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Stress changes associated with reservoir depletion have been frequently observed. Stress evolution within and around the drainage areas can affect the completion of infill wells and refracturing considerably. To accurately predict the stress distribution in shale gas reservoirs, a coupled fluid-flow/geomechanics model considering the microscopic seepage mechanism of shale gas and the distribution of complex natural fractures (NFs) was derived based on Biot's theory, the embedded discrete fracture model, and the finite volume method. Based on this model, stress can be predicted by considering the mechanisms of adsorption, desorption, diffusion, and slippage of shale gas and the random distribution of NFs. The results show that in the process of stress evolution, there will be extremes of σxx, σyy, σxy, Δσ, α, and stress reversal area at a certain point, and the time of occurrence of extremes differs at different positions. The key to determining this law is the pore pressure gradient, with a spatiotemporal evolution effect. Different microscopic seepage mechanisms significantly influence the storage and transmission of shale gas, leading to significant differences in the distributions of reservoir pressure and stress. The larger the initial stress difference, the more difficult the stress reversal. When the initial stress difference exceeds a certain limit, stress reversal does not occur in the reservoir. Under the influence of the distribution difference of the NFs, the shape of the pressure-depletion area and magnitude of the pressure gradient differed significantly. As the approaching angle of NFs increased, the range of stress reversal in the top and bottom parts of the domain gradually decreases; At the same time, the orientation of maximum horizontal stress (MHS) near the fractures also gradually decreases. When the approaching angles of the NFs are the same, the number of natural fractures has little effect on the stress. Owing to the effect of NFs and hydraulic fracture, the anisotropy of stress is enhanced, the occurrence time of extreme value of local stress and stress reversal area differ significantly, and selecting the timing of infill well fracturing and refracturing becomes difficult. This research is essential to understanding the stress evolution law of shale gas reservoirs and guiding the completion of infill wells and refracturing design.

In response to the unclear understanding of fracture propagation and intersection interference in zipper fracturing under the factory development model of deep shale gas wells, a coupled hydro-mechanical model for zipper fracturing considering the influence of natural fracture zones was established based on the finite element – discrete element method. The reliability of the model was verified using experimental data and field monitoring pressure increase data. Taking the deep shale gas reservoir in southern Sichuan as an example, the propagation and interference laws of fracturing fractures under the influence of natural fracture zones with different characteristics were studied. The results show that the large approaching angle fracture zone has a blocking effect on the forward propagation of fracturing fractures and the intersection of inter well fractures. During pump shutdown, hydraulic fractures exhibit continued expansion behavior under net pressure driving. Under high stress difference, as the approaching angle of the fracture zone increases, the response well pressure increase and the total length of the fractured fracture show a trend of first decreasing and then increasing, and first increasing and then decreasing, respectively. Compared to small approach angle fracture zones, natural fracture zones with large approach angles require longer time and have greater difficulty to intersect. The width of fractures and the length of natural fractures are negatively and positively correlated with the response well pressure increase, respectively, and positively and negatively correlated with the time required for intersection, the total length of hydraulic fractures, and fracturing efficiency, respectively. As the displacement distance of the well increases, the probability of fracture intersection decreases, but the regularity between displacement distance and the response well pressure increase and the total length of fractures is not obvious.

Based on the elastic theory of porous media, embedded discrete fracture model and finite volume method, and considering the micro-seepage mechanism of shale gas, a fully coupled seepage-geomechanical model suitable for fractured shale gas reservoirs is established, the optimization method of refracturing timing is proposed, and the influencing factors of refracturing timing are analyzed based on the data from shale gas well in Fuling of Sichuan Basin. The results show that due to the depletion of formation pressure, the percentage of the maximum horizontal principal stress reversal area in the total area increases and then decreases with time. The closer the area is to the hydraulic fracture, the shorter the time for the peak of the stress reversal area percentage curve to appear, and the shorter the time for the final zero return (to the initial state). The optimum time of refracturing is affected by matrix permeability, initial stress difference and natural fracture approach angle. The larger the matrix permeability and initial stress difference is, the shorter the time for stress reversal area percentage curve to reach peak and return to the initial state, and the earlier the time to take refracturing measures. The larger the natural fracture approach angle is, the more difficult it is for stress reversal to occur near the fracture, and the earlier the optimum refracturing time is. The more likely the stress reversal occurs at the far end of the artificial fracture, the later the optimal time of refracturing is. Reservoirs with low matrix permeability have a rapid decrease in single well productivity. To ensure economic efficiency, measures such as shut-in or gas injection can be taken to restore the stress, and refracturing can be implemented in advance.

