Discuss Application of Real-world Data from the Boao Lecheng Pilot Zone to Support Premarket Clinical Evaluation of Medical Device / 中国医疗器械杂志

The real-world data of Hainan Boao Lecheng International Tourism Pilot Zone has the advantage of supporting pre-market clinical evaluation of medical devices. Based on the relevant requirements of clinical evaluation of medical devices and based on the practical experience of pilot devices in the early stage, the application of Boao Lecheng real-world data in the pre-market clinical evaluation path of medical devices from the perspective of review is discussed. At the same time, the elements that should be considered in real-world study design and the way of data quality evaluation are proposed. Expect to provide a reference in order to allow registration applicants to use real world data wisely to help declare device registration for marketing.

Anti-inflammatory effect and mechanism of the ethanol extract and the drug-containing serum of Zhuang medicine Stahlianthus involucratus on LPS-induced RAW264.7 cell inflammation / 中国药房

OBJECTIVE To study the anti-inflammatory effect and mechanism of the ethanol extract and the drug-containing serum of Zhuang medicine Stahlianthus involucratus on lipopolysaccharide （LPS）-induced RAW264.7 cell inflammation. METHODS The drug-containing serum or blank serum was obtained by intragastrical administration of ethanol extract of S. involucratus （75.35 g/kg） or purified water. Using RAW264.7 cells as objects， RAW264.7 cells were divided into normal control group， LPS group （1 μg/mL）， S. involucratus ethanol extract high-dose， medium-dose and low-dose groups （50， 25， 12.5 μg/mL）， 4% or 15% blank serum groups， 4% or 15% blank serum+LPS groups， 4% or 15% drug-containing serum groups， 4% or 15% drug-containing serum+LPS groups. After culturing for 24 h， cell viability， the contents of nitric oxide tumor necrosis factor α （TNF-α）， interleukinand IL-6 as well as mRNA expressions of Toll-like eceptor 4 （TLR4） and nuclear factor κB （NF- κB） and protein expressions of nitric oxide synthase （NOS） and cyclooxygenase 2 （COX-2） were all detected in each group. 0771-4953513。E-mail：zhuhuagx@163.com RESULTS After culturing for 24 h， there was no statisticalsignificance in the difference of cell viability. Compared with normal control group， the contents of NO， TNF-α， IL-1β and IL-6， mRNA expressions of TLR4 and NF-κB， and protein expressions of NOS and COX-2 were increased significantly in LPS group （P＜0.05）. Compared with 4% or 15% blank serum groups， the levels of above indexes were increased significantly in 4% or 15% blank serum+LPS groups （P＜0.05）. Compared with LPS group， the levels of above indexes were decreased significantly in S. involucratus ethanol extract groups （P＜0.05）. Compared with 4% or 15% blank serum+LPS groups， the levels of above indexes were decreased significantly in 4% or 15% drug-containing serum+LPS groups （P＜0.05）. CONCLUSIONS The ethanol extract and the drug-containing serum of S. involucratus can significantly alleviate LPS-induced inflammatory reaction， the mechanism of which may be associated with inhibiting the activity of TLR4/NF-κB signaling pathway， down-regulating the protein expressions of COX-2 and NOS， and reducing the release of inflammatory factors.

Study on spectrum-toxicity relationship of in vitro hepatotoxicity of aqueous extract from Euodia rutaecarpa / 中国药房

