目的基于多元统计分析和网络药理学分析预测炒酸枣仁饮片潜在的质量标志物(Q-Marker)。方法利用超高效液相色谱-四极杆-静电场轨道阱质谱联用(ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap ma...目的基于多元统计分析和网络药理学分析预测炒酸枣仁饮片潜在的质量标志物(Q-Marker)。方法利用超高效液相色谱-四极杆-静电场轨道阱质谱联用(ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap mass spectrometry,UHPLC-Q-Orbitrap-MS)解析生、炒酸枣仁饮片的主要成分,运用多元统计分析结合VIP>1和P<0.05筛选出炮制前后潜在的差异化学成分。结合网络药理学筛选核心靶点构建"成分-靶点-通路"网络关系,预测炒酸枣仁潜在的Q-Marker,以潜在Q-Marker为指标对市售样品进行含量测定,验证Q-Marker的科学性。结果生、炒酸枣仁共鉴定54个化学成分,包括斯皮诺素、当药黄素等黄酮类成分,酸枣仁皂苷A、酸枣仁皂苷B等皂苷类成分,以及木兰花碱、乌药碱等生物碱类成分;结合多元统计分析共找到木兰花碱、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A、白桦脂酸等28个差异性成分;经网络药理学分析筛选出包括17个差异成分的Q-Marker库,分别为酸枣仁皂苷A、酸枣仁皂苷B、美洲茶酸、白桦脂酸、木兰花碱、乌药碱、去甲荷叶碱、巴婆碱、斯皮诺素、当药黄素、维采宁Ⅱ、6"’-对-香豆酰斯皮诺素、6"’-阿魏酰斯皮诺素、芹菜素、桦木酮酸、牡荆素、异牡荆素;结合课题组前期研究及市售样品测定结果,最终确定木兰花碱、乌药碱、斯皮诺素、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A和B作为炒酸枣仁的Q-Marker。结论分析预测的Q-Marker为炒酸枣仁的整体质量控制及临床应用提供科学依据,同时也为其功效关联物质的研究及作用机制的阐释奠定基础。展开更多
Backgrounds Embolic stroke is one of the main mechanisms of ischaemic stroke.Even if treated with recommended antithrombotic agents,stroke recurrence remains high.The Shuxuetong injection,a purified extract of traditi...Backgrounds Embolic stroke is one of the main mechanisms of ischaemic stroke.Even if treated with recommended antithrombotic agents,stroke recurrence remains high.The Shuxuetong injection,a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China,could be a promising agent to prevent stroke recurrence.Aims To describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms.Design The Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism(SPACE)trial is a multicentre,randomised,double-blind,placebo-controlled,parallel-group,superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days.An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days.The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation.Conclusion The SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke.展开更多
A herringbone water-sediment separation structure(hereinafter referred to as "herringbone structure") has been shown to be effective in separating coarse inorganic debris; however, less is known regarding th...A herringbone water-sediment separation structure(hereinafter referred to as "herringbone structure") has been shown to be effective in separating coarse inorganic debris; however, less is known regarding the large wood(LW) filtration effect in this structure. This paper presents preliminary research on the wood filtration effect of the herringbone structure based on physical model tests.The results show that the herringbone structure exhibited effective performance in large wood size segregation, with a 100% component filtration rate for LW that diameter(D) larger than ribbed beam opening width(a). The total filtration rate also exceeded 80% when the Fraud number(Fr) is larger than 2.64 and increased with the increase of Fr. After exceeding Frmax, total filtration rate would be decreased due to overflow. Beside flow condition,structure parameters influence significantly on LW filtration rate. We attempt to explain the filtration process via particle contact trajectory and particle movement trajectory. The inclined angle of ribbed beam(γ) contributed the most variation to the filtration rate via influencing the coincidence with particle contact trajectory and particle movement trajectory. The high sensitivity coefficient of ribbed beam(θ) under relatively low Fr conditions implies remarkable influences on LW filtration effects by causing clogging problem. The ribbed beam opening width(a) together with LW diameter(D) influenced the size segregation performance.展开更多
Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons.Here,we introduced and evaluated a newly modified Mathieu technique,Mathieu combined tunnel(MCT),which involves multiple...Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons.Here,we introduced and evaluated a newly modified Mathieu technique,Mathieu combined tunnel(MCT),which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations;we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence.This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University(Guangzhou,China)for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020;sixteen patients underwent surgery using the MCT(MCT group)and ten patients underwent surgery using the tubularized incised plate(TIP)technique(TIP group).The operative time,blood loss,postoperative complications,normal urethral meatus rate,success rate,and Hypospadias Objective Penile Evaluation(HOPE)score were compared between the two groups.The MCT group achieved an overall satisfactory penile appearance and voiding function,with a higher rate of normal urethral meatus(15/16,93.8%)and a lower rate of glans dehiscence(1/16,6.2%),compared with the TIP group(70.0%and 30.0%,respectively).However,these differences were not statistically significant,possibly because of the limited number of patients(all P>0.05).Mean postoperative HOPE scores were similar in the MCT group(mean±standard deviation:8.83±0.89)and TIP group(8.94±0.57)(P>0.05).No significant differences were found between the two groups in terms of blood loss and success rate,nor in the rates of various complications(e.g.,fistula,urethral stricture,and glans dehiscence).In conclusion,the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.展开更多
Organic semiconductor materials with low reorganization energy have various applications such as in organic light-emitting diodes (OLEDs),organic field-effect transistor (OFETs) and organic solar cells (OSCs).In this ...Organic semiconductor materials with low reorganization energy have various applications such as in organic light-emitting diodes (OLEDs),organic field-effect transistor (OFETs) and organic solar cells (OSCs).In this work,we have designed a new class of gridspiroarenes (GS-SFX and GS-SITF) with #-shaped structures,which have novel crisscross geometrical structures compared to widely used spirocyclic arenes-SFX and SITF.The structure electronic properties,adiabatic ionization potentials (IPa),adiabatic electron affinities (EAa) and reorganization energies (λ) of GS-SFX and GS-SITF have been calculated using density functional theory (DFT) method.The calculated HOMO and LUMO spatial distributions suggest that GS-SFX and GS-SITF have better transport properties.The noncovalent interaction analysis shows the weak intramolecular interactions between their arms.The results indicate that the reorganization energies of GS-SFX and GS-SITF are significantly reduced compared to the dimer structures-DSFX and DSITF.Furthermore,the GS-SITF1 which is one of the isomers of GS-SITF exhibits the lowest values for λ(h)(0.067 eV) and λ(e)(0.153 eV).Therefore,we believe the predicted structure,electronic property,and reorganization energy are good indicator for transport materials.This work has systematically studied the effect of gridization,which provides insights to design organic semiconductor materials with excellent charge transport properties.展开更多
