. Prior to surgery, 79 (79.17%) of the patients had 25-(OH)D deficiency (< 20 μg/L), 16 (16.67%) had 25-(OH)D insufficiency (≥ 20 μg/L and < 30 μg/L) and 23 (23.96%) had high PTH levels (> 70 ng/L). After the surgery, 25-(OH)D level was transiently increased in the short term ( P = 0.01) but declined thereafter in the long term ( P < 0.01) to levels lower than baseline ( P = 0.023). Long-term PTH level was higher than baseline ( P = 0.012), with 11 patients showing PTH levels higher than normal (> 70 ng/L). Serum phosphorus level was increased in both the short term and the long term ( P < 0.01). Conclusions:Obese patients have 25-(OH)D deficiency/insufficiency before metabolic surgery and experience further decrease in the long term after surgery, despite a transient increase. Secondary increase in PTH level occurs in some of the patients after surgery. Long-term nutritional supplements and comprehensive nutritional management play important roles in postoperative management of obese patient.

Objectives To explore the effect of exogenous erythropoietin (EPO) on the expression of glial fibrillary acidic protein (GFAP) in hippocampal CA1 region and 5- bromide -2- uracil (BrdU) in hippocampal DG region in neonatal Wistar rats with hypoxic-ischemic brain damage (HIBD). Methods Forty-eight Wistar rats aged 7 days were randomly divided into HIBD model group and EPO experimental group, and another 24 rats as sham operated group. The HIBD model was established by ligating the right common carotid artery and inhaling hypoxia gas mixture (8％ O2 and 92％ N2) for 2 h. The expression of GFAP in hippocampal CA1 region and the number of BrdU positive cells in the hippocampus were detected by immunohistochemical method on at 14 d, 21 d, and 28 d after operation and compared among three groups. Results On 14 d and 21 d after operation, the expression of GFAP in CA1 region and the number of BrdU positive cells were statistically different among three groups (P<0.01) with EPO experimental group having the highest, HIBD model group having the second highest and sham operation group having the lowest in both, . On 28 d after operation, there was no difference in the expression of GFAP and the number of BrdU positive cells in the DG among three groups (P>0.05). At different time point (14 d, 21 d, 28 d) in every group, the expression of GFAP in CA1 region and the number of BrdU positive cells in DG region were all statistically different (P<0.01), all with the highest on 14 d after operation, second highest on 21 d, and the lowest on 28 d. Conclusions Early administration of exogenous EPO can promote the expression of GFAP in hippocampal CA1 region and increase the number of BrdU positive cells in DG region, which indicates that EPO can promote the proliferation and regeneration of damaged neurons. EPO had neuroprotective effect on neonatal rats with hypoxic-ischemic brain damage.

Objective To study the protective effect of recombinant human erythropoietin (EPO) on brain and to explore the changes in the diversity of intestinal microbial flora in neonatal rats with hypoxic-ischemic encephalopathy (HIE) by establishing a neonatal rat model of HIE, and to provide an experimental basis for clinical application of EPO in the treatment of neonatal HIE. Methods The HIE model was established in 7-day-old neonatal SD rats. The rats were randomly divided into the HIE model group, EPO-treated group and control group. The changes of nestin expression were detected by immunohistochemistry. Feces of the rats were collected to detect the changes in intestinal microbial flora by 16s rRNA sequencing. Results The expressions of nestin at the same time point in each group were significantly different (P ＜0. 05). The nestin level in the control group was the lowest, that in the EPO-treated group was the highest, and the HIE model group in between. The Shannon-Wiener index of the HIE model group showed a tendency to decrease compared with the control group. Conclusions Exogenous EPO can promote the growth of neural cells in neonatal rats with HIE, indicating a certain protective effect. Meanwhile, the diversity of intestinal microbial flora of the HIE neonatal rats is also changed.

Objective To study the effect of adjuvant chemotherapy on the survival of patients with ER ≥ 50％,HER2 negative,lymph node negative breast cancer.Methods 428 patients from Jan 1,2004 to Dec 31,2010 were enrolled.All patients received operation plus chemoendocrine therapy (CET,n =239) or endocrine therapy (ET,n =189).Result The median follow-up time was 76.5 months,with 8.2％ loss to follow-up.The recurrence-free survival (RFS) was 93.7％ in CET group and 95.2％ in ET group,the distant disease-free survival (DDFS) was 94.6％ and 97.4％ in CET and ET group respectively.Multivariate regression indicated that the risk of tumor size ＞ 2 cm was higher than that of tumor size ≤2 cm in recurrence (HR=2.31,95％ CI 1.07-5.29,P =0.047) and metastasis (HR=4.71,95％ CI 1.47-11.85,P =0.01).Compared with CET group,however,no statistical significance was found on RFS (HR =1.08,95 ％ CI 0.46-2.57,P =0.86) and DDFS (HR =0.72,95 ％ CI 0.17-1.37,P =0.55) in ET group.Conclusions Adjuvant chemotherapy cannot improve the RFS and DDFS of ER≥50％,HER2 negative,lymph node negative breast cancer.Tumor size ＞ 2 cm was the risk factor of recurrence and distant metastasis.