OBJECTIVE To study the spectru m-toxicity relationship of in vitro hepatotoxicity of aqueous extract from Euodia rutaecarpa. METHODS The aqueous extract from 16 batches of E. rutaecarpa from different habitats were prepared. The fingerprints of aqueous extract from E. rutaecarpa were established by ultra high performance liquid chromatography （UPLC） method and Similarity Evaluation System of TCM Fingerprint （2012A edition ），and common peaks were identified and the similarity was evaluated. Using normal human hepatocytes L 02 as subject ，inhibitory effect of aqueous extract from 16 batches of E. rutaecarpa to them were investigated. The spectrum-toxicity relationship of UPLC fingerprint of aqueous extract from E. rutaecarpa with the hepatotoxicity of hepatocytes L 02 was analyzed by grey relational analysis （GRA）and partial least squares regression analysis （PLSR）. The corresponding compound of the chromatographic peak with the greatest correlation with the in vitro hepatotoxicity of E. rutaecarpa were isolated ，prepared and identified. RESULTS There were 27 common peaks in UPLC fingerprints of aqueous extract from 16 batches of E. rutaecarpa ，with similarity of 0.375-0.995. Totally 9 peaks were confirmed ，i.e. neochlorogenic acid （peak 5），chlorogenic acid （peak 9），cryptochlorogenic acid （peak 10），caffeic acid （peak 12），rutin （peak 16），hyperin（peak 17），dehydroevotarine（peak 19），evotarine（peak 24），rutecarpine（peak 25）. The aqueous extract from 16 batches of E. rutaecarpa showed significant inhibitory effect on the growth of L 02 cells（P＜0.05 or P＜0.01），and the inhibitory rate ranged from 6.68％ to 67.95％. GRA showed that there were 18 common peaks with correlation degree greater than 0.8，which were peak 8＞peak 3＞peak 23＞peak 7＞peak 4＞peak 9＞peak 12＞peak 2＞peak 19＞peak 6＞ 4928381。E-mail：799247687@qq.com peak 15＞peak 5＞peak 1＞peak 17＞peak 21＞peak 26＞ peak 20＞peak 14 in descending order of correlation degree. PLSR showed that there were 14 peaks with regression coefficient＞0 and variable importance projection value ＞1，and the order of regression coefficient was peak 8＞peak 3＞peak 23＞ peak 2＞peak 7＞peak 4＞peak 12＞peak 9＞peak 19＞peak 5＞peak 17＞peak 26＞peak 10＞peak 15. Peak 8 had the greatest correlation with in vitro hepatotoxicity，and the corresponding compound of this peak was identified as 6-O-trans caffeoyl gluconic acid. CONCLUSIONS The in vitro hepatotoxicity of aqueous extract from E. rutaecarpa is the result of multiple component interaction，among which 6-O-trans caffeoyl gluconic acid shows closest relation with in vitro hepatotoxicity.

Study on Spectrum-effect Relationship of Anti-inflammatory and Analgesic Effects of Ethyl Acetate Extract from Zhuang Medicine Stahlianthus involucratus / 中国药房

OBJECTIVE：To i nvestigate the spectrum-effect relationship of analgesic and anti-inflammatory effects of ethyl acetate extract from Zhuang medicine Stahlianthus involucratus from different habitats. METHODS ：Ten batches of S. involucratus from different habitats were used as samples to investigate the anti-inflammatory and analgesic activities of ethyl acetate extracts by xylene induced ear swelling test and acetic acid induced writhing test in mice. HPLC fingerprints of 10 batches of ethyl acetate extract from S. involucratus were established and their similarity was evaluated by using Similarity Evaluation System of TCM Chromatogram Fingerprint （2012 edition），and the common peaks were identified by comparison with the control. The spectrum-effect relationship of anti-inflammatory and analgesic effects of ethyl acetate extract from S. involucratus were analyzed on the basis of Pearson correlation coefficient （auricle swelling degree and writhing times in 15 min as pharmacodynamic indexes ）and Grey relational analysis （inhibition rate of ear swelling and analgesic rate as pharmacodynamic indexes ）. RESULTS ： batches of ethyl acetate extract from S. involucratus had obvious anti-inflammatory and analgesic effects ； inhibition rates of ear swelling in mice were 46.43％-55.16％，and the analgesic rates of mice were 45.56％-52.72％. A total of 18 common peaks were identified in 10 batches of samples ，andthe similarity between them and the control fingerprint was 0.994-0.997. Compared with substance control ，the pea ks 1，2 and 4 were identified as protocatechuic acid ， p-hydroxy- 0771-4953513。E-mail：liangjie1101@126.com benzoic acid and p-hydroxybenzaldehyde，respectively. Results of Pearson correlation analysis showed that peak 10 and peak 18 were significantly negative correlated with auricle swelling degree and writhing times in 15 min（r were values －0.853，－0.738，P values were 0.002，0.015，respectively）. Results of Gray correlation degree analysis showed that the correlation degree of 18 common peaks with inhibition rate of ear swelling and analgesic rate were all greater than 0.65；among them ，peaks 14，1（protocatechuic acid ），17，9，4（p-hydroxybenzaldehyde），2（p-hydroxybenzoic acid ）， 16，7 and 6 showed the relatively high correlation degree （correlation degree ＞0.7）；peak 1（protocatechuic acid ），17，14，9，16，2 （p-hydroxybenzoic acid ）and 4（p-hydroxybenzaldehyde）showed the relatively high correlation degree （correlation degree ＞0.7）. CONCLUSIONS：The ethyl acetate extract of S. involucratus show good anti-inflammatory and analgesic effects. Peak 1 （protocatechuic acid ），2（p-hydroxybenzoic acid ），10，14，17，18 may be its main active ingredients.

