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Objective:The study aims to analyze the problems faced in the clinical research and management of stem cells, explore the construction of the entire process of stem cells clinical research, and promote the healthy and orderly development of the clinical research of stem cells.Methods:By consulting the literature and retrieval of relevant policies and regulations, this study analyzed the problems faced by the supervision and management department, medical institutions and researchers, this study and discussed the countermeasures for strengthening the management of the entire process of clinical research of stem cells in medical institutions.Results:There were imperfect internal system and poor management process, insufficient quality control of cell products, low quality of project management, and insufficient clinical research consciousness of stem cell clinical research management in medical institutions.Conclusions:Combined with the current management measures, guidance principles and medical institutions, we should improve the internal system of medical institutions, promote the centralized management and informatization construction of projects, strengthen cell quality control in the hospital, cultivate talent echelons and improve academic and ethical review capabilities, actively explore the management model that is suitable for the entire process of stem cell clinical research for medical institutions in China.
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Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which seriously affects physical and mental health in children.Its etiology and pathogenesis are complex and have not been fully elucidated.Currently, the theory of Dopamine (DA) deficits has been widely recognized and studied in the international academic community.The DA system is considered as the key to the pathogenesis of ADHD.The causes of DA deficits are complex.In addition to the well-established reuptake disorder caused by abnormal DA transporter function, DA deficits are also associated with the activation of DA vesicle cycle enzymatic inactivation, vesicle transport dysfunction, and receptor dysfunction, which are of great significance in analyzing disease pathogenesis and drug development.This article reviews the research on the causes of DA deficits proposed in recent years based on the theory of DA deficits, aiming to provide ideas and references for the research on the pathogenesis of ADHD in China.
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Objective:To analyze and study the difficulties and countermeasures in the implementation of the Qualified Person(QP) system for stem cell clinical research, and share the experience of QP management practice in our hospital in order to promote and improve the construction of the QP management system in medical institutions.Methods:Comprehensive investigations were conducted to summarize and analyze the shortage of talents, unclear qualifications, unclear responsibilities, and lack of assessment standards in the QP system of medical institutions.Results:In view of the difficulties in the implementation of the current QP system, it is suggested to consider a combination of improving the system of laws and regulations, strengthening the top-level design of stem cell research institutions, clarifying the qualification threshold, refining QP responsibilities, continuing training and assessment system, establishing QP support system, etc.Conclusions:Medical institutions are responsible for stem cell clinical research, and the improvement of the QP system can promote the development of the cell industry in China.
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Objective:To explore the application of information management platform for Investigator Initiated clinical trials (IIT).Methods:Elaborate the design and application of Clinical Information Management Platform (CIMP). Discuss the obstacles in platform development.Results:Compared with regions where clinical research is more developed, there is still a lack of standardized and efficient information management methods in China. Through the construction of the IIT information management platform, the scientific management of the IIT and the SWOT analysis of the use of the platform have been conducted. Further exploration and improvement are needed in terms of the collaboration of the information platform, data standardization, and information sharing security.Conclusions:The management efficiency can be improved by applying CIMP, which will also promote the smooth implementation of IITs.
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Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.
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Objective With the fast development of Investigator-Initiated Trials (IIT),more and more resources from the national and local governments,universities and hospitals were invested.It is important to clarify the content and methodologies of quality evaluation of the IITs at the early approval stage to assure more complete and systematic quality assessment,improve resource allocation,enhance the research ability,as well as the protection of human subject.Methods This article summarized the content and related safeguarding measures of quality assessment during the early stage of project setup.Discussed relative practice and experiences of our center.Results The contents of quality evaluation include research topic,study protocol,research team and qualifications,quality assurance plan and risk management.The organizing work and attention of the research administrative department,qualified departments and experts,as well as information platform are the required safeguarding measures for effective assessment.Conclusions Quality evaluation of IITs at the early approval stage is critical segment of study quality assurance.More attention should be paid to make every effort counts.
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Objective To prepare gemcitabine hydrochloride thermosensitive gel injection and to stablish the determina‐tion methods of its contents .Methods Gemcitabine hydrochloride thermosensitive gel injection was prepared using PLGA‐PEG‐PLGA as thermosensitive viecle .The contents of gemcitabine hydrochloride were determined by HPLC .Results The formulation contained 40 mg/ml gemcitabine and 20% (wt) PLGA‐PEG‐PLGA with phase‐transition temperature of (37 ± 0 .15) ℃ ,showing the best viscosity around human body temperature .Gemcitabine hydrochloride presented a good linearity in the range of 5‐500 μg/ml(r=0 .999 8) ,which had good precision and reproducibility .The recovery rate of low ,middle and high concentrations of gemcitabine hydrochloride were (99 .5 ± 3 .2)% ,(100 .4 ± 2 .4)% ,(102 .1 ± 2 .4)% ,n=3 ,respectively . The average contents of gemcitabine hydrochloride in three batches of sample were (101 .87 ± 2 .95)% ,(99 .4 ± 2 .73)% , (98 .98 ± 0 .71)% ,n=3 ,respectively .Conclusion The quality of gemcitabine hydrochloride thermosensitive gel injection with PLGA‐PEG‐PLGA as matrix could be controlled .It is a promising new drug for pancreatic cancer .
