Objective: Realgar–Indigo Naturalis formula (RIF) is a well-known arsenic-containing preparation that is used to treat acute promyelocytic leukemia (APL) in China. In recent multicenter clinical trials, complete remission rates in APL patients have ranged from 96.08% to 100%. RIF has a satisfactory therapeutic effect, but its safety is a widespread concern, since the preparation contains arsenic, a wide-ranging and naturally occurring toxicant. In this study, in order to determine the toxic potential of RIF, acute toxicity and sub chronic toxicity assays were performed to evaluate the toxic potential of Realgar and the adjuvant components of RIF in addition to Realgar's synergy with these adjuvant components. Methods: KM mice and Wistar rats were selected for these experiments. To evaluate acute toxicity, the toxic effects of a single dose of a gradient of concentrations of Realgar were firstly determined. Then, the toxic effects of combinations of gradient doses of Realgar and fixed doses of Indigo naturalis and Salvia miltiorrhiza were evaluated. Results: The results showed that when Realgar was used alone, the LD50 was 2756.73 mg/kg (equivalent to 23.6 mg/kg As2O3). However, the LD50 dropped to 936.90 mg/kg when Realgarwas used with I. naturalis. By contrast, the LD50 increased to 7538.86 mg/kg when Realgar was used with S. miltiorrhiza. Hence, I. naturalis strengthened the toxicity of Realgar, whereas S. miltiorrhiza displayed the opposite effect. The sub chronic toxicity assessment results revealed a trend that was consistent with acute toxicity. Changes in the levels of different valence states of arsenic were also taken into account. The test results of the effects of in vitro combinations of Realgar and adjuvant components on soluble arsenic dissolution showed that I. naturalis increased the level of soluble arsenic in Realgar extracts and I. naturalis suspensions when theRealgar/I. naturalis ratio was 2, 1.5, and 1.0. However, S. miltiorrhiza did not affect it. Conclusion: Based on the collective experimental results presented here, it can be concluded that the toxicity of RIF is the result of the soluble arsenic in Realgar and that the I. naturalis and S. miltiorrhiza in the RIF exert completely opposite effects on the toxicity of Realgar. This maybe an intelligent explanation for the compatibility of this formula, and this RIF study may therefore be viewed as a classic case of traditional Chinese medicine research on compatibility.

Aim To investigate the effects of pyrrolidine dithiocarbamate (PDTC) on D-galactosamine/lipopolysaccharides (GalN/LPS)-induced acute apoptotic liver injury and its mechanism.Methods All mice were randomly divided into four groups.Mice in GalN/LPS group were co-injected with GalN (600 mg·kg~(-1),ip) and LPS (20 μg·kg~(-1), ip). Mice in PDTC+GalN/LPS group were injected with two doses of PDTC,one (100 mg·kg~(-1), ip) at 24 h before LPS and the other at 2 h before LPS (20 μg·kg~(-1), ip).Mice in control groups were treated with PDTC (100 mg·kg~(-1), ip) or saline. Ten mice in each group were observed for animal survival within 72 h after LPS treatment. Six mice in each group were sacrificed 1.5 h after LPS for collecting blood and isolating livers. The expression of hepatic TNF-α mRNA was determined by reverse transcription and polymerase chain reaction (RT-PCR). Hepatic nuclear factor-κB (NF-κB) binding activity was measured with electrophoretic mobility shift assay (EMSA).Twelve mice in each group were sacrificed 8 h after LPS treatment. Serum was collected for measurement of alanine aminotransferase (ALT) and hepatocellular apoptosis and histological examination.Results Co-injection of GalN and LPS markedly increased serum ALT activity. Histopathological examination of liver sections revealed that GalN/LPS induced hepatic congestion, necrosis and massive macrophages infiltration, and increased the number of TUNEL-positive cells in mouse liver.GalN/LPS treatments, led to 90% mortality within 72 h with severe congestion and necrosis in the liver of all the dead mice. PDTC pretreatment significantly inhibited GalN/LPS-induced hepatic NF-κB activation and TNF-α expression. In contrast, PDTC aggravated GalN/LPS-triggered hepatocellular apoptosis, increased serum ALT activity, exacerbated hepatic hemorrhage and necrosis, and accelerated death.Conclusion PDTC aggravates GalN/LPS-induced acute apoptotic liver injury via inhibiting NF-κB-mediated anti-apoptotic effects.

