Optimization of tight gas reservoir fracturing parameters via gradient boosting regression modeling.

In China, the exploitation of most unconventional oil and gas reservoirs is dependent on hydraulic fracturing, which is a key method employed when developing tight gas formations. Numerous scholars and field engineers, both domestically and internationally, have conducted extensive numerical simulations and physical experiments to study crack propagation and predict post-fracturing productivity in hydraulic fracturing. Although some progress has been reported in this regard, it is difficult to accurately predict the well productivity using mechanistic models owing to the vertical multilayered development of tight gas reservoirs. In this study, vertical fractured wells in a block of Sulige gas field were examined. The block relied on hydraulic fracturing to produce tight gases. However, as development progressed, the available reservoir environment deteriorated, large differences emerged between wells after fracturing, and the fracturing results did not meet the expectations. In this study, geological, construction, and generation data for this block that had been collected since 2007 were analyzed. After applying multiple machine-learning methods to filter outliers and fill in missing values, k-means clustering, classification enhancement, extreme gradient enhancement, and LightGBM algorithms were used to establish a regression model. The analysis results revealed that the regression accuracy of the cluster test set was as high as 70% and that the LightGBM model had the best regression effect among the 227 stripper wells in the block. After optimizing the fracturing construction parameters (fracturing fluid volume, proppant volume, liquid-nitrogen volume, and pumping rate), the average fracturing fluid and liquid-nitrogen volumes per well decreased, whereas the unit reservoir proppant and liquid-nitrogen volumes increased. The results also revealed that 182 wells showed an improved initial production capacity during fracturing. The average gas production index per meter increased by 22.04%. This approach enabled rapid and efficient production forecasting and construction optimization. Moreover, this represents a novel fracture design method that is applicable to onsite engineers in tight gas production fields in the Ordos region.

Incidence rate and implications of splenic ischemia during sleeve gastrectomy and its related procedure.

Splenic ischemia (SI) is a common finding during sleeve gastrectomy (SG) procedures; however, reports are still lacking. In this study, we retrospectively analyzed our SG patients to understand better the incidence rate and implications of SI. Patients' data from the beginning of the year 2021 until December 2022 that underwent bariatric surgery at our university hospital were retrospectively analyzed. Patient surgery video was reviewed by all the authors to investigate the incidence of SI. Thereafter, the corresponding patient age, height, weight, BMI, and their postoperative day 1 (POD1) temperature and blood routine test results (patients were routinely discharged at POD2) were collected and analyzed. 204 patients were included in this study. The mean age and preoperative BMI were 31.7 ±â€…7.4 years old and 38.8 ±â€…5.6 kg/m2, respectively. SI was observed in 18 cases (8.8%). 30-day readmission rate was seen in 3 patients (1.5%, all without SI during the primary surgery). There was no statistical difference with regard to the POD1 temperature and blood test results between the patients with and without SI. The incidence of SI during sleeve gastrectomy-related procedures is a common finding in our study. We did not observe significant differences postoperatively between the patients with and without SI before discharge. Further study is needed to understand the mechanism for the incidence of SI during SG.

Spatio-temporal distribution characteristics and driving factors of phytoplankton community in Duchang Migratory Bird Nature Reserve of Lake Poyang, China: a 9-year study.

Eutrophication of water bodies used as migratory bird habitats will lead to a sharp increase in the abundance of phytoplankton, mainly cyanobacteria. These changes will affect the species distribution of migratory birds, thus damaging the ecological balance of affected habitats. We used 9-year field quarterly data of phytoplankton and environmental factors in the Duchang Reserve (2011 to 2016 and 2019 to 2021) as the basis to analyze the temporal and spatial distribution characteristics of phytoplankton, and explore the phytoplankton community succession and its driving factors through redundancy analysis. The results show that (1) during our sampling, 7 phyla and 93 genera of phytoplankton were identified; (2) the nutrient content of the water in Duchang Nature Reserve decreased, but the phytoplankton increased; (3) the factors influencing phytoplankton shifted from initially nutrient controlled to hydrological control; and (4) the driving factors of phytoplankton are seasonal. Nutrients are the main driving factor of phytoplankton in the dry season (January), while hydrological factors have a greater impact on phytoplankton in the wet season (July) and dry season (October).

