Objective:To determine the location of the conus medullaris termination (CMT) in children under the magnetic resonance imaging (MRI).Methods:The children, aged 1 day to 15 yr, underwent MRI performed on the lumbosacral spine, were retrospectively analyzed.The CMT corresponding to the position of vertebral body was sequentially numbered.Each vertebral body was divided into upper (U), middle (M), and lower 1/3 unit (L), while the intervertebral disc was considered as an independent segment.From top to bottom of vertebral body, T 12-U1/3 was marked as 0, T 12-M1/3 was marked as 1, T 12-L1/3 was marked as 2, and T 12-L 1 was marked as 3, respectively.The children including male group and female group were divided into different age groups: <1 month, 1-5 months, 6-11 months, 1 yr, 2-4 yr, 5-9 yr and 10-15 yr.The children were divided into male group (M group) and female group (F group) according to gender, and the positions of CMT were compared. Results:A total of 231 children were enrolled in this study, including 122 males and 109 females, aged (4±4) yr.The corresponding number for the position of CMT in children aged <1 month, 1-5 months, 6-11 months, 1 yr, 2-4 yr, 5-9 yr and 10-15 yr was 7.3±2.0, 7.3±2.3, 6.4±1.8, 6.5±2.6, 5.4±2.2, 5.5±1.8, and 5.0±1.8, respectively.There was no statistically significant difference in the position of CMT between group M and group F ( P>0.05). Conclusion:The corresponding number for the position of CMT is 7.3, 7.3, 6.4, 6.5, 5.4, 5.5 and 5.0 in children aged <1 month, 1-5 months, 6-11 months, 1 yr, 2-4 yr, 5-9 yr and 10-15 yr, respectively.

OBJECTIVETo prepare cytochrome (CYP)2E1-silenced hepatocytes by lentivirus-mediated RNA interference technology and to investigate the hepatotoxicity of trichloroethylene (TCE) in CYP2E1-silenced hepatocytes.

METHODSShort hairpin RNA fragments were designed and synthesized and were then ligated into the lentiviral vector; single colonies were screened; the plasmid was extracted after PCR and sequence identification and then transferred into L02 hepatocytes; the CYP2E1-silenced hepatocytes were selected; real-time quantitative PCR and Western blot were used to evaluate the interference effects. The obtained CYP2E1-silenced hepatocytes, as well as normal L02 hepatocytes, were treated with TCE (0, 0.25, 0.50, 1.00, 2.00, and 4.00 mmol/L). The cell viability and half maximal inhibitory concentration (IC50) of TCE were measured; the apoptotic rate of cells was measured by flow cytometry; the mRNA expression levels of apoptosis genes and oncogenes were measured by real-time quantitative PCR.

RESULTSThe IC50s of TCE for L02 hepatocytes and CYP2E1-silenced hepatocytes were 15.1 mmol/L and 23.6 mmol/L, respectively. The apoptotic rate increased as the dose of TCE rose in the two types of cells; the CYP2E1-silenced hepatocytes hada significantly lower apoptotic rate than L02 hepatocytes when they were exposed to 2.0 and 4.0 mmol/L TCE (P < 0.05 or P < 0.01). The mRNA expression level of bcl-2 (anti-apoptosis gene) in CYP2E1-silenced hepatocytes was 15% ∼ 60% higher than that in L02 hepatocytes (P < 0.01), while the mRNA expression levels of caspase-3 and caspase-9 (apoptosis genes) in CYP2E1-silenced hepatocytes were 30% ∼ 60% lower than those in L02 hepatocytes (P < 0.01). The mRNA expression level of p53 (cancer suppressor gene) in CYP2E1-silenced hepatocytes was 81 - 278% higher than that in L02 hepatocytes (P < 0.01), while the mRNA expression levels of c-fos and k-ras (oncogenes) in CYP2E1-silenced hepatocytes were 20-68% lower than those in L02 hepatocytes (P < 0.01).

