Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM d...Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.展开更多
Considering that thermodynarmic irreversibility and hydrodynamic equations can not be derived rigorously and unifiedly from the Liouville equations, the anomalous Langevin equation in the Liouville space is proposed a...Considering that thermodynarmic irreversibility and hydrodynamic equations can not be derived rigorously and unifiedly from the Liouville equations, the anomalous Langevin equation in the Liouville space is proposed as a fundamental equation of statistical physics. This equation reflects that the law of motion of particles obeying reversible, deterministic laws in dynamics becomes irreversible and stochastic in thermodynamics. From this the fundamental equations of nonequilibrium thermodynamics, the principle of entropy increase and the theorem of minimum entropy production have been derived. The hydrodynamic equations, such as the generalized Navier-Stokes equation and the mass drift-diffusion equation etc. have been derived rigorously from the kinetic kinetic equation which is reduced from the anomalous Langevin equation in Liouville space. All these are unified and self consistent. But it is difficult to prove that entropy production density σ can never be negative everywhere for all the isolated inhomogeneous systems far from equilibrium.展开更多
AIM:To evaluate the safety and effectiveness of twostage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register o...AIM:To evaluate the safety and effectiveness of twostage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register of Controlled Trials and the Science Citation Index up to September 2011,were searched to identify all randomized controlled trials(RCTs).Data were extracted from the studies by two independent reviewers.The primary outcomes were stone clearance from the common bile duct,postoperative morbidity and mortality.The secondary outcomes were conversion to other procedures,number of procedures per patient,length of hospital stay,total operative time,hospitalization charges,patient acceptance and quality of life scores.RESULTS:Seven eligible RCTs [five trials(n = 621) comparing preoperative endoscopic retrograde cholangiopancreatography(ERCP)/endoscopic sphincterotomy(EST) + laparoscopic cholecystectomy(LC) with LC + laparoscopic common bile duct exploration(LCBDE);two trials(n = 166) comparing postoperative ERCP/EST + LC with LC + LCBDE],composed of 787 patients in total,were included in the final analysis.The metaanalysis detected no statistically significant difference between the two groups in stone clearance from the common bile duct [risk ratios(RR) =-0.10,95% confidence intervals(CI):-0.24 to 0.04,P = 0.17],postoperative morbidity(RR = 0.79,95% CI:0.58 to 1.10,P = 0.16),mortality(RR = 2.19,95% CI:0.33 to 14.67,P = 0.42),conversion to other procedures(RR = 1.21,95% CI:0.54 to 2.70,P = 0.39),length of hospital stay(MD = 0.99,95% CI:-1.59 to 3.57,P = 0.45),total operative time(MD = 12.14,95% CI:-1.83 to 26.10,P = 0.09).Two-stage(LC + ERCP/EST) management clearly required more procedures per patient than single-stage(LC + LCBDE) management.CONCLUSION:Single-stage management is equivalent to two-stage management but requires fewer procedures.However,patient's condition,operator's expertise and local resources should be taken into account in making treatment decisions.展开更多
Treats of dynamical systems with finite number of degrees of freedom such that the time evolution of the configuration variables for given initial conditions can well be described by controlled diffusions.Two suitable...Treats of dynamical systems with finite number of degrees of freedom such that the time evolution of the configuration variables for given initial conditions can well be described by controlled diffusions.Two suitable forms of stochastic action associated with the controlled diffusions are introduced in the general framework of stochastic control theory.By discretizing the stochastic action,the dynamical equations for the controlled diffusions of the given systems are derived in terms of generalized coordinates.These equations,together with the continuity equation,describe exactly the probability approach of the diffusion motion.展开更多
Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-qual...Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-quality observational studies, one low bias-risk randomized controlled trial(RCT), and one moderate biasrisk RCT included 1,652 patients [c TACE, 1,124; TARE(90 Y), 528], from whom data were extracted for this systematic review and meta-analysis.Results: The extracted study outcomes included 1-year and 2-year overall survival(OS) rates, objective responses(ORs), and serious adverse events(AEs). 1-year OS rates: OR = 0.939, 95 % CI: 0.705-1.251, P = 0.66. 2-year OS rates: overall pooled OR =0.641, 95% CI: 0.382-1.075, P = 0.092; observational study subgroup OR = 0.575, 95% CI: 0.336-0.984, P = 0.043; RCT subgroup OR* = 0.641, 95% CI: 0.382-1.075, P = 0.346. OR: overall pooled OR = 0.781, 95% CI: 0.454-1.343, P = 0.371; m RECIST subgroup OR = 0.584, 95 % CI: 0.349-0.976, P = 0.040; WHO subgroup OR = 1.065; 95% CI: 0.500-2.268, P = 0.870. Serious AEs: overall pooled RR = 1.477, 95% CI: 0.864-2.526, P = 0.154; RCT subgroup RR = 0.680, 95% CI: 0.325-1.423, P = 0.306; observational study subgroup RR = 1.925; 95 % CI: 0.978-3.788, P = 0.058.Conclusions: TARE(90 Y) increased 2-year OS rates in the observational subgroup and resulted in better OR rates, according to m RECIST criteria, in comparison with c TACE. Furthermore, a lower risk of AEs was observed for TARE(90 Y) than for c TACE.展开更多
The nonlinear mixed-effects model with stochastic differential equations （SDEs） is used to model the population pharmacokinetic （PPK） data that are extended from ordinary differential equations （ODEs） by adding ...The nonlinear mixed-effects model with stochastic differential equations （SDEs） is used to model the population pharmacokinetic （PPK） data that are extended from ordinary differential equations （ODEs） by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.展开更多
基金National Natural Science Foundation of China(22073030)the Oriental Scholars of Shanghai Universities。
文摘Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.
