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The aim was to obtain bone repair materials with sustained release of minocycline and evaluate the effect in periodontal bone defect repair. Two complex material, hydroxyapatite/chitosan (HA/CS) and minocycline-hydroxyapatite/chitosan (Mino-HA/CS), were prepared by the co-precipitation method. The physical and chemical property, cytotoxicity, release of minocycline and the bacteriostasis examination of the materials were evaluated, they were applied to the rabbit model of mandible bone defect to evaluate their effects on the regeneration of periodontal bone defect. After minocycline was added to HA/CS, the setting time of the material was prolonged, the compressive strength was reduced and the pore size and porosity were increased significantly. The pH value did not change obviously and stayed in the neutral range. Mino-HA/CS could promote the growth of osteoblasts effectively compared with control medium. In vivo, Mino-HA/CS material showed better effect of promoting periodontal bone formation.

Background & Aims: Transjugular intrahepatic portosystemic shunt is an important method for the treatment of complications related to portal hypertension. However, a prediction model based on Chinese population has not been established. The aim of our study was to develop a prognostic model based on the Chinese population. Methods: We screened cirrhotic patients received TIPS between January 2014 and December 2021 at 11 hospitals in China and collected the available clinical data of all eligible patients. Using random assignment, patients were divided into training and validation cohorts in a 7:3 ratio. Independent risk factors for prognosis were screened by multivariate Cox regression and were used to develop a nomogram based on the training cohort. Validation cohort data was used to conduct external validation. Results: A total of 794 patients were recruited, 556 in the training cohort and 238 in the validation cohort. Age, ascites, serum albumin, total bilirubin and serum sodium levels were independent prognostic factors, and these variables were incorporated to establish nomogram scoring model named the Chongqing index of post-TIPS survival (CIPS). The C-indices were 0.753 [0.684-0.812] in the training cohort and 0.786 [0.715-0.857] in the validation cohort. Compared with the Child-Pugh, iMELD, ALBI and FIPS scores, the CIPS showed better prognosis discrimination at 1 and 3 years after TIPS. The CIPS could identify high-risk patients after TIPS implantation with a cutoff point of 149. Conclusion: The CIPS is more superior to predict 1-year and 3-years survival in Chinese patient cohorts and can identify high-risk patients with poor prognosis after TIPS implantation, which can be used to guide clinical patient management.

Lost-circulation is one of the major challenges in fractured formations limiting the optimized fast drilling, which is prone to huge economic and environmental losses. The leakage pressure prediction has been a major concern in the industry. To solve this problem, a method for the construction of leakage pressure body in fractured formations is proposed in this paper. First, a leakage pressure prediction model for different fracture scales is optimized. Secondly, a fitted relationship between leakage pressure differential and leakage rate is developed based on the leakage data of the actual drilled wells, which is used to correct the leakage pressure in the priority formation. Finally, a three-dimensional (3D) body of regional stratigraphic leakage pressure is established based on kriging interpolation. This paper presents an example analysis of a fractured formation in the Halfaya oil field. The result shows that the modified formation leakage pressure profile matches the field drilling conditions. The 3D visualization of the regional leakage pressure provides a more intuitive understanding of the distribution of leak-prone formations in the area, which can provide a targeted decision basis for leakage prevention and plugging in the area.

Rock-breaking efficiency is not so satisfied using the conventional PDC bit, especially in the hard, soft–hard interbedded, and strong abrasive formations in ultra-deep wells. A method is proposed to make full use of stress-releasing effect at bottomhole, thereby improving the rock-breaking efficiency, and a supporting weight-on-bit (WOB) self-adjusting dual-diameter PDC bit (WSDB) has been invented. The WSDB can dynamically adjust the depth-of-cut control characteristics, which could improve the rate of penetration (ROP) while mitigating the stick–slip vibration caused by the rapid change of depth of cut. The stress field of the rock at the bottomhole is calculated with a numerical method, and the working mechanism of the bit is analyzed. The application effect of the WSDB is evaluated through laboratory tests preliminarily. The results show that the stress concentration area on the shoulder of the reaming bit is decreased obviously and a larger stress unloading area emerges in the intersection between reaming and pilot bit. Thus, mechanical specific energy (MSE) can be greatly reduced when the reaming bit drills into this section. Indoor tests show that the maximum ROP of WSDB can be reached up to 70% higher compared to the conventional PDC bit, and higher ROP could be obtained with a relatively lower bit torque. With drilling parameters greater than the critical revolution and WOB, the reduction in MSE can be reached up to 36% during the rock-breaking process. Making further efforts into the optimization of bit structure to reduce the vibration intensity is expected to achieve more improved bit performance.

