Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Elevated blood pressure is one of the major contributors to cardiovascular disease and premature death. The exposure to ambient fine particulate matter (PM_2.5) is closely associated with changes in blood pressure, and even short-term exposure to PM_2.5 can lead to an increase in blood pressure. PM_2.5 is a complex mixture that exerts different toxicities and triggers increased blood pressure through various mechanisms. Therefore, in this article, we provided a comprehensive review of published studies on the effects of short-term exposure to PM_2.5 and its components on blood pressure, and elaborated potential mechanisms from four aspects, including oxidative stress and inflammatory response, endothelial dysfunction, autonomic nervous system disorders and hypothalamus-pituitary-adrenal axis activation, and epigenome alteration. Given the limitations of existing research, future prospective studies can be conducted on diverse populations, using more precise exposure measurement methods and multi-omics approaches, to further elucidate the mechanisms underlying the effects of PM_2.5 and its various components on blood pressure. The findings would provide a theoretical foundation for effective protection of public health, particularly vulnerable groups.

Objective:Analyze the hemagglutinin(HA) gene of influenza A strains in Liaoning Province from 2018 to 2019, calculate and evaluate the matching degree of influenza A strains and vaccine strains.Methods:49 influenza A strains from 2018 to 2019 were selected for sequencing, and the HA gene was analyzed for evolution; the mutation of antigen epitopes, glycosylation sites and receptor binding sites were studied; the matching degree between the epidemic strain and the vaccine was analyzed by pepidope model.Results:The 2018-2019 influenza pandemic season was concentrated in November-March, and the main pandemic strain was H1N1 pdm virus. Through evolutionary analysis, H1N1 pdm virus belonged to the 6B.1 branch, and the seasonal H3N2 strain was distributed in the 3C.2a branch, all of which belonged to the same branch as the vaccine strain this year. Some strains mutated at epitope and receptor binding sites. In some strains, glycosylation sites increased or were absent compared with vaccine strains, and no new glycosylation sites were present. The Pepitope model was used to evaluate the vaccine effect. H1N1 pdm virus vaccine of this year showed good protective effect, but the seasonal H3N2 vaccine strain showed negative protective effect for epidemic strain, which could not play an effective protective role. Conclusions:In 2018-2019, H1N1 epidemic strain in Liaoning Province had some variation, and the matching degree between H3N2 subtype epidemic strain and 2018-2019 vaccine strain was low. We should pay close attention to the gene variation of the epidemic strains and update the vaccine strains in time.

Objective:To understand the composition of the pathogen spectrum of hand, foot and mouth disease(HFMD)in Xi′an from 2017 to 2018 and the genetic characteristics of enterovirus 71 (EV-A71).Methods:From 2017 to 2018, 1735 anal swab specimens from HFMD patients in Xi′an HFMD sentinel hospitals were collected, and qPCR was used to identify EV-A71, Coxsackie virus A 16 (CV-A16) and other enteroviruses. Selected EV-A71 strains were isolated, and VP1 region was amplified and sequenced, then phylogenetic tree and homologic comparison were conducted.Results:A total of 1 565 positive samples of enterovirus RNA were detected, positive rate was 90.20%(1565/1735), of which 24.79%(388/1 565)were positive for EV-A71, 21.85%(342/1 565)were positive for CV-A16, and 53.36%(835/1 565)were positive for other enterovirus. The main pathogen in 2017 was EV-A71(45.08%) and in 2018 was non-EV-A71-non-CV-A16 enteroviruses (73.38%), and the difference in pathogen composition was statistically significant ( χ2=370.57, P<0.001). HFMD caused by EV-A71 was concentrated in April to July, accounting for 73.97% (287/388) of the total cases. The homology analysis of the EV-A71 VP1 region showed that the 20 isolated EV-A71 strains belonged to the C4a subtype, with nucleotide and amino acid homology of 94.4%-96.1% and 99.4%-100% respectively, which were separated from those of the previous Xi′an City, the homology of EV-A71 obtained was above 91.5%. The result of the genetic evolution analysis of the EV-A71 VP1 region showed that the EV-A71 strain and the representative strain of the C4a subtype in Xi′an from 2008 to 2018 were in the same branch, forming multiple epidemic clusters, the variation degree of VP1 region increased with time. Conclusions:Non-EV-A71-non-CV-A16 enteroviruses were the main pathogens of HFMD in Xi′an from 2017 to 2018, and C4a subtype EV-A71 is still circulating in Xi′an. The monitoring of the pathogen spectrum and molecular epidemiology of HFMD should be strengthened to provide work for further effective prevention and treatment of HFMD.

Objective To establish the fingerprint spectrum and assay three active components (hesperidin, salvianolic acid B and chrysophanol) in Shenshuaining granule by HPLC method. Methods The chromatographic separation was achieved on SunFireTM C₁₈ column with acetonitrile-0.1% formic acid aqueous solution as mobile phase. Gradient elution program was applied with flow rate of 1.0 ml/min, detection wavelength at 254 nm and the column temperature at 25 ℃. The fingerprint spectrum was established and three active components in Shenshuaining granule were assayed. Results There were 22 common peaks on the fingerprints after analyzing chromatograms from 10 batches of Shenshuaining granules. Good fingerprint similarities (≥0.9) between different batches and the control chromatogram were found. This method has great repeatability, stability and precision, which meets all the assay requirements. Conclusion A simple and reliable HPLC method was developed, which is suitable for the fingerprint establishment of Shenshuaining granules. It provides a method for the quality control of Shenshuaining granules.

