This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further...This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further research ideas for clinical researchers.展开更多
In the Jiaoshiba block of the Fuling shale gas field,the employed reserves and recovery factor by primary well pattern are low,no obvious barrier is found in the development layer series,and layered development is dif...In the Jiaoshiba block of the Fuling shale gas field,the employed reserves and recovery factor by primary well pattern are low,no obvious barrier is found in the development layer series,and layered development is difficult.Based on the understanding of the main factors controlling shale gas enrichment and high production,the theory and technology of shale gas three-dimensional development,such as fine description and modeling of shale gas reservoir,optimization of three-dimensional development strategy,highly efficient drilling with dense well pattern,precision fracturing and real-time control,are discussed.Three-dimensional development refers to the application of optimal and fast drilling and volume fracturing technologies,depending upon the sedimentary characteristics,reservoir characteristics and sweet spot distribution of shale gas,to form"artificial gas reservoir"in a multidimensional space,so as to maximize the employed reserves,recovery factor and yield rate of shale gas development.In the research on shale gas three-dimensional development,the geological+engineering sweet spot description is fundamental,the collaborative optimization of natural fractures and artificial fractures is critical,and the improvement of speed and efficiency in drilling and fracturing engineering is the guarantee.Through the implementation of three-dimensional development,the overall recovery factor in the Jiaoshiba block has increased from 12.6%to 23.3%,providing an important support for the continuous and stable production of the Fuling shale gas field.展开更多
Comprehensive quantitative evaluation of shale gas content and the controlling factors in different occurrence states is of great significance for accurately assessing gas-bearing capacity and providing effective well...Comprehensive quantitative evaluation of shale gas content and the controlling factors in different occurrence states is of great significance for accurately assessing gas-bearing capacity and providing effective well-production strategies. A total of 122 core samples from well JY-A in the Fuling shale gas field were studied to reveal the characteristics of S_1 l shale,15 of which were selected to further predict the shale gas content in different occurrence states, which are dependent on geological factors in the thermal evolution process. Geological parameters were researched by a number of laboratory programs, and the factors influential in controlling shale gas content were extracted by both PCA and GRA methods and prediction models were confirmed by the BE method using SPSS software. Results reveal that the adsorbed gas content is mainly controlled by TOC, Ro, SSA, PD and pyrite content, and the free gas content is mainly controlled by S_2, quartz content, gas saturation and formation pressure for S_1 l in well JY-A. Three methods, including the on-site gas desorption method, the empirical formula method, and the multiple regression analysis method were used in combination to evaluate the shale gas capacity of well JY-A, all of which show that the overall shale gas content of well JY-A is in the range of 2.0–5.0 m^3/t and that the free gas ratio is about 50%, lower than that of well JY-1. Cause analysis further confirms the tectonics and preservation conditions of S_1 l in the geological processes, especially the influence of eastern boundary faults on well JY-A, as the fundamental reasons for the differences in shale gas enrichment in the Jiaoshiba area.展开更多
One of the important indicators of shale gas reservoir excavation is capacity evaluation,which directly affects whether large-scale shale gas reservoirs can be excavated.Capacity evaluation is the basis of system anal...One of the important indicators of shale gas reservoir excavation is capacity evaluation,which directly affects whether large-scale shale gas reservoirs can be excavated.Capacity evaluation is the basis of system analysis and dynamic prediction.Therefore,it is particularly important to conduct capacity evaluation studies on shale gas horizontal wells.In order to accurately evaluate the horizontal well productivity of shale gas staged fracturing,this paper uses a new method to evaluate the productivity of Fuling shale gas.The new method is aimed at the dynamic difference of horizontal wells and effectively analyzes the massive data,which are factors affecting the productivity of shale gas horizontal wells.According to the pressure system,production dynamic characteristics,well trajectory position,fracturing transformation mode and penetration depth,32 wells were divided into four types.Then,based on the classification,the principal component analysis methods can be used to evaluate the horizontal well productivity of shale gas.The new method of capacity evaluation has improved the accuracy by 10.25%compared with the traditional method,which provides a theoretical basis for guiding the efficient development of the horizontal wells of Fuling shale gas.展开更多
The Fuling shale gas field in China is the largest shale gas field as well as the largest of its type discovered in any Lower Paleozoic formation.In this study,the geology and production of the upper and lower gas lay...The Fuling shale gas field in China is the largest shale gas field as well as the largest of its type discovered in any Lower Paleozoic formation.In this study,the geology and production of the upper and lower gas layers in the Fuling shale gas field are evaluated in terms of structure,shale quality,fault,initial production,and estimated ultimate recovery(EUR).The shale in the lower gas layer of the Jiaoshiba anticline is a high-quality reservoir,where the space is dominated by organic pores in kerogen,and the gas content is high.The shale gas wells reveal relatively high initial production and EUR.However,the shale in the upper gas layer of the Jiaoshiba anticline has reservoir space mainly composed of clay mineral pores and organic pores within bitumen,and the gas content is low.In terms of structure,primary gas migration may occur in the upper gas layer,resulting in free gas accumulation in the structural high,where the development effects are generally better than those in the structural low.The lower gas layer in the Pingqiao anticline,is the main interval for shale gas accumulation and development due to the high-quality shale.Under the influence of faults,the efficiency of exploration wells emplaced on top of the anticline is much lower a compared with those in the flanks.The residual synclines close to the Sichuan Basin,including the Baima and Baitao anticlines,are characterized by more recent uplifts,larger area,greater distance from the deep and large faults,and early fracture closure.Therefore,we recommend that the shale gas exploration and development should be carried out preferentially in areas close to the center of the residual synclines,featuring relatively high-pressure coefficient and moderate burial depth.展开更多