Preliminary Review of Relationship between Medical Device Evaluation and Quality Management System in Premarket Approval / 中国医疗器械杂志

This paper analyzed the current reform of review and approval mechanism for medical devices and discussed the method for technical review process extending to product quality controllable direction and found the measures and suggestions to strengthen technical review for quality management system with the help with complementary relationship between the technical review and the quality management system assessment of the pre-market registration. Nowadays, because of the demand of eRPS， MAH and the amendment of regulation, the integration of technical review and quality management system is more important, necessary and scientific. Scientific and systematic evaluation should be carried out to strengthen the pre-market approval of medical devices and ensure the safety and effectiveness of medical products.

Application of International Medical Device Electronic Registration / 中国医疗器械杂志

The eRPS system for medical device registration of National Medical Products Administration was officially launched on June 24, 2019. This paper focused on the following two aspects of the electronic declaration process of medical device regulatory agencies in the whole world:one is whether the electronic submission format is consistent, the other is whether the electronic submission path is convenient. Suggestions are put forward for the next nationwide implementation of the electronic submission so as to speed up the process of the electronization of medical device evaluation in China.

Analysis of key technical points of diagnostic reagents for diabetes / 中华检验医学杂志

Detecting the concentration of glucose and hemoglobin A1cin blood can be used in the diagnosis and treatment monitoring of diabetes. With the high incidence of diabetes worldwide, these diagnostic reagents for diabetes have gradually become the hot spot of registration. In view of the characteristics of these reagents, this review analyzes the main technical issues referring to internal and overseas related technical documentation, to providing ideas and help for product development and registration.

Discussion on Quality Management System Construction for Evaluation of Medical Devices / 中国医疗器械杂志

The quality management system is of great significance for improving efficiency and promoting sustainable development. This article introduces and discusses the related definitions, construction principles, improvements of document control and measurement analysis, and system construction, etc. of quality management system for evaluation of medical devices in order to provide references for relevant researchers.

Effects of Different Dose Compatibility of Scutellaria baicalensis-Rheum palmatum-Coptis chinensis Based on Sanhuang Xiexin Decoction on Dissolution Rate of Baicalin and Baicalein / 中国药房

OBJECTIVE: To investigate the effects of different dose compatibility of Scutellaria baicalensis-Rheum palmatum-Coptis chinensis based on Sanhuang Xiexin decoction (shorted for Xiexin decoction) on dissolution rate of baicalin and baicalein, and to provide reference for studying chemical mechanism of TCM compound dose composition compatibility. METHODS: HPLC method was used to determine the contents of baicalin and baicalein. By fixing the dose of S. baicalensis (3 g), using the dose of R. palmatum and C. chinensis as factors, dissolution rate of baicalin and baicalein as response value, two-factor and five-level central composite test was designed. The optimal dose compatibility of S. baicalensis-R. Palmatum-C. chinensis was optimized by response surface method, and compared with the dissolution rate of baicalin and baicalein in classic dose Xiexin decoction (S. baicalensis 3 g, R. Palmatum 6 g, C. chinensis 3 g). RESULTS: When the doses of S. baicalensis, R. palmatum, C. chinensis were 3, 1. 76, 0. 17 g, total dissolution rate of baicalin and baicalein was the highest in extract. The average total dissolution rate of baicalin and baicalein in validation test was 21. 89％ (RSD=0. 46％, n=3),and the relative error was 2. 88％ with the predicted value of 22. 54％. Compared with the classical dose of Xiexin decoction, the total dissolution rate of baicalin and baicalein in the optimum dose of S. baicalensis-R. Palmatum-C. chinensis in extract was increased by 47. 21％. CONCLUSIONS: The different dose compatibility of S. baicalensis-R. Palmatum-C. chinensis based on Xiexin decoction influence the dissolution of baicalin and baicalein to certain extent. When the doses of S. baicalensis, R. palmatum, C. chinensis are 3, 1. 76, 0. 17 g, dissolution rate of baicalin and baicalein are higher than that of classic dose.

