Alagille syndrome (ALGS) is an autosomal dominant disorder which is mainly caused by JAG1 gene mutation and can affect multiple systems including the liver, heart, eyes, skeleton and face. This paper reports the clinical and genetic features of an ALGS patient. A 2-year-and-9-month-old boy was referred to the hospital with the complaint of abnormal liver function and heart murmur discovered over two years. Jaundice of the skin and sclera was not observed. The child had a prominent forehead, left esotropia, depressed nasal bridge and micromandible. The two lungs were clear on auscultation, but a systolic cardiac murmur of grade 2/6 could be heard between the 2nd and 3rd intercostal space at the left sternal border. Neither abdominal distension nor enlarged liver or spleen was discovered. X-ray radiography uncovered butterfly malformation of the 6th and 8th thoracic vertebrae. Serum biochemistry analysis revealed elevation of total bile acids, bilirubin and transaminases. Based on the clinical characteristics and the consultation opinion of the ophthalmologist, the child was diagnosed to have ALGS with Duane retraction syndrome. DNA direct sequencing detected a novel JAG1 mutation c.2419delG(p.Glu807AsnfsX819) in the child. Symptomatic and supportive therapy was performed thereafter and clinical follow-up was conducted until he was 4 years and 2 months. In the follow-up visits, his general condition remained stable, but the facial malformations, left esotropia, cardiac murmur and abnormal liver function persistend. The long-term outcome needed to be observed.
Alagille Syndrome ; genetics ; therapy ; Child, Preschool ; Humans ; Jagged-1 Protein ; genetics ; Male ; Mutation

OBJECTIVETo implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs).

METHODSSIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans.

RESULTSThe plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9.

CONCLUSIONSFive to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.

Aged ; Dose-Response Relationship, Radiation ; Esophageal Neoplasms ; radiotherapy ; Female ; Humans ; Male ; Radiation Dosage ; Radiotherapy Planning, Computer-Assisted ; methods

Objective To investigate the mitochondrial damage and its effect in early stage of pressure ulcer in rats.Methods Forty rats were randomly divided into 5 groups(n=8), control group(Con group) rats without stress, the experimental group was treated with of 170 mmHg for 2 h and relax 0.5 h as one cycle(1C), experi-mental group was divided into 3C, 6C, 9C and 12C group.The pathological changes of the compressed muscle tissue of the rats in each group were observed by HE staining , Western blot was used to detect the expression of Bcl-2 and Bax in the compressed tissue , and the ultrastructure of muscle fibers and mitochondria were observed by transmission electron microscope .Results There were pathological damage and gradually increased in the ex-perimental groups, with the increase of compression cycle; the expression of Bcl-2 in each experimental group was significantly increased as compared with the control group(P<0.05), in the 3C group reached the peak, and then decreased; the expression of Bax was increased gradually with the increase of compression cycle ( P<0.05) , and in the 12C group reached the peak;with the increase of the compression cycle the muscle fibers of each experimental group appeared gradually increased pathological damage:disorder, dissolution and fracture, the ridge of the mitochondria disappeared, vacuolar degeneration, et al.Conclusions In the early stage of pres-sure ulcer in a rat , it brings occurred mitochondrial damage and induces apoptosis .

Objective To evaluate the effect of long-term microwave radiation on the expression of N-methyl-D-aspartate receptor(NMDAR),brain derived neurotrophic factor(BDNF) and related molecules in signal pathways in the hippocampus of rats.Methods Fifty male Wistar rats were exposed to microwave radiation at an average power density of 0,5,10,20 and 30 mW/cm2for 6 min/time,3 times/week,and for 6 weeks,which were sacrificed and the hippocampus was quickly removed at 14 d and 28 d after exposure.The changes in NMDAR (NR1,NR2A,NR2B),postsynaptic density protein(PSD)-95,cortactin,BDNF and tyrosine kinase receptor B (TrkB) in hippocampal neurons of each group were detected by Western blotting and image analysis techniques.Results Compared with the control group,the expressions of related proteins did not change significantly after microwave irradiation of 5 mW/cm2 at each time point.After 20 mW/cm2 microwave radiation,the expression of NR1 was increased at 14 and 28 d (P ＜0.05),the expression of NR2A was increased at 28 d (P ＜ 0.05),but the expression of NR2B was decreased at 14 and 28 d (P ＜ 0.05).At a average power density of 30 mW/cm2,the expressions of NR1,NR2A and PSD-95 and the expression of NR2B were decreased at 14 and 28 d(P ＜0.05),and cortactin,BDNF and TrkB were increased at 14 d after irradiation (P ＜ 0.05).Conclusion The effect of different dosages of long-term microwave radiation on the proteins of NMDAR and its signal pathway related molecules is different.Microwave radiation may affect the NMDAR of postsynaptic information transmission through the BDNF-TrkB signaling pathways,which might play an important role in the impediment of learning and memory function caused by microwave radiation.

