Vascular endothelial growth factor (VEGF) has been found to be the most powerful angiogenic factor. Studies have shown that cerebral ischemia and hypoxia stimulate the expressions of VEGF and its receptors in the brain, while exogenous VEGF promotes the formation of new blood vessels in the ischemic brain penumbra, and reduce the volume of cerebral infarction. The effect of VEGF on cerebral ischemia was previously explained the mechanism that VEGF had a specific mitogenetic roles in cerebral endothelial cells and thus promoted neovascularization; however recent evidence has shown that VEGF also has direct effects on neural and glial cells. Its multiple protection roles on central nervous system involve vascularization, neurogenesis, direct neurotrophic and neuroprotective effect, as well as antiapoptosis effect, especially when brain ischemia occurs. Further elucidation of these mechanisms on central nervous system may serve as a key procedure in understanding the main aspects of neural repair and neural protection, and develop effective therapeutic measures for intervention in stroke.
Animals ; Brain Ischemia ; drug therapy ; physiopathology ; Dose-Response Relationship, Drug ; Neovascularization, Physiologic ; drug effects ; Nerve Regeneration ; drug effects ; Neuroprotective Agents ; pharmacology ; Vascular Endothelial Growth Factor A ; administration & dosage ; pharmacology

OBJECTIVETo investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype.

METHODSClinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated.

RESULTSPHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000).

CONCLUSIONSMissense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH.

Adolescent ; Child ; Child, Preschool ; Familial Hypophosphatemic Rickets ; genetics ; Female ; Humans ; Infant ; Male ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Retrospective Studies

Female ; Hepatitis C, Chronic ; complications ; Humans ; Hypopituitarism ; complications ; Middle Aged

AIMTo study the effects of 9-cis-retinoic acid (9-cis-RA) on cell cycle and expression of cyclin D1 and cdk4 in lung cancer cells.

METHODS9-cis-RA (1 x 10(-6) mol.L-1) was used to treat lung cancer cells for 24 h; Flow cytometry (FCM) was used to detect the percent of G0/G1 phase and S phase cells of three groups including blank control, DMSO control and 9-cis-RA groups; RT-PCR was used to analyze the expression changes of cyclin D1 and cdk4 before and after treatment with 9-cis-RA in lung cancer cells.

RESULTSThe percent of G0/G1 phase cells of 9-cis-RA groups was significantly higher than that of the control groups (P < 0.01 or P < 0.05) and the percent of S phase cells of 9-cis-RA groups was lower than that of the control groups (P < 0.01 or P < 0.05); the expression of cyclin D1 of PG, SPC-A1 and L78 cells was decreased (P < 0.01) and the expression of cdk4 of PG, A549 and L78 cells was also decreased (P < 0.01) after treatment with 9-cis-RA.

CONCLUSIONMost of the proliferation and the expression of cyclin D1 and cdk4 of PG, A549, SPC-A1 and L78 were inhibited by 9-cis-RA.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents ; pharmacology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Division ; drug effects ; Cell Line, Tumor ; Cyclin D1 ; biosynthesis ; Cyclin-Dependent Kinase 4 ; Cyclin-Dependent Kinases ; biosynthesis ; G1 Phase ; drug effects ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins ; Resting Phase, Cell Cycle ; drug effects ; S Phase ; drug effects ; Tretinoin ; pharmacology

Female ; Humans ; Liver Failure, Acute ; blood ; Liver Neoplasms ; blood ; Liver Transplantation ; Male ; Thrombelastography ; Whole Blood Coagulation Time

Objective: To determine the molecular weight and p urity of porcine platelet-derived growth factor (pPDGF) and to investigate its effect on DNA synthesis of human umbilical vein endothelial cells. Metho ds: In the present experiment, the high performance liquid chromatograph y was used and the molecular weight and purity of pPDGF were studied. Human umbi lical vein endothelial cells was cultured and effects of pPDGF on DNA synthesis of endothelial cells was observed by 3H-TdR incorporation in vitro. Results: The findings of high performance liquid chromatography showed that the molecular weight of pPDGF was 29 120 and the purity was 89.46%, a nd pPDGF significantly promoted DNA synthesis of quiescent endothelial cells wit h a maximal response at a concentration of 40 ng/ml at 48 h. Conclusion: The molecular weight of pPDGF is 29 120, and it can promote DNA synthes is of cultured human umbilical vein endothelial cells.

