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ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.
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Objective:To investigate the relationship between intracranial arterial remodeling and imaging markers in patients with cerebral small vessel disease (CSVD).Methods:One hundred and fifty-six patients with CSVD who were admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University or the Public People′s Hospital of Xinzheng from January 2020 to May 2022 were selected, and their brain artery remodeling (BAR) score was calculated. The patients with BAR score≤-1 standard deviation (SD) were defined as individuals with constrictive remodeling of intracranial arteries, and the patients with BAR score≥1 SD were defined as individuals with dilated remodeling of intracranial arteries. Imaging markers of CSVD [white matter hyperintensities (WMHs), lacune, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy] were quantified, total CSVD load was calculated and patients were divided into low load group (0-2 points, n=91) and high load group (3-4 points, n=65) according to the total CSVD load scores. The correlation between intracranial artery remodeling and various imaging markers of CSVD and total load was analyzed by using univariate analysis and binary Logistic regression analysis. A nomogram prediction model was established and a receiver operating characteristic curve (ROC) was drawn to assess the predictive value of intracranial artery remodeling on high total CSVD load. Results:Dilated intracranial arterial remodeling was an independent influence factor on severe WMHs ( OR=3.66, 95% CI 1.38-9.72, P=0.009), lacune ( OR=3.78, 95% CI 1.17-12.19, P=0.026), cerebral atrophy ( OR=3.11, 95% CI=1.10-8.81, P=0.033), and high total CSVD load ( OR=6.66, 95% CI=2.14-20.77, P=0.001). Age was an independent influencing factor for high total CSVD load ( OR=1.12, 95% CI 1.07-1.16, P<0.01). A nomogram prediction model for high total CSVD load with age and BAR score≥1 SD as dependent variables had a good effect (C-index=0.826) and calibration ( P=0.024). The best cut-off point of ROC curve was 0.50, with an area under the curve of 0.83 (95% CI 0.76-0.89, P<0.01), the sensitivity and specificity of 0.72 and 0.82. Conclusions:Patients with dilated intracranial arterial remodeling may have a heavier CSVD load. Dilated intracranial arterial remodeling may serve as a new biomarker for assessing CSVD, but the mechanism of the association needs further study.
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In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.
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Objective To investigate the effects and mechanism of Shexiang Baoxin Pills on insulin resistance (IR) in patients with coronary heart disease.Methods From January 2016 to March 2017,82 patients with coronary heart disease in The Second People's Hospital of Nanyang were selected as the research object.All the patients were divided into observation group and control group with 41 cases in each group according to the principle of random envelope drawing.The control group was given conventional treatment,and the observation group was treated with Shexiang Baoxin Pills on the basis of the treatment of the control group.The observation periods of the two groups were 3 months.Results The total effective rates of the observation group and control group were 97.6％ and 82.9％,respectively,and the observation group was better than that of the control group (P ＜ 0.05).The IR indexes of the observation group and control group after treatment were (1.79 ± 0.45) and (2.44 ± 0.51),respectively,which were significantly lower than before treatment of (4.01 ± 0.44) and (4.00 ± 0.56) (P ＜ 0.05),and the IR index in the observation group after treatment was significantly higher than that in the control group (P ＜ 0.05).The serum CRP levels of the observation group and control group were significantly lower than those before treatment (P ＜ 0.05),and the level of serum CRP in the observation group after treatment was also significantly lower than that in the control group (P ＜ 0.05).Atter treatment,the coronary artery remodeling,no reconstruction and negative reconstruction in the observation group were 4 cases,25 cases and 13 cases,while the control group were 15 cases,10 cases and 16 cases,the difference between the two groups was statistically significant (P ＜ 0.05).Conclusion Shexiang Baoxin Pill can improve the therapeutic effect and improve the IR status in patients with coronary heart disease,and its mechanism may be related to inhibiting the expression of inflammatory factors and improving coronary artery remodeling.
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Objective To investigate the effects and mechanism of Shexiang Baoxin Pills on insulin resistance (IR) in patients with coronary heart disease.Methods From January 2016 to March 2017,82 patients with coronary heart disease in The Second People's Hospital of Nanyang were selected as the research object.All the patients were divided into observation group and control group with 41 cases in each group according to the principle of random envelope drawing.The control group was given conventional treatment,and the observation group was treated with Shexiang Baoxin Pills on the basis of the treatment of the control group.The observation periods of the two groups were 3 months.Results The total effective rates of the observation group and control group were 97.6％ and 82.9％,respectively,and the observation group was better than that of the control group (P ＜ 0.05).The IR indexes of the observation group and control group after treatment were (1.79 ± 0.45) and (2.44 ± 0.51),respectively,which were significantly lower than before treatment of (4.01 ± 0.44) and (4.00 ± 0.56) (P ＜ 0.05),and the IR index in the observation group after treatment was significantly higher than that in the control group (P ＜ 0.05).The serum CRP levels of the observation group and control group were significantly lower than those before treatment (P ＜ 0.05),and the level of serum CRP in the observation group after treatment was also significantly lower than that in the control group (P ＜ 0.05).Atter treatment,the coronary artery remodeling,no reconstruction and negative reconstruction in the observation group were 4 cases,25 cases and 13 cases,while the control group were 15 cases,10 cases and 16 cases,the difference between the two groups was statistically significant (P ＜ 0.05).Conclusion Shexiang Baoxin Pill can improve the therapeutic effect and improve the IR status in patients with coronary heart disease,and its mechanism may be related to inhibiting the expression of inflammatory factors and improving coronary artery remodeling.