Geological characteristics,geomechanical behavior and hydraulic fracture propagation mechanism in the Marcellus shale gas play are analyzed and compared with China’s Fuling shale play.Successful experiences in hydrau...Geological characteristics,geomechanical behavior and hydraulic fracture propagation mechanism in the Marcellus shale gas play are analyzed and compared with China’s Fuling shale play.Successful experiences in hydraulic fracturing and shale gas development in the Marcellus shale gas play are summarized,which might be applicable in other shale plays.The main factors contributing to the successful development of the Marcellus shale gas play include adoption of advanced drilling and completion technologies,increases of hydraulic fracturing stages,proppant concentration and fluid injection volume.The geological and geomechanical mechanisms related to those technologies are analyzed,particularly the in-situ stress impacts on hydraulic fracturing.The minimum horizontal stress controls where the fractures are initiated,and the maximum horizontal stress dominates the direction of the hydraulic fracture propagation.Hydraulic fracturing performed in the shale reservoir normally has no stress barriers in most cases because the shale has a high minimum horizontal stress,inducing hydraulic fractures propagating beyond the reservoir zone,resulting in inefficient stimulation.This is a common problem in shale plays,and its mechanism is studied in the paper.It is also found that the on-azimuth well has a higher productivity than the off-azimuth well,because shear fractures are created in the off-azimuth well,causing main fractures to kink and increasing fracture tortuosity and friction.The Fuling shale gas play has a markedly higher minimum horizontal stress and much smaller horizontal stress difference.The high minimum horizontal stress causes a much higher formation breakdown pressure;therefore,hydraulic fracturing in the Fuling shale gas play needs a higher treatment pressure,which implies higher difficulty in fracture propagation.The small difference in the two horizontal stresses in the Fuling shale gas play generates shorter and more complex hydraulic fractures,because hydraulic fractures in this case are prone to curve to preexisting fractures.To overcome these difficulties,we recommend reducing well spacing and increasing proppant concentration to increase gas productivity for the Fuling shale gas development.展开更多
Marine shale gas in South China is widely distributed and demonstrates an enriched resource. Compared with the North American commercial shale gas field, the shale formation in South China is featured by old age, mult...Marine shale gas in South China is widely distributed and demonstrates an enriched resource. Compared with the North American commercial shale gas field, the shale formation in South China is featured by old age, multiple stages tectonic movements, and high thermal evolution degree and complex reservoir forming conditions. As a result, the existing theories and technical methods of exploration in North America cannot be simply applied to South China. Since 2007, based on the in-depth study on a large quantity of analytical test data, we have conducted the theory and technology research for the southern marine shale gas, found Wufeng-Longmaxi Group deep water shelf high-quality shale gas critical parameters coupling laws, proposed the “Binary Enrichment” theory for highly evolved marine shale gas in southern complex tectonic zone, and established a zone selection and evaluation criteria, which are based on the quality of shale, for the key of preservation condition, and for the purpose of economy. Taking this as a guide, we selected Longmaxi formation Lower Silurian of Fuling area in southeastern Sichuan Province as the preferred breakthrough field for the shale gas exploration. The Jiaoye 1 well has the daily gas production of 20.3 × 10<sup>4</sup> m<sup>3</sup>, which embarked the found of China’s first large-scale business development gas field, the Fuling shale gas field. And we submit the first domestic shale gas proven reserves of 1067.5 × 10<sup>8</sup> m<sup>3</sup>. The Fuling shale gas reservoirs are deep water shelf marine high-quality shale, with favorable thickness and even distribution, without dissection in the middle. They are typical self-generation and self-storage shale gas reservoirs. The gas fields have high production gas well;high pressure gas reservoir, good gas components and good exploit results, and there for the Fuling shale gas field is characterized by mid-depth, high pressure, high reservoir pressure, and high quality gas accumulation. Up to March 24, 2014, all of the 101 fracture-gas testing wells have obtained middle and upper shale airflow, with the average single well test production of 32.6 × 10<sup>4</sup> m<sup>3</sup>/d. In the exploration and development process, technology series in geological evaluation, horizontal well, drilling, well completion, piecewise fracturing techniques have been gradually formed. It is of great importance to commercially develop the domestic shale gas and promote the restructuring of China’s energy structure.展开更多
Enhancing Schwann cell proliferation may be beneficial for peripheral nerve repair and nerve regeneration. A traditional herbal formula composed of Fuling (poria cocos), Baizhu (Atractylodes macrocephala), and Dan...Enhancing Schwann cell proliferation may be beneficial for peripheral nerve repair and nerve regeneration. A traditional herbal formula composed of Fuling (poria cocos), Baizhu (Atractylodes macrocephala), and Danggui (Angelica sinensis) (FBD) improves neuronal survival and growth, and FBD may promote the secretion of brain-derived neurotrophic factor. However, the mechanism underlying Schwann cell proliferation remains unclear. We tested whether FBD enhanced the proliferation of human Schwann cells. FBD (20 ug/mL) increased Schwann cell viability and survival and increased the number of cells at G2/M and S phases. FBD also increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, with maximum efficacy at 20 ug/mL.展开更多
OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fraction...OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.展开更多
Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine syste...Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine system pharmacology database and analysis platform were used to define the bioavailability(OB)30%and drug-likeness(DL)0.18.Database to mine genetic targets related to gouty arthritis disease.Finally,the two genes are intersected to construct a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease.The genes in the network are used to construct a protein interaction network to find core genes for analysis of GO and KEGG.Results:There were a total of 84 active ingredients in Chinese medicine Poria and Poria cocos,and 17 effective ingredients and 180 genetic targets were obtained after screening.600 disease targets for gouty arthritis were identified,and 58 were common target genes for both.PPI network analysis revealed that IL1β,VEGFA,MAPK1,IL10,and PTGS2 may be drugs for treating gouty arthritis.Key targets.GO enrichment analysis identified 1,399 entries(P<0.05),of which biological processes mainly include biological stimulation,biological regulation,cell metabolism,etc;KEGG pathway enrichment analysis identified 152 signal pathways,of which signal pathways involved inflammation,metabolism,In terms of aging,mainly including the IL-4,IL-10,IL-13,IL-17signal pathway,etc.Conclusion:"Bi xie and Tu fuling"drugs have anti-inflammatory and immunological effects on gouty arthritis through multiple targets and multiple pathways.The mechanism of lowering uric acid and protecting liver and kidney is not clear.It needs molecular biology research to improve it.The mechanism of the action of the"Bi xie and Tu fuling"medicine pair provides new ideas for the clinical prescriptions.展开更多
Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to ...Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill.The main active components of the medicine were screened through the network analysis function of Cytoscape software,and the target of the main active components of the medicine was found in UniProt database.Using genecards,OMIM,digsee,TTD,and drugbank database to retrieve the related targets of ovarian cancer.The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software.The intersection targets are imported into string database for PPI analysis,and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in.KEGG pathway analysis and go enrichment analysis were carried out in metascape database.At last,autodock tools was used to verify the main active ingredients and the selected target proteins.PyMOL and LigPlus software visualized the results.Results:The main active components of Guizhi Fuling pills were quercetin,β-sitosterol,kaempferol,hederagenin,catechin,ellagic acid,stigmasterol and Douglas fir.There are 20 pivotal genes of drug effect on ovarian cancer,including VEGFA,AKT1,mapk8,Jun,MMP9,IL6,TNF,CXCL8,PTGS2,TP53,CASP3,mapk1,EGF,ESR1,EGFR,Myc,FOS,CCL2,CXCL8 and IL1B.According to KEGG pathway analysis,10 pathways with the highest correlation were found:cancer signaling pathway,MAPK signaling pathway,fluid shear stress and atherosclerosis,hepatitis B,trypanosomiasis,age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,pertussis,IL-17 signaling pathway,and bladder cancer.Go enrichment analysis has screened out 10 important items in molecular biological function,cell components and biological process.The proteins encoded by IL6,mapk1,VEGFA,AKT1,TP53,TNF and CCL2 were used as targets to dock with the main active components of the drug respectively,and the best results were TNFαand ellagic acid.Conclusion:The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6,VEGFA,CCL2,TNF,MMP9 and other cytokines,and inhibit the proliferation and metastasis of cancer cells.展开更多
Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME f...Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME features on Traditional Chinese Medicine Systems Pharmacology platform,and their targets were obtained.Targets of atherosclerosis were extracted and screened from GeneCards database,OMIM database,DrugBank database and DisGeNET database,and the intersection of component targets and disease targets were regarded as potential targets.The protein-protein interaction network of potential targets was constructed by STRING database and Cytoscape 3.7.2.GO analysis and KEGG pathway analysis of potential targets were performed by Metascape platform.The“drugs-componenst-targets-pathways”network was constructed by Cytoscape 3.7.2.SwissDock was used for molecular docking of active components and key targets.Results:The main components of Guizhi Fuling pill in the treatment of atherosclerosis were quercetin,beta-sitosterol,kaempfero,hederagenin,baicalein,etc.The key targets mainly included PGST2,RELA,AKT1,etc.Molecular docking analysis showed that the binding energy of the main active components to the core target was less than-7 kcal/mol.The associated pathways mainly included fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway and AGE-RAGE signaling pathway.Conclusion:Through this study,we initially revealed the possible mechanism of Guizhi Fuling pill in treating atherosclerosis through anti-inflammatory,reducing blood lipids,and regulating endothelial function.展开更多
Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroid...Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroids who were treated in our hospital from August 2016 to August 2017 were selected according to the order of treatment and divided into observation group and control group, 60 cases each. Mifepristone was administered to the control group and mifepristone combined with Guizhi Fuling Capsules was administered to the observation group. The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups.Result:The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups. After treatment, hemoglobin levels increased significantly in the two groups, VEGF, sex hormones FSH, LH and E2, tumor markers HE4, CA125, inflammatory cytokines TNF-α and IFN-γ levels decreased significantly. The hemoglobin level of the observation group was (117.09±11.51) g/L higher than that of the control group , and the level of VEGF was (0.69±0.06) pg/mL lower than that of the control group. The levels of sex hormone FSH, LH and E2 in the observation group were (15.87±1.56) U/L, (10.69±1.06) U/L and (4.95±0.51) pmol/L lower than those of the control group. The levels of HE4, CA125, TNF-α and IFN-γ gamma in the observation group were (52.47±5.24) pmol/L, (15.46±1.53) U/mL, (40.41±4.05) and (16.72±1.62) pg/mL lower than those of the control group.Conclusion:Guizhi Fuling Capsule can significantly improve the level of sex hormones and tumor markers, relieve inflammatory stress and improve the therapeutic effect.展开更多
Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis...Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.展开更多
Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructe...Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.展开更多
OBJECTIVE:To observe and explore the effect of Fuling(Poria) in alleviating the spleen deficiency symptom pattern(SDSP).METHODS:We established an animal model of SDS in Sprague-Dawley(SD) rats by treating them with de...OBJECTIVE:To observe and explore the effect of Fuling(Poria) in alleviating the spleen deficiency symptom pattern(SDSP).METHODS:We established an animal model of SDS in Sprague-Dawley(SD) rats by treating them with deficiency-inducing factors,including irregular feeding and tail clamping.Mice were administered Fuling(Poria) and its extracts(raw/cooked powder,aqueous/alcohol extract) by gavage once a day for 21 d.The body weight,rectal temperature,and spleen and thymus organ coefficients were calculated.The levels of motilin(MTL),gastrin(GAS),aquaporin 2(AQP2),interleukin 2(IL-2),IL-4,and 5-hydroxytryptamine(5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay.RESULTS:Fuling(Poria) and its extracts did not change the body weight,rectal temperature,and organ coefficients of the spleen and thymus.However,it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2.In addition,the levels of IL-4 and 5-HT showed no significant alteration.CONCLUSIONS:These results suggested the crucial function of Fuling(Poria) in SDSP,especially promoting digestive function and water metabolism.展开更多
Objective: To observe the effects of Guizhi Fuling Capsule(GZFLC) on myeloma cells and explore the mechanisms. Methods: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell exp...Objective: To observe the effects of Guizhi Fuling Capsule(GZFLC) on myeloma cells and explore the mechanisms. Methods: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative(10%, 20% and 40%) groups, GZFLC(10%, 20%, and 40%)groups and a control group. Cell counting kit-8(CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie(ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide(JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), cleaved caspase-3,-9, cytochrome C(Cytc)and apoptotic protease-activating factor 1(Apaf-1). RPMI 8226 cells(2×107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC(840, 420, or 210 mg/kg per day,respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry. Results: GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells(P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential(P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3,-9,Cytc and Apaf-1 were increased(all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLCadministered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLCadministered groups revealed that the Cytc and Apaf-1 expression levels were increased(P<0.05). Conclusion:GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.展开更多
Guizhi Fuling capsule(GFC), a traditional Chinese medicine(TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various c...Guizhi Fuling capsule(GFC), a traditional Chinese medicine(TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry(UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend–C18 column(2.1 mm × 50 mm, 1.8 μm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method provided a reasonable and powerful manner for quality control of GFC.展开更多
Although shale gas resources are abundant in China,commercial discoveries have not been made before the discovery of Fuling Shale Gas Field.SINOPEC has done lots of theoretical and technological studies on marine shal...Although shale gas resources are abundant in China,commercial discoveries have not been made before the discovery of Fuling Shale Gas Field.SINOPEC has done lots of theoretical and technological studies on marine shale gas development in China.Research shows shale gas has dynamic accumulations with early preservation and late reconstruction and proposes high-quality shale developed in deep-water shelf as the base and good preservation conditions as the key factor for shale gas accumulation.Key technologies and facilities were developed for geophysical survey of shale gas,design and optimization of shale gas development,drilling and completion of horizontal wells,and fracturing stimulation.As the first and largest shale gas field in China,the discovery and successful development of Fuling Shale Gas Filed has made China the first country to achieve large-scale development of shale gas after North America.By August 2017,Fuling Shale Gas Field had declared 6008.14×10^(8)m^(3) proven reserves,76.8×10^(8)m^(3) production capacity and 133.9×10^(8)m^(3) cumulative production.The construction of Fuling Shale Gas Field with high level,high speed and high quality has been a good example of shale gas development in China.Its successful experiences can be used to other fields and play an important role in optimizing energy structure and improving environment.展开更多
文摘This paper reviews the research progress of Guizhi Fuling Pill in the clinical application of gynecology,such as the treatment of uterine leiomyoma,ovarian cyst,infertility and dysmenorrhea,in order to provide further research ideas for clinical researchers.
基金Supported by the Sinopec Science and Technology Project(P22183).
文摘In the Jiaoshiba block of the Fuling shale gas field,the employed reserves and recovery factor by primary well pattern are low,no obvious barrier is found in the development layer series,and layered development is difficult.Based on the understanding of the main factors controlling shale gas enrichment and high production,the theory and technology of shale gas three-dimensional development,such as fine description and modeling of shale gas reservoir,optimization of three-dimensional development strategy,highly efficient drilling with dense well pattern,precision fracturing and real-time control,are discussed.Three-dimensional development refers to the application of optimal and fast drilling and volume fracturing technologies,depending upon the sedimentary characteristics,reservoir characteristics and sweet spot distribution of shale gas,to form"artificial gas reservoir"in a multidimensional space,so as to maximize the employed reserves,recovery factor and yield rate of shale gas development.In the research on shale gas three-dimensional development,the geological+engineering sweet spot description is fundamental,the collaborative optimization of natural fractures and artificial fractures is critical,and the improvement of speed and efficiency in drilling and fracturing engineering is the guarantee.Through the implementation of three-dimensional development,the overall recovery factor in the Jiaoshiba block has increased from 12.6%to 23.3%,providing an important support for the continuous and stable production of the Fuling shale gas field.
