Objective To improve the synthetic procedure of the HIV integrase inhibitor raltegravir. Methods With 2-ami-no-2-methyl-propionitrile hydrochloride as starting material,the target compound raltegravir was synthesized through amino protection by benzyl chloroformate ,amidoxime formation,cyclization induced by michael addition&Claisen rearrangement,N-methylation,N-acylation,hydroxyl protection by trimethylacetyl chloride,hydrogenolysis by the system of Pd/C and formic acid,amidation with the 5-methyl-1,3,4-oxadiazol-formyl chloride,and immediate hydrolysis without more purification. Results The chemical structure of raltegravir and the intermediates were characterized by 1H NMR,13C NMR and MS. The overall yield was about 19.45%. Conclusion Compared with the preceding process,the developed route is easy to operate,safe and suitable for industrialized production in accor-dance with the quality standard of active pharmaceutical ingredient(API).

OBJECTIVE:To improve the detection method for the dissolution of dihydroartemisinin in Dihydroartemisinin and piperaquine phosphate tablets. METHODS:The dissolution experiment adopted paddle method using 0.1 mol/L hydrochloric acid so-lution 500 mL as solvent with rotating speed of 75 r/min and sampling time of 45 min. In sample pre-treatment,the volume of 3.6% sodium hydroxide solution was increased from 5 mL to 20 mL,and that of phosphoric acid was increased from 0.2 mL to 0.7 mL. HPLC was adopted to determine the dissolution of dihydroartemisinin. The determination was performed on YMC-Pack ODS-A column with mobile phase consisted of 0.02 mol/L disodium hydrogen phosphate solution(pH adjusted to 2.4 using phosphoric ac-id)-acetonitrile(65 : 35,V/V)at the flow rate of 1.0 mL/min. The detection wavelength was set at 237 nm,and column temperature was 30 ℃. The sample size was 20 μL. RESULTS:The linear range of dihydroartemisinin were 7.802-117.03 μg/mL(r=0.9999). The limit of quantitation was 2.0 ng,and the limit of detection was 0.6 ng. RSDs of precision and reproducibility tests were all low-er than 1.0%. The recoveries were 99.18%-100.46%(RSD=0.45%,n=9). Average dissolutions of dihydroartemisinin in 3 batch-es of samples were 94.9%,77.9%,89.6%,respectively. CONCLUSIONS:Improved method enhance the accuracy for the limit of sensitivity,dissolution and detection results.

0.05). The targets of Group B were elevated than those of Group A (P0.05). Conclusion HTJQ Capsule can decrease the levels NO and NOS in lung tissues of asthmatic guinea pigs and has preventive therapeutic effect for asthma.

Objective To analyze the clinical features of Hashimoto thyroiditis with thyroid cancer, and provide scientific basis for clinical diagnosis and treatment. Methods The clinical data of 87 patients of Hashimoto thyroiditis with thyroid cancer and 105 patients of Hashimoto thyroiditis were retrospectively analyzed. Results The rates of Hashimoto thyroiditis with thyroid cancer in age <30, 30-39, 40-49, 50-59 and≥60 years were 1/3, 47.5%(29/61), 51.4%(38/74), 36.0%(18/50) and 1/4. The rates of Hashimoto thyroiditis with thyroid cancer in patients of age 30-39 years and 40-49 years were higher than that in patients of age ≥60 years, but there were no statistical differences (χ2=0.327 and 0.418, P>0.05). There were statistical differences in total thyroxine (TT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) levels between Hashimoto thyroiditis with thyroid cancer and Hashimoto thyroiditis, there were statistical differences (P<0.05 or <0.01). Multiariable Logistic regression analysis result showed that the decreased serum level of TT4 and the increased levels of TSH, TgAb and TPOAb were the correlated factors of Hashimoto thyroiditis with thyroid cancer (P<0.05 or <0.01). Conclusions Low level of TT4 and high levels of TSH, TgAb and TPOAb may increase the risk of Hashimoto thyroiditis with thyroid cancer. The 30-49 years male patients with Hashimoto thyroiditis should be highly suspected of the possibility of merger thyroid cancer.

Objective To evaluate the effect of sevoflurane on the expression of calcium-sensing receptor (CaSR) in the myocardium of rats with high-level spinal cord injury (SCI).Methods Thirty healthy male Wistar rats, weighing 250-300 g, were randomly divided into 3 groups using a random number table: sham operation group (group S, n = 6) , SCI group (n =12) and sevoflurane group (group Sev).SCI was induced in anesthetized rats by dropping a l0-g weight onto C7 spinal cord from 5.0 cm height falling freely inside a vertical hollow glass tube.Group SCI inhaled 2 L/min pure oxygen for 30 min, and group Sev inhaled 2％ sevoflurane for 30 min starting from 30 min after SCI.At 12 and 24 h after SCI (T1,2) , 6 rats were selected randomly, and blood samples from the abdominal aorta were drawn for determination of serum cardiac troponin I (cTnI) concentrations.The rats were then sacrificed, and myocardial specimens were obtained for determination of CaSR protein and mRNA expression (using fluorescent quantitative real-time reverse transcriptase-polymerase chain reaction or Western blot) and for examination of myocardial ultrastructure (with transmission electron microscope).Results Compared with group S, the serum cTnI concentrations and CaSR protein and mRNA expression were significantly increased at T1,2 in SCI and Sev groups.Compared with group SCI, the serum cTnI concentrations and CaSR protein and mRNA expression were significantly decreased at T1,2 in Sev group.The damage to myocardial cells was significantly reduced in group SCI compared with group Sev.Conclusion Sevoflurane reduces myocardial damage through inhibiting CaSR expression in the myocardium of rats with high-level SCI.

