Real-time intelligent lithology identification while drilling is vital to realizing downhole closed-loop drilling. The complex and changeable geological environment in the drilling makes lithology identification face ...Real-time intelligent lithology identification while drilling is vital to realizing downhole closed-loop drilling. The complex and changeable geological environment in the drilling makes lithology identification face many challenges. This paper studies the problems of difficult feature information extraction,low precision of thin-layer identification and limited applicability of the model in intelligent lithologic identification. The author tries to improve the comprehensive performance of the lithology identification model from three aspects: data feature extraction, class balance, and model design. A new real-time intelligent lithology identification model of dynamic felling strategy weighted random forest algorithm(DFW-RF) is proposed. According to the feature selection results, gamma ray and 2 MHz phase resistivity are the logging while drilling(LWD) parameters that significantly influence lithology identification. The comprehensive performance of the DFW-RF lithology identification model has been verified in the application of 3 wells in different areas. By comparing the prediction results of five typical lithology identification algorithms, the DFW-RF model has a higher lithology identification accuracy rate and F1 score. This model improves the identification accuracy of thin-layer lithology and is effective and feasible in different geological environments. The DFW-RF model plays a truly efficient role in the realtime intelligent identification of lithologic information in closed-loop drilling and has greater applicability, which is worthy of being widely used in logging interpretation.展开更多
Background:As of 2023,coronavirus disease 2019(COVID-19)is still spreading globally.Therefore,we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for cl...Background:As of 2023,coronavirus disease 2019(COVID-19)is still spreading globally.Therefore,we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for clinical prescriptions to improve COVID-19-related symptoms.Materials and methods:The information on non-critical COVID-19 high-frequency Chinese medicines in the diagnosis and treatment of COVID-19 was obtained by the TCM inheritance support platform.Using network pharmacology and molecular docking technology,high-targeting Chinese medicines with good docking activity with COVID-19 receptors angiotensin-converting enzyme-II(ACE2),3CLpro and tyrosine-protein kinase receptor UFO(AXL)were obtained.A new prescription for non-critical COVID-19 was established by integrating high-frequency and high-targeting Chinese medicines.Rats with acute lung injury induced by lipopolysaccharide were used as the experimental model.The histopathological changes in the lungs of rats in each group were observed by hematoxylin-eosin staining.The lung coefficient of rats was measured.The levels of IL-6,TNF-α,and IL-1βin serum were detected by enzyme-linked immunosorbent assay.The mRNA and protein levels of ACE2 and AXL in lung tissue were detected by real-time quantitative polymerase chain reaction and western blot.Results:Through data mining,it was found that there were 39 high-frequency traditional Chinese medicines for non-critical COVID-19 in the diagnosis and treatment guidelines.According to network pharmacology and molecular docking,30 highly targeted traditional Chinese drugs for COVID-19 were found.The new prescriptions for non-critical COVID-19 were comprehensively obtained,including Glycyrrhizae Radix,Ephedra Herba,Amygdalus Communis Vas,Gypsum Fibrosum,Descurainiae Semen,Atractylodes Lancea,Scutellariae Radix,Amomum Tsao-Ko Crevostet,Forsythiae Fructus,Pogostemon cablin,Magnolia Officinalis.Compared with the LPS-induced lung injury model group,the medium dose of the new prescription group had significantly alleviated pathological changes in lung tissue,decreased lung coefficient,decreased contents of IL-6,TNF-αand IL-1β,and increased mRNA and protein expression of ACE2 and AXL(P<0.05).Conclusion:Based on data mining,network pharmacology and molecular docking technology,the new prescription for non-critical COVID-19 established by this method has an anti-inflammatory effect on rats with acute lung injury induced by lipopolysaccharide and can provide a reference for clinicians to alleviate the symptoms related to non-critical COVID-19.展开更多
