Objective To observe changes of dynamic functional connectivity(dFC)of brain networks in different stages of Parkinson disease(PD).Methods Totally 52 early-stage PD patients(early PD group),36 late-stage PD patients(late PD group)and 38 healthy controls(HC group)were prospectively enrolled,and resting-state functional MRI were performed.The sliding window,independent component analysis and k-means clustering were used to extract dFC intensity and temporal properties,including fractional windows,dwell time and transition frequency.Results Network connectivity patterns within and between visual network(VIS),sensorimotor network(SMN),default mode network(DMN),cerebellar network(CB)and cognitive executive network(CEN)were altered in PD patients.Four dFC states were identified,in which connections between components in states Ⅰ and Ⅱ were compact,while in states Ⅲ and Ⅳ were sparse.The fractional window and dwell time of late PD group,early PD group and HC group successively increased under state Ⅱ,but successively decreased under state Ⅲ(all P＜0.05).Under state Ⅰ and Ⅳ,no significant difference of fractional window nor dwell time was found between early PD group and late PD group(both P＞0.05),and the above indexes under state Ⅰ were both lower than those in HC group(all P＜0.05),the fraction window under state Ⅳ was higher than that in HC group(both P＜0.05).Conclusion The temporal properties of dFC in PD patients were altered,characterized by increased tendency toward segregated states.Furthermore,fractional windows and dwell time were associated with PD disease stages,suggesting that dFC parameters might serve as novel biomarkers for assessing clinical progression of PD.

Objective To observe changes of dynamic functional connectivity(dFC)of brain networks in different stages of Parkinson disease(PD).Methods Totally 52 early-stage PD patients(early PD group),36 late-stage PD patients(late PD group)and 38 healthy controls(HC group)were prospectively enrolled,and resting-state functional MRI were performed.The sliding window,independent component analysis and k-means clustering were used to extract dFC intensity and temporal properties,including fractional windows,dwell time and transition frequency.Results Network connectivity patterns within and between visual network(VIS),sensorimotor network(SMN),default mode network(DMN),cerebellar network(CB)and cognitive executive network(CEN)were altered in PD patients.Four dFC states were identified,in which connections between components in states Ⅰ and Ⅱ were compact,while in states Ⅲ and Ⅳ were sparse.The fractional window and dwell time of late PD group,early PD group and HC group successively increased under state Ⅱ,but successively decreased under state Ⅲ(all P＜0.05).Under state Ⅰ and Ⅳ,no significant difference of fractional window nor dwell time was found between early PD group and late PD group(both P＞0.05),and the above indexes under state Ⅰ were both lower than those in HC group(all P＜0.05),the fraction window under state Ⅳ was higher than that in HC group(both P＜0.05).Conclusion The temporal properties of dFC in PD patients were altered,characterized by increased tendency toward segregated states.Furthermore,fractional windows and dwell time were associated with PD disease stages,suggesting that dFC parameters might serve as novel biomarkers for assessing clinical progression of PD.

Insomnia has become a common central nervous system disease. At present, the pathogenesis of insomnia is not clear. Animal models can help us understand the pathogenesis of the disease and can be used in transformational medicine. Therefore, it is very necessary to establish an appropriate model of insomnia. Clinical data show that insomnia patients with high levels of thyroxine and often accompanied by cardiovascular problems, a common mechanism underlying all of these physiological disruptions is the sympathetic nervous system. Combined with the characteristics of chronic onset of clinical insomnia, an insomnia model induced by long-term intraperitoneal injection of thyroid hormone has been created in our laboratory. In this paper, the insomnia-like state of the model was evaluated based on three validity criteria. Face validity has been demonstrated in metabolism, the Morris water maze, electrocardiogram (ECG) and electroencephalogram (EEG). Structure validity has been proved by the results of targeted metabolomics. After treatment with diazepam, a commonly used clinical anti-insomnia drug, the above physiological and pathological disorders were reversed. The results of comprehensive analysis show that the established thyrotoxicosis-associated insomnia model meets the validity requirement to establish an appropriate animal model of insomnia. The model presented in this article might help to study pathogenetic mechanisms of clinical insomnia, as well as to test promising methods of insomnia treatment.