OBJECTIVETo evaluate the feasibility, therapeutic effects and complications of three-dimensional conformal radiotherapy (3DCRT) for small-cell lung cancer (SCLC).

METHODSThe data of 19 SCLC patients treated between June 2001 and August 2003, with 3DCRT were reviewed and analyzed. Eighteen patients were treated by radiotherapy plus chemotherapy while only 1 patient by radiotherapy alone. Radiotherapy was delivered at 2 Gy/fraction, 5 fractions per week with a median total dose of 54 Gy. Chemotherapy consisted of 4 - 6 cycles of etoposide and cisplatin or carboplatin. The median follow-up time was 24 months.

RESULTS(1) The overall response rate after 3DCRT was 79.0%, with a complete remission rate of 31.6% (6/19), partial remission rate of 47.4% (9/19). The 1- and 2-year overall survival (OS) was 71.7% and 35.8% respectively, with a median survival time (MST) of 19 months, and both the 1- and 2-year local progression free survival (LPFS) were 94.7%. (2) Of these 19 patients, grade 2 acute radiation pneumonitis developed in 5.3%, grade 2 late radiation pneumofibrosis in 5.3%, grade 2 acute radiation esophagitis in 10.5% and grade 2 acute hematologic toxicity in 10.5%.

CONCLUSIONThree-dimensional conformal radiotherapy is feasible in the treatment of SCLC with high response rate and acceptable complications. Further observation, more patients treated by 3DCRT and prolonged follow-up are needed to evaluate remote survival.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Small Cell ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms ; drug therapy ; radiotherapy ; Male ; Middle Aged ; Radiotherapy Dosage ; Radiotherapy, Conformal ; methods

OBJECTIVETo retrospectively analyze the effects of different chemotherapy regimens for concurrent chemoradiation on locally advanced non-small cell lung cancer (NSCLC).

METHODSThe data from 106 patients diagnosed as locally advanced NSCLC (IIIa: 29, IIIb: 77), who received various chemotherapy regimens for concurrent chemoradiotherapy, were retrospectively analyzed. Paclitaxel-based chemotherapy regimen was administered in 55 patients, topotecan regimen in 21 patients, PE (cisplatin and etopside) regimen in 26 patients, and other regimens in the remaining 4 patients. The effect of different chemotherapy regimens on overall survival and toxicity was analyzed.

RESULTSThe median survival time was 18.6 months, and the overall 1- and 3-year survival rates were 72.2% and 27.5%, respectively. The median survival time of 102 patients treated with paclitaxel-containing, topotecan-containing or PE regimens was 16.3, 27.3 and 29.1 months, respectively. The overall survival times of topotecan and PE groups were superior to that of paclitaxol-based group, but not significantly different (P = 0.32). Both univariate and multivariate analysis showed that paclitaxol-based chemotherapy regimen was significantly associated with a poorer survival (P < 0.05). N stage was another significant prognostic factor determined by COX multivariate regression model. Compared with the other regimens (10.6%), paclitaxel-based regimen (27.3%) had more acute radiation pneumonitis (grade >or= 2, P = 0.03), but no significant differences were observed in blood toxicity and esophagitis.

CONCLUSIONThere is a correlation between different chemotherapy regimens for concurrent chemoradiotherapy and the overall survival and acute radiation pneumonitis in patients with locally advanced NSCLC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Etoposide ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paclitaxel ; therapeutic use ; Proportional Hazards Models ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; Retrospective Studies ; Survival Rate ; Topotecan ; therapeutic use

OBJECTIVETo explore effects of exendin-4 on the metabolism of extracellular matrix (ECM) in human mesangial cells (HMC) cultured in the presence of high glucose and explore the possible mechanism.

