The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.
Algorithms ; Bayes Theorem ; Carbamazepine ; analogs & derivatives ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Models, Biological ; Monte Carlo Method ; Nonlinear Dynamics ; Regression Analysis ; Tacrolimus ; pharmacokinetics

Psoriasis is a non-infectious chronic inflammatory skin disease. It′s acknowledged that interleukin (IL)-17 signaling pathway dominantly drives the development of psoriasis. Recently, the role of neuro-immune axis in psoriasis has attracted widespread attention. Lidocaine, a local anesthetic, has ability to block the conduction of nerve impulses, while its therapeutic efficacy on psoriasis remains to be confirmed. Here, we evaluated the therapeutic efficacy of topical application of compound lidocaine cream (LIDO) on imiquimod (IMQ)-induced mouse psoriasis model. Animal welfare and experimental procedures follow the regulations of the Ethics Committee of China Pharmaceutical University. The psoriasis area and severity index (PASI) scoring was used to evaluate the severity of psoriasis-like symptoms. Hematoxylin-eosin staining was used to examine histopathological changes and epidermal thickness was measured. Ki67 immunofluorescence staining was used to evaluate the proliferation of keratinocytes. The relative mRNA expression of inflammatory cytokines (including Il17, Il22, Il23 and Il36) in skin was measured by real-time quantitative PCR. Results show that IMQ-induced increases in the PASI score, epidermal thickness, number of Ki67⁺ cells and the mRNA expression of inflammatory cytokines are significantly alleviated by topical application of LIDO, whose therapeutic efficacy is also better than that of the positive control drug calcipotriol. Our study suggests that LIDO could be used for psoriasis treatment.

Manganese-oxidizing microorganisms are able to oxidize soluble Mn(II) into insoluble Mn oxides. Such microorganisms are very useful in treatment of Mn-contaminated water. In this research, a Mn(II)- oxidizing bacterium Bacillus sp. MK3-1 was isolated from Mn-contaminated soil. This bacterium has high MnCl2 resistance with a MIC of 20 mmol/L. The results showed that it is able to oxidize and remove more than 96% of Mn(II) in the culture medium. The immobilized solid-embedding Bacillus sp. MK3-1can re- moved 87.12% of manganese contaminated water. The final concentration of MnCl2 after the treatment reached the national discharge standard level. Scan electron microscope observation showed that the pro- duced Mn oxides located on the cell surfaces of Bacillus sp. MK3-1. Energy dispersive spectrdmeter analy- sis indicated that the content of manganese of cell surfaces of Bacillus sp. MK3-1 was 19.60% (W/W). At last we amplified a 903 bp multicopper oxidase gene mnxG encoding the putative Mn(II)-oxidizing protein.The product of mnxG showed 86% identity to the reported multicopper oxidase.

Objective Toexploretheclinicalefficacyandtoxicityofintensitymodulatedradiationtherapy(IMRT)combined with high intensity focused ultrasound(HIFU) for inoperatable recurrent hepatic carcinoma after operation and TACE .Methods Total 60 patients with inoperatable recurrent hepatic carcinoma after operation and TACE were randomly divided into two group ,30 patients in observation group received IMRT and HIFU ,while 30 patients in control group received only IMRT .For both groups , the same radiotherapy technic was given with IMRT in 6 MV X‐ray ,the total dose was 54 -70 Gy/6 -7 weeks .In observation group ,HIFU was carried out concurrently with IMRT (5 days/week ,6-7 weeks) .Results The difference of the short‐term effi‐cacy between the observation group and the control group was statistically significant (P<0 .05) ,there was no significant difference in acute radioactive toxicity between the two groups (P>0 .05) .The one and two year overall survival rate 89 .9% ,78 .9% in obser‐vation group ,while 72 .8% ,36 .2% in control group ,the differnces were statistically significant (P<0 .05);the one and two year progression‐free survival rate were 85 .9% and 50 .9% in observation group ,while 64 .3% and 28 .1% in control group ,the differ‐ences between two groups were statistically significant (P<0 .05) .The medium survival time was 36 months in observation group , and 24 months in control group;the medium progression‐free survival was 27 months in observation group ,and 17 months in control group .Conclusion For recurrent unresectable or reject surgery after TACE in patients with primary hepatic carcinoma ,the efficacy of IMRT combined with HIFU treatment is effective ,the toxicity can be tolerated ,and has certain application value .

