Intracoronary Sarcoplasmic Reticulum CalciumATPase Gene Therapy in Advanced Heart Failure Patients with reduced Ejection Fraction: A Prospective Cohort Study

OBJECTIVE: Heart failure is a progressive and debilitating disease. Intracoronary sarcoplasmic reticulum calciumATPase gene therapy may improve the function of cardiac muscle cells. This study aimed to test the hypothesis that intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy can improve outcomes and reduce the number of recurrent and terminal events in advanced heart failure patients with reduced ejection fraction. METHODS: A total of 768 heart failure patients with reduced ejection fraction and New York Heart Association classification II to IV were included in this prospective cohort study. Patients either underwent intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy (CA group, n=384) or received oral placebo (PA group; n=384). Data regarding recurrent and terminal event(s), treatment-emergent adverse effects, and outcome measures were collected and analyzed. RESULTS: After a follow-up period of 18 months, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduced the number of hospital admissions (p=0.001), ambulatory treatments (p=0.0004), and deaths (p=0.024). Additionally, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy improved the left ventricular ejection fraction (po0.0001) and Kansas City Cardiomyopathy Questionnaire score (po0.0001). The number of recurrent and terminal events/patients were higher in the PA group than in the CA group after the follow-up period of 18 months (p=0.015). The effect of the intracoronary sarcoplasmic reticulum calciumATPase gene therapy was independent of the confounding variables. No new arrhythmias were reported in the CA group. CONCLUSIONS: Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduces the number of recurrent and terminal events and improves the clinical course of advanced heart failure patients with reduced ejection fraction

Laser induced arc dynamics destabilization in laser-arc hybrid welding

The interaction between laser and arc plasma is a central issue in laser-arc hybrid welding. We report a new interaction phenomenon called laser destabilizing arc dynamics in kilowatt fiber laser-TIG hybrid welding of 316L stainless steel. We found the laser action significantly oscillates the arc tail with a 1–3 kHz high frequency. Direct numerical simulation demonstrates that the destabilization mechanism is due to the high-speed oscillated metal vapor ejecting from the mesoscopic keyhole. More interestingly, the high-speed metal vapor could contrict the arc plasma by physical shielding. This provides a fundamentally different explanation from the generally adopted metal vapor ionization theory for laser constrict arc plasma phenomenon. Also, the results substantiate that the arc plasma cannot easily enter into the keyhole because of the violent metal vapor

Multi-tests for pore structure characterization-A case study using lamprophyre

The pore structure plays an important role to understand methane adsorption, storage and flow behavior of geological materials. In this paper, the multi-tests including N2 adsorption, mercury intrusion porosimetry (MIP) and CT reconstruction have been proposed on Tashan lamprophyre samples. The main findings are listed: (1) The pore size distribution has a broad range ranging from 2-100000nm, among which the adsorption pores (\u3c100nm) occupies the mainly specific surface areas and pore volume while the seepage pores (\u3e100nm) only account for 34% of total pore volume. (2) The lamprophyre open pores are mainly slit-like/plate-like and ink-bottle-shaped pores on a two-dimensional level. The lamprophyre 3D pore structure shows more stochastic and anisotropic extension on the z axis to form a complex pore system on a three-dimensional level. (3) The closed pores (\u3e647nm) occupy averaged 74.86% and 72.75% of total pores (\u3e647nm) volume and specific surface area indicating a poor connectivity pore system. The revealed results provide basic information for understanding the abnormal methane emission reasons in similar geological conditions with lamprophyre invasions

Dynamic influence of coal fine intrusion on propped fracture permeability

Coal fine intrusion into hydraulic propped fractures of coal seam easily leads to the blockage of the fracture, resulting in the decrease of the conductivity and the reduction of coal reservoir permeability, which seriously affects the stable discharge and production of coalbed methane well. In this paper, the permeability dynamic evolution models of coal fine intrusion into propped fractures were established before the shutdown and after the restart of coalbed methane well, and the experiments of coal fine intrusion into propped fracture under continuous and intermittent flow conditions were carried out by using the coal-rock conductivity test system, which verified the correctness of the models and studied the influence of coalbed methane well stoppage and drainage velocity on the permeability spatial and temporal evolution laws. The results indicate that with the increase of coal fine migration time, the permeability of propped fracture decreases slowly after a sudden drop, and along the direction of coal fine migration, the spatial pore loss rate of propped fracture decreases gradually, resulting in the permeability of fracture decreases along the direction of coal fine migration. With the continuous coal fine intrusion into propped fracture, the propped fracture pore loss rate after the shut-in and restart of coalbed methane wells is larger than that before the shutdown, and the permeability cannot be restored to the level before the shutdown. The slower the flow rate of drainage, the slower the permeability attenuation rate of coal fine intrusion into propped fracture, and the higher the permeability. During the coal fine invasion into proppant fracture at the low drainage flow rate, the fracture permeability is more sensitive to the flow rate change, and the less damage to the propped fracture permeability caused by the well shutdown. In the process of coal fine intrusion, the larger the deposition coefficient of coal fine is, the smaller the proximal fracture permeability and the larger the distal fracture permeability. The larger the diffusion coefficient is, the smaller the distal fracture permeability of the propped fracture is. The permeability of the proximal fracture is very little affected by the diffusion coefficient, and the damage to the proximal fracture permeability is more serious. In the process of coal fine intrusion, the proximal fracture permeability declines faster, while the distal fracture permeability declines slowly. The deposition coefficient changes have a significant influence on the proximal fracture permeability, while the diffusion coefficient changes have a more significant influence on the distal fracture permeability