AIM:To investigate the relationship between overexpression of urokinase plasminogen activator(uPA) and hepatitis B virus(HBV) related liver diseases in a transgenic mouse model.METHODS:Albumin-tetracycline reverse tra...AIM:To investigate the relationship between overexpression of urokinase plasminogen activator(uPA) and hepatitis B virus(HBV) related liver diseases in a transgenic mouse model.METHODS:Albumin-tetracycline reverse transcriptional activator and tetO-uPA transgenic mice were generated respectively through pronuclear injection and crossed to produce the double transgenic in-alb-uPA mice,for which doxycycline(Dox)-inducible and liver-specific over-expression of uPA can be achieved.Hydrodynamic transfection of plasmid adeno-associated virus(AAV)1.3HBV was performed through the tail veins of the Dox-induced in-alb-uPA mice.Expression of uPA and HBV antigens were analyzed through double-staining immunohistochemical assay.Cytokine production was detected by enzyme linked immunosorbent assay and α-fetoprotein(AFP) mRNA level was evaluated through real-time quantitative polymerase chain reaction.RESULTS:Plasmid AAV-1.3HBV hydrodynamic transfection in Dox-induced transgenic mice not only resulted in severe liver injury with hepatocarcinoma-like histological changes and hepatic AFP production,but also showed an increased serum level of HBV antigens and cytokines like interleukin-6 and tumor necrosis factor-α,compared with the control group.CONCLUSION:Over-expression of uPA plays a synergistic role in the development of liver injury,inflammation and regeneration during acute HBV infection.展开更多
Background:This study gets a classic prescription of Song Dynasty medicine for the treatment of waist and leg pain through analyzing the inheritance of traditional Chinese medicine auxiliary platform.Further,the poten...Background:This study gets a classic prescription of Song Dynasty medicine for the treatment of waist and leg pain through analyzing the inheritance of traditional Chinese medicine auxiliary platform.Further,the potential mechanism of the classic prescription was analyzed based on molecular docking and network pharmacology.Methods:Based on the frequency statistics,association rules and cluster analysis,the core herbal combination and the classic prescription was digged out.Use of network pharmacology methods and molecular docking to explore the pharmacological mechanism of classic prescriptions for treatment of lumbar disc herniation.Then gene ontology biological function annotation and Kyoto Encyclopedia of Genes and Genomes enrichment of pathways were performed.Finally,the compounds of herbs were docked with the important targets of MMP1 and CRP.Results:The high-frequency Chinese medicines for treating waist and leg pain were found and we further unearthed the“Rougui-Fuzi-Niuxi(Cinnamoni cortex-Aconm lateralis radix praeparaia-Achyranthis bidentatae radix”as the core herbal combination,and matched the classic ancient prescription of Chinese medicine Jiawei Shenzhuo decoction(CAPCMJWSZD).The targets of CAPCMJWSZD were mapped to the targets of lumbar disc herniation and 48 potential targets were obtained.The core potential targets were obtained in the protein-protein interaction network,such as CRP,IL2,FOS,MMP1,CASP3.Through the DAVID database,a total of 129 gene ontology function annotation terms(P<0.01)and 91 Kyoto Encyclopedia of Genes and Genomes pathways(P<0.01)were obtained.Molecular docking results showed that quercetin has the lowest binding energy for docking with MMP1and CRP,and these two methods of molecular docking are most likely to occur.Conclusion:The most important bioactive components in CAPCMJWSZD can eliminate inflammation and slow disc degeneration through some potential targets,such as CRP,IL-2,MMP1,and these targets can rich in the following pathways,such as metalloendopeptidase activity,MAP kinase activity,osteoclast differentiation,et al.展开更多
