BACKGROUND:The mechanical index is an important method for the evaluation of the therapeutic efficiency of drug treatment for osteoporosis animal models. OBJECTIVE: To explore the effects of various drug treatments on osteoporosis through a mechanical performance test about the femoral compression of rats. METHODS: Thirty-six Wistar female rats were randomized into six groups: normal control group, model group, Dan Qiparticles group, alpha-D3 group, premarin group, ipriflavone group, with six rats in each group. Osteoporosis models were made in al groups except for the normal control group, and after modeling, the rats in different groups were treated withDan Qi particles, alpha-D3 group, premarin and ipriflavone, respectively. After 15 weeks, the rats were kiled by abdominal aortic bloodletting to take out the left and right femurs that were placed on a universal testing machine to perform a compressive test at a speed of 5 mm/min. RESULTS AND CONCLUSION:The maximum load, maximum stress, maximum displacement, maximum strain, and elastic modulus were significantly lower in the model group than the other four groups (P < 0.05). There was no difference in different mechanical parameters between alpha-D3 group and model group as wel as between Dan Qi particles group and normal control group (P> 0.05). These findings indicate that osteoporosis leads to the variation of compression mechanical properties of the femur. There are good compression mechanical properties of the femur after treatment with premarin and ipriflavone, andDan Qi particles has the best effect.

Objective To determine the electrocardiographic (ECG) characteristics of myocardial infarction (MI) evolution in rats and the intervention effect of Chinese herbs, and to provide basis for the establishment of the criteria for ECG diagnosis and assessment of drug therapeutic effects of rats MI. Methods Totally 140 male SD rats were randomly divided into sham operation group, model group, replenishing qi group, activating blood group, replenishing qi and activating blood (1∶2) and (2∶1) group as well as Tongxinluo group, each group with 20 rats. The rat MI model was established by ligating the left anterior descending coronary artery. The treatment groups were administrered with corresponding drugs by gavage from the first day after operation. The sham operation group and model group were given the same volume of distilled water. The 12-lead ECGs were recorded before, immediately after, 1st and 2nd week after operation respectively. The voltage value of ST segment deviation, the time limit of QRS complex and the number of animals with pathologic Q wave were evaluated for statistical analysis. Results Model group showed the elevation of ST segment, significantly prolonged time limit of QRS complex (P<0.01), and no pathologic Q wave showed immediately after operation compared with sham operation group. And all above observational indexes reached the peak at 1st week and declined at 2nd week after operation. Compared with model group at 2nd week after operation, replenishing qi and activating blood (1∶2) group and (2∶1) group all presented remarkable dropping of ST segment, shortening in time limit of QRS complex and reduction in number of rats with pathologic Q wave, of which 2∶1 group showed the most (P<0.01). Activating blood group only displayed decreases in time limit of QRS and number of rats with pathologic Q wave (P<0.05), and no significant decline in ST segment. Replenishing qi group demonstrated no significant changes in above three observational indexes (P>0.05). Thus, we proposed the criterion for the ECG diagnosis of rats MI as well as the criterion for the ECG assessment of drug therapeutic effects of rats MI. Conclusion ECG can overall and sensitively evaluate the evolution and drug therapeutic effects of MI in rats, thus providing a relatively objective and available assessment method for the experimental studies of myocardial ischemic diseases.

Objective:To observe the changes of LHX4 and DIS3L mRNA and protein expression in Nthy-ori-3-1 cells after the treatment of thyroid disruptor p, p'-DDE. Methods:Nthy-ori-3-1 cells in logarithmic growth phase were treated with 0, 0.5, 1.0, 2.0 and 5.0 μg/ml p, p'-DDE solution. The growth state and morphology of the cells were observed by microscope. The mRNA levels of LHX4 and DIS3L were detected by real-time fluorescent quantitative PCR, and the protein expression levels of LHX4 and DIS3L were detected by Western blot. Results:when the concentrations of p, p'-DDE were 0, 0.5, 1.0 and 2.0 μg/ml, Nthy-ori-3-1 cells grew normally. There were 33 differential genes in 2.0 μg/ml group, among which 13 genes were down regulated and 20 genes were up-regulated. Compared with the control group, the protein expression levels of LHX4 and DIS3L in 1.0 and 2.0 μg/ml groups were significantly decreased ( P<0.05) , and the relative expression levels of LHX4 and DIS3L protein mRNA in 1.0 μg/ml group were significantly decreased ( P<0.05) . Conclusion:p, p'-DDE can affect the protein expression of LHX4 and dis3l in nthy-ori-3-1 cells.