OBJECTIVE：To identi fy chemical components of Actinidia chinensis root rapidly ，and to provide reference for further material basis and quality control study of the crude medicine. METHODS ：UHPLC-Q-TOF-MS/MS technique was used to detect chemical components of A. chinensis root. The separation was performed on Waters XSelect HSS T 3 column with mobile phase consisted of 0.1％ formic acid acetonitrile solution- 0.1％ formic acid water solution （gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 40 ℃，and sample size was 3 μL. Electrospray ion source was adopted，the data was collected under negative ion mode ；the scanning range was m/z 50-1 500；the drying gas temperature was 350 ℃，the atomizing air pressure was 45 psi，the capillary voltage was 3 500 V，and sheath gas temperature was 350 ℃. According to the information of excimer ion and secondary fragment ion ，the chemical components were identified by combining with the relevant literature ，the retention time of the reference substance and the law of mass spectrometry cracking. RESULTS & CONCLUSIONS ：Totally 58 chemical components was identified ，which included 16 pentacyclic triterpenes （such as hydroxyasiatic acid ，asiatic acid ，maslinic acid，corosolic acid ，oleanic acid ，ursolic acid ，etc.），12 flavonoids（such as rutin ，quercitrin，cynaroside，astragalin，etc.），17 organic acids （such as cryptochlorogenic acid ，chlorogenic acid ，isochlorogenic acid A ，isochlorogenicacid C ，etc.）. There were 9 components（such as procydanidin B 1，B2 and luteolin ，etc.）identified for the first time in A. chinensis root. UHPLC-Q-TOF-MS/ MS technique can be used for the rapid identification of chemical components in A. chinensis root.

Objective To investigate the extraction methods for active components from oral ulcer film and optimize the determination methods of active components dexamethasone sodium phosphate and metronazole. Methods Different extraction solvents(methanol, water and 70% methanol aqueous) were applied to extract the active components dexamethasone sodium phosphate and metronazole from oral ulcer film, which contents were quantified by a HPLC method. Results the extraction solvent water had the best efficacy and more simpler compared to the other two solvents. Clotriazole showed a good linear relationship within 5.014 5-200.5800 μg/ml (r=0.999 8), and the average extraction recovery was (104.23±0.63)%, and for dexamethasone sodium phosphate, a good linear relationship was obtained in the range of 0.482-16.328 μg/ml (r=0.9999), and the average extraction recovery was (103.97±1.02)%. Conclusion The water extraction method established in this study was simple and efficient, which showed features of simplicity, accuracy and repeatable.

Objective : To learn the epidemic distribution of avian influenza virus in external environments in Liaoning Province,and to provide evidence for the prevention and control of avian influenza. Methods : The environmental samples were collected monthly during 2016 and 2017（including samples from emergency monitoring in June to August,2016 and March to May,2017）from live poultry markets,live poultry wholesale markets,large-scale poultry farms（households）,free-range poultry famers and poultry processing factories in Liaoning Province. Real-time polymerase chain reaction assay was used to detect nucleic acid of Influenza A as well as H5,H7 and H9 subtypes in the environmental samples. The distribution of avian influenza virus in external environments in Liaoning Province was analyzed. Results : A total of 4 037 environmental samples were collected and detected from 2016 to 2017,there were 177 copies of type A avian influenza virus and the positive rate of avian influenza A virus was 4.38%. The positive rate in 2017 was 6.26%, which was higher than 2.40% in 2016（P<0.05）. H9 subtype had the highest positive rate of 3.07%;H7 subtype was first detected in 2017. The positive rates of avian influenza virus from the first to fourth quarters of a year were 8.54%,4.88%,2.17% and 1.45%,respectively. The positive rates of avian influenza virus in live poultry markets were 8.08%,the highest among different sites,and the subtypes were mainly H9. The positive rates of avian influenza virus in samples of poultry cage and poultry washing sewage were 23.47% and 15.96%. H5 and H9 subtypes were detected in all types of samples,and H7 subtypes or mixed types were detected in samples of feces,poultry cage,poultry drinking water and chopping board. Conclusion The subtypes of avian influenza virus in the environments of Liaoning Province were mostly H9 and H5,and the H7 was first detected in 2017. Live poultry markets should be the key monitoring sites,especially in winter and spring.

At present,the production equipment and process of Chinese patent medicines still have many problems including high energy consumption,low efficiency,high pollution,and low intelligence,which seriously hinder the transformation,upgrading and modernized development of traditional Chinese medicine industry. With the emergence of various new pharmaceutical technologies and the application of technologies of other fields in traditional Chinese medicine industry,the development of Chinese patent medicine has ushered in new opportunities. The processes such as pulverization,mixing,extraction,separation,concentration,drying and sterilization are unique for the production of Chinese patent medicine. These main features can be distinguished from the manufacturing process of chemical drugs,determining the characteristics of the production process and equipment of Chinese patent medicine. In this paper,each operation unit was mentioned to summarize and analyze the new equipment and new technologies with advantages and characteristics in recent years from the perspectives of definition,principle,classification and application. Among them,the automatic spray device of the mixer,the extraction and separation equipment of volatile oil,and the crane basket-type circulation extraction technology,composite multi-layer spiral vibration countercurrent drying,and vibration sterilization equipment all have rapid development in recent years,with great prospects in the production of Chinese patent medicines. In this paper,we also analyzed some problems existing in the production equipment and technology of Chinese patent medicine and the key factors restricting the development of Chinese patent medicine,discussed the transformation of Chinese patent medicine production from traditional to modern and from semi-automatic to intelligent,and put forward three suggestions to help Chinese patent medicine achieve the goal of improving quality,efficiency and green manufacturing in production.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Quality Control ; Technology, Pharmaceutical