基金financially supported by the Natural Science Foundation of China (NSFC Grant 41572106)+1 种基金the National Science and Technology Major Project "The enrichment conditions, evaluation technology and application of shale gas in the Sichuan Basin and its periphery" (Item No. 2017ZX05035002-006)State Key Laboratory of oil and gas resources and exploration, Chinese University of Petroleum-Beijing
文摘Comprehensive quantitative evaluation of shale gas content and the controlling factors in different occurrence states is of great significance for accurately assessing gas-bearing capacity and providing effective well-production strategies. A total of 122 core samples from well JY-A in the Fuling shale gas field were studied to reveal the characteristics of S_1 l shale,15 of which were selected to further predict the shale gas content in different occurrence states, which are dependent on geological factors in the thermal evolution process. Geological parameters were researched by a number of laboratory programs, and the factors influential in controlling shale gas content were extracted by both PCA and GRA methods and prediction models were confirmed by the BE method using SPSS software. Results reveal that the adsorbed gas content is mainly controlled by TOC, Ro, SSA, PD and pyrite content, and the free gas content is mainly controlled by S_2, quartz content, gas saturation and formation pressure for S_1 l in well JY-A. Three methods, including the on-site gas desorption method, the empirical formula method, and the multiple regression analysis method were used in combination to evaluate the shale gas capacity of well JY-A, all of which show that the overall shale gas content of well JY-A is in the range of 2.0–5.0 m^3/t and that the free gas ratio is about 50%, lower than that of well JY-1. Cause analysis further confirms the tectonics and preservation conditions of S_1 l in the geological processes, especially the influence of eastern boundary faults on well JY-A, as the fundamental reasons for the differences in shale gas enrichment in the Jiaoshiba area.
文摘One of the important indicators of shale gas reservoir excavation is capacity evaluation,which directly affects whether large-scale shale gas reservoirs can be excavated.Capacity evaluation is the basis of system analysis and dynamic prediction.Therefore,it is particularly important to conduct capacity evaluation studies on shale gas horizontal wells.In order to accurately evaluate the horizontal well productivity of shale gas staged fracturing,this paper uses a new method to evaluate the productivity of Fuling shale gas.The new method is aimed at the dynamic difference of horizontal wells and effectively analyzes the massive data,which are factors affecting the productivity of shale gas horizontal wells.According to the pressure system,production dynamic characteristics,well trajectory position,fracturing transformation mode and penetration depth,32 wells were divided into four types.Then,based on the classification,the principal component analysis methods can be used to evaluate the horizontal well productivity of shale gas.The new method of capacity evaluation has improved the accuracy by 10.25%compared with the traditional method,which provides a theoretical basis for guiding the efficient development of the horizontal wells of Fuling shale gas.
基金supported by the National Natural Science Foundation of China(Grant No.41872124 and 91755211)and several Sinopec in-house projects.We thank Sinopec Petroleum Exploration and Production Research Institute,Sinopec Exploration Company,Sinopec Jianghan Oilfield,and Sinopec East China Petroleum Company for valuable data and information.
文摘The Fuling shale gas field in China is the largest shale gas field as well as the largest of its type discovered in any Lower Paleozoic formation.In this study,the geology and production of the upper and lower gas layers in the Fuling shale gas field are evaluated in terms of structure,shale quality,fault,initial production,and estimated ultimate recovery(EUR).The shale in the lower gas layer of the Jiaoshiba anticline is a high-quality reservoir,where the space is dominated by organic pores in kerogen,and the gas content is high.The shale gas wells reveal relatively high initial production and EUR.However,the shale in the upper gas layer of the Jiaoshiba anticline has reservoir space mainly composed of clay mineral pores and organic pores within bitumen,and the gas content is low.In terms of structure,primary gas migration may occur in the upper gas layer,resulting in free gas accumulation in the structural high,where the development effects are generally better than those in the structural low.The lower gas layer in the Pingqiao anticline,is the main interval for shale gas accumulation and development due to the high-quality shale.Under the influence of faults,the efficiency of exploration wells emplaced on top of the anticline is much lower a compared with those in the flanks.The residual synclines close to the Sichuan Basin,including the Baima and Baitao anticlines,are characterized by more recent uplifts,larger area,greater distance from the deep and large faults,and early fracture closure.Therefore,we recommend that the shale gas exploration and development should be carried out preferentially in areas close to the center of the residual synclines,featuring relatively high-pressure coefficient and moderate burial depth.
文摘Geological characteristics,geomechanical behavior and hydraulic fracture propagation mechanism in the Marcellus shale gas play are analyzed and compared with China’s Fuling shale play.Successful experiences in hydraulic fracturing and shale gas development in the Marcellus shale gas play are summarized,which might be applicable in other shale plays.The main factors contributing to the successful development of the Marcellus shale gas play include adoption of advanced drilling and completion technologies,increases of hydraulic fracturing stages,proppant concentration and fluid injection volume.The geological and geomechanical mechanisms related to those technologies are analyzed,particularly the in-situ stress impacts on hydraulic fracturing.The minimum horizontal stress controls where the fractures are initiated,and the maximum horizontal stress dominates the direction of the hydraulic fracture propagation.Hydraulic fracturing performed in the shale reservoir normally has no stress barriers in most cases because the shale has a high minimum horizontal stress,inducing hydraulic fractures propagating beyond the reservoir zone,resulting in inefficient stimulation.This is a common problem in shale plays,and its mechanism is studied in the paper.It is also found that the on-azimuth well has a higher productivity than the off-azimuth well,because shear fractures are created in the off-azimuth well,causing main fractures to kink and increasing fracture tortuosity and friction.The Fuling shale gas play has a markedly higher minimum horizontal stress and much smaller horizontal stress difference.The high minimum horizontal stress causes a much higher formation breakdown pressure;therefore,hydraulic fracturing in the Fuling shale gas play needs a higher treatment pressure,which implies higher difficulty in fracture propagation.The small difference in the two horizontal stresses in the Fuling shale gas play generates shorter and more complex hydraulic fractures,because hydraulic fractures in this case are prone to curve to preexisting fractures.To overcome these difficulties,we recommend reducing well spacing and increasing proppant concentration to increase gas productivity for the Fuling shale gas development.
