OBJECTIVE:To establish a method for the determination of4major caffeine metabolites and to discuss the significance of which in the evaluation of the activity of drug-metabolizing enzyme CYP1A2.METHODS:The caffeine metabolites in the urine like5-acetylamino-6-formamido-3-methyluric acid(AFMU),1-methyluric acid(1U),1-methylxanthine(1X)and1,7-dimethyluricacid(17U)were determined by RP-HPLC gradient elution method,the ratios of metabolins(AFMU+1X+1U)/17U was calculated,the frequency distribution histogram was drawn and the activity of CYP1A2was evaluated.RESULTS:The mean value of the ratio of the metabolins in the subjects was4.27,which was in normal distribution.CONCLUSION:The method is simple,accurate and rapid,which is suitable for the determination of caffeine metabolites in urine and the study of the activities of CYP1A2.

A 54-year-old female presented with indurated nodules and plaques on the left chest and back for 32 years.Skin examination showed little finger- to soybean-sized,slightly whitish indurated nodules with little mobility arising on skin-colored indurated plaques following Blaschko's lines on the left chest and back.The lesional skin was sclerotic and atrophic,and the lesions were distributed unilaterally.Serum levels of calcium,phosphate,alkaline phosphatase and parathyroid hormone were normal.Histopathological examination revealed fibrous scar with flake-like calcification.The diagnosis was idiopathic calcinosis cutis following Blaschko's lines.

Adult ; Herpesvirus 4, Human ; Humans ; Lymphohistiocytosis, Hemophagocytic ; virology ; Male ; Nose Neoplasms ; virology ; Paranasal Sinus Neoplasms ; virology

Photoacoustic imaging (PAI) is an emerging new biomedical imaging technique integrated with the high spatial resolution of ultrasonic imaging and high contrast of optical imaging for real-time molecular imaging.PAI is well-suited for in vivo cellular/molecular signatures imaging in cancer diagnosis, therapy management and treatment response, with a promising potential in clinical and translational medicine.This review summarizes the current state of PAI application research on cancer theranostics, and gives insights on future translational medicine research.

Objective:To investigate the relationship between EGFR mutations and pulmonary tuberculosis in lung adenocarcino-ma. Methods:We detected EGFR mutations in 506 patients with lung adenocarcinoma by PCR amplification and sequencing and ana-lyzed the relationship between the mutations observed and pulmonary tuberculosis. Survival analysis was performed using the Ka-plan-Meier method with log-rank tests. Result:A total of 218 patients showed EGFR mutations;of these patients, 25 had a clinical his-tory of pulmonary tuberculosis. Compared with lung adenocarcinoma patients with no history of tuberculosis, patients with a history of pulmonary tuberculosis showed higher incidence rates of EGFR mutations, especially of exon 21 (P=0.047, P=0.002). Higher incidence rates of EGFR mutations, especially of exon 21, were observed in patients with lung cancer and tuberculosis in the same lobe or the same side of the lung than in those who had lung cancer and tuberculosis in opposite sides of the lung (P=0.02, P=0.03). Survival analy-sis showed that adenocarcinoma patients with a history of pulmonary tuberculosis have 2-year survival rates lower than that of adeno-carcinoma patients with no history of the disease (P=0.039). In patients adenocarcinoma associated with tuberculosis patients without EGFR-TKIs treatment, the 2-year survival rates of EGFR mutation patients and those without EGFR mutation showed no statistically significant difference (P=0.948). At the same time, we got the same results in adenocarcinoma associated with tuberculosis patients with EGFR-TKIs treatment (P=0.425). Conclusion:Lung adenocarcinoma patients with a history of pulmonary tuberculosis have high-er incidence rates of EGFR mutations, and EGFR mutations are not related to disease prognosis.

