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.

Objective To evaluate the impact of fish oil (ω-3 fatty acids) parenteral nutrition (PN) on outcomes for non-ICU postoperative patients.Methods PubMed,Embase,Cochrane,China National Knowledge Infrastructure (CNKI) and Wanfang Database etc.were searched to retrieve the eligible studies published from January 2010 to June 2016.The studies included were randomized controlled trials (RCTs) that evaluated the effects of supplementation of fish oil (Omegawen) in PN regimens for postoperative patients on clinical outcomes.The methodological quality assessment was based on Jadad scale and Schulz allocation concealment tool.Meta-analysis was conducted by RevMan 5.3 software.Results 19 RCTs,1 170 surgical patients,were included.Meta-analysis indicated that short-term fish oil supplementation significantly reduced the incidence of infectious complications [RR =0.44,95％ CI (0.31,0.64),P ＜0.000 1] and shortened the length of hospital stay [MD =-0.85,95％ CI (-1.67,-0.03),P=0.04],while with no significant effect on mortality [RR =0.42,95％ CI (0.07,2.63),P =0.36] and total expenditure of hospitalization [MD =-216.60,95％ CI (-718.94,285.75),P =0.40].Sensitivity analysis showed similar results.Conclusion According to existing evidence,fish oil in PN for surgical patients could reduce the incidence of postoperative infectious com-plications and shorten the length of hospital stay.

BACKGROUND:Peripheral facial nerve injury first involves the retrograde reactions of central nervous system axons, and nerve regeneration wil depend on the survival and functional status of neuronal cel bodies. OBJECTIVE:To explore the expression of neuronal cadherin and placental cadherin in facial nuclei after facial nerve injury. METHODS:New Zealand white rabbits were randomly divided into model group (n=48) and control group (n=8). In the model group, every eight rabbits were used to carry out the test respectively at 1, 4, 7, 14, 21 days after the model of facial nerve injury (right side) was established. SP and real-time quantitative PCR methods were taken to test the expression of neuronal cadherin and placental cadherin in the facial nerve nucleus at mRNA and RESULTS AND CONCLUSION:The control group had neuronal cadherin-and placental cadherin-positive neurons. In the model group, neuronal cadherin and placental cadherin positively expressed in the facial motorneurons (right side), and their expressions were peaked at 14 days. Compared with the control group, the mRNA expression of neuronal cadherin in the facial motorneurons was increased significantly at 4-28 days after injury;the mRNA expression of placental cadherin in the facial motorneurons was decreased significantly at 1 day after injury, and then increased significantly at 7-28 days. It is suggested that the expression of neuronal cadherin and placental cadherin is positive in the early stage of facial nerve injury, and the expression of placental cadherin is always present, while the expression of neuronal cadherin relatively lasts for a short time. After facial nerve injury, the expression of neuronal cadherin and placental cadherin in the facial nerve nucleus is both increased, which indicates that the facial nerve regeneration may be related to the high expression of adhesion molecules.

Objective:To establish an HPLC-MS/MS method for the determination of vinblastine in rat plasma. Methods:Aceto-nitrile was used to precipitate protein in the samples after the addition of internal standard, and then the concentration was analyzed by HPLC/MS/MS. All the separations were carried out on an Ultimate C18 column (150 mm × 2. 1 mm, 5. 0 μm). The mobile phase was composed of acetonitrile and 10 mmol·L-1 ammoniumacetate (containing 0. 1% formic acid) (49 ∶51) and was pumped at a flow rate of 0. 3 ml·min-1 under 40 °C. The detection was performed with multiple reactions monitoring (MRM) using electrospray ioniza-tion (ESI). The precursor/product ion transitions were monitored at m/z 811. 4→m/z 224. 2 (positive ion mode) for vinblastine and m/z 825. 4→m/z 807. 4(positive ion mode) for internal standard vincristine. Results:Good linearity of vinblastine was obtained with-in the range of 0. 457-950 ng·ml-1(r=0. 997 1). The lower limit of quantification was 0. 457 ng·ml-1. The extraction recoveries were within the range of 89. 15%-95. 28%. The precision of intra-and inter-day was not more than 7. 95%. T1/2 of vinblastine in rats was (5. 86 ± 2. 37) h, and AUC(0-t) and AUC(0-∞) was (68. 45 ± 14. 51) and (95. 03 ± 33. 09)μg·L-1 ·h, respectively. Conclu-sion:The method is fast, sensitive and accurate, which provides research basis for the development of vinblastine and transporters re-search in medicine. The concentration of vinblastine in rats is low, and the half-life is long.

Objective To evaluate postprandial pharmacokinetics and bioequivalence of two preparations of cefdinir capsules in Chinese healthy volunteers. Methods In a two-way cross-over study, 24 healthy male volunteers were divided into two groups randomly and a single dose of cefdinir capsules of test and reference preparation were administered orally, respectively.The concentration in plasma was determined by LC-MS/MS. Pharmacokinetic parameters and bioequivalence were calculated and evaluated by DAS. Results The main pharmacokinetic parameters of test and reference were as follows: AUCt (4.35±1.09) μg??h??mL-1 and (4.12±1.22) μg??h??mL-1, AUC0-∞(4.53±1.12) and (4.53±1.73) μg??h??mL-1, t1/2 (1.74±0.29) h and (2.13±1.65) h, tmax(4.44±0.86) h and (4.54 ±1.16) h, Cmax(900±250) ng??mL-1 and (876±269) ng??mL-1 . Conclusion The test and reference preparation of cefdinir capsules are bioequivalent.