Objective To explore the effect of progesterone on the expression of O4 and O1 in the white matter of neonatal rat model with periventricular leukomalacia (PVL). Methods 2-day-old neonatal SD rats were randomly divided into model group, experimental group, and sham operation group. Rats' left common carotid artery was ligated and exposed to hypoxia (8%O2+92%N2) for 0.5 h in both the model group and experimental group to build the PVL animal model. The rats in experimental group was injected intraperitoneally with progesterone 10 mg/(kg·d) immediately after cerebral hypoxia ischemia. In sham operation group, rats' left common carotid artery was only isolated without ligation and hypoxia. 1, 4, 7, and 14 days after operation, the pathological changes of brain tissue were compared among three groups. Immunohistochemical staining was used to detect the expression of O1 and O4 in the cerebral cortex of rats in three groups at different time points. Results There were no abnormal pathological changes in the white matter in the sham operation group at each time point. The left ventricular enlargement and periventricular leukomalacia were found in both model and experimental groups, while the pathological damages of white matter in experimental group were significantly lighter than those in model group at each time point. The integral optical density (IOD) of O1 and O4 positive cells in the cerebral cortex of the three groups was gradually increased at day 1, day 4, and day 7 after operation and reached the peak level at day 7 , then was decreased at day 14 after operation. There was statistically significant difference (P<0.01). At day 1, day 4, day 7, and day 14, the integral optical density (IOD) of O1 and O4 positive cells in the cerebral cortex of sham operation group was highest, followed by experimental group and model group, and there was significant difference (P<0.01). Conclusion Progesterone can reduce the pathological damage in the cerebral cortex in neonatal rats with PVL, and promote the expression of O1 and O4 in the periventricular white matter, which can promote the differentiation and maturation of oligodendrocytes.

Objective To investigate the effect of preventive antidepressants application on the prognosis of and serum brain derived neurotrophic factor(BDNF) level in acute cerebral infarction(ACI).Methods One hundred and forty-one patients with ACI were prospectively and randomly selected.Seventy-two cases in the intervention group was added with sertraline for 12 weeks on the basis of the routine therapy,while 69 cases in the control group only used the routine therapy.The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the nervous function impairment degree and daily living ability.The Hamilton Depression Rating Scale-17 was used to evaluate the emotion after stroke.The cognition function was evaluated by the Mini-Mental State Examination (MMSE).The BDNF level was detected by using the double antibody sandwich enzyme-linked immunosorbent assay.Results The NIHSS and HAMD scores after 3-month treatment were (1.77±0.58)points and (5.43±1.77)points in the intervention group,and (4.06±0.79)points and(10.27±3.78)points in the control group,which were significantly decreased compared with before treatment(P＜0.05);the BI value in the intervention group and control group were (96.24±4.58) and (77.64±6.96),which weresignificantly increased compared with before treatment (P＜0.05),and serum BDNF levels were (8.38±0.74)ng/mL and (5.72 ±0.67)ng/mL respectively,which were significantly increased compared with before treatment,moreover the change in the intervention group was more obvious than that in the control group (P＜0.05).The MMSE score had no statistical difference between the two groups (P＞0.05).The PSD occurrence rate was 10.0％ in the intervention group,which was significantly decreased compared with 53.6％ in the control group (P＜0.05).Conclusion Preventive antidepressants application in the patients with ACI can increase the serum BDNF level,improves the prognosis and is worth promotion and application.

BACKGROUNDBlood pressure variability (BPV) is a reliable prognostic factor for cardiovascular events. Currently there is a worldwide lack of large sample size studies in visit-to-visit BPV. Based on the Kailuan Study, we analyzed the visit-to-visit BPV of patients to investigate the range and influencing factors of BPV.

METHODSIn 11 hospitals in the Kailuan Company, 4 441 patients received routine health checkups. Physical examination measured blood pressure (BP), body height, body weight, and waist circumference, and body mass index was calculated. Blood samples were analyzed for plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and high-sensitivity c-reactive protein (hs-CRP).

RESULTSThe effect of gender on systolic BPV was investigated. The average systolic BPV was 10.35 mmHg (1 mmHg = 0.133 kPa) overall, 10.54 mmHg in males and 10.06 mmHg in females. Multivariate Logistic regression analysis revealed that the age (RR = 1.022), systolic BP (SBP, RR = 1.007), LDL-C (RR = 1.098), and history of hypertension (RR = 1.273) were significant risk factors for higher systolic BPV. We found that aging (RR = 1.022), increased SBP (RR = 1.007), and a history of hypertension (RR = 1.394) were determinants of systolic BPV in males. The risk factors for systolic BPV of females were aging (RR = 1.017), increased SBP (RR = 1.009), increased LDL (RR = 1.136), and increased TG (RR = 1.157).

CONCLUSIONOur findings indicated that the systolic BPV is closely associated with age, SBP and history of hypertension.

Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; physiology ; C-Reactive Protein ; metabolism ; China ; Cities ; Female ; Humans ; Hypertension ; physiopathology ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Logistic Models ; Male ; Middle Aged ; Triglycerides ; blood ; Waist Circumference ; physiology