2.Association of toll-like receptor 4 signaling pathway with steroid-induced femoral head osteonecrosis in rats.
Lei, TIAN ; Dong-Sheng, ZHOU ; Kun-Zheng, WANG ; Wei, ZHANG ; Zhi-Bin, SHI ; Li-Hong, FAN ; Shui, SUN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(5):679-86
Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacrificed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-κB p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentration of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in control rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased significantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.
3.Early diagnosis of prostate cancer by combined use of Trp-p8 expression and PSA density of the transition zone.
Xin-sheng ZHANG ; Ying ZHANG ; Pan-xing WU ; Shui-jiao LIU ; Jian-yu ZHOU ; Shi-xiong LIU
National Journal of Andrology 2015;21(8):724-728
OBJECTIVETo study the expression of the Trp-p8 protein in the prostate tissue of the PSA "grey zone" with different PSA density of the transition zone (PSADTZ) and explore the value of determining Trp-p8 expression and PSADTZ in the early diagnosis of prostate cancer (PCa).
METHODSThis study involved 30 cases of benign prostatic hyperplasia (BPH) and another 30 cases of PCa with different PSADTZ values. Using a data imaging and analysis system, we determined the expression levels of Trp-p8 in BPH and PCa tissues and analyzed their correlation with PSADTZ.
RESULTSThe expression of Trp-p8 was weak or negative in the BPH but strong in the PCa tissue and even stronger in the PCa tissue with high PSADTZ (F = 34. 05, P < 0.05).
CONCLUSIONThe Trp-p8 protein is expressed differently in BPH and PCa tissues of the PSA " grey zone" and its expression is positively correlated with PSADTZ. Determination of the Trp-p8 expression and PSADTZ contributes to the early diagnosis of prostate cancer.
Biomarkers, Tumor ; metabolism ; Early Detection of Cancer ; methods ; Humans ; Male ; Prostate ; metabolism ; Prostate-Specific Antigen ; metabolism ; Prostatic Hyperplasia ; diagnosis ; metabolism ; Prostatic Neoplasms ; diagnosis ; metabolism ; TRPM Cation Channels ; metabolism
4.The effect of urokinase on hepatic fibrogenesis in rats.
Xi-run WU ; Qi WANG ; Ling WANG ; Shui-sheng SHI ; Wen-dong GUO
Chinese Journal of Hepatology 2009;17(12):910-914
OBJECTIVETo investigate the effect of urokinase on hepatic fibrogenesis in rats.
METHODSHepatic fibrosis was induced in rats by complex pathogenic factors including subcutaneous injections of carbon tetrachloride, alcohol and cholesterol feeding. Animals were randomly divided into 3 groups: normal control group, hepatic fibrosis group (complex pathogenic factors for 6 weeks), UK prevention group (complex pathogenic factors+UK for 6 weeks). The animals were sacrificed at the end of week 6. The expression of alpha-SMA, uPA, PAI-1, TGFb1, TIMP-1, collagen type I and type III proteins in hepatic fibrosis tissue was detected by immunohistochemistry, the expression of PAI-1 and TGFb1 mRNA in the hepatic fibrosis tissue was quantified by real time RT-PCR. The serum levels of hyaluronicacid (HA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (TBil) and the content of liver hydroxyproline (Hyp) were detected using ELISA kits.
RESULTSThe serum ALT, AST, TBil, HA and the content of liver Hyp were (46.66+/-6.30) U/L, (126.26+/-31.65) U/L, (31.11+/-4.20) micromol/L, (109.70+/-18.81) microg/L and (0.98+/-0.09) mg/(g liver), respectively, in UK prevention group, which were significantly lower than those [(101.57+/-11.97) U/L, (205.89+/-56.26) U/L, (67.75+/-2.75) micromol/L, (184.43+/-32.36) microg/L and (1.65+/-0.16) mg/(g liver), respectively] in hepatic fibrosis group (q = 3.3801-20.0061, P < 0.01). The levels of a-SMA, collagen type I, type III, TIMP-1, PAI-1, TGFb1 proteins were (299.27+/-37.36), (210.05+/-27.17), (192.94+/-24.48), (213.70+/-32.21), (204.25+/-17.92), (205.97+/-23.81), respectively, in UK prevention group, which were significantly lower than those [(418.83+/-30.21), (323.77+/-21.53), (302.37+/-31.43), (376.63+/-25.19), (313.53+/-26.67) and (327.42+/-36.75), respectively] in hepatic fibrosis group. The level of uPA protein was increased, and the expression of PAI-1, TGFb1 mRNA in hepatic fibrosis tissue was decreased in UK prevention group.
