Effect of Juanbi Qianggu Formula on biological behaviors of fibroblast-like synoviocytes in rheumatoid arthritis by regulating FGFR1 signaling pathway based on network pharmacology and cell function experiments / 中国中药杂志

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.

Clinical study of temperature contrast injection procedure in prevention of bone cement leakage during vertebroplasty / 中国骨伤

OBJECTIVE@#To observe the effect of temperature contrast injection procedure on prevention and reduction of bone cement leakage in vertebroplasty (PVP).@*METHODS@#The clinical data of 42 patients(48 vertebral bodies) with osteoporotic vertebral compression fractures(OVCFs) treated from July 2014 to July 2018 were retrospectively analyzed. There were 19 males and 23 females, aged from 62 to 80 years old with an average of 72 years. The vertebral fracture segment was T₈-L₅, including 30 lumbar vertebrae and 18 thoracic vertebrae. The course of the disease ranged from 3 d to 2 months. Twenty cases (20 vertebral bodies) were treated by single vertebroplasty (group A) and 22 cases (28 vertebral bodies) were treated by temperature contrast injection procedure(group B). The operative time, amount of bone cement injection, VAS score at 3 days after surgery, leakage rate and refracture rate were compared between two groups.@*RESULTS@#The operative time, amount of bone cement injection and VAS score at 3 days after surgery in group B were (40.05±7.78) min, (3.93±0.19) ml, (3.55±0.74) points, respectively, and in group A were(38.90±6.81) min, (4.03±0.24) ml, (4.05±1.00) points, there was no significant difference between two groups(>0.05). The leakage rate in group B was lower than that in group A (9.1% vs 40.0%, 0.05).@*CONCLUSIONS@#Temperature contrast injection procedure is an effective method to reduce the bone cement leakage in vertebroplasty.

Effects of different interventional modalities on vascular endothelial dysfunction of obese rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the effect of diet-control only, diet-control with swimming training or with polysaccharide sulfate (PSS), a kind of blood lipid-lowering drug on the serum lipid level and vascular endothelial function in obese rats fed by fat-rich-diet.</p><p><b>METHODS</b>Forty Wistar rats were randomly divided into the following 5 groups: group F (n = 8), group N (n = 8), group A (n = 8), group B (n = 8) and group C (n = 8), where the rats were given fat-rich-diet, basic-diet, 12 weeks of diet-control after 8 weeks of fat-rich-diet, 12 weeks of diet-control with swimming training after 8 weeks of fat-rich-diet and 12 weeks of diet-control with PSS after 8 weeks of fat-rich-diet, respectively. All rats were sacrificed after 12 weeks of intervention. Then the levels of Lee index, serum total cholesterol (TC), triglyceride (TG), plasma endothelin (ET), nitric oxide (NO) and von Willebrand Factor (vWF) were measured. The protein expression of intercellular adhesion molecule-1 (ICAM-1) in artery endothelium was evaluated by immunohistochemistry (IHC) and the gene expression of ICAM-1 was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>After the interventions for 12 weeks, the levels of serum TC, TG and ET decreased in group A (P < 0.05). The levels of Lee index, TC, TG, ET, vWF, ICAM-1 protein and ICAM-1 mRNA decreased in group B and C (P < 0.05). Three interventions increased serum NO production (P < 0.05) in group B.</p><p><b>CONCLUSIONS</b>Diet-control could a meliorate the hyperlipidemia and vascular function. Diet-control with swimming training and diet-control with PSS could result in weight loss of rats and meliorate the hyperlipidemia, vascular endothelial function, coagulatory activities and adhesive dysfunction. The effects of diet-control with swimming on vascular endothelial function were prominent.</p>

Significance of Chronic Aplastic Anemia in Children by Determining Soluble Stem Cell Factor and Its Receptor / 实用儿科临床杂志

Objective To investigate the function of soluble stem cell factor receptor(s-kit)and stem cell factor(SCF) in chronic aplastic anemia(CAA).Methods ELISA assay was employed to determine the levels of s-kit and SCF in peripheral blood of CAA patients and umbilical cord blood.Results The levels of s-kit and SCF in peripheral blood of CAA patients are lower than those of normal group and umbilical cord blood group.Conclusions The decreased levels of s-kit and SCF show that s-kit and SCF may play a role in CAA mechanism.The raised levels of s-kit and SCF show that s-kit and SCF may be applied in the field of cord blood transplantation.