The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China...The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-Co V-2 epidemics in several large cities or provinces of China. However,information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-Co V-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-Co V-2 transmission profiles. Genomic epidemiology revealed multiple SARS-Co V-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size.Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-Co V-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-Co V-2 strains during the early COVID-19 epidemic in China.展开更多
The herringbone water-sediment separation structure(HWSSS) was developed to prevent debris flows. This paper mainly focuses on evaluating the sediment separation efficiency of HWSSS in debris flow prevention and deter...The herringbone water-sediment separation structure(HWSSS) was developed to prevent debris flows. This paper mainly focuses on evaluating the sediment separation efficiency of HWSSS in debris flow prevention and determining the grid opening width D, a crucial structure parameter for HWSSS design. Theoretical analysis on the total sediment separation rate Pt reveals that the efficiency of sediment separation is much related with sediment grain size distribution(GSD) and grid opening width. The lower limit of Pt is deduced from the perspective of safety consideration by transforming debris flow into sediment-laden flow. Hydraulic model tests were carried out. Based on the regression analysis of the experimental data, the quantitative relationships between Pt and D and GSD characteristic values were finally established. A procedure for determining optimal grid opening width is proposed based on these analyses. These results are of significance in evaluating sediment separation effect by HWSSS in debris flow prevention and contribute to a more explicit methodology for design of HWSSS.展开更多
目的:本研究拟通过地塞米松体外短期处理外周血淋巴细胞探讨地塞米松对调节性T细胞包括自然调节性T细胞(Natural regulatory T cell,Treg)和Ⅰ型调节性T细胞(Type I regulatory T cell,Tr1)的影响。方法:取健康人外周血淋巴细胞,分为地...目的:本研究拟通过地塞米松体外短期处理外周血淋巴细胞探讨地塞米松对调节性T细胞包括自然调节性T细胞(Natural regulatory T cell,Treg)和Ⅰ型调节性T细胞(Type I regulatory T cell,Tr1)的影响。方法:取健康人外周血淋巴细胞,分为地塞米松处理组和阴性对照组,处理3 d后按多色分析法进行染色,用流式细胞仪检测并分析CD25、CD127、淋巴细胞活化因子3(Lymphocyte-activation 3,LAG-3)和叉头样转录因子3(Forkhead box P3,Foxp3)的表达及Treg和Tr1的频率变化。结果:相对于对照组,地塞米松处理3 d后CD4+T细胞频率增加且呈剂量依赖性;CD4^+T细胞上CD25和Foxp3的表达显著降低(P=0.006,P<0.000 1),而CD127和LAG-3表达显著升高(P<0.000 1、P=0.011);Treg频率显著降低(P<0.001),而Tr1频率显著升高(P=0.051),且增加Tr1/Treg细胞比率(P=0.044)。结论:地塞米松体外短期处理上调Tr1比率,下调Treg比率,改变Tr1与Treg细胞平衡。展开更多
文摘目的基于多元统计分析和网络药理学分析预测炒酸枣仁饮片潜在的质量标志物(Q-Marker)。方法利用超高效液相色谱-四极杆-静电场轨道阱质谱联用(ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap mass spectrometry,UHPLC-Q-Orbitrap-MS)解析生、炒酸枣仁饮片的主要成分,运用多元统计分析结合VIP>1和P<0.05筛选出炮制前后潜在的差异化学成分。结合网络药理学筛选核心靶点构建"成分-靶点-通路"网络关系,预测炒酸枣仁潜在的Q-Marker,以潜在Q-Marker为指标对市售样品进行含量测定,验证Q-Marker的科学性。结果生、炒酸枣仁共鉴定54个化学成分,包括斯皮诺素、当药黄素等黄酮类成分,酸枣仁皂苷A、酸枣仁皂苷B等皂苷类成分,以及木兰花碱、乌药碱等生物碱类成分;结合多元统计分析共找到木兰花碱、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A、白桦脂酸等28个差异性成分;经网络药理学分析筛选出包括17个差异成分的Q-Marker库,分别为酸枣仁皂苷A、酸枣仁皂苷B、美洲茶酸、白桦脂酸、木兰花碱、乌药碱、去甲荷叶碱、巴婆碱、斯皮诺素、当药黄素、维采宁Ⅱ、6"’-对-香豆酰斯皮诺素、6"’-阿魏酰斯皮诺素、芹菜素、桦木酮酸、牡荆素、异牡荆素;结合课题组前期研究及市售样品测定结果,最终确定木兰花碱、乌药碱、斯皮诺素、6"’-阿魏酰斯皮诺素、酸枣仁皂苷A和B作为炒酸枣仁的Q-Marker。结论分析预测的Q-Marker为炒酸枣仁的整体质量控制及临床应用提供科学依据,同时也为其功效关联物质的研究及作用机制的阐释奠定基础。
基金This work was supported by grants from the Ministry of Science and Technology of the People’s Republic of China[2017YFC1310901,2017YFC1307905,2018YFC1312903]grants from Beijing Municipal Administration of Hospitals’Mission Plan[SML20150502]+3 种基金grants from National Natural Science Foundation of China[81600999]grants from Beijing Municipal Science&Technology Commission[D171100003017002,D151100002015003]grants from National Science and Technology Major Project[2014ZX09201022-010,2017ZX09304018]Mudanjiang Youbo Pharmaceutical Co.,Ltd.
