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 investigate the association between nucleotide polymorphisms (rs1569723 in CD40 gene) and clinical characteristics in Kawasaki disease (KD) in Han Chinese children. Methods A case-control study was performed,and 179 children with KD and other 197 normal children served as controls were included. The SNP genotypes were detected using PCR-RFLP, and all data were analyzed by SPSS 19.0. Results It was found that the SNP (rs1569723) was associated with KD (P=0.048), and the frequency of A allele in KD group was higher than that in control group (OR=1.505, 95%CI:1.095-2.070, P=0.012). SNP genotypes were associated with rash and lymphadenopathy (P=0.041, 0.047), but not associated with conjunctival hyperemia, hand-foot edema, oral mucosa lesions, and coronary artery lesion (P=0.688,0.758, 0.557, 0.552). Conclusions Genotypes of SNP (rs1569723) were associated with KD susceptibility, and A-allele is a risk allele. The SNP loci might be associated with rash and lymphadenopathy in KD in Han Chinese.

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.

ObjectiveTo investigate the association of two single nucleotide polymorphisms (SNPs) (rs2736340 and rs2618476) inBLK gene with Kawasaki disease (KD) and coronary artery lesion in Chinese Han children.MethodsIn the case-control study, 179 children with KD were selected and 182 healthy check-up children during the same period were selected as normal controls. The genotypes of two SNPs inBLK gene were detected using PCR-RFLP and the data were analyzed. ResultsThere was no difference in distribution of three genotypes (TT, CT, and CC) of SNP rs2736340 between KD group and control group (P=0.093). However, T allele frequency in KD group was signiifcantly higher than that in control group (P=0.021). The distribution of three genotypes (CC, CT, and TT) of SNP rs2618476 between KD group and control group was signiifcantly different (P=0.021). C allele frequency in KD group was signiifcantly higher than that in control group (P=0.006). The two SNPs inBLK gene were not associated with rash, hand-foot edema and coronary artery lesion (CAL), but SNP (rs2618476) was asso-ciated with oral mucosa lesions (P=0.018).ConclusionsThe SNP (rs2736340) inBLK gene was not associated with KD, but the T-allele was associated with KD. The SNP (rs2618476) was associated with KD in Han Chinese, and was also associated with oral mucosa lesions in KD patients.

Objective To explore the imaging features of giant cell tumor of tendon sheath(GCTTS) so as to improve the accuracy of imaging diagnosis. Methods Thirty?nine cases of GCTTS confirmed by pathological examination were retrospectively analyzed.Of the 39 cases, 32 were diffuse form and 7 were localized form.Seventeen patients underwent X?ray examination,18 had CT pain examination,37 had pain MR imaging and 17 had contrast?enhanced MR imaging.Results X?ray showed local soft tissue masswith slightly high density, and the adjacent bones were shown destruction or erosion tovarious degrees(10/17). No obvious calcification and periosteal reaction were shown.CT scans could provide images better than X?ray films.CT showed local soft tissue masses in the peri?articular muscle gaps. Some tumors were lobulated with cross?jointed growth(8/18),and the adjacent bones were shown destruction or erosion tovarious degrees(11/18).No obvious calcification and periosteal reaction were shown. On MRI,most cases were isointense on T1WI(32/37),and hyperintense on T2WI(27/37). Most cases tended to be heterogeneously enhanced following Gd?DTPA administration(14/17).The lesions were typically located adjacent to a tendon or partially/completely encasing it. Conclusions The imaging findings of GCTTS have some certain characteristics. MRI is able to depict the characteristic internal signal of GCTT and its relationship with adjacent tissues, which is valuable for diagnosis, treatment and follow?up.

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.

OBJECTIVE:To establish a RP-HPLC method for the determination of Esculetine in Dinglian tablets.METHODS:The chromatographic column was Hypersil ODS C18(200mm?4.6mm,5?m)at a temperature of 25℃;the mobile phase was methyl-water-glacial acetic acid(40∶60∶0.4)at a flow velocity of 1.0mL?min-1,and the detection wavelength was set at 353nm.RESULTS:The linear concentration range of Esculetine was within 0.045～0.360?g(r=0.999 5).The average recovery rate was 97.72%(RSD=1.87%,n=5).CONCLUSION:This procedure is simple,accurate and reliable,and it can be used for the quality control of Dinglian tablets.

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.