[Expression of Ras-Associated Protein 1 in the Vascular Endothelium of Bone Tissue with Non-Traumatic Osteonecrosis of Femoral Head].

Objective: To investigate the difference in the expression of Ras-associated protein 1 (Rap1) in necrotic and healthy areas of non-traumatic osteonecrosis of femoral head (NONFH) patients. Methods: Femoral head tissue samples from 30 cases of NONFH and 30 cases of traumatic osteonecrosis of the femoral head (TONFH) were collected after hip replacement surgery, respectively. No significant difference of Association Research Circulation Osseous (ARCO) staging was found between the NONFH and the TONFH groups ( Z=-0.769, P=0.442). In the NONFH group, 8 patients were ARCO stage IIIb, 10 were stage IV, and 12 were stage V, while in the TONFH ground, 11 patients were ARCO stage IIIb, 9 were stage IV, and 10 were stage V. There were 19 males and 11 females in the NONFH group, with an average age of 49.6 yr. (26-69 yr.), and 16 males and 14 females in the TONFH group, with an average age of 54.2 yr. (37-68 yr.). There was no significant difference in gender or age between the two groups ( P>0.05). Specimens were collected from different bone areas, including those from the necrotic areas (area A) and the healthy areas (area B) of the NONFH group, and those from the healthy areas (area B') of the TONFH group, i.e., the control group. Western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were used to analyze the different expression of Rap1, vascular endothelial growth factor (VEGF) protein, phosphoinositide 3-kinase (PI3K), and Akt protein and their corresponding mRNA in the three areas of bone tissue. HE staining and immunohistochemisty staining were done in order to observe the morphological changes of each area. Results: Western blot results indicated that there was no statistical difference in the relative expression of Rap1, VEGF, PI3K, and Akt proteins ( P>0.05). The relative expressions of Rap1, VEGF, PI3K, and Akt proteins in the area A were lower than those in the area B and the difference was statistically significant ( P<0.05). qRT-PCR results showed that the relative expressions of Rap1, VEGF, PI3 K and Akt mRNA in area A were lower than those of area B, and a statistical difference was found ( P<0.05). The relative expression of the mRNA of Rap1, VEGF , PI3 K and Akt in area B and area B' were not significantly different ( P>0.05). HE staining and immunohistochemisty staining showed that chondrocytes decreased in the necrotic area (area A) of NONFH, chondrocytes nucleus disappeared, subchondral bone trabeculae were broken, bone trabeculae thickened, and empty bone lacunae appeared. Granulation tissues composed of new capillaries and fibrous cells have proliferated and crawled around the necrotic area. Positive expressions of the Rap1, VEGF, PI3K and Akt proteins in area A were weaker than those of the normal area. In addition, there were positive expressions of Rap1, PI3K and Akt on the trabecular bone of both area A and area B at similar intensity of expression. There were strong positive expressions of Rap1, VEGF, PI3K and Akt on the intima of arterioles and venules, and on the peripheral stromal cell membrane, but the positive expression in area A was significantly lower than that in area B. However, the positive expression positions and intensity of all indicators were similar in area B and area B'. Conclusion: The necrosis in NONFH may be related to vascular endothelial damages caused by the inhibition of the Rap1-PI3K/Akt signaling pathways and the subsequent decline in the protein expression.

A terbium(III)-complex-based on-off fluorescent chemosensor for phosphate anions in aqueous solution and its application in molecular logic gates.

A new Tb(III) complex based on a tripodal carboxylate ligand has been synthesized for the selective fluorescent recognition of phosphate anions, including inorganic phosphates and nucleoside phosphates (e.g., ATP), in Tris buffer solution. The resulting L · Tb complex shows the characteristic emission bands centered at about 495 and 550 nm from the Tb(III)-centered (5)D4 excited state to (7)FJ transitions with J = 6 and 5, where the chelating ligand acts only as an "antenna". Upon the addition of phosphate anions to the aqueous solution of Tb(III) complex, significant "on-off" fluorescence changes were observed, which were attributed to the inhibition of the "antenna" effect between the ligand and Tb(III) after the incorporation of phosphate anions. Furthermore, this unique Tb(III) complex has been successfully utilized to detect phosphate anions with filter papers and hydrogels. Notably, the Tb(III) complex also can be used for the construction of molecular logic gates with TRANSFER and INHIBIT logic functions by using the above fluorescence changes.

