Pharmacokinetics and pharmacodynamics constitute the foundation of modern pharmacology. PK/PD modeling is to profile the time process of pharmacological effects after a certain dosage is given. Investigating the relationship between PK and PD is helpful not only in instructing the clinical application, but also in the evaluation of new drugs and exploitation of new preparations etc. The present situation concerning the application of PK/PD modeling in the pharmacology,toxicology and development of new medicine is reviewed.

ObjectiveTo study the pharmacokinetics of iguratimod in rats. MethodsThe concentration ofiguratirnod in the samples was determined by HPLC method. The pharmacokineties parameters were calculated withDAS softwrare. ResultsThe mainpharmacokineties parameters of normal group(6mg/kg) were as follows:t1/2Ke:3.56h, tpeak: 4.00h, Cmax : 8.87μg/ml, AUC0.24 : 74.76μg· ml-1·h-1. The main pharmacokineties parameters of threemodel groups(3,6,12mg/kg) were as follows: t1/2Ke: 4.54,3.20,3.17h, tpcak:3.83,3.83,4.67h,Cmax:3.84, 8.31,12.69μg/ml, AUC0.24 :40.21,76. 72,117.06μg·ml-1·h-1. Except Cmax and AUC, no significant differenceswere found between the three model groups. And the differences between normal group and model group were notsignificant. ConclusionThe pharmacokinetics of rats ks fit to one-compartment model.

Aim To investigate the effects of polyI:C on angiogenesis in mouse prostate carcinoma and its mechanisms.Methods Prostate carcinoma bearing mice were randomly divided into two groups according to tumor volume:contrl group and polyI:C group.After seven times′treatment,the mice were sacrificed.The content of NO in tumor was measured by nitric oxide assay kit.Tumor tissues were partly performed hematoxylin-eosin staining to observe morphological changes and distribution of vasa.Immunohisto chemical staining was used to observe the expression of VEGF,eNOS and AQP1.Results The content of NO in polyI:C group and the control was(1.22?0.77)?mol and(8.73?5.34)?mol respectively,and there was significant difference between two groups(P

Objective To investigate whether activation of protein kmase C (PKC) can induce the activation and nuclear translocation of nuclear factor enthroid 2-related factor 2 (Nrf2) in retinal pigment epithelial (RPE) cells in vitro,and explore whether PKC activation may affect the expression of Nrf2 in RPE cells.Methods PKC-specific activator phorbol ester PMA was used to culture rabbit RPE cells and RPE cells pretreated with Nrf2 inhibitor for 24 hours.Immunofluorescence and Western blot were used to detect Nrf2 in the nucleus of the expression of the situation,the data were obtained for statistical analysis.Results The expression of Nrf2 protein in the nucleus of PRE cells was detected by immunofluorescence.Compared with the control group,the expression of Nrf2 protein in the nucleus of RPE cells increased in the experimental group,and the increase of PMA + Nrf2 inhibitor group was lower than that of PMA group.The difference between the two groups was statistically significant (P ＜0.05).Western blot analysis showed that the Nrf2 protein in the nucleus of PRE was quantitatively analyzed by image analysis.The gray value of the control group was significantly different (0.286 ± 0.013 in the control group,1.304 ± 0.033 in the PMA group and 0.671 ± 0.087 in the PMA + Nrf2 inhibitor group,P ＜ 0.05).Conclusion PKC can activate nuclear translocation of Nrf2 in rabbit RPE cytoplasm,and Nrf2 inhibitor can attenuate the effect of PKC.

To understand the possibility of schistosomiasis transmission on the East Route Project of the South-to-North Water Diversion Project, a survey of endemic status of schistosomiasis in Weishan Lake area was conducted. A cluster sampling of 2086 boatmen were screened with DDIA Kit, and the positive ones were examined with Kato-Katz technique. Meanwhile, a questionnaire survey about schistosomiasis control was carried out to collect the data about the boatmen's general information and knowledge , attitude and practice (KAP). The results showed there were no schistosomiasis patients. However, there exist potential risk factors for schistosomiasis transmission because of the bad hygiene habits and the poor knowledge of schistosomiasis prevention in boatmen.

Objective:To explore the attitude of clinical nurses toward vital sign monitoring and analyze its influencing factors.Methods:From May to July, 2020, clinical nurses from three Class Ⅲ general hospitals in Liaocheng City were selected by convenient sampling and surveyed using a general information questionnaire, the Chinese version of the Vital Signs Monitoring Attitude Scale, and the Chinese version of the NASA Task Load Index (NASA-TLX) . A total of 747 questionnaires were collected in this study, and 721 of them were valid, accounting for an effective recovery rate of 96.5%.Results:The total score of the 721 clinical nurses' attitude toward vital signs monitoring was (56.48±6.72) . The results of multivariate analysis showed that working years, department, and workload were the influencing factors of clinical nurses' attitude toward vital signs monitoring ( P<0.05) . Conclusions:The positive attitude of clinical nurses toward vital monitoring needs to be improved, and nursing managers can start from human resource allocation to reduce their workload, encourage them to perform vital sign monitoring timely and properly, and identify changes in patients' conditions early.

