Assessing the causal role of physical activity and leisure sedentary behaviours with chronic obstructive pulmonary disease: a Mendelian randomisation study.

BACKGROUND: Observational studies show that patients with chronic obstructive pulmonary disease (COPD) tend to be sedentary during leisure time. Physical activity (PA) may reduce the risk of COPD, but the causal relationship is unclear. We used a Mendelian randomisation (MR) method to elucidate the association of leisure sedentary behaviours (LSB) and PA with lung function and COPD. METHODS: Data on LSB (n=422 218), PA (n=608 595), COPD (n=299 929) and lung function (n=79 055) were obtained from the large-scale genome-wide association study. Causal inference used inverse variance-weighted, MR-Egger and weighted median. Sensitivity analysis was performed to assess heterogeneity and pleiotropy, and radial MR was used to distinguish outliers. The primary outcome was analysed by multifactorial MR adjusted for daily smoking. RESULTS: The inverse variance weighted analysis indicated that increased moderate-to-vigorous PA (MVPA) is associated with higher levels of forced vital capacity (FVC) (beta=0.27, 95% CI 0.12 to 0.42; p=3.51×10-4). For each increment of 2.8 hours in television watching, the odds of COPD were 2.25 times greater (OR=2.25; 95% CI 1.84 to 2.75; p=2.38×10-15). For early-onset COPD, the odds were 2.11 times greater (OR=2.11; 95% CI 1.56 to 2.85; p=1.06×10-6), and for late-onset COPD, the odds were 2.16 times greater (OR=2.16; 95% CI 1.64 to 2.84; p=3.12×10-8). Similarly, the odds of hospitalisation for COPD were 2.02 times greater with increased television watching (OR=2.02; 95% CI 1.59 to 2.55; p=4.68×10-9). Television watching was associated with lower FVC (beta=-0.19, 95% CI -0.28 to -0.10; p=1.54×10-5) and forced expiratory volume in the 1 s (FEV1) (beta=-0.16, 95% CI -0.25 to -0.08; p=1.21×10-4) levels. The results remained significant after adjustment for smoking. CONCLUSIONS: Our study suggests a potential association with LSB, particularly television watching, is associated with higher odds of COPD and lower indices of lung function as measured continuously, including FEV1 and FVC. Conversely, an increase in MVPA is associated with higher indices of lung function, particularly reflected in increased FVC levels.

Preparation and evaluation of stingray skin collagen/oyster osteoinductive composite scaffolds.

The regeneration of bone defects is a major challenge for clinical orthopaedics. Herein, we designed and prepared a new type of bioactive material, using stingray skin collagen and oyster shell powder (OSP) as raw materials. A stingray skin collagen/oyster osteoinductive composite scaffold (Col-OSP) was prepared for the first time by genipin cross-linking, pore-forming and freeze-drying methods. These scaffolds were characterized by ATR-FTIR, SEM, compression, swelling, cell proliferation, cell adhesion, alkaline phosphatase activity, alizarin red staining and RT-PCR etc. The Col-OSP scaffold had an interconnected three-dimensional porous structure, and the mechanical properties of the Col-OSP composite scaffold were enhanced compared with Col, combining with the appropriate swelling rate and degradation rate, the scaffold was more in line with the requirements of bone tissue engineering scaffolds. The Col-OSP scaffold was non-toxic, promoted the proliferation, adhesion, and differentiation of MC3T3-E1 cells, and stimulated the osteogenesis-related genes expressions of osteocalcin (OCN), collagen type I (COL-I) and RUNX2 of MC3T3-E1 cells.

In-situ formable dextran/chitosan-based hydrogels functionalized with collagen and EGF for diabetic wounds healing.