文摘Considering that thermodynarmic irreversibility and hydrodynamic equations can not be derived rigorously and unifiedly from the Liouville equations, the anomalous Langevin equation in the Liouville space is proposed as a fundamental equation of statistical physics. This equation reflects that the law of motion of particles obeying reversible, deterministic laws in dynamics becomes irreversible and stochastic in thermodynamics. From this the fundamental equations of nonequilibrium thermodynamics, the principle of entropy increase and the theorem of minimum entropy production have been derived. The hydrodynamic equations, such as the generalized Navier-Stokes equation and the mass drift-diffusion equation etc. have been derived rigorously from the kinetic kinetic equation which is reduced from the anomalous Langevin equation in Liouville space. All these are unified and self consistent. But it is difficult to prove that entropy production density σ can never be negative everywhere for all the isolated inhomogeneous systems far from equilibrium.
文摘AIM:To evaluate the safety and effectiveness of twostage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register of Controlled Trials and the Science Citation Index up to September 2011,were searched to identify all randomized controlled trials(RCTs).Data were extracted from the studies by two independent reviewers.The primary outcomes were stone clearance from the common bile duct,postoperative morbidity and mortality.The secondary outcomes were conversion to other procedures,number of procedures per patient,length of hospital stay,total operative time,hospitalization charges,patient acceptance and quality of life scores.RESULTS:Seven eligible RCTs [five trials(n = 621) comparing preoperative endoscopic retrograde cholangiopancreatography(ERCP)/endoscopic sphincterotomy(EST) + laparoscopic cholecystectomy(LC) with LC + laparoscopic common bile duct exploration(LCBDE);two trials(n = 166) comparing postoperative ERCP/EST + LC with LC + LCBDE],composed of 787 patients in total,were included in the final analysis.The metaanalysis detected no statistically significant difference between the two groups in stone clearance from the common bile duct [risk ratios(RR) =-0.10,95% confidence intervals(CI):-0.24 to 0.04,P = 0.17],postoperative morbidity(RR = 0.79,95% CI:0.58 to 1.10,P = 0.16),mortality(RR = 2.19,95% CI:0.33 to 14.67,P = 0.42),conversion to other procedures(RR = 1.21,95% CI:0.54 to 2.70,P = 0.39),length of hospital stay(MD = 0.99,95% CI:-1.59 to 3.57,P = 0.45),total operative time(MD = 12.14,95% CI:-1.83 to 26.10,P = 0.09).Two-stage(LC + ERCP/EST) management clearly required more procedures per patient than single-stage(LC + LCBDE) management.CONCLUSION:Single-stage management is equivalent to two-stage management but requires fewer procedures.However,patient's condition,operator's expertise and local resources should be taken into account in making treatment decisions.
文摘Treats of dynamical systems with finite number of degrees of freedom such that the time evolution of the configuration variables for given initial conditions can well be described by controlled diffusions.Two suitable forms of stochastic action associated with the controlled diffusions are introduced in the general framework of stochastic control theory.By discretizing the stochastic action,the dynamical equations for the controlled diffusions of the given systems are derived in terms of generalized coordinates.These equations,together with the continuity equation,describe exactly the probability approach of the diffusion motion.
文摘Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-quality observational studies, one low bias-risk randomized controlled trial(RCT), and one moderate biasrisk RCT included 1,652 patients [c TACE, 1,124; TARE(90 Y), 528], from whom data were extracted for this systematic review and meta-analysis.Results: The extracted study outcomes included 1-year and 2-year overall survival(OS) rates, objective responses(ORs), and serious adverse events(AEs). 1-year OS rates: OR = 0.939, 95 % CI: 0.705-1.251, P = 0.66. 2-year OS rates: overall pooled OR =0.641, 95% CI: 0.382-1.075, P = 0.092; observational study subgroup OR = 0.575, 95% CI: 0.336-0.984, P = 0.043; RCT subgroup OR* = 0.641, 95% CI: 0.382-1.075, P = 0.346. OR: overall pooled OR = 0.781, 95% CI: 0.454-1.343, P = 0.371; m RECIST subgroup OR = 0.584, 95 % CI: 0.349-0.976, P = 0.040; WHO subgroup OR = 1.065; 95% CI: 0.500-2.268, P = 0.870. Serious AEs: overall pooled RR = 1.477, 95% CI: 0.864-2.526, P = 0.154; RCT subgroup RR = 0.680, 95% CI: 0.325-1.423, P = 0.306; observational study subgroup RR = 1.925; 95 % CI: 0.978-3.788, P = 0.058.Conclusions: TARE(90 Y) increased 2-year OS rates in the observational subgroup and resulted in better OR rates, according to m RECIST criteria, in comparison with c TACE. Furthermore, a lower risk of AEs was observed for TARE(90 Y) than for c TACE.
基金The National Natural Science Foundation of China(No.11171065,81130068)the Natural Science Foundation of Jiangsu Province(No.BK2011058)the Fundamental Research Funds for the Central Universities(No.JKPZ2013015)
文摘The nonlinear mixed-effects model with stochastic differential equations （SDEs） is used to model the population pharmacokinetic （PPK） data that are extended from ordinary differential equations （ODEs） by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.
