Pharmacokinetics and pharmacogenetics of high-dose methotrexate in Chinese adult patients with non-Hodgkin lymphoma: a population analysis.

PURPOSE: High-dose methotrexate (HD-MTX) is widely used in the treatment of non-Hodgkin lymphoma (NHL), but the pharmacokinetic properties of HD-MTX in Chinese adult patients with NHL have not yet been established through an approach that integrates genetic covariates. The purposes of this study were to identify both physiological and pharmacogenomic covariates that can explain the inter- and intraindividual pharmacokinetic variability of MTX in Chinese adult patients with NHL and to explore a new sampling strategy for predicting delayed MTX elimination. METHODS: A total of 852 MTX concentrations from 91 adult patients with NHL were analyzed using the nonlinear mixed-effects modeling method. FPGS, GGH, SLCO1B1, ABCB1 and MTHFR were genotyped using the Sequenom MassARRAY technology platform and were screened as covariates. The ability of different sampling strategies to predict the MTX concentration at 72 h was assessed through maximum a posteriori Bayesian forecasting using a validation dataset (18 patients). RESULTS: A two-compartment model adequately described the data, and the estimated mean MTX clearance (CL) was 6.03 L/h (9%). Creatinine clearance (CrCL) was identified as a covariate for CL, whereas the intercompartmental clearance (Q) was significantly affected by the body surface area (BSA). However, none of the genotypes exerted a significant effect on the pharmacokinetic properties of MTX. The percentage of patients with concentrations below 0.2 µmol/L at 72 h decreased from 65.6 to 42.6% when the CrCL decreased from 90 to 60 ml/min/1.73 m2 with a scheduled dosing of 3 g/m2, and the same trend was observed with dose regimens of 1 g/m2 and 2 g/m2. Bayesian forecasting using the MTX concentrations at 24 and 42 h provided the best predictive performance for estimating the MTX concentration at 72 h after dosing. CONCLUSIONS: The MTX population pharmacokinetic model developed in this study might provide useful information for establishing personalized therapy involving MTX for the treatment of adult patients with NHL.

Morphological Changes of Amygdala in Turner Syndrome Patients.

AIMS: Turner's syndrome (TS) losts one of the X chromosomes and exhibits social cognition deficits. Previous studies have reported that women with TS demonstrated structural and functional abnormalities in brain, including increased volume in amygdala. However, most studies regarded the amygdala as a whole, and the abnormalities in the specific subregions of amygdala in TS have not been studied. Here, we aimed to investigate the local morphological changes of amygdala in TS using the surface morphology analysis method. METHODS: A total of 19 adolescents with 45XO TS and 20 matched adolescents with typical development were evaluated using magnetic resonance imaging. The amygdalae of all participants were manually delineated. 3D surface remodeling and parameterization were performed based on the outlined boundaries of amygdalae. We extracted two surface metrics, namely direct Euclidean displacement and normal projection that were used to represent the morphology of amygdala. RESULTS: Statistical analysis showed significant outward deformation in the laterobasal subregion of left amygdala in patients with TS, compared with the controls using either direct Euclidean displacement or normal displacement. CONCLUSIONS: Our findings provide novel insight into the pathological changes in the amygdala of patients with TS.

[Application Progress of Holographic Lithgraphy in Fabrication of Micro-Nano Photonic Structures].

Micro-nano photonic structures are developing vigorously based on the progress of photonics, semiconductor physics and microfabrication technology. A series of results are achieved in structure characterization, theory, and fabrication of them. Most high quality photonic structures are man-made ones; however, there are still some challenges in fabricating artificial large-area and high-quality photon materials. With the advantages of photonic structure processing technology, holographic lithography, a low-cost, time-saving and high-efficiency microfabrication method, performs superior application potentials in making metamaterials as well as photonic crystal templates. In this article, we introduced the principles of holographic lithography and described the applications in fabricating various micro-nano photonic structures, such as three dimensional face-center-cubic, wood-pile, diamond-like photonic crystals, as well as quasi-crystalline structure, chiral metamaterials and periodic defect-mode structures. Moreover, the applications of some structures in solar cell and optical fiber sensing are discussed. The success of fabricating micro-nano photonic structures by holographic lithography would pave the way for more applications of these structures in wide fields.

[The color analysis of peacock feather].

Peacock feather is one of the typical cases with structural colors. In the present article, we found that flamboyant colors in the "eye spot" of male peacock came from photonic crystal structure by observing the surface texture with SEM and reflectance spectrum with fiber spectrometer, and different color regions correspond to various structure cycles and surface appearances of the microstructure. The reflectance spectrum showed that the location of reflective peak shifted with the changes in the incident angles. The theory that the color is caused by microstructure was verified by the phenomenon that reflective peak exhibited red-shift with the time-varying after soaking in isopropyl alcohol. This study paves the way for fabricating functional composite materials with peacock feather-like photonic crystal structure.

[Expression and significance of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in hepatocyte steatosis model].

