Clopidogrel is an antiplatelet drug widely used in clinical practice now.It has been used as the secondary prevention medication for myocardial infarction,ischemic stroke,and peripheral vascular disease.However,the anti-platelet aggregation effect of clopidogrel has significant individual differences.A large part of patients have clopidogrel resistance phenomenon.The mechanism of clopidogrel resistance is not fully understood.The genetic polymorphism is an important cause of clopidogrel resistance,including ABCB1,CYP2C19,CYP3A4,CYP3A5,P2Y12,and ITGB3.

Objective To determine the changes in brain dopamine transporter and serotonin transporter in mice receiving propofol anesthesia, 125I-?-CIT binding was studied.Methods Twenty-seven Kunming mice ,weighing 18-22g ,were randomly assigned to receive either intraperitoneal propofol 100 mg/kg (n=9) or 200 mg/kg(n=9) or 10% intralipid (used as control,n=9) in equal liquid volume respectively. 10 min after intraperitoneal administration, 0.1ml 2?Ci 125I-?-CIT was given intravenously via the tail vein. Two hours later animals were decapitated. Brains were rapidly removed and dissected on ice and cerebellum, hypothalamus, striatum and cerebral cortex were separated. Brain tissues were weighed and the radioactivity of 125I-?-CIT in different brain regions was measured.Results 125I-?-CIT binding to dopamine transporter or serotonin transporter decreased significantly in propofol groups as compared with that in control group. The decrease in binding was greater in 200 mg/kg propofol group (P

Objective To observe the influences of stemona alkaloids on esterase isozymes activities and glycogen content of Oncomelania hupensis in order to explore the molluscicidal mechanism of stemona alkaloids.Methods O.hupensis snails were immersed in the liquid of stemona alkaloids at the concentration of 6.5 mg/L(72 h LC50),the surviving ones were picked out and sampled after being immersed for 12,24,48,72,96 h,then PAGE and anthrone colorimetry methods were used to observe the changes of liver esterase isozymes activities and tissue glycogen content of O.hupensis during the immersion period.A group of snails immersed in de-chlorinous water served as control.Results Esterase isozymes activities firstly increased,and then decreased until almost lost completely during the 96 h immersion period.Meanwhile,glycogen content gradually decreased as the immersion time extended.After being immersed for 96 h,glycogen content decreased by 72.00% compared with the control group.Conclusion Stemona alkaloids could inhibit the viability of O.hupensis by causing decrease of esterase isozymes activities and glycogen content.

Objective To analyze the epidemiological characteristics of food poisoning deaths in Wenshan Prefecture of Yunnan Province from 2010 to 2019, so as to provide the basis for formulating the strategies and measures for prevention and control of food poisoning deaths in Wenshan Prefecture. Methods The data of food poisoning deaths in Wenshan Prefecture from 2010 to 2019 were collected and analyzed by Excel software. Results From 2010 to 2019, 65 food poisoning deaths were reported, accounting for 7.5% of the food poisoning incidents in the same period.The fatality rate of food poisoning deaths was 36.7%, and the mortality rate of food poisoning events in the same period was 2.1%.The high incidence of food poisoning deaths occurred in summer and autumn, with the highest in June and July.Wild mushroom poisoning was the main cause of death in food poisoning, and the incidence was mainly in rural families. Conclusion Wild mushroom poisoning should be the focus of controlling food poisoning deaths in Wenshan Prefecture.It is necessary to strengthen public education, improve people′s ability to identify edible wild mushrooms, strengthen the building of capacity of medical institutions in towns and villages, and establish a long-term mechanism for food safety management.

Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.

Objective To investigate the role of rotational alignment reference landmarks of the proximal tibia in total knee arthroplasty.Methods Fifteen healthy adult volunteers were enrolled in this study,including 10 males and 5 females,aged from 21 to 38 years (average,28.1±6.0).CT scans of 26 knees were taken as the knees were placed in full extension.Two anteroposterior axes were drawn on the CT images:one line connected the middle of the posterior cruciate ligament insertion site and the medial edge of the patellar tendon,and another line connected the middle of the posterior cruciate ligament insertion site and the middle-medial 1/3 of the patellar tendon.The surgical epicondylar axis was also drawn on the CT images.Angles were measured between a line perpendicular to the surgical epicondylar axis and the two anteroposterior axes,and the angles were compared with the ideal tibial rotational alignment reference axis (0°).Results Angles between the line perpendicular to the surgical epicondylar axis and the line connecting the middle of the posterior cruciate ligament insertion site and the medial edge of the patellar tendon averaged 0.7°±2.8° (range,-5.1°-5.8°),there was no significant difference compared with 0°.Angles between the line perpendicular to the surgical epicondylar axis and the line connecting the middle of the posterior cruciate ligament insertion site and the middle-medial 1/3 of the patellar tendon averaged 6.9°±5.3° (range,-3.4°-14.1°),there was significant difference compared with 0°.Significant difference existed in angles between the two anteroposterior axes and the line perpendicular to the surgical epicondylar axis.Conclusion The line connecting the middle of the posterior cruciate ligament insertion site and the medial edge of the patellar tendon is a more reliable reference axis for the tibial component rotational alignment,which makes the femoral and tibial components in a more matching rotational position.