Objective: To study the effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction. Methods:The patients with massive cerebra...Objective: To study the effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction. Methods:The patients with massive cerebral infarction who received treatment in our hospital between January 2016 and December 2017 were selected and randomly divided into the group A receiving Butylphthalide treatment, the group B receiving Urinary Kallidinogenase treatment and the group C receiving Butylphthalide combined with Urinary Kallidinogenase treatment on the basis of conventional treatment. 14 d after treatment, serum levels of nerve markers, coagulation indexes, growth factors and oxidative stress indexes were determined. Results:After treatment, visinin-like protein-1 (VILIP-1), neuron-specific enolase (NSE), S100B protein (S100B), thromboxane A2 (TXA2), lysophosphatidic acid (LPA), D-dimer (D-D), 8-isoprostanes F2α (8-iso-PGF2α) and malondialdehyde (MDA) levels of 3 groups significantly decreased whereas nitric oxide (NO), nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels significantly increased, and VILIP-1, NSE, S100B, TXA2, LPA, D-D, 8-iso-PGF2α and MDA levels of the group C after treatment were significantly lower than those of the group A and group B whereas NO, NOS, VEGF, BDNF, IGF-I, SOD and T-AOC levels were significantly higher than those of the group A and group B. Conclusion: Butylphthalide combined with Urinary Kallidinogenase is better than monotherapy in improving the pathological course of nerve damage in patients with massive cerebral infarction.展开更多
Messenger RNA(mRNA)vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic.Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use.Recently...Messenger RNA(mRNA)vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic.Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use.Recently,we have developed a lipid nanoparticle-encapsulated mRNA(mRNA-LNP)encoding the receptor-binding domain(RBD)of SARS-CoV-2(termed ARCoV),which confers complete protection in mouse model.Herein,we further characterized the protection efficacy of ARCoV in nonhuman primates and the Iong-term stability under normal refrigerator temperature.Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques.More importantly,ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2,and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV.No evidenee of antibody-dependent enhancement of infection was observed throughout the study.Finally,extensive stability assays showed that ARCoV can be stored at 2-8℃ for at least 6 months without decrease of immunogenicity.All these promising results strongly support the ongoing clinical trial.展开更多
基金financially supported by the National Natural Science Foundation of China(No.52174001)the National Natural Science Foundation of China(No.52004064)+1 种基金the Hainan Province Science and Technology Special Fund “Research on Real-time Intelligent Sensing Technology for Closed-loop Drilling of Oil and Gas Reservoirs in Deepwater Drilling”(ZDYF2023GXJS012)Heilongjiang Provincial Government and Daqing Oilfield's first batch of the scientific and technological key project “Research on the Construction Technology of Gulong Shale Oil Big Data Analysis System”(DQYT-2022-JS-750)。
文摘Real-time intelligent lithology identification while drilling is vital to realizing downhole closed-loop drilling. The complex and changeable geological environment in the drilling makes lithology identification face many challenges. This paper studies the problems of difficult feature information extraction,low precision of thin-layer identification and limited applicability of the model in intelligent lithologic identification. The author tries to improve the comprehensive performance of the lithology identification model from three aspects: data feature extraction, class balance, and model design. A new real-time intelligent lithology identification model of dynamic felling strategy weighted random forest algorithm(DFW-RF) is proposed. According to the feature selection results, gamma ray and 2 MHz phase resistivity are the logging while drilling(LWD) parameters that significantly influence lithology identification. The comprehensive performance of the DFW-RF lithology identification model has been verified in the application of 3 wells in different areas. By comparing the prediction results of five typical lithology identification algorithms, the DFW-RF model has a higher lithology identification accuracy rate and F1 score. This model improves the identification accuracy of thin-layer lithology and is effective and feasible in different geological environments. The DFW-RF model plays a truly efficient role in the realtime intelligent identification of lithologic information in closed-loop drilling and has greater applicability, which is worthy of being widely used in logging interpretation.
基金Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine(No.2021175).