SummaryThe debonding of cementing interfaces caused by perforation will increase the possibility of microannuli/microcrack propagation during hydraulic fracturing. This phenomenon will pose a threat to well integrity not only with stimulation operations but also subsequent long-term production. The objective of this work is to quantitatively investigate the debonding degree of cementing interfaces after perforation. A numerical model was used to simulate the process of the wellbore being penetrated by the perforating gun. Then, a real dimensional perforation experiment was conducted with a circular target specimen. The numerical debonding area of the casing/cement interface was verified by this experiment with the method of computerized tomography (CT).The numerical-simulation and experiment results show that the cementing-interface debonding is mainly caused by the displacement difference between the casing, cement sheath, and formation during perforation. The debonding area and the microannuli of the casing/cement interface are larger than those of the cement/formation interface. Sensitivity analysis reveals that the debonding area of the cementing interface shows a positive relationship with the hexogen explosive (RDX) load and the elastic modulus of casing. Therefore, the casing with lower elastic modulus should be preferred to reduce the debonding area of the cementing interface caused by perforation if the principal casing-design criteria were met.

Blowout is one of the most serious accidents in the drilling process of hydrogen sulfide (H2S) oil and gas wells, often accompanied by the leakage of H2S and other toxic gases, which easily causes casualties and huge economic and environmental losses. Therefore, this article uses DEMATEL and ISM hybrid algorithms to establish a blowout accident-causing network model for oil and gas wells with H2S content, thus strengthening the risk management. In this model, firstly, the general causative factors of blowout accidents are extracted by accident statistics. Secondly, expert knowledge is adopted to determine the correlation matrix among factors. Thirdly, based on the DEMATEL algorithm, the degree of the relationship among the factors is analyzed. The importance degree (centrality) of each factor and its status as well as role (causality) in the accident-causing system are given. Finally, the ISM algorithm is used to classify the factors and establish an accident-causing network diagram with hierarchical relationship. The proposed model has been applied in a gas field containing H2S in East Sichuan, China. The results show that causative factors of blowout accidents can be divided into cause group and effect group according to the influence relationship among them. The cause group implies the meaning of the causative factors, and the effect group denotes the meaning of the causative factors. Hence, it would be necessary to control and pay great attention to the cause group factors beforehand. The key causative factors of blowout accidents are geological exploration technology, safety monitoring facilities and on-site safety culture, which belong to the cause group and are at the basic level of the accident-causing network diagram. This model has provided effective decision-making guidance for HSE work in gas field and reduced the incidence of blowout accidents. This model uses a combination of qualitative and quantitative methods to analyze the causes of blowout accidents, not only considering the relationships between factors and accidents, but also considering the relationships between factors and factors. As a result, it provides decision-making basis for the prevention and control of blowout accidents in H2S oil and gas wells.

Perforation will cause local damage to the cement and cementing interface, increasing the possibility of fluid channeling during hydraulic fracturing. Perforation experiment of ring target is extremely dangerous and cementing interface damage is difficult to observe, so the numerical model based on LS-DYNA software is set up in this paper. Cylindrical target penetration test is used to verify the interface damage area caused by perforation. Then, the effects of confining pressure, shear modulus of cement and diameter of shaped charge on interface damage area are analyzed. The results reveal that the damage area of casing/cement interface and the confining pressure shows a quadratic function relationship. The interface damage area has a logarithm function relationship with cement shear modulus and a strongly linear relationship with diameter of the shaped charge. In order to reduce interface damage caused by perforation, cement with lower shear modulus should be selected.

