OBJECTIVEIn recent years, the survival rate of premature infants is increased, but the incidence of cerebral palsy did not decrease, instead, there was a tendency of increase. The incidence of cerebral palsy of premature infants was 29.13 per thousand in 7 provinces in China in an investigation of over 30,000 children 1 - 6 years of age in 1997, which is 25.16 times higher than that of full term infants. Each year, about 1 million premature infants are born in China, which may include an increase of approximately 29,000 cerebral palsy infants. The rehabilitation expense of cerebral palsy infants is high, older patients cannot be cured; only improved life quality is possible. Therefore, we carried out this research from March 1, 2000 to the end of February 2003 to explore the effects of early intervention in lowering the incidence of cerebral palsy among premature infants.

METHODSA total of 1053 cases of survived premature infants, gestational age under 37 weeks, excluding those with congenital deformity and hereditary metabolic diseases, born or treated in all collaborative units were classified into 2 groups: early intervention group (551 cases) and routine care group (502 cases). Method of classification: all premature infants born within 1 year before beginning of the study and premature infants born after beginning of the study whose parents did not want to receive early intervention were included in the routine care group; all premature infants born after beginning of the study whose family intended to actively participate in early intervention were included in the intervention group. The numbers of infants in the two groups were quite close in each collaborative unit. In the intervention group, the premature infants received early intervention after discharge from hospital, in addition to routine care, once a month before corrected age of 6 months and once every two months after 6 months. The parents were instructed to cultivate the infant's cognition, language, emotion and communication ability, and the infants were given massage, subjected to exercise and received active motor training. All infants with abnormal motor manifestations were given appropriate rehabilitation training. In the routine care group, infants received similar routine care only.

RESULTSIn the 2 groups, no significant differences (P > 0.05) were found in complications of pregnant mothers, average gestational age and birth weight, proportion of small for gestational age (SGA), proportion of single and multiple births, fetal stress, postnatal asphyxia, incidence of neonatal hypoxic inschemic encephalopathy (HIE) and intracranial hemorrhage, Apgar Score and Neonatal Behavioral Neurological Assessment Score at 40 weeks of gestational age. These indicate that the two groups were comparable. At 1 year of age, the incidence of cerebral palsy was 0.91% (5/551) in the intervention group and 3.19% (16/502) in the routine care group (P < 0.01). Of the 5 cases with cerebral palsy in the interventional group, 3 were mild and 2 severe. Of the 16 cases in the routine care group, 7 were moderate and 9 severe.

CONCLUSIONEarly intervention can reduce the incidence of cerebral palsy of premature infants. This conclusion awaits confirmation from studies with larger sample size.

Apgar Score ; Birth Weight ; Cerebral Palsy ; epidemiology ; prevention & control ; China ; epidemiology ; Early Intervention (Education) ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Pregnancy

Antigens, CD20 ; metabolism ; Female ; Follow-Up Studies ; Humans ; Interferon Regulatory Factors ; metabolism ; Leg ; pathology ; Lymphoma, Large B-Cell, Diffuse ; complications ; metabolism ; pathology ; surgery ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Skin Neoplasms ; complications ; metabolism ; pathology ; surgery ; Thrombocytopenia ; complications

Sphingolipids, especially ceramide and S1P, are structural components of biological membranes and bioactive molecules which participate in diverse cellular activities such as cell division, differentiation, gene expression and apoptosis. Emerging evidence demonstrates the role of sphingolipids in hepatocellular death, which contributes to the progression of several liver diseases including ischaemia-reperfusion liver injury, steatohepatitis or hepatocarcinogenesis. Furthermore, some data indicate that the accumulation of some sphingolipids contributes to the hepatic dysfunctions. Hence, understanding of sphingolipid may open up a novel therapeutic avenue to liver diseases. This review focuses on the progress in the sphingolipid metabolic pathway with a focus on hepatic diseases and drugs targeting the sphingolipid pathway.
Apoptosis ; Ceramides ; metabolism ; Fatty Liver ; metabolism ; physiopathology ; Humans ; Liver Diseases ; metabolism ; physiopathology ; Lysophospholipids ; metabolism ; Reperfusion Injury ; metabolism ; physiopathology ; Sphingolipids ; metabolism ; Sphingosine ; analogs & derivatives ; metabolism

OBJECTIVETo study the relationship between collgen (Col) IV, VEGF secreted by the tumor cells and vasculogenic mimicry (VM).

