The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.
Anticoagulants ; pharmacology ; Body Weight ; Cytochrome P-450 CYP2C9 ; genetics ; Genotype ; Humans ; International Normalized Ratio ; Nonlinear Dynamics ; Polymorphism, Genetic ; Vitamin K Epoxide Reductases ; genetics ; Warfarin ; pharmacokinetics

Background Age-related cataract is one of the common causes of blindness.Although the pathophysiology of age-related cataract is far from clearly understood,it is well accepted that DNA damage plays an important role in the disease pathogenesis.Objective The purpose of this study was to quantitatively evaluate the DNA damage in peripheral lymphocytes of age-related cataract.Methods A cross-sectional study was carried out.This study complied Declaration of Helsinki and approved by Ethic Committee of Affiliated Hospital of Nantong University.Written informed consent was obtained from each subject.Two hundred and eleven patients with agerelated cataract and 147 normal subjects were enrolled from a “ Jiangsu Eye Study:Funing 2011 Eye Disease Epidemic Survey”.All the subjects aged from 50 through 80 years with matched age and gender between the two groups.The percentage of tail DNA and Olive tail moment (OTM) were detected by comet assay to assess the extent of DNA damage in peripheral lymphocytes.Statistical analyses were performed with SPSS 17.0 software,and the differences of the percentage of tail DNA and OTM were compared between the age-related cataract group and normal control group by independent sample t test as well as among the 50-59 years group,60-69 years group and ≥70 years group by one-way analysis of variance.Results Comet assay showed a round lymph cell with the clear border in the normal group;while in the age-related cataract group,the cell was bigger with a comet-like tail.The percentage of tail DNA and OTM in peripheral lymphocytes were (21.75 ± 3.51) ％ and 6.54 ± 1.65 in the age-related cataract group,and those in the normal control group were (9.31 ±3.60)％ and 2.18 ± 1.10,respectively,with significant differences between them (t =32.67,P =0.00 ; t =28.02,P =O.00).In the 50-59 years subgroup of the age-related cataract group,the percentage of tail DNA and OTM in peripheral lymphocytes were (20.04±2.86) ％ and 5.92± 1.14,and in the 60-69 years subgroup of the age-related cataract group,the percentage of tail DNA and OTM in peripheral lymphocytes were (20.77 ±2.93) ％ and 6.13 ± 1.14,which were significantly reduced in comparison with (22.79 ± 3.67)％ and 6.95±1.91 of the ≥70years subgroup(TailDNA％:q=2.75,P=0.00; q=2.02,P=0.00;OTM:q=1.03,P =0.02 ; q =0.82,P =0.00).Conclusions The pathogenesis and development of age-related cataract probably is associated with DNA damage.

G protein-coupled receptor 119 (GPR119) has been a promising target for the treatment of type 2 diabetes. It can not only directly promote insulin secretion, but also indirectly increase insulin secretion by stimulating the release of glucose-dependent GIP/CLP-1 without causing hypoglycemia. The remarkable advantages of small molecule GPR119 agonists make it one of the research hotspots for the development of type 2 diabetes drugs. This article reviews the anti-diabetic small molecules based on the GPR119 target in the past five years.

Multi-component traditional Chinese medicines are an innovative research mode for traditional Chinese medicines. Currently, there are many design methods for developing multi-component traditional Chinese medicines, but their common feature is the lack of effective connection of the traditional Chinese medicine theory. In this paper, the authors discussed the multi-component traditional Chinese medicine design methods based on medicinal property combination modes, provided the combination methods with the characteristics of traditional Chinese medicine for the prescription combinations, and proved its feasibly with hypertension cases.
Animals ; Antihypertensive Agents ; administration & dosage ; chemistry ; Blood Pressure ; drug effects ; Drug Combinations ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Hypertension ; drug therapy ; physiopathology ; Medicine, Chinese Traditional ; Rats

Objective To discuss a optimal culture method of primary hippocampal neurons and a more suitable method of mor-phological observation ,and provide basis to the study of synapse in Alzheimer′s Disease .Methods Postnatal 0 -1 days (P0 -1 ) C57BL/6J mice were decollated and bilateral hippocampus were separated .Low level concentration of trypsin and mechanical disso-ciation were adopted .And culture medium without serum was used to culture neurons .After 17 days culturing ,transfected neurons with Green Fluorescent Protein(GFP) by calcium phosphate precipitation ,and then observed neurons and spines by fluorescence mi-croscope .Results The neurons looked good and healthy by using this method .And the axons ,dendrites and spines which were typ-ical structure of neurons were observed clearly after transfected with GFP .Conclusion The cultured hippocampal neurons look good by this method .And the morphological characteristics of neurons and spines are observed much more clearly after transfected GFP by calcium phosphate precipitation .