Effects of various interventions on non-alcoholic fatty liver disease (NAFLD): A systematic review and network meta-analysis.

Background: With the increasing prevalence of obesity and metabolic syndrome, the incidence of non-alcoholic fatty liver disease (NAFLD) is also increasing. In the next decade, NAFLD may become the main cause of liver transplantation. Therefore, the choice of treatment plan is particularly important. The purpose of this study was to compare several interventions in the treatment of NAFLD to provide some reference for clinicians in selecting treatment methods. Methods: We searched Public Medicine (PubMed), Medline, Excerpta Medica Database (Embase), and Cochrane Library from January 2013 to January 2023 to identify randomized controlled trials (RCTs) published in English. The network meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Forty-three studies accounting for a total of 2,969 patients were included, and alanine aminotransferase (ALT), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL) were selected as outcome measures for analysis and comparison. Results: We evaluated the results of drug, diet, and lifestyle interventions between the intervention and control groups. Curcumin (CUN) and probiotics (PTC) were selected for medication, the Mediterranean diet (MDED) was selected for special diet (SPD), and various kinds of exercise and lifestyle advice were selected for lifestyle interventions (LFT). The SUCRA was used to rank interventions according to the effect on ALT indicators (SUCRA: PTC 80.3%, SPD 65.2%, LFT 61.4%, PLB 32.8%, CUN 10.2%), TC indicators (SUCRA: PTC 89.4%, SPD 64%, CUN 34%, LFT 36.6%, PLB 17%), and LDL indicators (SUCRA: PTC 84.2%, CUN 69.5%, LFT 51.7%, PLB 30.1%, SPD 14.5%). The pairwise meta-analysis results showed that MDED was significantly better than NT in improving ALT [SMD 1.99, 95% CI (0.38, 3.60)]. In terms of improving TC and LDL, ATS was significantly better than NT [SMD 0.19, 95% CI (0.03, 0.36)] [SMD 0.18, 95% CI (0.01, 0.35)]. Conclusion: Our study showed that PTC is most likely to be the most effective treatment for improving NAFLD indicators. Professional advice on diet or exercise was more effective in treating NAFLD than no intervention.

Proton irradiation of SiPM arrays for POLAR-2.

POLAR-2 is a space-borne polarimeter, built to investigate the polarization of Gamma-Ray Bursts and help elucidate their mechanisms. The instrument is targeted for launch in 2024 or 2025 aboard the China Space Station and is being developed by a collaboration between institutes from Switzerland, Germany, Poland and China. The instrument will orbit at altitudes between 340km and 450km with an inclination of 42 ∘ and will be subjected to background radiation from cosmic rays and solar events. It is therefore pertinent to better understand the performance of sensitive devices under space-like conditions. In this paper we focus on the radiation damage of the silicon photomultiplier arrays S13361-6075NE-04 and S14161-6050HS-04 from Hamamatsu. The S13361 are irradiated with 58MeV protons at several doses up to 4.96Gy, whereas the newer series S14161 are irradiated at doses of 0.254Gy and 2.31Gy. Their respective performance degradation due to radiation damage are discussed. The equivalent exposure time in space for silicon photomultipliers inside POLAR-2 with a dose of 4.96Gy is 62.9years (or 1.78years when disregarding the shielding from the instrument). Primary characteristics of the I-V curves are an increase in the dark current and dark counts, mostly through cross-talk events. Annealing processes at 25 ∘ C were observed but not studied in further detail. Biasing channels while being irradiated have not resulted in any significant impact. Activation analyses showed a dominant contribution of ß + particles around 511 keV. These resulted primarily from copper and carbon, mostly with decay times shorter than the orbital period.

Efficacy and safety of hypoglycemic drugs in improving cognitive function in patients with Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis.

