Molecular Dynamics Simulation of Shock Response of CL-20 Co-crystals Containing Void Defects

To investigate the effect of void defects on the shock response of hexanitrohexaazaisowurtzitane(CL-20)co-crystals,shock responses of CL-20 co-crystals with energetic materials ligands trinitrotoluene(TNT),1,3-dinitrobenzene(DNB),solvents ligands dimethyl carbonate(DMC) and gamma-butyrolactone(GBL)with void were simulated,using molecular dynamics method and reactive force field.It is found that the CL-20 co-crystals with void defects will form hot spots when impacted,significantly affecting the decomposition of molecules around the void.The degree of molecular fragmentation is relatively low under the reflection velocity of 2 km/s,and the main reactions are the formation of dimer and the shedding of nitro groups.The existence of voids reduces the safety of CL-20 co-crystals,which induced the sensitivity of energetic co-crystals CL-20/TNT and CL-20/DNB to increase more significantly.Detonation has occurred under the reflection velocity of 4 km/s,energetic co-crystals are easier to polymerize than solvent co-crystals,and are not obviously affected by voids.The results show that the energy of the wave decreases after sweeping over the void,which reduces the chemical reaction frequency downstream of the void and affects the detonation performance,especially the solvent co-crystals.

Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Research on the Impact of the Centralized Drug Procurement Policy on China’s Pharmaceutical Enterprises

Objective To analyze the impact of the centralized drug procurement policy on pharmaceutical enterprises,and put forward some suggestions for improving China’s centralized drug procurement policy.Methods Through literature analysis and comparative research,the relevant policies and implementation effects from the“4+7”drug procurement pilot to the seventh batch of volume procurement were sorted out,and the impact of the procurement policy on pharmaceutical enterprises was analyzed.Results and Conclusion The centralized drug procurement policy has continuously improved the enthusiasm of enterprises to participate in bidding,and the consistency evaluation work has been carried out well.However,there are also some problems,such as the reduction of enterprise profits,the difficulty of enterprise operation,the decline in the quality of winning drugs,and the insufficient innovation ability and the supply capacity of enterprises.In this regard,enterprises should reasonably control the cost of drugs to ensure the stable supply of winning drugs.Besides,enterprises should create brand effect for their timely transformation and development.While strengthening pharmaceutical innovation,they can change from low-level generic drug production to R&D innovation.The government should pay close attention to the impact of centralized procurement on the quality and efficiency of enterprise drugs.For instance,the government should improve the pricing rules for drug procurement and increase supervision of drug quality and supply.At the same time,it should give certain policy and financial support to enterprises’technological innovation and talent introduction.

Digital Transformation Trend of the Pharmaceutical Distribution Industry in the Context of New Infrastructure in China

Objective To study the pharmaceutical distribution industry against the background of new infrastructure construction since it is vital to the health and life of the public,and to offer some suggestions to further improve the industry quality and achieve industry upgrading.Methods The national strategies for new infrastructure as well as the underlying logic for enterprise digital transformation were analyzed to provide the outlook on the digital transformation trend of the pharmaceutical distribution industry.Results and Conclusion In the future,the pharmaceutical distribution industry shall transform the pattern,channel,management and control,and experience in the entire business chain in a digital way by focusing on connection efficiency,data efficiency and decision-making efficiency.

Research on the Improvement of Incentive Mechanism for Pharmaceutical Sales Personnel - Taking Company A as an Example

Objective To analyze the improvement of the incentive mechanism of sales personnel in pharmaceutical company A,and to promote the smooth operation and further development of the company in a long term.Methods Compensation incentive,performance appraisal,welfare benefit,training incentive,promotion motivation and enterprise cultural inspiration were explored through questionnaires,telephone interviews and in-person interviews.Results and Conclusion This company’s incentive mechanism has problems in two aspects:Material incentives and spiritual incentives.As to the company’s characteristics and strategic development,the optimization countermeasures of incentive mechanism are proposed from the following three aspects:constructing a reasonable incentive system,establishing an efficient spiritual incentive mechanism,and implementing the dynamic incentive and differentiated incentive simultaneously.