Ultrasonic monitoring of gas kick in risers is an effective method for early gas kick detection in deepwater drilling operations. At present, the research on the ultrasonic propagation in gas-liquid two-phase flow within the risers and the response rules of ultrasonic signals under actual working conditions is not deep enough. In this paper, the numerical simulation method that can accurately control parameters such as the distribution and size of bubbles was introduced, and its effectiveness and accuracy were verified by experimental means. Through the analysis of the effective sensitivity fields under different gas-fraction conditions, the key monitoring parameters (emission frequency and receiving probe position) were optimized first. On this basis, the characteristic parameters of ultrasonic signals were optimized and their applicable conditions were also analyzed: The response law of coda wave velocity to the gas fraction was gained by using the coda wave interference method and it is suitable for the condition of small gas fraction (less than 0.42%); The response rule of main frequency on gas fraction was obtained through frequency domain analysis; The arrival time of head wave was relatively sensitive to the gas fraction of 2–8%. Finally, the conditions of the eccentricity of drill pipe and the non-uniform distribution of bubbles were discussed. The influence of drill pipe eccentricity on ultrasonic propagation under different frequencies was noted, and the monitoring solution under the condition of non-uniform distribution of bubbles was proposed based on the effective sensitivity of different receiving positions. This study not only optimized the key parameters of ultrasonic monitoring method, but also explored its applicable conditions and the influence rules of actual working conditions on the ultrasonic propagation.

The ultrasonic transmission monitoring in risers is a promising method for the early detection of gas kick in deepwater drilling. It is difficult to obtain satisfactory results using only theoretical calculation because the ultrasonic wave propagation in the multiphase flow in risers is very complicated. In addition, the key parameters such as bubble shape and void fraction of two-phase flow are hard to be accurately controlled and measured. In view of the above-mentioned facts, this paper aims to analyze the principle and physical model of ultrasonic monitoring of gas kick in risers, and to establish a numerical simulation model based on COMSOL platform. Through an analysis of the numerical simulation results, it was found that the time domain diagram of the received signals contains longitudinal wave, transverse wave, surface wave and coda wave. The cross-correlation function was used to quantitatively analyze the waveform of the received signals under different void fraction conditions. It also suggested that the direct wave was insensitive to the void fraction while the coda wave was sensitive to the void fraction, which was verified through frequency domain analysis. By establishing the experimental system, the attenuation coefficient was used to verify the numerical simulation results. After comparing and analyzing data, this paper argued that the numerical simulation method established in the project can be used as an effective supplement to experiments, and it can be used to calculate and analyze the ultrasonic propagation and attenuation under conditions, such as different bubble sizes and densities, and bubble non-uniform distribution, which can not be accurately and quantitatively measured or controlled in the experiments.

The longitudinal vibration of the drill pipe contains considerable energy which can be used to improve the rock-breaking efficiency during drilling. It is very important to the development of drilling speed-up tools to have a comprehensive understanding of the energy conversion efficiency of downhole drill string vibration. In this paper, the characteristics of downhole bit load and longitudinal vibration of drill string under different conditions were studied in the experiment, and the analysis method of energy conversion efficiency from drill string vibration to spring potential energy was proposed. The experimental analysis showed that the fluctuation of the downhole bit load was reduced by 10%–90% after the spring was installed in the bottom hole assembly. The rotation rate and the spring elastic stiffness had a significant and positive influence on the fluctuation amplitude of the downhole bit load. Meanwhile, the longitudinal vibration amplitude and acceleration of the drill string peaked at the elastic stiffness of 1 kN/mm. The closer the spring position to the drill bit was, the more severe the longitudinal vibration of the drill string above the spring component was. The bit load and the rotation rate had a positive influence on the severity of longitudinal vibration. The analysis of energy conversion efficiency showed that the available mechanical energy range of the longitudinal vibration of the drill pipe was about 200–420 kW. The work power of the drill string vibration to the spring component increased sharply and then decreased with the increasing of elastic stiffness. The energy conversion efficiency came to the optimal value when the elastic stiffness was between 1 kN/mm and 2 kN/mm. Increasing the rotation rate, keeping the bit load below 134.5 kN and installing the spring component near the drill bit are beneficial for improving the energy conversion efficiency of drill string vibration. This paper reveals the main factors affecting the energy conversion efficiency of drill string vibration and their influencing laws, and determines the range of WOB, rotation speed, spring position and stiffness to obtain the best energy conversion efficiency.

