AIM　To prepare naftopidil bioadhesive sustained-release capsule and study their pharmacokinetics and relative bioavailability in the dog. METHODS　Bioadhesive polymers such as hydroxypropyl methylcellulse (HPMC) and Carbopol 934 (CP 934) were used in capsule prescriptions. Naftopidil capsule and two formulations of bioadhesive sustained-release capsules (I and II) were given to five healthy male dogs in a cross-over test. The naftopidil concentrations in plasma were determined by a newly developed HPLC method and the pharmacokinetic parameters as well as the relative bioavailability were measured. RESULTS　The C0→∞, Cmax and Tmax of naftopidil capsule was (3728±573) h*ng*mL-1, (697±94) ng*mL-1 and (1.2±0.5) h. These parameters of bioadhesive sustained-release capsule I and II, respectively, were (5518±391) h*ng*mL-1 and (5636±427) h*ng*mL-1; (468±61) ng*mL-1 and (512±72) ng*mL-1; both (4.0±0.7) h. Results from statistics showed that there were significant difference between bioadhesive formulations and the non-bioadhesive one in C0→∞, Cmax and Tmax. The bioadhesive formulations and the non-bioadhesive one were not bioequivalent, the relative bioavailability of the two bioadhesive sustained-release capsules were respectively 150%±14% and 154%±23% when compared with the non-bioadhesive capsule. CONCLUSION　It is much improving bioavailability of naftopidil by using bioadhesion.

Objective To evaluate the effect ofcytochrome P450 isoenzyme subfamily 2C19 (CYP2C19)gene polymorphism on the clopidogrel antiplatelet therapy in cirrhosis patients after receiving transjugular intrahepatic portosystemic shunt (TIPS).Methods The clinical data of 171 cirrhosis patients,who were treated with TIPS during the period from January 2013 to December 2014,were retrospectively analyzed.During operation both the portal vein and the elbow vein blood samples were collected and sent for CYP2C19 gene testing.After TIPS,clinical follow-up checkup was made once every 3 months.The gene detection results and clinical follow-up findings were comparatively analyzed.Results A total of 110 patients,who had not received blood transfusion before TIPS and who had regularly taken clopidogrel antiplatelet therapy after TIPS were enrolled in the study.The mean time to take clopidogrel was 192.4 days (31-517 days),and the gene detection results of portal vein and elbow vein were quite consistent.CYP2C19 genotype of *1/*1 was found in 49 patients (44.5％),CYP2C19 genotype of *1/*2 in 27 patients (24.6％),CYP2C19 genotype of *1/*3 in 18patients (16.4％),CYP2C19 genotype of *2/*2 in 11 patients (10.0％),CYP2C19 genotype of *2/*3 in 3patients (2.7％),and CYP2C 19 genotype of *3/*3 in 2 patients (1.8％).Following-up examinations showed that the incidence of shunt dysfunction in patients carrying slow metabolic gene was 87.5％ (14/16),which was significantly higher than that in patients carrying moderate metabolic gene (20.0％,9/45;x2=22.9,P=0.006)as well as in patients carrying fast metabolic gene (8.2％,4/49;x2=37.91,P=O.O00 1).Multivariate analysis of Cox regression model indicated that CYP2C19 slow metabolic gene variation was an important predictive factor for shunt dysfunction (95％CI:1.80-9.03,P=O.O00 7).Conclusion CYP2C19 slow metabolic gene variation,including genotype of *2/*2,*2/*3 and *3/*3,is an important factor that can influence the efficacy of clopidogrel treatment after TIPS.Preoperative CYP2C19 gene detection results can provide useful information,which is very helpful in making an effective and reliable anti-platelet treatment plan for patients after TIPS.

Nuclear magnetic resonance (1H-NMR) fingerprint of Rhodiola rosea medicinal materials was established, and used to distinguish the quality of raw materials from different sources. Pulse sequence for water peak inhibition was employed to acquire 1H-NMR spectra with the temperature at 298 K and spectrometer frequency of 400.13 MHz. Through subsection integral method, the obtained NMR data was subjected to similarity analysis and principal component analysis (PCA). 10 batches raw materials of Rhodiola rosea from different origins were successfully distinguished by PCA. The statistical results indicated that rhodiola glucoside, butyl alcohol, maleic acid and alanine were the main differential ingredients. This method provides an auxiliary method of Chinese quality approach to evaluate the quality of Rhodiola crenulata without using natural reference substances.
Magnetic Resonance Spectroscopy ; methods ; Principal Component Analysis ; Rhizome ; chemistry ; Rhodiola ; chemistry

Objective To evaluate the clinical feasibility of localization CT enhanced image replacing plain CT scan image for target delineation and dose calculation.Methods Forty cases of NPC were collected and divided into two groups with different concentrations of contrast agents.The contours of planning target volume (PTV) and organs at risk (OARs) of each case were delineated in the plain scan image,and the contours of PTV and OARs were copied to the enhanced image.Two plans based on the plain scan image and the enhanced image were designed in the planning system of Eclipse.The dose distribution and OARs and MU were compared between the groups.Results No statistical differences were found in the dosimetry of PTV,OARs and MU (P＞0.05).Conclusion The image intensifier has little effect on the dose calculation of Eclipse for NPC.In the radiotherapy for NPC,the localization CT enhanced image can be used to replace the plain CT scan image for target delineation and dose calculation.