OBJECTIVE: To investigate the expression of IGF-1 and IGFBP-3 in nonalcoholic fatty steatosis hepatocyte models induced by oleic acid. METHOD: Nonalcoholic fatty steatosis hepatocyte models induced by oleic acid on immortalized human hepatocyte, Oil red O staining and intracellular triglycerides were detected for observing the situation of IHH cells fatty degeneration. IHH cells were divided into control group, NAFLD group, which the control group cultured in DMEM/F12 medium, NAFLD group were treated with oleic acid, 0.5 mmol/L treatment for 72 h. The expression of mRNA and protein of IGF-1 and IGFBP3 were measured by immunofluorescent staining, Western blot and RT-PCR methods. Between the two groups were compared using the t- test. RESULTS: The steatosis models of the hepatocytes were established successfully with 0.5 mmol/L oleic acid. Lipid droplets were observed through Oil red O staining. The level of hepatocyte TG was increased (275.7+/-27.2) mug/mg from (150.2+/-15.6) mug/mg (t = 21.67, P less than 0.01). Compared with the control group, the mRNA of IGF-1 (0.76+/-0.04 vs 4.82+/-1.51, t = 17.915, P less than 0.01), IGFBP-3 (1.58+/-0.93 vs 5.41+/-1.37, t = 12.893, P less than 0.01) and protein expression of IGF-1 (1.00+/-0.29 vs 2.56+/-0.71, t = 29.17, P less than 0.01), IGFBP-3 (0.65+/-0.36 vs 1.23+/-0.91, t = 32. 12, P less than 0.01) significantly decreased in oleic acid-treated group. The results of immunofluorescence staining also confirm the significantly decreased protein expression of IGF-1 and IGFBP-3 in NAFLD group compared with control group. CONCLUSION: The expression of IGF-1 and IGFBP-3 decreased in nonalcoholic fatty steatosis hepatocyte models, which will provide the experimental basis for the further study of the mechanism of the limited height of some children with non-alcoholic fatty liver disease in clinical.

The effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats.

OBJECTIVE: To study the effect of polyethylene glycol recombinant human growth hormone on growth and glucose metabolism in hypophysectomized rats, and compare the effect of treatment between recombinant human growth hormone (rhGH) and polyethylene glycol rhGH (PEG-rhGH). METHODS: Hypophysectomy was performed in juvenile rats to build the animal model of GH deficiency. The hypophysectomized animals were randomly assigned into three groups and treated with saline (negative control, n=20), rhGH (n=20) and PEG-rhGH (n=20). A sham operation was performed to set up the normal control (n=20). Body weight, body length and tail length were recorded every 2days for a 14-day treatment and bone growth was measured at the end of therapy. Glucose infusion rate (GIR) determined by euglycemic hyperinsulinemic clamp was used to evaluate insulin sensitivity after GH treatment. We also examined plasma glucose and serum insulin levels RESULTS: Compared with the negative control, the body weight, body length, tail length and bone growth increased significantly in hypophesectomized rats treated by GH (P<0.01). Although the weight gain in the first 10days was higher in the PEG-rhGH group than in the rhGH group (P<0.05), the growth promoting effect was similar between rhGH and PEG-rhGH (P>0.05). Neither rhGH nor PEG-rhGH impaired glucose tolerance of rats after hypophesectomy. Compared with negative controls, according to decreased serum insulin, reduced insulin expression in pancreatic cells and increased GIR in the clamp, both rhGH and PEG-rhGH groups had improved insulin sensitivity within 14 days (P<0.01). However, with prolonged treatment, the GIR in the rhGH-treated rats decreased significantly (P<0.05); while PEG-rhGH did not interfere with GIR, even after a doubled dose (P>0.05). CONCLUSIONS: PEG-rhGH had the same linear growth promoting efficacy as unmodified rhGH. The short-term GH replacement could improve insulin sensitivity in hypophysectomized rats, especially after PEGylation.

Fabrication of two-dimensional superposed microstructure by interference lithography.

In this paper, we report the basic theory and method of single exposure interference lithography (IL) to fabricate two-dimensional (2D) superposed microstructures. Distribution of six-beam interference intensities with different azimuth angle is discussed, and 2D superposed microstructures with different periodic constants are obtained by computer simulations. The experiment results using CHP-C positive photoresist show a 2D superposed photonic crystal composed of a periodically repeated hexagonal pattern of hexagonal lattice cells, which is in close agreement with the computer simulation. Fabrication of a superposed structure by single exposure IL paves the way for studying 2D photonic crystal fabrication, surface lasing, optical waveguides, and so on.

[Observation on therapeutic effect of electroacupuncture combined with functional training for treatment of peripheral nerve incomplete injury of upper limbs].