Objective To investigate the different expressions of pathological tissue and serum microRNAs (miRNAs)in Hirschsprung disease(HSCR). Methods Pathological colon tissues and serum samples were obtained from 52 confirmed HSCR cases respectively by surgery and pathology and from 52 matched controls,respectively. An initial screening of the tissues and serum microRNA expression were performed through TaqMan Low Density Array. The candidate tissue and serum miRNAs were validated by quantitative real - time - PCR in the 20 paired array samples and extra 32 paired samples after the integration of the screening result. The bioinformatical software online including miR-base,Target Scan,PicTar and MiRanda were used to predict the target mRNA of the consistent microRNAs in the tis-sues and the serum. Results Compared with the controls,47 microRNAs were differently expressed in HSCR tissues, including 17 up - regulated miRNAs and 30 down - regulated miRNAs;32 upregulated miRNAs were also detected to be differently expressed in the HSCR serum. Among these microRNAs,miR - 218 - 1 and miR - 885 - 5p were identi-fied to have a consistent significant different expression in both tissues and the serum,which were validated as high -expressed in microarray samples and expanded 32 paired samples(miR - 218 - 1:tissue array 0. 017 58 ± 0. 002 29 vs 0. 003 37 ± 0. 000 50,P ﹤ 0. 001;tissue expanded expression 0. 013 53 ± 0. 001 74 vs 0. 004 43 ± 0. 000 60,P ﹤0. 001. miR - 885 - 5p:tissue array 0. 000 30 ± 0. 000 11 vs 0. 000 04 ± 0. 0000 08,P = 0. 027 6;tissue expanded ex-pression 0. 004 59 ± 0. 000 16 vs 0. 000 04 ± 0. 000 01,P = 0. 014 5. miR - 218 - 1:serum array 0. 769 60 ± 0. 285 50 vs 0. 045 14 ± 0. 015 07,P = 0. 015 5;serum expanded expression 1. 151 00 ± 0. 430 00 vs 0. 023 07 ± 0. 003 81,P =0. 008 7. miR -885 -5p:serum array 1. 595 00 ±0. 441 70 vs 0. 169 40 ±0. 034 46,P =0. 001 2;serum expanded expres-sion 1. 689 00 ±0. 453 00 vs 0. 146 10 ± 0. 031 24,P = 0. 001 2). Specifically,the target genes of these 2 microRNAs were RET,PLAG1 and NeuroD1,which had been reported to be directly related to HSCR. Conclusions Significantly dif-ferential expressed miRNAs exist in the pathological tissue and the serum of HSCR. MiR - 218 - 1 and miR - 885 - 5p, which showing consistent differential expression,may be involved in the pathogenesis of HSCR.

Objective To investigated the serum level of carcinoma antigen 125 (CA-125) and its clinical significance in patients with Budd-Chiari syndrome.Methods We reviewed medical records and laboratory tests of patients with BCS first diagnosed in our hospital between August 2011 and April 2013.235 patients were included as experiment group,while 120 healthy adult volunteers were randomly selected as control group.The serum level of CA-125 were detected by electrochemilumescence immunization assay in this single-center retrospective control study.Results The average serum level of CA-125 in experiment group is higher than that of control group [(147.9 ±246.6) kU/L vs (16.0 ±7.2) kU/L,P ＜0.001].In experiment group,the relative coefficient for serum CA-125 with ascites,alanine aminotransferase,aspartate aminotransferase,albumin and Rotterdam BCS scores was 0.79,0.45,0.29,-0.393 and 0.71,respec tively,P ＜0.001.As of October 2013,we found that the 68 BCS patients with serum CA-125 level 5-fold higher than the upper limit of normal (＞ 175 kU/L) presented much lower survival rates and asymptomatic survival rates than the rest 167 BCS patients after intervention therapy:(95.6％ and 79.8％) vs (98.8％ and 92.0％),P ＜ 0.05.Conclusions The serum level of CA-125 in BCS patients have positive correlation with ascites volume,liver injury degree and Rotterdam BCS scores.Serum CA-125 evaluation appears to be a valuable examination option in BCS as CA-125 levels negatively correlate with worse prognosis,thus could be applied as an efficient tool for prognostication.

In this paper, the five strains of Polygonatum odoratum were used as the experimental materials to test the supercooling point, freezing point, the degree of supercooling, the transition stage time, cooling time and water composition of the plant tissue. The cold resistance of P. odoratum was analyzed with the Gray Correlation Method. The results showed that the cold resistances of the five strains of P. odoratum were different, and the water content of plant tissue had some relevance with freezing point and supercooling point, whereas, it could not be measured when the moisture content was too low. The order of cold resistance of the five strains of P. odoratum was ZJCY, DYYZ, XYYZ, CYYZ and JZ I.
Cold Temperature ; Plant Roots ; chemistry ; physiology ; Polygonatum ; chemistry ; classification ; physiology ; Water ; analysis

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Liver ; drug effects ; pathology ; Mice ; Silymarin ; pharmacology ; Ursodeoxycholic Acid ; pharmacology

Objective To investigate the effect of partial body-weight supported treadmill training ( PBW- STT) on function of lower limbs, walk function, ADL performance and quality of life of hemiplegic patient induced by cerebral infarction. Methods A total of 132 cerebral infarction patients were divided into a control group (n = 69) and a training group( n = 63) randomly. Both groups accepted routine rehabilitation therapy, and the training group accepted PBWSTT at the same time in addition. Both groups were evaluated with regard to their walking ability, func- tion of lower limbs, ADL performance and their quality of life by using Functional Ambulation Category (FAC) , Fugl-Meyer assessment (FMA) , Barthel index (BI) and SF-36 before and after rehabilitation treatment. Results The function of lower limb, walking ability, ADL performance and the quality of life of both groups were improved significantly after treatment, and those in the training group were improved to a significantly greater extent than those in the control group ( P