Abstract Purpose Our study was to investigate the correlation correlation between FDG uptake and PD-L1 expression of liver metastasis in patients with colon cancer, and to determine the value of FDG-PET in predicting PD-L1 expression in liver metastasis of colon cancer. Methods A total of 72 patients with confirmed liver metastasis of colon cancer were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of liver metastasis lesions were assessed using 18 F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. Results PD-L1 expression was significantly correlated with FDG uptake (SUVmax), tumor size, differentiation, survival and cytotoxic T cells infiltration in liver metastasis of colon cancer (P

Spontaneous imbibition behavior of fracturing fluid retained in reservoirs is considered to be one of the important mechanisms of spontaneous oil–water displacement in tight reservoirs. However, the mechanism of imbibition displacement in oil-wet rocks remains unclear. Inspired by the principle of the Marangoni effect, a mathematical model of oil displacement driven by an interfacial tension gradient in an oil-wet capillary tube was established, and the effects of osmotic pressure and hydraulic mechanical dispersion were coupled in the model. The results show that the key component of this mechanism is the breakdown of the initial capillary equilibrium state due to the diffusion of solute, which changes the pressure distribution in the capillary and drives the water to drive oil out of the pores. This can explain the spontaneous imbibition of low-salinity fracturing fluid into the oil-wet tight sample and displace oil without any external force, despite its low permeability. In addition, the related factors were analyzed, including initial concentration, contact angle, solute type, osmotic behavior, and size of the capillary. The results show that for an oil wet reservoir with high salinity, the connate water interfacial tension gradient plays an important role in oil displacement, and the coupling effect of osmotic pressure and hydromechanical dispersion considerably improves recovery. This can provide new insight into the mechanism of spontaneous imbibition of fracturing fluid.

A multi-process (fracturing, shut-in and production) multi-phase flow model was derived considering the osmotic pressure, membrane effect, elastic energy and capillary force, to determine the optimal shut-in time after multi-cluster staged hydraulic fracturing in shale reservoirs for the maximum production. The accuracy of the model was verified by using production data and commercial software. Based on this model and method, a physical model was made based on the inversion of fracture parameters from fracturing pressure data, to simulate the dynamic changes of pore pressure and oil saturation during fracturing, soaking and production, examine effects of 7 factors on the optimal shut-in time, and find out the main factors affecting the optimal shut-in time through orthogonal experiments. With the increase of shut-in time, the increment of cumulative production increases rapidly first and then tended to a stable value, and the shut-in time corresponding to the inflection point of the change was the optimal shut-in time. The optimal shut-in time has a nonlinear negative correlation with matrix permeability, porosity, capillary pressure multiple and fracture length, a nonlinear positive correlation with the membrane efficiency and total volume of injected fluid, and a nearly linear positive correlation with displacement. The seven factors in descending order of influence degree on optimal shut-in time are total volume of injected fluid, capillary force multiple, matrix permeability, porosity, membrane efficiency, salinity of fracturing fluid, fracturing fluid displacement.

The first fractured shale gas well of China was constructed in 2010. After 10 years of development, China has become the second country that possesses the core technology of shale gas development around the world, realized the shale gas fracturing techniques from zero to one and from lagging to partially leading, and constructed the fracturing theory and technology system suitable for middle–shallow marine shale gas exploitation. In order to provide beneficial guidance for the efficient exploitation of shale gas in China in the future, this paper comprehensively reviews development history and status of domestic fundamental theories, optimized design methods, fluid systems, tools and technologies of shale gas fracturing and summarizes the research results in fundamental theories and optimized design methods, such as fracturing sweet-spot cognition, fracture network propagation simulation and control, rock hydration and flowback control, and SRV (stimulated reservoir volume) evaluation and characterization. The development and application of slick-water fracturing fluid system and new fracturing fluid with little or no water is discussed. The development and independent research & development level of multi-stage fracturing tools are evaluated, including drillable composite plug, soluble plug, large-diameter plug and casing cementing sleeve. The implementation situations of field technologies and processes are illustrated, including the early conventional multi-stage multi-cluster fracturing and the current “dense cluster” fracturing and temporary plugging fracturing. Based on this, the current challenges to domestic shale gas fracturing technologies are analyzed systematically, and the development direction of related technologies is forecast. In conclusion, it is necessary for China to continuously research the fracturing theories, technologies and methods suitable for domestic deep and ultra-deep marine shale gas, terrestrial shale gas and transitional shale gas to facilitate the future efficient development of shale gas in China.