Inorganic mineral plugging removal characteristics by acid etching and foam drainage in low-producing coalbed methane well

The blocking of inorganic minerals in coalbed methane development will cause the low production of coalbed methane well, which will seriously restrict the continuous and stable production of coalbed methane well. Acid dissolution is an effective means to clean up inorganic minerals. Based on the experiment of multi-component acid dissolution of inorganic minerals, combined with the wetting and carrying effect of foam drainage on inorganic minerals, the inorganic mineral plugging removal characteristics by acid etching and foam drainage in low-production coalbed methane wells were studied. The results indicate that hydrofluoric acid has better dissolution effect on inorganic minerals with silicate rock as the main component than hydrochloric acid and acetic acid. The dissolution rate of inorganic minerals does not increase significantly when the acid concentration exceeds 12%. The multi-component acid has higher dissolution rate of minerals than single component acid, generally reaching 40%−80%. When the concentration of foaming agent is less than 0.6%, the surface tension of the solution and the contact angle between the solution and inorganic minerals gradually decrease with the increase of the concentration of foaming agent. Under the action of foam discharge, the foam becomes denser, the foaming ability gradually increases, the foam half-life gradually prolongates, and the foam powder carrying content is higher with the increase of the concentration of foaming agent. When the concentration of foaming agent exceeds 0.6%, the surface tension tends to be disturbed and the foam stability becomes worse. The large bubble diameter of BS-12 foam system has more serious influence on the foam half-life than that of AEO foam system. The surface tension of APG compound acid is minimal with the stable and dense foam, and it has the best wettability to inorganic minerals. APG as non-ionic surfactant with strong acid resistance is selected as the foaming agent, compound with acid is the preferred solution to etch inorganic minerals. Foam drainage promotes the dissolution rate of inorganic minerals to increase slightly, and the acid concentration inhibited the stability and foam half-life, with the smaller particle size of inorganic minerals discharged from the foam and the narrower particle size range

Experimental study and application of hydraulic fracturing in underlying coal seam

The coalbed methane resource under goaf is rich, but has not been effectively developed for a long time. Hydraulic fracturing technology stands as an effective means to augment coalbed methane recovery. The extraction and re-compaction of overlying coal seam will directly affect the expansion behavior of hydraulic fractures in the underlying coal seam. Though the large-scale (300 mm×300 mm×300 mm) true triaxial hydraulic fracturing experiments, the mechanical and acoustic emission response characteristics of coal were analyzed under different levels of loading and unloading stress perturbations. The damage variable T was proposed to characterize the degree of coal damage, and the relationship between damage and the initiation and expansion patterns of hydraulic fractures was elucidated. The results revealed that, the damage induced by vertical stress loading in the underlying coal significantly exceeded that in the unloading stage. When the vertical loading stress was below 11 MPa, the coal remained in an elastic stage with minimal damage. Loading between 11~15 MPa corresponded to the yielding stage, witnessing a substantial increase in damage. Loading between 15~18 MPa led to the strengthening stage, the pores and fractures of coal were gradually compacted. Damage variables T can effectively characterize the degree of internal damage of coal. When T=Tc, the internal damage of coal was comparable to that of a coal that has not disturbed by loading and unloading stress.Tc is the damage variable of coal without loading and unloading stress disturbance. When T＞Tc , the coal exhibited a stress-damaged state, with higher values of T corresponding to increasing damage levels. Conversely, when T＜Tc, the coal demonstrated a stress-compacted state, with smaller values of T indicating higher compaction degrees. The degree of stress damage in coal was negatively correlated with the fracture pressure, a high degree of damage made coal more prone to fracture, and it was favor to form the primary hydraulic fractures near the wellbore, which was conducive to hydraulic fracturing. The degree of compaction of coal was positively correlated with fracture pressure. The high degree of compaction weakened the effect of horizontal stress difference on hydraulic fracture expansion, and the hydraulic fracture near the wellbore was more developed, which hindered the formation of primary hydraulic fractures. Based on the research results, the principle of hydraulic fracturing construction scheme optimization for underlying coal seam in goaf was formulated and applied in the field. The hydraulic fracturing ability of the optimized scheme was significantly improved

Methane Extraction from Abandoned Mines by Surface Vertical Wells: A Case Study in China

Considerable methane resources exist in abandoned coal mines. However, methane extraction from abandoned mines in China is still in the exploratory stage. This study presents technologies and engineering practices suitable for the extraction of gob methane from abandoned mines using surface vertical wells, including methane drainage systems, well bottom locations, and an intermittent drainage method. Seven surface wells in the Yongan abandoned mine in China were selected for gob methane extraction. Field results showed that the methane volumetric flow rate of a well whose bottom was close to the gob bottom was 2.5 times greater than that of a well with a bottom located in the gob fractured zone. Moreover, intermittent extraction can enable a well to extract methane cyclically at a high volumetric flow rate. A well drilled mistakenly into a coal pillar can be reused through hydraulic fracturing. The overall maximum methane volumetric flow rate, average concentration, and extraction span were 210 m3/h, 83%, and 1100 days, respectively