Purpose To examine the expression of Fascin-1 and β-catenin protein and K-ras gene mutation in colorectal adenocarcinoma, and to explore their role in progression of colorectal neoplasm and their relevance. Methods Fascin-1 and β-catenin were analyzed by use of immunohistochemistry En Vision two-step. K-ras gene mutation was detected by ARMS method.Relationship between overexpression of Fascin-1, the nuclear expression of β-catenin, and the mutations of K-ras gene and clinicopathologic parameters was analyzed, the correlation between them was also analyzed. Results In 112 colorectal adenocarcinoma samples, the overexpression rate of Fascin-1 protein was 27.7％ (31/112), significantly higher than non-neoplastic mucosa (P < 0.01). The high nuclear expression rate of β-catenin was 29.5％ (33/112) in adenocarcinoma and non-neoplastic mucosa respectively with a significant difference between two groups (P < 0.01). High expression rate of Fascin-1 protein and β-catenin were correlated significantly with lymph node metastasis (P = 0.022, P = 0.027), and TNM staging (P =0.042, P = 0.019) in colorectal adenocarcinoma. The overexpression of Fascin-1 protein was correlated with tumor location (P = 0.004). The mutation rate of K-ras gene was 34.8％ (39/112), which showed no correlation with age, gender, tumor size, grade of differentiation, lymph node metastasis and TNM staging (P> 0.05). There was a correlation between the overexpressison of Fascin-1 protein, the nuclear expression of β-catenin and the mutation of K-ras gene (rs= 0.252, rs= 0.258, P < 0.05). The overexpression of Fascin-1 protein positively correlated with the nuclear expression of β-catenin (rs= 0.213, P < 0.05). Conclusion Fascin-1 protein and β-catenin protein are involved in invasion and metastasis of colorectal cancer and are associated with K-ras gene mutation. K-ras may promote the overexpression of Fascin-1 by virtue of nuclear expression ofβ-catenin, which provided a new research direction on the treatment of K-ras gene mutated colorectal adenocarcinoma.

OBJECTIVETo explore the association between the progression of gastric cancer and the aberrant methylation of CDH1 gene in preoperative abdominal lavage fluid.

METHODSReal-time methylation-specific polymerase chain reaction(qMSP) was used to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands from preoperative abdominal lavage fluid in 92 patients with gastric cancer. The associations between methylation of CDH1 genes and clinicopathologic features and prognosis were investigated.

RESULTSAmong the 92 patients with gastric cancer, aberrant methylation of CDH1 gene was detected in 45(48.9%) patients, including total aberrant methylation in 12(13.0%) cases and partly aberrant methylation in 33(35.9%) cases. Significant associations were found between CDH1 methylation status and tumor size, growth pattern, differentiation, lymphovascular invasion, infiltration depth, lymph node metastasis, distant metastasis, and clinical staging(all P<0.05). However, there were no significant associations between CDH1 methylation status with gender, age, tumor location, or Helicobacter pylori infection(all P>0.05). The median progression-free survival was 20 months for CDH1 methylation group and 38 months for non-methylated group, and the difference was statistically significant(P<0.01). Cox model analysis revealed that CDH1 methylation status in preoperative peritoneal lavage fluid was an independent factor associated with postoperative survival in patients with gastric cancer(P=0.000, RR=332.88, 95%CI:21.71-5105.07).

CONCLUSIONSThe aberrant methylation of 5'-CpG of CDH1 gene promoter is common in gastric cancer. The examination of CDH1 methylation status of abdominal lavage should be considered in the progression of gastric cancer.

