Objective: To discuss the therapeutic regimen for warfarin resistant patients with the help of clinical pharmacists. Methods:The pharmacist analyzed the cause of warfarin resistance and provided the dose adjustment for a pulmonary embolism pa-tient. Results:The genotype of the patient was identified as VKORC1-1639AG by gene test. The patient was diagnosed as hereditary warfarin resistance excluding other causes. With the assistance of pharmacist, the problem of warfarin resistant was solved. Conclu-sion:For warfarin resistant patients, clinical pharmacists must definite the reason of warfarin resistant firstly and then carry out the therapeutic strategy. Gene detection may be used as an important guide for warfarin resistance.

Objective To study the influencing factors and clinical characteristic of High Intensity Focused Ultrasound(HIFU) abhtion analgesic in middle-late stage pancreatic carcinoma.Methods Seventyone cases pancreatic cancer patients underwent HIFU treatment were grouped according to the pain efficacy of related influencing factors and the data was analyzed by single factor correlation analysis.The relationship between influencing factors and analgesic effect were analyzed through the pain outcome score.Results Pain score decreased ≥50％ in advanced pancreatic cancer patients occurred in ＜60 years old,Body mass index (BMI) ＜ 22 kg/m2,tumor location in the pancreatic head and neck,tumor size of 2-5 cm,and the average power of HIFU treatment ＞ 400 W,Ductal adenocarcinoma of the tumor histological type were related to the degree of pain rehef,and the difference was statistically significant (P ＜ 0.05).And fewer complications occurred after HIFU ablation.Conclusion Analysis of the relationship between the different factors and the analgesic effect in advanced pancreatic carcinoma can be used to predict the efficacy of HIFU treatment.

Objective To study the characteristics of the working memory in patients with Chinese aphasia in different ways of tasks and test materials .Methods Fifteen aphasia patients (aphasia group ,54~70 years old) and fifteen matched normal cases (control group) were requested to finish auditory retelling and auditory recognition tests of numerical materials ,content and function words .The maximum length of the string correctly completed was referred to as the working memory span .The working memory span was compared between the two groups .Results The working memory span of the aphasia group was significantly smaller than that of in the normal group (P<0 .01) .The working memory span of in patients with the aphasia group in the positive sequence retelling tasks were significantly greater than in reverse retelling ,positive recognition and reverse recognition (P<0 .01) .Reverse retell-ing was significantly greater than reverse recognition (P<0 .01) .The positive recognition was significantly greater than the reverse recognition(P<0 .01) .In retelling tasks ,the order of the working memory span was numbers , function words ,content words from high to low in the aphasia group ,but there was no significant difference be-tween them .In the positive recognition tasks ,the average working memory span for the numerical material was sig-nificantly greater than the content words(P< 0 .01) and the function words(P< 0 .01) .The content words were greater than the function words(P<0 .01) .In the reverse recognition tasks ,average working memory span for the numerical material was significantly greater than the function words (P<0 .01) .Conclusion The working memoryspan of in patients with aphasics significantly lags behind the normal people .Numbers are the easiest for aphasics . In different task modes ,the difficulties from high to low are as follow :positive retelling ,reverse retelling ,positive recognition and reverse recognition .

Objective;To explore the mechanism ofSimiaosan drug-containing serum on prevention and treatment of renal fibrosis.Methods Human renal tubular epithelial cells (HK-2) were divided into blank group, model group, control group, and drug-containing serum high dosage group, medium dosage group and low dosage group. The expressions of CTGF and BMP-7 were determined by real-time PCR assay and immunocytochemistry.Results After the HK-2 cell was induced by uric acid (UA), the expression of CTGF significantly increased (P<0.05), the expression of BMP-7 significantly decreased (P<0.05). After intervened bySimiaosan, the expression of CTGF significantly decreased (P<0.05), the expression of BMP-7 significantly increased (P<0.05) and present dosage dependent.Conclusion Reducing the expression of CTGF and up-regulation the expression of BMP-7 and controlling epithelial-myofibroblast transdifferentiation may be the mechanism ofSimiaosan on prevention and treatment of renal fibrosis.