Effects of Huangkui Capsules on Oxidative Stress and Micro-inflammation State in Diabetic ;Nephropathy Patients with Maintenance Hemodialysis / 中国中医药信息杂志

Objective To investigate the effects of Huangkui Capsules on oxidative stress and micro-inflammation state in diabetic nephropathy patients with maintenance hemodialysis. Methods Forty-six patients with diabetic nephropathy who had received maintenance hemodialysis for over six month in Gansu Provincial People's Hospital were randomly divided into observation group (23 cases) and treatment group (23 cases) from January to December in 2014. Twenty healthy subjects who had physical examinations were selected as the control group at the same time. Observation group were given conventional hemodialysis for 4 hours, 3 times a week; treatment group were given conventional hemodialysis combined with Huangkui Capsules, orally, 2.5 g each time, 3 times a day. Both groups were treated for 8 weeks. Blood was collected before and after treatment for detection of hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), white blood cell (WBC), malondialdehyde (MDA), cycle of advanced oxidation protein products (AOPP), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Results The levels of IL-6, TNF-α, AOPP, WBC, MDA and hs-CRP were significantly higher in the observation group and the treatment group compared with the control group before treatment (P0.05). After treatment, the levels of IL-6, hs-CRP, MDA and AOPP increased in the observation group (P0.05);The levels of AOPP, TNF-α, hs-CRP, WBC, MDA and IL-6 in treatment group significantly decreased (P<0.01), GSH-Px and SOD significantly increased (P<0.01); there was statistical significance between the observation group and the treatment group (P<0.01). Conclusion Micro-inflammation state and oxidative stress exist generally in diabetic nephropathy maintenance hemodialysis patients. Huangkui Capsules can improve oxidative stress and micro-inflammation state in diabetic nephropathy maintenance hemodialysis patients.

Technology Optimization and Content Determination of Caffeic Acid in 10 Batches of Laggera alata from Different Areas / 中国药房

OBJECTIVE:To optimize the extraction technology of caffeic acid in Laggera alata,and establish a method for its content determination. METHODS:The caffeic acid in L. alata was extracted by reflux extraction. Using extraction content as inves-tigation index,orthogonal test was used to investigate the effects of ethanol volume fraction,material-liquid ratio and extraction time on caffeic acid,and the extraction technology conditions were optimized. HPLC was adopted to determine the content of caffe-ic acid in 10 batches of L. alata from different areas,using caffeic acid as reference substance,at wavelength of 320 nm. RE-SULTS:The optimized extraction technology conditions were as follows as ethanol volume fraction of 10%,material-liquid ratio of 1 : 40 and extraction time of 3 h. Under the condition,verification test for caffeic acid was carried out,and the average content of caffeic acid in L. alata was 0.5211 mg/g(RSD=1.18%,n=3). The content of caffeic acid in 10 batches of L. alata from dif-ferent areas ranged in 0.3752-0.7766 mg/g,and the content showed great differences. CONCLUSIONS:The content of caffeic ac-id in L. alata is related to area and harvest season. The caffeic acid extration by optimized technology shows good reproducibility;and the established method for content determination is stable and feasible.

