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In order to effectively simulate the process of random propagation of hydraulic fractures in fractured shale reservoirs, a new method of random propagation of hydraulic fractures based on the finite element mesh embedded with zero-thickness cohesive elements is proposed. This new method is based on the topological data structure of element nodes and the splitting mode of mesh nodes. The accuracy and effectiveness of the random propagation method are verified by comparing with the analytical solution of KGD model and two kinds of laboratory experiments. Meanwhile, the influences of horizontal in-situ stress difference and reservoir heterogeneity on the process of random propagation of hydraulic fractures are evaluated by running numerical examples. The results show that: (1) the new method makes up for the deficiency that the cohesive element built-in ABAQUS platform can not effectively simulate the random propagation of hydraulic fractures; (2) under a higher horizontal in-situ stress difference condition, the stronger the heterogeneity of a shale reservoir is, the easier it is to reopen a high-angle natural fracture intersecting with hydraulic fractures. The proposed method can accurately describe the random propagation behavior of complex hydraulic fractures, and thus provide a novel means for numerical simulation of naturally fractured shale reservoirs.

Age-related neurodegenerative disorders such as Alzheimer's disease (AD) have become a critical public health issue due to the significantly extended human lifespan, leading to considerable economic and social burdens. Traditional therapies for AD such as medicine and surgery remain ineffective, impractical, and expensive. Many studies have shown that a variety of bioactive substances released by physical exercise (called "exerkines") help to maintain and improve the normal functions of the brain in terms of cognition, emotion, and psychomotor coordination. Increasing evidence suggests that exerkines may exert beneficial effects in AD as well. This review summarizes the neuroprotective effects of exerkines in AD, focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise. The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages, genders, and health conditions., Competing Interests: None

Background: In China, patients with rheumatoid arthritis (RA) are often treated with traditional Chinese herbal medicine. There are certain advantages of traditional Chinese medicine therapy in treatment of RA., Objective: To assess the efficacy and adverse reaction of Shenshi Qianghuo Dihuang Decoction (SQDD), a compound traditional Chinese herbal medicine, in treatment of RA., Design, Setting, Participants and Interventions: This was a 24-week prospective, randomized, controlled trial. Ninety RA patients meeting inclusion criteria from Shanghai Municipal Hospital of Traditional Chinese Medicine were randomly assigned to receive SQDD or methotrexate (MTX) with 45 cases in each group. The patients in SQDD group were orally administered with SQDD twice daily, and the patients in MTX control group were treated by oral administration of 15 mg MTX once a week. All the RA patients were treated for 24 weeks., Main Outcome Measures: The primary outcome was the number of patients achieving the American College of Rheumatology 20% response. Clinical and laboratory parameters including tender joint count and swollen joint count, patient's global assessment and physician's global assessment (using a 0-10 cm visual analogue scale), duration of morning stiffness, plasma C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and value of anti-cyclic citrullinated peptide (CCP) antibody were assessed., Results: After 24-week treatment, the response rates in SQDD group and MTX group were 62.53% (24/41) and 67.5% (28/40) respectively, and there was no statistical difference between the two groups (P>0.05). The patient's global assessment and physician's global assessment, morning stiffness, grip strength, tender joint count, swollen joint count and the levels of ESR, CRP and anti-CCP antibody in SQDD and MTX groups were improved significantly as compared with those before treatment, and there were no significant differences between the two groups. The efficacy of MTX in improving rest pain and joint tenderness was better than that of SQDD (P<0.05). The incidence rate of adverse reactions in SQDD group was 9.75%(4/41), significantly lower than 32.5% (13/40) in MTX group (P<0.05)., Conclusion: SQDD has a therapeutic effect on RA, and the adverse reactions are less than MTX.

Objective: To observe the effects of Yanghe Decoction on vascular endothelial growth factor (VEGF) in cartilage cells of osteoarthritis rabbits., Methods: Fifteen New Zealand white rabbits were randomly divided into normal group, untreated group and Yanghe Decoction-treated group. The rabbit model of osteoarthritis was established according to Hulth's method. The rabbits were sacrificed at the 8th week after administration of Yanghe Decoction for 14 days, and then rabbit tibia articular cartilage was removed. Sections of the cartilage were stained with Safranin O for histological examination. The cartilage histological characteristics were observed according to the method of Mankin. Immunohistochemical staining was performed to investigate the expression of VEGF. Articular cartilages were observed with microscopy and image analysis method was used to measure the expression intensity of VEGF., Results: There were significant differences in Mankin score between normal group and untreated group (P<0.01), and between untreated group and Yanghe Decoction-treated group (P<0.01). Immunohistochemical staining indicated that the expression intensity of VEGF in untreated group was significantly increased as compared with that in normal group (P<0.01), and also obviously higher than Yanghe Decotion-treated group., Conclusion: VEGF plays an important role during early stage of OA. Yanghe Decoction can protect the articular cartilage through suppressing the VEGF expression in chondrocytes and then suppress angiogenesis.