On May 24, 2021, the American Heart Association and the American Stroke Association (AHA/ASA) issued the 2021AHA/ASA Guidelines: Stroke Prevention in Patients with Stroke and Transient Ischemic Attack.The statement covers the diagnosis and evaluation of secondary stroke prevention, the management of vascular risk factors, etiology management and systematic nursing of secondary stroke.This paper intends to interpret the statement and compare the guidelines of antithrombotic drugs, so as to provide reference for the prevention of future stroke in survivors of ischemic stroke and transient ischemic attack in China.
Objective To investigate the effect of n-butanol extracts of Aitongfang (BTE) on apoptosis,proliferation and calcitonin gene related peptide (CGRP)/ cAMP-response element binding protein (CREB) signal pathway in Lewis lung cancer mice. Methods A total of 20 C57BL/6 mice Lewis lung cancer mouse models were established by subcutaneous injection of tumor cells.They were randomly divided into model control group and BTE group,with 10 animals in each group.The BTE group was given 1.97 g·kg-1·d-1 BTE by gavage,and the model control group was given 0.9% sodium chloride solution by gavage for 14 consecutive days.The animals were sacrificed and the tumor tissue was stripped.The tumor mass and volume changes of the two groups were detected.The HE staining was used to analyze the morphological changes of tumor tissues,and the ratio of BRDU positive cells and the ratio of TUNEL positive cells were detected by immunofluorescence,as well as the changes of CGRP/p-CREB signal pathway were analyzed by Western blotting. Results The tumor mass of model control group and BTE group were (2.20±0.82) and (1.38±0.41) g,respectively. The volumes were (3.34±1.35) and (1.35±0.34) cm3,respectively (all P<0.05).The tumor cells in the BTE group were swollen and the nucleus was pyknotic, at the same time,the ratio of BRDU positive cells was significantly reduced (P<0.01).The ratio of the number of TUNEL positive cells in the BTE group was increased significantly (P<0.01).Compared with the model control group,the expression of CGRP and p-CREB protein of the BTE group were decreased significantly (P<0.05,P<0.01). Conclusion The BTE could inhibit proliferation and increase apoptosis of cancer cell in Lewis lung carcinoma.The CGRP/p-CREB signal pathway may mediate the inhibitory effect of BTE on cancer pain.
Objective To investigate the protective effect of Naozhenning formula on neuron in rats with concussion. Methods The concussion model was established by means of closed strike of metal pendulum.Succeed model rats were randomly divided into model control group(equal volume of purified water was given),piracetam group (0.324 g·kg-1) and 3 Naozhenning groups in different dosage (2.5,5.0,10.0 g·kg-1),with 10 normal rats as normal control group(equal volume of purified water was given).Rats in each group were gavaged in 10 mL·kg-1,once a day for 21 consecutive days.The changes of myelin sheath and Nissl body in brain were detected by Weil staining and toluidine blue staining,and the positive expressions of IL-6,iNOS,GFAP and MMP-9 in brain were detected by immunohistochemistry. Results Naozhenning could relieve mental manic injury in rats with cerebral concussion,reduce myelin sheath’s rupture,flexion and swelling,promote nissl body’s recovery,increase the expression of GFAP and MMP-9,and inhibit the expression of IL-6,iNOS,in brain tissue. Conclusion Naozhenning formula can alleviate mental abnormality after concussion to reduce nerve injury mainly caused by the myelin sheath and nissite of neurons' pathological change; the mechanism may related to the inhibition of brain tissue inflammation by suppressing ERK signal pathway.