BACKGROUND: Matrix metalloproteinase (MMP) is a kind of protease family, its activity can be inhibited by tissue inhibitor of metalloproteinase (TIMP), especially by TIMP-3.OBJECTIVE: To fully isolate and purify natural TIMP-3, and to create enzyme-linked immunoassay of TIMP-3.DESIGN: Single-sample observation SETTING: Central Laboratory of Shenyang Medical College MATERIALS: Human placenta from Department of Obstetrics & Gynecology, Fengtian Hospital Affiliated to Shenyang Medical College (Informed consent was obtained from the relatives of patients) and MMP-1 from Research Institute. Fuji Chemical Industries, Ltd.METHODS: This experiment was conducted in the Central Laboratory of Shenyang Medical College between March 2001 and May 2002. Firstly,4 mol/L urea Tris-buffer solution (pH8.0) was used to prepare homogenate solution of placenta. Secondly, homogenate solution was performed chromatography through CM52 positive ion-exchange resin and Sephacryl S200 gel filtration. Thirdly, relative molecular weight and purity were detected by SDS- polyacrylamidedel gel electrophoresis (SDS-PAGE).Fourthly, Western blotting was used to identify the characters of purified protein. Fifthly, the inhibitory rate of TIMP-3 to MMP-1 was measured with immumofluorescence method.MAIN OUTCOME MEASURES: ① The relative molecular mass of protein showed by PAGE. ② Results of Western blot. ③ The inhibitory rate of TIMP-3 for MMP-1. ④ The recovery rate of TIMP-3 following purification.RESULTS: ①The isolated and purified TIMP-3 from human placenta consisted of non-glycosylated and glycosylated protein, with relative molecular mass of 24 000 and 27 000, respectively. ② The inhibitory concentration of non-glycosylated and glycosylated TIMP-3 was 1.1×1010 mol/L and 1.2×1010 mol/L respectively to MMP-1. The inhibitory concentration of placenta-derived TIMP-3 was significantly higher than that of recombinant TIMP-3 for MMP-1. ③ The recovery rate of TIMP-3 was 23.4% following two-step chromatography.CONCLUSION: Extracellular matrix of human placenta-derived TIMP-3 consists of non- glycosylated protein and glycosylated protein; Two kinds of purified TIMPs-3 have remarkable inhibitory concentration for MMP-1, and significantly higher in comparison with recombinant metalloproteinase inhibitory factor-3.

Objective To investigate four methods for establishing animal models of human breast cancer bone metastasis. Methods Thirty-two female nude mice aged 4-6 weeks were divided randomly into four groups (n=8 in each group). 5×105 MDA-MB-231 cells were injected into the body via the left second mammary fat pads (group A), the tail veins (group B), the left heart ventricles (group C) and the left tibia marrow cavities (group D), respectively. Tumor formations in situ were recorded in group A. Deaths after the injection were recorded. The surviving nude mice 49 days after the injection were subjected to pathological examination to determine bone metastasis. Results The rate of tumor formation in situ of group A was87.5 %(7/8). One mouse in group C died after the injection of MDA-MB-231 cells. The bone metastasis rate in groups A, B, C and D was zero (0/8), 12.5 % (1/8), 71.4 % (5/7) and 100 % (8/8), respectively. There was statistically significant difference in the bone metastasis rate between group A and group C, group A and group D, group B and group C; and group B and group D. Conclusion Injections of tumor cells via the breast fat pads and tail veins were not suitablemethods to establish animal models of human breast cancer bone metastasis. The bone metastasis model could be established efficiently by injecting tumor cells into the left heart ventricles or the bone marrow cavity of nude mice.

Objective To observe and analyze the CT and MR imaging of the structures in the region of the jugular foramen (JF) on the base of thin-slice anatomic study. Methods Having been scanned by multislice CT and 1.5T MR scanner, two formalin-preserved adult cadavers were dissected into 1.0 mm thickness contiguous sections in transverse plane. Twenty cases without skull base and nasopharyngeal history received routine and post-contrast CT examinations with spiral and HQ mode. Twenty healthy volunteers received MR scanning, including SE T 1WI, FSE T 2WI, and 3D RF-FAST (3D Radio-Frequency Fourier Acquired Steady-State) sequences. Results JF region was divided into three levels, which included inner aperture, the jugular cavity, and the outer aperture. At the entrance of JF, there were glossopharyngeal canal and vagal canal, which wrapped the Ⅸ nerve and Ⅹ and Ⅺ nerves, respectively. CT images could display these canals in 20 cases (100%). Furthermore, the Ⅸ, Ⅹ, and Ⅺ nerves could be identified on different MR sequences. 17 cases (85%) were displayed on 3D RF-FAST, 14 cases (70%) on SE T 1WI, and 10 cases (50%) on FSE T 2WI, respectively. From the anterior to the posterior compartment within the JF cavity, the structures ranged as follows: the Ⅸ nerve, the inferior petrosal sinus, the Ⅹ and Ⅺ nerves, and the jugular bulb. These neuro-vessel structures could not be distinguished on CT, SE T 1WI, and FSE T 2WI images, except for 3D RF-FAST (16 cases, 80%). The outer aperture of JF was adjacent to the hypoglossal canal. The shape of JF outer aperture could be evaluated on CT images. On the oblique plane, which was parallel to the hypoglossal canal, the posterior cranial nerves could be detected to enter/exit the skull through the JF and hypoglossal canal separately. Conclusion The complement of CT and MR imaging would be helpful to distinguish the structures in the region of JF.

