Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

OBJECTIVETo evaluate the fatality rate of pneumoconiosis as well as the contributory factors in China in order to provide a foundation for prolonging the patients' lives.

METHODSChina National Knowledge Infrastructure (CNKI) and Wanfang Databases were searched to collect observational studies published between Jan, 2000 and Oct, 2013 on pneumoconiosis case fatality rate. Articles meeting the inclusion criteria were reviewed systematically, and analyzed by using Stata/SE 12.0, according to stage and type of pneumoconiosis and whether complicated with tuberculosis.

RESULTS41 papers were included for meta-analysis. The pooled total case fatality rate of pneumoconiosis was 31.2%. The pooled case fatality rate of pneumoconiosis patients of stage 1, 2 and 3 were 25.4%, 39.8%and 57.5%, respectively. The pooled case fatality rate of patients with silicosis, coal worker's pneumoconiosis, foundry worker's pneumoconiosis, asbestosis and cement pneumoconiosis were 35.8%, 32.4%, 24.7%, 35.1%and 5.5%, respectively. The complication with tuberculosis was a risk factor for the death of pneumoconiosis patients and the pooled RR was 1.82 (95%CI: 1.59∼2.08).

CONCLUSIONThere are significant differences in the case fatality rate of pneumoconiosis among different stages and different types of pneumoconiosis and whether complicated with tuberculosis.

Anthracosis ; mortality ; Asbestosis ; mortality ; China ; Humans ; Life Support Care ; Occupational Exposure ; Pneumoconiosis ; mortality ; Risk Factors ; Silicosis ; mortality ; Tuberculosis ; complications