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

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.

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.

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.

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

OBJECTIVETo investigate the pathogenesis of globozoospermia, fertilization ability of round-headed sperm, and the application value of assisted oocyte activation in intracytoplasmic sperm injection (ICSI) for the wives of glohozoospermia men.

METHODSWe collected oocytes from the wives of 2 globozoospermia patients and randomly divided them into two groups after ICSI to receive calcium ionophore A23187-activation and conventional treatment, respectively. We reviewed the relevant literature published at home and abroad, and discussed the etiology of globozoospermia, fertilization ability of round-headed sperm, and treatment options for this disease.

RESULTSQuality embryos were obtained in the A23187-activation group while no fertilized oocytes, oocyte cleavage, quality embryos, or blastular formation were found in the conventional treatment group. Both women achieved pregnancy and gave birth to healthy neonates after transfer of the quality embryos from the A23187-activation group.

CONCLUSIONCalcium ionophore A23187 can be applied to ICSI for the wives of globozoospermia men and bring about desirable clinical outcomes. Meanwhile, attention should be paid to its safety.

Calcimycin ; therapeutic use ; Calcium Ionophores ; therapeutic use ; Female ; Humans ; Infertility, Male ; drug therapy ; Male ; Oocytes ; Pregnancy ; Sperm Injections, Intracytoplasmic ; Spermatozoa ; abnormalities

To study the protective effect of Danshen Tongluo capsule on rat hearts in the myocardial infarction (MI) model. After being fed with high fat diets for one month, the SD rats were randomly divided into the sham group and the model group according to the left ventricular ejection fraction (EF). The MI model group was duplicated by ligating coronary artery and then divided into five groups: the model group, the positive control group (model + captopril), the small dose group (model + Danshen Tongluo), the medium dose group (model + Danshen Tongluo) and the high dose group (model + Danshen Tongluo). Four weeks later, changes in myocardium ultra-structure were observed by hemodynamics, cardiac ultrasound and electron microscope. The results showed: (1) All doses of Danshen Tongluo capsule could significantly reduce the left ventricular end diastolic pressure (LVEDP) (P <0.01), increase the maximum internal pressure of the left ventricle (+ dp/dtmax), and lower the drop rate of left ventricular pressure (- dp/dtmax), with statistical significances in medium and high dose groups; (2) The B ultrasound results showed increase in EF and left ventricular shortening fraction (FS) in all dose groups of Danshen Tongluo capsule; (3) The medium dose group showed significant decrease in myocardial infarction index (P <0.01) and injured and fractured myofilament and sarcomere of ischemic myocardium in myocardial ultra-structure; All of Danshen Tongluo capsule-treated groups revealed reduction in myocardial injury and myocardial infraction area. The study preliminarily proves that Danshen Tongluo capsule can improve hemodynamic function, and has a protective effect on myocardial ischemia.
Animals ; Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Myocytes, Cardiac ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left ; drug effects