Objective To assess the effect of family doctor team care on morbidity of disabled elderly in home care.Methods Eighty six disabled elderly patients with home care in Shanghai Xujiahui community were enrolled from February 2014 to January 2015.The patients were randomly divided into intervention group and control group with 43 cases in each.In intervention group,the family doctor team provided long-term,comprehensive and integrated care,and in control group the conventional home care was provided.The rates of morbidity and readmission to hospital were documented during the 3,6 and 12 monthfollow-up,and compared between two groups.Results The incidence rates of bedsore,pneumonia and deep vein thrombosis in intervention group was significantly lower than those in control group [after 6 months:4.9％ (2/41) vs.28.9％(11/38),x2 =8.311;2.4％ (1/41) vs.21.1％ (8/38),x2 =6.769;2.4％ (1/41) vs.15.8％ (6/38),x2 =4.353,respectively;after 12 months:2.4％ (1/41) vs.42.1％ (16/38),x2 =18.374;4.9％ (2/41)vs.28.9％ (11/38),x2 =8.311;7.3％ (3/41)vs.28.9％ (11/38),x2 =6.328,respectively;all P ＜0.05].The number of cases with bedsore healing(6/7 vs.0,x2 =18.555)and pneumonia recovery[5/6 vs.4.3％ (1/23),x2 =18.092] was significantly more and that with pneumonia deterioration (0 vs.52.2％ (12/23),x2 =5.340)was significantly less in intervention group than those in control group (all P ＜ 0.05).More cases with deep vein thrombosis improved(1/3 vs.0,x2 =3.949) and less cases with deep vein thrombosis deteriorated(0 vs.8/11,x2 =5.091) in intervention group than those in control group (P ＜ 0.05).And both the readmission rate for home care patients [2.4％ (1/41) vs.36.8％ (14/38),x2 =15.175] and for patients with complications [1/12 vs.43.8％ (14/38),x2 =4.872] was much lower in intervention group than that in control group (both P ＜ 0.05).Conclusion The family doctor team care can reduce the risk of complications and readmission to hospital,and also can improve the quality of life of home care disabled elderly,as well as reduce the burden of family and society.

Background Econazole nitrate is not effective as an antifungal eyedrop because of its poor intraocular permeability,therefore changing the formulation of econazole nitrate to improve its intraocular permeability become a critical point in the treatment of intraocular fungal infection. Objective The present study was to observe the penetration of 0.5％ econazole nitrate nanoparticles in the corneas and aqueous humors following its topicaladministration. Methods Econazole nitrate nanoparticles were prepared by quasi-emulsion solvent diffusion.Characteristics and size of nanoparticles were examined with transmission electron microscope and laser scatteringmethod,respectively.Econazole nitrate nanoparticles drops (0.5％ )was topically administered in 27 New Zealandwhite rabbits bilaterally,and aqueous humor and corneas were obtained after the application of the eye drops for 5,15,30,45,60,90,120,180,240 minutes respectively to detect the concentration of econazole nitrate with highperformance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated with 3 p97pharmacokinetic computer software.The use of the animals followed the Regulation for the Administration of AffairsConcerning Experimental Animals by State Science and Technology Commission. Results The diameter of thenanoparticles was 50 nm with the round shape and encapsulation efficiency was 96.0％.Econazole nitrate nanoparticlesat the concentration of 0.5％ could be rapidly separated with other elements by HPLC with a lowest quantitativeconcentration of 0.1 mg/L.The mean recovery rates of econazole nitrate nanoparticles were 98.09％ in cornea and 99.66％ in aqueous humor,respectively after topical administration.The peak levels of econazole nitrate nanoparticles in cornea and aqueous humor were achieved at 5 minutes after application ( cornea:40.620 μg/g± 7.756 μg/g;aqueous humor:0.504 mg/L±0.153 mg/L),and its half-life( t1/2 )in cornea and aqueous humor was 23.5 minutes and 18.6 minutes,respectively. Conclusions Econazole nitrate nanoparticles at 0.5％ concentration can remain a feasible bioavailability in ocular tissue and therapeutic level in cornea and aqueous humor.