文摘Background:As of 2023,coronavirus disease 2019(COVID-19)is still spreading globally.Therefore,we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for clinical prescriptions to improve COVID-19-related symptoms.Materials and methods:The information on non-critical COVID-19 high-frequency Chinese medicines in the diagnosis and treatment of COVID-19 was obtained by the TCM inheritance support platform.Using network pharmacology and molecular docking technology,high-targeting Chinese medicines with good docking activity with COVID-19 receptors angiotensin-converting enzyme-II(ACE2),3CLpro and tyrosine-protein kinase receptor UFO(AXL)were obtained.A new prescription for non-critical COVID-19 was established by integrating high-frequency and high-targeting Chinese medicines.Rats with acute lung injury induced by lipopolysaccharide were used as the experimental model.The histopathological changes in the lungs of rats in each group were observed by hematoxylin-eosin staining.The lung coefficient of rats was measured.The levels of IL-6,TNF-α,and IL-1βin serum were detected by enzyme-linked immunosorbent assay.The mRNA and protein levels of ACE2 and AXL in lung tissue were detected by real-time quantitative polymerase chain reaction and western blot.Results:Through data mining,it was found that there were 39 high-frequency traditional Chinese medicines for non-critical COVID-19 in the diagnosis and treatment guidelines.According to network pharmacology and molecular docking,30 highly targeted traditional Chinese drugs for COVID-19 were found.The new prescriptions for non-critical COVID-19 were comprehensively obtained,including Glycyrrhizae Radix,Ephedra Herba,Amygdalus Communis Vas,Gypsum Fibrosum,Descurainiae Semen,Atractylodes Lancea,Scutellariae Radix,Amomum Tsao-Ko Crevostet,Forsythiae Fructus,Pogostemon cablin,Magnolia Officinalis.Compared with the LPS-induced lung injury model group,the medium dose of the new prescription group had significantly alleviated pathological changes in lung tissue,decreased lung coefficient,decreased contents of IL-6,TNF-αand IL-1β,and increased mRNA and protein expression of ACE2 and AXL(P<0.05).Conclusion:Based on data mining,network pharmacology and molecular docking technology,the new prescription for non-critical COVID-19 established by this method has an anti-inflammatory effect on rats with acute lung injury induced by lipopolysaccharide and can provide a reference for clinicians to alleviate the symptoms related to non-critical COVID-19.
基金Supported by National Program of Infection Diseases,No. 2012ZX10004-502The National High Technology Program ("863" Program) of China,No.2007AA02Z151
文摘AIM:To investigate the relationship between overexpression of urokinase plasminogen activator(uPA) and hepatitis B virus(HBV) related liver diseases in a transgenic mouse model.METHODS:Albumin-tetracycline reverse transcriptional activator and tetO-uPA transgenic mice were generated respectively through pronuclear injection and crossed to produce the double transgenic in-alb-uPA mice,for which doxycycline(Dox)-inducible and liver-specific over-expression of uPA can be achieved.Hydrodynamic transfection of plasmid adeno-associated virus(AAV)1.3HBV was performed through the tail veins of the Dox-induced in-alb-uPA mice.Expression of uPA and HBV antigens were analyzed through double-staining immunohistochemical assay.Cytokine production was detected by enzyme linked immunosorbent assay and α-fetoprotein(AFP) mRNA level was evaluated through real-time quantitative polymerase chain reaction.RESULTS:Plasmid AAV-1.3HBV hydrodynamic transfection in Dox-induced transgenic mice not only resulted in severe liver injury with hepatocarcinoma-like histological changes and hepatic AFP production,but also showed an increased serum level of HBV antigens and cytokines like interleukin-6 and tumor necrosis factor-α,compared with the control group.CONCLUSION:Over-expression of uPA plays a synergistic role in the development of liver injury,inflammation and regeneration during acute HBV infection.
基金The 2020 Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine(NO:2020365)The 2019 Hebei University College Student Innovation Training Project(S201910075030).