Objective: The purpose of this study was to compare the effects of oral hypoglycaemic drugs (HDs) on cognitive function and biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) through a network meta-analysis of randomized controlled trials (RCTs). Methods: We conducted systematic searches for English- and Chinese-language articles in the PubMed, Medline, Embase, Cochrane Library and Google Scholar databases, with no date restrictions. We performed a network meta-analysis, which we report here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The 16 studies included a total of 3,081 patients. We selected the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living section (ADCS-ADL) and amyloid beta (Aß) 42 as the outcome measures for analysis and comparison. Result: We selected seven treatments and assessed the clinical trials in which they were tested against a placebo control. Of these treatments, intranasal insulin 20 IU (ITSN20), glucagon-like peptide-1 (GLP-1), and dipeptidyl peptidase 4 inhibitor (DPP-4) were associated with significantly improved MMSE scores (7 RCTs, 333 patients, 30≥MMSE score≥20: mild) compared with placebo [standardized mean difference (SMD) 1.11, 95% confidence interval (CI) (0.87, 1.35); SMD 0.75, 95% CI (0.04, 1.41); and SMD 4.08, 95% CI (3.39, 4.77), respectively]. Rosiglitazone 4 mg (RLZ4), rosiglitazone 10 mg (RLZ10), intranasal insulin 40 IU (ITSN40), and ITSN20 significantly decreased ADAS-Cog scores (11 RCTs, 4044 patients, 10 ≤ ADAS-Cog scores ≤ 30: mild and moderate) compared with placebo [SMD -1.40, 95% CI (-2.57, -0.23), SMD -3.02, 95% CI (-4.17, -1.86), SMD -0.92, 95% CI (-1.77, -0.08), SMD -1.88, 95% CI (-3.09, -0.66)]. Additionally, ITSN20 and ITSN40 significantly improved ADCS-ADL scores (2 RCTs, 208 patients, ADCS-ADL scale score ≤ 10: mild) compared with placebo [SMD 0.02, 95% CI (0.01, 0.03), and SMD 0.04, 95% CI (0.03, 0.05), respectively]. In the 16 included studies, the degree of AD was classified as mild or moderate. For mild cognitive impairment, DPP-4 performed best, but for mild to moderate impairment, ITSN40 had excellent performance. Conclusion: Various HDs can improve the cognitive function of MCI and AD patients. Different drug regimens brought different degrees of improvement, which may be related to their dosage, duration, and mechanism of action. Systematic review registration: www.crd.york.ac.uk/prospero.

Decrease of morphine-CPP by sinomenine via mediation of tyrosine hydroxylase, NMDA receptor subunit 2B and opioid receptor in the zebrafish brain.

To study the effects of sinomenine on conditioned place preference (CPP) zebrafish induced by morphine and expression levels of intracephalic tyrosine hydroxylase (TH), NMDA receptor subunit 2B (NR2B), µ-opioid receptor (zfmor) and δ-opioid receptors (zfdor1 and zfdor2), morphine (40mg/kg) was administrated to zebrafish and the effect of CPP was detected in these zebrafish treated with sinomenine. The expression of TH and NR2B was detected by immunohistochemistry; and the mRNA expression of opioid receptors zfmor, zfdor1 and zfdor2 in the zebrafish brain was assayed by RT-qPCR. In the CPP test, morphine induced significant behavioral alteration, while pretreatment with sinomenine or methadone, resulted in decreased activity time in the morphine-paired compartment significantly. Morphine also increased the integral optical density value of TH- and NR2B-positive cells in the zebrafish brain, and reduced the amount of opioid receptors. However, the compound sinomenine could attenuate these effects. These findings demonstrate that sinomenine (80mg/kg) decreased the CPP effects of zebrafish induced by morphine significantly, downregulated expression of TH and NR2B, and upregulated µ-opioid (zfmor) and δ-opioid (zfdor1 and zfdor2) receptor expression in the CPP zebrafish brains.

Real-Time Monitoring System of Automobile Driver Status and Intelligent Fatigue Warning Based on Triboelectric Nanogenerator.

To improve automobile safety, identifying driver fatigue is considerably crucial because it is one of the main causes of traffic accidents. In this research, smart systems based on a triboelectric nanogenerator are designed, which can provide driver status monitoring and fatigue warning in real time. The smart system consists of a self-powered steering-wheel angle sensor (SSAS) and a signal processing unit. The SSAS, which comprises a stator, a rotor, and a sleeve, is mounted on the steering rod, and the electrodes are designed with a phase difference to improve the resolution of the sensor. The turning angle of the steering wheel operated by the driver is recorded by the SSAS; meanwhile, the number of rotations, the average angle, and other parameters in the driver's recorded data are analyzed by the signal processing unit from which a warning threshold for each parameter is determined. The system assesses the status of the driver in real-time by comparing these parameters and threshold values, and experimental results demonstrate that driver status is accurately judged. This work has important potential applications in the fields of traffic safety and intelligent driving.

