Background & Objective: No clinical study of any interferon beta therapy has yet been successfully conducted in Chinese multiple sclerosis patients, probably due to the low incidence of this disease in China. The primary objective of this study was to demonstrate that treating multiple sclerosis patients of Chinese origin with interferon beta-1b has a beneficial effect on disease course, as measured by the decrease of newly active lesions on magnetic resonance imaging. Methods: Chinese patients diagnosed with relapsing-remitting or secondary-progressive multiple sclerosis were enrolled in this multicenter, open label, single-arm study. Following a 3-month pre-treatment phase, patients were treated with 250 µg interferon beta-1b subcutaneously every other day for 6 months. Patients had regular assessments for treatment safety and efficacy of the treatment. Results: Thirty seven patients completed the trial. Significant decreases in the number of newly active lesions were observed in the 6-month treatment period compared with the pre-treatment period (median decrease 1.5 lesions, p<0.001). Most adverse events were mild and transient and no serious ones were observed. Conclusions: Treatment with interferon beta-1b significantly reduced the occurrence of new lesions and was well tolerated in this Chinese population. These findings support the use of interferon beta- 1b for treating Chinese MS patients.

OBJECTIVE: To study the characteristics of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H-ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in predicting the outcome of syndrome. METHODS: Five hundred and forty cases fulfilling the criteria of MODS were divided into four groups according to the altitude of their inhabitation area: control group (on plain, CG, n=113, altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517 m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the diagnostic criteria of Lushan conference and Marshall (1995) commonly used on plain, and Lanzhou criteria drafted by the authors, three data analyzing models were set up to draw the receiver operating characteristic (ROC) curves, the Yordon Index and the optimum cutoff points of the parameters were calculated and the accuracy of the three respective diagnostic criteria was evaluated in predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of MODS were analyzed using the method of stepwise forward regress model. RESULTS: Following the increase in altitude, Lanzhou criteria was clearly superior to the other two criteria in the area of ROC, the sensitivity, the specificity, and also for the optimum cutoff points of MODS. Multi-variable regression analysis showed that the impacting factor of Lanzhou criteria was the highest (P<0.05). CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS are not suitable in moderately high or high altitude areas. It is necessary to set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics might change in areas 1,500 m altitude or higher. The pathophysiological mechanism might be attributable to peculiar biologic reactions due to hypoxia stress reaction, and it is worth further study.
Altitude ; Multiple Organ Failure/*diagnosis ; Prognosis ; ROC Curve ; Regression Analysis ; Respiratory Distress Syndrome, Adult/*diagnosis ; Severity of Illness Index