CONCLUSIONCYP2E1-silenced cells can be successfully prepared by lentivirus-mediated RNA interference technology. Silencing CYP2E1 gene can reduce the hepatotoxicity of TCE and inhibit the expression of some apoptosis genes and oncogenes, suggesting that CYP2E1 gene plays an important role in TCE metabolism and is related to the hepatotoxicity of TCE.

Apoptosis ; drug effects ; genetics ; Cell Line ; Cell Survival ; drug effects ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; metabolism ; Genetic Vectors ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lentivirus ; genetics ; RNA Interference ; Trichloroethylene ; toxicity

OBJECTIVETo investigate the effect of apelin on vasodilatation of isolated pulmonary arterial rings in rats and its relationship to the nitric oxide (NO) pathway, and to observe the difference of vasodilatation between hypoxic rats and normoxic rats.

METHODSThirty-six male Sprague-Dawley (SD) rats were randomly divided into hypoxic group and normoxic group. The effects of accumulated apelin on pulmonary arterial rings preconstricted with norepinephrine (NE) were observed by using tissue organ bath system. After pulmonary arterial rings were pretreated with three methods: removing the endothelium, pretreating with nitric oxide synthase inhibitor L-NAME or soluble guanylatecyclase inhibitor ODQ, the different effect of apelin was observed. In addition, the difference of vasodilatation between hypoxic rats and normal rats were observed.

RESULTS(1) Exposure of intact endothelium pulmonary arterial rings preconstricted by NE to apelin at concentration (0.01 - 100 nmol/L) induced a significant concentration dependent relaxation. The maximal vasorelaxant effect of apelin was 10.62% +/- 2.60%, which was inhibited by removal of the endothelium (P < 0.01), pretreatment with L-NAME (P < 0.01) or ODQ (P < 0.01). (2) Response of pulmonary arterial rings from hypoxic pulmonary hypertension rats was decreased (P < 0.05). Compared to normal rats, at a concentration of 100 nmol/L, the response to apelin on arteries from hypoxic rats decreased 60.45% (P < 0.01). But the values of EC50 were not significantly different (P > 0.05).

CONCLUSIONThese results indicate that apelin relaxes the pulmonary arterial rings of rats in an endothelium dependent manner, which may have a relationship to NO signaling pathway. The response of vasodilatation is decreased in the pulmonary arterial rings from the hypoxic rats.

Animals ; Apelin ; Hypoxia ; physiopathology ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; pharmacology ; Male ; Nitric Oxide ; metabolism ; Pulmonary Artery ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vasodilation ; drug effects

BACKGROUNDCyclosporine A (CsA) has been widely used in the treatment of aplastic anemia (AA), but the application of CsA was limited in patients who had liver diseases or abnormal liver function due to its liver toxicity. Glycyrrhizin has long been used in China in the treatment of various liver diseases to lower transaminases. In this study, we observed the efficacy and safety of glycyrrhizic acid combined with CsA in the treatment of newly diagnosed patients with non-severe AA (NSAA).

METHODSA total number of 76 patients with newly diagnosed NSAA were enrolled into the study at our hospital between July 2005 and June 2010. The patients were divided randomly into two groups: the glycyrrhizin-treatment group (group A) and the control group (group B) with 38 patients in each group. All patients received 3 - 5 mg×kg(-1)×d(-1) CsA for at least 4 months and were treated either with or without glycyrrhizin for 4 months.

RESULTSsixty-eight patients were eligible for evaluation. In the control group, 9.09% patients (n = 3) achieved a complete response while 51.52% (n = 17) attained a partial response. The overall response rate was 60.61% (n = 20). The remaining 13 patients (39.39%) did not have any response. In the glycyrrhizin-treatment group, complete response rate was 20% (n = 7) and partial response rate was 62.86% (n = 22). The overall response rate was 82.86% (n = 29) and the non-response rate was 17.14% (n = 6). Response rate was significantly increased with the addition of glycyrrhizin to CsA compared with CsA alone (P < 0.05).