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Approximate 17 monoclonal antibodies have been approved as cancer therapeutics since 1997. Antibody-drug conjugates (ADC) are powerful new treatment options for cancer, and naked antibodies have recently achieved remarkable success. The safety and effectiveness of therapeutic mAbs in oncology vary depending on the nature of the target antigen and the mechanisms of tumor cell killing. This review provides a summary of the current state of antibody-based cancer therapy, including the mechanisms of tumor cell killing by antibodies, tumor antigens as antibody targets, clinical effectiveness of antibodies in cancer patients and nanoparticles-based ADCs.
Antibodies, Monoclonal ; immunology ; therapeutic use ; Antigens, Neoplasm ; immunology ; Antineoplastic Agents ; therapeutic use ; Humans ; Immunoconjugates ; therapeutic use ; Nanoparticles ; Neoplasms ; immunology ; therapy

Currently, the herbal prescription therapy for corresponding constitutional diseases is a common constitution regulating method. This method has an obvious effect in treating and regulating constitution-related diseases. However, for people who do not have disease, they prefer to regulate constitution with dietary therapy. In this paper, the researchers came up with a design method of constitution regulating and healthcare foods based on medicinal property combination mode of clinical empirical formulas. With "Yupinfeng San", a common formula for Qi-insufficiency constitution and specific endowment constitution, as the example for constitution regulating and healthcare foods, the researchers proved the effectiveness and rationality of healthcare food schemes in terms of the efficacy of single herb and the modern pharmacological study.
Diet ; Diet Therapy ; Humans ; Plants, Medicinal ; chemistry ; metabolism ; Prescriptions

Objective To discuss the application of post quantification inspection in nursing quality management in ICU of Siehuan cancer hospital. Methods According to the nursing quality criteria, work specification and different requirements in each post and weighted value of each post, quantification inspection regulations and score standardization were formulated and brought into effect in each post. Results After theapplication of post quantification inspection, the nursing service quality and patients' satisfaction to nursingservice were improved. This method could scientifically embody the quality of nursing work, and alsoconsummated the head nurses' administration, thereby improving the professional level of nurses to some extent.Conclusions The application of post quantification inspection enhances the science and operation of nursingmanagement, and helps to improve the level of nursing management.

Objective To evaluate the effectiveness of blood gas analysis in samples from two regions.Methods 112 patients with APACHE Ⅱ scores 27 ～ 43 were taken arterial blood from dorsalis pedis artery and femoral artery respectively. Compare the clinical effect of the samples. Results There is no statistically significant difference between results of two blood collection methods ( P ＞ 0. 05 ), While there is statistically significant difference in puncture success ( 110 vs 100, χ2 = 14.23, P ＜ 0. 05 ), vein mistaken injury, hematoma formation, thrombosis, and compression time ( 12 vs 1,7 vs 0,6 vs 0,5.5 ±0.7 vs 2.5 ±0.5 ;χ2 =9.32,5.99,4.85,t = 38. 06, P ＜ 0. 05 ). Conclusions Blood collection method should be determined by the different situation of critically ill patients. Femoral artery blood sample should be taken with caution in order to prevent complication and improve quality of nursing care.

Objective To evaluate the value of endobronchial ultrasound elastography in diagnosis of mediastinal lymph nodes by measuring the parameters of endobronchial ultrasound elastography. Methods Between 2016 and 2017, 46 patients with 63 lesions underwent EBUS-TBNA examination were included. Conventional ultrasound and ultrasound elastography were performed respectively to examine 63 lymph nodes before aspiration. Then various features of conventional ultrasound and parameters of ultrasound elastography were analyzed and recorded. Then evaluate the value of ultrasound elastography by pathological results and three-month follow-up data. Result The diagnostic value of ultrasound elastography image type, elasticity score, strain ratio and blue area ratio for malignant lymph nodes were higher than that of conventional ultrasound features in accuracy, sensitivity and specificity (P < 0.05); The accuracy of the boundary was the highest in the diagnosis of malignant lymph nodes. In the ultrasound elastography parameters, the accuracy of the elasticity score was the highest, and the blue area ratio had the largest area under the curve. When the boundary was used as the joint index to judge malignant lymph nodes with elasticity score and area ratio respectively, significantly higher than the diagnostic accuracy of conventional ultrasound and ultrasound elastography alone (P < 0.05). Conclusion The value of ultrasound elastography parameter in mediastinal lymph nodes diagnosis is higher than the conventional ultrasound features and a combination of both applications can improve discrimination accuracy of benign and malignant lymph nodes.