Hydraulic oscillator is one of the effective tools to solve the problem of high friction in directional drilling and horizontal drilling. However, there are some problems with this kind of tools such as high pressure loss and insufficient vibration force. Because of its self-excited oscillation characteristics, pulse oscillation amplifier can realize the amplification of pulse jet pressure under the condition of lowpressure loss, which is one of the effective ways to solve the above problems of hydraulic oscillator. In this paper, according to the working characteristics of hydraulic oscillator and the demand of pulse amplification, the structure of pulse oscillator amplifier was optimized based on numerical simulation method. Firstly, the geometric and numerical models of the pulse oscillator amplifier were constructed, and the flow field distribution and pulse amplification effect of the pulse oscillation amplifier under different structural parameters were simulated and analyzed, and the influence of different structural parameters on the pulse amplification effect was explored. Secondly, the structure of the pulse oscillator amplifier was optimized by Response Surface Method, and the optimal structure based on the effect of outlet pressure amplification was obtained: upper nozzle diameter D1=22mm, upper nozzle length L1=26mm, lower nozzle diameter D2=28mm, lower nozzle length L2=28mm, cavity length L=58mm, cavity diameter d=80mm, angle 60°. Its pressure loss was 0.3MPa and outlet pressure peak value was 4.5MPa, which was 1.8 times of the inlet pressure peak value of 2.5MPa. Finally, the minimum relative error between the experimental results and the numerical simulation results was 4%, which has verified the credibility of the numerical simulation and structural optimization results.

The cement sheath are damaged around the hole after perforation, and the micro-cracks in the cement sheath will cause fluid channeling during hydraulic fracturing. Focused on this problem, a numerical model was set up to calculate the crack propagation length in cement sheath during hydraulic fracturing by using the Cohesive Zone Method (CZM). Then the influence of different parameters on the unsealing length of cement sheath during hydraulic fracturing was analyzed. The results show that higher casing pressure can help to reduce the unsealing length of cement sheath. It is significant to perforate with lower density and phase to ensure the sealing integrity of the cement sheath. This research can evaluate the sealing performance of the cement sheath during hydraulic fracturing and give some guiding for the design of fracturing schemes.

In the field of petroleum drilling engineering, passive magnetic ranging technology is generally used for specialized drilling operations such as connecting relief wells, preventing wellbore collisions, guiding parallel horizontal wells, etc. Although pre-magnetized casing strings have been used to improve the detection distance and accuracy, the theoretical mechanism is not well understood. Based on the equivalent current model of a permanent magnet, a theoretical magnetic field model around the pre-magnetized casing string was established by using the vector potential method and vector superposition principle and validated by the COMSOL Multiphysics software. Our results show that connecting pre-magnetized individual casings with homogeneous magnetic poles can enlarge the magnetic induction intensity around the total casing string. Furthermore, the magnitude close to the casing coupling is significantly larger than that close to the middle of the individual casing. Connecting pre-magnetized individual casings with heterogeneous magnetic poles results in a low magnetic induction intensity around the total casing string. In order to improve the detection distance and accuracy of the magnetic ranging, the pre-magnetized individual casings should be connected with homogeneous magnetic poles. The results of this study can provide guidelines for the development of passive magnetic ranging technology.

A hybrid methodology is presented to predict equivalent circulating density (ECD), which combines autoregressive integrated moving average (ARIMA) and back propagation neural network (BPNN) models. Research results are compared to previously published ECD prediction method that is based on theoretical calculation of hydraulic parameters. The hybrid methodology is based on data analysis theory. It uses ARIMA model to capture the linear trends of ECD, and then the BP neural network is used to predict the nonlinear and stochastic change law of ECD. Finally BP neural network prediction results are used to correct the prediction error of ARIMA to get the ECD prediction results. With a deepwater well in the South China Sea, a simulation experiment is carried out to verify the comprehensiveness and accuracy of the method presented in this paper. The prediction results are similar to those of the traditional hydraulics model, which considers the effect of temperature and pressure on drilling fluid density and rheological parameters. Comparisons are also provided for three classical time series prediction models, including the support vector machine, multiple linear regression and grey prediction. The root mean square error (RMSE) and the mean absolute deviation (MAD) were selected as evaluation indicators. The comparison results show that the hybrid model can reflect the variation law of ECD more accurately. Therefore, relative to the traditional methods of prediction, the hybrid methodology has the advantages of advanced modeling thought and simple operation, and it can be selected for prediction of ECD. Because of the effects of high temperature, high pressure and uncertain factors, the accurate prediction of ECD is very difficult. This paper provides a novel idea for accurately predicting ECD by analyzing the implicit relationship of ECD series data through data mining.