Delayed or non-healing skin wounds causing gangrene or even amputation, greatly threats diabetic patients lives. Herein, a bioactive, in-situ formable hydrogel based wound dressing was designed through simple Schiff base reaction. Oxidized dextran (OD) and carboxyethyl chitosan (CEC) were crosslinked together and applied as the main porous framework of hydrogel. To improve the mechanical strength and biocompatibility, collagen (Col) and EGF (Epidermal Growth Factor) were introduced into OD-CEC precursors: (1) after addition of only Col, the mechanical strength of hydrogels was improved by participating the functional -NH2 group of Col into the crosslinking process. Moreover, swelling ratio was as high as 750% on 3%OD-3%CEC-Col (water retention rate was 65 wt% after 7 days). (2) Once we introduced both Col and EGF into the OD-CEC hydrogel, the proliferation of mouse embryonic fibroblast (NIH 3T3) cells was promoted using 3%OD-3%CEC-Col/EGF, an accelerated wound healing was observed with 86% wound closure after only 14 operative days. Hematoxylin and eosin (H&E) staining and Masson staining indicated the synergy of Col and EGF might promote new tissue's formation, well collagen distributions and thus accelerate skin regeneration, presenting great potentials in wound healing of diabetic patients.

[Mechanism of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma on SIRT1 autophagy pathway of endothelial cell senescence induced by hydrogen peroxide].

This study aims to explore the effect of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma(hereinafter referred to as GNS) on the SIRT1-autophagy pathway of endothelial cell senescence induced by hydrogen peroxide(H_2O_2). To be specific, vascular endothelial cells were classified into the blank control group(control), model group(model), model + DMSO group(DMSO), resveratrol group(RESV), and GNS low-dose(GNS-L), medium-dose(GNS-M), and high-dose(GNS-H) groups. They were treated with H_2O_2 for senescence induction except the control. After intervention of cells in each group with corresponding drugs for 24 h, cell growth status was observed under an inverted microscope, and the formation of autophagosome under the transmission electron microscope. In addition, the changes of microtubule-associated protein 1 light chain 3ß(LC3 B) were detected by immunofluorescence staining. The autophagy flux was tracked with the autophagy double-labeled adenovirus(mRFP-GFP-LC3) fusion protein. Dansylcadaverine(MDC) staining was employed to determine the autophagic vesicles, and Western blot the expression of sirtuin 1(SIRT1), ubiquitin-binding protein p62, and LC3Ⅱ. After H_2O_2 induction, cells demonstrated slow growth, decreased adhesion ability, raised number of SA-ß-gal-stained blue ones, a certain number of autophagosomes with bilayer membrane and secondary lysosomes in the cytoplasm, and slight rise of autophagy flux level. Compared with the model group, GNS groups showed improved morphology, moderate adhesion ability, complete and smooth membrane, decreased SA-ß-gal-stained blue cells, many autophagosomes, autophagic vesicles, and secondary lysosomes in the cytoplasm, increased autophagolysosomes, autophagy flux level, and fluorescence intensity of LC3 B and MDC, up-regulated expression of SIRT1 and LC3Ⅱ, and down-regulated expression of p62, suggesting the improvement of autophagy level. GNS can delay the senescence of vascular endothelial cells. After the intervention, the autophagy flux and related proteins SIRT1, LC3Ⅱand p62 changed significantly, and the autophagy level increased significantly. However, EX527 weakened the effect of Chinese medicine in delaying vascular senescence. GNS may delay the senescence of vascular endothelial cells through the SIRT1 autophagy pathway.

[Development of Thrombus Aspiration Catheter].

Coronary disease is one of the highest mortality diseases in the world,and interventional therapy has been the best treatment choice for its low risks,high efficiency,less wound and rapid recovery after the operation.Thrombus aspiration catheter is one of the most important equipment in the interventional therapy instrument of coronary disease.This paper is based on the demand of clinical and market,designed and manufactured aspirated catheter for the treatment of coronary thrombosis.Through the performance comparison of the material,confirmed the main material quality of thrombus aspiration catheter and its organization.We also made the appraisement for the function of the material and the main performance of the thrombus aspiration catheter.The experiment turned out that our catheter performance is stable and also with highly reliable,which is absolutely fit for the using requirements of the clinical.

