Knee osteoarthritis pendulum therapy : in vivo evaluation and a randomised, single-blind feasibility clinical trial

Background. Exercise is recommended as the first-line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg-swinging exercise practiced in China, called ‘KOA pendulum therapy’ (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism in vivo in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial. Methods. IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up. Results. The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was −11.32 ± 0.21 (cmH2O), whereas in KOA patients, it was −3.52 ± 0.34 (cmH2O). Measures were completed by 100% of participants in all groups with 95–98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (p < 0.01), but no significant differences between the two groups. Conclusion. We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer-term intervention and a large sample randomized-single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises

Study of SPRC Impact Resistance Based on the Weibull Distribution and the Response Surface Method

Silica-fume–polyvinyl-alcohol-fiber-reinforced concrete (SPRC) is a green and environmentally friendly composite material incorporating silica fume and polyvinyl alcohol fiber into concrete. To study the impact resistance of SPRC, compressive-strength and drop hammer impact tests were conducted on SPRC with different silica-fume and polyvinyl-alcohol-fiber contents. The mechanical and impact resistance properties of the SPRC were comprehensively analyzed in terms of the compressive strength, ductility ratio and impact-energy-dissipation variation. Based on the impact resistance of the SPRC, the impact life of SPRC with different failure probabilities was predicted by incorporating the Weibull distribution model, and an impact damage evolution equation for SPRC was established. The impact life of SPRC under the action of silica-fume content, polyvinyl-alcohol-fiber content and failure probability was analyzed in depth by the response surface method (RSM). The research results show that, when the content of silica fume is 10% and the content of polyvinyl alcohol fiber is 1%, the compressive strength and impact resistance of SPRC are the best. The RSM response model can effectively predict and describe the impact life of SPRC specimens under the action of three factors

The miR-31/FIH1 pathway involved in TGFβ-induced liver fibrosis

Abstract MicroRNAs (miRNAs) are small, non-coding RNAs that regulate various biological processes, including liver fibrosis. Hepatic stellate cells (HSC) play a central role in the pathogenesis of liver fibrosis. By microarray profiling and real-time PCR, we noted that micorRNA-31 (miR-31) expression was significantly increased during activation of HSC from rat, mouse and human respectively. We found miR-31 was particularly upregulated in HSC but not in Hepatocyte during fibrogenesis. Thus, we hypothesized that miR-31 may mediate liver fibrosis. In our study, we observed that reduction of miR-31 expression significantly inhibited HSC activation while overexpression of its expression obviously promoted HSC activation. Moreover, overexpression of miR-31 promoted HSC migration while inhibition of miR-31 had an opposite effect. The biological function of miR-31 during HSC activation might be through targeting FIH1, a suppressor of hypoxia-inducible factor (HIF-1), as knockdown of FIH1 by short hairpin RNA (shRNA) could mimic the effects of miR-31. In addition, we found that only TGFβ, a pivotal regulator in liver fibrosis, remarkably increased miR-31 expression in HSC. And that the effects of TGFβ upon HSCs can be partially counteracted by inhibition of miR-31. Additionally, ChIP experiments and Luciferase reporter assay demonstrated that Smad3, a major TGF--downstream transcription factor, stimulated the transcription activity of miR-31 by binding directly to the promoter of miR-31. In conclusion, miR-31/FIH1 pathway associates with liver fibrosis, perhaps by participating TGFβ/Smad3 signaling in HSC. A c c e p t e d M a n u s c r i p

Antiproliferative Evaluation of Novel 4-Imidazolidinone Derivatives as Anticancer Agent Which Triggers ROS-Dependent Apoptosis in Colorectal Cancer Cell

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide, and more therapies are needed to treat CRC. To discover novel CRC chemotherapeutic molecules, we used a series of previously synthesized novel imidazolidin-4-one derivatives to study their anticancer role in several cancer cell lines. Among these compounds, compound 9r exhibited the best anticancer activity in CRC cell lines HCT116 and SW620. We further investigated the anticancer molecular mechanism of compound 9r. We found that compound 9r induced mitochondrial pathway apoptosis in HCT116 and SW620 cells by inducing reactive oxygen species (ROS) production. Moreover, the elevated ROS generation activated the c-Jun N-terminal kinase (JNK) pathway, which further accelerated apoptosis. N-acetylcysteine (NAC), an antioxidant reagent, suppressed compound 9r-induced ROS production, JNK pathway activation, and apoptosis. Collectively, this research synthesized a series of imidazolidin-4-one derivatives, evaluated their anticancer activity, and explored the molecular mechanism of compound 9r-induced apoptosis in CRC cells. The present results suggest that compound 9r has a potential therapeutic role in CRC. Hence, it deserves further exploration as a lead compound for CRC treatment

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

Background. Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism. Methods. Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot. Results. Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis. Conclusion. Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule

Detection and size measurements of pulmonary nodules in ultra-low-dose CT with iterative reconstruction compared to low dose

Background: In this study, the accuracy of ultra-low-dose computed tomography (CT) with iterative reconstruction (IR) for detection and measurement of pulmonary nodules was evaluated. Methods: Eighty-four individuals referred for lung cancer screening (mean age: 54.5 +/- 10.8 years) underwent low-dose computed tomography (LDCT) and ultra-low-dose CT. CT examinations were performed with attenuation-based tube current modulation. Reference tube voltage and current were set to 120 kV/25 mAs for LDCT and 80 kV/4 mAs for ultra-low-dose CT. CT images were reconstructed with filtered back projection (FBP) for LDCT, and with FBP and IR for ultra-low-dose CT datasets. A reference standard was established by a consensus panel of 2 different radiologists on LDCT. Volume and diameter of the solid nodules were measured on LDCT with FBP and ultra-low dose CT with FBP and IR. Interobserver and interscan variability were analyzed and compared by the Bland-Altman method. Results: A total of 127 nodules were identified, including 105 solid nodules, 15 part solid nodules, 7 ground glass nodules. On ultra-low-dose CT scans, the effective radiation dose was 0.13 +/- 0.11 mSv. A total of 113 (88.9%) and 110 (86.6%) true-positive nodules with FBP versus 117 (92.1%) and 118(92.9%) with IR were detected by two observers, respectively. The volume and size of the 105 solid nodules were measured, with mean volume/diameter of 46.5 +/- 46.6 mm(3) /5.1 +/- 1.6 mm. There was no significant difference in nodule volume or diameter measurements between ultra-low-dose CT and LDCT protocols for solid nodules. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Hepatitis E Virus Genotype 4, Nanjing, China, 2001–2011

During 2001–2011, hepatitis E virus (HEV) was found in the blood of patients in Nanjing, China. All HEV-positive patients had virus genotype 4; subgenotype 4a was predominant. The effective population of HEV in Nanjing increased in ≈1980 and continued until ≈2003 when it plateaued