OBJECTIVE:To improve the synthesis technology of sorafenib tosylate (Ⅰ). METHODS:The intermediate N-methyl-(4-chlorpyridin-2-yl)carboxamide(Ⅳ)was obtained by chlorination and amidation with 2-picolinic acid as the starting com-pound. Meanwhile,N-[4-chloro-3-(triflouromethyl)phenyl]-N′-(4-hydroxyphenyl)urea (Ⅶ) was prepared from aminophenol and 4-chloro-3-trifluoromethyl phenyl isocyanate,which was obtained from 4-chloro-3-(trifluoromethyl)aniline(Ⅴ)by reaction with initiator triethylamine. Sorafenib tosylate was synthesized from Ⅳ and Ⅶ with potassium tert-butoxide by condensation and salt for-mation. The target compound was characterized by 1H-NMR. RESULTS:The target compound was confirmed as Ⅰ,with the over-all yield of 74% [based on 4-chloro-3-(trifluoromethylanilin)]. The purification of chromatogram was 94%. Optimized technology improves yield and simplifies multi-step intermediate decompression,distillation and purification process;the application of initia-tor shortens the duration of reaction. CONCLUSIONS:Ⅰ is prepared successfully,and raw material can be obtained easily and is easy to operate with high yield.

Adult ; Device Removal ; methods ; Ductus Arteriosus, Patent ; Heart Septal Defects, Atrial ; therapy ; Humans ; Male

0.05). Positive expression of 2 or all 3 markers of neuroendocrine cell was detected in all 16 samples; negative expression of all 5 peptide hormones was observed in only 25% of samples. At a mean follow-up of 44.2 months (range 4 months-7 years ), the mean time from resection to relapse or metastasis was 29.8 months; 7 cases survived more than 5 years, of which 2 have survived for 7 years. Two cases, who subjected non-operative treatment, survired 39,61 months, respectively.Conclusions Clinical manifestations of NPNEC are non-specific. Only a few tumors in NPNEC patients do not yield peptide hormones. Treatment of NPNEC (including patients with liver metastasis) with aggressive surgical resection followed by interventional methods can result in excellent overall long-term survival.

AlM: To find out the weaknesses of the cultivation of the Chinese ophthalmology physicians and the gap between Chinese and the international ophthalmology physicians, so that provide the advice on the future cultivation of the Chinese ophthalmology physicians.
METHODS: The passrate of the 2013 lCO examinations taken by worldwide examiners by common statistical methods was analyzed.
RESULTS:The results indicated that the test scores of Chinese candidates' were lower than that of the international average level, there was a obvious gap existed between Chinese and other countries' ophthalmology physicians. lt showed that Chinese candidates were not quite adaptable to this examination, basic science and clinical level needed to be improved.
CONCLUSlON:lt may shows that the effects on the mid-anaphase of our country's ophthalmology residency training are not so good, which area we should pay more attentions.

To investigate the utility of optomap panoramic 200Tx in screening fundus disease among the patients after cataract surgery.
●METHODS: From November 18 th to December 31st , 2013 all 146 post- cataract surgery patients were recruited. All non - mydriatic fundus images were taken with the optomap panoramic 200Tx and were diagnosed by one masked retinal specialist. Non - mydriatic direct ophthalmoscope exam and mydriatic slit-lamp lens exam were also done by other two masked specialists. Comparisons of the three methods were made.
●RESULTS: Among 146 patients ( 161 eyes), 40 eyes (24. 8%) of retinal lesions was detected by non-mydriatic direct ophthalmoscope exam, 59 ( 36. 7%) by non -mydriatic optomap 200Tx exam, and 61 (37. 9%) by slit-lamp lens exam. Nine eyes ( 5. 6%) needed medical intervention immediately. Results of optomap 200Tx exams and slit - lamp lens exams were similar without statistically significant difference ( P > 0. 05), better than direct ophthalmoscope exam ( P < 0. 05) with statistically significant difference.
● CONCLUSlON: Opacification of the refractive medium makes thorough fundus examination impossible. So post-operative fundus examination is highly necessary and should be a routine. Optomap panoramic 200Tx, which shows no statistically difference from mydriatc slit- lamp lens exam, is a convenient and feasible method in discovering fundus pathological changes.

AIM: To investigate the effect of cycloheximide on the T cells activation by mitogen in vitro with CD69 expression as activation marker for the application of this drug clinically. METHODS:Lymphocytes were isolated from lymphoid nodes of C57BL/6 mouse. The cells were preincubated with cycloheximide(CHX), 5% serum containing CHX respectively for an hour, then further incubated with polyclonal activators (Con A or PDB). Harvesting the cells after whole incubation for 24 h, we estimated the expression rates of CD69 on T cells by flow cytometry following two-color immunofluorescent staining. RESULTS: The expression rates of CD69 on the T cells preincubated with CHX, serum containing CHX after the stimulation in response to Con A or PDB all showed significant difference with the expression rates of control group, respectively ( P