Fluvastatin prevents renal injury and expression of lactin-like oxidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery.</p><p><b>METHODS</b>Twenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin [10 mg.kg(-1).d(-1)]. After 16 weeks, serum total cholesterol (TC), low-density lipoprotein (LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using (99m)Tc-DTPA single photon emission computed tomograph ((99m)Tc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry.</p><p><b>RESULTS</b>High cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits.</p><p><b>CONCLUSIONS</b>Fluvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries.</p>

Early intervention on atherosclerosis by fluvastatin and lectin-like oxidized low-density lipoprotein receptor-1 expression in atherosclerotic arteries in immature rabbits / 中华儿科杂志

<p><b>OBJECTIVE</b>The present study was designed to investigate the preventive and therapeutic effect of 3-hydroxy-3-methylglutanyl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on the development of atherosclerosis (AS) in immature rabbits and its possible mechanism by detecting the expression level of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the abdominal aorta.</p><p><b>METHODS</b>A model of hypercholesterolemia (HC) was established by high-cholesterol diet and 24 immature rabbits were divided randomly and equally into control group, HC-diet group and fluvastatin group. At the beginning of the study and after 12 weeks, the body height (BH) and body weight (BW) of the rabbits were measured and their body mass index (BMI) was calculated. At the end of 12 weeks, serum total cholesterol (TC) and low-density lipoprotein (LDL) levels were examined. The intima-medial thickness of the abdominal aorta (aIMT) was measured by using non-invasive high-resolution (14 MHz) B-mode ultrasound imaging. Histological changes in abdominal arteries were studied by H&E-staining and histomorphometric analysis. The gene expression of LOX-1 in abdominal aorta was evaluated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and its protein expression was examined by immunohistochemistry.</p><p><b>RESULTS</b>High cholesterol diet induced hypercholesterolemia and early AS in immature rabbits. In HC-diet group serum TC and LDL levels in rabbits elevated. B mode echocardiography showed that aIMT was thickened and pathomorphology indicated that extensive aortic intima (I) and intima and media (I + M) became thickened and the ratio of the area of intima to media (S(I)/S(M)) was increased. Aortic intimal proliferation in HC-diet group was associated with a marked increase in LOX-1 expression (protein and mRNA) in endothelium and neointima of the abdominal aorta. Treatment with fluvastatin at a dosage of 10 mg/(kg.d) deduced serum lipid, attenuated artery intimal proliferation and markedly decreased the enhanced LOX-1 expression level in endothelium and neointima in immature rabbits. There were no significant differences of BH, BW or BMI among the three groups.</p><p><b>CONCLUSIONS</b>These findings suggested that early treatment with fluvastatin not only induced a significant regression of arterial lesions of HC and early AS in immature rabbits, but also had a crucial endothelial protective effect by down-regulating LOX-1 expression level in atherosclerotic arteries in early AS.</p>

