Polypeptide drugs have attracted much attention in the field of drug research and development due to their wide range of indications,especially in pharmaceutical R&D of new drugs with endocrine related indications such as diabetes and osteoporosis.With the advancement of peptide synthesis and delivery technologies,the research and application of peptide drugs have made significant breakthroughs.However,the R&D and nonclinical safety assessment of peptide drugs still face many challenges,and there are no specific guidelines for the nonclinical safety evaluation of this class of drugs domestically or abroad.This article focuses on the field of endocrine indications.By analyzing the nonclinical studies of approved peptide drugs,and considering the current R&D status and specific regulatory requirements,this paper proposes considerations on the nonclinical safety assessment of peptide drugs,including the selection of relevant animal species,key study contents,specific considerations for peptides containing non-natural amino acids,etc.The aims are to provide references for optimizing and improving the nonclinical safety evaluation of peptide drugs.

Polypeptide drugs have attracted much attention in the field of drug research and development due to their wide range of indications,especially in pharmaceutical R&D of new drugs with endocrine related indications such as diabetes and osteoporosis.With the advancement of peptide synthesis and delivery technologies,the research and application of peptide drugs have made significant breakthroughs.However,the R&D and nonclinical safety assessment of peptide drugs still face many challenges,and there are no specific guidelines for the nonclinical safety evaluation of this class of drugs domestically or abroad.This article focuses on the field of endocrine indications.By analyzing the nonclinical studies of approved peptide drugs,and considering the current R&D status and specific regulatory requirements,this paper proposes considerations on the nonclinical safety assessment of peptide drugs,including the selection of relevant animal species,key study contents,specific considerations for peptides containing non-natural amino acids,etc.The aims are to provide references for optimizing and improving the nonclinical safety evaluation of peptide drugs.

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.
Male ; Humans ; Adult ; Middle Aged ; Female ; Coronary Artery Disease/complications* ; Cholesterol, HDL ; Cholesterol, LDL ; Prospective Studies ; Myocardial Infarction/etiology* ; Stroke ; Risk Factors

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Professor Mao Xiejun wrote a report about dental education of China in 1935. From 1948 to 1950, he published three articles containing the educational idea of "developing dentistry into stomatology". When he served as the director of the Faculty of Dentistry of Peking University Medical School in July 1950, he proposed to rename the Faculty of Dentistry into the Faculty of Stomatology,which were approved by the Ministry of Health and the Ministry of Education of the People's Republic of China in one month. The Chinese Medical Association established the Society of Stomatology the next year. Later, dentistry was successively changed into stomatology, and medical content was integrated into dental education, which was of great significance and far-reaching influence. During the developments of the thought of stomatological education in China, Professor Mao Xiejun evidently played a pivotal role. In this paper, the formation process of the thoughts of stomatological education related to professor Mao Xiejun's contribution is elucidated through studying the archives, personal letters, and historical documents, so as to enrich the researches on the history of stomatology in China and to facilitate better understanding and promoting the development of stomatology.
Humans ; Oral Medicine/education* ; Education, Dental ; China ; Universities