Objective To investigate the diagnostic performance of stress cardiac magnetic resonance(CMR) for evaluating low-risk patients with suspected acute coronary syndrome(ACS).Methods Twenty-two patients with low risk of suspected ACS were prospectively and consecutively enrolled in this study.Diagnostic performance of stress CMR was compared with single-photon emission computed tomography(SPECT) for diagnosis of myocardial ischemia with coronary angiography (CAG) as the reference method.Results On the patient-based level analysis,the diagnostic performance of CMR for detection of ACS was sensitivity 93% and specificity 75%.The corresponding value of SPECT was 79%,63%.The area under the ROC (AUC) of CMR was 0.897, which was slightly superior to that of SPECT at 0.723 (P=0.19).On the per-vessel assessment, the diagnostic value of CMR was sensitivity 89%,specificity 87%, while the corresponding value of SPECT was 68%,83%.The AUC of CMR was 0.923,which was significantly higher than that of SPECT at 0.774 (P<0.05).Furthermore, the AUC of CMR was significantly superior to that of SPECT with AUC being 0.900 and 0.553 in the left anterior descending (LAD) vessels (P=0.009 6).Conclusion Stress perfusion CMR has excellent diagnostic performance in low risk ACS patients.Compared with SPECT,stress perfusion CMR performed better in the low-risk ACS populations.

Objective To study effectiveness and effect on the internal environment of exchange transfusion using peripheral arteries and veins.Methods Exchange transfusion were performed through the peripheral arteries and veins on 22 cases of newborn infants with severe hyperbilirubinemia.Blood electrolyte,blood routine,blood bio- chemistry were measured before and after change blood.Vital signs were monitored electronically recorded.Results Total bilirubin was(595.28?134.44)?mol/L before exchange transfusion and(275.17?74.05)?mol/L after ex- change transfusion(P

ObjectiveTo investigate the methylation of the promoter region in miRNA in pancreatic cancer cell line PANC1 and normal pancreatic tissue,to discover the miRNA with hypermethylation associated with pancreatic cancer.MethodsThe genomic DNA of PANC1 and normal pancreatic tissue was extracted,and fractured by ultrasound.Methylation DNA fragments were obtained by 5-methyl of pyrimidine nucleoside antibodies and immunomagnetic beads.The hypermethylation miRNA differentially expressed between PANC1 and normal pancreatic tissue was selected by using methylation DNA chip.BSP ( bisulfite genomic sequencing PCR) and TA clone sequencing was performed for further validation.The genomic DNA of pancreatic cancer cell lines BXPC3,CFPAC1,PANC1 and SW1990 was extracted.The COBRA (combined bisulfite restriction analysis) was used to validate differentially expressed hypermethylation miRNA.ResultsEight differentially expressed hypermethylation miRNAs were screened from the DNA methylation chips,then five of them were selected for sequencing.The methylation status of miRNA-615,-663,-663b was significantly higher in the PANC1 than in normal tissues (60.6％ vs 7.6％,88.8％ vs 22.2％,94.4％ vs 13.0％ ) ; the methylation status of miRNA-675 was not significantly different between PANC1 and normal pancreatic tissue (76.0％ vs 100％ ).Due to large error in sequencing,miRNA1826 was excluded.The results of COBRA confirmed all the 4 miRNAs were highly methylated in PANC1 ; except for miRNA-675,other 3 miRNAs were highly methylated in BxPC,miRNA-663,miRNA-663b were highly methylated in CFPAC1,while miRNA-615,miRNA-663 were highly methylated in SW1990.ConclusionsHypermethylation miRNAs were differentially expressed between pancreatic cancer cell lines and normal pancreatic tissue,among them,highly methylated miRNA-663 was possibly associated with pancreatic cancer.

OBJECTIVETo investigate the effects of Wuhuang Tangkangling on tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) in serum of patients with type 2 diabetes mellitus (T2DM).

METHODOne hundred cases of type 2 diabetes mellitus patients were randomly divided into two groups. The control group was treated with pioglitazone (15 mg x d(-1)) orally once a day in the morning, combined with insulin subcutaneous injection based on blood glucose level. The treatment group was treated with decoction of Wuhuang Tangkang Ling daily, 8 weeks as a course. TNF-alpha, IL-6, hs-CRP, fasting blood glucose (FBG) and postprandial blood glucose (PBG) were tested for two groups of patients before and after the treatment And other 50 healthy cases were tested for comparison.

RESULTBefore treatment, the level of cytokine, FBG and PBG in the serum of patients with T2DM were significantly higher than healthy cases (P < 0.01). In treatment group, difference between before and after the treatment had statistical significance (P < 0.01); after treatment, difference between treatment group and control group had statistical significance (P < 0.01).

CONCLUSIONWuhuang Tangkangling could significantly decrease the level of TNF-alpha, IL-6, hs-CRP, FBG and PBG in patients with T2DM, and could decrease blood glucose, anti inflammatory, and improve insulin resistance. According to testing these cytokines, a new criteria for evaluating the progress of T2DM and the treatment may be approached.

C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Interleukin-6 ; blood ; Tumor Necrosis Factor-alpha ; blood