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.

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.

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.

Flow injection spectrophotometric determination of vitamin E in pharmaceuticals,milk powder and blood serum using potassium ferricyanide-Fe(Ⅲ) detection system

A simple and sensitive flow injection spectrophotometric method is reported for the determination of vitamin E using potassium ferricyanide-Fe(Ⅲ) detection system.In the presence of vitamin E,Fe(Ⅲ)/ferricyanide reduces.The in situ reduced ions are then reacted with unreduced portion of ferricyanide/Fe(Ⅲ) to make soluble Prussian blue,which is monitored at absorption wavelength of 735 nm.Linear calibration graph was obtained in the concentration range of 0.1-40μg mL^(-1).The relative standard deviations (n=4) were in the range of 1.1-3.6%,with limits of detection(3 s blank) of 0.04μg mL^(-1).The proposed method allowed 12 injections h^(-1).The method is applied to determine vitamin E in pharmaceuticals,infant milk and blood serum samples using hexane extraction with the recoveries in the range of 93±3 to 97.5±4%.The method is validated using certified reference materials SRM 968c for blood serum samples.

Analytical methods for determination of terbinafine hydrochloride in pharmaceuticals and biological materials

Terbinafine is a new powerful antifungal agent indicated for both oral and topical treatment of myco- sessince. It is highly effective in the treatment of determatomycoses. The chemical and pharmaceutical analysis of the drug requires effective analytical methods for quality control and pharmacodynamic and pharmacokinetic studies. Ever since it was introduced as an effective antifungal agent, many methods have been developed and validated for its assay in pharmaceuticals and biological materials. This article reviews the various methods reported during the last 25 years.

Flow-injection Determination of Cysteine,N-Acetyl Cysteine and Glutathione in Pharmaceuticals via Potassium Ferricyanide-Fe(Ⅲ) Spectrophotometric System

A simple flow injection spectrophotometric method is reported for the determination of cysteine,N-acetyl cysteine and glutathione based on the reduction of Fe（Ⅲ）/ferricyanide,the in situ reduced ions are reacted with unreduced portion of ferricyanide/Fe（Ⅲ） to form soluble Prussian blue,which is monitored at 735 nm.The calibration graphs are linear in the concentration ranges of（1―100）×10-6 mol/L for cysteine and N-acetyl cysteine,and（1―50）×10-6 mol/L for glutathione.The relative standard deviations of 1.8%,2.5% and 1.9% were found for eleven replicate analyses of 5×10-6 mol/L cysteine,N-acetyl cysteine and glutathione.The limits of detection（3σ blank） at 5×10-7 mol/L for cysteine,and 3×10-7 mol/L for N-acetyl cysteine and glutathione were obtained.The proposed method allowed 60 injections/h.The effects of common substances present in pharmaceuticals and human physiological fluids were examined.The method was applied to determining cysteine in pharmaceutical formulations with the recoveries in a range of 97% to 106% and the results obtained are agreed well with labeled values.

Hollow fiber-based liquid phase microextraction followed by analytical instrumental techniques for quantitative analysis of heavy metal ions and pharmaceuticals

Hollow-fiber liquid-phase microextraction(HF-LPME)and electromembrane extraction(EME)are miniaturized extraction techniques,and have been coupled with various analytical instruments for trace analysis of heavy metals,drugs and other organic compounds,in recent years.HF-LPME and EME provide high selectivity,efficient sample cleanup and enrichment,and reduce the consumption of organic sol-vents to a few micro-liters per sample.HF-LPME and EME are compatible with different analytical in-struments for chromatography,electrophoresis,atomic spectroscopy,mass spectrometry,and electrochemical detection.HF-LPME and EME have gained significant popularity during the recent years.This review focuses on hollow fiber based techniques(especially HF-LPME and EME)of heavy metals and pharmaceuticals(published 2017 to May 2019),and their combinations with atomic spectroscopy,UV-VIS spectrophotometry,high performance liquid chromatography,gas chromatography,capillary elec-trophoresis,and voltammetry.

