Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China.

OBJECTIVES: To evaluate the cost-effectiveness of 10 mg ilaprazole once-daily vs 20 mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China. METHODS: A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results. RESULTS: Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China's average GDP per capita is considered. LIMITATION: This study didn't have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy. CONCLUSIONS: The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.

New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts.

The cytoskeleton mediates various cellular processes such as differentiation and fusion, including in the filopodia and podosomes. However, apart from cell migration and formation of the sealing zone, little is known regarding the changes and related regulatory mechanisms of the cytoskeleton and additional roles of the filopodia and podosomes during the differentiation and fusion of osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the differentiation process were evaluated using tartrate-resistant acid phosphatase staining and immunofluorescence staining. Moreover, the expression levels of Rho GTPases and enzymes related to osteoclast differentiation and bone resorption were detected by quantitative reverse transcription-polymerase chain reaction. We detected 3 types of filopodia in osteoclast precursors and only 1 type of filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of filopodia. Interestingly, cell fusion was highly specific, and the fusion initially occurred to the filopodia. Confocal images revealed that F-actin and microtubules significantly differed among fused cells. These results suggest that filopodia and podosomes not only play important roles in cell migration and the formation of sealing zones but also in the pre-fusion selectivity of 2 cells and the movement direction of the cell nucleus and cytoplasm during the fusion process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types of filopodia during various stages of differentiation, while Rac1, Rac2, and filament A may be associated with cell selectivity during the fusion process.

Detection of human cytomegalovirus antigen and DNA in lymph nodes and peripheral blood mononuclear cells of patients with angioimmunoblastic lymphadenopathy with dysproteinemia.

The cause of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) remains unknown. It is characterized by acute onset, severe constitutional symptoms, cervical or generalized lymphadenopathy, lymphopenia, and polyclonal hypergammaglobulinemia, all of which are highly suggestive of a viral origin. Using immunohistochemical methods, employing murine monoclonal antibody as the primary antibody, we detected human cytomegalovirus antigen in the lymph nodes of eight of 11 patients with AILD. Cytomegalovirus DNA was also detected in the peripheral blood mononuclear cells by DNA dot hybridization in all five of the patients with AILD who were tested using this technique. None of the lymph nodes from the 11 patients stained positive for the rubella virus antigen. Based on the above evidence and the similarity of the immunologic abnormalities found in both AILD and cytomegalovirus infection, the possible role of cytomegalovirus as one of the causative agents for AILD is proposed.

Spontaneous and induced demographic change.

When some scholars from abroad analyze the role of family planning policies in developing countries in changes in the fertility rate, they differentiate 2 categories of change: one is "developmental change in the fertility rate" and the other is "induced change in the fertility rate". Professor Tian Xinyuan, of American nationality, quotes this concept in his analysis of changes in China's fertility rate, and believes that changes in China's fertility rate belong to fairly successful "induced change in fertility behavior". The author agrees with this differentiation, and feels that there is a need to incorporate this kind of differentiation in all analysis of the characteristics and mechanism of demographic change in China. Due to the inclusion of a set of intervening social variables, in fact demographic change in all countries has already evolved the 2 fundamental types of demographic change, spontaneous and induced. However, until now, the authors have not seen a systematic discussion of the differences and the relationship between these 2 types of demographic change. This paper attempts to make some theoretical investigations into the above, and firmly believes that this has definite significance for enriching theories of demographic change and guiding China's family planning practices.

Circadian variation of 5-fluorouracil catabolism in isolated perfused rat liver.

The catabolism of 5-fluorouracil (FUra) was measured in isolated perfused rat liver (IPRL) at various times of the day. IPRLs were prepared from rats sacrificed at 3-h intervals and the elimination rate of FUra and FUra catabolites (i.e., rate leaving the IPRL in the effluent perfusate) following infusion of [3H]FUra was analyzed for circadian periodicity. Animals were housed under standardized conditions of light and dark and divided into two groups of 24 animals each. The first group was housed under "normal" light conditions (lights on from 6:00 a.m. to 6:00 p.m.; off from 6:00 p.m. to 6:00 a.m.), while the second group was housed under "reverse" light conditions (lights on from 10:00 p.m. to 10:00 a.m.; off from 10:00 a.m. to 10:00 p.m.). A circadian rhythm was observed in the elimination rate of FUra and FUra catabolites by both groups (P less than 0.0001, Cosinor analysis). Under "normal" light conditions, peak and trough elimination rate of FUra was at 19 h after light onset (HALO; 183.8 +/- 3.4 nmol/min/g liver) and 7 HALO (123.8 +/- 3.4 nmol/min/g liver), respectively. There was a reciprocal relationship between the elimination rates of FUra and FUra catabolites with peak and trough values for FUra catabolites at 7 HALO (70.5 +/- 3.6 nmol/min/g liver) and 19 HALO (17.5 +/- 3.6 nmol/min/g liver), respectively. Animals housed under the "reverse" conditions of light and dark also exhibited a circadian pattern. Under the "reverse" conditions, the peak and trough elimination rate of FUra was at 18.5 HALO (170.0 +/- 1.7 nmol/min/g liver) and 6.5 HALO (130.0 +/- 1.7 nmol/min/g liver), respectively. The peak and trough elimination rate of FUra catabolites under these conditions occurred at 6.5 HALO (64.3 +/- 2.2 nmol/min/g liver) and 18.5 HALO (29.7 +/- 2.2 nmol/min/g liver), respectively. These results demonstrate that the elimination rate of FUra and FUra catabolites by IPRL varies over a 24-h period with a circadian rhythm in association with the light/dark cycle. Such a variation in the hepatic elimination rate of FUra in humans could result in a variation in the systemic level of drug during chemotherapy thus affecting the therapeutic efficacy of FUra. This study suggests that a circadian pattern in the hepatic catabolism of FUra needs to be considered when planning chemotherapeutic regimens with FUra.

Circadian rhythm of rat liver dihydropyrimidine dehydrogenase. Possible relevance to fluoropyrimidine chemotherapy.

The activity of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in pyrimidine catabolism, was measured at various times over a 24-hr period in the livers of rats housed under standardized conditions of light and dark. Under "normal" conditions, i.e. lights on from 6:00 a.m. to 6:00 p.m. and off from 6:00 p.m. to 6:00 a.m., a circadian rhythm of DPD activity was observed (P less than 0.0001, Cosinor analysis) with the peak of activity at 4:00 p.m. (2.96 nmol catabolites/min/mg) and the trough at 4:00 a.m. (0.40 nmol catabolites/min/mg). Maximum enzyme activity exceeded minimum activity by more than 7-fold. Reversing the light-dark cycle (i.e. lights on from 6:00 p.m. to 6:00 a.m. and off from 6:00 a.m. to 6:00 p.m.) resulted in a corresponding shift in enzyme activity. Under these "reverse" conditions, a circadian rhythm was observed (P less than 0.0001, Cosinor analysis) with the peak of activity at 6:00 a.m. (2.87 nmol catabolites/min/mg) and the trough at 6:00 p.m. (0.92 nmol catabolites/min/mg). These studies demonstrated that DPD activity in rat liver varies over a 24-hr period in association with the light-dark cycle.