Burial depth interval of the shale brittle–ductile transition zone and its implications in shale gas exploration and production

Brittleness and ductility of shale are closely related to shale gas exploration and production. How to predict brittleness and ductility of shale is one of the key issues in the study of shale gas preservation and hydraulic fracturing treatments. The magnitude of shale brittleness was often determined by brittle mineral content(for example, quartz and feldspars) in shale gas exploration.However, the shale brittleness is also controlled by burial depth. Shale brittle/ductile properties such as brittle, semibrittle and ductile can mutually transform with burial depth variation. We established a work flow of determining the burial depth interval of brittle–ductile transition zone for a given shale. Two boundaries were employed to divide the burial depth interval of shale brittle/ductile properties. One is the bottom boundary of the brittle zone(BZ), and the other is the top boundary of the ductile zone(DZ). The brittle–ductile transition zone(BDTZ) is between them.The bottom boundary of BZ was determined by the overconsolidation ratio(OCR) threshold value combined with pre-consolidation stress which the shale experienced over geological time. The top boundary of DZ was determined based on the critical confining pressure of brittle–ductile transition. The OCR threshold value and the critical confining pressure were obtained from uniaxial strain andtriaxial compression tests. The BZ, DZ and BDTZ of the Lower Silurian Longmaxi shale in some representative shale gas exploration wells in eastern Sichuan and western Hubei areas were determined according to the above work flow. The results show that the BZ varies with the maximum burial depth and the DZ varies with the density of the overlying rocks except for the critical confining pressure.Moreover, the BDTZ determined by the above work flow is probably the best burial depth interval for marine shale gas exploration and production in Southern China. Shale located in the BDTZ is semi-brittle and is not prone to be severely naturally fractured but likely to respond well to hydraulic fracturing. The depth interval of BDTZ determined by our work flow could be a valuable parameter of shale gas estimation in geology and engineering.

Intraoperative single administration of neutrophil peptide 1 accelerates the early functional recovery of peripheral nerves after crush injury

Neutrophil peptide 1 belongs to a family of peptides involved in innate immunity. Continuous intramuscular injection of neutrophil peptide 1 can promote the regeneration of peripheral nerves, but clinical application in this manner is not convenient. To this end, the effects of a single intraoperative administration of neutrophil peptide 1 on peripheral nerve regeneration were experimentally observed. A rat model of sciatic nerve crush injury was established using the clamp method. After model establishment, a normal saline group and a neutrophil peptide 1 group were injected with a single dose of normal saline or 10 μg/mL neutrophil peptide 1, respectively. A sham group, without sciatic nerve crush was also prepared as a control. Sciatic nerve function tests, neuroelectrophysiological tests, and hematoxylin-eosin staining showed that the nerve conduction velocity, sciatic functional index, and tibialis anterior muscle fiber cross-sectional area were better in the neutrophil peptide 1 group than in the normal saline group at 4 weeks after surgery. At 4 and 8 weeks after surgery, there were no differences in the wet weight of the tibialis anterior muscle between the neutrophil peptide 1 and saline groups. Histological staining of the sciatic nerve showed no significant differences in the number of myelinated nerve fibers or the axon cross-sectional area between the neutrophil peptide 1 and normal saline groups. The above data confirmed that a single dose of neutrophil peptide 1 during surgery can promote the recovery of neurological function 4 weeks after sciatic nerve injury. All the experiments were approved by the Medical Ethics Committee of Peking University People's Hospital, China(approval No. 2015-50) on December 9, 2015.

Changes in proteins related to early nerve repair in a rat model of sciatic nerve injury

Peripheral nerves have a limited capacity for self-repair and those that are severely damaged or have significant defects are challenging to repair. Investigating the pathophysiology of peripheral nerve repair is important for the clinical treatment of peripheral nerve repair and regeneration. In this study, rat models of right sciatic nerve injury were established by a clamping method. Protein chip assay was performed to quantify the levels of neurotrophic, inflammation-related, chemotaxis-related and cell generation-related factors in the sciatic nerve within 7 days after injury. The results revealed that the expression levels of neurotrophic factors(ciliary neurotrophic factor) and inflammationrelated factors(intercellular cell adhesion molecule-1, interferon γ, interleukin-1α, interleukin-2, interleukin-4, interleukin-6, monocyte chemoattractant protein-1, prolactin R, receptor of advanced glycation end products and tumor necrosis factor-α), chemotaxis-related factors(cytokine-induced neutrophil chemoattractant-1, L-selectin and platelet-derived growth factor-AA) and cell generation-related factors(granulocyte-macrophage colony-stimulating factor) followed different trajectories. These findings will help clarify the pathophysiology of sciatic nerve injury repair and develop clinical treatments of peripheral nerve injury. This study was approved by the Ethics Committee of Peking University People's Hospital of China(approval No. 2015-50) on December 9, 2015.