The study aims to solve the instability problem of methylphenidate (MPH) in plasma, and establish a LC-MS/MS method for simultaneous determining of MPH in human plasma. The stabilities of MPH in different media were studied, and the degradation characteristics of MPH in these media were also investigated by HPLC and LC-MS/MS. To a 200 microL aliquot of freshly collected plasma sample, 10 microL 2% formic acid was added immediately to prevent the hydrolysis of MPH in human plasma samples. Chromatographic separation was performed on a Sapphire C18 column using the mobile phase of methanol - 5 mmol.L-1 ammonium acetate buffer solution containing 0.1% formic acid (46 : 54). MPH was quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring. The detection used the transitions of protonated molecules at m/z 234.2-->84.1 for MPH and m/z 260.3-->183.1 for propranolol (IS), separately. The intra- and inter-assay precisions were all below 5.0%. The accuracies were all in standard ranges. The linear calibration curve was obtained in the concentration range of 0.035-40 ng.mL-1. The methods fulfilled the demand. The method was used to determine the concentration of MPH in human plasma after a single dose of 36 mg MPH tablet to 6 healthy Chinese volunteers. The method is suitable for the precisely determination of MPH and for pharmacokinetic study of MPH in human plasma.
Adult ; Central Nervous System Stimulants ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drug Stability ; Humans ; Male ; Methylphenidate ; blood ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; Young Adult

Objective:To study the relationship between the expression of carnitine palmitoyltransferase 1α (CPT1α) and progression of renal interstitial fibrosis and chronic kidney disease (CKD), and to evaluate the value of CPT1α as a biomarker in pathological diagnosis of renal interstitial fibrosis and CKD.Methods:As a retrospective cohort study, information of CKD patients dignosed with tubulointerstitial fibrosis by renal biopsy and receiving follow-up from March 1, 2010 to July 30, 2017 in the Second Affiliated Hospital of Nanjing Medical University were collected. Renal tissues were stained by immunohistochemistry to detect the expression of CPT1α protein and then divided into three groups according to the quartile of proportion of CPT1α positive staining cells, including group Q1(>67.89%), group Q2(49.84%-67.89%) and group Q3(<49.84%). The degree of renal interstitial fibrosis was measured by Masson staining and lipid deposition was represented by Bodipy staining. Messenger RNA of CPT1α and collagen as well as other extracellular matrix genes were detected by real time-PCR. Relationships between proportion of CPT1α positive staining cells and renal interstitial fibrosis and renal function were analyzed by linear regression analysis. The relationship between CPT1α positive cell number ratio and renal function progression was measured by Pearson correlation analysis and generalized linear model. The effect of lipid-lowering medicine on renal function of CKD patients was analyzed by paired comparative analysis.Results:Ninety patients with CKD were included in this study. Renal interstitial fibrosis and lipid droplets deposition area increased in Q2/Q3 group compared with Q1 group by Masson and Bodipy staining (all P<0.05). Messenger RNA level of extracellular matrix-related proteins increased in Q2/Q3 group by real time-PCR than those of Q1 group (all P<0.05). Linear regression analysis showed that fibrosis area was negatively correlated with the proportion of CPT1α positive staining cells ( r=-0.309, P<0.01). The baseline expression of CPT1α in renal issues was negatively related with serum creatinine (Scr) ( r=-2.801, P<0.001), positively related with estimated glomerular filtration rate (eGFR) ( r=1.240, P<0.001). After a medium follow-up of 3.47 years, CPT1α positive cell number ratio was positively correlated with eGFR change rate by Pearson analysis ( r=0.220, P=0.038). Paired stratified analysis showed that taking lipid-lowering medicines attenuated the decrease of eGFR in Q2 group and Q3 group but not in Q1 group (both P<0.05). Conclusions:The decline of CPT1α in renal tissues of CKD patients is associated with the increase of Scr, the decrease of eGFR and renal interstitial fibrosis. CPT1α is a promising molecular marker to evaluate the degree of renal fibrosis and the progression of CKD.

vides com-parable efficacy with medical castration in regard of decreasing PSA level and reducing prostate vol-ume. It is a safe and well tolerated treatment option as well.