Perforation is the key to the successful implementation of hydraulic fracturing, and the study of perforation parameters is of great significance for reservoir reconstruction and oil and gas exploitation. A finite element model is established to simulate multi-hole fractures' initiation and propagation based on the global embedded cohesive zone model. In the model, the reservoir is considered a dense, low-permeability porous elastic medium, wherein the coupling effect of fluid and geomechanics during fracturing is considered. The KGD analytical solution is consistent with the simulation results, verifying the cohesive zone model's accuracy. The results show that there are four competitive modes for multi-hole crack initiation. Firstly, the cracks open initially and remain open; secondly, the hole is open but not cracked; thirdly, the initial initiation extends and then closes; finally, the initial crack did not start in the late crack. With the increase of perforation density, the perforation initiation rate and average fracture pressure gradually decrease, and the fracture complexity in the near-wellbore area increases. With the increase of displacement and viscosity, the initial crack rate, the number of main cracks and microcracks formed in the hole tend to increase, while horizontal stress difference has an inversely proportional trend. In the presence of multiple perforating holes, the crack propagation presents a change from complex to simple, and the number of cracks presents a change from more to less. The expansion mode is formed with 2–4 main cracks and micro-cracks as auxiliary.

Abstract The study on induced stress of hydraulic fracturing is an important part of hydraulic fracturing design, temporary plugging and steering fracturing design, and completion design in oil and gas development. Based on fracture continuum method (FCM), cohesive unit method, and finite volume method (FVM), the propagation behavior of multiple hydraulic fractures (HFs) in fractured‐porous media reservoir is simulated from the perspective of fluid and geological stress coupling. The influence of natural fractures (NFs) on stress distribution and stress inversion sensitive factors are studied. NFs in the model are equivalent to physical models controlled by tension and shear bonds. The proposed model can deal with any number of NFs, which greatly improves the computational efficiency of the model. Then PKN analytic solution and Abaqus software results were used to verify the correctness of our model. The results show that the NF will make the reservoir stress show strong heterogeneity after fracturing, and the prominent feature is the regional stress mutation. The sudden change of stress shows the sudden increase or decrease in stress; with the increase in the initial stress difference, the stress inversion becomes more difficult. When the stress difference exceeds 3 MPa, the stress inversion area is almost 0. The stress interference increases with the decrease in cluster spacing. The stress inversion region between HFs decreases, while the external stress inversion region increases; Biot coefficient has great influence on stress and stress inversion. With the decrease in Biot coefficient, stress inversion region will decrease obviously. When the Biot coefficient is 0.4, there is no stress inversion area in the whole reservoir. Poisson's ratio has little influence on stress inversion. When Poisson's ratio changes between 0.1 and 0.3, the change range of stress is within 1 MPa, and the stress inversion area is almost unchanged. Our results can be helpful for understanding the stress distribution after hydraulic fracturing in fractured‐porous media.

Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophagosome and then delivered to lysosome for destruction. Recently, tremendous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or autophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.

The fracture propagation in hydraulic fracturing is described as a nonlinear problem dynamic boundary. Due to the limitation of mesh refinement, it is difficult to obtain the real crack propagation path using conventional numerical methods. Meshless methods (MMs) are an effective method to eliminate the dependence on the computational grid in the simulation of fracture propagation. In this paper, a hydraulic fracture propagation model is established based on the element-free Galerkin (EFG) method by introducing jump and branch enrichment functions. Based on the proposed method, three types of fracturing technology are investigated. The results reveal that the stress interference between fractures has an important impact on the propagation path. For the codirectional fracturing simultaneously, fractures propagate in a repel direction. However, the new fracture is attracted and eventually trapped by the adjacent fracture in the sequential fracturing case. For the opposite simultaneous fracturing in multiwells, two fractures with a certain lateral spacing will deflect toward each other. The effect of stress shadow should be used rationally in the optimization of construction parameters; for the single well multistage fracturing, the stage spacing should be out of stress inversion area, while for the simultaneous fracturing of multiple wells, stress inversion zones should be used to maximize communication between natural fractures. Overall, this study establishes a novel and effective approach of using MM to simulate the propagation of hydraulic fractures, which can serve as a useful reference for understanding the mechanism of hydraulic fracture propagation under various conditions.