Objective To construct a transgenic zebrafish model of bone loss induced by metronidazole,and to provide a convenient in vivo model for screening drugs protected the islet of pancreas and promoted bone formation. Methods Enzyme digestion was used to identify the correct recombinant plasmid (p-Iscei-INS:nfsB) for micro-injection to establish the islet mesenchymal transgenic zebrafish line.Thirty hours after fertilization,transgenic zebrafish embryos were exposed to metronidazole solution of different concentrations,and 1% DMSO was set as the negative control group.NfsB protein transformed the non-toxic precursor drug into a cytotoxin and directly destroyed the pancreatic islet cells in vivo.After 48 hours,the destruction of metronidazole was stopped by replacing the embryo culture water.The zebrafish was cultured in 24-well plate at 28.5 ℃ till the skull formation.After the experiment,blood glucose level of zebrafish was measured.Alizarin red was used to stain zebrafish bones,and the bone staining areas were quantitatively analyzed by means of microscopic examination and digital imaging. Results Compared with the negative control group,the staining area and optical density of zebrafish bones in the 5,10 and 15 μmol·L-1 metronidazole groups were significantly reduced,suggesting that the bone mineralization and bone mineral density of transgenic zebrafish were significantly reduced when metronidazole was used,and the zebrafish bone loss model was successfully established.In this model,the effect of disodium etiphosphonate on osteoporosis was verified. Conclusion The transgenic zebrafish model of bone loss induced by the destruction of islet cells was successfully established and it is a new animal model for screening small molecular compounds and the Chinese herbal medicines that can protect the islet formation at the whole animal level.
There are several existing prominent problems in children's drug using in China,such as the lack of suitable dosage forms and specifications for clinical use,off-label use of drugs and empirical medication.Drug evaluation can judge the clinical value of drugs by multi-dimensional evidence evaluation,which provides a new method for solving and ameliorting the current problems of children's clinical medication.Recently,the importance of real-world study in the evaluation of children's medication has been widely recognized,which makes the real-world evidence and real-world data important roles in medical and health decision-making.By analyzing the opportunities and challenges of the current real-world drug evaluation in the decision-making of children's medication,this paper aims to provide a reference for further development of real-world drug evaluation and promotion of children's clinical rational drug use.
Evaluation of drug and medical device effectiveness using real-world study (RWS) based on real-world data (RWD) to obtain real-world evidence (RWE) has become an important topic in clinical and regulatory decision-making,in which one of the key issues is to find comparable controls.This paper discusses external control (EC),covering its definition,application scenarios,study design,statistical analysis,risk of bias and the report standards of the study with EC, to facilitate the generation and application of RWE for evidence-based decision-making in China.
In recent years, the researches on the real world have been paid more and more attention by the public. The various applications of real-world study in many fields such as drug evaluation also show ethical value, but also bring many ethical problems.The really important ethical value lies in following the practical character of ethics, which not only confirms the basic feature of the extensive applicability of medical ethics, but also better realizes the mutual unification of personal and public interests.At the same time, this paper analyzes a series of problems existing in informed consent, protection of privacy and intellectual property rights, authenticity of evaluation and ethical review in real-world drug evaluation, and puts forward corresponding countermeasures and methods.
Objective To excavate and analyze the safety signals of liraglutide, so as to provide a reference for clinical safety and rational use. Methods The ratio of reporting odd ratio (ROR) method and the proportional reporting ratio (PRR) method were used to perform data on the liraglutide-related reports included in American Food and Drug Administration Adverse Event Reporting System (FAERS) from January 25, 2010 to the first quarter of 2021. The safety signals were analyzed from the three dimensions: preferred language (PT), high-level language (HLT), and standardized MedDRA (Medical Dictionary for Regulatory Activities) query (SMQ) of MedDRA. Results There were 24 957 ADE reports with liraglutide as the primary suspected drug, of 53 signals were obtained at the HLT level, 12 signals at the SMQ level, and 21, 15, and 9 signals were detected at the top 30 events reported by the PT/HLT/SMQ level, respectively. The signals of these algorithms were completely coincident. Signal results were mainly manifested as gastrointestinal adverse reactions, acute and chronic pancreatitis, acute gallbladder disease, and hypoglycemia. The signals were organized and compared, and the 10 events involved not included in drug label. Conclusion Post-marketing adverse reaction signal monitoring is helpful to understand the characteristics of liraglutide safety events, which can lay the foundation for further pharmacovigilance work.