In this study, an extended two-fluid model (TFM) describing the gas-liquid two-phase flow when gas influx occurs and an acoustic model describing sound propagation within section of marine riser are proposed. The TFM and acoustic model are validated by comparison of the simulation results and filed data for pit gain, and the experimental tests on a custom-designed acoustic gas influx equipment respectively. These two models are coupled by the pressure of sound and solved using finite volume method. Moreover, two signal processing methods in acoustic gas influx detection based on Fourier transform (FT) and Hilbert-Huang transform (HHT) are introduced. Fourier spectrums and Hilbert-Huang spectrums of the simulated signals are presented in time-frequency or time-amplitude distributions respectively. The results show that compared with wellhead detection methods (WDM) which detect the variation of parameters such as pit gain, the two acoustic detection methods which are based on FT and HHT are more sensitive, and the sensitivity of the HHT method is the highest. The acoustic detection method based on HHT is effective and reliable to be further employed for well control and gas influx detection.

In deepwater drilling, the subsea wellhead is in a complicated stress state and carries the risk of instability. The mechanical stability of subsea wellhead has gradually become one of the key factors in the design and construction of deepwater drilling. In this paper, through the analysis of stress and deformation of subsea wellhead system in deepwater drilling, the characteristic parameters that characterize the mechanical stability of subsea wellhead were determined. On this basis, the influence of different factors on characteristic parameters was analyzed based on dimensionless processing and sensitivity analysis. Factors that were more sensitive and had greater impact on the wellhead mechanical stability of the instance well were screened. Aiming at the problem of greater uncertainty of resistance coefficient, the risk assessment method of subsea wellhead instability considering of uncertain factors was established. Using this method, the wellhead instability risks could be quantitatively evaluated in the drilling process, construction parameters and monitoring values of environmental loads which meet the wellhead safety requirements that could also be proposed. Example shows that: according to the selected parameters such as center value of drag coefficient $$\mu = 0.8$$ , fluctuation coefficient of drag coefficient $$\sigma = 0.05$$ , safety limit of subsea wellhead displacement $$S_{\mathrm{wm}} = 0.37\,\hbox {m}$$ , and safety limit of subsea wellhead deflection angle $$\theta _{\mathrm{wm}} = 3.1{^{\circ }}$$ , there was 24% probability of occurrence of wellhead instability for the target well. Meanwhile, the platform drift $$S_{\mathrm{w}}$$ should be

In the drilling of deepwater wells, early detection of gas kicks is a crucial and difficult well-control task. A common and advantageous method is the underwater ultrasonic monitoring of the gas–liquid two-phase flow of deepwater risers. This study focuses on the problems of the early-stage ultrasonic monitoring of gas kicks in deepwater risers, and combines theoretical analysis and experimental verification to establish a method for finite element numerical simulation of ultrasonic wave propagation in the gas–liquid two-phase flow of a deepwater riser annulus. The acoustic-solid coupling module of COMSOL Multiphysics software was adopted. Through pattern analysis of ultrasonic wave propagation under different conditions, the sensitivity analysis was carried out by combining time domain and frequency domain analysis. Through analysis, two characteristic parameters of ultrasonic signals sensitive to the gas–liquid ratio, namely, the amplitude standard deviation (S) and frequency domain mean (μ) were selected. Their degrees of sensitivity to gas bubble size and density were analyzed to determine the optimal installation location of an ultrasonic receiver probe. And the optimal installation locations were located at 66°–88° and −66°−−88° of the arc area. Finally, a quantitative relationship between the ultrasonic signal characteristic parameters (S and μ) and the void fractions of risers ( β ) was established by using two-factor regression analysis. It was proved that its relative error was 4.5%, which was less than the acceptable error threshold of 5%, thus meeting the engineering requirements.

Nowadays, the oil and gas exploration and development have been developed into the deep and complex formations. More and more abnormal pressure is encountered, which gives a great challenge to the safe and efficient drilling. Accurate description of pore pressure is of great significance to avoid drilling risk. The complexity of petroleum geology, the incompleteness of the logging or seismic data, the precision of the mathematical model and other issues can all lead to uncertainty in pore pressure prediction. The uncertainty of pore pressure is one of the fundamental causes for drilling risk. In order to address these challenges, a new quantitative description method for uncertainty of pore pressure was established. Firstly the sources of the pore pressure prediction uncertainty were analyzed. Then the uncertainties of Eaton index and normal compaction trend were, respectively, described. Finally the uncertainty interval of pore pressure was established based on Monte–Carlo simulation and normal information diffusion theory. The pore pressure prediction result obtained in this paper was not a single value, but an interval with probability distribution characteristic. The results of example showed that the measured values of pore pressure were all in pore pressure interval with confidence of 90%. Case study validated the feasibility and effectiveness of the proposed method.