The key point of study on CO2 removal by microalgae cultured in a photobioreactor is to improve CO2 removal capability. In this paper, a model of air-lift photobioreactor was developed by combination of conditions including the velocity of flow, the degree of mixing, the gas-liquid mass transfer and the rate of photosynthesis, and two corresponding simplified methods, such as time discretization and lumped parameters were put forward. Using a method of lumped parameters, the model for simulation of time course of DO, pH in the column air-lift photobioreactor and prediction of CO2, O2 concentrations in the outlet gas under different CO2 concentration in the aeration gas was thoroughly discussed. Experimental data were also used to verify the model which could potentially be applied to rational design of the photobioreactor, high-density culture of microalgae and efficient removal of CO2.
Bioreactors ; Carbon Dioxide ; isolation & purification ; Hydrogen-Ion Concentration ; Models, Theoretical ; Photosynthesis

Objective To evaluate the effects of end tidal pressure of carbon dioxide (PETCO2) at different levels on the central drive and respiratory response in patients with chronic obstructive pulmonary disease (COPD). Methods After the completion of a pulmonary function test, 13 moderate COPD patients in stable stage and 10 healthy volunteers were studied with a CO2 rebreathing method by improving PETCO2 from 45 mm Hg to 70 mm Hg. The parameters of the central drive and respiratory response were monitored continuously and calculated at different PETCO2 levels. Results The experiment duration was respectively (8.5±1.6) rain in the COPD group and (16.3±3.2) min in the normal group when PETCO2 reached 70 mm Hg. Both groups experienced a linear increase in respiratory rate(RR), and the RR of normal group was higher than that of the COPD group. When PETCO2 was increased from 45 mm Hg to 55 mm Hg, the COPD group resulted in a linear increase in the tidal volume (VT) and minute ventilation (VE); VT increased from (0.68±0.25) L to (1.04±0.44) L and VE increased from (10.59±3.36) L/min to (20.13±4.52) L/min. But when PETCO2 was 55-70 mm Hg, VT and VE appeared a plat in the COPD group, while VT and VE maintained a linear increase in the normal group and higher than those of the COPD group. The ratio ofinspiratory time to duration of one breath (Ti/Ttot) was higher in the normal group than in the COPD group (P<0.05), while the Borg scale scores were lower in the normal group than in the COPD group (P<0.05). Both groups showed a linear increase in mean inspiratory volume per second (VT/T1) and root mean square (RMS), but when PETCO2 was increased from 65 mm Hg to 70 mm Hg, VT/T1 in the COPD group, it was obviously lower than that in the normal group (P<0.05). While RMS in the COPD group was higher than that in the normal group on different PETCO2 levels (P<0.05). COPD group showed a parabolic change in VE/RMS, which was significantly lower than that in the normal group (P<0.001). Conclusion During the early stage of CO2 rebreathing, the respiratory response and central drive of COPD patients show a linear increase, but during late stage, the ventilation appears a plat and ventilation-central coupling is obviously abnormal. The normal group shows a linear increase in respiratory response and central drive, in which respiratory response is higher and central drive is lower than in COPD group.

OBJECTIVETo dynamically investigate the morphology of human gastric cancer SGC-7901 cell clones, and then compare the tumorigenic ability of different clones in order to identify the tumor stem cell clones.

METHODSClones derived from gastric cancer SGC-7901 cells were assessed by morphological observation, and the clone formation rate and proportion of each clone were calculated. The expression of CD44 and CDX2 in different clones was detected by immunofluorescence microscopy and Western blot. Furthermore, different clones were isolated and cultured, and their self-renewal property was assayed. Cells of different clones were subcutaneously inoculated into nude mice and the tumorigenic ability of each group was determined.

RESULTSClones derived from gastric cancer SGC-7901 cells had three types, i.e. clones of tight, transitional and loose types. The total clone formation rate was (9.80 ± 1.07)%, and the proportion of tight, transitional and loose type clones was 10.2%, 56.0% and 33.8%, respectively. The results of immunofluorescence microscopic examination showed that the signal of CD44 was significantly stronger in the tight clones than in the transitional and loose clones, however, the signal of CDX2 was weakest in the tight colonies. The results of Western blot were consistent with that of immunofluorescence microscopic observation. SGC-7901 cells of tight clones possessed strong ability of self-renewal and in vivo tumorigenicity in the nude mice.

CONCLUSIONSGC-7901 cell clones vary in morphology and differentiation, and the tight type clones may include rich gastric cancer stem cells.

Animals ; CDX2 Transcription Factor ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Clone Cells ; classification ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplastic Stem Cells ; cytology ; metabolism ; Random Allocation ; Stomach Neoplasms ; metabolism ; pathology