Objective:To examine the trend of stroke disease burden and its main risk-attributable factors in China and regions with different Socio-Demographic Index (SDI) from 1990 to 2017.Methods:With 2017 Global Burden of Disease (GBD) data, years lived with disability (YLDs), years of life lost (YLLs) and disability-adjusted of life years (DALYs) were applied to describe the disease burden and major risk factors of stroke in China and different SDI regions from 1990 to 2017, and to analyze the changing trend of the disease burden and major risk factors of stroke.Results:From 1990 to 2017, the YLD crude rate, YLL crude rate and DALY crude rate for stroke in China showed an increasing trend and the rate of change was 126.5%, 14.6%, and 24.4%, respectively. In 2017, the YLD crude rate, YLL crude rate and DALY crude rate for stroke in China were 502.6 per 100 000, 2 633.1 per 100 000 and 3 135.7 per 100 000, respectively. Among them, the YLD crude rate, YLL crude rate, and DALY crude rate of stroke were the highest in the ≥70 age group, which were 2 617.2 per 100 000, 16 789.4 per 100 000 and 19 406.6 per 100 000, respectively. The YLD crude rate in male was 475.5 per 100 000, which was slightly lower than that of female (530.9 per 100 000), while the DALY crude rate and YLL crude rate for stroke were 3 657.1 per 100 000 and 3 181.7 per 100 000, respectively, which were significantly higher than that of female (2 591.8 per 100 000 and 2 060.9 per 100 000). Compared with regions with different SDI, the age standardized YLD rate, the age standardized YLL rate, the age standardized DALY rate in China were all at a high level. Among them, the age-standardized YLD rate increased from 286.2 per 100 000 to 374.5 per 100 000, with a rate of change of 30.9%; the age-standardized YLL rate decreased from 3 215.6 per 100 000 to 1 967.8 per 100 000, with a rate of change of -38.8%; the age-standardized DALY rate increased from 3 501.8 per 100 000 to 2 342.3 per 100 000, with a rate of change of -33.1%. The top five risk factors for stroke in China were hypertension, excessive sodium intake, insufficient fruit intake, insufficient cereal intake, and smoking in 1990 and 2017. High Body-Mass Index and Alcohol Use′s rankings rose from the 9th and 10th in 1990 to the 6th and 7th in 2017, respectively.Conclusion:The burden of stroke disease in China is at a high level, and hypertension is the primary risk factor.

Objective:To observe the changes of LHX4 and DIS3L mRNA and protein expression in Nthy-ori-3-1 cells after the treatment of thyroid disruptor p, p'-DDE. Methods:Nthy-ori-3-1 cells in logarithmic growth phase were treated with 0, 0.5, 1.0, 2.0 and 5.0 μg/ml p, p'-DDE solution. The growth state and morphology of the cells were observed by microscope. The mRNA levels of LHX4 and DIS3L were detected by real-time fluorescent quantitative PCR, and the protein expression levels of LHX4 and DIS3L were detected by Western blot. Results:when the concentrations of p, p'-DDE were 0, 0.5, 1.0 and 2.0 μg/ml, Nthy-ori-3-1 cells grew normally. There were 33 differential genes in 2.0 μg/ml group, among which 13 genes were down regulated and 20 genes were up-regulated. Compared with the control group, the protein expression levels of LHX4 and DIS3L in 1.0 and 2.0 μg/ml groups were significantly decreased ( P<0.05) , and the relative expression levels of LHX4 and DIS3L protein mRNA in 1.0 μg/ml group were significantly decreased ( P<0.05) . Conclusion:p, p'-DDE can affect the protein expression of LHX4 and dis3l in nthy-ori-3-1 cells.

Objective:To examine the trend of stroke disease burden and its main risk-attributable factors in China and regions with different Socio-Demographic Index (SDI) from 1990 to 2017.Methods:With 2017 Global Burden of Disease (GBD) data, years lived with disability (YLDs), years of life lost (YLLs) and disability-adjusted of life years (DALYs) were applied to describe the disease burden and major risk factors of stroke in China and different SDI regions from 1990 to 2017, and to analyze the changing trend of the disease burden and major risk factors of stroke.Results:From 1990 to 2017, the YLD crude rate, YLL crude rate and DALY crude rate for stroke in China showed an increasing trend and the rate of change was 126.5%, 14.6%, and 24.4%, respectively. In 2017, the YLD crude rate, YLL crude rate and DALY crude rate for stroke in China were 502.6 per 100 000, 2 633.1 per 100 000 and 3 135.7 per 100 000, respectively. Among them, the YLD crude rate, YLL crude rate, and DALY crude rate of stroke were the highest in the ≥70 age group, which were 2 617.2 per 100 000, 16 789.4 per 100 000 and 19 406.6 per 100 000, respectively. The YLD crude rate in male was 475.5 per 100 000, which was slightly lower than that of female (530.9 per 100 000), while the DALY crude rate and YLL crude rate for stroke were 3 657.1 per 100 000 and 3 181.7 per 100 000, respectively, which were significantly higher than that of female (2 591.8 per 100 000 and 2 060.9 per 100 000). Compared with regions with different SDI, the age standardized YLD rate, the age standardized YLL rate, the age standardized DALY rate in China were all at a high level. Among them, the age-standardized YLD rate increased from 286.2 per 100 000 to 374.5 per 100 000, with a rate of change of 30.9%; the age-standardized YLL rate decreased from 3 215.6 per 100 000 to 1 967.8 per 100 000, with a rate of change of -38.8%; the age-standardized DALY rate increased from 3 501.8 per 100 000 to 2 342.3 per 100 000, with a rate of change of -33.1%. The top five risk factors for stroke in China were hypertension, excessive sodium intake, insufficient fruit intake, insufficient cereal intake, and smoking in 1990 and 2017. High Body-Mass Index and Alcohol Use′s rankings rose from the 9th and 10th in 1990 to the 6th and 7th in 2017, respectively.Conclusion:The burden of stroke disease in China is at a high level, and hypertension is the primary risk factor.