文摘Marine shale gas in South China is widely distributed and demonstrates an enriched resource. Compared with the North American commercial shale gas field, the shale formation in South China is featured by old age, multiple stages tectonic movements, and high thermal evolution degree and complex reservoir forming conditions. As a result, the existing theories and technical methods of exploration in North America cannot be simply applied to South China. Since 2007, based on the in-depth study on a large quantity of analytical test data, we have conducted the theory and technology research for the southern marine shale gas, found Wufeng-Longmaxi Group deep water shelf high-quality shale gas critical parameters coupling laws, proposed the “Binary Enrichment” theory for highly evolved marine shale gas in southern complex tectonic zone, and established a zone selection and evaluation criteria, which are based on the quality of shale, for the key of preservation condition, and for the purpose of economy. Taking this as a guide, we selected Longmaxi formation Lower Silurian of Fuling area in southeastern Sichuan Province as the preferred breakthrough field for the shale gas exploration. The Jiaoye 1 well has the daily gas production of 20.3 × 10<sup>4</sup> m<sup>3</sup>, which embarked the found of China’s first large-scale business development gas field, the Fuling shale gas field. And we submit the first domestic shale gas proven reserves of 1067.5 × 10<sup>8</sup> m<sup>3</sup>. The Fuling shale gas reservoirs are deep water shelf marine high-quality shale, with favorable thickness and even distribution, without dissection in the middle. They are typical self-generation and self-storage shale gas reservoirs. The gas fields have high production gas well;high pressure gas reservoir, good gas components and good exploit results, and there for the Fuling shale gas field is characterized by mid-depth, high pressure, high reservoir pressure, and high quality gas accumulation. Up to March 24, 2014, all of the 101 fracture-gas testing wells have obtained middle and upper shale airflow, with the average single well test production of 32.6 × 10<sup>4</sup> m<sup>3</sup>/d. In the exploration and development process, technology series in geological evaluation, horizontal well, drilling, well completion, piecewise fracturing techniques have been gradually formed. It is of great importance to commercially develop the domestic shale gas and promote the restructuring of China’s energy structure.
基金the Korea Health R&D Project,No.A080863,Granted by Ministry of Health and Welfare,Republic of Korea
文摘Enhancing Schwann cell proliferation may be beneficial for peripheral nerve repair and nerve regeneration. A traditional herbal formula composed of Fuling (poria cocos), Baizhu (Atractylodes macrocephala), and Danggui (Angelica sinensis) (FBD) improves neuronal survival and growth, and FBD may promote the secretion of brain-derived neurotrophic factor. However, the mechanism underlying Schwann cell proliferation remains unclear. We tested whether FBD enhanced the proliferation of human Schwann cells. FBD (20 ug/mL) increased Schwann cell viability and survival and increased the number of cells at G2/M and S phases. FBD also increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, with maximum efficacy at 20 ug/mL.
基金supported by National Science and Technology Major Projects of China(2013ZX09402203,2013ZX09508104)Medical and Health Science and Technology Innovation Engineering of Chinese Academy of Medical Sciences(2016-I2M-3-007)National Natural Science Foundation of China(81573454)
文摘OBJECTIVE To evaluate the effect of Guizhi Fuling Capsule active pharmaceutical ingredient(API)and its fractions on human breast cancer cells proliferation by high-throughput screening assay.METHODS The crude fractions were obtained from the extraction and elution of the API of Guizhi Fuling Capsule,and 929 standard fractions were obtained by the optimal separation conditions.Sulforhodamine B(SRB)method was used to evaluate the effects of the Guizhi Fuling capsule API and929 kinds of fractions on the proliferation of human breast cancer cells MCF-7 and MDA-MB-231.RESULTS The Guizhi Fuling capsule API had a strong ability to inhibit the proliferation of MCF-7 cells at high concentration and the ability to inhibit MDA-MB-231 cells' proliferate at low concentration following 72 h treatment;some samples of 929 fractions(5μg·mL^(-1))was found to have a breast cancer cell growth inhibition rate above 50%,without toxicity on HUVECs proliferation.CONCLUSION The API of Guizhi Fuling capsule had significant cytotoxicity effects on these two human breast cancer cells,with significant concentration-and time-dependent manner.