Objective: To explore and compare the effect of standard or prolonged dual antiplatelet therapy (DAPT) on the long-term prognosis of elderly patients with coronary heart disease complicated with diabetes mellitus after drug-eluting stent (DES) implantation. Methods: Consecutive patients with diabetes mellitus, ≥65 years old, underwent DES implantation, and had no adverse events within 1 year after operation underwent percutaneous coronary intervention (PCI) from January to December 2013 in Fuwai Hospital were enrolled in this prospective cohort study. These patients were divided into three groups according to DAPT duration: standard DAPT duration group (11 ≤ DAPT duration≤ 13 months) and prolonged DAPT duration group (1324 months). All the patients were followed up at 1, 6 months, 1, 2 and 5 years in order to collect the incidence of major adverse cardiovascular and cerebrovascular events (MACCE), and type 2 to 5 bleeding events defined by the Federation of Bleeding Academic Research (BARC). MACCE were consisted of all cause death, myocardial infarction, target vessel revascularization or stroke. The incidence of clinical adverse events were compared among 3 different DAPT duration groups, and Cox regression model were used to analyze the effect of different DAPT duration on 5-year long-term prognosis. Results: A total of 1 562 patients were enrolled, aged (70.8±4.5) years, with 398 female (25.5%). There were 467 cases in standard DAPT duration group, 684 cases in 1324 months group. The patients in standard DAPT duration group and the prolonged DAPT duration groups accounted for 29.9% (467/1 562) and 70.1% (1 095/1 562), respectively. The 5-year follow-up results showed that the incidence of all-cause death in 13P=0.011) and DAPT duration>24 month group(4.1%(17/411) vs. 8.6%(40/467),P=0.008) were significantly lower than in standard DAPT group. The incidence of myocardial infarction in 13P=0.002). The incidence of MACCE in 1324 month group were 19.3% (90/467), 12.3% (84/684), 20.2% (83/411), respectively, P<0.001). There was no significant difference in the incidence of stroke and bleeding events among the three groups (all P>0.05). Multivariate Cox analysis showed that compared with the standard DAPT group, prolonged DAPT to 13-24 months was negatively correlated with MACCE (HR=0.601, 95%CI 0.446-0.811, P=0.001), all-cause death (HR=0.568, 95%CI 0.357-0.903, P=0.017) and myocardial infarction (HR=0.353, 95%CI 0.179-0.695, P=0.003). DAPT>24 months was negatively correlated with all-cause death (HR=0.687, 95%CI 0.516-0.913, P=0.010) and positively correlated with revascularization (HR=1.404, 95%CI 1.116-1.765, P=0.004). There was no correlation between prolonged DAPT and bleeding events. Conclusions: For elderly patients with coronary heart disease complicated with diabetes mellitus underwent DES implantation, and had no MACCE and bleeding events within 1 year after operation, appropriately prolonging of the DAPT duration is related to the reduction of the risk of cardiovascular adverse events. Patients may benefit the most from the DAPT between 13 to 24 months. In addition, prolonging DAPT duration does not increase the incidence of bleeding events in this patient cohort.
Aged ; Coronary Artery Disease/surgery* ; Diabetes Mellitus ; Drug Therapy, Combination ; Drug-Eluting Stents/adverse effects* ; Female ; Hemorrhage ; Humans ; Male ; Myocardial Infarction/epidemiology* ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prognosis ; Prospective Studies ; Stroke ; Treatment Outcome

In order to understand the structural characteristics of squalene synthase genes in the triterpenoids biosynthesis pathway of Crataegus pinnatifida, the squalene synthase genes of C. pinnatifida was cloned and analyzed by bioinformatics and prokaryotic expression. Two squalene synthase genes CpSQS1 and CpSQS2 were cloned from C. pinnatifida fruit by RT-PCR. The ORF length of CpSQS1 and CpSQS2 were 1 239 bp and 1 233 bp respectively, encoding 412 aa and 410 aa respectively. CpSQS1 and CpSQS2 were predicted to be stable acidic proteins by online tools. The secondary structure was mainly composed of α-helix structure, and the tertiary structure was predicted by homology modeling. Structural functional domain analysis showed that 35-367 aa of CpSQS1 and CpSQS2 cDNA containing conserved trans-isoprenyl pyrophosphate synthase domains. Transmembrane domain analysis predicted that two transmembrane domains were founded in CpSQS1 and CpSQS2. The squalene synthase amino sequence of C. pinnatifida had higher homology with the known SQS of Salvia miltiorrhiza and Glycyrrhiza glabra. Phylogenetic tree analysis showed that CpSQS1 and CpSQS2 were clustered into one branch of MdSQS1 and MdSQS2, which were consistent with the phylogenetic rule. Prokaryotic expression vector pGEX-4 T-1-CpSQS1 and pGEX-4 T-1-CpSQS2 were transformed into Escherichia coli Transetta(DE3) for induction, and the target protein was successfully expressed at 65 kDa. The expression levels of CpSQS2 were significantly higher than that of CpSQS1 in three different developmental stages of C. pinnatifida. In this study, the full-length cDNA sequences of C. pinnatifida SQS1 and SQS2 were cloned and analyzed for the first time, which provided the foundation for further study on the metabolic pathway of C. pinnatifida triterpenoids.
Amino Acid Sequence ; Cloning, Molecular ; Crataegus/genetics* ; Farnesyl-Diphosphate Farnesyltransferase/genetics* ; Fruit/enzymology* ; Phylogeny ; Plant Proteins/genetics*