Reinnervation of spinal cord anterior horn cells after median nerve repair using transposition with other nerves

Our previous studies have confirmed that during nerve transposition repair to injured peripheral nerves, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively repair distal nerve and target muscle tissue and restore muscle motor function. To observe the effect of nerve regeneration and motor function recovery after several types of nerve transposition for median nerve defect(2 mm), 30 Sprague-Dawley rats were randomly divided into sham operation group, epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group. Three months after nerve repair, the wrist flexion test was used to evaluate the recovery of wrist flexion after regeneration of median nerve in the affected limbs of rats. The number of myelinated nerve fibers, the thickness of myelin sheath, the diameter of axons and the cross-sectional area of axons in the proximal and distal segments of the repaired nerves were measured by osmic acid staining. The ratio of newly produced distal myelinated nerve fibers to the number of proximal myelinated nerve fibers was calculated. Wet weights of the flexor digitorum superficialis muscles were measured. Muscle fiber morphology was detected using hematoxylin-eosin staining. The cross-sectional area of muscle fibers was calculated to assess the recovery of muscles. Results showed that wrist flexion function was restored, and the nerve grew into the distal effector in all three nerve transposition groups and the epineurial neurorrhaphy group. There were differences in the number of myelinated nerve fibers in each group. The magnification of proximal to distal nerves was 1.80, 3.00, 2.50, and 3.12 in epineurial neurorrhaphy group, musculocutaneous nerve transposition group, medial pectoral nerve transposition group, and radial nerve muscular branch transposition group, respectively. Nevertheless, axon diameters of new nerve fibers, cross-sectional areas of axons, thicknesses of myelin sheath, wet weights of flexor digitorum superficialis muscle and cross-sectional areas of muscle fibers of all three groups of donor nerves from different anterior horn motor neurons after nerve transposition were similar to those in the epineurial neurorrhaphy group. Our findings indicate that donor nerve translocation from different anterior horn motor neurons can effectively repair the target organs innervated by the median nerve. The corresponding spinal anterior horn motor neurons obtain functional reinnervation and achieve some degree of motor function in the affected limbs.

Brain functional remodeling caused by sciatic nerve transposition repair in rats identified by multiplemodel resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis

Lower extremity nerve transposition repair has become an important treatment strategy for peripheral nerve injury;however, brain changes caused by this surgical procedure remain unclear. In this study, the distal stump of the right sciatic nerve in a rat model of sciatic nerve injury was connected to the proximal end of the left sciatic nerve using a chitin conduit. Neuroelectrophysiological test showed that the right lower limb displayed nerve conduction, and the structure of myelinated nerve fibers recovered greatly. Muscle wet weight of the anterior tibialis and gastrocnemius recovered as well. Multiple-model resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis revealed functional remodeling in multiple brain regions and the re-establishment of motor and sensory functions through a new reflex arc. These findings suggest that sciatic nerve transposition repair induces brain functional remodeling. The study was approved by the Ethics Committee of Peking University People's Hospital on December 9, 2015(approval No. 2015-50).

Repair of peripheral nerve defects by nerve transposition using small gap bio-sleeve suture with different inner diameters at both ends

During peripheral nerve transposition repair, if the diameter difference between transposed nerves is large or multiple distal nerves must be repaired at the same time, traditional epineurial neurorrhaphy has the problem of high tension at the suture site, which may even lead to the failure of nerve suture. We investigated whether a small gap bio-sleeve suture with different inner diameters at both ends can be used to repair a 2-mm tibial nerve defect by proximal transposition of the common peroneal nerve in rats and compared the results with the repair seen after epineurial neurorrhaphy. Three months after surgery, neurological function, nerve regeneration, and recovery of nerve innervation muscle were assessed using the tibial nerve function index, neuroelectrophysiological testing, muscle biomechanics and wet weight measurement, osmic acid staining, and hematoxylin-eosin staining. There was no obvious inflammatory reaction and neuroma formation in the tibial nerve after repair by the small gap bio-sleeve suture with different inner diameters at both ends. The conduction velocity, muscle strength, wet muscle weight, cross-sectional area of muscle fibers, and the number of new myelinated nerve fibers in the biosleeve suture group were similar to those in the epineurial neurorrhaphy group. Our findings indicate that small gap bio-sleeve suture with different inner diameters at both ends can achieve surgical suture between nerves of different diameters and promote regeneration and functional recovery of injured peripheral nerves.