Countermeasures and Suggestions for Strengthening Human Resource Management in China’s Pharmaceutical Industry

Objective To provide reference and enlightenment for the development of human resource management in China’s pharmaceutical industry and to put forward some suggestions to promote the further development of pharmaceutical industry.Methods The method of literature review was used to analyze the current situation and existing problems of human resource management in China’s pharmaceutical industry.Results and Conclusion Only by continuously improving the human resource management skills and innovating management methods can pharmaceutical enterprises achieve long-term benefits with sustainable development.The formulation of human resource management strategy in pharmaceutical industry must be conducive to the realization of the business goals of enterprises.To achieve this overall goal,the human resources management department of enterprises must make the plan from a strategic perspective,formulate talent strategic planning which serves the overall strategic goal of the enterprise.As a result,human resource management will play an important role in the development of China’s pharmaceutical industry.

Comparative Analysis of Profit Model of Typical Pharmaceutical O2O Enterprises in China

Objective To study the profit model of Chinese pharmaceutical O2O enterprises.Methods A case study of three typical pharmaceutical O2O enterprises was conducted,and their profit models were compared.Results and Conclusion The pharmaceutical O2O enterprises in China are divided into three categories according to the profit models.It is found that the current pharmaceutical O2O enterprises have problems such as simple profit model and low corporate profits.Based on these problems,it is recommended that relevant enterprises develop various business models to increase profit channels.Besides,they should establish and improve internal cost control systems.

Research on the Threshold Effect of China’s Pharmaceutical Export Trade on Internal and External R&D Investment

Objective To study the threshold effect of export trade on internal and external R&D investment in China’s pharmaceutical industry,and to provide reference for some pharmaceutical enterprises to improve the investment.Methods The panel data of pharmaceutical industry in 25 provinces and cities in China from 2009 to 2019 were selected to conduct empirical analysis by establishing a threshold regression model,and a better export trade interval was obtained.Results and Conclusion There is a threshold value for the effect of new product export on both internal and external R&D expenditures,and the threshold values are 845.2788 million yuan and 318.4198 million yuan,respectively.There is a single threshold effect of export trade on both internal and external R&D investment in China’s pharmaceutical industry,and the effect of export trade on internal and external R&D investment changes from negative to positive as the export trade develops from low to high.

Research on the Status Quo and Countermeasures of Human Resource Management Outsourcing in China’s Pharmaceutical Enterprises

Objective To explore the current situation of human resource management outsourcing in China’s pharmaceutical enterprises,and to put forward some suggestions for enterprises and the government.Methods The current situation of human resource management outsourcing in China’s pharmaceutical enterprises was analyzed through the method of literature research.Results and Conclusion At present,the status of human resource management outsourcing in China’s pharmaceutical companies is that the level of human resource outsourcing companies is not high,and there are no relevant industry norms and laws.The information asymmetry between pharmaceutical enterprises and outsourcing companies results in adverse selection and moral hazard.Besides,the different culture of pharmaceutical enterprises and outsourcing companies leads to inefficient communication between enterprises and employee.To solve these problems,the government should promote and improve industry norms and laws to regulate the market.In addition,enterprises should clarify the motivation for outsourcing and make good decision on the outsourcing content.Meanwhile,enterprises should strengthen communication with employees to eliminate employees’concerns.

The Development and Experience of American Pharmaceutical Industry Associations and Its Enlightenment to China

Objective To study the development history and current situation of pharmaceutical industry associations in the United State and to provide reference for China’s pharmaceutical industry associations.Methods Literature research and comparative study were used to investigate the development history and current situation of pharmaceutical associations in the United States.Then,their characteristics and experiences were summarized.Some countermeasures and suggestions were put forward for the existing problems of pharmaceutical associations in China.Results and Conclusion The institutional environment of pharmaceutical associations in the United States is relatively good,reflecting the characteristics of emphasizing process management and neglecting entrance management with and the help of public supervision.At the same time,the government advocates market competition by adhering to the market-oriented services for the public.American pharmaceutical industry associations have strong innovation capacity and perfect credit system.Drawing on the experience of pharmaceutical industry associations in the United States,China should strengthen the construction of pharmaceutical industry associations.Firstly,the supervision mechanism should be improved.Secondly,these associations should have good partnerships with the government and offer the public the best services.Finally,the fund-raising mechanism of pharmaceutical industry associations should be optimized to ensure the innovative development of the pharmaceutical industry.

