Exploration of the Minimum Necessary FVIII Level at Different Physical Activity Levels in Pediatric Patients with Hemophilia A

BACKGROUND: Physical activity can increase joint stability and reduce the risk of injury in hemophilia patients. There is limited clinical data on target trough FVIII levels during physical activity in hemophilia A patients. Hence, this study aimed to explore the target trough FVIII level required to avoid bleeding during different physical activities in hemophilia A patients. METHODS: Patients with severe or moderate hemophilia A, who underwent pharmacokinetics (PK) tests at our center were enrolled in this study. Physical activities and clinical information such as bleeding were recorded. The FVIII level during physical activity was calculated by the WAPPS-Hemo. RESULTS: A total of 105 patients were enrolled in this study. A total of 373 physical activities were recorded, of which 57.6% (215/373) was low-risk activities and the remaining 42.4% (158/373) was medium-risk activities. Most common physical activities were bicycling (59.0%), swimming (43.8%), running (48.6%), and jumping rope (41.0%). The FVIII trough level of low-risk physical activity was 3.8 IU/dl (AUC = 0.781, CONCLUSION: The minimum necessary FVIII level increased with higher risk physical activity, irrespective of arthropathy

What Is the Amount of China’s Building Floor Space from 1996 to 2014?

The amount of building floor space (BFS) plays a key role in the energy and material demand prediction. Unfortunately, BFS estimation has faced the challenge of ineffective and inadequate approaches, and thus reliable data concerning China’s BFS is unavailable. This study proposes a new estimation method for China’s BFS and then estimates historical BFS by type in China from 1996 to 2014. The results show that total Chinese BFS grew from 28.1 billion m2 in 1996 to 61.3 billion m2 in 2014, increasing more than twice, with an annual growth rate of 4.4% from 1996 to 2014. During 1996–2014, urban residential BFS witnessed the highest annual increase rate (9.3%), while the growth rate for commercial and rural residential BFS was lower: 4.4% and 1.6%, respectively. By comparing with available statistics data, this study finds the model deviations are well below 5%, which indicates the reliability of the proposed method and robustness of the results. The proposed method not only can address the deficiencies of statistic yearbook and overcome the shortages of previous estimation approaches but also can derive more accurate and reliable data. This study lays a sound basis for the following study on building stock and building energy efficiency work

Research on abutment stress distribution of roof-cutting coalface: numerical simulation and field measurement

Abstract During the processing of deep mining, revealing the distribution of abutment pressure is significant for controlling stability of the entry. In this study, the abutment pressure distribution of roof-cutting coalface was investigated by FLAC3D and self-developed flexible detection unit (FDU). In the numerical simulation, the double-yield model was built to analyze the goaf abutment pressure under the fracturing roofs to maintain entry (FRME). Compared with the non-fracturing side, the peak value of the advanced abutment pressure on the fracturing side is reduced by 19.29% on average, the influence range (span) increases by 30.78% and the distance between the peak value and the working face increases by 66.7%. The goaf abutment pressure within 23m near the cutting side is significantly higher than other areas along the dip. The FDU was employed in the coalface to record the change of advanced abutment stress. And the field measured results are in well agreement with the numerical results

Metabolic profiling of parthenolide: Characterized by bioactive organosulfur compounds involving in hydrogen sulfide regulation

Parthenolide (PA) shows promising therapeutic effect on ulcerative colitis and colorectal cancer, and can ameliorate colon inflammation in a gut microbiota-dependent manner. In the present study, an effective UHPLC-QTOF-MS method aided by rat intestinal microbiota biotransformation was applied to characterize 34 metabolites (including a series of characteristic R-Sn-R type organosulfur compounds) of PA for the first time. Noteworthy, organosulfur metabolites PA-S2-PA and PA-S3-PA could react with cysteine to generate H2S via persulfide/polysulfide intermediates and significantly inhibit colonic cancer HT-29 and HCT116 cells viability and pro-inflammatory cytokine IL-6 release. These results indicated that PA and its organosulfur metabolites involved in H2S regulation in intestinal tract, which should be beneficial for a more in-depth understanding of the action mechanism of PA

A semiquantitative color Doppler ultrasound scoring system for evaluation of synovitis in joints of patients with blood-induced arthropathy

Abstract Background Intra-articular bleeds in patients with inherited bleeding disorders lead to active synovitis which may progress to a chronic state over time. We explored the diagnostic value of color Doppler ultrasound in detecting synovitis in boys with bleeding disorders. Results Sixty boys with hemophilia and 3 boys with type 3 von Willebrand disease aged 5 to 18 years (median 12.3 years) were imaged by gray-scale and color Doppler ultrasound (US) in three centers (Beijing, China [n = 22], Guangzhou, China [n = 12] and Toronto, Canada [n = 29])) in this observational study. Images were independently reviewed by two radiologists blinded to clinical data using a subjective semi-quantitative scoring system and objective measurements of synovial thickness and vascularity. Inter-reader reliability for using subjective versus objective color Doppler US methods for assessing synovial vascularity was excellent for the subjective method and moderate/lower range of substantial for the objective method. Agreement between degree of vascularity on color Doppler and extent of synovial hypertrophy on gray-scale US was overall poor for Canada data and moderate for China data. Correlations between degree of vascularity on color Doppler and synovial hypertrophy on gray-scale US, and clinical constructs (total and itemized HJHS scores and total Pettersson X-ray scores) for assessment of blood-induced arthropathy were all poor. Conclusion Color Doppler US is a valuable scoring method for evaluating reactive synovitis in joints of subjects with inherited bleeding disorders and holds potential for assessing post-bleed reactive synovitis once further information on its association with timing of the joint bleed becomes available in the literature

Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo

Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues but low in many normal tissues, GA could therefore produce tissue-specific proteasome inhibition and tumor-specific toxicity, with clinical significance for designing novel strategies for cancer treatment