Emergency caudate lobectomy for ruptured hepatocellular carcinoma with multiple primary cancers.

We report a case of metachronous multiple primary malignancies involving both rectum and liver with colonic metastasis from hepatocellular carcinoma (HCC) through hematogenous pathway. A 72-year-old woman was admitted to the emergency department with right upper abdominal pain for 4 h. Considering her surgical history of Mile's procedure plus liver resection for rectal cancer with liver metastasis three years ago and the finding of urgent computed tomography scan on admission, the preoperative diagnosis was spontaneous rupture of rectal liver metastasis located in caudate lobe and colonic metastasis from rectal cancer. The patient underwent an emergency isolated caudate lobectomy at a hemorrhagic shock status. Pathology reported a primary HCC in the caudate lobe and colonic metastasis of HCC with tumor embolus in the surrounding vessels of the intestine. No regional lymph node involvement was found. It is hypothesized that HCC may disseminate hematogenously to the ascending colon, thus making it a rare case.

[Enteral versus parenteral nutrition after gastrointestinal surgery: a meta-analysis of randomized controlled trials].

OBJECTIVE: To compare the different prognosis between enteral nutrition (EN) and parenteral nutrition (PN) in patients after gastrointestinal surgery (GIS), and to investigate a reasonable regimen of enteral nutrition (EN) after GIS. METHODS: Randomized controlled trials (RCTs) on EN/PN after GIS from 1970 to 2008 retrieved from the data bank of Pubmed, EMBASE and Cochrane Library were analyzed. Evaluation endpoints were anastomotic dehiscence, infection (catheter sepsis, wound infection, pneumonia, intra-abdominal abscess and urinary tract infection), vomiting and abdominal distention, other complications, length of hospital stay and mortality rate. RESULTS: Twenty-three RCTs including 2784 patients met the entering criteria. Compared with PN, EN was beneficial in the reduction of anastomotic dehiscence (RR = 0.67, 95%CI: 0.50 - 0.91; P = 0.010), infections (RR = 0.72, 95% CI: 0.64 - 0.81; P < 0.001), other complication (RR = 0.82, 95%CI: 0.73 - 0.92; P < 0.001) and duration of hospital stay (weighted mean difference: -3.60; 95%CI: -3.88 - -3.32; P < 0.001). But the risk of vomiting was increased among patients with EN (RR = 1.39, 95%CI: 1.21 - 1.59; P < 0.001), and there was no significant differences in mortalities between the two groups (P = 0.400). CONCLUSIONS: There is no advantage in treating patients 'nil by mouth' after gastrointestinal surgery. It indicated that early commencement of enteral feeding is beneficial.

[Efficacy and safety of adjuvant post-surgical therapy with imatinib in gastrointestinal stromal tumor patients with high risk of recurrence: interim analysis from a multicenter prospective clinical trial].

OBJECTIVE: To evaluate the efficacy and safety of postoperative adjuvant chemotherapy with imatinib in gastrointestinal stromal tumor(GIST) patients who had high risk of recurrence. METHODS: A prospective, open-label, multi-center trial conducted in sixteen teaching hospitals in China was carried out. The criteria of the enrolled patients included age more than 18 years old, CD117 positive GIST, tumor size more than 5 cm, pathological mitosis counts more than 5/50 HPF, and treatment beginning within 4 weeks after complete resection and with imatinib (400 mg, once a day) for at least 12 months. The 1, 3 year recurrence rates, disease free survival, overall survival rate and quality of life were evaluated. RESULTS: From Aug. 16th 2004 to Sep. 13th 2005, there were totally 74 patients screened and 57 patients (34 men, 23 women) enrolled in the imatinib treatment group. The primary tumors were located in the stomach in 50.9%, the small intestine in 38.6% and the colorectum in 10.5% of the cases. All the patients received radical resection. Until the cut-off date of interim analysis, there was no evidence of tumor relapse or metastasis in all patients and no death was reported either. Among the 57 enrolled patients with intention to treat(ITT), twelve patients finished the protocol (per protocol, PP). The disease free survival was (268.3 +/-120.2) d in ITT analysis, and (396.7+/-38.2) d in the PP analysis. The incidence of adverse effect was 44.4% . The score in quality of life showed no statistically significant difference between the baseline visit and the follow-up visits. CONCLUSION: Imatinib is a promising postoperative adjuvant chemotherapy in GISTs patients with high risk of recurrence, and the adverse effects are receivable.