OBJECTIVE: To search for the best program for treatment of peripheral nerve incomplete injury. METHODS: Ninety cases were randomly divided into a treatment group, a control group I and a control group II, 30 cases in each group. The treatment group were treated with electroacupuncture at Jianyu (LI 15), Hegu (LI 4), Quchi (LI 11), etc. plus functional training, and the control group I with electroacupuncture and the control group H with functional training. After treatment for 3 months, basic function, practical function, EMG, nerve conduction velocity were compared among the 3 groups. RESULTS: The good rate of basic function of 50.0%, the curemarkedly effective rate of practical function of 50.0% and the total effective rate of neurophysiology of 64.3% in the treatment group were better than 20.7%, 17.2%, 41.4% in the control group I (P < 0.05) and 23.3%, 20.0% and 36.O7% in the control group II (P 0.05). CONCLUSION: Electroacupuncture combined with functional training can accelerate nervous repair, promote functional recovery of the denervated muscles, so as to shorten the restoring time of nerve-muscle and increase life quality of the patient.

[Studies of the possible mechanisms for protective effects of recombinant human growth hormone on intestinal mucosa barrier in rat sepsis].

OBJECTIVE: To investigate the protective effects of recombinant human growth hormone (rhGH) on intestinal mucosal barrier in rat sepsis and explore its possible mechanisms. METHODS: E. coli was injected intraperitoneally to produce rats sepsis models. Forty-two female SD rats were randomly divided into the control group (group C), sepsis group (group S) and treatment group (group T). Group S and group T were further divided into 1 d and 3 d subgroups (T1d,T3d, Sld, S3d), respectively. The expression of IGF-1 mRNA in liver, expression of Bcl-2 protein in intestine, bacteria translocation, the levels of growth hormone(GH) and insulin-like growth factor-1 (IGF-1) in plasma, and the histological appearance of intestine were determined dynamically by means of RT-PCR, radioimmunoassay, immunohistochemical staining and other corresponding methods, respectively. RESULTS: (1) rhGH could significantly attenuate intestinal mucosal injuries and ameliorate bacteria translocation on sepsis rats. (2) The levels of Bcl-2 protein expression in intestine in group T (T1d:2441 +/- 117; T3d: 3628 +/- 235) were obviously higher than those of group S (S1d: 321 +/- 36; S3d: 1873 +/- 57) (P < 0.01). (3) The plasma levels of GH in group T (T1d: 1.28 +/- 0.24 microg/L; T3d: 2.14 +/- 0.48 microg/L) increased markedly than those of group S (S1d: 0.74 -/+ 0.12 microg/L; S3d: 0.60 +/- 0.18 microg/L) (P < 0.01). (4) The plasma levels of IGF-1 in group T (Tld: 168.94 +/- 65.67 microg/L; T3d: 201.56 +/- 64.98 microg/L) elevated significantly than those of group S (Sld: 116.72 +/- 13.96 microg/L; S3d:107.50 +/- 23.53 microg/L) (P < 0.05). (5) The levels of liver IGF-1 mRNA in group T (Tld: 0.98 +/- 0.20; T3d: 1.76 +/- 0.17) were significantly higher than those in group S (S1d: 0.38 +/- 0.09; S3d: 0.46 +/- 0.10) (P < 0.01). CONCLUSION: rhGH conferred protective efficacy in maintaining the integrity of intestinal mucosal barrier against sepsis in rat. The possible mechanisms might involve the rhGH-diminished apoptosis of intestinal mucosa cells and the rhGH-maintained intestinal mucosa barrier via the roles of GH and IGF-1.

[Study on acute pancreatitis-associated lung injury induced by L-arginine in mice].

OBJECTIVE: To establish the model of acute pancreatitis (AP)-associated lung injury induced by L-arginine and study the role of TNF-alpha and ICAM-1 in the model mice. METHODS: For the establishment of the AP model, the mice were given the first injection (2 g/kg) of L-arginine intraperitoneally and then the second injection in the same way an hour later. At 12 h after the second injection, the animals' serum amylase activities were assayed by colorimetry, and the tumor necrosis factor-alpha (TNF-alpha) contents of their pancreatic tissue were determined by radioimmunoassay. At 24 h after the second injection, the histopathological changes in the animals' pancreatic and pulmonary tissues were observed. The pulmonary expression and cellular localization of intercellular adhesion molecule-1 (ICAM-1) were characterized by immunohistochemistry. RESULTS: The serum amylase activities, TNF-alpha content and ICAM-1 expression in lung tissue significantly increased in the AP group as compared with those in the control group. Histopathological examinations revealed that the acinar architecture was partially destroyed with necrosis, interstitial edema and inflammatory infiltration at 24 h after the second injection. CONCLUSION: TNF-alpha and ICAM-1 may play important roles in the mice with acute pancreatitis-associated lung injury.

[Testing research of achromatic phase retarder's spectral character].

Using established testing system by principle of normalized polarizing modulation, we measured the spectral characters of normal Fresnel rhomb, improved Fresnel rhomb, oblique-incidence rhomb and rectangle prism compound rhomb phase retarders. Through the measured spectral we yield the characteristic achromatism curves of all kinds of achromatic phase retarders, and analyse the results. The results indicate that the achromatism of the improved Fresnel rhomb and rectangle prism compound rhomb phase retarders is superior to others. Currently the improved Fresnel rhomb and retangle prism compound rhomb phase retarders are the ideal and utility-type achromatic phase retarders.