Objective The pandemic of COVID-19 has brought unprecedented disaster to humans. This study was aimed to evaluate the safety of treatments for SARS-CoV-2 and other β-coronaviruses. Methods We meta-analyzed random controlled trials (RCTs), cohort studies and quasi-random controlled trials (quasi-RCTs) investigating treatments for five β-coronaviruses with data from PubMed, Embase, Web of Science, Cochrane library, SinoMed, China National Knowledge Infrastructure and WanFang Database. Results From 2003 to June 2020, a total of 59 studies involving 9598 participants met the inclusion criteria, with 49 studies included 27 RCTs, 19 cohort studies and three quasi-RCTs on SARS-CoV-2, nine studies on SARS-CoV, and one cohort study on MERS-CoV. Within the included literature, the following results were of significance. Compared with standard of care (SOC) for patients with SARS-CoV-2, two cohort studies conducting lopinavir/ritonavir (LPV/RIT) treatment [RR=2.68,95%CI(1.48,4.85), I2=34.3%, low quality] and one RCT delivering high dose hydroxychloroquine or chloroquine (CQ) [RR=3.43, 95%CI(1.55,7.58), moderate quality] reported more overall adverse events (OAEs). Nevertheless, in an RCT and a non-randomized RCT, LPV/RIT /corticosteroids groups had less incidences of acute respiratory distress syndrome (ARDS) than those of SOC [RR=0.46, 95%CI(0.25,0.86) low quality; RR=0.65, 95%CI(0.44,0.98), very low quality, respectively]. Two RCTs implementing 10-day remdesivir treatment [RR=0.94, 95%CI(0.80,1.11), I2=28.8%, moderate quality] and 11 RCTs employing traditional Chinese medicine (TCM) [RR=0.77, 95%CI(0.53,1.10), I2=0.0%, low quality] demonstrated no significant difference from SOC. Compared with SOC for patients with SARS-CoV, six RCTs with TCM treatment reported lower OAEs [RR=0.38%, 95%CI(0.21,0.71), I2=0.0%, low quality]. Conclusion Overall, LPV/RIT and high dose CQ showed OAE issues treating SARS-CoV-2, while remdesivir and TCM seemed safe considering all considered safety outcomes.
Objective To conduct a thematic analysis of the real-world study based on hospital information system, in order to provide reference for further studies. Methods CNKI, Wanfang Data, SinoMed, VIP, PubMed, EMBASE databases for real-world studies based on hospital information system were searched. The main contents,such as keywords, authors, organizations, journals, were extracted by the VOS viewer 1.6.15 software as well as generated a high-frequency keywords clustering network map and a cooperation network map of authors and organizations. The Microsoft Visio software was used to draw a mind map of the research content. Results A total of 367 real-world studies based on hospital information systems were published in 134 journals, of which the Zhongguo zhongyao zazhi was the most productive journal. The authors and institutions with the most publications are Researcher Xie Yanming and the China Academy of Chinese Medical Sciences, respectively. The authors and institutions that have a cooperative relationship have formed 5 author cooperative groups and 14 institutional cooperative bodies, respectively. The keywords network diagram showed that the real-world studies based on the hospital information system mainly focuses on six topics, and the keyword density diagram showed that hospital information system, real world, combination medication and propensity scoring method were the most popular contents. The top three of most frequency drugs were Compound Kushen Injection, Shenfu Injection, and Dengzhan xixin Injection, respectively. The most concerned system disease and disease were digestive system diseases and coronary heart disease, respectively. The real-world studies based on hospital information system mainly concerned six aspects: clinical characteristics of diseases or drugs, drug evaluation, influencing factors, intervention effect evaluation, correlation studies and exploratory studies. The most frequently used analysis method was the descriptive analysis combined with the association analysis. Conclusion Chinese real-world study based on hospital information systems is still in its infancy. The attention of researchers is low, and the cooperation between various institutions and authors is relatively lacking. The research methods and data analysis methods are simple and crude, and the data utilization rate is low. The most concerned aspects are usage characteristics of drugs, clinical characteristics of diseases, and drugs evaluation, however pay more attention to its external characteristics, less research on internal laws, and the degree of attention to the real world research of western medicine needs to be improved.