CONCLUSIONIn the early stage of hepatic fibrogenesis, urokinase can attenuate the progression of rat hepatic fibrosis via upregulation of uPA, downregulation of TGFb1, and inhibition of HSC activation.
Actins ; metabolism ; Animals ; Disease Models, Animal ; Hydroxyproline ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; pathology ; prevention & control ; Liver Function Tests ; Male ; Plasminogen Activator Inhibitor 1 ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Urokinase-Type Plasminogen Activator ; pharmacology
5.The plasma levels of transforming growth factor beta1 and the protein expressions of alpha-SMA, urokinase plasminogen activator and plasminogen activator inhibitor-1 in liver of patients with different grades of hepatic fibrosis.
Xi-Run WU ; Min-He LV ; Qi WANG ; Shui-Sheng SHI ; Wen-Dong GUO
Chinese Journal of Hepatology 2004;12(7):400-402
OBJECTIVETo measure the plasma levels of transforming growth factor beta1 (TGFbeta1), the protein expression of alpha-SMA in hepatic stellate cells and urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1), and study on the relationships between the plasma levels of TGFbeta1, the protein expression and the serum hyaluronic acid (HA) in patients with different grades of hepatic fibrosis.
METHODSThirty seven cases with hepatic fibrosis of different grades were classified according to HE and VG staining categories from 0 to 4, in which there were 8 cases in grade 1, 9 cases in grade 2, 7 cases in grade 3, 13 cases in grade 4. The plasma levels of TGFbeta1 and the serum levels of HA were detected by ELISA. The protein expressions of a-SMA, uPA and PAI-1 in fibrotic liver tissue were observed by immunohistochemistry.
RESULTSWith the progression of hepatic fibrosis, the plasma levels of TGFbeta1 and the protein expression of a-SMA, uPA and PAI-1 in fibrotic liver tissue were increased. In grade 3 and 4, the plasma levels of TGFbeta and the protein expression of a-SMA and PAI-1 in fibrotic liver tissue were significantly increased, but the protein expression of uPA in cirrhosis liver tissue did not increased.
CONCLUSIONTGFbeta1, a-SMA, uPA and PAI-1 play an important role in the progression of hepatic fibrosis. Inhibiting the early activation of latent TGFbeta1 or increasing uPA and inhibiting PAI-1 over express may contribute to matrix degradation and retard the progression of hepatic fibrosis.
Actins ; blood ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; blood ; complications ; Humans ; Liver Cirrhosis ; blood ; etiology ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1 ; blood ; Transforming Growth Factor beta ; blood ; Transforming Growth Factor beta1 ; Urokinase-Type Plasminogen Activator ; blood
6.The plasma levels of urokinase plasminogen activator and urokinase plasminogen activator receptor and plasminogen activator inhibitor-1 in patients with different stages of liver cirrhosis following chronic hepatitis B.
Xi-run WU ; Qi WANG ; Shui-sheng SHI ; Ming-he LU ; Wen-dong GUO
Chinese Journal of Hepatology 2004;12(2):82-84
OBJECTIVESTo measure the plasma levels of urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), and study the relationship between the plasma levels of uPA, PAI-1 and the serum albumin (Alb), collagen type IV (CIV), the serum hyaluronic acid (HA), prothrombin time (PT) and prothrombin activity (PTA) in patients with different stages of liver cirrhosis following chronic hepatitis B.
METHODS72 cases with liver cirrhosis of different stages were classified according to child-pugh's categories A, B, C, in which there were 23 cases in child A, 29 cases in child B, and 20 cases in child C. The plasma levels of uPA, uPAR, PAI-1 and the serum levels of HA, CIV were detected by ELISA. The serum PCIII concentration was determined by radioimmunoassay.
