Physical simulation technologies and testing system for cavern shape control from single-well solution mining in rock salt.

The shape of the salt cavern is very important for the safe operation of gas storage facilities in rock salt. A physical simulation test is an effective means to study the shape control of salt caverns. To accurately simulate the process and parameters of single-well solution mining in rock salt, we developed simulation technologies and a testing system for cavern shape control. Based on the flow similarity principle, we established a sealing technology for dynamic-static disturbance and successfully replicated the solution mining process for forward and reverse circulations. Based on the requirement of protective fluid in the field, we developed a protection liquid unit to control the oil pad height to avoid overdissolution or uneven dissolution at the top of the salt cavern. From the principle of distance determination by laser and video, we developed a salt cavern shape visualization and micro-distance detection system that can realize the size measurement and real-time visualization of the salt cavern in pressurized corrosive environment. We put forward the control technology of the testing system that can achieve the integrated and collaborative control of inner and outer pipe spacing, water flow during injection-production circulations, and the height of protection fluid. Finally, we carried out a physical simulation test of solution mining for cavern shape control. The shape and size of the salt cavern from the test are in good agreement with the design. This study can provide an important basis for determining the optimal solution in mining technology and the parameters for cavern shape control.

A convenient and practical triaxial coupled seepage testing apparatus for deep buried coal.

As the world's shallow coal resources are being depleted, resource development continues to progress faster. To explore the coupled hydromechanical behavior of coal reserves that are buried deep underground under high stress, complex seepage, high temperature, adsorption, and desorption, we have developed a triaxial seepage testing apparatus under multifactor coupling effect. The system consists of a high-pressure and high-precision servo control loading system, a triaxial core holder (TEMCO), a seepage dynamic control system, a low-field Nuclear Magnetic Resonance (NMR) test system, a constant temperature control system, and a data acquisition and monitoring system. This system is capable of applying high pressure and long-term loading for specimens under adsorption or desorption. In addition, both steady-state method and pressure transient methods can be applied, thus covering the entire range for coal reserves buried deep from ultralow permeability to high permeability and significantly shortening the testing time. The characteristics of pores and fractures in the specimens and their impacts on permeability can be quantitatively evaluated by the low-field NMR experimental technique. We conducted experiments to understand the evolution of permeability of different gases under different stress conditions and to study the impact of adsorption on pore size distribution. Our experimental results show that the performance of this system is stable and reliable, which allow it to reflect the coupled hydromechanical response of coal buried deep underground. We envision this apparatus has a wide range of application value and can provide a scientific experimental basis for improving the recovery of coalbed methane and geological sequestration of CO2 in the future.

Effects of Dexmedetomidine on the Pharmacokinetics of Dezocine, Midazolam and Its Metabolite 1-Hydroxymidazolam in Beagles by UPLC-MS/MS.

OBJECTIVE: We developed and validated a sensitive and reliable UPLC-MS/MS method for simultaneous determination of dezocine (DEZ), midazolam (MDZ) and its metabolite 1-hydroxymidazolam (1-OH-MDZ) in beagle plasma and investigated the effect of dexmedetomidine (DEX) on the pharmacokinetics of DEZ, MDZ and 1-OH-MDZ in beagles. MATERIALS AND METHODS: Diazepam was used as the internal standard (IS); the three analytes and IS were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column using acetonitrile-0.1% formic acid as mobile phase in gradient mode. In positive ion mode, the three analytes and IS were monitored by multiple reaction monitoring (MRM). Six beagles were designed as a double cycle self-control experiment with 0.15 mg/kg in the first cycle (Group A). After a 1-week washout period, the same six beagles were slowly injected intravenously with 2 µg/kg DEX in the second cycle (Group B), with continuous injection for 7 days. On the seventh day, 0.5 hr after intravenous injection of 2 µg/kg DEX, the six beagles were intramuscularly given with DEZ 0.33 mg/kg and MDZ 0.15 mg/kg. RESULTS: Under the conditions of this experiment, this method exhibited a good linearity for each analyte. The accuracy and precision were all within the acceptable limits in the bioanalytical method, and the results of recovery, matrix effect and stability have also met the requirements. CONCLUSION: The developed UPLC-MS/MS method for simultaneous determination of DEZ, MDZ and 1-OH-MDZ in beagles plasma was accurate, reproducible, specific, and suitable. DEX could inhibit the metabolism of DEZ and MDZ and increase the exposure of DEZ and MDZ in beagles. Therefore, the change of therapeutic effect and the occurrence of adverse reactions caused by drug-drug interaction should be paid attention to when the drugs were used in combination.