Refracturing, temporary plugging, and infilling well design play an important role in the development of reservoirs. The prediction of stress distribution can provide the basic guiding theory for the design and implementation of these techniques. In this paper, a fully-coupled three-dimensional production model based on the finite element method (FEM) and fracture continuum method (FCM) for naturally fractured reservoirs is presented to study the effects of fluid consumption on the reservoir stress. Furthermore, the effects of natural fractures on the stress re-distribution and stress re-orientation are also studied. The model also considers the influence of natural fractures on the permeability, and the effect of the effective stress on natural fracture openings, pore-elastic deformation, and fluid consumption. An analytical solution model and Eclipse were used for the comparison, which verifies the accuracy of the model results. Based on two cases of one cluster of fractures and three clusters of non-planar fractures, the research results revealed that natural fractures have a significant influence on the surrounding drainage, stress distribution, and stress re-orientation during the development. Under the influence of natural fractures, the production of the fluid along the direction of natural fractures is significantly easier, and it is highly probably that the insufficient consumption area is perpendicular to the direction of natural fractures. Compared with the conventional model, the stress distribution in the proposed model is deflected to a certain extent under the flow mode dominated by natural fractures, which is significantly prominent in the non-planar fracture model. Due to the effect of natural cracks, the absolute values of the stress, displacement, and stress difference in this model are relatively larger than those in the conventional model. Moreover, the re-orientation angles of the maximum principal stress are significantly different. After considering the natural cracks, there was an increase in the change in re-orientation and the re-orientation range. The research findings reported in this paper can be used to predict the initiation, extension, and steering process of temporary plugging fracturing fractures and refracturing fractures in fractured reservoirs.

In this paper, a novel porous media permeability model is established by using particle model, capillary bundle model and fractal theory. The three-dimensional irregular spatial characteristics composed of two ideal particles are considered in the model. Compared with previous models, the results of our model are closer to the experimental data. The results show that the tortuosity fractal dimension is negatively correlated with porosity, while the pore area fractal dimension is positively correlated with porosity; The permeability is negatively correlated with the tortuosity fractal dimension and positively correlated with the integral fractal dimension of pore surface and particle radius. When the tortuosity fractal dimension is close to 1 and the pore area fractal dimension is close to 2, the faster the permeability changes, the greater the impact. Different particle arrangement has great influence on porous media permeability. When the porosity is close to 0 and close to 1, the greater the difference coefficient is, the more the permeability of different arrangement is affected. In addition, the larger the particle radius is, the greater the permeability difference coefficient will be, and the greater the permeability difference will be for different particle arrangements. With the increase of fractal dimension, the permeability difference coefficient first decreases and then increases. When the pore area fractal dimension approaches 2, the permeability difference coefficient changes faster and reaches the minimum value, and when the tortuosity fractal dimension approaches 1, the permeability difference coefficient changes faster and reaches the minimum value. Our research is helpful to further understand the connotation of medium transmission in porous media.

Based on fractal geometry theory, the Hagen−Poiseuille law, and the Langmuir adsorption law, this paper established a mathematical model of gas flow in nano-pores of shale, and deduced a new shale apparent permeability model. This model considers such flow mechanisms as pore size distribution, tortuosity, slippage effect, Knudsen diffusion, and surface extension of shale matrix. This model is closely related to the pore structure and size parameters of shale, and can better reflect the distribution characteristics of nano-pores in shale. The correctness of the model is verified by comparison with the classical experimental data. Finally, the influences of pressure, temperature, integral shape dimension of pore surface and tortuous fractal dimension on apparent permeability, slip flow, Knudsen diffusion and surface diffusion of shale gas transport mechanism on shale gas transport capacity are analyzed, and gas transport behaviors and rules in multi-scale shale pores are revealed. The proposed model is conducive to a more profound and clear understanding of the flow mechanism of shale gas nanopores.