RESULTSWith the progression of hepatic fibrosis, the plasma levels of uPA, uPAR and PAI-1 were (1.36+/-0.43) microg/L, (3.03+/-1.48) microg/L and (24.09+/-7.14) microg/L respectively in group A, (1.79+/-0.62) microg/L, (4.80+/-2.22) microg/L and (41.40+/-17.52) microg/L respectively in group B. The highest levels were in child C, whose levels were (1.88+/-0.64) microg/L, (4.82+/-2.02) microg/L and (52.60+/-16.87) microg/L respectively, compared with group A and group B, t value were from 2.81 to 7.38, all of P value were less than 0.01. There was negative correlation between the plasma levels of uPA and the serum PCIII (r=-0.4785, P<0.05) in child A, but, positive correlation between the plasma PAI-1 and the serum HA (r=0.5447, P<0.01) in child C. The value of PAI-1/uPA was significantly decreased in child A, but increased in child B and child C.
CONCLUSIONIn the late of liver cirrhosis, increased PAI-1 together with uPA, uPAR are associated with overall inhibition of matrix degradation. The plasma levels of uPA and PAI-1 were correlation to the progression of liver cirrhosis.
Female ; Hepatitis B, Chronic ; complications ; Humans ; Liver Cirrhosis ; blood ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1 ; blood ; Receptors, Cell Surface ; blood ; Receptors, Urokinase Plasminogen Activator ; Urokinase-Type Plasminogen Activator ; blood
7.Expression of vascular endothelial growth factor C and survivin in gastric carcinoma and their clinical implications.
Yuan-shui SUN ; Zai-yuan YE ; Zhong-sheng ZHAO ; Dun SHI ; Shou-chun ZOU
Chinese Journal of Gastrointestinal Surgery 2006;9(3):264-267
OBJECTIVETo investigate the expression of vascular endothelial growth factor C (VEGF-C) and survivin protein in human gastric carcinoma,and to evaluate their clinical implications.
METHODSThe expressions of VEGF-C and survivin protein in tumor tissues,matched para- tumor tissues from 97 cases with gastric cancer and normal tissues form 20 normal controls,were determined by immunohistochemistry. Their relationships with clinicopathological parameters were analyzed.
RESULTSThe positive rate of VEGF-C and survivin protein in tumor tissues (66.0% and 57.2%) was significantly higher than those in matched para-tumor tissues normal tissues (P< 0.05). There were no significant differences in VEGF-C expression considering tumor size,localization,histological grade,venous invasion,and distant metastasis (P > 0.05), while its expression was correlated with serosal infiltration, lymphatic invasion, lymph node metastasis and TNM stage III-IV (P< 0.05). The survivin expression was significantly related with serosal infiltration,lymphatic invasion, regional lymph node metastasis,distant metastasis, and TNM stage III- IV (P< 0.05), but not with histological grade, localization,venous invasion,and tumor size (P > 0.05). The 1, 3 and 5-year survival rates of the patients with positive VEGF-C or survivin protein were significantly lower than those of the patients with negative VEGF-C or survivin (P< 0.05), respectively. In additional,the expression of VEGF-C was positively correlated with survivin expression in gastric carcinoma (P< 0.01).
CONCLUSIONThe expressions of VEGF-C and/or survivin may be indicators for poor prognosis of gastric carcinoma.
Adult ; Aged ; Carcinoma ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; biosynthesis ; Middle Aged ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms ; metabolism ; pathology ; Vascular Endothelial Growth Factor C ; metabolism
8.Association of toll-like receptor 4 signaling pathway with steroid-induced femoral head osteonecrosis in rats.
Lei TIAN ; Dong-Sheng ZHOU ; Kun-Zheng WANG ; Wei ZHANG ; Zhi-Bin SHI ; Li-Hong FAN ; Shui SUN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(5):679-686
Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacrificed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-κB p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentration of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in control rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased significantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.