METHODS158 bi-phase differential malignant tumor specimens were alloted and made into tissue microarray. These tissue microarray sections were stained with CD31, periodic acid-Schiff (PAS) and Col IV. Subsequently, distributive trait of Col IV and the difference of VEGF expression were analyzed.

RESULTSThe basement membrane of VM was PAS and Col IV positive. The expression of VEGF in bi-phase differential malignant tumor with VM was less than that in those without VM. The difference of VEGF expression in malignant melanoma and alveolar rhabdomyosarcoma was significant (P < 0.05).

CONCLUSIONCollgen IV and periodic acid-Schiff positive material take part in constructing the basement membrane of vasculogenic mimicry. The difference of the VEGF expression proves that vasculogenic mimicry can sustain the tumor blood supply.

Collagen Type IV ; analysis ; Humans ; Immunohistochemistry ; Neoplasms ; blood supply ; chemistry ; pathology ; Periodic Acid-Schiff Reaction ; Vascular Endothelial Growth Factor A ; analysis

Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.
Animals ; Antiviral Agents ; pharmacology ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Glycyrrhizic Acid ; pharmacology ; Inflammation ; immunology ; Influenza A Virus, H1N1 Subtype ; drug effects ; Interleukin-1beta ; immunology ; Interleukin-6 ; immunology ; Lung ; immunology ; virology ; Mice ; Orthomyxoviridae Infections ; drug therapy ; Pneumonia, Viral ; drug therapy ; Ribavirin ; pharmacology ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVEBone-marrow derived mesenchymal stem cells (BMSC) have the potential to differentiate into endothelial cells. The aim of the study was to investigate the induction process of BMSC by B16 melanoma cells in vitro and to analyze the role of VEGF-a in the process.

METHODSA co-culture system containing BMSC and B16 melanoma cells based on transwell indirect model was established, and the induction process of BMSC by B16 melanoma cells was studied in vitro.

RESULTSBMSC were isolated from the bone marrow of C57 mice. BMSC expressed CD105, CD90, CD73, CD44 and CD166, and acquired expressin of endothelial phenotype markers including VEGFR-1, VEGFR-2 and Factor VIII after co-culture with B16 melanoma cells for 48 hours. The expression level of VEGFR-2 would be double and Factor VIII threefold more by extending the co-culture time to 72 hours. In the co-culture system, B16 melanoma cells also up-regulated the expression of VEGF-a.

CONCLUSIONSVEGF-a plays a significant role in the differentiation of BMSC into cells of endothelial phenotype, therefore, is important to tumor angiogenesis.

Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cell Differentiation ; Cell Line, Tumor ; Coculture Techniques ; Endothelial Cells ; cytology ; metabolism ; Factor VIII ; metabolism ; Male ; Melanoma, Experimental ; metabolism ; pathology ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Mice ; Mice, Inbred C57BL ; Pilot Projects ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo investigate the mutation in mitochondrial DNA displacement-loop (mtDNA D-loop) region in oncocytoma and its relationship with tumorigenesis and tumor development.

METHODSThe mtDNA D-Loop region of 20 thyroid or renal oncocytomas and the adjacent normal tissues were amplified by PCR, and then sequenced. Five human fetal renal tissues were collected as matched controls.

RESULTSAmong the 20 oncocytomas, 21 mutations which focused on hypervariable region I (HVI) were found in 7 tumor tissues and 1 normal tissue with the mutation rates of 35% and 5%, respectively. At the same time, 191 polymorphisms were found in the 20 cases.

CONCLUSIONmtDNA D-loop region, especially HV I, is the mutational hotspot of oncocytomas, which may be closely related with mtDNA duplicating rate and the function of mitochondria.