Establishment and Evaluation of the Metabolic Syndrome Models in Rats / 医学研究杂志

Objective To replicate the rats model of human metabolic syndrome (MS),determine the standard of the model,evaluate the success rate of model,provide the experimental basis for the study of the pathogenesis and therapeutic study of MS.Methods Eighty specific pathogen free male Wistar rats aged 7 weeks were randomly divided into the normal group (n =10) and the experimental group (n =70),which were respectively fed with normal diet and high fat,high sugar,high salt diet for 16 weeks.The rats' body weight,abdominal circumference,body length,blood pressure and fasting plasma glucose (FPG) were measured every 4 weeks.The experimental group rats were injected with streptozocin(STZ) 35mg/kg intraperitoneally once at the fifteenth week,the blood lipids (TC,TG,LDL-C and HDL-C) and FINS were measured,and HOMA-IR was calculated a week late.Results With the feeding time gradually extended,the rats' body weight,abdominal circumference,blood pressure,FPG,TG,TC,FINS,HOMA-IR and LDL-C levels were all significantly higher in the experimental group than in the normal group (P ＜ 0.05),while HDL-C was lower than that of the normal group (P ＜0.05).There was no significant difference in body length between the two groups(P ＞0.05).The success rate of MS rats models were 74.3％.Conclusion High fat,high sugar,high salt diet combined with a small dose of STZ intraperitoneal injection can successfully replicate the rat model of MS.This kind of rat models conforms to the pathological characteristic of MS,which can be easily operated and with high success rate.Therefore,it could be applied as an ideal MS animal model for the study of MS and drugs therapeutic effect.

The system setting for diagnostic reagents of polymerase chain reaction nucleic acid amplification / 中华检验医学杂志

Diagnostic reagents of polymerase chain reaction ( PCR ) nucleic acid amplification is growing more and more important in the field of clinical diagnosis along with the development of the PCR technology.During to the complexity of the detection target and the clinical requirements for measuring linearity, accuracy, specificity, subtype detection, precision, limit of detection/quantification and interfering substance , the diagnostic reagents of nucleic acid amplification have a very strict control system . In order to ensure the quality of the experimental data of quantitative PCR , there have been standards such as The Minimum Information for Publication of Quantitative Real-Time PCR Experiments ( MIQE) , aiming to putting forward specific requirements for sample processing , experimental designing , system setting and quality control.But in the clinical application of nucleic acid amplification products , lots of requirements are not clear for the PCR system setup .This article discussed the requirements of PCR system setting , quality control system and Methodology of nucleic acid extraction and purification , aiming to promote the related design and the establishment of the standards of relevant .

Technical requirements for point-of-care testing in vitro diagnostic reagents registration / 中华检验医学杂志

POCT in vitro diagnostic reagents featuring with easy operation , on-site testing, low requirements for specimen processing , fast results , usually applied small testing equipment , is a strong complement to high-throughput , large automated tests in clinical laboratory centers.According to the State Council issued in 2014 “Supervision and Regulation of Medical Devices ” and series regulations and management practices issued by the China Food and Drug Administration , conduct an investigation in POCT IVD registration relevant technical requirements and give some advice for the relevant personnel of register work.

Large vascularized tissue-engineered bone for repair of bone defects / 中国组织工程研究

BACKGROUND:Currently, there are many problems existing in the construction of large tissue-engineered bone, and the most important is ischemic necrosis. Vascularization is critical for the biological function of large tissue-engineered bone. OBJECTIVE:To prepare large pieces of vascularized tissue-engineered bone for orthotopic transplantation in repairing large femoral defects of rabbits, and to explore tissue regeneration methods and characteristics. METHODS:Rabbit femoral structure was firstly imitated to construct a vascularized prefabricated model, based on which, we constructed large pieces of vascularized tissue-engineered bone. A total of 18 New Zealand white rabbit 18, aged 8 weeks, were divided into experimental group and control group. The experimental group was subject to orthotopic transplantation of large vascularized tissue-engineered bone, while the control group was treated with orthotopic transplantation of large tissue-engineered bone without vascularization processing. After 2, 4, 8 weeks, gross observation, X-ray films, and tissue section were compared between the two groups. RESULTS AND CONCLUSION:Gross observation and imaging observation showed that the osteogenesis in the experimental group at 2, 4, 8 weeks were better than that in the control group. The ratio of new bone tissue to total area of bone graft was significantly higher in the experimental group than the control group at 2, 4, 8 weeks postoperatively (P<0.01). These findings indicate that large vascularized tissue-engineered bone is preferred to the repair of large bone defects.

Technical requirements of the pathogen-specific IgM qualitative detection reagents / 中华检验医学杂志

To offer the guidance of the registration application of in vitro diagnostic (IVD) reagents,the technical requirements for registration of the pathogen-specific Immunoglobulin M (IgM) qualitative test reagents were discussed.The application paperwork including the evaluation of analytical performance was analyzed based on the the legal requirement from the China Food and Drug Administration (CFDA)and the experience of the IVD registration.