Serum lipid profiling of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma by ultra fast LC/IT-TOF MS.

In this study, an ultra fast LC/IT-TOF MS (UFLC/IT-TOF MS)-based serum lipidomics method was employed to characterize the serum lipid profile of patients with chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). After data collection and processing, 96 lipids including lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, triacylglycerides, and cholesterol esters were identified and used for subsequent data analysis. Partial least squares-discriminant analysis revealed that patients with liver diseases had distinctly different serum lipid profile from that of healthy controls; while cirrhosis and HCC patients had a similar serum lipid profile, but different from that of hepatitis patients. The ANOVA analysis found 75 of the 96 identified lipids to be abnormally regulated, among which most of these lipids were downregulated in cirrhosis and HCC patients compared with those of healthy controls and hepatitis patients, while hepatitis patients induced several lipids downregulated and others upregulated compared with those of healthy controls, indicating the aberrant lipid metabolism in patients with liver diseases. This work demonstrated the utility of UFLC/IT-TOF MS-based serum lipidomics as a powerful tool to investigate the lipid metabolism of liver diseases.

A support vector machine-recursive feature elimination feature selection method based on artificial contrast variables and mutual information.

Filtering the discriminative metabolites from high dimension metabolome data is very important in metabolomics study. Support vector machine-recursive feature elimination (SVM-RFE) is an efficient feature selection technique and has shown promising applications in the analysis of the metabolome data. SVM-RFE measures the weights of the features according to the support vectors, noise and non-informative variables in the high dimension data may affect the hyper-plane of the SVM learning model. Hence we proposed a mutual information (MI)-SVM-RFE method which filters out noise and non-informative variables by means of artificial variables and MI, then conducts SVM-RFE to select the most discriminative features. A serum metabolomics data set from patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma analyzed by liquid chromatography-mass spectrometry (LC-MS) was used to demonstrate the validation of our method. An accuracy of 74.33±2.98% to distinguish among three liver diseases was obtained, better than 72.00±4.15% from the original SVM-RFE. Thirty-four ion features were defined to distinguish among the control and 3 liver diseases, 17 of them were identified.

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases.

Patients with chronic liver diseases (CLD) including chronic hepatitis B and hepatic cirrhosis (CIR) are the major high-risk population of hepatocellular carcinoma (HCC). The differential diagnosis between CLD and HCC is a challenge. This work aims to study the related metabolic deregulations in HCC and CLD to promote the discovery of the differential metabolites for distinguishing the different liver diseases. Serum metabolic profiling analysis from patients with CLD and HCC was performed using a liquid chromatography-mass spectrometry system. The acquired large amount of metabolic information was processed with the random forest-recursive feature elimination method to discover important metabolic changes. It was found that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the non-malignant liver diseases, accompanied with corresponding alterations of enzyme activities. However, the general changing extent was smaller in HCC than in CIR, possibly due to the special energy-consumption mechanism of tumor cells. These observations may help to understand the mechanism of HCC occurrence and progression on the metabolic level and provide information for the identification of early and differential metabolic markers for HCC.

Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis.

The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target metabolomics method, and test their usefulness in early human HCC diagnosis. The serum metabolic profiling of the diethylnitrosamine-induced rat HCC model, which presents a stepwise histopathological progression that is similar to human HCC, was performed using liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Three metabolites, taurocholic acid, lysophosphoethanolamine 16:0, and lysophosphatidylcholine 22:5, were defined as "marker metabolites," which can be used to distinguish the different stages of chemical hepatocarcinogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients. To test their diagnosis potential 412 sera from 262 patients with HCC, 76 patients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumor (solitary nodules of less than 2 cm in diameter) patients, achieved a sensitivity of 80.5% and a specificity of 80.1%,which is better than those of α-fetoprotein (53 and 64%, respectively). Moreover, they were also effective for the discrimination of all HCCs and chronic liver disease patients, which could achieve a sensitivity of 87.5% and a specificity of 72.3%, better than those of α-fetoprotein (61.2 and 64%). These results indicate metabolomics method has the potential of finding biomarkers for the early diagnosis of HCC.