ABSTRACT
Nourishing kidney-yin (NKY) granules and warming kidney-yang (WKY) granules represent one of the prescriptions that prescribed in treating primary osteoporosis (POP) in light of tonifying kidney and nourishing essence principle as well as the theory of "treating both the disease and traditional Chinese medicine (TCM) syndrome".Both granules were created through the systematic analysis of clinic prescriptions by Professor Shi Qi.Consequently clinical investigations have well established that NKY granules significant improved bone mineral density (BMD) as well as relieved the kidney-yin deficiency syndromes in POP patients.Meanwhile,WKY granules relieve kidney-yang deficiency syndrome and the quality of life (QOL).What is more,pharmacological study established the application of common cnidium fruit,and fructus ligustri lucidi alleviated bone loss in OVX-induced mice.In addition,investigation with effective components identified that both NKY and WKY granules play systematic pharmacological effects on bone remodeling by regulating the expression of BMP/Smad,Wnt/β-catenin,RANKL/RANK/OPG axis,and Notch.The drug discovery was performed by the lead of traditional Chinese medicine (TCM) theory.It is one successful transformation investigation based on pharmacological effects,clinical intervention,animal model,cell culture and molecular investigation.
ABSTRACT
BACKGROUND:Osteoporosis caused by chemotherapy has become one of the serious side effects that impact the skeletal system. Icarin shows a strong anti-osteoporosis activity, which can have protective effect on osteoporosis induced by chemotherapy. OBJECTIVE: To study the protective effect and mechanism of icarin against cyclophosphamide-induced obstacle of mouse bone marrow mesenchymal stem cels differentiating into osteoblasts. METHODS:MTT assay and alkaline phosphatase (ALP) staining were used to determine the optimal protective concentration of icarin against cyclophosphamide-induced obstacle of mouse bone marrow mesenchymal stem cels differentiating into osteoblasts. mRNA expressions of osteoblast-specific transcription factors, OC, ALP, Runx2, and Wnt/β-catenin signaling pathway target genes, β-catenin, C-Myc, cyclin D1, were determined using RT-PCR method at different time after intervention with the optimal concentration of icarin. Expressions of Runx2, β-catenin, c-Myc, cyclin D1 regulated by the optimal concentration of icarin were detected using western blot assay at the protein level. RESULTS AND CONCLUSION:Cel viability and ALP activity decreased significantly in the cyclophosphamide group compared with the control group, but there was no significant difference in cel viability between icarin group and cyclophosphamide group. Icarin at 100 μmol/L showed the best protective effect against cyclophosphamide-induced obstacle of osteogenic differentiation of bone marrow mesenhymal stem cels. Compared with the control group, cyclophosphamide chemotherapy reduced the expressions of ALP, OC, Runx2 at mRNA level and Runx2 at protein level, weakened the expressions ofβ-catenin, cyclin D1 at mRNA level and active β-catenin, Cyclin D1, c-myc at protein level, and increased the expression of DKK1. Compared with the cyclophosphamide group, 100 μmol/L icarin increased the expression of osteoblast-specific transcription factors and Wnt/β-catenin signaling pathway genes at mRNA and protein levels, and reduced the expression of DKK1 protein. These results show that cyclophosphamide can lead to osteogenic differentiation disorder of mouse bone marrow mesenchymal stem cels, and in contrast, icarin shows a protective effect and its optimal intervention concentration is 100 μmol/L. Additionaly, the protective roleof icarin is probably related to activation of Wnt/β-catenin signal pathway.
ABSTRACT
This study aimed to evaluate the expressions and clinical significance of bone Gla-protein [BGP], bone alkaline phosphatase [B-ALP] and C-terminal telopeptide of type I collagen [CTX] in patients with osteoporosis [OP], and to provide evidence for developing individualized treatment plans. Seventy-two OP patients in our hospital were selected as an OP group, and another 72 healthy subjects were used as a control group. Their BGP, B-ALP and CTX levels as well as bone mineral density [BMD] values were measured. The correlations between BGP, B-ALP and CTX levels and BMD values were determined. The BGP level of the OP group [[5.61 +/- 5.52] ng/ml] was significantly higher than that of the control group [P<0.05], but the levels of B-ALP and CTX did not differ significantly [P>0.05]. The BMD values of femoral neck and Ward's triangle in the OP group were negatively correlated with the B-ALP levels [P<0.05]. For women OP patients, the BMD values of femoral neck and Ward's triangle were also negatively correlated with the B-ALP levels [P<0.05]. The BMD of femoral neck in the control group was negatively correlated with the CTX level [P<0.05]. Determining BGP, B-ALP and CTX levels can evaluate the bone metabolism degree, which provides evidence for clinical typing of OP and developing treatment strategies
ABSTRACT
Objective To investigate the clinical significance of expression of P53,Ki67 in proliferation,invasion and metastasis of cancer cells of patients with esophageal carcinoma.Methods Eighty-six patients with esophageal carcinoma were selected as tumor group from January 2006 to May 2008.And another 86 patients without tumor were as control group.ABC-immunohistochemistry was used to detect the expression of P53 and Ki67 in 172 cases of patients with esophageal carcinoma.Results The expression of P53 in patients with esophageal carcinoma was different from that in control subjects (x2 =4.045,P ＜ 0.05),and the P53 expression rate in two group were 66.3％ (57/86) and 51.1％ (44/86) respectively.The rate of P53 expression reaching to + + in two groups was also significant (x2 =8.592,P ＜ 0.01).Ki67 expression in patients with esophageal carcinoma was higher than that of control patients (76.7％ (66/86) vs.60.5％ (82/86),x2 =5.291,P ＜ 0.05).Additionally,there was significant difference regarding of Ki6 expression reaching to + + positive(x2 =13.661,P ＜ 0.01).Moreover,the expression of P53 and Ki67 were found to be a positively correlation(r =0.400,P =0.00).The expression of P53 and Ki67 were related with invasion and differentiation of cancer cells (x2 =3.945,5.794 respectively,all P ＜ 0.05) and lymph node metastasis (x2 =5.570,4.354 respectively,all P ＜ 0.05).Conclusion Over-expression of P53 and Ki67 were involved in the process of proliferation,invasion and metastasis of cancer cells in esophageal carcinoma,which coherently impacted the occurrence and development of esophageal cancer.The combined detection of P53 and Ki67 seems to help the early diagnosis of esophageal cancer and evaluation of the degree of malignancy,invasion,metastasis and prognosis.Over-expression of P53,Ki67 might be served as a reference marker in screening for chemotherapy for esophageal cancer.
