[Clinical significance and cost-benefit analysis of serum calcitonin assay in diagnosis and treatment of medullary thyroid carcinoma].

Objective: To study the clinical significance of serum calcitonin in the diagnosis and treatment of medullary thyroid carcinoma and to analyze its cost-benefit. Methods: One hundred and forty one patients with medullary thyroid carcinoma who undertook calcitonin test and frozen pathological examination were enrolled in this study from Oct 2012 to Mar 2018. Using the method of χ(2) test, the positive rate of calcitonin test and frozen pathological examination in diagnosis of medullary thyroid carcinoma(MTC) were compared. Firstly, we compared the correct checkout cost of calcitonin test and that of frozen pathological examination (total number of patients×cost of examination/the correctly detected number of patients) . Secondly, we calculated whether calcitonin test help patients save money(average cost of treatment in hospital for MTC×number of patients who were evaluated to be candidate for surgery-cost of calcitonin test×total number of patients)/total number of patients. Results: 139 patients were positive in calcitonin test among 141 patients, and the positive rate was 98.58%. 91 patients were positive in frozen pathological examination, and the positive rate was 64.54% (χ(2)=97.821, P<0.000 1) . Cost-benefit analysis showed that the correct checkout cost of calcitonin test and frozen pathological examination were 71.01 yuan and 426.10 yuan, also,1 371 938.64 yuan could be saved totally and 9 730.06 yuan could be saved per patient because of calcitonin test. Conclusion: Serum calcitonin test had a significant effect on the diagnosis and treatment of medullary thyroid carcinoma and was economical and practical.

miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer.

Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.

Two distinct genomic regions, harbouring the period and fruitless genes, affect male courtship song in Drosophila montana.

Acoustic signals often have a significant role in pair formation and in species recognition. Determining the genetic basis of signal divergence will help to understand signal evolution by sexual selection and its role in the speciation process. An earlier study investigated quantitative trait locus for male courtship song carrier frequency (FRE) in Drosophila montana using microsatellite markers. We refined this study by adding to the linkage map markers for 10 candidate genes known to affect song production in Drosophila melanogaster. We also extended the analyses to additional song characters (pulse train length (PTL), pulse number (PN), interpulse interval, pulse length (PL) and cycle number (CN)). Our results indicate that loci in two different regions of the genome control distinct features of the courtship song. Pulse train traits (PTL and PN) mapped to the X chromosome, showing significant linkage with the period gene. In contrast, characters related to song pulse properties (PL, CN and carrier FRE) mapped to the region of chromosome 2 near the candidate gene fruitless, identifying these genes as suitable loci for further investigations. In previous studies, the pulse train traits have been found to vary substantially between Drosophila species, and so are potential species recognition signals, while the pulse traits may be more important in intra-specific mate choice.

Relationship of P450 2C9 genetic polymorphisms in Chinese and the pharmacokinetics of tolbutamide.

AIM: To study the relationship between P450 2C9 genetic polymorphisms and the pharmacokinetics of tolbutamide in Chinese subjects. METHODS: P450 2C9 genotype was determined by oligonucleotide microarray. Using tolbutamide as a probe of P450 2C9 activity, P450 2C9 phenotype in 20 healthy individuals expressing the P450 2C9*1/*1, *1/*3 and *3/*3 genotypes were evaluated. After administration of 500 mg tolbutamide, plasma and urine samples were collected from each subject over a 24-h period. The tolbutamide and its metabolites' concentrations in human plasma and urine were determined by solid-phase extraction and HPLC. RESULTS: Tolbutamide AUC0-->infinity increased by 20 and 116%, and T(1/2) increased by 60 and 813%, respectively, in subjects expressing the P4502C9*1/*3 and *3/*3 genotypes compared with *1/*1 subjects. Reductions in tolbutamide oral clearance (68 and 11%) and formation clearance (39 and 3%) were detected in the *1/*3 and *3/*3 individuals, respectively, compared with */*1 subjects. CONCLUSION: The P450 2C9 activity was significantly reduced in *1 heterozygotes compared with *1 homozygotes, and the metabolism of tolbutamide was more severely impaired in *3/*3 individuals compared with those expressing *1/*3. Using tolbutamide as a P450 2C9 probe, P450 2C9 genotype was the major determinant of P450 2C9 phenotype.

[The inhibitory effects of hepatocyte targeting pH-sensitive liposome mediated phosphorothioate antisense oligonucleotide on gene expression controlled by HCV 5'NCR].

Antisense oligodeoxynucleotide is a negative charged macromolecule and hence is difficult to penetrate cell membrane and liable to degradation. To increase the effective concentration of antisense drugs in the target cells, a hepatocyte-targeting liposome directed to asialoglycoprotein receptors exclusively expressing on the hepatocyte membrane was designed and prepared based on the receptor-mediated gene transfer. In order to accelerate endosomal exit of nucleic acid drugs, the liposomal formulation with pH-sensitive property was adopted. The hepatocyte-targeting and pH-sensitivity of liposome were analyzed by galactose-receptor competitive inhibition and hemolysis of chicken red blood cell. Antisense oligodeoxynucleotide, HCV363 against HCV 5'NCR, was delivered via prepared liposome to transgenic cell HepG2.9706 and evaluated for its inhibitory effect on luciferase expression controlled by HCV 5'NCR in HepG2.9706 using Luciferase Assay System The results showed that different concentrations (10, 20, 30 mmol/L) of galactose solutions reduce the delivery effects of liposome to some extend that were up to saturation when the concentrations of galactose solution exceed 20 mmol/L. Prepared liposomes mixed with chicken RBC are put into PBS buffers with different pH values(4.0-8.0), it was observed that the amount of heme is greatly released in acidic PBS (pH < 6) due to the fusion of liposome and RBC membranes. Liposome-mediated HCV363 has dose-dependent inhibitory activities on luciferase expression controlled by HCV 5'NCR in HepG2.9706 and the inhibitory rate is 86% at a concentration of 1.0 mumol/L. In conclusion, the liposome is proven to be a hepatocyte-targeting pH-sensitive delivery system that can increase the pharmaceutical effects of antisense drugs.

Plaque-type blue nevus. Review and an unusual Case.

A 31-year-old male presented with a 13-15-mm blue-black plaque tumor on his left forearm, which had existed since birth. Histological examination showed a common blue nevus. Its small size and its location are unusual. A review of plaque-type blue nevus is given.

[Chemistry and antitumor activity of hainanensine analogues].

A synthetic analogue of hainanensine 2a was further modified in order to improve its antitumor activity. Six compounds 3-8, were obtained, and among these compounds 8 showed significant activity. The diastereomer (+/-)8B was resolved by (+) tartaric acid and (-)benzoyl-tartaric acid to the corresponding enantiomers (-)8B and (+)8B, respectively and their optical purities were determined by isotope dilution method as 93% and 96%. The antitumor activity of the newly obtained compounds were tested in vitro, and (-)8B was found to have an IC50 of 1.9 mol/L, eighteen times higher than the original compound 2a.

Raman spectroscopic and X-ray diffraction studies of the effect of temperature and Ca2+ on phosphatidylethanolamine dispersions.

Raman spectroscopy and X-ray diffraction are used to study the effect of heat and Ca2+ on dimyristoylphosphatidylethanolamine dispersions. Unlike phosphatidylcholine dispersions, dimyristoylphosphatidylethanolamine bilayers (at pH 8) require heating above Tm in order for hydration to occur and apparently bind Ca2+ at very low levels. These results are related to models for membrane fusion.