Expression of miR-133a-5p and ROCK2 in Heart in Methamphetamine-Induced Rats and Intervention of Rhynchophylline.

INTRODUCTION: Rhynchophylline, as a traditional Chinese medicine, was used for the treatment of drug addiction. OBJECTIVE: To investigate miRNAs expression profile in the rat hearts of methamphetamine dependence and the intervention mechanisms of rhynchophylline. MATERIALS AND METHODS: This study detected the expression profile of miRNAs in the methamphetamine-induced rat hearts by microarray and verified the expression of miR-133a-5P and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) protein. RESULTS: After conditioned place preference training, methamphetamine significantly increased the time spent in the drug-paired compartment, while rhynchophylline and MK-801 could reduce the time. Cluster analysis results of miRNAs showed that compared with the control group, the expression of miR-133a-5p in methamphetamine-induced rat hearts was decreased significantly; rhynchophylline could significantly increase the expression of miR-133a-5p. The result was verified by real-time polymerase chain reaction. The results of target gene predictive software and related research showed that ROCK2 protein may be the target gene of miR-133a-5p. The immunohistochemistry results of heart tissues showed that the expression of ROCK2 protein was significantly upregulated in the methamphetamine group and downregulate in the rhynchophylline group; the difference between the MK-801 group and the methamphetamine group was not significant. The result of western blot was consistent with the immunohistochemistry. CONCLUSION: The active ingredient of Chinese herbal medicine rhynchophylline can effectively inhibit the formation of methamphetamine-dependent conditional place preference (CPP) effect in rats to some extent. MiR-133a-5p may participate in the cardioprotective effects of CPP rats by targeting ROCK2.

Sinomenine Protects Against Morphine Dependence through the NMDAR1/CAMKII/CREB Pathway: A Possible Role of Astrocyte-Derived Exosomes.

Sinomenine is a nonaddictive alkaloid used to prevent morphine dependence, even thoughits mechanism isnot fully understood. Astrocytes aggravate the pathological process in their neighboring cellsthrough exosomes in central nervous system diseases. However, the effect of sinomenine on astrocyte-derived exosomes for the amelioration of morphine dependence has not been reported yet. In this study, we found that sinomenine prevented the morphine-induced conditionedplace preference in mice. Sinomenine reduced the levels of cAMP and intracellular Ca2+ in morphine-treated SH-SY5Y cells. Moreover, sinomenine inhibited the expressions of p-NMDAR1/NMDAR1, p-CAMKII/CAMKII, and p-CREB/CREB in the hippocampusof morphine-dependent mice and SH-SY5Y cells. Furthermore, we found that sinomenine inhibitedthe morphine-induced activation of astrocytesin vivo and in vitro. Afterwards, exosomes were isolated from cultured primary astrocytes treated with phosphate buffer saline (PBS, ctl-exo), morphine (mor-exo), or morphine and sinomenine (Sino-exo). Subsequently, morphine-treated SH-SY5Y cells were treated with ctl-exo, mor-exo, and Sino-exo. Results showed that Sino-exo reduced the level of cAMP, intracellular Ca2+, and the expression of p-CAMKII/CAMKII and p-CREB/CREB in morphine-treated SH-SY5Y cells. In conclusion, we demonstrated that sinomenine exhibited protective effects against morphine dependencein vivo and in vitro through theNMDAR1/CAMKII/CREB pathway. Sinomenine-induced alterationof the function of astrocyte-derived exosomes may contribute to the antidependence effects of sinomenine in morphine dependence.

Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine-Induced Rats and Intervention of Rhynchophylline.