METHODSHuman mesangial cells (HMC) were treated with exendin-4 under high glucose conditions. The cell proliferation was observed using CCK8 assay, and the expressions of collagen type I, fibronectin, transforming growth factor-β1 (TGFβ1) expression and extracellular signal- regulated kinase (ERK) signaling pathway activity were assessed using Western blotting.

RESULTSExendin-4 inhibited cell proliferation and the expressions of collagen type I, fibronectin and TGFβ1 and reversed ERK phosphorylation in high glucose-induced HMC.

CONCLUSIONExendin-4 can regulate ECM metabolism in HMC cultured in high glucose by inhibiting TGFβ1/ERK pathway, suggesting the beneficial effects of exendin-4 in preventing and treating diabetic nephropathy.

Cell Proliferation ; Cells, Cultured ; Collagen Type I ; metabolism ; Culture Media ; chemistry ; Diabetic Nephropathies ; Extracellular Matrix ; metabolism ; Fibronectins ; metabolism ; Glucose ; chemistry ; Humans ; MAP Kinase Signaling System ; Mesangial Cells ; drug effects ; Peptides ; pharmacology ; Phosphorylation ; Signal Transduction ; Transforming Growth Factor beta1 ; metabolism ; Venoms ; pharmacology

OBJECTIVETo detect the disparity of three cytokines interleukin-6 (IL-6), interferon-inducible protein 10 (IP-10) and interleukin-17 (IL-17) in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA).

METHODSerum concentrations of the three cytokines were measured in 27 patients with 13 systemic-onset JIA (sJIA), 14 polyarticular JIA (pJIA) and 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Nineteen patients with no marked arthritis symptom or only temporary arthralgia were enrolled in probable sJIA group. SF from 18 patients with 7 sJIA, 11 pJIA were examined for cytokine levels.

RESULT(1) The statistically significant difference in serum IL-6 was detected between sJIA and healthy control group [28.0(4.2-59.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P < 0.05], but no significant difference between probable sJIA and healthy control group [11.8(7.7-39.2) ng/L vs. 12.3 (2.1-13.8) ng/L, P > 0.05] was found. There were statistically significant differences between sJIA group and healthy control group in serum concentrations of IL-17 [14.0(9.8-34.3) ng/L vs. 9.8 (7.9-16.2) ng/L, P < 0.05], yet compared to healthy control group, no significant difference in concentration level of IL-17 was found in pJIA Group [14.2(9.9-16.9) ng/L vs. 9.8(7.9-16.2) ng/L, P > 0.05].(2) In sJIA and pJIA SF, the median IP-10 level was significantly higher compared to respective PB levels [619.7 (160.9, 873.1) ng/L vs. 64.8 (27.4-111.9) ng/L;660.9 (401.9, 1349.8) ng/L vs. 97.4 (41.9-222.1) ng/L, P < 0.01, respectively], but there was only significant difference in IL-17 between pJIA SF and PB [22.9 (17.1, 45.8) ng/L vs. 14.2 (9.9-16.9) ng/L, P < 0.01].

CONCLUSIONIL-6 may play more important role in the pathogenesis of sJIA. Moreover, IL-6 may be the biomarker associated with arthritis in early JIA stage. Both autoinflammation and autoimmune response may be involved in the pathogenesis of sJIA. IL-17 enrichment may only occur in local joint, the levels of IL-17 in PB may not be significantly increased. The prominent expression gradient between SF and PB of IP-10 maybe the basis of performing chemotaxis and further causing joint damage.

Adolescent ; Arthritis, Juvenile ; blood ; immunology ; metabolism ; Case-Control Studies ; Chemokine CXCL10 ; blood ; metabolism ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukin-17 ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Knee Joint ; metabolism ; Male ; Synovial Fluid ; immunology ; metabolism

OBJECTIVETo investigate whether low molecular weight heparin (LMWH) may suppress the expression and secretion of vascular endothelial growth factor (VEGF) from tumor cells in vitro and inhibit the VEGF-induced proliferation of human tumor vascular endothelial cells.