Objective To study the feasibility and safety of interventional closure for the treatment of infant’s perimembranous ventricle septal defect (PmVSD). Methods During the period from Jan. 2012 to Jan. 2013, a total of 229 single PmVSD infants less than three years of age were admitted to authors ’ hospital. The infantile patients were divided into intervention group (n = 88) and surgery group (n = 141). Patients in the intervention group underwent interventional closure procedure , while patients in the surgery group received conventional cardiac surgery. The operation success rate , the main and minor complication rates, the operation time, the postoperative hospitalization days, the incidence of postoperative pulmonary infection and the medical cost were recorded , and the results were compared between the two groups. Results No statistically significant differences in the operation success rate, the main complication rate, the postoperative hospitalization days and the medical cost existed between the two groups (P > 0.05). But the minor complication rate and the operation time of the intervention group were better than those of the surgery group. In the surgery group, the minor complication was mainly the respiratory infection, which was manifested as higher leukocyte count, higher C-reactive protein level, higher myocardial damage marker level as well as higher vasoactive drug scores in 24 hours after the operation , and the above items were significantly higher than those in the intervention group. Conclusion For the treatment of infant’s perimembranous ventricle septal defect, percutaneous transcatheter closure is clinically feasible. This technique is safe and reliable with obvious advantages when the indication is strictly observed and the procedure is carefully manipulated. This treatment can partly replace the conventional surgery.

OBJECTIVE:To prepare nanostructured lipid carrier of adefovir dipivoxil(ADV-NLC),and optimize the formula-tion. METHODS:Using stearic acid and glycerin monostearate as solid lipid,oleic acid as liquid lipid,Gemini surfactant and poly-sorbate 80 as emulsifier,sodium dodecyl sulfate (SDS) as stabilizer,solvent dispersion ultrasonic method was used to prepare ADV-NLC. And using particle size,polydispersity index,Zeta potential,encapsulation efficiency as indexes,single factor test was conducted to screen Gemini surfactant-polysorbate 80 ratio,emulsifier dosage(ratio of emulsifier to water phase),drug-lipid ratio, solid-liquid lipid ratio. RESULTS:The formula was as follow as 3% emulsifier (Gemini surfactant-polysorbate 80 ratio of 1:2), 4.5% drug-lipid ratio,solid-liquid lipid ratio of 6:5. The average particle size of the prepared ADV-NLC was(48.83±2.65)nm, polydispersity index<0.3,Zeta potential was(-28.7±1.8)mV,encapsulation efficiency was(77.65±0.03)%(n=3). CONCLU-SIONS:ADV-NLC is successfully prepared,and the formulation is reasonable and feasible.

OBJECTIVE:To establish the method for simultaneous determination of 6 components in Lonicera japonica,and to study the content changes of them before and after before and after carbonized. METHODS:UPLC method was adopted. The deter-mination was performed on Agilent Eclipse Plus C18 RRHD column with mobile phase consisting of 0.1% phosphoric acid solu-tion-acetonitrile(gradient elution)at the flow rate of 0.2 mL /min. The detection wavelength was set at 350 nm,and column tem-perature was 25 ℃. The sample size was 1 μL. RESULTS:The linear ranges of chlorogenic acid,rutin,galuteolin,isochlorogenic acid A,isochlorogenic acid B and isochlorogenic acid C were 21.2-424 μg(r=0.9993),1.17-23 μg(r=0.9995),2.18-43 μg(r=0.9998),5.10-102 μg(r=0.9993),2.60-52 μg(r=0.9991),4.95-99 μg(r=0.9998),respectively. RSDs of precision,stability and repeatability tests were all lower than 2.0%. Recoveries were 97.11%-99.76%(RSD=1.20%,n=6),95.20%-99.90%(RSD=2.20%,n=6),95.71%-100.30%(RSD=2.20%,n=6),95.00%-96.98%(RSD=0.88%,n=6),96.47%-103.00%(RSD=2.40%, n=6),95.78%-103.80%(RSD=3.20%,n=6). Compared with before processing,the contents of rutin,isochlorogenic acid B and isochlorogenic acid C in L. japonica were increased along with processing,the contents of chlorogenic acid and isochlorogenic acid A were decreased significantly,while the content of galuteolin had no significant change. CONCLUSIONS:The method is sim-ple,precise,stable and repeatable,and can be used for simultaneous determination of 6 components in L. japonica. Those chemi-cal components have certain changes before and after carbonized.