Estrogen has anti-colorectal cancer effects which are thought to be mediated by mismatch repair gene (MMR) activity. Estrogen receptor (ER) expression is associated with microRNA (miRNA) expression in ER-positive tumors. However, studies of direct link between estrogen (especially estradiol E2), miRNA expression, and MMR in colorectal cancer (CRC) have not been done. In this study, we first evaluated the effects of estradiol (E2) and its antagonist ICI182,780 on the expression of miRNAs (miR-31, miR-155 and miR-135b) using COLO205, SW480 and MCF-7 cell lines, followed by examining the association of tissue miRNA expression and serum E2 levels using samples collected from 18 colorectal cancer patients. E2 inhibited the expressions of miRNAs in COLO205 cells, which could be reversed by E2 antagonist ICI 182.780. The expression of miR-135b was inversely correlated with serum E2 level and ER-beta mRNA expression in CRC patients' cancer tissues. There were significant correlations between serum E2 level and expression of ER-beta, miR-135b, and MMR in colon cancer tissue. This study suggests that the effects of estrogen on MMR function may be related to regulating miRNA expression via ER-beta, which may be the basis for the anti-cancer effect in colorectal cells.
Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adult ; Aged ; Cell Line, Tumor ; Colorectal Neoplasms/*genetics/metabolism ; DNA Mismatch Repair/*genetics ; Estradiol/analogs & derivatives/blood/*pharmacology ; Estrogen Antagonists/pharmacology ; Estrogen Receptor beta/genetics/*metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/genetics/*metabolism ; Middle Aged ; MutS Homolog 2 Protein/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; RNA, Messenger/biosynthesis

Objective:To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS).Methods:① In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). ② In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. Results:① In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. ② In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. Conclusion:HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

3' Untranslated Regions ; Animals ; Biomarkers ; metabolism ; Cell Proliferation ; Cell Survival ; Embryonic Stem Cells ; cytology ; metabolism ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mice ; Swine ; Transcription Factors ; genetics ; metabolism

Objective:To investigate the effect of inhibitory activity of high mobility group protein B1 (HMGB1), signal transduction and activator of transcription 3 (STAT3) on myocardial ischemia-reperfusion injury in rats.Methods:In vivo and in vitro models of MIRI were established. SD rats were randomly divided into a sham group, a model group, a glycyrrhizic acid group, and a NSC74859 group, with 6 rats in each group. Rats in the sham group were not ligation, and rats in the sham group and model group were not given medication. The rats in the glycyrrhizic acid group and the NSC74859 group were injected with HMGB1 antagonist glycyrrhizic acid or STAT3 inhibitor NSC74859 5 mg/kg in the tail vein at 12 h 30 min before ischemia/reperfusion and 30 min after ischemia, respectively. Left ventricular shortening fraction (FS) and left ventricular ejection fraction (EF) were evaluated by echocardiography, and apoptosis of cardiomyocytes was evaluated by hematoxylin-eosin (HE) and TUNEL staining. The expression levels of HMGB1, STAT3, and phosphorylated STAT3 (p-STAT3) were detected by real-time fluorescence quantitative PCR and Western Blot. The viability of H9C2 cells was determined by the MTS assay, intracellular ATP content was determined, and the mitochondrial membrane potential of H9C2 cells was measured by flow cytometry to evaluate the survival of cardiomyocytes. The action mode of HMGB1/STAT3 was studied by the immunoprecipitation method. The expression and migration of HMGB1/STAT3 in the nucleus and cytoplasm were detected by immunostaining. Results:After inhibiting the expression of HMGB1 or STAT3, EF and FS were increased, and immune infiltration and apoptosis of cardiomyocytes were decreased. Inhibition of HMGB1 expression could decrease the expression of STAT3, but inhibition of STAT3 expression didn’t affect the expression of HMGB1. Hypoxia could lead to increased expression of HMGB1 and p-STAT3, and decreased expression of STAT3. After 8 hours of hypoxia, the expression level of STAT3 suddenly increased. After reoxygenation, the expression of HMGB1 and STAT3 decreased, and the expression of p-STAT3 increased, but p-STAT3 (Ser 727) didn’t participate in this process. After ischemia-reperfusion injury, HMGB1 and STAT3 binded firmly in cardiomyocytes, but inhibition of STAT3 or HMGB1 weakened this binding. Inhibition of HMGB1 or STAT3 expression could reduce myocardial ischemia-reperfusion injury. The expression of HMGB1 in reoxygenated cardiomyocytes increased after hypoxia, and HMGB1 migrated from the nucleus to the cytoplasm.Conclusions:Inhibiting the activity of the HMGB1/STAT3 axis effectively reduces MIRI in rats.