文摘Background:This study gets a classic prescription of Song Dynasty medicine for the treatment of waist and leg pain through analyzing the inheritance of traditional Chinese medicine auxiliary platform.Further,the potential mechanism of the classic prescription was analyzed based on molecular docking and network pharmacology.Methods:Based on the frequency statistics,association rules and cluster analysis,the core herbal combination and the classic prescription was digged out.Use of network pharmacology methods and molecular docking to explore the pharmacological mechanism of classic prescriptions for treatment of lumbar disc herniation.Then gene ontology biological function annotation and Kyoto Encyclopedia of Genes and Genomes enrichment of pathways were performed.Finally,the compounds of herbs were docked with the important targets of MMP1 and CRP.Results:The high-frequency Chinese medicines for treating waist and leg pain were found and we further unearthed the“Rougui-Fuzi-Niuxi(Cinnamoni cortex-Aconm lateralis radix praeparaia-Achyranthis bidentatae radix”as the core herbal combination,and matched the classic ancient prescription of Chinese medicine Jiawei Shenzhuo decoction(CAPCMJWSZD).The targets of CAPCMJWSZD were mapped to the targets of lumbar disc herniation and 48 potential targets were obtained.The core potential targets were obtained in the protein-protein interaction network,such as CRP,IL2,FOS,MMP1,CASP3.Through the DAVID database,a total of 129 gene ontology function annotation terms(P<0.01)and 91 Kyoto Encyclopedia of Genes and Genomes pathways(P<0.01)were obtained.Molecular docking results showed that quercetin has the lowest binding energy for docking with MMP1and CRP,and these two methods of molecular docking are most likely to occur.Conclusion:The most important bioactive components in CAPCMJWSZD can eliminate inflammation and slow disc degeneration through some potential targets,such as CRP,IL-2,MMP1,and these targets can rich in the following pathways,such as metalloendopeptidase activity,MAP kinase activity,osteoclast differentiation,et al.
文摘Objective: To study the effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction. Methods:The patients with massive cerebral infarction who received treatment in our hospital between January 2016 and December 2017 were selected and randomly divided into the group A receiving Butylphthalide treatment, the group B receiving Urinary Kallidinogenase treatment and the group C receiving Butylphthalide combined with Urinary Kallidinogenase treatment on the basis of conventional treatment. 14 d after treatment, serum levels of nerve markers, coagulation indexes, growth factors and oxidative stress indexes were determined. Results:After treatment, visinin-like protein-1 (VILIP-1), neuron-specific enolase (NSE), S100B protein (S100B), thromboxane A2 (TXA2), lysophosphatidic acid (LPA), D-dimer (D-D), 8-isoprostanes F2α (8-iso-PGF2α) and malondialdehyde (MDA) levels of 3 groups significantly decreased whereas nitric oxide (NO), nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels significantly increased, and VILIP-1, NSE, S100B, TXA2, LPA, D-D, 8-iso-PGF2α and MDA levels of the group C after treatment were significantly lower than those of the group A and group B whereas NO, NOS, VEGF, BDNF, IGF-I, SOD and T-AOC levels were significantly higher than those of the group A and group B. Conclusion: Butylphthalide combined with Urinary Kallidinogenase is better than monotherapy in improving the pathological course of nerve damage in patients with massive cerebral infarction.
基金This work was supported by the National Key Research and Development Project of China(2020YFC0842200,2020YFA0707801,and 2021YFC0863300)the National Natural Science Foundation(Nos.82041044 and 32130005)+2 种基金Cheng-Feng Qin was supported by the National Science Fund for Distinguished Young Scholars(81925025)the Innovative Research Group(81621005)from the NSFCthe Innovation Fund for Medical Sciences(2019-I2M-5-049)from the Chinese Academy of Medical Sciences.
文摘Messenger RNA(mRNA)vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic.Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use.Recently,we have developed a lipid nanoparticle-encapsulated mRNA(mRNA-LNP)encoding the receptor-binding domain(RBD)of SARS-CoV-2(termed ARCoV),which confers complete protection in mouse model.Herein,we further characterized the protection efficacy of ARCoV in nonhuman primates and the Iong-term stability under normal refrigerator temperature.Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques.More importantly,ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2,and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV.No evidenee of antibody-dependent enhancement of infection was observed throughout the study.Finally,extensive stability assays showed that ARCoV can be stored at 2-8℃ for at least 6 months without decrease of immunogenicity.All these promising results strongly support the ongoing clinical trial.