OBJECTIVE: To compare the expressions of miRNAs (microRNAs) in serum exosomes and in hippocampus and to provide insights into the miRNA-mediated relationship between peripheral and central nervous systems in the presence of methamphetamine. METHODS: Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine were replicated. The expressions of miRNAs in serum exosomes and hippocampus were determined by gene-chip sequencing. We then predicted the potential target genes of selected, differentially expressed (DE) miRNAs and then carried out functional analysis of these target genes. We also verified our results by RT-qPCR. RESULTS: Methamphetamine reward could greatly increase the activity time and distance in the intrinsically nonpreferred side of the behavioral apparatus compared with control rats (P < 0.01). Rhynchophylline treatment significantly counteracted these changes (P < 0.01). Methamphetamine-induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log2 FC < -1, P < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log2 FC > 1 or <-1, P < 0.01). When methamphetamine induced CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We selected six DE miRNAs from each of serum exosomes and hippocampus for target gene prediction and functional analysis. We found that, in both, the DE miRNAs and their target genes may be related to neuronal information transmission and synaptic transmission. CONCLUSIONS: Rhynchophylline blocked the alteration of behavior and the expression of some DE miRNAs induced by methamphetamine. The biological functions of these DE miRNAs target genes are correlated between serum exosomes and hippocampus. As to these biological processes and pathways which are involved in the development of addiction at multiple stages, we speculate that these DE miRNAs in serum exosomes and hippocampus are closely related to methamphetamine addiction.

Expression of microRNAs in the serum exosomes of methamphetamine-dependent rats vs. ketamine-dependent rats.

Drug abuse is a public health and social problem. A number of studies have reported that drug addiction is associated with microRNAs (miRNAs). By comparing the expression of miRNAs in the serum exosomes of methamphetamine-dependent and ketamine-dependent rats, the aim of the present study was to provide insights into the miRNA-mediated associations between the two groups. Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine and ketamine were replicated. The expression of miRNAs in serum exosomes were determined by gene-chip sequencing. The potential target genes of differentially expressed (DE) co-miRNAs were predicted in the methamphetamine and ketamine rats, then functional analysis of their target genes was performed. Methamphetamine and ketamine reward greatly increased the activity time and distance in the intrinsically non-preferred side of the behavioral apparatus when compared with controlled rats (P<0.01). In addition, methamphetamine upregulated the expression of 276 miRNAs and downregulated 25 miRNAs, while ketamine only downregulated the expression of 267 miRNAs. Ten DE co-miRNAs in the two model groups were identified. Functional analysis revealed that DE co-miRNAs are involved in the development of addiction at different stages, and their target genes were enriched in 'vesicular transport', 'amphetamine addiction', 'dopaminergic synapse' and 'GABAergic synapse'. Therefore, it was suggested that these co-miRNAs may have a strong association with drug addiction, and they may be involved in the different addiction processes, which partly explains methamphetamine and ketamine addiction.

Effects of rhynchophylline on the hippocampal miRNA expression profile in ketamine-addicted rats.

In the past few years, ketamine, a noncompetitive NMDA antagonist, has been widely abused worldwide as a new type of synthetic drug, severely affecting the physical and mental health of ketamine abusers. Previous studies have suggested that rhynchophylline can alleviate drug abuse and reverse the conditioned place preference caused by the abuse. MicroRNAs (miRNAs) are important factors regulating gene expression and are involved in the drug addiction process. The hippocampus is a critical area in the brain involved in causing drug addiction. However, the hippocampal miRNA expression profile and the effects of rhynchophylline on miRNA expression during ketamine abuse have not been reported. Thus, this study analyzed the hippocampal miRNA expression profile during ketamine-dependence formation and the effects of rhynchophylline on the differential expression of miRNAs induced by ketamine. The results of microarray analysis suggested that the expression levels of miR-331-5p were significantly different among three groups (the control, ketamine, and ketamine + rhynchophylline groups). miR-331-5p levels were significantly decreased in the ketamine model group and were upregulated in the ketamine + rhynchophylline group. Bioinformatics analysis of miR-331-5p and the 3' UTR of nuclear receptor related 1 protein (Nurr1) identified binding sites and showed downregulation, and the overexpression of miR-331-5p in hippocampal tissues showed that miR-331-5p is a negative transcription regulatory factor of Nurr1. Interestingly, we found that the downstream protein of Nurr1, brain-derived neurotrophic factor (BDNF), showed identical expression trends in the hippocampus as Nurr1. However, the transcription of the protein upstream of Nurr1, cyclic adenosine monophosphate response element-binding protein (CREB), did not show any significant differences between the ketamine group and the ketamine + rhynchophylline group. However, after rhynchophylline intervention, p-CREB showed significant differences between the ketamine and the ketamine + rhynchophylline groups. In summary, miR-331-5p is a key regulatory factor of Nurr1, and rhynchophylline can participate in the process of resistance to ketamine addiction through the miR-331-5p/Nurr1/BDNF pathway or inhibition of CREB phosphorylation.