Designing and maintaining the long-term integrity of an entire wellbore system is important to all its operations and to prolonging the service life of the oil and gas well. Some analytical or finite-element mechanical models have been built to calculate the stress distribution of the wellbore system, but most models ignored its loading history and took no account of its initial loaded state. Due to the shrinkage effect, nonexpandable cement systems likely induce tensile radial stresses on the cementing faces and aggravated cement-sheath failures, yet due to the expansion effect, expandable cement systems likely produced compressive radial stresses on the cementing faces and repressed cement-sheath failures. Now, more and more researchers have realized the importance to consider the initial loaded state. Some researcher have presented multistage methods to simulate the overall process before drilling, during drilling, and after drilling. However, because it is more complex and difficult to simulate the cement solidifying stage, some researchers tried to skip the simulation of cement solidifying process. To simplify the multistage method reasonably and accommodate the importance of the initial loaded state, we propose a new analytical mechanical model with a vertical wellbore and isotropic horizontal in-situ stresses. The model is derived according to the elastic mechanics theory, which can consider the loading history of the entire wellbore system and take account of its initial loaded state. The influences on stress distribution due to the initial state are discussed using a real-life example. We determined that considering the initial loaded state can cause substantial differences in the estimated stress distribution of the entire wellbore system. Taking the initial loaded state into account is essential for accurate design and examination of wellbore integrity.

Horizontal well is of great significance to the development of unconventional oil and gas resources. Considering the wellbore cleaning and pressure system safety, a model is established based on the influence of cuttings on the hydrostatic column pressure, horizontal annular pressure drop and annular geometrical shape to provide a specific extreme horizontal extension length (EHEL). This model is controlled by minimum cutting-carry pump rate, bottomhole pressure, circulation pressure loss and drilling pump pressure. The solving process and method is also given to realize the prediction of any horizontal well. The analysis shows that there is a limit to EHEL in order to maintain the wellbore cleaning degree and effective cutting transport. The limiting factors to EHEL change from formation fracture pressure and bottomhole pressure to total circulation pressure loss and pump pressure as minimum cutting-carry pump rate increases. The EHEL increases and then keeps constant as acceptable cutting bed height increases. Higher drilling fluid density is adverse to EHEL although it can reduces minimum cutting-carry pump rate. Lower consistency index and flow behavior can increase EHEL because it can reduce minimum cutting-carry pump rate and circulation pressure drop. The carve of EHEL with rate of penetration is divided into three sections, and the rate of penetration should remain in slowdown section to balance drilling cost and EHEL.

Trapped annular pressure is caused by liquid thermal expansion in oil and gas wells. A casing is developed to mitigate trapped annular pressure with low cost and overcome the limitation of well structure and location. This casing consists of coupling, relief valve, inner wall, relief space and outer wall. It can increase annular volume change rate by using relief valve to connect trapped annulus and casing relief space. Higher annular volume change rate can reduce or even eliminate trapped annular pressure. To prove the feasibility and optimize parameters of mitigation casing, models are built to calculate trapped annular pressure and annular temperature change of multiple annuli. The analysis indicates mitigation casing can effectively and permanently reduce trapped annular pressure. The extreme annular pressure change and pressure in case well are as high as 120.02 °C and 139.74 MPa, but annular pressure no longer exists when 36 mitigation casings are installed. Optimal number of mitigation casing is determined by annular temperature change and mitigation objective. Suitable design can reduce the number of mitigation casing while maintain strong mitigation effect. Mitigation casing number of case well is reduced 27.27% after optimization.