CONCLUSIONThe combination of glycyrrhizin and cyclosporine regimen was an effective treatment for NSAA in terms of improvement of response rate, reduction in CsA-related liver injury, and attenuation of severity of nausea and other adverse events in the treatment of patients with NSAA.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; drug therapy ; immunology ; Cyclosporine ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Glycyrrhizic Acid ; administration & dosage ; adverse effects ; Humans ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Male ; Middle Aged

Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications.
Antigens, Neoplasm ; metabolism ; Antineoplastic Agents ; chemistry ; therapeutic use ; Carbonic Anhydrase IX ; Carbonic Anhydrase Inhibitors ; chemistry ; therapeutic use ; Carbonic Anhydrases ; metabolism ; Humans ; Neoplasms ; drug therapy ; enzymology

OBJECTIVE: To observe the changes of apolipoprotein E (apoE) protein expression of pulmonary tissue in mice with pulmonary hypertension induced by hypoxia. METHODS: The animal model of hypoxic pulmonary hypertension was established by exposing the mice to isobaric hypoxic chamber for 3 weeks (23 h/d, regular chow feed).Twenty male wild type (WT) C57BL/6 mice and twenty apoE gene knockout (apoE-KO) mice were randomly divided into normoxia group and hypoxia group. The plasma concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and total cholesterol were detected by ELISA method. The protein expression of apoE in lung and liver, and peroxisome proliferators-activated receptor gamma (PPARγ) in lung were measured by Western blot. RESULTS: ①In WT mice, the right ventricular systolic pressure (RVSP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) of hypoxia group were significantly higher than those of normoxia group by 68% and 59% (<0.05), respectively. The plasma concentration of HDL and HDL/LDL of hypoxia group were significantly lower than those of normoxia group by 17% and 40% (<0.05), respectively.The protein expression of apoE in lung and in liver of hypoxia group were significantly down-regulated than those of normoxia group by 48% and 52% (<0.05), respectively.The protein expression of PPARγ in lung was significantly down-regulated than that of normoxia group by 37%(<0.05).RVSP were significantly negative correlated with the protein levels of apoE and PPARγ in lung (<0.01).② In apoE-KO mice, RVSP and the weight ratio of RV to LV+S of hypoxia group were significantly higher than those of normoxia group by 96% and 86% (<0.05), respectively.RVSP and RV to (LV+S) of hypoxia group in apoE-KO mice were significantly higher than those of hypoxia group in WT mice by 29% and 24% (<0.05), respectively. CONCLUSIONS Down-regulated expression of apoE in lung tissue participates in the pathological proceeding of pulmonary hypertension induced by hypoxia.
Animals ; Apolipoproteins E ; Hypertension, Pulmonary ; Hypoxia ; Lung ; Male ; Mice ; Mice, Inbred C57BL

This study was conducted to produce pectin-doxorubicin conjugate (PDC) nanosuspensions by high-pressure homogenization, and investigating the physico-chemical properties, the cumulative release rate in vitro and in vivo, and the anti-tumor activity. The major production parameters such as pressure, cycle numbers and types of stabilizers on the mean particle size and polydispersity index (PI) of PDC nanosuspensions were investigated. The cumulative release rate in phosphate buffer saline (PBS) at pH 5.1 or 7.0 were studied. The concentration of doxorubicin (DOX) in plasma of rabbit were recorded after intraperitoneal injection of PDC nanosuspensions (DOX was equivalent to 10mg·kg^-1) or DOX (10mg·kg^-1). We established an animal model of the nude mice with SKOV₃ cell, and injected the PDC nanosuspensions (DOX was equivalent to 10, 5, 2.5 mg·kg^-1) in the first day, and observed the growth state of nude mice. The particle size of PDC nanosuspensions was 118.8±6.93 nm, PI was 0.14±0.03, as well as the zeta potential was -27.2±0.36mV. It shows that no drug release was found in PBS at pH 7.4. About 40% cumulative release was determined in PBS at 5.1 after 30 h. The concentration of DOX in plasma of PDC group was 60 ng·mL^-1, and was lower than that of DOX group. Compared with control group, high-dose-group decreased the weight of nude mice's ascites tumor and burrknot. PDC nanosuspensions can inhibit the growth of SKOV₃ cell line in nude mice. In summary, PDC nanosuspensions are target-specific drugs with high efficiency and low toxicity in the ascites cancer model.

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome