OBJECTIVE:To establish physiological pharmacokinetic (PBPK) model of cefdinir in healthy volunteers,and to predict pharmacokinetic process of cefdinir in volunteers after oral administration. METHODS:Using“toubao dini”“cefdinir”“logP”“pKa”as keywords,related literatures about physico-chemical constants of cefdinir were retrieved from CNKI,ScienceDi-rect,PubMed and other databases;according to related guidelines and preliminary clinical trial plan of FDA,GastroPlusTM 8.6 soft-ware was used to establish PBPK model of oral administration of cefdinir;the effectiveness of the model was evaluated by multiple error. The model was used to simulate the absorption of cefdinir in the gastrointestinal tracts. The bioequivalence of test preparation and reference preparation were evaluated through single and population(n=500)simulation tests using cmax and AUC0-∞ of cefdinir reference preparation (capsule and granular formulation) as factors when release rate t85%=15 min (i.e. accumulatively released 85% within 15 min). RESULTS:The blood concentration-time curves of cefdinir predicted by PBPK model fitted well with mea-sured value(R2≥0.95);the pharmacokinetic parameters(cmax,tmax,AUC0-∞)were close to measured results,and the multiple er-rors were less than 2. After oral administration,cefdinir was mainly absorbed by the intestinal tract (45.6%),especially by seg-ment 1 of jejunum(14.8%);the absorption amount was significantly lower than the release amount of absorption site,and reached the maximal value(about 40%)within 4 h. The results of single simulation test showed that there was no statistical significance in cmax and AUC0-∞ between cefdinir test and reference preparations (P>0.05). The results of population simulation test showed that the relative bioavailability of cefdinir test particle and test capsule respectively were 99.01%-102.99% and 97.60%-105.90%;90%CI of cmax and AUC0-∞ values were within 80%-125% of reference preparation. CONCLUSIONS:The PBPK model is accurate and reliable in this study,can provide reference for pharmacokinetic study and bioequivalence evaluation of cefdinir preparations. Test preparation and reference preparation are equivalent.

Objective:To establish an LC–MS/MS method for the determination of the active metabolite(SN-38) and secondary metabolite(SN-38G) of irinotecan in rat liver microsomes incubation system, and optimize the incubation conditions. Methods:Meth-anol was selected to precipitate protein in the samples, and then the concentrations were analyzed by LC–MS/MS. All the separation was carried out on a ZORBAX Eclipse XDB-C18 column(2. 1 mm × 50 mm, 3. 5 μm) with the mobile phase of acetonitrile – water (containing 0. 1% formic acid) (23 :77) at a flow rate of 0. 3 ml·min-1. The mass spectrometer was operated with multiple reac-tions monitoring ( MRM) using electrospray ionization ( ESI) . The incubation conditions were optimized by single factor design. Re-sults:SN-38 and SN-38G showed a good linearity ( r≥0. 9972) respectively within the range of 2. 3-920 ng·ml-1 and 2. 5-1000 ng ·ml-1. The intra-and inter-day RSD was below 14. 6%(n=6). The average recovery was within the range of 74. 1%-123. 4% with RSD below 13. 5% (n=6). The optimal incubation conditions were as follows:the concentration of liver microsomal protein was 0. 3 mg·ml-1 and the incubation time was 30 min. Conclusion:The method is rapid, sensitive and accurate in the quantification of SN-38 and SN-38G in the incubation system,which provides methodological basis for the activity determination of UGT1A1 enzyme in vitro.

ObjectTo study the application of ultrasonic circulation technique for the extraction of triterpenoids from Ganoderma lucidum (Leyss.ex Fr.) Karst. Methods On the basis of conventional method, the processing steps of ultrasonic circulation treatment were added. Results The comparative experiments showed that less amounts of various solvents and shorter extraction time were needed for ultrasonic circulation extraction, with the product ratio of about 40 percent higher than that of conventional method. Furthermore, a good consistency of the target product analyzed by HPLC was found between two different extraction methods. Conclusion The ultrasonic circulation technique has a potential application to the extraction of triterpenoids from G. lucidum.

Objective To explore the best mode of diabetic dietary education in the nursing specialist outpatient service,which is suit for China's national situation.Methods A total of 100 diabetic patients consulting diabetes diet in the nursing specialist outpatient service were divided into observation group and control group with 50 cases each by random digits table method.The routine sermonic education mode was used in control group,while the error-correction education mode was used in observation group.The question-real-time evaluation was performed at the end of the education and a follow-up evaluation after 6 months of intervention was evaluated.Results Grasp of the knowledge of diabetes diet in observation group immediately after education and 6 months after education were better than those in control group,t=3.07,3.06,P＜0.01.In the follow-up evaluation after 6 months of intervention,fasting blood glucose and glycosylated hemoglobin were (6.84±0.79) mmol/L,(6.83±0.36) ％ in observation group and (7.56±0.93) mmol/L,(7.67±0.87) ％ in control group.The indices in observation group were significantly better than those in control group,t=-4.17,-6.32,P＜0.01.Conclusions Using the error-correction education mode can correct the false dietary behavior of patients and improve the effect of the diabetic dietary education more effectively.