Adult ; Aged ; Cadherins ; genetics ; CpG Islands ; genetics ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Promoter Regions, Genetic ; Stomach Neoplasms ; genetics ; pathology

OBJECTIVEHemolytic uremic syndrome (HUS) is a common primary disease that can cause acute renal failure in childhood. Renal disease is the most important long-term complication in patients who survived the acute stage of HUS. Use of angiotensin-converting enzyme inhibitors (ACEI) and a restricted protein intake may be beneficial to the patients. However, it is not established whether such patients should be treated with steroids and immunosuppressors. The present study aimed to probe into the benefit of using steroid and immunosuppressor in patients after acute stage of HUS.

METHODSThe subjects included 17 patients (aged 9 months to 15 years, 12 males, 5 females) with HUS. Thirteen patients recovered from the acute stage of HUS, and underwent continuative treatment and follow-up. All the patients were treated with ACEI and early restriction of protein intake. Additionally, 2 children manifested as glomerulonephritis, one was treated with triperygium glycosides. Other 11 children who manifested as nephrotic syndrome were treated with prednisone, among them 5 children had no response or had incomplete response to prednisone, for these children short-term high dose cyclophosphamide or methylprednisolone pulse treatment were added; in 3 of the children short-term high dose methylprednisolone treatment was applied additionally for membranoproliferative glomerulonephritis and/or focal segmental glomerulosclerosis and crescentic glomerulonephritis.

RESULTSAfter follow-up for 2 months to 8 years, 4 patients with milder disease recovered, their blood pressure, renal function and urinalysis became normal, but 1 patient had recurrence. Among 9 patients with severe disease, 6 maintained normal blood pressure, recovered renal function and urinalysis, the other 3 patients failed to comply with treatment protocol and died during the 3rd, 9th and 13th month. The remainder (4 cases) gave up therapy and died on the 27th to 48th days of the course.

CONCLUSIONThe treatment applied in this study could improve the prognosis of patients after acute phase of HUS evidently by using the steroid and immuno suppressor according to clinical classification and pathological findings. It is recommended that triperygium glycosides is beneficial to children with glomerulonephritis, proteinuria and hematuria after acute stage of HUS. Adjustment of therapeutic schedule based on pathological findings after renal biopsy is helpful. To the patients with progressive renal failure who have no response to the steroid and immunosuppressors, steroid and immunosuppressor should be discontinued and dialysis treatment should be applied. Protocol compliance is also an important factor.

Acute Disease ; Adolescent ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Child ; Child, Preschool ; Combined Modality Therapy ; Diet, Protein-Restricted ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Hemolytic-Uremic Syndrome ; diet therapy ; drug therapy ; physiopathology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Prognosis ; Steroids ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the effects of the ventralateral approach in treating severe Pilon fracture.

METHODSFrom February 2002 to March 2008, 63 patients with Ruedi II-III Pilon fractures were treated with the ventralateral approach, including 36 males and 27 females with an average age of 37 years ranging from 19 to 71 years. The mean time from injury to operation was 8 days (ranged for 2 h-19 d). According to the Ruedi classification system, type II was 32 cases (6 cases of them combined with soft tissue lesion, 4 with open fracture) and type III was 31 cases (9 cases of them combined with soft tissue lesion, 8 with open fracture). The clinical effects were evaluated according to Helfet criteria and the complications were observed including condition of wound healing, infection, bone union, deformity union, motion of the ankle, the degree of the pain and so on.

RESULTSThe first intention achieved in 59 cases, the delayed healing in 4 cases. Stiffness of the ankle was found in 5 cases because of bone disunion. All patients were followed up from 8 to 31 months with an average of 15.3 months. The ranging in bone healing time was from 8 to14 weeks with an average of 10 weeks. According to the Helfet criteria, 28 cases obtained excellent results, 30 good, 5 poor.

CONCLUSIONThe operative treatment of Ruedi I-III Pilon fractures with the ventralateral approach can obtain satisfactory results and avoid complications effectively.

Adult ; Aged ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Tibial Fractures ; surgery