[Investigation of clinical practice and side effects of Shenfu injection].

OBJECTIVE: To investigate the status of clinical practices and side effects related to Shenfu injection. METHOD: It was searched the Chinese medical citation index (CMCI) database and China national knowledge infrastructure (CNKI) database using the word "Shenfu injection". Original clinical studies of Shenfu injection which were published from January 1 987 to March 2012 in Chinese magazines were included. RESULT: A total of 1 433 relevant clinical studies were identified. It was investigated and analyzed the side effects of Shenfu injection. For cases with side effects, the diseases for treatment, the medication dosage, the course, and menstrum of treatment for the side effects were evaluated. All the side effects were mild except five cases of serious adverse reaction. CONCLUSION: Shenfu injection has been widely used in clinical patients since it came into the market in 1987. However, there are some problems in its clinical practices, such as deficiency in selecting and expanding diseases for treatment, evaluating the dosage and treatment method. Therefore, it is imperative to evaluate drugs by literature and good clinical application after the drugs come into the market with evidence-based medicine.

[Discussion on methods of sample size estimation in conducting clinical reevaluation of postmarketing Chinese medicine].

Sample size is one of important factors determining the results of a clinical trial, and the choice of sample size estimation methods is related to the specific design of clinical trials. On clinical safety reevaluation of postmarketing Chinese medicine, we often design cohort study, case-control study, nested case-control study or hospital centralized monitoring, which need large sample sizes. In evaluating the effectiveness of postmarketing Chinese medicine widely applied in the large population, pragmatic randomized controlled trial (PRCT) is more suitable than explanatory randomized controlled trial (ERCT). ERCT is necessary to conduct confirmatory study for new indications of postmarketing Chinese medicine. According to the specific purpose, design type and evaluation index, we choose the suitable sample size estimation method, and determine the corresponding parameters. We must estimate and determine the suitable sample size according to the specific clinical evaluation design, with comprehensive consideration of the test power, research cost and practical operability.

[Study on building index system of risk assessment of post-marketing Chinese patent medicine based on AHP-fuzzy neural network].

Currently massive researches have been launched about the safety, efficiency and economy of post-marketing Chinese patent medicine (CPM) proprietary Chinese medicine, but it was lack of a comprehensive interpretation. Establishing the risk evaluation index system and risk assessment model of CPM is the key to solve drug safety problems and protect people's health. The clinical risk factors of CPM exist similarities with the Western medicine, can draw lessons from foreign experience, but also have itself multi-factor multivariate multi-level complex features. Drug safety risk assessment for the uncertainty and complexity, using analytic hierarchy process (AHP) to empower the index weights, AHP-based fuzzy neural network to build post-marketing CPM risk evaluation index system and risk assessment model and constantly improving the application of traditional Chinese medicine characteristic is accord with the road and feasible beneficial exploration.

[Sample size calculation in clinical post-marketing evaluation of traditional Chinese medicine].

In recent years, as the Chinese government and people pay more attention on the post-marketing research of Chinese Medicine, part of traditional Chinese medicine breed has or is about to begin after the listing of post-marketing evaluation study. In the post-marketing evaluation design, sample size calculation plays a decisive role. It not only ensures the accuracy and reliability of post-marketing evaluation. but also assures that the intended trials will have a desired power for correctly detecting a clinically meaningful difference of different medicine under study if such a difference truly exists. Up to now, there is no systemic method of sample size calculation in view of the traditional Chinese medicine. In this paper, according to the basic method of sample size calculation and the characteristic of the traditional Chinese medicine clinical evaluation, the sample size calculation methods of the Chinese medicine efficacy and safety are discussed respectively. We hope the paper would be beneficial to medical researchers, and pharmaceutical scientists who are engaged in the areas of Chinese medicine research.