Dynamic changes in myocardial matrix metalloproteinase activity in mice with viral myocarditis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Matrix metalloproteinases (MMPs) are the major regulators of collagen degradation involved in the pathogenesis of several diseases of the heart. The purpose of this study was to investigate the dynamic changes in myocardial MMP activity in mice with viral myocarditis (VM), the relationship between MMP activity and both cardiac function and the quantity of myocardial collagen, and the role MMPs playing in the pathological lesions of VM.</p><p><b>METHODS</b>Sixty-five six-week-old male DBA/2 mice were divided into two groups. Mice in the infected group (n = 50) were inoculated intraperitoneally with 0.14 ml of Coxsackievirus B3 (CVB3, Nancy strain). Control mice (n = 15) were inoculated intraperitoneally with 0.14 ml of Eagle's medium. Eight infected mice and three control mice were sacrificed on each of days 3, 7, 10, 21 and 30 after inoculation. MMP activity was measured on an SDS-PAGE substrate gel embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate administered intraperitoneally (0.01 ml/g - 0.015 ml/g). Cardiac systolic function indices, such as peak velocity of the aorta (Vp), flow velocity integral of the aorta (Vi), ejection fraction (EF), and fractional shortening (FS) were determined by echocardiography. Histological cross sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope. The amount of myocardial collagen was measured by means of hydroxyproline quantification.</p><p><b>RESULTS</b>In virus-infected mice, both MMP-2 and MMP-9 activities were significantly higher than in control mice, reaching a peak on day 10 (P < 0.01). On day 10, cardiac systolic function indices (EF, FS, Vp, and Vi) were all significantly lower compared both to other stages following viral inoculation and to the control group (P < 0.05). In the acute stage, the amount of myocardial collagen in mice with VM was not significantly different from normal control mice (P > 0.05). However, the amount of myocardial collagen in infected mice at the recovery stage (on days 21 and 30) was significantly greater than those of the control mice. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores (r = 0.801, 0.821, P < 0.01) and negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi (r = -0.711, -0.755, P < 0.01). However, Vp negatively correlated with myocardial histopathological scores (r = -0.756, P < 0.01).</p><p><b>CONCLUSIONS</b>In mice with VM, the activities of myocardial MMP-2 and MMP-9 increase significantly during the acute stage, and the total quantity of myocardial collagen increases by the time of recovery. These changes are associated with myocardial interstition remodeling and cardiac dysfunction. MMP activity is an important reference marker for myocardial pathological lesions and can be used to evaluate the severity of myocardial interstitial damage and cardiac dysfunction.</p>

Myocardial matrix metalloproteinases activities in mice with viral myocarditis and their relationship with cardiac function and myocardial collagen amount / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of myocardial matrix metalloproteinases (MMPs) activities in mice with viral myocarditis (VM) and their relationships with cardiac function and myocardial collagen amount and to explore the role of MMPs in the pathologic lesion of VM.</p><p><b>METHODS</b>Sixty-five six-week-old male DBA/2 mice were obtained from the Chinese Academy of Medical Sciences. They were divided into two groups randomly. Mice in infected group (n=50) were inoculated intraperitoneally with 0.14 ml of coxsackievirus B3 (CVB3, Nancy strain). Control mice (n=15) were inoculated intraperitoneally with 0.14 ml of Eagle's solution. Eight infected mice were sacrificed on day 3, 7, 10, 21 and 30, respectively and fifteen control mice were killed on day 30 after inoculation. Total protein concentration was determined according to the method of Bradford, while MMPs activities were measured with SDS-PAGE type substrate gels embedded with type I gelatin (zymography). Echocardiographic studies were performed under anesthesia with 3% chloralhydrate intraperitoneally (0.01-0.015 ml/g). Cardiac systolic function indexes, such as peak velocity of aorta (Vp) and flow velocity integral of aorta (Vi) were determined by echocardiography. Histological cross sections of hearts were stained with hematoxylin-eosin and myocardial histopathologic scores were counted under optical microscope. Myocardial collagen amount was measured by determination of hydroxyproline quantification.</p><p><b>RESULTS</b>In virus-infected mice, both MMP-2 and MMP-9 activities were increased significantly compared with those in controls and reached the peak on day 10 (P < 0.01). On day 10, cardiac systolic function indexes (Vp and Vi) were all significantly lower than those at other stages after virus inoculation and in control group (P < 0.05). There was no obvious elevation in myocardial collagen amount in mice with VM at acute stage (P > 0.05). While the myocardial collagen amount in infected group at recovery stage (on day 21 and 30) increased significantly compared with controls. MMP-2 and MMP-9 activities positively correlated with myocardial histopathological scores, respectively (r =0.801, 0.821 P < 0.01), while they negatively correlated with Vp (r = -0.649, -0.683, P < 0.01) and Vi, respectively (r = -0.711, -0.755, P < 0.01). However, Vp and Vi negatively correlated with myocardial histopathological scores (r = -0.756, -0.584, P < 0.01).</p><p><b>CONCLUSIONS</b>In mice with VM, the activities of myocardial MMP-2 and MMP-9 at acute stage increased significantly, then myocardial collagen amount elevated in recovery stage. These changes were associated with myocardial remodeling and cardiac dysfunction. Myocardial MMP activities are important markers of myocardial pathologic lesion. They are of value in the evaluation of the severity of myocardial damage and cardiac dysfunction in mice with VM.</p>