In vitro and in vivo anti-malignant melanoma activity of Alocasia cucullata via modulation of the phosphatase and tensin homolog/phosphoinositide 3-kinase/AKT pathway.

Alocasia cucullata, a Chinese herb, has been used as an anticancer treatment in southern China. Phosphatase and tensin (PTEN), is a tumor suppressor gene and the loss of PTEN expression may activate the phosphoinositide-3-kinase (PI3K)/AKT signaling pathway which play a key role in tumors formation and progression. In this study, we evaluated the anti-melanoma effect and the underlying mechanism of 50% ethanolic extract of A. cucullata (EAC) in vitro and in vivo. Using MTT, wound healing, and transwell assays, we found that EAC suppressed the proliferation, migration, and invasion of melanoma cells (B16-F10, A375 and A2058) in a dose-dependent manner. We also found that EAC suppresses B16-F10 tumor growth in a xenografted mouse model. Western blot analysis revealed that the expression level of PTEN was up-regulated, and phosphorylation of PI3K and AKT reduced in B16-F10 cells and tumor tissues after EAC treatment. No significant differences were observed in PI3K and AKT expression. Moreover, immunohistochemistry showed that the number of PTEN-positive cells in tumor tissues increased and that of p-AKT-positive cells decreased with EAC treatment, corroborating the western blot results. Our data reveal that EAC can inhibit malignant melanoma in vitro and in vivo and suggest that its anti-tumor effect is associated with modulation of the PTEN/ PI3K/AKT signaling pathway. In summary, our findings highlight a promising herbal remedy for the treatment of malignant melanoma, which warrants further study.

[Changes in plasma pharmacokinetics and urinary excretion characteristics before and after combined administration of Ephedrae Herba-Gypsum Fibrosum].

In this study, UPLC-MS/MS was adopted to determine the contents of five ephedrine alkaloids (Norephedrine, Norpseudoephedrine, Ephedrine, Pseudoephedrine, Methylephedrine) in plasma and urine in rats after the combined administration of Ephedrae Herba-Gypsum Fibrosum and calculate relevant pharmacokinetic parameters, in order to discuss the effect of the combined administration of Ephedrae Herba-Gypsum Fibrosum on plasma pharmacokinetics and urinary excretion characteristics. According to the results, after being combined with Gypsum, the five ephedrine alkaloids showed similar pharmacokinetic changes, such as shortened t(max), accelerated absorption rate, but reduced AUC(0-t) and V(z)/F, which may be related to the increase in urine excretion. Besides, Gypsum was added to enhance C(max) of Pseudoephedrine and prolong MRT(0-t) of Methylephedrine, so as to enhance the anti-asthmatic effect of Ephedrae Herba and resist the toxic effect of Norephedrine and Ephedrine. This study proved the scientific compatibility of Ephedrae Herba-Gypsum Fibrosum and provided a reference for studies on the prescription compatibility regularity and relevant practices.

Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts.

The combination of Herba Ephedrae (Mahuang in Chinese) and Radix Aconiti Lateralis (Fuzi in Chinese) is a classical preparation in traditional Chinese medicine and used for treating colds and rheumatic arthralgia. However, herbal medicines containing ephedrines and Aconitum alkaloids are strictly regulated because of the potential for adverse effects on the cardiovascular system and the central nervous system. We aimed to investigate the pharmacokinetics of 11 alkaloids in the Mahuang-Fuzi combination and single-herb extracts after oral administration in rats. The alkaloids were norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine. Simultaneous determination of the alkaloids, including two pairs of diastereomers, was achieved in 14.5 min by a simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method. The separation was performed on a Zorbax SB-Aq column (100 mm × 2.1 mm, 3.5 µm) at a flow rate of 0.3 mL/min using acetonitrile-0.1% formic acid aqueous solution as the mobile phase. The validated method demonstrated adequate sensitivity, selectivity and process efficiency for the quantitative analysis of complex herbal components. Compared with single-herb extracts, alkaloids in plasma (except methylephedrine, benzoylmesaconine and benzoylhypaconine) showed slower elimination (the mean residence time or half-life was longer), although the maximum plasma concentration and area under the plasma concentration curve values decreased. Accumulation may occur with continuous drug intake. These results suggest that drug monitoring may be essential for the safe use of the Mahuang-Fuzi combination.