Objective:To investigate the enantiomer separation for atropine by capillary electrophoresis .Methods:Capillary elec-trophoresis was used with an elastic quartz capillary column (60 cm ×75 mm, effective length of 40 cm).The concentration of phos-phate buffer was 30 mmol· L-1 .The high and time of injection was 10 cm and 5 s, respectively.The detection wavelength was 225 nm.The best separation conditions were selected including the type and concentration of chiral resolving agent , pH of the buffer solu-tion, operating voltage and organic solvent.Results:The optimum conditions of separation were as follows:the pH of buffer solution was 7.0, the concentration of S-β-CDP was 10 mg· ml-1 , and the operating voltage was 12 kV.Conclusion: The method is simple and fast, which can be used to se parate the optical isomers of atrpo ine.

Objective:Use the droplet digital PCR (ddRCR) technology to establish, optimize and evaluate the method of EGFR-T790M mutation detection.Methods:The relevant probes and primers were designed for EGFR-T790M mutations. The ddPCR reaction system was established, the optimal annealing temperature was set and the basic performance of the method was tested. On this basis, from January 2019 to October 2019, 72 cell-free DNA (cfDNA) samples from NSCLC patients were collected from Shandong Cancer Hospital Affiliated to Shandong First Medical University, and clinically verified. The consistency of the gene mutation detections with Bole ddPCR products was analyzed using Kappa test.Results:The ddPCR reaction system was established and optimized. Linear evaluation showed the R2 value was greater than 0.99. Using ddPCR, the blank detection limit was determined to be the numbers of mutant droplets≥2, with excellent specificity. For the sensitivity analysis, the lower limit of mutation detection was determined to be at least 0.05%. In the repeatability and inter-assay precision tests, the results had a coefficient of variation( CV)<20%. The relative deviation of the results was within the range of±10% for the accuracy analysis. Using the established T790M mutation detection method, 72 samples from the NSCLC patients were tested for genetic mutation in cfDNA, and the overall agreement with the Bole ddPCR products was 91.67% (66/72, Kappa=0.749; P<0.001). Conclusion:Using ddPCR, the method of EGFR-T790M mutation detection for NSCLC was successfully established.

OBJECTIVEWe aims to evaluate the therapeutic effect of maxillary protraction on maxillary maldevelopment using Coben analysis to illustrate the advantages of Coben analysis in identifying pathogenic mechanisms and in designing treatment plans for Class III malocclusions.

METHODSA total of 120 patients were diagnosed to have skeletal Class I maloc- clusions with maxillary maldevelopment. These patients were selected as the subjects of the present research. Maxillary protraction was exerted to promote maxilla growth. Cephalometric analysis was conducted by using Coben analysis and angle analyses of Beijing Medical University to collect data before and after maxillary protraction.

RESULTSAccording to Coben analysis measurements, the height of facies cranii increased after maxillary protraction. The depth of lower face decreased, whereas that of mid-face increased and the Ptm-A value increased significantly in the mid-face (P < 0.001). In the angle ana- lysis of Beijing Medical University, SNA, ANB, U1/NA, U1/SN, MP/SN, and Y-axis angles increased significantly (P < 0.001), whereas SNB, U1/L1 (P < 0.001), and L1/MP (P < 0.05) decreased.

CONCLUSIONMaxillary protraction has a significant effect on growing skeletal Class III malocclusions withthe chief mechanism of Ptm-A value just diagnosed as minor by Coben analysis. Coben analysis is visual and clear in identifying pathogenic mechanisms of Class III malocclusions.