Research on the Influence of Government R&D Funding and Enterprise R&D Investment on the Innovation Efficiency of Pharmaceutical Industry

Objective To study the effect of government R&D funding and enterprise R&D input on innovation efficiency of China’s pharmaceutical industry.Methods Based on the inter-provincial panel data of China’s pharmaceutical industry from 2009 to 2019,the stochastic frontier analysis method was used to study the influence of government R&D funding and enterprise R&D input on the innovation efficiency.Results and Conclusion With 1%increase in government R&D funding,the innovation efficiency of enterprises will increase by 0.122%.When R&D investment increases by 1%,innovation efficiency will increase by 0.169%.Both government R&D funding and enterprise R&D investment promote the innovation efficiency of pharmaceutical enterprises,but the increase of enterprise R&D investment contributes more to the improvement of pharmaceutical innovation efficiency.

Pyrolysis of CL20-BTF Co-crystal via ReaxFF-lg Reactive Force Field Molecular Dynamics Simulations

To obtain detailed information on the potential energy, the evolution of species, the initial reaction paths, and thermal decomposition products, we conducted simulations on pyrolysis process of CL20/BTF co-crystal using the ReaxFF/lg reaction force field, with temperature set at 2000 K to 3000 K. With the analysis of evolution curves of potential energy based on exponential function, we obtain the overall characteristic time. Via a description of the total package reaction with classical Arrhenius law, we obtain the activation energy of CL20/BTF co-crystal： Ea=60.8 kcal/mol. Based on the initial path of CL20/BTF co-crystal thermal decomposition we studied, we conclude that N-NO2 bond of CL20 molecules breaks first, working as a dominant role in the initial stage of thermal decomposition under the condition of different temperatures, and that all CL20 molecules completely decompose before BTF molecular regardless of different temperatures. We also find that the main products of CL20/BTF co-crystal are NO2, NO, NO3, HNO, O2, N2, H2O, CO2, N2O, and HONO, etc., on which the temperature forms certain influence.

超越pharmaceutical care,呼唤中国特色的药学实践规范

本文将各种药学实践模式及中国药学实践规范加以阐述。药学实践在美国可分为 5个阶段 ,Pharmaceuticalcare (PC)是美国药学发展的一个新阶段 ,此概念已进入国内药学。虽然国外药学已走上规范化发展 ,但国内药学存在许多问题 ,药学工作离规范化发展相距甚远 ,因而建立中国药学实践规范极有必要。为此 ,我们提出了中国药学实践规范的初步建议。

Clinical Application and Pharmaceutical Values of Levant Cotton Root

Levant cotton root is a folk traditional herb with a long history in China. This article gave a brief introduction on recent research work related to main com- position, pharmacologic effect and clinical application of levant cotton root and pro- posed existing problems and countermeasures for pharmaceutical industrialization.

