Objective To develop an HPLC-MS/ MS method for quantitative determination of PA-824 in rat plasma and to study the pharmacokinetics of PA-824 in rat after oral administration. Methods An HPLC-MS/ MS method was developed and validated for determination of PA-824 in rat plasma using metronidazole as internal standard.The proteins in plasma samples were precipitated with methanol,and PA-824 was enriched for analysis by HPLC-MS/ MS.An Inertsil? ODS3 C18 column (150 mm×4.6 mm,5 μm) was applied with mobile phase composed of methanol- 0.03% triethylamine (TEA) in water (90:10) ,at a flow rate of 0. 5 mL ? min-1 and column temperature of 30 ℃ . Quantitation was performed on a triple quadrupole mass spectrometer applying electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode with transitions at 360.1/ 175.0 for PA-824 and 172.0/ 128.0 for metronidazole.The concentration of PA-824 in plasma was tested after oral administration at various time points and the data were processed with software DAS.2.0. Results The standard calibration curve for spiked rat plasma containing PA-824 was linear over the range of 0. 1 - 10. 0 μg?mL-1 . The recoveries obtained for PA-824 were greater than 92.13%.Intra-day and inter-day coefficient of variation were less than 6.6%.After oral administration,the main pharmacokinetic parameters were AUC(0-t) : ( 3 297. 503 ± 320. 958) mg ? L-1 ? min-1 , AUC(0-∞ ) :(3 558.315±338.860)mg?L-1?min-1 ,tmax:(360.000±64.143)min,Cmax:(3.5±0.3)μg?mL-1 . Conclusion The method is rapid,accurate,simple,and successfully applied in a pharmacokinetic study of fixed dose oral administration of PA-824 in rats.

BACKGROUND/AIMS: To establish an animal model of laryngopharyngeal reflux (LPR) and study the effect of LPR on the laryngopharyngeal mucosal ultrastructure. METHODS: Ten Bama minipigs were randomly divided into control group and stent group. Every pig underwent endoscope, and baseline pH was monitored for 4 hours at laryngopharynx and distal esophagus, then specimens from laryngopharyngeal mucosa were biopsied. For the control group, these procedures were repeated on the 14th day. In the stent group, a custom-designed esophageal stent suit was implanted into esophagus, laryngopharyngeal and distal esophageal pH monitoring lasted for 2 hours, then stent suit was removed 3 days later. At last, the same procedures were done as the control group on the 14th day. Specimens were observed under transmission electron microscope to measure the intercellular space and desmosome number. RESULTS: In the control group, there was no laryngopharyngeal reflux on the first day and 14th day. Before the stent was implanted, there was also no laryngopharyngeal reflux in the stent group. In both 2 hours and 14 days after stent implantation, the num -ber of reflux, reflux time, and percentage time of pH < 4.0 were significantly increased (P < 0.05) in the stent group. There was no difference in intercellular space and desmosomes in the control group between baseline and 14th day. In the stent group, intercellular space of laryngopharyngeal mucosa was significantly increased (0.37 mum vs 0.96 mum, P = 0.008), and the number of desmosomes was significantly decreased (20.25 vs 9.5, P = 0.003). CONCLUSIONS: A Bama minipig model of LPR was established by implanting a custom-designed stent suit. LPR might destroy the laryngophar yngeal mucosal barrier.
Desmosomes ; Endoscopes ; Esophageal pH Monitoring ; Esophagus ; Extracellular Space ; Hydrogen-Ion Concentration ; Hypopharynx ; Laryngopharyngeal Reflux* ; Models, Animal ; Mucous Membrane ; Stents ; Swine, Miniature*

Objective:To construct a risk prediction and column chart model for venous thromboembolism (VTE) in patients with nephrotic syndrome and provide reference for VTE prevention.Methods:To use the retrospective cohort study design, the nephrotic syndrome patients who were hospitalized in Peking University Third Hospital from January 2018 to December 2022 were selected as the study subjects by convenient sampling method. Using univariate and multivariate Logistic regression analysis to analyze the risk factors for VTE in patients with nephrotic syndrome, establish a risk prediction model, and draw a column chart. The receiver operating characteristic (ROC) working curve and Hosmer Lemeshow test were used to verify the predictive performance of the model.Results:Among the 279 collected patients,187 males and 92 females, aged (54.25 ± 16.29) years, 43 cases developed thrombosis, with an incidence rate of 15.4%. The results of univariate analysis showed that different genders, ages, activity ability, alcohol consumption history, use of diuretics, albumin, hematocrit, fibrinolytic products, activated partial thromboplastin, D-dimer quantification and glomerular filtration rate showed differences in the occurrence of VTE in patients with nephrotic syndrome ( χ2=4.22, 4.62, 12.30, Z values were -5.73 to 6.07, t=-2.07,all P<0.05). The results of multivariate Logistic regression analysis showed that age, whether diuretics were used, activated partial thromboplastin, D-dimer and glomerular filtration rate were independent influencing factors for VTE ( OR values were 0.913- 3.285, all P<0.05). The above factors were five independent variables to construct a column chart. The area under the ROC curve of the model was 0.810, and the maximum value of the Jordan index was 0.518, the sensitivity was 66.67% and the specificity was 85.15%. The Hosmer-Lemeshow goodness-of-fit test showed that the model fit well ( χ2=12.00, P=0.151). Conclusions:The constructed column chart can personalized predict the risk of thrombosis in patients with nephrotic syndrome and help nursing staff in quickly identifying high-risk patients for thrombosis and taking corresponding intervention measures in a timely manner.