DNA marker-assisted selection of medicinal plants is based on the DNA polymorphism, selects the DNA sequences related to the phenotypes such as high yields, superior quality, stress-resistance and so on according to the technologies of molecular hybridization, polymerase chain reaction and high-throughput sequencing, and assists the breeding of new cultivars. This study bred the first disease-resistant cultivar of notoginseng "Miaoxiang Kangqi 1" using the technology of DNA marker-assisted selection of medicinal plants and systematic breeding. The disease-resistant cultivar of notoginseng contained 12 special SNPs based on the analysis of Restriction-site Associated DNA Sequencing (RAD-Seq). Among the SNP (record_519688) was related to the root rot-resistant characteristics, which indicated this SNP could serve as genetic markers of disease-resistant cultivars and assist the systematic breeding. Compared to the conventional cultivated cultivars, the incidence rate of root-rot and rust-rot in notoginseng seedlings decreased by 83.6% and 71.8%, respectively. The incidence rate of root-rot respectively declined by 43.6% and 62.9% in notoginseng cultivation for 2 and 3 years compared with those of the conventional cultivated cultivars. Additionally, the potential disease-resistant groups were screened based on the relative SNP, and this model enlarged the target groups and advanced the breeding efficiency. DNA marker-assisted selection of medicinal plants accelerated the breeding and promotion of new cultivars, and guaranteed the healthy development of Chinese medicinal materials industry.

To evaluate the correlation of the serum uric acid and free fatty acid (FFA) levels in Shandong coastal residents. To investigate the correlation between serum uric acid and FFA based on 3860 individuals who have been long staying in Qingdao, Yantai, Weihai, Rizhao with a randomized, stratified cluster sampling method. According to FFA quartile, subjects were divided into four groups: group Q1 of 908, group Q21016, group Q3958, and group Q4978 cases. The prevalence of hyperuricemia and serum uric acid levels increased with the increasing FFA quartile. Compared with Q1, Q2, and Q3 groups, the prevalence of hyperuricemia in Q4 group and the increase of serum uric acid were statistically significant(P<0. 05). And in the group Q4, hyperuricemia prevalence is twice as the group A. According to the serum uric acid level, subjects were divided into the normal uric acid group(n=3331) and the hyperuricemia group ( n = 529). In the hyperuricemia group, their systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), glucose, uric acid, FFA, body mass index etc. were significantly higher than those of the normal uric acid group (all P<0. 01), while the high density lipoprotein-cholesterol ( HDL-C), cystatin, glomerular filtration rate (eGFR) are significantly lower than those of the normal uric acid group( all P<0. 01). Serum uric acid levels are positively correlated with systolic and diastolic blood pressures, waist and hip circumferences, triglycerides, total cholesterol, LDL-C, FFA, blood glucose, body mass index (all P<0. 01); and negatively correlated with eGFR (P<0. 01). Multiple regression analysis showed that systolic blood pressure, FFA, total cholesterol, triglycerides, LDL-C, blood glucose, body mass index, eGFR were factors influencing serum uric acid independently. Multivariate binary logistic regression analysis showed that systolic blood pressure, waist circumference, total cholesterol, blood glucose, and FFA are independent risk factors to predict hyperuricemia onset while eGFR is a protective factor. Serum uric acid level is closely related to the free fatty acid, and FFA seems to be involved in the development and progression of hyperuricemia.

Objective:To investigate the relationship between the expression of hepatocyte nuclear factor-1 α (HNF-1α) and the occurrence and development of liver inflammation and fibrosis in liver tissues of patients with chronic hepatitis B.Methods:Sixty-four patients with chronic hepatitis B who were diagnosed and treated in our hospital from 2011 to 2018 were selected. All patients underwent ultrasound-guided aspiration liver biopsy. The pathological results of liver biopsy were collected for inflammation grading and fibrosis staging. The liver puncture biopsies was collected by paraffin sectioning. The expression of HNF1α in the liver tissue was detected by immunohistochemical staining. Mantel-Haenszel χ2 test was used for bidirectional ordered grouping data, and Spearman’s rank-correlation test was used for rank correlation analysis. Results:There were varying degrees of inflammatory necrosis and fibrosis in the liver tissues of patients with chronic hepatitis B. There was a linear relationship between the expression of HNF1α and the level of inflammation in liver tissues ( χ2MH = 40.70, P < 0.05). The expression of HNF1α in liver tissues of patients with chronic hepatitis B was decreased with the increase of liver inflammation. The expression intensity of HNF1α was negatively correlated with the inflammation grade ( rs = -0.815, P < 0.05). There was a linear relationship between the expressions of HNF1α and the degree and stage of liver fibrosis ( χ2MH = 31.95, P < 0.05). The expression level of HNF1α in liver tissue was gradually decreased with the aggravation of liver fibrosis. The expression intensity of HNF1α was negatively correlated with fibrosis stage ( rs = -0.713, P < 0.05). Conclusion:HNF1α is closely related to the occurrence and development of liver tissue inflammation and fibrosis, and is expected to be a sensitive indicator for evaluating the level of liver tissue inflammation and fibrosis in patients with chronic hepatitis B. In addition, its down-regulation may be involved in the process of occurrence and development of liver inflammation and liver fibrosis, and may become a new target for the treatment of chronic hepatitis B.

Mineralocorticoid receptor(MR) overactivation plays an important role in the development and progression of diabetic kidney disease(DKD) by mediating pro-inflammatory and pro-fibrotic processes, making it a key therapeutic target for DKD. Finerenone, a third-generation, highly selective, novel nonsteroidal mineralocorticoid receptor antagonist(MRA), mitigates MR overactivation through anti-inflammatory and anti-fibrotic effects and by improving the immune-inflammatory environment. This significantly reduces cardiovascular and renal composite endpoints in patients with type 2 diabetes mellitus(T2DM) and chronic kidney disease(CKD), and improve cardiorenal outcomes. Based on its novel molecular structure, Finerenone exhibits a lower incidence of adverse effects compared to the previous MRAs. This article elucidates the molecular structure and pathophysiological role of MR, and explores the molecular mechanisms through which finerenone provides cardiorenal benefits. It also discusses the advantages and safety of finerenone compared to first- and second-generation MRAs from a molecular structure perspective, providing evidence for its clinical application.