Objective To investigate the relationship between extracellular matrix metalloproteinase inducer (EMMPRIN), the upstream regulatory factor of matrix metalloproteinase (MMPs), and the formation of atherosclerosis and the clinical type of coronary heart disease. Methods A total of 223 patients were classified into four groups according to results of coronary angiography (CAG) and clinical data: STEMI group (65 patients with ST-segment elevation myocardial infarction), NSTE ACS group (42 patients with non-ST-segment elevation acute coronary syndrome), SAP group (75 patients with stable angina pectoris) and normal control group (41 patients of CAG-negative). The mean fluorescence intensity (MFI) of EMMPRIN on monocytes of peripheral blood (PBMCs)were examined by flow cytometry. MMP-9 in serum was measured with ELISA; high-sensitivity C-reactive protein (hs-CRP) in serum was measured with immune velocity method. Results The EMMPRIN MFI on PBMCs in SAP group, STEMI group and NSTE ACS group was higher than that in the normal control group (P<0.05 or P<0.01). The EMMPRIN MFI in STEMI group and NSTE ACS group was higher than that in SAP group (P<0.05 or P<0.01). The expression characteristic of EMMPRIN on the PBMCs was consistent with that of hs-CRP and MMP-9 in each group. The EMMPRIN MFI of the PBMCs had positive correlation with the level of MMP-9 and hs-CRP in serum (r=0.168,P<0.05;r=0.305,P<0.01). Conclusion EMMPRIN may has promotive effect on the formation of atherosclerosis and unstablility of coronary heart disease as an upstream regulatory factor of MMPs

AIM: To observe of cataract phacoemulsification and intraocular lens implantation in patients with postoperative tear film, and to explore its clinical significance.
METHODS: A total of 106 patients ( 140 eyes ) undergone phacoemulsification were randomly chosen. Subjective dry foreign body sensation were observed at six nodes of period 1d, 1, 2, 3wk, and 1mo. Corneal fluorescein ( FSC ) , basal tear secretion ( SIT ) and tear film break-up time ( BUT) were used to detect functional changes of the tear film. And the correlation between tear film stability and corneal sensitivity was analyzed.
RESULTS: Dry eye cumulative score of postoperative 1d, 1, 2wk was higher than preoperative ( t= 8. 53, P=0.000;t=6. 27, P=0. 000; t=9. 02, P=0. 000). There was no significant difference in dry eye cumulative score at postoperative 3wk, 1mo compared with preoperative ( t=1.91, P= 0. 824; t= 1. 27, P= 0. 069). Corneal epithelial fluorescein staining points of postoperative 1d, 1, 2wk were increased compared with preoperative (t=11. 64, P=0. 000;t=9. 61, P=0. 000; t=8. 87, P=0. 001). There was no significant difference in corneal epithelial fluorescein staining points of postoperative 3wk and 1mo compared with preoperative (t=2. 52, P=0. 746; t=1. 16, P=0. 094). Corneal sensitivity detection values of postoperative 1d, 1, 2wk were significantly higher than that of preoperative (t=9.61, P=0.000;t=9.27, P=0.000;t=11.39, P=0.024), and there was no difference postoperative 3wk and 1mo compared with preoperative (t=1. 19, P=0. 562;t=2. 17, P=0. 501).
CONCLUSION: Phacoemulsification with intraocular lens implantation will reduce the tear film stability in the short term, but after a long rest will be improved to a certain extent.