Probing the degradation of pharmaceuticals in urine using MFC and studying their removal efficiency by UPLC-MS/MS

Nutrient recovery from source-separated human urine has attracted interest as it is rich in nitrogen and phosphorus that can be utilized as fertilizer.However,urine also contains pharmaceuticals,steroid hormones,etc.and their removal is crucial as they have detrimental effects on the environment and human health.The current study focuses on investigating the degradation of pharmaceuticals using a double-chamber microbial fuel cell(MFC).Urine was spiked with four pharmaceuticals(trimethoprim,lamivudine,levofloxacin,and estrone)at a concentration of 2 mg/mL.The MFC was operated for 7 months in batch mode with this spiked urine as feed.The degradation efficiency of the MFC was studied,for which a selective liquid chromatography-tandem mass-spectrometric method was developed for the quantitation of compounds used in the spiking experiments and was validated with a lower limit of quantification of 0.39 ng/mL.The maximum removal rate achieved was 96%±2%.The degradation mechanism involved processes like sorption and anoxic biodegradation.The voltage curve obtained showed that the presence of pharmaceuticals had an initial negative impact on power generation along with increased organic content;however,after the reactor acclimatization,increased power output was achieved with maximum organics removal at 30 h of retention time.This work opens a new perspective for the anoxic biodegradation of pharmaceuticals and can be useful in future bioremediation studies.

Guarapiranga Reservoir—Pharmaceuticals and Historical Urban Occupation in a Water Source

The pharmaceutical compounds were analyzed in 14 sampling sites and pointed out the pollution sources related to raw sewage input and urban drainage discharge. Five medicine compounds, one illicit drug, and its metabolite were the higher measured content using analytical improvements tailored to identify and quantify organic compounds in low water content. The use of SPE cartridges followed by liquid chromatography with tandem mass spectrometry (LC-ESI-MS/MS) points out the Guavirutuba tributary as the primary water pollution source with higher concentrations in 2011 for pharmaceuticals, cocaine, and benzoylecgonine (metabolite) in the range of 6.7 ± 0.9 ng L-1 to 27.386 ± 142 ng L-1. The Jaceguay stream also located in Guarapiranga was the most preserved area and provided analytical values correspondent which lowered contamination content. Such concentrations mean a possible and feasible water restoration target. The most common compounds (above 90% samples) were: caffeine, atenolol, carbamazepine, cocaine, and benzoylecgonine. The integrated risk index for aquatic chemical pollution (IRICAP) confirms the higher contamination near Guavirutuba stream and the lower near the Jaceguay stream. Published results of cocaine and benzoylecgonine content in Guarapiranga basin corroborated with the analytical results.

Detection of Human Pharmaceuticals in the Surface Water of East Fork Stones River

Pharmaceuticals have been detected nationwide in different environmental matrices including wastewater effluents and surface water. In recent studies, pharmaceuticals have also been found in aquatic plants, fish tissues and plasma of shark bulls. Pharmaceuticals that were detected as indicated in published literature, included steroids, prescription drugs such as antibiotics, anti-depressants, anti-inflammatory drugs, hormones and over the counter (OTC) drugs. We conducted a monitoring study to detect the presence of pharmaceuticals in East fork of the Stones River located in Rutherford County in Middle Tennessee. East Fork Stones River is a six (6) order river that drains a large portion of Rutherford County including Murfreesboro, Tennessee. Grab water samples were collected from Stones River for three seasons: (summer and fall of 2014 and 2015 and winter of 2015 and 2016) each year. Water quality parameters were also determined in situ using Eureka Water ProbesTM multi-parameter sondes. Water samples were analyzed for the presence of pharmaceutical compounds using GC-MS. Chemical Abstract Service Registry Numbers (CASRN or CAS) for detected pharmaceuticals were identified. Pharmaceuticals detected included those used for treatment of chronic alcoholism (Disulfiram: CAS # 97-77-8), a compound (Thiazolidine: CAS # 504-78-9) in the drug Thiazolidinedione which is used for the treatment of type II diabetes, a compound associated with the prevention of anti-inflammatory conditions (Methyl palmitate: CAS # 112-39-0), and emollient in skincare (Undecane: CAS # 1120-21-4). While the quantitative concentrations of these drugs were not determined in this study, their qualitative presence in surface water is noteworthy.

Medicinal Mushroom Products:Nutriceuticals and/or Pharmaceuticals?