文摘Backgrounds Embolic stroke is one of the main mechanisms of ischaemic stroke.Even if treated with recommended antithrombotic agents,stroke recurrence remains high.The Shuxuetong injection,a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China,could be a promising agent to prevent stroke recurrence.Aims To describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms.Design The Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism(SPACE)trial is a multicentre,randomised,double-blind,placebo-controlled,parallel-group,superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days.An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days.The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation.Conclusion The SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke.
基金funded by the National Science and Technology Support Program(2011BAK12B00)the International Cooperation Project of the Department of Science and Technology of Sichuan Province(Grant No.2009HH0005).
文摘A herringbone water-sediment separation structure(hereinafter referred to as "herringbone structure") has been shown to be effective in separating coarse inorganic debris; however, less is known regarding the large wood(LW) filtration effect in this structure. This paper presents preliminary research on the wood filtration effect of the herringbone structure based on physical model tests.The results show that the herringbone structure exhibited effective performance in large wood size segregation, with a 100% component filtration rate for LW that diameter(D) larger than ribbed beam opening width(a). The total filtration rate also exceeded 80% when the Fraud number(Fr) is larger than 2.64 and increased with the increase of Fr. After exceeding Frmax, total filtration rate would be decreased due to overflow. Beside flow condition,structure parameters influence significantly on LW filtration rate. We attempt to explain the filtration process via particle contact trajectory and particle movement trajectory. The inclined angle of ribbed beam(γ) contributed the most variation to the filtration rate via influencing the coincidence with particle contact trajectory and particle movement trajectory. The high sensitivity coefficient of ribbed beam(θ) under relatively low Fr conditions implies remarkable influences on LW filtration effects by causing clogging problem. The ribbed beam opening width(a) together with LW diameter(D) influenced the size segregation performance.
基金supported by grants from the National Natural Science Foundation of China(No.81971314)。
文摘Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons.Here,we introduced and evaluated a newly modified Mathieu technique,Mathieu combined tunnel(MCT),which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations;we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence.This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University(Guangzhou,China)for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020;sixteen patients underwent surgery using the MCT(MCT group)and ten patients underwent surgery using the tubularized incised plate(TIP)technique(TIP group).The operative time,blood loss,postoperative complications,normal urethral meatus rate,success rate,and Hypospadias Objective Penile Evaluation(HOPE)score were compared between the two groups.The MCT group achieved an overall satisfactory penile appearance and voiding function,with a higher rate of normal urethral meatus(15/16,93.8%)and a lower rate of glans dehiscence(1/16,6.2%),compared with the TIP group(70.0%and 30.0%,respectively).However,these differences were not statistically significant,possibly because of the limited number of patients(all P>0.05).Mean postoperative HOPE scores were similar in the MCT group(mean±standard deviation:8.83±0.89)and TIP group(8.94±0.57)(P>0.05).No significant differences were found between the two groups in terms of blood loss and success rate,nor in the rates of various complications(e.g.,fistula,urethral stricture,and glans dehiscence).In conclusion,the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.
基金This work was supported by the National Natural Science Foundation of China (Nos. 21503114, 21774061, 61605090, 91833306)Synergetic Innovation Centre for Organic Electronics and In formation Displays, Nanji ng Un iversity of Posts a nd Telecommunications Scientific Foundation NUPTSF (NY215056, NY21417& NY215172, 2016XSG03)the Six Peak Talents Foundation of Jiangsu Province (XCL-CXTD-009), and the High Performanee Computing Center of Nanjing Tech University.