ABSTRACT
BACKGROUND: Previously, more researches are about the pathological changesinskeleton, nerveandmuscularofcongenitalclubfoot(CCF). Researches are exploring the changes in the surrounding soft tissues of the deformed feet.OBJECTIVE: To investigate the relationships between the pathogeny,pathology and pathogenesis of CCF and extracellular matrix (ECM).DESIGN: A completely randomized controlled trial.SETTING: Institute of Orthopeadics of the Fourth Military Medical University.PARTICIPANTS: The study was conducted in the Institute of Orthopeadics of the Fourth Military Medical University from November 1997 to August 2003. The deep fascia of study group was obtained from 15 CCF patients who received operative corrections including 11 males and 4 females with an average of 9 months. Five infant corpses who died from non-neural muscular diseases and non-collagen diseases aged between 4 and 21 months with an average age of 11 months were selected in the control group.METHODS: Immunohistochemical investigation was used for the assay of both study and control group. Slices were quantitatively analyzed by Letica Q,570c color image analysis and management system.MAIN OUTCOME MEASURES: Positive expressions of collagen Ⅰ, Ⅱ and Ⅲ, and the relative contents in the deep fascia of both groups.RESULTS: The grey values for relative contents of collagen Ⅰ, Ⅱ and Ⅲ in the interior foot were 116. 43 ± 11. 80, 132. 91 ± 8. 88, and 184. 40 ± 11.82respectively in the study group, and 169.28 ± 8.17, 176. 33 ± 9.47, and 194. 38 ±5.87 in the control group. The contents of collagen Ⅰ, Ⅱ and Ⅲincreased in the contractured tissues of CCF group with the most significant increase in collagen Ⅰ, followed by collagen Ⅲ and the increase of collagen Ⅱwas least. Additionally, collagen Ⅰ was negatively correlated with collagen Ⅲ. The positive expression of collagen Ⅱ might be an accompanying phenomenon, which had no correlation with collagen Ⅰ and Ⅲ.CONCLUSION: ECM changes in CCF are accorded with fibrosis in tissues and organs and general fibroelastosis. Therefore, CCF might be caused by the fibrosis of interior foot.
ABSTRACT
BACKGROUND: At present, most researches on simulated weightlessness are confined to its effect on the artery. Therefore, the effect on the vein needs to be further studied.OBJECTIVE: To probe into the effect of simulated weightlessness on the ultrastructure of rabbit femoral vein and the remodeling of femoral vein.DESIGN: A completely randomized and controlled trial based on experimental animals.SETTING: Department of Aerospace and Aviation Medical Science, Fourth Military Medical University of Chinese PLA.MATERIALS: The experiment was completed in the Department of Aerospace and Aviation Medical Science, Fourth Military Medical University of Chinese PLA from December 2000 to December 2001. Altogether 24healthy male New Zealand rabbits, weighing 2.0-2.5 kg were obtained.INTERVENTIONS: The model of Head-Down Tilt( -20°) (HDT) simulated weightlessness was established in rabbits. A total of 24 healthy male New Zealand rabbits were randomly divided into control group, 10-day simulated weightlessness group and 21-day simulated weightlessness group, with 8rabbits in each group. The ultrastructure of the rabbit femoral vein was observed under transmission electron microscope.MAIN OUTCOME MEASURES: Changes and degeneration of endothelial cell, mitochondrion, internal elastic membrane, and smooth muscle.RESULTS: Cell organelles in endothelial cell of the femoral vein of HDT rabbits decreased, mitochondrion dissolved and disappeared, vacuolar degeneration in endothelial cell increased and phagolysosome in endothelial cell could be found. Internal elastic membrane became thinner and was broken. The smooth muscle layer became thinner and some smooth muscle cells became degenerated. Cell interstitial substance increased. There was significant difference in changes between 21-day and 10-day simulated weightlessness groups.CONCLUSION: The vascular remodeling of femoral vein occurs with atrophic changes during simulated weightlessness. The longer duration of simulated weightlessness is, the more obviously the structure of femoral vein changes.