Pharmacokinetic comparisons of five ephedrine alkaloids following oral administration of four different Mahuang-Guizhi herb-pair aqueous extracts ratios in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Ephedra (Mahuang in Chinese), is derived from dried Ephedra sinica Stapf stems and has been widely used to treat the common cold, coughs, asthma, and edema for thousands of years. The Mahuang-Guizhi herb-pair is a famous formula composed of Mahuang and Ramulus Cinnamomi (Guizhi in Chinese, the dried twig of Cinnamomum cassia Presl.), used to improve pharmacological effects and reduce toxicity. In order to investigate the influence of Mahuang-Guizhi herb-pair ratios on bioavailability, the plasma pharmacokinetics profiles of five ephedrine alkaloids were compared following oral administration of four different ratios to rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned to four groups and orally administered Mahuang-Guizhi (ratios 3:0; 3:1; 3:2; 3:4, w/w). Assays for five ephedrine alkaloids (ephedrine, pseudoephedrine, methylephedrine, norephedrine, and norpseudoephedrine) were developed and validated using ultra-high-performance liquid chromatography tandem mass spectrometry coupled with liquid-liquid extraction. RESULTS: Key pharmacokinetic parameters of the five ephedrine alkaloids (maximal plasma concentration, mean residence time, and half-life) were significantly different (p<0.05) after oral administration of Mahuang-Guizhi herb-pair ratios, as compared to those of Mahuang. CONCLUSION: Ephedrine alkaloid pharmacokinetic differences in rat plasma could help explain previous findings of pharmacological and toxicity differences between Mahuang and Mahuang-Guizhi herb-pair preparations. These results could facilitate future studies to increase the efficacy and decrease the toxicity of Mahuang and Guizhi.

[Pharmacokinetic and Tissue Distribution Study of Ephedrae Herba and Herbal Pair of Ephedrae Herba-Atractylodis Macrocephalae Rhizoma in Rats].

OBJECTIVE: Five kinds of Ephedra alkaloids (NME, NMP, E, PE and ME) in Ephedrae Herba extracts and Ephedrae Herba-Atractylodis Macrocephalae Rhizoma herbal pair extracts of plasma pharmacokinetic and tissue distribution study in rats were carried out, to discuss the changes of Ephedrae Herba compatibility with Atractylodis Macrocephalae Rhizoma before and after METHODS: HPLC- MS method was used and the condition was as flollows: ZORBAX SB-C18 column (100 mm x 2.1 mm, 3.5 µm), column temperature of 35 °C, mobile phase of ACE-0.1% formic solution in gradient elution mode, flow rate at 0.4 mL/min; MRM positive ion detection mode. RESULTS: The distribution trends of Ephedra alkaloids were changing in plasma and tissues of rats after Ephedrae Herba compati- bility with Atractylodis Macrocephalae Rhizoma. CONCLUSION: Ephedrae Herba compatibility with Atractylodis Macrocephalae Rhizoma may increase drug efficacy and reduce the toxicity of Ephedra alkaloids at the same time.

Investigation on the thermal stability of PVC filled with hydrotalcite by the UV-vis spectroscopy.

The thermal stability of the polyvinyl chloride (PVC) filled with hydrotalcite was studied in this paper. It was found that the stability of the PVC resin mixed with organic Sn and hydrotalcite was better than that of the PVC resin mixed with organic Sn alone. The UV-vis spectra showed that under certain heat treatment conditions, the sample without hydrotalcite embodied relatively high content of the conjugated double bonds with the chain length of about 3-5, however, the content of the conjugated double bond with the chain length of about 7 was greatly increased when the hydrotalcite was filled into the PVC resin. The hydrotalcite could inhibit the thermal degradation process of PVC resin in ionic mechanism.