In this paper, the micro-video teaching mode was explored in the course construction of . The micro-video teaching contents include the academic thought, experience in diagnosis and treatment, characteristic technology and clinical manipulation of famous acupuncture experts in the Henan University of CM. Each micro-video film is designed within 15-18 min, including three sections of knowledge, i.e. basic theory, technological application and clinical manipulation. Each section is designed within 5-6 min. The construction of the teaching course of is the innovation of practice mode of TCM and the new approach to the inheritance of the experience of experts. The construction of micro-video teaching course propels the reform of teaching mode, improves the learning initiative of students and clinical manipulative ability so as to improve the teaching effect and quality.
Acupuncture Therapy ; Humans ; Learning ; Moxibustion ; Students ; Teaching

Objective: To explore the related factors of premature acute myocardial infarction(AMI), and to compare the the long-term outcomes in patients with and without premature AMI after percutaneous coronary intervention (PCI). Methods: This study was a prospective cohort study.From January 2013 to December 2013, 10 724 consecutive patients with coronary heart disease undergoing PCI in Fuwai Hospital were enrolled. Among them 1 920 patients with the diagnosis of AMI were divided into two groups: premature AMI (man≤50 years old, woman≤60 years old) and non-premature AMI. The baseline characteristics were collected, and multivariate logistic regression was uesed to analysis the related factors of premature AMI. The clinical outcomes, including the major adverse cardiovascular and cerebrovascular events(MACCE) which was the composite of cardiac death, myocardial infarction, revascularization, stroke and stent thrombosis, as well as bleeding events, during hospitalization, at 2 years and 5 years follow-up were analyzed. Results: A total of 1 920 AMI patiens were included(age was (56.5±11.3) years old)，with 1 612(84.0%) males. There were statistically significant differences between the two groups in gender, body mass index, blood lipid, complications, inflammatory markers, etc (all P<0.05). Multivariate logistic regression analysis showed body mass index(OR=1.06, 95%CI 1.01-1.10, P<0.01), triglyceride(OR=1.47, 95%CI 1.14-1.90, P<0.01), serum uric acid level(OR=1.02, 95%CI 1.01-1.04, P<0.01), high density lipoprotein cholesterol level(OR=0.33, 95%CI 0.14-0.78, P=0.01) and history of hypertension(OR=0.72, 95%CI 0.56-0.93, P=0.01) were independent related factors of premature AMI. The incidence of all-cause death and cardiac death were lower during hospitalization, at 2 years and 5 years follow-up in the premature AMI group than in non-premature AMI group(all P<0.05). In the premature AMI group, the incidence of MACCE and stroke was lower, with more bleeding events in 5 years follow-up(all P<0.05). Conclusions: Metabolic abnormalities, including high BMI, high triglyceride level and high serum uric acid, low high-density lipoprotein cholesterol level are the related factor of premature AMI. The incidence of ischemic events in patients with premature AMI is lower, while the incidence of bleeding events is higher than non-premature AMI patients.
Aged ; Coronary Artery Disease ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prospective Studies ; Risk Factors ; Treatment Outcome ; Uric Acid

Objective: The aim of this study was to investigate high performance liquid chromatography (HPLC) fingerprint,anti-inflammatory activity as well as the correlation between them in Speranskiae Tuberculatae Herba. Method: Fingerprint by HPLC was established on Speranskiae Tuberculatae Herba from different sources. The common peaks were evaluated on the basis of similarity evaluation together with hierarchical cluster analysis (HCA) and principal component analysis (PCA). Ear swelling induced by xylene in mice model was used to study the anti-inflammatory activity. Grey relational analysis (GRA) and partial least square regression analysis (PLSR) were used to study the relationship between the HPLC fingerprint and the anti-inflammatory activity. Result: The HPLC fingerprint of Speranskiae Tuberculatae Herba was established and 24 common peaks were determined,with the similarity above 0.907 (except for S2 and S5). Four peaks were identified by comparing to reference substances. The result of HCA showed that Speranskiae Tuberculatae Herba from different sources were clustered into four categories,in consistent with the result of PCA. Combined with discriminant analysis of partial least squares discrimination analysis (PLS-DA),three signature compounds represented by 5,6,7 peaks were responsible for the differences between groups. Different sources of Speranskiae Tuberculatae Herba differed in anti-inflammatory activity. The sectrum-activity relationship showed that the peaks 1,4,5,6,and 10 were positively correlated with the anti-inflammatory activity. Conclusion: The HPLC fingerprint of Speranskiae Tuberculatae Herba was established,and 5 components closely related to the anti-inflammatory activity were determined. The present study provide more comprehensive reference for quality control of the Speranskiae Tuberculatae Herba.