OBJECTIVE: To observe the effect of different doses and timing of normal saline (NS) resuscitation combined with norepinephrine (NE) on endothelial glycocalyx in rabbits with early septic shock. METHODS: Thirty New Zealand male rabbits were randomly divided into sham group, model group, 30 mL and 60 mL timely resuscitation groups (30 mL and 60 mL timely group), and 30 mL delayed resuscitation group (30 mL delayed group) with 6 rabbits in each group. The rabbit model of septic shock was reproduced by cecal ligation and puncture (CLP). The rabbits in sham group were only received abdominal cavity open without cecal and ligation. The rabbits in 30 mL and 60 mL timely groups and 30 mL delayed group were intravenous infused with 30 mL/kg or 60 mL/kg NS immediately or 1 hour after model reproduction for 1 hour, and the mean arterial pressure (MAP) was maintained over 75 mmHg (1 mmHg = 0.133 kPa) compared with intravenous pumping of 0.02-0.05 μg×kg^-1×min^-1 NE followed by 5 mL/h NS infusion till the end of the experiment. The rabbits in sham and model groups were only given 5 mL/h NS. The changes in arterial blood gas before and immediately after resuscitation were observed in three fluid resuscitation groups. The internal jugular vein blood was collected at 0, 3, 6 hours after model reproduction. The levels of syndecan-1 (polysaccharide envelope marker) in plasma were determined by enzyme linked immunosorbent assay (ELISA). The rabbits were sacrificed at 6 hours after model reproduction, and the lung tissue was harvested. Western Blot was used to determine the protein expressions of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 2 (MMP-2) and syndecan-1. The positive expression of syndecan-1 in lung tissue was observed by immunohistochemical method. RESULTS: (1) Blood gas analysis: compared with the results before resuscitation, the levels of lactic acid (Lac) after resuscitation in three fluid resuscitation groups were significantly decreased, especially in 30 mL timely group; the central venous blood oxygen saturation (ScvO₂) was significantly increased, especially in 30 mL delayed group. Oxygenation index (PaO₂/FiO₂) was improved in 30 mL timely and 30 mL delayed resuscitation groups, which was decreased in 60 mL delayed group. (2) Plasma marker: compared with sham group, plasma syndecan-1 level in model group was significantly increased with a time-dependent manner. Plasma syndecan-1 levels at 3 hours in 30 mL timely and 30 mL delayed groups were significantly decreased as compared with those of model group (ng/L: 138.0±2.4, 139.7±15.7 vs. 161.5±4.1, both P < 0.05), but it was significantly increased at 6 hours in 30 mL delayed group (ng/L: 213.1±19.4 vs. 206.4±15.5, P < 0.05). The plasma syndecan-1 levels at 3 hours and 6 hours in 60 mL timely group were significantly higher than those in model group (ng/L: 233.0±28.9 vs. 161.5±4.1, 252.3±27.2 vs. 206.4±15.5, both P < 0.05). (3) Protein expression in lung tissue: compared with sham group, the protein expressions of ICAM-1 and MMP-2 in lung tissue of model group were significantly increased, and syndecan-1 protein expression was significantly decreased. After 30 mL timely or 30 mL delayed resuscitation, the protein expressions of ICAM-1 and MMP-2 in lung tissue were significantly decreased, and syndecan-1 protein expression was significantly increased, especially in 30 mL timely group, which showed statistical differences as compared with those of model group (ICAM-1 protein: 0.56±0.09 vs. 1.04±0.05, MMP-2 protein: 0.83±0.15 vs. 1.06±0.06, syndecan-1 protein: 2.09±0.08 vs. 0.99±0.03, all P < 0.05). The change tendency of protein expressions in 60 mL timely group was opposite to the other two resuscitation groups. (4) Immunohistochemistry: the positive expression of syndecan-1 in lung tissues was significant in the sham group, and it was lowered in model group. The positive expression of syndecan-1 was increased after 30 mL timely or 30 mL delayed resuscitation, but further weakened in 60 mL timely group. CONCLUSIONS The dose and timing of resuscitation with NS in septic shock can affect pulmonary vascular endothelial glycocalyx function. The timely resuscitation with 30 mL NS in combination with NE plays a protective effect on endothelial cell and glycocalyx. However, NS resuscitation which was not timely or excessive infusion can make the glycocalyx degradation more obvious, resulting in increased endothelial permeability, microcirculation damaged, thus aggravate lung injury.
Animals ; Fluid Therapy ; Glycocalyx ; Male ; Matrix Metalloproteinase 2 ; Rabbits ; Resuscitation ; Shock, Septic

The aim of this study was to investigate the effects of miR-155 inhibitor transfection on the proliferation and apoptosis of THP-1 cells. The miR-155 inhibitor was transfected into THP-1 cells (THP-1I) by using X-treme GENE siRNA transfection reagent. Cells without transfection (THP-1C) and cells with negative transfection (THP-1IC) were used as controls. Quantitative real-time polymerase chain reaction (RT-PCR) was performed to detect the expression of miR-155 and relative expression of SHIP1 mRNA in the cells. Cell proliferation was assayed using CCK-8 method. Cell apoptosis were detected by flow cytometry. The expression of SHIP1, TAKT and pAKT in THP-1 cells were detected by Western blot. The results indicated that compared with THP-1C and THP-1IC, the expression of miR-155 in THP-1I cells was significantly reduced; miR-155 inhibition significantly increased apoptosis rate in THP-1 cells (P < 0.05) ; miR-155 inhibition in THP-1 cells caused no significant alteration in SHIP1 mRNA level but significantly increased its protein content, indicating some post-transcriptional modulations might exist underlying the modulation of miR-155 to SHIP1, the miR-155 caused significantly reduced protein level of pAKT (P < 0.05) without interfering TAKT protein content. It is concluded that the miR-155 inhibition may promote THP-1 cell apoptosis through increasing SHIP1 protein content and impairing its downstream PI3K/AKT signaling pathway. This study suggests that miR-155 inhibition may be a promising therapy strategy for treating acute myeloid leukemia (AML).
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia ; genetics ; MicroRNAs ; genetics ; Phosphatidylinositol 3-Kinases ; RNA, Messenger ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Transfection