基金National administration of TCM base special fund(No.JDZX2015277)Beijing municipal science and technology commission science and technology star project(No.Z191100001119025)
文摘Objective:The mechanism of Chinese herbal medicine"Bi xie and Tu fuling"on the treatment of gouty arthritis was explored through network pharmacological methods.Methods:First,the TCMSP Chinese medicine system pharmacology database and analysis platform were used to define the bioavailability(OB)30%and drug-likeness(DL)0.18.Database to mine genetic targets related to gouty arthritis disease.Finally,the two genes are intersected to construct a Chinese medicine regulatory network of Chinese medicine-components-target genes-disease.The genes in the network are used to construct a protein interaction network to find core genes for analysis of GO and KEGG.Results:There were a total of 84 active ingredients in Chinese medicine Poria and Poria cocos,and 17 effective ingredients and 180 genetic targets were obtained after screening.600 disease targets for gouty arthritis were identified,and 58 were common target genes for both.PPI network analysis revealed that IL1β,VEGFA,MAPK1,IL10,and PTGS2 may be drugs for treating gouty arthritis.Key targets.GO enrichment analysis identified 1,399 entries(P<0.05),of which biological processes mainly include biological stimulation,biological regulation,cell metabolism,etc;KEGG pathway enrichment analysis identified 152 signal pathways,of which signal pathways involved inflammation,metabolism,In terms of aging,mainly including the IL-4,IL-10,IL-13,IL-17signal pathway,etc.Conclusion:"Bi xie and Tu fuling"drugs have anti-inflammatory and immunological effects on gouty arthritis through multiple targets and multiple pathways.The mechanism of lowering uric acid and protecting liver and kidney is not clear.It needs molecular biology research to improve it.The mechanism of the action of the"Bi xie and Tu fuling"medicine pair provides new ideas for the clinical prescriptions.
基金National Natural Science Foundation of China(No.81473566)。
文摘Objective:To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill.The main active components of the medicine were screened through the network analysis function of Cytoscape software,and the target of the main active components of the medicine was found in UniProt database.Using genecards,OMIM,digsee,TTD,and drugbank database to retrieve the related targets of ovarian cancer.The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software.The intersection targets are imported into string database for PPI analysis,and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in.KEGG pathway analysis and go enrichment analysis were carried out in metascape database.At last,autodock tools was used to verify the main active ingredients and the selected target proteins.PyMOL and LigPlus software visualized the results.Results:The main active components of Guizhi Fuling pills were quercetin,β-sitosterol,kaempferol,hederagenin,catechin,ellagic acid,stigmasterol and Douglas fir.There are 20 pivotal genes of drug effect on ovarian cancer,including VEGFA,AKT1,mapk8,Jun,MMP9,IL6,TNF,CXCL8,PTGS2,TP53,CASP3,mapk1,EGF,ESR1,EGFR,Myc,FOS,CCL2,CXCL8 and IL1B.According to KEGG pathway analysis,10 pathways with the highest correlation were found:cancer signaling pathway,MAPK signaling pathway,fluid shear stress and atherosclerosis,hepatitis B,trypanosomiasis,age-rage signaling pathway in diabetic complications,tumor necrosis factor signaling pathway,pertussis,IL-17 signaling pathway,and bladder cancer.Go enrichment analysis has screened out 10 important items in molecular biological function,cell components and biological process.The proteins encoded by IL6,mapk1,VEGFA,AKT1,TP53,TNF and CCL2 were used as targets to dock with the main active components of the drug respectively,and the best results were TNFαand ellagic acid.Conclusion:The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6,VEGFA,CCL2,TNF,MMP9 and other cytokines,and inhibit the proliferation and metastasis of cancer cells.
基金This study was supported by National Science Foundation of China(81973645,81673805,81704058,and 81774100)Natural Science Foundation of Guangdong(2019A1515011560)Traditional Chinese Medicine Bureau of Guangdong Province(20161167,20201392).
文摘Objective:To investigate the mechanism of action of Guizhi Fuling pill in the treatment of atherosclerosis with network pharmacology.Methods:The active components of Guizhi Fuling pill were screened by specific ADME features on Traditional Chinese Medicine Systems Pharmacology platform,and their targets were obtained.Targets of atherosclerosis were extracted and screened from GeneCards database,OMIM database,DrugBank database and DisGeNET database,and the intersection of component targets and disease targets were regarded as potential targets.The protein-protein interaction network of potential targets was constructed by STRING database and Cytoscape 3.7.2.GO analysis and KEGG pathway analysis of potential targets were performed by Metascape platform.The“drugs-componenst-targets-pathways”network was constructed by Cytoscape 3.7.2.SwissDock was used for molecular docking of active components and key targets.Results:The main components of Guizhi Fuling pill in the treatment of atherosclerosis were quercetin,beta-sitosterol,kaempfero,hederagenin,baicalein,etc.The key targets mainly included PGST2,RELA,AKT1,etc.Molecular docking analysis showed that the binding energy of the main active components to the core target was less than-7 kcal/mol.The associated pathways mainly included fluid shear stress and atherosclerosis,PI3K-Akt signaling pathway and AGE-RAGE signaling pathway.Conclusion:Through this study,we initially revealed the possible mechanism of Guizhi Fuling pill in treating atherosclerosis through anti-inflammatory,reducing blood lipids,and regulating endothelial function.
文摘Objective:To investigate the effect of Guizhi Fuling Capsule on sex hormones and tumor markers in patients with uterine fibroids, and observe its clinical efficacy.Methods: A total of 120 patients with uterine fibroids who were treated in our hospital from August 2016 to August 2017 were selected according to the order of treatment and divided into observation group and control group, 60 cases each. Mifepristone was administered to the control group and mifepristone combined with Guizhi Fuling Capsules was administered to the observation group. The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups.Result:The levels of hemoglobin, vascular endothelial growth factor (VEGF), sex hormones, tumor markers, and inflammatory factors before and after treatment were compared between the two groups. After treatment, hemoglobin levels increased significantly in the two groups, VEGF, sex hormones FSH, LH and E2, tumor markers HE4, CA125, inflammatory cytokines TNF-α and IFN-γ levels decreased significantly. The hemoglobin level of the observation group was (117.09±11.51) g/L higher than that of the control group , and the level of VEGF was (0.69±0.06) pg/mL lower than that of the control group. The levels of sex hormone FSH, LH and E2 in the observation group were (15.87±1.56) U/L, (10.69±1.06) U/L and (4.95±0.51) pmol/L lower than those of the control group. The levels of HE4, CA125, TNF-α and IFN-γ gamma in the observation group were (52.47±5.24) pmol/L, (15.46±1.53) U/mL, (40.41±4.05) and (16.72±1.62) pg/mL lower than those of the control group.Conclusion:Guizhi Fuling Capsule can significantly improve the level of sex hormones and tumor markers, relieve inflammatory stress and improve the therapeutic effect.