[Effect of 5-fluorouracil in combination with Astragalus membranaceus on amino acid metabolism in mice model of gastric carcinoma].

OBJECTIVE: To study the effect of 5-fluorouracil-FU in combination with astragalus membranaceus(AM) on amino acid metabolism in mice model of gastric carcinoma induced by 3-methylcholanthrene(MC). METHODS: Mice gastric carcinoma models were established by 3-methylcholanthrene induction and randomly divided into different groups, and received 5-FU treatment (group A) 5-FU plus AM (group B), 5-FU plus a high dose of AM(group C), no treatment (group D). Normal mice were used as control (group N). Free amino acid in the tumor specimens were examined. RESULTS: The levels of free Valine, Methionine, Leucine, Arginine and cystine in the tumor specimens in group D were significantly higher than that in group N(P< 0.05). The levels of free serine in group A, B, C, D were significantly higher than that in group N. The levels of free glutamic acid in group A, B were significantly higher than that in group N(P< 0.05). The levels of free proline in group C, D were significantly higher than that in group P, N(P< 0.05). CONCLUSIONS: The increasing levels of free serine and proline in tumor specimens in gastric cancer mice model reveals metabolic disturbance of amino acid. 5-FU plus astragalus membranaceus can decrease the level of free glutamic acid in the mice models, and inhibit tumor growth.

[Clinical value of the sixth edition TNM stages analysing prognosis of colorectal cancer].

OBJECTIVES: To study the clinical value analyzing of colorectal cancer prognosis by the Sixth Edition TNM Stages. METHODS: 5481 cases with colorectal cancer and treated by operational methods, were collected. All the cases were separately staged by the Fifth Edition or Sixth Edition TNM Stages standards. The 5-year survival rates were analyzed by the life table method. RESULTS: The 5-year survival rates of the Fifth Edition TNM Stages of I, II, III and IV were 80.1%, 68.0%, 40.5% and 9.8% respectively. The 5-year survival rates of the Sixth Edition TNM Stages of II(A) and II(B) were 71.6% and 66.4% respectively, and of the stages III(A), III(B) and III(C) were 46.2%, 40.1% and 28.3% respectively. There were statistical differences among the sub-stages II and III, P < 0.05. CONCLUSION: The Sixth edition TNM Stages laid more stress on effect of the local infiltration depths and lymphatic metastasis in the prognosis of colorectal cancer, therefore, the stages were more fine, to analyze prognosis of the colorectal cancer were more precise. It is high clinical value for the individual complex treatment with every sub-stages.

[Diagnosis and surgical treatment of 48 cases of parathyroid adenoma and parathyroid carcinoma].

OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of parathyroid adenoma and carcinoma (PTA and PTC) in our department. METHODS: The clinical and pathological data of 48 cases admitted in our department from Jan 1995 to Dec 2005 were reviewed. Among the 48 cases, 46 cases were of parathyroid adenoma and 2 cases of parathyroid carcinoma. The average clinical history of the 48 cases was 3.65 +/- 2.83 years. The serum calcium and PTH levels were elevated in all the 48 cases. In 31 cases ultrasonographic results were consisted with that of 99mTc-MIBI scintigraphy. Unilateral neck exploration was performed in 18 cases and no case with post-operative tumor remnants was found. In other 13 cases bilateral exploration was performed but no one case was found to be tumor positive in the opposite side of the glands. Tumors resection was performed in all the 48 cases, among which in the 2 cases with PTC, ipsilateral thyroid lobe excision and modified neck dissection were also performed. RESULTS: Clinical symptoms of all the patients were relieved after operation. No recurrent case was found during the follow-up periods (from 1 month to 10 years). The average level of serum calcium and PTH declined significantly after operation. The post-operational serum calcium and PTH levels at 3 days after operation were even lower than normal. Transient post-operational hypocalcemia was found in almost all the patients. The serum calcium and PTH levels in all patients recovered to normal level within a periods from 1 week to 3 months after operation. The sensitivity and positive prediction value of localization methods were 97.0% and 94.1% of ultrasonography, respectively, and 100% and 97.3% of 99mTc-MIBI scintigraphy, respectively. CONCLUSION: Patients with chronic bone diseases, repeatedly recurrent nephrolithiasis, peptic ulcer disease or pancreatitis should be regarded as suspicious cases of PTA and PTC, and serum calcium assay should be performed as a routine screening procedure. Serum calcium and PTH assays are both reliable methods for the diagnosis of PTA and PTC. A combination of ultrasonography and 99mTc-MIBI scintigraphy is sufficient for locating adenomas. Accompanied by intraoperative pathological examination, unilateral neck exploration is an acceptable approach for patients with definitely preoperative confirmed adenoma localization.