Viable but Non-culturable Bacteria in Bioreactorbased Pharmaceutical Wastewater

We aimed to investigate the composition and phylogenetic rela-tionships of the viable but non-culturable （VBNC） state bacteria in pharmaceutical wastewater. [Method] Soil filter was used for constructing bioreactor. Based on the resuscitation- and growth-promoting function of Resuscitation Promoting Factor （Rpf） for VBNC bacteria, VBNC bacteria were isolated by most probable number （MPN） method and dilution-plating method and 16S rRNA gene phylogenetic analysis was carried out. [Result] In MPN culture system, Rpf could promote the resuscitation and growth of some bacteria. There were VBNC advantage floras that sensitive to Rpf in pharmaceutical wastewater. The culturable VBNC bacteria in pharmaceutical wastewater consisted of high-GC gram-positive actinomycetes including genera Mi-crobacterium, Gordonia and Leucobacter, and gram-negative bacteria including gen-era Candidimonas, Xanthobacter and Aminobacter. Four strains （ZYM1, ZYM3, ZYZR4, ZYXR1） could be potential novel species. [Conclusion] This research re-vealed there were VBNC bacteria in pharmaceutical wastewater. These results could provide important ideas and methods for further studies on VBNC bacteria in the pharmaceutical wastewater, especial y the formation mechanism and recovery mech-anism of VBNC bacteria and the advanced degradation process improvement of pharmaceutical wastewater.

Application of microfluidic chip technology in pharmaceutical analysis:A review

The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.

Recent advances in electrogenerated chemiluminescence biosensing methods for pharmaceuticals

Electrogenerated chemiluminescence(electrochemiluminescence, ECL) generates species at electrode surfaces, which undergoes electron-transfer reactions and forms excited states to emit light. It has become a very powerful analytical technique and has been widely used in such as clinical testing, biowarfare agent detection, and pharmaceutical analysis. This review focuses on the current trends of molecular recognition-based biosensing methods for pharmaceutical analysis since 2010. It introduces a background of ECL and presents the recent ECL developments in ECL immunoassay(ECLIA), immunosensors, enzyme-based biosensors, aptamer-based biosensors, and molecularly imprinted polymers(MIP)-based sensors. At last, the future perspective for these analytical methods is briefly discussed.

Preparation and application of pharmaceutical wastewater treatment by praseodymium doped SnO_2/Ti electrocatalytic electrode

Praseodymium was selected as a promoter for SnO2/Ti electrode to improve the electrocatalytic performance by electrodeposition in pharmaceutical wastewater treatment; the micrograph and the structure were characterized by SEM and XRD. Mixture uniform design was used in the optimization of the electrolytic conditions; mathematical model was established according to the rate of wiping COD off, which revealed the relationship between the current intensity, time of electrolysis, the amount of doped Pr, and the ratio of area （SnOJTi：Al）. On the basis of the analysis of the empirical model, the optimized parameters had been obtained; the rate of wiping COD off was up to 94.9%, it decreased from 392 to 20 mg/L. Experimental results showed that the electrocatalytic performance of the electrode doped with Pr was superior for the treatment of pharmaceutical wastewater.

Preparation of reduced sensitivity co-crystals of cyclic nitramines using spray flash evaporation

The present day weapon technology demands novel energetic materials that exhibit simultaneous high explosive yield and reduced sensitivity.This article demonstrates application of spray evaporation to prepare reduced sensitive co-crystals of high performance nitramine explosives like HMX and CL-20 with a relatively less insensitive explosive 1,1-diamino-2,2-dinitroethylene or FOX-7.Stronger intermolecurar hydrogen bonding in FOX-7 is responsible for limited solubility in nost of o rganic solvents.Large solubility differences of FOX-7 with HMX and CL-20 restricts ifs co-crystallization through classical methods that yields thermodynamically favorable product.Spray flash evaporation,a kinetic crystallization method,has been therefore adopted and could successfully produce CL-20/FOX-7(2:1) and HMX/FQX-7(4:1) co-crystals.The fine powdered materials obtained were characterized by SEM,powder XRD,Raman spectro scopy,DSC-TGA etc.Multipoint Raman spectra showed consistent occurrence of spectral features indicating stoichiometric co-existence of ingredients in the crystal lattices.DSC analysis showed absence of all thermally assisted solidsolid phase transformation in the co-crystals as they were observed in pristine materials.The thermal stability calculated in terms of activation barrier fordecomposition,revealed the CL-20/FOX-7 co-crystal to be interlediately stable on comparison to their constituents while,the HMX/FOX-7 co-crystal is more stable.Compared to pure HMX and CL-20,both the co-crystals have shown higher insensitivity to impact force,suggesting them to be suitable for future generation insensitive munitions.