Acid Phosphatase
;
metabolism
;
Animals
;
Blotting, Western
;
Chemokine CCL2
;
genetics
;
metabolism
;
Femur Head
;
metabolism
;
pathology
;
Gene Expression
;
Immunohistochemistry
;
Isoenzymes
;
metabolism
;
Male
;
Methylprednisolone
;
Myeloid Differentiation Factor 88
;
genetics
;
metabolism
;
Osteonecrosis
;
chemically induced
;
genetics
;
metabolism
;
Rats, Sprague-Dawley
;
Reverse Transcriptase Polymerase Chain Reaction
;
Signal Transduction
;
TNF Receptor-Associated Factor 6
;
genetics
;
metabolism
;
Tartrate-Resistant Acid Phosphatase
;
Time Factors
;
Toll-Like Receptor 4
;
genetics
;
metabolism
;
Transcription Factor RelA
;
genetics
;
metabolism
9.Primary clinical result of digital template as navigation to supper cervical pedicle instrumentation.
Sheng LU ; Yong-qing XU ; Yuan-zhi ZHANG ; Yan-bing LI ; Ji-hong SHI ; Guo-ping CHEN ; Dong-ping LI ; Quan-shui FAN
Chinese Journal of Surgery 2009;47(5):359-362
OBJECTIVETo observe the primary clinical result of digital template as navigation to the upper cervical pedicle instrumentation.
METHODSCT scan of upper cervical vertebrae was performed. 3-D model of upper cervical vertebrae was reconstructed by software Amira 3.1 and was preserved in STL format. Then 3-D model was run in software UG Imageware 12.0, the best pedicle channel was extracted according to the reverse engineering principle. A virtual navigational template was established according to he lamina anatomic trait, and the best pedicle channel. The virtual vertebrae and navigational template were manufactured using rapid prototyping. The navigational template was sterilized and used intra operative to assist with the placement of pedicle screw. The Accuracy of screw placement was confirmed with postoperative X-ray and CT scanning.
RESULTSThe digital navigational template had been established and used in the 3 cases, the good trajectory of cervical pedicle had been showed by the CT scan of post operation. There were not complications of related pedicle screw insertion.
CONCLUSIONSA novel method of upper cervical pedicle location using Reverse Engineering and rapid prototyping has been developed; the navigational template is found to be highly accuracy and has great expectation.
Adult ; Bone Screws ; Cervical Vertebrae ; diagnostic imaging ; surgery ; Computer Simulation ; Female ; Humans ; Imaging, Three-Dimensional ; Middle Aged ; Models, Anatomic ; Neuronavigation ; Spinal Fusion ; Surgery, Computer-Assisted ; Tomography, X-Ray Computed
10.Trephine arthrodesis of subtalar joints: operative technique and clinical effect.
Hua-shui LIU ; Sheng-jun DUAN ; Shi-dong LIU ; Xin-min XIE ; Tao LUAN ; Lai-feng LI ; Jin-peng BU ; Xue-chun ZHAO
Chinese Journal of Traumatology 2009;12(4):218-222
OBJECTIVETo review the operative technique of trephine arthrodesis of subtalar joints and evaluate its clinical effect.
METHODSFrom June 1998 to October 2006, we performed subtalar arthrodesis on 38 feet of 34 patients for a variety of painful disorders of hindfoot with trephine technique. Clinical and radiologic follow-up evaluations were performed for 45 months on average (range, 21 to 110 months) after arthrodesis.
RESULTSNo severe complications were found in this study except one patient with dropfoot and two with skin necrosis. The average ankle-hindfoot scores of the American Orthopaedic Foot and Ankle Society (AOFAS) was improved from 48.3 preoperatively to 79.2 postoperatively (P<0.05). The pain scores of visual analogue scales (VAS) decreased from 7.2 (range, 3 to 10) preoperatively to 2.6 (range, 1 to 6) postoperatively (P<0.05). Subjectively, the patients experienced improvements in pain, function, cosmesis, and shoewearing. Overall, 30 patients were satisfied and all patients would have this procedure again under similar circumstances. Postoperative radiology showed that complete union was found in 35 feet 6 months after operation, with the successful union rate of 92.1%. There was an increase in arthritic scores for 5 ankles, 4 talonavicular joints, 4 calcaneocuboid joints, and 4 midfoot joints. Nonunion occurred in 3 subtalar joints with anterolateral approach, which required revision arthrodesis.
CONCLUSIONIsolated subtalar arthrodesis with trephine method is an effective procedure for painful malalignment of hindfoot.
Adult ; Aged ; Arthrodesis ; adverse effects ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pain Measurement ; Subtalar Joint ; surgery