METHODSHuman lung cancer cell line A549, human liver cancer cell line HepG2, human colon carcinoma cell lines HCT116 and HCT8 were used in this study. The expression levels of VEGF and TNF-alpha (tumor necrosis factor-alpha) in the tumor cells with or without pretreatment of LMWH/heparin were measured by standard sandwich ELISA technique. The VEGF mRNA level of HepG2 cells cultured with or without LMWH/heparin was determined by RT-PCR and real time PCR. Human umbilical vein endothelial cells (HUVEC) were cultured in tissue culture medium (TCM) with or without LMWH/heparin for 3 days. Then non-radioactive cell proliferation assay (MTS) kit and cell cycle assay by flow cytometry were performed to measure the proliferation of HUVEC.

RESULTSThe VEGF levels in the control, LMWH, and heparin groups of the pulmonary adenocarcinoma cell line A549 were (1045.89 +/- 165.30) pg/ml, (782.45 +/- 67.17) pg/ml and (916.54 +/- 71.25) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups of the colon adenocarcinoma cell line HCT116 were (955.76 +/- 51.14) pg/ml, (822.89 +/- 142.39) pg/ml and (951.77 +/- 188.22) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in the colon adenocarcinoma cell line HCT8 were (1290.62 +/- 41.23) pg/ml, (1063.34 +/- 63.82) pg/ml and (1257.14 +/- 11.40) pg/ml, respectively. The VEGF levels in the control, LMWH, and heparin groups in the liver cancer cell line HepG2 were (1083.00 +/- 134.35) pg/ml, (758.00 +/- 84.85) pg/ml and (874.00 +/- 22.62) pg/ml, respectively. The VEGF expression levels in the above mentioned cell lines cultured in TCM were significantly reduced in the LMWH-treated groups compared with that of the control group (P < 0.05). But the level of TNF-alpha in TCM-cultured cells was unaffected by LMWH. The VEGF mRNA was reduced in the LMWH-treated HepG2 cell line. Moreover, TCM exhibited stimulating effect on proliferation of HUVEC and the effect was significantly impaired by LMWH treatment. Flow cytometric analysis revealed that LMWH treatment arrested HUVECs at the G1 phase of cell cycle.

CONCLUSIONLMWH can suppress the expression and secretion of VEGF by tumor cell lines and therefore have a potential inhibiting effect on angiogenesis induced by VEGF.

Adenocarcinoma ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media, Conditioned ; Endothelial Cells ; cytology ; HCT116 Cells ; Hep G2 Cells ; Heparin ; pharmacology ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Umbilical Veins ; cytology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism ; secretion

OBJECTIVETo evaluate the effect of thoracic radiation therapy (TRT) on patients with extensive stage small-cell lung cancer (SCLC).

METHODSOne hundred and fifty-four patients with extensive stage SCLC treated in our department between January 2003 and December 2006 were enrolled in this study. Eighty nine patients received chemotherapy and thoracic radiation therapy (ChT/TRT), and 65 patients were treated with chemotherapy alone (ChT without TRT). The chemotherapy was CE (carboplatin and etoposide), PE (cisplatin and etoposide) or CAO (CTX, ADM and VCR) regimens. The total dose of thoracic irradiation was 40-60 Gy with 1.8 - 2.0 Gy per fraction.

RESULTSFor the whole group, the median survival time (MST) was 13.7 months, the 2-year and 5-year overall survival rates were 27.9% and 8.1%, respectively. The MST, overall survival rates at 2 years and 5 years in the ChT/TRT group and ChT without TRT group were 17.2 months, 36.0%, 10.1% and 9.3 months, 16.9%, 4.6%, respectively (P = 0.001). The median progression-free survival (PFS) for all patients was 8.0 months, the 2-year and 5-year PFS were 13.6% and 8.2%, respectively. The median PFS, 2-year and 5-year PFS in the ChT/TRT group and ChT without TRT group were 10.0 months, 17.4%, 10.5% and 6.2 months, 9.8%, 4.9%, respectively (P < 0.001). The incidence of intra-thoracic local failure was 29.6% in the ChT/TRT group and 70.0% in the ChT/without TRT group (P = 0.000).

CONCLUSIONSChemotherapy plus thoracic radiation therapy can improve the overall survival, progress free survival and reduce local regional failure rate in patients with extensive stage SCLC compared with that by chemotherapy alone.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; therapeutic use ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Disease-Free Survival ; Etoposide ; administration & dosage ; Humans ; Lung Neoplasms ; drug therapy ; radiotherapy ; Prognosis ; Small Cell Lung Carcinoma ; drug therapy ; radiotherapy ; Survival Rate