Synovial sarcoma in the plantar region: A case report and literature review

BACKGROUND Synovial sarcoma (SS),a rare malignant soft tissue tumor whose histological origin is still unknown,often occurs in limbs in young people and is easily misdiagnosed.CASE SUMMARY We report a 24-year-old man who sought treatment for plantar pain thought to be caused by a foot injury that occurred 4 years prior.Currently,he had been seen at another hospital for a 1-wk history of unexplained pain in the left plantar region and was treated with acupuncture,a kind of therapy of Chinese medicine,which partly relieved the pain.Because of this,the final diagnosis of biphasic SS was made after two subsequent treatments by pathological evaluation after the last operation.SS is rarely seen in the plantar area,and his history of a left plantar injury confused the original diagnosis.CONCLUSION This study shows that pathological and imaging examinations may play a vital role in the early diagnosis and treatment of SS.

Combining CUBIC Optical Clearing and Thy1-YFP-16 Mice to Observe Morphological Axon Changes During Wallerian Degeneration

Objective:Wallerian degeneration is a pathological process closely related to peripheral nerve regeneration following injury,and includes the disintegration and phagocytosis of peripheral nervous system cells.Traditionally,morphological changes are observed by performing immunofluorescence staining after sectioning,which results in the loss of some histological information.The purpose of this study was to explore a new,nondestmetive,and systematic method for observing axonal histological changes during Wallerian degeneration.Methods:Thirty male Thy1-YFP-16 mice(SPF grade,6 weeks old,20±5 g)were randomly selected and divided into clear,unobstructed brain imaging cocktails and computational analysis(CUBIC)optical clearing(n=15)and traditional method groups(n=15).Five mice in each group were sacrificed at 1st,3rd,and 5th day following a crush operation.The histological axon changes were observed by CUBIC light optical clearing treatment,direct tissue section imaging,and HE staining.Results:The results revealed that,compared with traditional imaging methods,there was no physical damage to the samples,which allowed for three-dimensional and deep-seated tissue imaging through CUBIC.Local image information could be nicely obtained by direct fluorescence imaging and HE staining,but it was difficult to obtain image information of the entire sample.At the same time,the image information obtained by fluorescence imaging and HE staining was partially lost.Conclusion:The combining of CUBIC and Thy1-YFP transgenic mice allowed for a clear and comprehensive observation of histological changes of axons in Wallerian degeneration.

天然气扩散系数研究现状及存在问题

天然气扩散系数表征天然气在地层中的扩散能力,是油气藏盖层封堵性能、油气保存条件与油气资源潜力评价的重要参数,确定其符合地层条件的数值并提高精度,对油气勘探具有重要理论意义和实用价值。目前获取方法主要是实验模拟和数值模拟2种。前人研究表明,温压条件、岩石物性条件和孔隙流体性质是影响天然气扩散系数的主要因素。在实验室扩散系数测定过程中,温压条件的设置普遍低于地层实际情况,多会在饱和介质与温度条件方面进行系数校正,这影响了逼近实际地层条件的真实性。在数值模拟中,一些参数的设定仍然依赖于实验所得,不同模式的数学扩散模拟在实际中难以应用。通过文献资料分析认为,梳理实验室测定的扩散系数计算方法,总结现阶段天然气扩散系数研究的主要校正措施及天然气扩散的数值模拟现状,对存在的问题进行系统分析并强化天然气扩散系数测定装置与系统性能,可以有效提高天然气扩散系数测定的准确性;加强目标地层孔隙度与扩散模式研究并基于扩散模式采用相应的扩散系数计算方法,可以提高数值模拟结果精度。实验模拟与分子动力学融合将是今后实现天然气扩散系数准确获取的主要研究方向。

Wnt5a Affects Schwann Cell Proliferation and Regeneration via Wnt/c-Jun and PTEN Signaling Pathway

To the Editor： Peripheral nerve injury has been a common clinical disease, and delayed treatment may ultimately lead to long-term physical dysfunction. The repair of peripheral nerve injury has become a major challenge in clinical practice. Different from the central nervous system, the peripheral nervous system has the capacity to regenerate after injury. However, the peripheral nerve regeneration after injury is a slow process, and more than 3 months is usually needed for the axons regenerating to the distal target organs or tissues, when the distal nerve stump and skeletal muscle usually become atrophy and the regenerated axons lost the ability to remodel in next few months.