Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B.

INTRODUCTION AND OBJECTIVES: Hepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB. PATIENTS AND METHODS: Patients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models. RESULTS: Sixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study. CONCLUSION: Although it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.

The effects of alloying elements Al and In on Ni-Mn-Ga shape memory alloys, from first principles.

The electronic structures and formation energies of the Ni(9)Mn(4)Ga(3-x)Al(x) and Ni(9)Mn(4)Ga(3-x)In(x) alloys have been investigated using the first-principles pseudopotential plane-wave method based on density functional theory. The results show that both the austenite and martensite phases of Ni(9)Mn(4)Ga(3) alloy are stabilized by Al alloying, while they become unstable with In alloying. According to the partial density of states and structural energy analysis, different effects of Al and In alloying on the phase stability are mainly attributed to their chemical effects. The formation energy difference between the austenite and martensite phases decreases with Al or In alloying, correlating with the experimentally reported changes in martensitic transformation temperature. The shape factor plays an important role in the decrease of the formation energy difference.

Superoxide dismutase activity and malondialdehyde level in plasma and morphological evaluation of acute severe hemorrhagic shock in rats.

OBJECTIVES: The aim of the study was to investigate the changes of the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in plasma and organ damage during the acute severe hemorrhagic shock (ASHS), as well as to analyze their relationship. METHODS: Twenty male Wistar rats (230-270 g) were randomly divided into sham hemorrhage shock (SHS) group and ASHS group. Acute severe hemorrhagic shock rats were induced by drawing blood through a femoral arterial catheter for 15 minutes with the final mean arterial blood pressure decreased to 35 to 40 mm Hg. The animals were killed after the mean arterial blood pressure was maintained at this level for 1 hour. The activity of SOD and the level of MDA in plasma were measured, and pathologic changes of the major organs (heart, liver, spleen, lung, kidney, and brain) were observed by microscopy. RESULTS: The SOD activities and MDA levels in the ASHS group both increased continuously during the whole experiment. The SOD activities and MDA levels in plasma were not significantly different between the prehemorrhagic stage of ASHS and that of SHS (P > .05). The SOD activities and MDA levels were significantly higher in the ASHS initial stage than in the prehemorrhagic stage (P < .01). Compared with the ASHS initial stage, there was a significant (P < .01) increase in SOD activities and MDA levels in the ASHS end stage. Severe microscopic injuries appeared in the major organs (heart, liver, spleen, lung, kidney, and brain) of ASHS rats. CONCLUSION: The changes of the activity of SOD and the level of MDA in ASHS may have a positive correlation.

Thoracic aggressive vertebral hemangioma with neurologic deficit: A retrospective cohort study.

The aim of this study is to evaluate the safety and effectiveness in the treatment of thoracic aggressive vertebral hemangiomas (AVHs) with neurologic deficit by multiple surgical treatments.The clinical and radiographic data of 5 patients suffering from thoracic AVHs with neurologic deficit and treated by multiple surgical treatments, including percutaneous curved vertebroplasty (PCVP) combined with pedicle screw fixation and decompressive laminectomy, were reviewed and analyzed retrospectively.Five patients (3 women and 2 man, with a mean age of 57.40 ±â€Š11.93) were diagnosed with AVHs from July 2010 to April 2016. All of them had objective neurologic deficit, myelopathy, and back pain. They underwent multiple surgical treatments and were followed-up for 12 to 23 months. At final follow-up, Frankel Grade D was achieved in all 5 patients. Patients were free from pain and neurologic symptoms, and the functional status was improved. No major complication was found.The treatment of AVHs with neurologic deficit is a challenge for surgeons. PCVP combined with pedicle screw fixation and decompressive laminectomy is safe and effective, and can be used for AVHs with neurologic deficit. Further studies with more samples are required to validate the effectiveness and safety of PCVP combined with pedicle screw fixation and decompressive laminectomy.

Magnetic nanochains of metal formed by assembly of small nanoparticles.

Ni nanochains are synthesized with diameters of 150-250 nm and lengths of 0.5-2 microm by assembly of small nanoparticles, which exhibit a magnetic coercivity over two orders of magnitude larger than that of bulk Ni.

[Effect of phosphatase PHLPP1 gene transfer on the proliferation of human umbilical vein endothelial cells].

OBJECTIVE: To investigate the constituent expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in human umbilical vein endothelial cells (HUVECs) and the effect of PHLPP1 gene transfer on the proliferation of the cells in vitro. METHODS: Cultured HUVECs were transfected with pcDNA3-GFP or pcDNA3HA-PHLPP1 via lipofectamine 2000. The cell proliferation ability was determined by cell counting and MTT colorimetric assay, and Western blotting was used to detect the protein expression of PHLPP1 in the cells. RESULTS: No PHLPP1 protein was detected in the non-transfected cells or pcDNA3-GFP-transfected cells. pcDNA3HA-PHLPP1 gene transfection significantly increased PHLPP1 expression in the HUVECs (P<0.01), but the cell proliferation status remained unchanged (P>0.05). The absorbance of the cells measured by MTT assay was 0.134-/+0.0152, 0133-/+0.014 and 0.137-/+0.016, with cell counts of (8.293-/+0.962)x10(5), (7.937-/+0.101)x10(5) and (8.127-/+0.112)x10(5), respectively, showing no significant differences between the 3 groups (P>0.05). CONCLUSIONS: Phosphatase PHLPP1 may not be the most important signal protein in the regulation of HUVEC proliferation.

[Expression of human apolipoprotein A- I in baculovirus-insect cell system].

Apolipoprotein A- I is the major apolipoprotein in high-density lipoprotein known to have a wide range of physiological functions, the best-studied one of which is in regulating cholesterol metabolism and preventing arteriosclerosis. Human blood has been the only source of this protein. To facilitate further research and application, it is essential to produce it through genetic engineering. In the current research, the baculovirus-insect cell system was used to overexpress human apolipoprotein A- I . Two recombinant baculoviruses were constructed. The first one expressed a pro form of apoA- I lacking native signal peptide. The recombinant protein was found to remain mainly inside cells in the early phase of infection, while being largely excreted to the medium late in infection. The second one used a heterologous signal peptide, snake phospholipase A2 inhibitor alpha subunit signal peptide, to lead the secretion of mature apoA- I. In contrast to the first virus, recombinant apoA- I was found in the culture medium at the early phase of virus infection. The mature apoA- I was purified from culture medium using Phenyl Sepharose hydrophobic interaction chromatography (HIC) and eluted with water and Propylene. This work shows that snake phospholipase A2 inhibitor a subunit signal peptide can be used to secret human apoA- I in insect cells, but the efficiency of its secretion is limited when the expression level is high.