ObjectiveTo investigate the diagnostic value of ultrasound on patients with papillary thyroid carcinoma(PTC) coexisted with Hashimoto thyroiditis(HT).Methods The preoperative ultrasonography data of 2144 cases with PTC from January 2006 to December 2011 who treated with operation and diagnosed by pathology were analyzed retrospectively.Among them,265 cases coexisted with HT (PTC coexisted with HT group),1879 cases were not coexisted with HT (non-PTC coexisted with HT group).ResultsMost of the cancerous nodes in two groups exhibited in the ultrasonographic performance just like irregular shape,unclear boundary and so on (P ＞ 0.05).Most of the cancerous nodes in non-PTC coexisted with HT group exhibited hypoechoic nodules with microcalcifications,those in PTC coexisted with HT group exhibited various internal echoes with mainly microcalcifications,and the coarse calcification occupied a certain proportion(P＜ 0.01 ).The cancerous nodes in PTC coexisted with HT group were not rich in blood flow compared with non-PTC coexisted with HT group,but mostly exhibited blood disorders.When compared with non-PTC coexisted with HT group,the rate of ultrasound diagnosis in PTC coexisted with HT group was lower [ 52.8 ％( 140/265 ) vs.75.0 ％ (1409/1879),P ＜ 0.01 ],and the false positive rate in lymph node was higher [84.0％(487/580) vs.74.8％ (77/103)] (P ＜0.05).ConclusionsThe nodules are malignant when they appear as hypoechoic solid nodules,have unclear boundary and have microcalcifications should be highly suspected.The hyperechoic solid nodules or coarse calcification nodules should also be awared and taken further observation of the characteristics around the echoes and the internal blood flow,making comprehensive analysis to determine whether it could be malignant transformation and try best to reduce the misdiagnosis and missed diagnosis rates of this disease.

Objective To demonstrate the value of eombined application of prenatal ultrasonography with fetal magnetic resonance imaging(MRI) in the diagnosis of monochorionic muhifetal realformations. Methods Fourteen cases of muhifetal malformations,detected by prenatal ultrasonography,received MRI within 48 h afterwards.All diagnosis were confirmed after delivery or mid-term termination.All imaging results of the 14 cases were retrospectively reviewed. Results Among the 14 cases,there were 7 acardias,5 Conjoined twins and 2 demise of multifetuses.Comparing ultrasound with MRI,we found that:(1)In cases with acardia and demise of multifetusea,ultrasound could diagnose correctly and be an important tool for follow-up,while MRI could demonstrate organs and structures of the acardiac recipient more clearly and detect the secondary changes of brain in the donor and survived fetus.(2)In Conjoined twins,ultrasound was superior to MRI in demonstrating the structure and function of cardiovascular system : and equivalent to MRI in identifying stomach,kidney,bladder and limbs;but inferior to MRI in identifying esophagus,lung,liver and intestinal,especially in the brain. And MRI could demonstrate two fetuses and the relationship between them in COnjoined twins simultaneously. Conclusions Prenatal ultrasonography and MRI have their own advantages and disadvantages in diagnosing monochorionic multifetal malformations.But the combination of prenatal ultrasonography and fetal MRI may be more valuable.

ObjectiveTo explore the clinical value of three-dimensional (3D) skeletal ultrasound mode imaging, 3D helical computer tomography (3D-HCT) and MRI in diagnosing lower limb skeletal malformations of fetal sirenomelia.MethodsSeven fetuses were suspected of sirenomelia with routine prenatal ultrasonography examination. Three-dimensional skeletal ultrasound mode imaging and MRI were used to conifrm the diagnosis, and the results were compared to those of pathology, 3D spiral CT or X-ray after termination. Five of them underwent chromosome examination including chorionic villus or umbilical cord biopsy.ResultsSix fetuses were singletons and one fetus was a conjoined twin. Three fetuses were male, while four fetuses were female. All fetuses with sirenomelia showed varying degrees of skeletal abnormalities: 1 case of typeⅢ, 2 cases of typeⅣ, 3 cases of typeⅤ and 1 case of typeⅥ. No foot was detected in one case and only single foot was detected in other 6 cases. In 7 cases, 3D skeletal ultrasound mode imaging could demonstrate all the lower limb skeletal malformations, including abnormal femur and tibioifbula, single foot or no feet. Prenatal MRI could demonstrate abnormal femur in 4 cases, abnormal tibioifbula in 1case, and no foot malformation. The results of 3D spiral CT after termination were consistent with X-ray and pathological examination results.ConclusionsAs a new imaging technology for detecting fetal skeletal malformations, prenatal 3D skeletal ultrasound mode imaging and postnatal 3D spiral CT both can display fetal bone clearly. They both have important clinical value in diagnosing lower limb skeletal malformations.