// Kuikui Ge 1, * , Jinjiang Huang 1, * , Wei Wang 1 , Meigang Gu 2 , Xinchuan Dai 1 , Yuqiang Xu 1 , Hongyu Wu 1, 3 , Guodong Li 3 , Hairong Lu 3 , Jiang Zhong 1 , Qingshan Huang 1 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China 2 Laboratory of Virology and Infectious Disease Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10065, USA 3 Shanghai High-Tech United Bio-Technological R&D Co., Ltd, Shanghai 201206, China * These authors contributed equally to this work Correspondence to: Qingshan Huang, email: qshuang@fudan.edu.cn Keywords: SPINK6, HCC, tumor suppressor, invasion, proliferation Received: April 11, 2016 Accepted: December 12, 2016 Published: December 16, 2016 ABSTRACT Hepatocellular carcinoma (HCC) causes significant medical burdens worldwide. Diagnosis, especially in the early stages, is still challenging. Therapeutic options are limited and often ineffective. Although several risk factors have been known important for development of HCC, the molecular basis of the process is rather complex and has not been fully understood. We have found that a subpopulation of HCC cells which are resistant to oncolytic parvovirus H1 superinfection highly express serine protease inhibitor Kazal-type 6 (SPINK6). This protein is specifically reduced in all HCC cell lines and tissues we analyzed. When upregulated, SPINK6 could suppress the malignant phenotypes of the HCC cells in several in vitro models. The putative tumor suppression role of SPINK6 is, however, independent of its protease inhibitory activity. To suppress the malignancy of HCC cells, SPINK6 has to be secreted to trigger signals which regulate an intracellular signaling molecule, ERK1/2, as well as a series of downstream factors involved in cell cycle progression, apoptosis and migration. Our study supports that SPINK6 is an important tumor suppressor in liver, and further investigations may help develop more effective diagnostic and therapeutic approaches.

The complex formations such as soft-hard interbedded and strong abrasive strata in ultra-deep wells make the PDC bit inefficient in rock-breaking, which greatly increases the development cost of oil and gas reservoirs. There are two basic ways to solve the above problems: one way is to relieve the force condition of the bit by changing the working mode and the other is to release the stress of the rock at bottomhole with special tools. A method is proposed in this paper to make full use of the stress-releasing effect to reduce the value of compressive stress of the rock at bottom hole, even turn it into partially tensile stress, and take advantage of the cutting method of ‘Hybrid Bits’ to improve rock-breaking efficiency (RBE). A supporting Weight-on-bit (WOB) Self-adjusting Dual-diameter PDC Bit (WSADB) is invented to realize the above idea. Based on Biot's theory of poroelasticity and considering the fluid-solid coupling effect, numerical calculation of the stress field at well bottom is performed. The results show that the WSADB can improve the RBE by enlarging the volume of the stress unloading area at well bottom; The rock damage function based on the 3D Mohr-Coulomb Criterion is used to analyze the effect of structural parameters of the bit on RBE and the optimal structural parameters are obtained. When the diameter ratio of the pilot bit to the reaming bit is 0.5, the rock to be drilled at the well bottom will be damaged to the greatest extent; When the length of the pilot bit is longer than 0.5 times of the borehole diameter, the longer the length is, the greater the degree of damage to the rock at well bottom will be. To verify the accuracy of the above calculations, a comparative test between the WSADB and conventional PDC bit is performed. The results show that the WSADB has great superiorities in improving the rate of penetration (ROP), lowering the torque on bit (TOB), reducing the mechanical specific energy (MSE) and enhancing the RBE. Making full use of the advantages of higher ROP, smaller TOB and higher mechanical energy utilization of the WSADB is expected to provide a solution to the problem of low RBE of conventional PDC bit in ultra-deep wells.

Study of the distribution of the stress field at the bottom-hole in ultra-deep wells is one of the keys to understand the rock-breaking mechanism and to optimize the design of drilling tools and bits, thus improving rock-breaking efficiency. To date, investigations of the stress field at bottom-hole considered only the static solution after stress redistribution, and neglected the dynamic evolution of the stress field and only considered uniaxial stress or biaxial stresses. Based on Biot's theory of poroelastic mechanics, the complex loading state of the rock at bottom-hole is considered and a fully coupled model of seepage field and stress field is proposed. Time effects are taken into consideration, and the model is combined with the three-dimensional Mohr-Coulomb criteria to predict strength failure of the rock at the bottom-hole. The dynamic response of the rock at the well bottom is obtained by numerical solution and the fail function is proposed to analyze the influence of stress at the well bottom on rock strength failure. The results show that the time effect of the poroelastic medium can be reflected by the dynamic response of the borehole or damping fluctuation of the pore pressure at the central line of the well bottom, and the influence range of this stress or the changes in pore pressure is within 5 well radii (R) of the borehole. For the scenario considered, under balanced drilling conditions and within 0–0.6R at the well bottom, the effective radial and hoop stresses remain in the tensile stress state after the borehole being drilled for several seconds, and the maximal values of effective radial and hoop stresses (compressive stress) appear near the borehole wall. The areas where tensile failure may occur are limited between the well bottom and 25 mm below the well bottom. The failure criteria calculated with the fail function shows that areas with smaller fail function values are concentrated in the convex part in the center of the wellbore and the junction part between the wellbore and the wellbore wall, where the rock strength failure is most likely to occur. Larger fail function values are found in a spherical area below the center of the wellbore, where the rock strength is greater due to the stress redistribution and resembles a tightly compacted core.