As a key component of glutamatergic system, metabotropic glutamate receptor 5 (mGluR5) has been extensively involved in the regulation of physiological processes such as synaptic transmission, synaptic plasticity and synaptic excitation/inhibition balance.Over the past few decades, mGluR5 has been found to be closely related to multiple neurological and psychiatric disorders, thus it is of considerable interest as a drug target in the treatment of such disorders.This review summarizes the structure and distribution of mGluR5, its normal physiological function, its pathological roles in related central nervous system (CNS) diseases, as well as the current status of its drug development, in order to provide reference for further investigation.

Objective To investigate the effect of Osthole on memory function of sleep deprivation(SD) mice. Methods Forty-eight male mice were randomly divided into 4 groups;normal control group(NC group ), large platform control group(TC group),sleep deprivation group(M group)and Osthole group(Ost group). The model of SD in mice was estabished by using improved multi platform method. The ability of learning and memory was tested by using Morris water maze test and pathological changes of hippocampal neurons in mice were observed by HE staining. The serum,hippcampus malondialdehyde(MDA)contents and superoxide dismutase(SOD)activity, so as the hippocampus No content,were detected. Results Compared with NC group and TC group,the escape la-tency of M group increased significiantly and the number of crossing platform decreased significantly. There were in-creased levels hippocampus tissue,serum MDA level,hippocampal SOD activity and NO content. After supplemen-tation of Osthole,the escape latency significantly shortened in mice. The number of crossing platform was increased while the contents of MDA both in hippocampus and serum were decreased,and the SOD activity in hippocampus re-turned to normal. However,the level of NO in hippocampus was not decreased. Conclusion Osthole can protect the memory function of SD mice by reducing the the damage of hippocampal neurons through antioxidant stress.

Objective:To document any improvement in the breathing control of stroke survivors with dysarthria after practicing Liuzijue qigong.Methods:A total of 157 stroke survivors with dysarthria and abnormal respiration control were randomly divided into an observation group and a control group. Both groups were given traditional breathing training and basic articulation training (including articulatory organ training and speech training). The observation group also received training in Liuzijue qigong. It requires inhaling through the nose and exhaling through the mouth while producing the speech sounds xu, he, hu, si, chui and xi. The training lasted two weeks. Both groups were then evaluated using the modified Frenchay dysarthria assessment. Maximum phonation time, maximum counting ability and volume were also recorded as secondary indexes.Results:After the 2-week intervention, significant improvement was observed in the average scores on all of the indexes, with all of the observation group′s average scores except for volume significantly better than those of the control group. The average volume scores were significantly improved, but not significantly different.Conclusion:Supplementing basic articulation training with Liuzijue qigong can improve respiratory function and the speaking ability of stroke survivors with dysarthria. It is worthy of wider clinical application.

ObjectiveTo analyze the value of grey-scale reversed T₁-weighted （rT₁） MRI in the detection of structural lesions of the sacroiliac joint （SIJ） in patients with axial spondyloarthritis （ax-SpA）. MethodsFifty-two ax-SpA patients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospectively included. Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior， middle and posterior portion. Two radiologists reviewed independently three groups of MRI including T1-weighted imaging （T₁WI）， rT₁ and T₁WI + rT₁ images to evaluate the structural lesions like erosions， sclerosis and joint space changes in each of the 6 regions of the SIJ. One of the radiologist did the evaluation again one month later. CT images were scored for lesions by a third radiologist and served as the reference standard. Intra-class correlation coefficients （ICC） were calculated to test the inter- and intra-reader agreement for the assessment of SIJ lesions. A Friedman test was performed to compare the lesion results of MRI and CT image findings. We examined the diagnostic performance ［accuracy， sensitivity （SE） and specificity］ of different groups of MRI in the detection of lesions by using diagnostic test. A McNemar test was used to compare the differences of three groups of MRI findings. ResultsCT showed erosions in 71 joints， sclerosis in 65 and joint space changes in 53. Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of lesions， with the best agreement in T₁WI + rT₁. There were no difference between T₁WI + rT₁ and CT for the assessment of all lesions， nor between rT₁ and CT for the assessment of erosions and joint space changes （P>0.05）. T₁WI + rT₁ yielded better accuracy and SE than T₁WI in detection of all lesions （Accuracy _erosions： 90.3% vs 76. 9%； SE _erosions： 91.6% vs 76.1%； Accuracy _sclerosis： 89.4% vs 80.8%； SE _sclerosis： 84.6% vs 73.9%； Accuracy _{joint space changes}： 86.5% vs 73.1%； SE _{joint space changes}： 84.9% vs 60.4%； P<0.05）. rT₁ yielded better accuracy and SE than T₁WI in detection of erosions and joint space changes （Accuracy _erosions： 87.5% vs 76.9%； SE _erosions： 88.7% vs 76.1%； Accuracy _{joint space changes}： 85.6% vs 73.1%； SE _{joint space changes}： 83.0% vs 60.4%； P<0.05）. ConclusionsIn the detection of SIJ structural lesions in ax-SpA， rT₁ improves the diagnostic performance and T₁WI + rT₁ is more superior to others.