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To investigate the pharmacokinetic and bioavailability of polydatin [PD] in rats after oral and intravenous administration, a simple, rapid and sensitive liquid chromatography-tandem mass spectroscopy [LC-MS/MS] method was developed and validated for the determination of polydation. After precipitating the plasma proteins with methanol, the analytes were separated on a C[18] column [3.5 microm, 2.1×100 mm] with an isocratic mobile phase consisting of methanol-acetonitrile-0.1% formic acid [18: 15: 67, v/v/v] at a flow rate of 0.3 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple reaction monitoring [MRM] mode and the electrospray ionization technique was in negative mode. Linear responses were obtained for PD ranging from 1.0-5000.0 ng/mL [r=0.9984] and the LLOQ was 1.0 ng/ml and was sufficient for the pharmacokinetic studies. The intra-day and inter-day accuracy and precision of the assay were less than 8.0%. The method is capable of quantifying PD. The pharmacokinetic parameters of polydatin after intragastric administration of PD with different doses [50, 100 and 300 mg/kg] and intravenous administration at the dose of 20 mg/kg, were obtained, with t[1/2] of 200.30 min, 210.30 min, 272.26 min, and 112.5 min, and AUC[0- infinity] of 125626.41 microg/L.min, 250433.47 microg/L.min, 693722.60 microg/L.min and 1723509.57 microg/L.min, respectively. The absolute bioavailability of PD was somewhat low to 2.9%. The results were firsly reported, as far as we know, about bioavailability of PD and seem important for linking PD and other phenolic glycosides-related drugs administration to their medicinal effects
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Animals, Laboratory , Stilbenes/pharmacokinetics , Pharmacokinetics , Biological Availability , Rats, Sprague-Dawley , Plasma , Chromatography, Liquid , Tandem Mass SpectrometryABSTRACT
In this study, we prepared various matrices of hydrogel patches and studied their cross-linking mechanism by observing their rheological properties, which could provide theoretical basis and deep technical support for further industrial development of hydrogel patch. Rheology method was used to do the amplitude scanning and single-frequency scanning for various hydrogel matrix, under the condition of oscillation mode of the rheometer. Then the linear viscoelastic region, composite modulus value, as well as changes in slope with time of the composite modulus and phase angle of various hydrogel matrix were analyzed in detail. The results showed that the stability of matrix was mainly determined by hydrogel frame; only in acidic environment, the cross-linking reaction between cross-linker and hydrogel frame can occur; elasticity of matrix can be decreased by organic acid and the effect level was related to the ratio of the number of carboxyl and hydroxyl (-COO(-)/-OH) in adjusters: if the ratio was not equal, the higher -COO(-)/-OH in adjusters would be the less elasticity of matrix decreased; the cross-linking speed of matrix was determined by adjuster, the cross-linking speed of matrix contain different adjusters was ranged in following order: matrix containing tartaric acid > matrix containing lactic acid > matrix containing malic acid > matrix containing citric acid; the cross-linking speed of matrix was not uniform in the whole cross-linking process.
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Objective:To prepare ginsenoside Rg3-loaded chitosan microspheres for intranasal administration.Methods:The chitosan microspheres were prepared by the O/W/O combined with multiple emulsification chemical crosslink technique.Quadratic polynomial equation and linear regression equation were fitted by the statistic software,and the resulting equations were used to produce response surface graphs.The best experiment conditions were screened by central composite design(CCD)using drug load,encapsulation efficiency,and the proportions of microspheres(with diameter of 40-60 ?m)as variables.The shape of microspheres was observed by scanning electron microscope.Results:The best ranges of the prescription included:drug to carrier material ratio:0.4-0.5;organic phase and water phase ratio:0.4-0.6;and first emulsion and oil phase ratio:0.13-0.17.The 3 batches of microspheres prepared according to the above condition were well-shaped(full sphere),with the mean drug loading capacity being(10.25?0.08)% and the encapsulation efficiency being(30.61?1.46)%.Conclusion:The optimized technique has a good reproducibility and can be used for preparation of Rg3-loaded chitosan microspheres for intranasal administration.
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Objective:To study the effects of penetration enhancers and their combinations on the transdermal delivery of fluoxetine hydrochloride and to discuss the feasibility of transdermal administration of drugs.Methods:The penetration rate of fluoxetine hydrochloride through rat skin in vitro was measured using Valia-Chien diffusion cells and high pressure liquid chromatography was used for analysis.Results:Penetration enhancers,such as Azone,N-methyl-2-pyrrolidone(NMP),oleic acid,and their combinations all had peneration enhancing effect except for propylene glycol(PG).Azone combined with PG or NMP had the most potent enhancing effect.Conclusion:Satisfactory penetration of fluoxetine hydrochloride through rat skin can be obtained by correct combination of enhancers.
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Objective: To prepare sustained-release polylactic acid microspheres containing bupivacaine (BUP-PLA-MS) and to measure its dissolution in vitro. Methods: BUP-PLA-MS was prepared with polylactic acid (PLA) as carriers using the water-in-oil-in-water (W/O/W) emulsion solvent evaporation method. The powder particle characteristics of BUP-PLA-MS were evaluated comprehensively, and its dissolution characteristics in vitro were studied. Results: It was indicated that bupivacaine formed molecular dispersion within PLA matrix by differential thermal analysis(DTA). The in vitro release behavior of bupivacaine could be best described by Higuchi equation, with t 1/2 =22.76 h. Conclusion: Release of bupivacaine from microspheres is sustained in vitro.