Objective:To investigate the application status of emergency radiology in China, and to provide data support for the standardized development, scientific management and big data research of emergency radiology.Methods:From August 12th to October 19th, 2022, a questionnaire survey was conducted through WeChat"Questionnaire Star"to send targeted questionnaires to investigate the relevant data of the current status of emergency radiology in China, mainly including digital radiography (DR) and computed tomography (CT). This study was initiated by the Chinese Emergency Radiology Database Collaboration Group, and comprehensively investigated emergency imaging personnel, equipment, workload, critical value reporting process, and artificial intelligence (AI) application status.Results:There were 123 hospitals in the study. The survey showed that emergency DR/CT reports were mainly completed by residents and above (69.1%). There were 21 DR brands, 10 CT brands and 8 MR brands used for emergency imaging examinations. The median number of DR examinations in tertiary hospitals and secondary hospitals investigated from January to June 2022 was 4 642 and 2 015 cases respectively, and the median number of CT examinations was 16 512 and 3 762 cases respectively. The average single-shift workload of DR in the emergency radiology department during the day and night shift in tertiary hospitals was mainly ≤20 copies and 21-50 copies, and the average single-shift workload of CT in the emergency radiology department during the day and night shift was mainly 21-50 copies and 51-100 copies, while the average single-shift workload of DR/CT in the emergency radiology department during the day/night shift in secondary hospitals was mainly ≤20 copies. In terms of critical value reporting process, 74.8% of emergency imaging doctors and 84.6% of emergency imaging technicians took the way of phone/text message to notify the clinical doctor or the patients′ family. The overall deployment rate of AI in emergency imaging was about 60.2%. 75% of the respondents believed that in the future, AI can improve emergency radiology work from aspects such as emergency screening, aided diagnosis and process optimization.Conclusions:The emergency medical imaging mainly based on DR and CT has the current situations such as generally low seniority of doctors, diverse brands of imaging equipments, large volume of examinations and intense workload per doctor, especially in tertiary hospitals, and dependence on traditional means for critical value reporting. At present, AI is emerging in the field of emergency imaging, and there is still a long way to go to play the huge potential of AI in the intelligent whole process of emergency imaging in the future.

Objective To investigate the risk factors of hyperbilirubinemia in late preterm infants. Methods The clinical data of 815 late preterm infants (449 males and 366 females) from 25 hospitals in Beijing were collected from October 2015 to April 2016, including 340 cases(41.7％) with hyperbilirubinemia (hyperbilirubinemia group), and 475 cases without hyperbilirubinemia (control group). The clinical data of two groups were compared, and the maternal factors influencing hyperbilirubinemia in late preterm infants were analyzed with logistic regression. Results There were no significant differences in gender ratio (M:F 1.39 vs. 1.12, t=1.811,P=0.172)and birth weight[(2502.6±439.6)g vs. (2470.2±402.9)g,χ2=2.330,P=0.127)]between two groups. The incidence rates of hyperbilirubinemia in infants of 34 wks, 35 wks and 36 wks of gestational age were 22.9％(87/174), 35％(119/300) and 42.1％(143/341) respectively (χ2=1.218,P=0.544). The multivariate logistic regression analysis indicated that the maternal age(OR=1.044,95％ CI:1.010-1.080,P=0.011)was independent risk factor and multiple births(OR=1.365,95％CI:0.989-1.883,P=0.048), premature rupture of membranes(OR=2.350,95％ CI:1.440-3.833,P=0.001), cesarean section(OR=1.540,95％CI:0.588-4.031,P=0.014)were risk factors for hyperbilirubinemia in late preterm infants. Conclusions The incidence of hyperbilirubinemia in late preterm infants is relatively high. Maternal age, multiple births, premature rupture of membranes and cesarean section are risk maternal factors related to hyperbilirubinemia in late preterm infants.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective:To study the respiratory morbidity and the risk factors of respiratory complications in late-preterm infants.Methods:The data of 959 late-preterm infants in 21 hospitals in Beijing from October 2015 to April 2016 were collected.These infants were divided into the respiratory morbidity group (237 cases) and the control group (722 cases) according to whether they had short-term respiratory morbidity after birth.Clinical data of the two groups were compared.Results:Among the 959 late-preterm babies, 530 were male and 429 were female.Two hundred and thirty-seven cases (24.7%) developed short-term respiratory morbidity after birth.Infectious pneumonia developed in the most cases (81 cases, 8.4%), followed by transient tachypnea (65 cases, 6.8%), amniotic fluid aspiration (51 cases, 5.3%), and respiratory distress syndrome (24 cases, 2.5%) successively.All the infants recovered and discharged.There were no differences between gender and maternal age between 2 groups (all P>0.05). Compared with the control group, more late-preterm infants were delivered by cesarean section (73.4% vs.59.7%, χ2=14.43, P<0.001) and the 1-minute Apgar score was lower [(9.41±1.66) scores vs.(9.83±0.53) scores, t=5.40, P<0.001] in the respiratory morbidity group.The differences were statistically significant.There were more cases with maternal complications in the respiratory morbidity group that in the control group (66.7% vs.58.6%, χ2=4.877, P=0.027), but no difference in various complications between 2 groups was observed ( P>0.05). In the respiratory morbidity group, the most frequent complications were maternal hypertension and preeclampsia (27.8% vs.22.6%, χ2=2.728, P=0.099). There were no differences between 2 groups in gestational age, birth weight and birth length (all P>0.05). There were more infants small for gestational age and large for gestational age in the respiratory morbidity group than in the control group (18.8% vs.14.1%, 6.3% vs.2.4%, χ2=8.960, P=0.011). The duration of hospitalization of the respiratory morbidity group was significantly longer than that of the control group [(9.00±4.42) d vs.(6.82±4.19) d, t=6.676, P<0.001] since the infants with respiratory morbidity needed to be hospita-lized. Conclusions:Respiratory diseases occur in about 1/4 of late-preterm infants.Infants who are delivered by cesarean section and whose mothers are complicated with the maternal hypertension and preeclampsia should be monitored closely.Respiratory support should be provided for infants not appropriate for gestational age who are more likely to suffer from respiratory diseases, so that they can successfully pass through the transition period.