文摘Organic semiconductor materials with low reorganization energy have various applications such as in organic light-emitting diodes (OLEDs),organic field-effect transistor (OFETs) and organic solar cells (OSCs).In this work,we have designed a new class of gridspiroarenes (GS-SFX and GS-SITF) with #-shaped structures,which have novel crisscross geometrical structures compared to widely used spirocyclic arenes-SFX and SITF.The structure electronic properties,adiabatic ionization potentials (IPa),adiabatic electron affinities (EAa) and reorganization energies (λ) of GS-SFX and GS-SITF have been calculated using density functional theory (DFT) method.The calculated HOMO and LUMO spatial distributions suggest that GS-SFX and GS-SITF have better transport properties.The noncovalent interaction analysis shows the weak intramolecular interactions between their arms.The results indicate that the reorganization energies of GS-SFX and GS-SITF are significantly reduced compared to the dimer structures-DSFX and DSITF.Furthermore,the GS-SITF1 which is one of the isomers of GS-SITF exhibits the lowest values for λ(h)(0.067 eV) and λ(e)(0.153 eV).Therefore,we believe the predicted structure,electronic property,and reorganization energy are good indicator for transport materials.This work has systematically studied the effect of gridization,which provides insights to design organic semiconductor materials with excellent charge transport properties.
基金supported by the China National Science Foundation (Excellent Scholar Grants 81822028 and 82041013 to P.Z.)Ministry of Science and Technology of China (grant 2020YFC0840900 to P.Z.)Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB29010101 to Z.-L. S.)。
文摘The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-Co V-2 epidemics in several large cities or provinces of China. However,information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-Co V-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-Co V-2 transmission profiles. Genomic epidemiology revealed multiple SARS-Co V-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size.Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-Co V-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-Co V-2 strains during the early COVID-19 epidemic in China.
基金supported by the National Science and Technology Support Program (2011BAK12B00)
文摘The herringbone water-sediment separation structure(HWSSS) was developed to prevent debris flows. This paper mainly focuses on evaluating the sediment separation efficiency of HWSSS in debris flow prevention and determining the grid opening width D, a crucial structure parameter for HWSSS design. Theoretical analysis on the total sediment separation rate Pt reveals that the efficiency of sediment separation is much related with sediment grain size distribution(GSD) and grid opening width. The lower limit of Pt is deduced from the perspective of safety consideration by transforming debris flow into sediment-laden flow. Hydraulic model tests were carried out. Based on the regression analysis of the experimental data, the quantitative relationships between Pt and D and GSD characteristic values were finally established. A procedure for determining optimal grid opening width is proposed based on these analyses. These results are of significance in evaluating sediment separation effect by HWSSS in debris flow prevention and contribute to a more explicit methodology for design of HWSSS.
文摘目的:本研究拟通过地塞米松体外短期处理外周血淋巴细胞探讨地塞米松对调节性T细胞包括自然调节性T细胞(Natural regulatory T cell,Treg)和Ⅰ型调节性T细胞(Type I regulatory T cell,Tr1)的影响。方法:取健康人外周血淋巴细胞,分为地塞米松处理组和阴性对照组,处理3 d后按多色分析法进行染色,用流式细胞仪检测并分析CD25、CD127、淋巴细胞活化因子3(Lymphocyte-activation 3,LAG-3)和叉头样转录因子3(Forkhead box P3,Foxp3)的表达及Treg和Tr1的频率变化。结果:相对于对照组,地塞米松处理3 d后CD4+T细胞频率增加且呈剂量依赖性;CD4^+T细胞上CD25和Foxp3的表达显著降低(P=0.006,P<0.000 1),而CD127和LAG-3表达显著升高(P<0.000 1、P=0.011);Treg频率显著降低(P<0.001),而Tr1频率显著升高(P=0.051),且增加Tr1/Treg细胞比率(P=0.044)。结论:地塞米松体外短期处理上调Tr1比率,下调Treg比率,改变Tr1与Treg细胞平衡。