[A study on correlation of hepatic metastasis of colorectal cancer to vascular endothelial growth factor, angiopoietin-2, and fibronectin].

OBJECTIVE: To study the correlation of hepatic metastasis of colorectal cancer to vascular endothelial growth factor (VEGF), angiopoietin- 2 and fibronectin (FN). METHODS: The transcription and expression of VEGF, angiopoietin- 2 and FN were detected by semiquantitative reverse transcription- polymerase chain reaction (SQRT- PCR) and immunohistochemical staining in the specimens from sixty patients with colorectal cancer. RESULTS: The mRNA transcription and expression levels of VEGF, angiopoietin- 2 and FN in colorectal cancer tissues were obviously higher than those in paratumor normal tissues P< 0.05. The transcription and expression levels of VEGF were correlated with tumor invasion P< 0.05,Dukes' stage P< 0.05,and lymph node and/or hepatic metastasis P< 0.05. Angiopoietin expression and transcription levels were correlated with tumor differentiation. The expression of FN in extra cellular matrix (ECM) was significantly higher (P< 0.05),whereas ECM in basement membrane was significantly lower in cancer tissues than that in paratumor normal tissues (P< 0.05),which both were correlated with tumor invasion P< 0.05,Dukes' stage P< 0.05,and lymph node metastasis P< 0.05. Absence of FN protein in basement membrane was also correlated with hepatic metastasis. CONCLUSION: Colorectal cancer cells can secrete VEGF and contribute to metastasis and proliferation of tumor by stimulating the growth of tumor vessel. Both of VEGF and angiopoietin- 2 contribute to angiogenesis and the decrease of FN in basement membrane of cancer tissue is an important primary factor of hepatic metastasis.

[Correlation between the activation of AP-1 signal transduction pathway and metastasis of colorectal carcinoma].

OBJECTIVE: To investigate the binding activity of activator protein-1 (AP-1) with DNA probe in the colorectal carcinoma (CRC) tissues and surrounding tissues and explore the correlation between the activation of AP-1 signal transduction pathway and metastasis of CRC. METHODS: The AP-1 DNA binding activities were investigated by electrophoretic mobility shift assay (EMSA) in CRC specimens (T), surrounding tissues including 2 cm (P(2)), 5 cm(P(5)) far away from primary tumor margin and distal resection margin of the specimens (N). The mRNA expression level of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) were measured by quantitive reverse transcription polymerase chain reaction (Q- RT-PCR). RESULTS: The AP-1 DNA binding activity in T was significantly higher than those in P(2), P(5) and N (P< 0.05) tissues. There were significantly positive correlations between AP-1 DNA binding activity in tumor and invasive degree, lymphatic metastasis respectively (P< 0.01), but no correlation with histological classification and differentiation (P> 0.05). The transcription levels of VEGF and MMP-9 in CRC were significantly higher than those in P(5) and N (P< 0.01, P< 0.05) tissues. The transcription levels of VEGF and MMP-9 were significantly correlated with increasing AP-1 DNA binding activity (P< 0.01). CONCLUSIONS: AP-1 is significantly correlated to the invasion and metastasis in CRC. The activation of AP-1 signal transduction pathway might be involved in the angiogenesis and of degradation extracellular matrix during tumor metastasis.