Study on bilingual teaching of functional experiment for medical undergraduates / 中华医学教育探索杂志

Functional experiment is an important course to cultivate medical undergraduates'comprehensive and creative thinking abilities. Based on the conduction of the course, prominent teaching factors like the qualifies of teachers and students, the making of the courseware, the choosing of experiment contents and the arrangement of teaching progress,have been analyzed and practical teaching suggestions have also been proposed for a better functional experiment bilingual teaching quality.

Determination of three chemical constituents in zhuang medicine Blumea megacephala (Randeria) by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method for content determination of protocatechuic acid, chlorogenic acid and caffeic acid in Zhuang medicine Blumea megacephala (Randeria), and explore the content variation of the 3 components of the herbs harvesting in different months, and provide the scientific basis of reasonable application.</p><p><b>METHOD</b>The determination was carried out on a Shimadzu VP-ODS column (4.6 mm x 250 mm, 5 microm) eluted with acetonitrile and water containing 0.1% phosphoric acid in a linear gradient elution. The flow rate was 1 mL min(-1), and the detected wavelength was set at 258, 327nm.</p><p><b>RESULT</b>The peak areas and the concentrations of the three components had good linear relationship in the range of 1.7-17 mg x L(-1) for protocatechuic acid, 15.6-156 mg x L(-1) for chlorogenic acid, 3.96-39.6 mg x L(-1) for caffeic acid. The average recoveries were 103.4%, 102.2%, 98.5%, respectively.</p><p><b>CONCLUSION</b>The method was proved to be simple, accurate and used for the quality evaluation of Blumea megacephala (Randeria).</p>

Proteomic study for serum biomarkers in Parkinson's disease using weak cation exchange magnetic beads and MALDI-TOF-MS / 中华神经科杂志

Objective To screen for the potential protein biomarkers in serum for the diagnosis of idiopathic Parkinson's disease (PD) using proteomic fingerprint technology. Methods Proteomic fingerprint technology combining weak cation exchange (WCX) magnetic beads with MALDI-TOF-MS was used to identify and compare the serum proteins from 61 patients with idiopathic PD, 29 patients with other neurodegenerative diseases (OND) and 30 healthy blood donors. Model of biomarkers and proteomics patterns associated with PD was analyzed by Biomarker Patterns Software. The model also was validated by 40 newly recruited PD cases. Results A total of 17 discriminating M/Z peaks which were related to PD were identified ( nonparametric test, Z:-4.039--2.633, P<0.01 ). Five biomarkers with M/Z of 6121, 5234, 2961,4309 and 8170 respectively generated an excellent model of distinguishing between PD and healthy groups. The sensitivity was 98.4% and the specificity was 83.1%. Blind testing in 40 newly recruited cases demonstrated a sensitivity of 85.0% (17 of 20 PD) and a specificity of 70. 0% (14 of 20 controls). Conclusions Combination of WCX magnetic beads with MALDI-TOF-MS is a useful method in establishing proteomic patterns associated with PD. It also may be used to construct a diagnostic model with PD Biomarkers. Although this model of biomarkers fails to distinguish between PD and OND controls, it is able to differentiate PD from healthy controls.

Effects of repeated hypoxic exposures on glycolysis, mitochondrial oxidative phosphorylation and energy charge in mouse brain / 基础医学与临床

Objective To study the effects of repeated hypoxic exposures (HEs) on glycolysis, mitochondrial oxi-dative phosphorylation and energy charge in mouse brain. Methods Adult BALB/c mice were repeatedly exposed to hypoxia for 5 times and the standard tolerant time and body temperature were recorded. The activities of PFK, PK and mitochondrial complex Ⅰ in the brain were assayed. Phosphoadenosines and energy charge were measured. Results Repeated HEs prolonged the hypoxic tolerance and reduced the body temperature. The activities of PFK and PK experienced regular changes, with an increase in 1st and 3rd HEs and a decline to control levels in 5th HE. The complex Ⅰ activity continued to decrease during HEs. The energy charge was stable. Conclusion HEs lead to a regular change of glycolysis, a continued inhibition of mitochondrial oxidative phosphorylation, and a main-tained energy charge in the brains of mouse.