Objective To analyze the research status and focus in Chinese real-world study. Methods The data bases of PubMed,EMBASE (Ovid),CENTRAL (Ovid),CNKI,VIP,Wanfang,and SinoMed were searched to collect real-world studies published by Chinese scholars from inception to 11th June 2020.Two researchers independently screened the literature, extracted and counted information by BICOMB 2.0 and clustering analysis was performed by CLUTO. Results Eventually,1612 real-world studies published by Chinese scholars were included.The number of articles is generally increasing,including 638 journals. Most articles are published from several institutions, including the Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences,Renmin University of China,the Sixth Medical Center of PLA General Hospital,etc.There are a wide range of research issues,including Chinese materia medica and syndromes,safety and adverse reactions in the drug clinical application,risk factors,treatment measures and clinical outcomes of cardiovascular and cerebrovascular diseases. Conclusion Rea-world study sprang up lately but developed rapidly in China,with extensive research issues.
Objective To observe the efficacy and safety of low-dose transdermal fentanyl patches(TDF 12.5 μg·h-1) in the treatment of opioid intolerant elderly patients with moderate to severe cancer pain,and to evaluate the effects of low-dose fentanyl transdermal patches on cognitive function and quality of life,in order to provide evidence for the optimal management of cancer pain in elderly patients with cancer. Methods Eleven tertiary hospitals in seven provinces and cities participated in this single-arm,non-random,open and prospective multicenter study.From September 2017 to December 2019,a total of 285 opioid-intolerant patients with moderate to severe cancer pain were included,including 62 patients over 70 years old.The initial dose of TDF is 12.5 μg·h-1.A total of 8 cycles of TDF treatment were completed with 3 days per cycle.An immediate-release form of any strong opioid equivalent to 10% to 20% morphine-equivalent daily dose (MEDD) was allowed for breakthrough pain.The effectiveness of low-dose fentanyl transdermal patches was assessed using the pain numerical score,pain relief,pain relief rate,and tumor patient Quality of Life score EORTC QLQ-C30 (V3.0) scale.The adverse events and safety of TDF were observed and evaluated.Meanwhile,cognitive function was assessed by the Cognitive Function Survey Scale (MMSE). Results Of the 62 patients enrolled,60 completed the study and 2 fell off.The median pain score decreased from 5.05 to 1.00,and the pain degree was significantly lower than before (P<0.01). Except for head and neck tumors,in the analysis of other subgroups,such as gender,previous treatment,baseline pain score,primary tumor site.The pain relief was more significant in the severe pain group than in the moderate pain group (5.49±0.75 vs.3.78±1.25,P<0.01). A total of 20 patients presented mild to moderate adverse reactions,including 8 cases of vomiting (12.90%),6 cases of nausea (9.68%),3 cases of constipation (4.84%),2 cases of drowsiness (3.23%) and 1 case of urinary retention (1.61%). Conclusion Low-dose TDF is safe and effective for opioid-naïve elderly patients with moderate to severe cancer pain.The adverse reactions are controllable,and the quality of life is significantly improved,with little impact on patients' cognitive function.
Maturity onset diabetes of the young (MODY) is a special type of monogenic diabetes,which has several subtypes caused by mutations in at least 14 known genes.The medicine of MODY subtype show variations according to mechanism of pathogenesis.Currently,most reports are about MODY-1,2,3,and 5 subtypes,and a few of reports are about other subtypes.The aim of this review is to summarize the prevalence,mechanism of pathogenesis, and precision medicine of the 14 known MODY subtype,providing references for the precision medicine.
Hypoxia and sustained inflammation stimulate pathological angiogenesis,which is the crucial elements resulting in liver fibrosis,cirrhosis and hepatocellular carcinoma (HCC).The purpose of this paper is to investigate the characteristics and differences of pathological neovascularization in the progression of hepatic fibrosis to cirrhosis and HCC,to summarize the application of tyrosine kinase inhibitors,monoclonal antibodies,traditional Chinese medicine prescriptions or single traditional Chinese medicine and other antiangiogenesis drugs in these three stages.