A 65-year-old male patient was treated with pyridostigmine bromide tablets (30 mg thrice daily), azathioprine tablets (75 mg twice daily), and prednisone acetate tablets (15 mg once daily) for myasthenia gravis. Two months later, the patient developed abdominal pain, nausea, and vomiting. The laboratory tests showed the blood lipase (LPS) 909 U/L and the urine amylase (AMS) 3 838 U/L. The results of abdominal ultrasonography and imaging examination were consistent with the manifestations of pancreatitis. Above-mentioned drugs were not stopped and the patient was treated according to the conventional treatment regimen of acute pancreatitis. However, the symptoms did not improved significantly. On the 11th day after the onset of the disease, he received subcutaneous infusion of octreotide injection, intravenous infusion of pantoprazole sodium for injection, oral metronidazole, and supportive treatments such as fluid supplement and correction of water electrolyte disorders. The laboratoty tests the next day showed that the patient′s blood LPS was 3 332 U/L and AMS was 139 U/L. The acute pancreatitis was considered to be related to azathioprine tablets. Then the drug was stopped and other treatments were continued. The patient′s symptoms improved quickly. Four days later, LPS was 546 U/L and AMS was 49 U/L.

A 65-year-old male patient was treated with pyridostigmine bromide tablets (30 mg thrice daily), azathioprine tablets (75 mg twice daily), and prednisone acetate tablets (15 mg once daily) for myasthenia gravis. Two months later, the patient developed abdominal pain, nausea, and vomiting. The laboratory tests showed the blood lipase (LPS) 909 U/L and the urine amylase (AMS) 3 838 U/L. The results of abdominal ultrasonography and imaging examination were consistent with the manifestations of pancreatitis. Above-mentioned drugs were not stopped and the patient was treated according to the conventional treatment regimen of acute pancreatitis. However, the symptoms did not improved significantly. On the 11th day after the onset of the disease, he received subcutaneous infusion of octreotide injection, intravenous infusion of pantoprazole sodium for injection, oral metronidazole, and supportive treatments such as fluid supplement and correction of water electrolyte disorders. The laboratoty tests the next day showed that the patient′s blood LPS was 3 332 U/L and AMS was 139 U/L. The acute pancreatitis was considered to be related to azathioprine tablets. Then the drug was stopped and other treatments were continued. The patient′s symptoms improved quickly. Four days later, LPS was 546 U/L and AMS was 49 U/L.

The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.

The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.

OBJECTIVE:To investigate the compatible stability of isosorbide mononitrate(ISO) and dopamine(DA) hydrochloride in glucose injection.METHODS:The contents of ISO and DA in the mixture of ISO and DA at 20 ℃ and 30 ℃ under natural illumination within 24 h,and the pH and appearance of the mixture were monitored.RESULTS:No significant change was noted in the concentrations of ISO and DA,the pH and the appearance of the mixture at 20 ℃ or 30 ℃.CONCLUSION:The mixture of ISO and DA in glucose injection was stable at 20 ℃ or 30 ℃,but which should be used up within 18 h after mixing.

Purpose　 The aim is to establish the HPLC method for the determination of Fluoro-deoxyuridine in plasma.Methods　The Chromatography conditions include: Chromatography column: Nova-pak C18(3.9mm×150mm,4μm), mobile phase: 0.05mol/L sodium phosphate monobasic -methanol-water(0.5∶7∶92.5)， UV detection at 260nm， FUDR was extracted with ethyl acetate. Results　The average recoveries were 96.4%，96.5%，97.8% for concentration 0.23、1.67、20.0μg/ml (n=5).The corresponding reproducibility were RSD 1.61%, 1.98%, 3.17% respectwely for iner-day and RSD 3.56%, 1.90%, 2.63% for the intra-day(n=5). The FUDR concentration was linear with a correlation coefficient of 0.999　4 over the range of 0.099～20.0μg/ml. Conclusion　 The method was sensitive and accurate and suitable for pharmacokinetics and bioavailability study of FUDR.

Objective: To evaluate the application of frontal flap in reconstructing the defect of nose, the clinical data of 12 cases were reported. Methods: Twelve patients with nasal skin cancers undertaking radical dissection of tumor accompanied frontal flap reconstructing one stage were reviewed retrospectively.Results: The overall following\|up rate was 100%, 10 of these patients curled slightly after reconstructing the nose, but influence of the nasal outline was little. Two cases were recurrent locally, one occurred 24 months after operation, the other occurred 38 months. Both of them received radiotherapy. Malformation arised after radiotherapy. The total successful rate of reconstruct nasal outlook was 83.33%, the 3\|year locally recurrent rate was 8.33%,5\|year survival rate ws 100%, 5\|year survival rate without tumor was 83.33%.Conclusion:The blood supply of frontal flap is abundance;healing up soon after reconstruction; the manipulation of surgery is simple and safe. It is worth applying this operation generally in clinical practice.