Objective To discuss the preservation and clinical significance of petrosal vein in microsurgical operation of acoustic neuroma. Methods 147 patients with acoustic neuroma were operated, with internal decompression of the tumor firstly then dissected the tumor with surrounding structures, the petrosal vein were protected well in 143 cases and failed to protect in 4 cases. Results No hemorrhagic infarction in cerebellar was observed in 143 cases with intact petrosal vein. One case occurred with extensive cerebellar edema, which has gait disturbance after 18 months follow-up. The other three cases occurred with vein infarction and hemorrhagic edema after petrosal vein damage. One was dead and the other two were recovered well after decompression of posterior cranial fossa. One has no significant neurological deficit after 33 months follow-up, while the other has difficulty in line walking after 12 months follow-up. Conclusion Petrosal vein should be well protected in the operation of acoustic neuroma, the decompression of posterior cranial fossa should be considered if petrosal vein failed to protect.

Objective:To study the effect of microsurgery for parasellar menningiomas and to analyze the impact factors of recurrence. Methods:Clinical and follow-up data in a consecutive series of 134 patients with parasellar meningiomas were retrospectively analyzed. Results:A total of 109 patients (81.3%) had radical removal (Simpson grade I and II), and 116 patients were followed up for an average period of 81.6 months. The mean quality of life score (KPS) was 91.9, 90 patients regained full daily activity and 16 patients were able to take care of themselves. Oculomotor paralysis occurred in 7 patients, epilepsy in 8, and another 9 patients suffered hemispheral paralysis. Tumor recurred atfer the radical removal in 12 out of the 96 follow-up patients (12.5%). Tumor progressed atfer subtotal removal in 12 out of the 20 follow-up patients (60%). Tumor with cavernous sinus (CS) invasion had significantly higher risk of recurrence campared with non-CS invasion (P=0.043). The recurrence rate increased with the pathological grade (P<0.01). Conclusion:Patients with parasellar meningiomas undergoing microsurgical resection may have a good long-term function outcome. For most patients, total removal by microsurgery is the ifrst choice. Careful follow-up is needed if tumor invaded the CS and radiosurgery is proposed for WHO grade 1 and 2.

BACKGROUND:The effects of engineered bone scaffold containing seeding cels with different shapes to repair bone defect are varied, while the loaded cellquantity is the important factor influencing the curative effect, but which is rarely reported. OBJECTIVE:By preparing self-made corrugated tissue-engineered bone scaffold and other three forms of bone tissue engineering scaffolds, to study the quantity of loaded cels on different scaffolds and osteogenesis of corrugated tissue-engineered bone scaffold so as to discuss the advantages and features of self-made corrugated tissue-engineered bone scaffold. METHODS: (1) Experimentin vitro: There were four kinds of scaffolds with the same volume and samples: calcium phosphate cement (CPC) corrugated surface scaffold group, smooth surface scaffold group, cylindrical scaffold group and porous cylindrical scaffold with holow tubes group, in which the latter three groups are control ones. A certain volume with same density of rabbit bone marrow mesenchymal stem cels (BMSCs) suspension after osteogenesis induction was seeded onto the scaffolds. After incubation, culture, digestion and colection, cellquantity was counted, absorbance value was finaly detected and cellactivity was proofed by alkaline phosphatase and alizarin red staining. (2) Experimentin vivo: New Zealand rabbits were randomly and equaly divided into recombinant human bone morphogenetic protein-2 (rhBMP-2)/CPC/BMSCs corrugated scaffold group, pure CPC corrugated scaffold group and cancelous bone implant group. Three kinds of scaffold implants with the same volume were inserted into the area between rabbit’s L5, 6 transverse processes bilateraly. At 4, 8, 12 weeks postoperatively, gross and histological observation was performed. RESULTS AND CONCLUSION:(1)Experimentin vitro: The drip of cellsuspension steadily stayed on the surface of corrugated scaffold because of corrugated shape groove and the surface tension of the liquid. The amount of cels per sample digested down from the CPC corrugated surface scaffold was significantly more than that from the other three groups (P < 0.05), while the absorbance values did not differ (P > 0.05). (2) Experimentin vivo: At each time point the osteogenesis quantity of rhBMP-2/CPC/BMSCs corrugated scaffold group was more than that of the pure CPC corrugated scaffold group (P < 0.05), while there was no difference from the cancelous bone implant group (P > 0.05). These findings indicate that the characteristics of the self-made corrugated engineered bone scaffold are beneficial to seed cellloading, which supports a large number of osteogenesis and provides feasibility to promote the healing of segmental bone defects.