Mammalian rapamycin target protein (mTOR) can sense various external signals (hypoxia,stress,nutrients,etc.),regulate body metabolism (including cell growth,survival,etc.),and affect biological functions.This paper reviews the different role of rapamycin,an inhibitor of mTOR,in cancer,metabolism,life span and so on.Furthermore,it provides reference for its clinical application.
Objective To establish a method for the detection of depressor substances in osteopeptide preparations. Methods According to the mothed in Pharmacopoeia of the People's Republic of China (2020),comparing the difference between bone peptide preparation and histamine reference substance,preparation and stock solution in the same enterprise,and in order to investigate the correlation between bone peptide stock solution and its preparations. Results A total of 22 batches of samples (including bone peptide injection,bone peptide for injection,compound bone peptide injection,bone peptide sodium chloride injection,bone melon extract injection,compound bone peptide for injection,bone melon extract for injection,bone melon extract for injection,and cervus melon peptide for injection) from 6 manufacturers were all in conformity with the requirements. Conclusion It was suggested that depressor substance test should be added into the quality standard of osteopeptide preparations,which is essential to ensure the quality of the drug.
Objective To establish a quality control system of benzoyl metronidazole drug substance,and to establish a gas chromatography (GC) method to determine residual solvents of ethanol,toluene and pyridine in benzoyl metronidazole. Methods The direct injection method was used,and the detection of three residual solvents was performed on a InertCap FFAP capillary column (30 m×0.32 mm,0.25 μm) with a temperature program: the initial temperature was 60 ℃,and it was maintained for 1 minute,raise the temperature to 100 ℃ at 4 ℃·min-1,maintain 1 minute,and then raise the temperature to 200 ℃ at 20 ℃·min-1.The detector was hydrogen flame ionization.The amount of each residual solvent in benzoyl metronidazole was calculated by external standard method. Results The stability of the mixed reference solution and the test solution at room temperature for 8 h was good.The detection limits of ethanol,toluene and pyridine were 7.42,2.54,5.52 μg·g-1,and the limits of quantification were 24.74,8.46,18.39 μg·g-1,respectively.When the concentration of ethanol is within the range of 50.33-1 006.60 μg·mL-1,toluene is within the range of 8.34-166.88 μg·mL-1,and pyridine is within the range of 2.25-45.00 μg·mL-1,respectively. The concentration of ethanol,toluene,and pyridine has a good linear relationship with the peak area.The recoveries of ethanol,toluene and pyridine were in the range of 92.45%-99.67%,91.92%-99.23%,92.22%-97.61%,respectively. Conclusion This method has good specificity and high sensitivity,and can be used to effectively control the residual amount of ethanol,toluene and pyridine in benzoyl metronidazole.
Through literature research and case study,the development status and implementation methods of pharmaceutical companies' patient assistance programs in the USA were sorted out to provide recommendations of the development of China's patient assistance programs,and to promote the coordinated development of China's multi-level medical security system.A typical patient assistance program in the USA concluded many drugs covered a wide range of diseases.The patient assistance programs in the USA have formed a mature and diverse system of implementation and advertising.The programs provide a safety net for patients who do not have prescription drug insurance or have insufficient coverage of prescription drug insurance.It is recommended Chinese pharmaceutical companies to develop their own patient assistance programs.It will help to complete the medical security system and promote the coordinated development of China's medical security system.
Based on the study of quality assurance requirements in the domestic and foreign Good Manufacturing Practice and the analysis of quality assurance system from quality management view,the key points and critical elements of the quality assurance system were defined.Through the analysis of observations of quality assurance system in domestic and overseas drug inspections in recent years, this paper summarizes and refines the common problems in each critical elements of quality assurance system,including document management,deviation handling,change control,quality review,self-inspection and external inspection,complaints,adverse reaction report and monitoring,corrective and preventive action,recall and management review.It provides suggestions and information for the pharmaceutical industry to further strengthen the quality assurance system, provides reference and consideration on how to inspect relevant elements of quality assurance system of pharmaceutical manufacturer efficiently.