Objective To observe the therapeutic effects of astragalus membranaceus parenteral solution on the elders with cerebral infarction and its influences on patients' nerve function,activities of daily living and hemorheology. Methods Ninety-two patients diagnosed with cerebral infarction who were older than 60 years were randomly divided into astragalus membranaceus group(n=50) and control group (n=42). The two groups were treated with conventional therapy. But based on conventional therapy, astragalus membranaceus parenteral solution (30 mL, 2 g/mL) added into 5%glucose saline was used in the astragalus membranaceus group once daily for 4 weeks. The clinical therapeutic effects, nerve function, ability of activities of daily living and hemorheology were compared between the 2 groups. Results The total effective rate of the astragalus membranaceus group was not significantly different from that of the control group (P＞0.05), while the excellent rate and therapeutic effects of the astragalus membranaceus group was significantly higher than that of the control group (P＜0.05). Compared with control group, the scores of the neurologic impairment were decreased significantly(P＜0.05), Barthel index was increased significantly (P＜0.05), whole blood viscosity, hematocrit and fibrinogen were decreased significantly (P＜0.05) in the astragalus membranaceus group. Conclusions Astragalus membranaceus parenteral solution can improve nerve function and the ability of activities of daily living of the gerontal cerebral infarction patients.

This study was aimed to investigate the chemical constituents from the leaves of Vitex negundovar. cannabifolia. Column chromatography including silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC were used to separate and purify the chemical constituents, and the structures were elucidated on the basis of physicochemical properties, MS and NMR spectroscopic data. As a result, 11 compounds were isolated from the ethyl acetate extract of V. negundo var. cannabifolia, and identified as apigenin (1), penduletin (2), chrysosplenol-D (3), quercetin (4), 1,4-dihydroxy-3R,5R-dicaffeoyloxy cyclohexane carboxylic acid (5), maeranthoin F (6), capsidiol (7), caryolandiol (8), β-sitosterol (9), p-hydroxybenzonic acid (10), and β-daucosterin (11). It was concluded that compounds 5 8were firstly isolated from the plants of Vitex genus, and compounds 1 and 4 were isolated from V. negundovar. cannabifolia for the first time.

Objective To examine the effects of different pre-treatment nutritional status and inflammatory markers on acute adverse reactions in esophageal cancer patients during concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy.Methods The acute adverse reactions of 338 eligible esophageal cancer patients who received concurrent IMRT and chemotherapy in our hospital from 2006 to 2014 were reviewed.The effects of different pre-treatment nutritional status, such as body mass index level (BMI), albumin level (ALB), total lymphocyte count (TLC), the presence or absence of anemia, and inflammatory indicators including neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), on acute adverse reactions in the patients were examined.Data were analyzed using the chi-square test with continuity correction and logistic regression analysis.Results The incidence rate of malnutrition in the patients based on their nutritional status was 5.62%-54.14%.The incidence rate of grade≥2 acute radiation esophagitis (RE) was significantly higher in the low ALB group than in the normal ALB group (P=0.000).The incidence rate of adverse reactions in the hematologic system increased as TLC decreased (P=0.006), but the incidence rate of acute radiation pneumonitis (RP) was reduced as TLC decreased (P=0.001).In addition, the incidence rate of grade ≥2 acute RE was significantly higher in the anemia group than in the non-anemia group.Inflammatory marker analysis demonstrated that the incidence rate of acute RE was significantly higher in the high NLR group and high PLR group than in the low NLR group and low PLR group (P=0.000 and P=0.024, respectively).Logistic regression analysis of nutritional status and inflammatory markers showed that TLC was an independent risk factor for acute adverse reactions in the hematologic system (P=0.001), and ALB and PLR were independent risk factors for acute RE (P=0.017 and P=0.011,respectively).Conclusions Nutritional status and inflammatory markers are associated with concurrent chemoradiotherapy-induced acute adverse reactions in esophageal carcinoma patients, and hence may be valuable indicators of acute adverse reactions during treatment.In addition, nutritional treatment and support care should be actively provided to the patients to prevent the development of acute adverse reactions during treatment.

Acute Kidney Injury ; etiology ; Adult ; Burns, Chemical ; complications ; surgery ; Chromates ; toxicity ; Humans ; Male ; Young Adult