0.6). And there was high internal consistency in major instruments. The validity was examined by comparing the responses of informants and responses (good standards) of the target person in normal control group. There was also a high validity(r=0.21~0.61).Conclusion: The information reconstructed from the informants has good reliability and validity. It is possible to study suicide with psychological autopsy in China.

Objective To evaluate the results of modified Ludloff osteotomy for the treatment of severe hallux valgus. Methods Fifty six patients (63 feet) with severe hallux valgus were treated with modified Ludloff osteotomy in combination with other procedures during 1999-2000. There were three males (3 feet) and fifty three females(60 feet); the average age of the patients was 46 years old (range from 16 to 65 years old). The severe hallux valgus patients whose first intermetatarsal angles were larger than 16? were treated with modified Ludloff osteotomy. In addition to modified Ludloff osteotomy, combined Reverdin osteotomies were performed in 4 feet, and Akin osteotomies in another three. All patients were followed up for an average of 10 months (6 to 18 months), and evaluated with Maryland clinical rating systems of AOFAS. Weight bearing X-ray films were taken and measured as well. A comparison study was made between the commonly used osteotomies. The advantages and disadvantages as well, of modified Ludloff osteotomy, were evaluated.Results There was no nonunion, delayed union or infection. Based on hallux metatarsophalangea interphalangeal scale of Maryland rating system, 41 feet (65%) were in the score range from 90-100, 17 feet (27%)80-89, 5 feet (8%) 70-79. The rate of excellent or good was 92%. Conclusion Modified Ludloff osteotomy has the advantages of less shortened metatarsal, rapid healing, ability to correct deformity and earlier weight-bearing. It is a perfect procedure for severe hallux valgus patients whose first intermetatarsal angles are larger than 16?, but their first metatarsophalangeal joints are without signs of osteoarthritis.

Objective To discuss the diagnosis and treatment of ductoscopy for intraductal non-protruding lesions. Methods A retrospective analysis was made on characteristics, morphological features, and curative effects of 165 cases of intraductal non-protruding lesions between December 2002 and October 2005. Results Among the 165 cases, there were 135 cases of plasma cell galactophoritis, 18 cases of cystic mastopathy, and 12 cases of galactophoritis. In 144 cases receiving non-surgical treatment, 82 cases were completely relieved and 62 improved. Other 21 cases of plasma cell galactophoritis were surgically treated. Conclusions Mammary ductoscopy is an important way for the diagnosis of intraductal non-protruding lesions. Furthermore, effective treatment can be achieved under ductoscopy in most of cases, and unnecessary surgery may be avoided.

Objective To explore efficacy of mammary ductoscopy in diagnosis and treatment of nipple discharge.Methods 206 cases of nipple discharge underwent 211 examinations of mammary ductoscopy from May 2001 to October 2006.Results Fifty-eight patients diagnosed as non-protrusion lesions under mammary ductoscopy were treated by irrigation therapy and followed up for 3-18 months(mean,12 months) without recurrence.One hundred and forty-eight cases were diagnosed as protrusion lesions,in which 125 cases received operation.115 cases of single mammary intraductal papilloma,7 cases of papillomatosis,and 3 cases of intraductal carcinoma were diagnosed under mammary ductoscopy,while 112 case of intraductal papilloma,10 cases of papillomatosis and 3 cases of ductal carcinoma were confirmed by postoperative pathology.Of the 125 cases,mammary ducts resection was carried out in 120 cases guided by locating needle,segment mammectomy in 1 case,"mammary gland displacement" in 1 case,quadrant resection with nipple-conserving combined with axillary lymph node dissection in 1 case,quadrant resection without nipple-conserving combined with axillary lymph node dissection in 2 cases.Follow-up for 4 to 20 months(mean,10 months) showed no recurrence.3 cases of ductal carcinoma in situ were followed up for 12-18 months,and survived with tumor-free.Conclusions Mammary ductoscopy examination makes accurate diagnosis of nipple discharge induced by intraductal carcinoma before operation,and has important clinical value to choose procedures.Locating needles to locate lesions in mammary ducts may be taken as a guide during operation.

Objective:To select the binding-peptide of the cell surface marker CD133 of cancer stem cells from phage peptide library,and to find a new tool for research on stem cells,tumor therapy and anti-metastasis of cancer.Methods:Biotined mouse CD133 extracellular fraction was used as a target to screen phage 7-peptide library by the high affinity of streptavidin and biotin,and the clones were identified by sandwich ELISA and competitive experiment.Single strand DNA was extracted from these positive clones and was analyzed by single-strand dideoxy-sequencing.Results:After three turn solution panning,five peptides with high affinity shared the same amino acid sequence:APSPMIW and three identical peptides with high affinity shared the same amino acid sequence:LQNAPRS.Conclusion:The peptides that bind with mouse CD133 extracellular fraction with high affinity and specificity were first screened from the phage peptide library for the first time,which initially indicates that the feasibility of screening from phage peptide library with small molecule polypeptide biotined as a target.