基金This work was supported by the National Natural Science Foundation of China(No.82074348)the Taishan Scholar Project(tsqn201812145)the Key Technology Research and Development Program of Shandong(No.2019GSF108162).
文摘Objective To observe the effects of Guizhi Fuling capsule(GZFLC)on RPMI 8226 cells and explore the mechanisms.Methods Cell Counting Kit-8(CCK-8)assays and flow cytometry were used to detect the viability and apoptosis levels of RPMI 8226 cells.The effects on mitochondria were examined by ROS and JC-1 assays.Western blotting was used to detect the expression of B cell lymphoma-2(Bcl-2),Bax,cleaved caspase-3,and Apoptotic protease-activating factor 1(Apaf-1).Results GZFLC drug serum decreased the viability and increased the apoptosis of RPMI 8226 cells.In addition,this drug increased ROS levels and decreased the mitochondrial membrane potential(MMP).Western blotting showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups,whereas the expression levels of cleaved caspase-3 and Apaf-1 were increased.Conclusion GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway.
文摘Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
基金Supported by National Key Research and Development Program of China:Study on the Core Efficacy Evaluation of Fuling(Poria)(No.2017YFC1703005)。
文摘OBJECTIVE:To observe and explore the effect of Fuling(Poria) in alleviating the spleen deficiency symptom pattern(SDSP).METHODS:We established an animal model of SDS in Sprague-Dawley(SD) rats by treating them with deficiency-inducing factors,including irregular feeding and tail clamping.Mice were administered Fuling(Poria) and its extracts(raw/cooked powder,aqueous/alcohol extract) by gavage once a day for 21 d.The body weight,rectal temperature,and spleen and thymus organ coefficients were calculated.The levels of motilin(MTL),gastrin(GAS),aquaporin 2(AQP2),interleukin 2(IL-2),IL-4,and 5-hydroxytryptamine(5-HT) in the serum and the level of AQP2 in the kidneys were evaluated by enzyme-linked immunosorbent assay.RESULTS:Fuling(Poria) and its extracts did not change the body weight,rectal temperature,and organ coefficients of the spleen and thymus.However,it reduced the levels of MTL and GAS and increased the levels of IL-2 and AQP2.In addition,the levels of IL-4 and 5-HT showed no significant alteration.CONCLUSIONS:These results suggested the crucial function of Fuling(Poria) in SDSP,especially promoting digestive function and water metabolism.
基金Supported by the National Natural Science Foundation of China(No.82074348)the Taishan Scholar Project(No.tsqn201812145)+1 种基金the Key Technology Research and Development Program of Shandong(No.2019GSF108162)the Natural Science Foundation of Shandong Province(No.ZR2020MH388)。
文摘Objective: To observe the effects of Guizhi Fuling Capsule(GZFLC) on myeloma cells and explore the mechanisms. Methods: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative(10%, 20% and 40%) groups, GZFLC(10%, 20%, and 40%)groups and a control group. Cell counting kit-8(CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie(ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide(JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), cleaved caspase-3,-9, cytochrome C(Cytc)and apoptotic protease-activating factor 1(Apaf-1). RPMI 8226 cells(2×107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC(840, 420, or 210 mg/kg per day,respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry. Results: GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells(P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential(P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3,-9,Cytc and Apaf-1 were increased(all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLCadministered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLCadministered groups revealed that the Cytc and Apaf-1 expression levels were increased(P<0.05). Conclusion:GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education(No.20130096140001)the 111 Project(No.B16046)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Guizhi Fuling capsule(GFC), a traditional Chinese medicine(TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry(UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend–C18 column(2.1 mm × 50 mm, 1.8 μm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method provided a reasonable and powerful manner for quality control of GFC.
基金The work was supported by the National Science and Technology Major Project of China(No.2016ZX05060).
文摘Although shale gas resources are abundant in China,commercial discoveries have not been made before the discovery of Fuling Shale Gas Field.SINOPEC has done lots of theoretical and technological studies on marine shale gas development in China.Research shows shale gas has dynamic accumulations with early preservation and late reconstruction and proposes high-quality shale developed in deep-water shelf as the base and good preservation conditions as the key factor for shale gas accumulation.Key technologies and facilities were developed for geophysical survey of shale gas,design and optimization of shale gas development,drilling and completion of horizontal wells,and fracturing stimulation.As the first and largest shale gas field in China,the discovery and successful development of Fuling Shale Gas Filed has made China the first country to achieve large-scale development of shale gas after North America.By August 2017,Fuling Shale Gas Field had declared 6008.14×10^(8)m^(3) proven reserves,76.8×10^(8)m^(3) production capacity and 133.9×10^(8)m^(3) cumulative production.The construction of Fuling Shale Gas Field with high level,high speed and high quality has been a good example of shale gas development in China.Its successful experiences can be used to other fields and play an important role in optimizing energy structure and improving environment.