Although the effectiveness of mushroom products(mushroom derivatives) has been confirmed repeatedly by numerous laboratory experiments and,in some cases,human trials,precisely how these products work is still a matter of conjecture.Studies on the effectiveness of mushroom products fall into two general categories.One approach has been to isolate and determine the bioactivity of individual mushroom components within a particular class of compounds(e.g.polysaccharides,lectins,triterpenoids,fungal immunomodulatory proteins).The active principal component is then sold in refined or purified form,e.g.the polysaccharide lentinan from the edible/medicinal mushroom Lentinula edodes.Such an approach is certainly valid if the objective is to focus on a single mushroom-derived substance for the treatment of specific disease conditions,e.g.cancers or strokes.In such cases,the products might be(and have been) developed and marketed as prescription drugs.However,an alternative approach is not to focus on a single component within a class of compounds but on groups of compounds that improve overall health and the general quality of life.These composite formulae,in which several different compounds together contribute to the beneficial effect of the mushroom,could then be used collectively as a dietary supplement(nutriceutical).Thus,the medicinal effects afforded by medicinal mushroom products may be attributable to several quite different types of compounds present in the mushrooms,e.g.polysaccharides,lectins,triterpenoids and fungal immunomodulatory proteins.These compounds,and possibly others yet to be identified,appear to act in concert in contributing to the documented anticancer,antitumour,antiviral,antibacterial and immunomodulating properties of the mushroom.Therefore,mushroom nutriceuticals may be deemed to have multifunctional values,the essence of which depends on the integrated effects of the various compounds.Certainly,the overwhelming majority of mushroom-based products currently available are not single components but combinations of several groups of compounds("crude extracts") that together contribute to the overall medicinal effect of the product.Therefore,it is important that future development of mushroom nutriceuticals places emphasis on investigating the functionality and interaction of the groups of compounds found in mushrooms.In some cases,it may be more desirable to consider the total medicinal effect(s) of mushroom "crude extracts"(comprising groups of compounds) and then to ascertain the contributions made to the overall activity by individual components.The consistency of the "crude extracts",both in terms of the overall chemical composition and in the actual levels of active components,between different batches could be standardized on the basis of one or two of the main components.This is essential for ensuring some degree of uniformity in prescribed dosages.Thus,while the minimum dosage of an active component required to bring about the desired therapeutic effect is often known for similar products,e.g.hypericin in extracts of St.John's Wort,this is generally not the case where mushroom "crude extracts" are concerned.This is an area where scientific validation can increase knowledge of the products themselves as well as contributing to product quality control.

Industry Dynamics in Pharmaceuticals

Pharmaceuticals is a relatively large and mature industry, and of growing significance. The industry has stimulated extensive research on determinants of its growth and development. Specifically, the distribution of firm size has attracted significant attention, due to tis relevance as an indicator of degree of industrial concentration. A large part of this literature has focused, since the early contributions, on the explanation of the shape of firm size distribution in the industry at a given point in time by reference to steady state arguments. The dynamics in question have been relatively neglected however. The main objective of this paper is to help fill this gap. It is shown that interesting issues arise when one considers how firm structure evolves over time, rather than simply attending to equilibrium implications of processes. Information on the shape and time-evolution of the size distribution of firms over an extended period of time can be used to make inferences about an underlying process;specifically, on which characteristics lead to which kinds of dynamics. To that end, we propose a diffusion model to examine the spatial dynamics of firm size. Instead of assuming a steady state as is standard practice, we consider that firm size fluctuates around its long run stationary equilibrium, according to a double process of temporal drift and random disturbance. An empirical application to real data from the Pharmaceutical industry helps fill a second gap in the literature, as only a few diffusion studies have employed real statistical data when analyzing firm size dynamics. Our empirical application confirms results presented elsewhere and offers some new insights.

Rapid and Sensitive CZE Method for Quality Control Analysis of Pharmaceuticals Containing Pseudoephedrine, Triprolidine and Paracetamol

A rapid and sensitive CZE (Capillary Zone Electrophoresis) method for pharmaceutical analysis was developed and fully validated. The active compounds: Pseudoephedrine hydrochloride (PSE), Triprolidine hydrochloride (TRI) and Paracetamol (PAR) were separated and quantitatively determined using the tris-borate 30 mM buffer at pH = 9.0 as a Background Electrolyte (BGE). The electrophoretic separation was carried out at 25 kV in an unmodified fused silica capillary of I.D. = 50 μm with a “bubble-cell” for UV detection at 210 nm and 25°C. The separation was reached in about 3 min. After calibration the method was applied for analysis of three commercially available pharmaceutical preparations. The repeatability (RSD%) of migration time (tm) was ranging between 0.47% and 0.90% and of peak areas (A) between 0.63% and 3.64%. The Limit of Detection (LOD) values was of 0.19 μg/mL, 0.31 μg/mL and 0.08 μg/mL for respectively PSE, TRI and PAR. The results obtained in this study showed that the proposed method was useful in routinely analysis of pharmaceuticals.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.