Objective To investigate the effects of the angle of external jugular vein on the incidence of PICC complications.Methods A total of 212 patients with external jugular vein tube from August 2013 to November 2015 were divided into acute angle type (100 cases) and obtuse angle type (112 cases) according to the angle of external jugular vein by the X-ray. PICC complications of two groups were evaluated.Results There were 4 cases of mechanical phlebitis, 2 cases of thrombosis and 0 case of infection in the obtuse angle type group, while in the acute angle type group there were 19 cases of mechanical phlebitis, 9 cases of thrombosis and 4 cases of infection. Statistically significant differences were observed between two groups (χ2=13.01, 5.58, 4.57;P<0.05).Conclusions External jugular vein with obtuse angle type has lower incidence of PICC complications.

Objective To observe and analyze the application of project achievement style quality control circle in constructing an outpatient intelligent pharmacy pre-job training model,and provide new ideas and systematic solutions for pre-job training of new pharmacists in intelligent pharmacies.Methods 70 pharmacists who were newly employed in outpatient pharmacy of Yantai Yuhuangding Hospital from January 2023 to March 2024 and had no working experience in this position were selected and divided into two groups(the control group and the experimental group)by random draw method.The control group implemented the traditional training mode,and the experimental group adopted the new mode of pre-job training of outpatient intelligent pharmacy constructed by project achievement style quality control circle.The theoretical,skill,and practical examination results at the end of the training period and the satisfaction with training of the newly-appointed pharmacists were collected.Results The assessment scores of theory,skills and practice,and the results of satisfaction with the training of newly recruited pharmacists in the experimental group were significantly higher than those of the control group(P＜0.05).Conclusion The new model of pre-job training for new pharmacists in the outpatient intelligent pharmacy has great advantages in the design of the training program,standardization of the training content,reasonable arrangement of the training cycle,and innovation of the training mode,which improves the pharmacists'satisfaction with the training and achieves good training results.

Objective:To investigate the impact of body mass index (BMI) on clinical effect and fresh cycle embryo transfer pregnancy outcome of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) in patients with early follicular phase prolonged protocol.Methods:From January 1st, 2018 to July 1st, 2020, 2 257 cases of early follicular long-term protocol in IVF/ICSI and embryo transfer were collected using the clinical assisted reproductive technologies management system software database of the First Affiliated Hospital of Nanjing Medical University. Patients were divided into three groups according to the recommended Asian BMI cut-off points: low body mass group (BMI<18.5 kg/m 2), normal body mass group (18.5≤BMI<24.0 kg/m 2), and high body mass group (BMI≥24.0 kg/m 2). The ovarian stimulation characteristics among the groups were investigated. Then 1 741 fresh embryo transfer cycles were selected and divided into three groups as above, and then the ovulation induction and clinical outcomes were analyzed among the groups. Results:There were significant differences in the starting dosage of gonadotrophin (Gn), total dosage of Gn and days of Gn used among the low body mass group, normal body mass group, and high body mass group in the 2 257 IVF/ICSI cycles (all P<0.01). The high body mass group needed the most amount of Gn [(2 159±668) U] and longest Gn days [(12.3±2.5) days]. The estradiol and progesterone levels [(7 474±4 852) pmol/L, (3.4±1.9) nmol/L] on hCG trigger day in the high body mass group were lower than those in the low body mass group and normal body mass group (all P<0.01). The oocytes retrieved in high body mass group (8.4±4.1) were significantly lower than normal body mass group ( P<0.05). The normal fertilization number, the available embryo number and high quality embryo number were all lower in the high body mass group than other two groups, while no significant difference showed (all P>0.05). In 1 741 cycles of fresh embryo transfer, the average number of transplanted embryos in the low body mass group (1.2±0.4) was decreased compared with the other two groups ( P<0.05), while the biochemical pregnancy rate, clinical pregnancy rate and live birth rate in the normal body mass group were higher compared with the other two groups, but the differences showed no statistically significance (all P>0.05). Conclusions:Increased BMI might affect ovulation induction response in early follicular phase prolonged protocol IVF/ICSI patients, leading to the increase of Gn dosage and the extension of Gn induction days. Although there is no significant difference in pregnancy outcome among different BMI groups, considering the increased risk of adverse perinatal outcomes during subsequent pregnancy in overweight or obese patients, certain attention should still be paid to the control of BMI in patients receiving assisted reproduction treatment with early follicular phase prolonged protocol.