Objective:To quantify any correlation between serum levels of omega-3 polyunsaturated fatty acids (ω3-PUFAs) and post-stroke cognitive impairment (PSCI).Methods:The clinical data of 77 patients hospitalized after a first stroke were analyzed. The Minimum Mental State Examination (MMSE) was used to divide them into impaired (PSCI) and unimpaired (non-PSCI) cohorts. The serum levels of ω3-PUFAs, α-linolenic acid (ALA), eieosapentaenoic acid (EPA) and dueosahexenoie acid (DHA) were compared between the two groups and correlated with the individuals′ MMSE scores.Results:The average ALA, EPA, DHA and total ω3-PUFAs levels of PSCI group were in most cases significantly lower than those of the non-PSCI group. Spearman correlation analysis showed that serum DHA level was a weak positive predictor of the MMSE scores (R=0.32, P≤0.05). Logistic regression analysis indicated that low serum DHA level was an independent risk factor for PSCI ( P≤0.01). Conclusions:Cognitively impaired stroke survivors tend to have lower serum ω3-PUFAs levels than those without cognitive impairment. There is a weak positive correlation between serum DHA levels and MMSE scores. Low serum DHA level is an independent risk factor for PSCI. The serum level of ω3-PUFAs is of high value in the auxiliary diagnosis and evaluation of PSCI.

We report a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia during pregnancy who was postnatally detected with a de novo mutation in the COL4A1 gene by genetic testing of umbilical cord blood. Multiple fresh hemorrhagic foci were detected in the fetal brain parenchyma and cerebellar hemisphere by ultrasound at 25 gestational weeks. Regular re-examination of the nervous system's ultrasound and magnetic resonance imaging (MRI) indicated recurrent multiple intraparenchymal hemorrhages followed by cystic leukomalacia. However, karyotyping and chromosomal microarray analysis of amniotic fluid showed no abnormality. The newborn was born by cesarean section at 37 +3 gestational weeks with an Apgar score of 10 at 1 and 5 min. Repeated apnea occurred after birth. MRI detected new intraparenchymal hemorrhage and cystic leukomalacia on the six-day of life. The infant's limb muscle tone remained low on the 90-day follow-up. The patient was lost to follow up. Whole-exome sequencing of the cord blood identified a de novo heterozygous mutation- c.4738G>A in the COL4A1 gene (NM_001845.4; p.G1580S) neither parent carried. It suggests that the genetic test of the COL4A1 mutation should be considered for fetuses with intracranial hemorrhage in the prenatal diagnosis, especially those with recurrent fetal intraparenchymal hemorrhage followed by cystic leukomalacia. Genetic tests could help analyze the fetal prognosis, and guide the delivery mode.

Objective To study the characteristics of gastroesophageal reflux (GER) in term neonates and the association between the reflux behaviors and gastroesophageal reflux events by multichannel intraluminal impedance-pH monitoring retrospectively.Method Full term neonates suspected to have gastroesophageal reflux,admitted to neonatal ward of our Hospital from November 2016 to December 2017 were enrolled for the study.All underwent 24-hour esophageal multichannel intraluminal impedance-pH (24 h MII-pH) monitoring.They were assigned into physiologic GER group and pathologic GER group.Data of demographic characteristics,clinical symptoms,24 h MII-pH results and indecies for evaluating the association between symptoms and reflux events were collected and analyzed.Result A total of 31 cases were enrolled.The median age of starting 24 MII-pH monitoring was 7 days (range from 2 to 28 days).15 cases were diagnosed with pathologic GER (48.4％),and 16 cases were diagnosed with physiologic GER.The symptoms and signs were persistent vomiting,incessant crying,desaturation (oxygen desaturation) and unexplained transient events (including cyanosis or suspected seizure),case number was 12,9,6,2,and 1 respectively.In the pathologic group,the median of total acid reflux 52 (7 to 80),total weakly acidic reflux 58 (19 to 114);In the physiologic group was 36 (3 to 55),35 (6 to 55) respectively.The neonates in pathologic group had more acidic reflux (both before and after feeding),total weak acid reflux and liquid reflux than physiological GER group,which showed statistical significance (P ＜ 0.05).While there was no significant difference in acid reflux time of total,before feeding and after feeding (P ＞0.05).It was proved that the percentage of positive symptom indices of vomiting,postprandial transient events,incessant crying after feeding,and desaturation associated with GER were 100％,100％,66.7％and 33.3％ retrospectively,which indicate that postprandial transient events were associate with GER,and incessant crying,desaturation were partially related to GER.And no association was found between bradycardia and reflux events.Conclusion Pathological GER of term neonates mainly manifest as reflux of weakly acidic and liquid.24 h MII-pH monitoring could detect weakly acidic reflux and weakly alkaline reflux,so it would be the recommended diagnostic tool for neonatal gastroesophageal reflux.Despite vomiting,special attention should be paid to symptoms associated with GER,such as incessant crying,and unexplained transient events et al.