The ultra-high pressure water jet assisted mechanical drilling technology is an effective approach to improve the rate of penetration (ROP), however, due to unreasonable design ideas and low reliability of the existing down-hole supercharger, this technology is not applied widely. To make breakthrough of this technology, a new idea of utilizing the drill string vibration energy to modulate ultra-high pressure jet is first proposed, and a novel down-hole supercharger, down-hole drill string absorption & hydraulic supercharging device (DSAHSD), is developed. The DSAHSD combines the advantages of reducing the axial drill string vibration and generating ultra-high pressure jet to effectively assist rock breaking. When the drilling fluid flows through this tool, part of the drilling fluid will be modulated to the ultra-high pressure jet by periodic compression of piston drove by drill string vibration. Because of hydraulic auxiliary rock breaking of the ultra-high pressure jet, the drillability of rock and the ROP will be enhanced. To analyse the feasibility and influence factors of the tool, mathematical model were established, the results show that the tool could produce more than 140 MPa pressure and the outer pressure increases with the increase of weight on bit and rotary speed. Moreover, there is an optimal diameter of ultra-high pressure nozzle to optimal performance of the tool. This tool has been applied to more than 60 wells in four oil fields throughout China. The results indicate that the maximum density of the test drilling fluid is 1.9 g/cm3, the single maximum footage is 1480 m, and the operation time of the tool is more than 200 h. Furthermore, the average ROP was increased by approximately 11–831%. In conclusion, the DSAHSD has the characteristics of a simple structure, has a long lifetime, is able to adapt well with existing drilling equipment, and can provide guarantee for wide application of the ultra-high pressure jet technology in oil fields.

Annular pressure build-up threatens deepwater well safety greatly, but the available mitigation methods are limited by well conditions and formation properties in some cases. Thermal-insulated pipes including casing and tubing are an alternative method due to low thermal conductivity. To optimize the application of thermal-insulted pipes, a model based on volume consistency and semi-steady approach is established to calculate the annular pressure in multiple annuli with thermal-insulated pipes. In the case well, the optimal setting depth is 2200 m, equal to cement top. Annular pressure decreases quickly when thermal conductivity is under 0.04 W/(m⋅k). Thermal-insulated pipes can reduce the rising speed of annular pressure as formation temperature increases. The effect of production rate can be ignored if it is higher than 400 t/d. The annular pressure of case well is reduced by as much as 63.97% and kept under maxim acceptable annular pressure in 10 years. Based on this model and analysis, a process is proposed to design the thermal pipes applied in deepwater well to mitigate annular pressure build-up.

Through the analysis of gas-cut features in deepwater drilling and shortages of existing gas-cut detection methods, the feasibility of early detection of gas cut at the bottom of riser was demonstrated, and a method was proposed for quantitative description of gas-cut degree in deepwater drilling based on ultrasonic monitoring at the bottom of riser. The problems of Doppler ultrasound gas-cut detection method was analyzed and the experimental device of gas-cut monitoring at the bottom of riser based on the ultrasonic transmission was built, which was used to analyze the sound attenuation characteristics under different conditions of void fraction. The solutions for using ultrasound to monitor gas-cut situation at the bottom of riser was proposed. Combined with the gas-liquid two-phase model of wellbore annulus in deepwater drilling and the formation pressure prediction method with credibility, the inverse calculation method of gas-cut degree in wellbore was established, which was based on the monitoring data of gas cut at the bottom section of riser. This method could detect the gas cut about four minutes in advance compared with conventional methods, and the gas cut occurring moment, the time left for gas to reach the wellhead, the total overflow rate at any moment, and the void fraction in different depth could be accurately determined based on the acoustic response data of the bottom of riser. Key words: deepwater drilling, gas-cut monitoring, ultrasonic transmission, gas-cut degree, inverse calculation method