Adenoma, Oxyphilic ; genetics ; Base Sequence ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Kidney Neoplasms ; genetics ; Male ; Middle Aged ; Mitochondria ; genetics ; Mutation ; Polymorphism, Genetic ; Thyroid Neoplasms ; genetics

OBJECTIVETo investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.

METHODSTo establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.

RESULTSTumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.

CONCLUSIONThe combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.

Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Doxycycline ; pharmacology ; Drug Combinations ; Drug Synergism ; Endostatins ; pharmacology ; Female ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Melanoma, Experimental ; blood supply ; enzymology ; pathology ; Mice ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Microvessels ; pathology ; Neoplasm Transplantation ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Tumor Burden ; drug effects

OBJECTIVETo study the expression of matrix metalloproteinases (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP)-2 in tumor cells of synovial sarcoma and its clinical significance.

METHODSExpression of MMP-2 and TIMP-2 in tumor cells of 72 cases of synovial sarcoma was studied by immunohistochemistry. The profile was correlated with clinicopathologic parameters, microvessel density (MVD) (analyzed by CD31 immunostaining) and survival rate.

RESULTS(1) There was a statistically significant negative correlation between expression of MMP-2 and TIMP-2 (r = -0.290 and P = 0.013). (2) The proportion of high MMP-2 expression to low TIMP-2 expression in patients with tumor metastasis was significantly higher than that in patients without metastasis (P = 0.010 and 0.002 respectively). (3) MVD of patients with high MMP-2 expression was higher than that in the low MMP-2 expression group (P = 0.005). MVD of patients with high TIMP-2 expression was lower than that in the low TIMP-2 expression group (P = 0.048). (4) Low TIMP-2 expression significantly correlated with poor prognosis of patients with synovial sarcoma, by univariate and multivariate survival analysis (P = 0.002 and 0.016 respectively).

CONCLUSIONSExpression of MMP-2 and TIMP-2 correlates with metastatic potential and tumor angiogenesis in synovial sarcoma. Low TIMP-2 expression often indicates poor prognosis and unfavorable clinical outcomes.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; statistics & numerical data ; Kaplan-Meier Estimate ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Microcirculation ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Neovascularization, Pathologic ; enzymology ; pathology ; Prognosis ; Proportional Hazards Models ; Sarcoma, Synovial ; blood supply ; enzymology ; pathology ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism

OBJECTIVETo explore if vasculogenic mimicry (VM) exists in hepatocellular carcinoma (HCC) and to explain the clinical significance of VM.

METHODSNinety-nine HCC resection specimens with complete clinical and prognostic data were collected. Immunohistochemical staining of CD31 and CD105, hepatocyte and PAS staining of the histological preparations were conducted to explore if VM exists in those HCC.

RESULTS12.12% (12 specimens) of the 99 specimens exhibited evidence of VM. One of 40 HCC specimens (2.5%) which belong to Edmondson pathologic grade I-II exhibited VM; 11 of 59 HCC specimens which belong to Edmondson pathologic grade III-VI (18.64%) exhibited VM, the low differentiated HCC (grade III-VI) exhibited more VM specimens than the high differentiated HCC (grade I-II) (chi2=4.416, P < 0.05). The biological behavior of VM was assessed and the stages of the cancers, using the TNM (tumor, node, metastases) classification criteria, were analyzed. These parameters of the VM and non-VM groups were compared. The mean TNM stage of the VM group was not more advanced than that of the non-VM group. The hematogenous metastases ( lung, bone, peritoneum et al) between the 2 groups were compared, and in the VM group the hematogenous metastasis rate was higher (chi2=8.873, P < 0.01). Kaplan-Meier actuarial survival curves were used to compare the VM group (n = 12) with the non-VM group (n = 87). Median survival time of the VM group was 9 months and that of the non-VM group was 31 months. The VM group had a lower survival rate than the non-VM group (P < 0.01).

CONCLUSIONVM exists in HCC, and the higher invasive HCCs exhibit more VM than the less invasive HCCs. The HCC patients in the VM group had a higher rate of hematogenous metastases, a lower survival rate, and a poorer prognosis.

Adult ; Aged ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology