Medical expenditure for lung cancer in China: a multicenter, hospital-based retrospective survey.

BACKGROUND: Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002-2011 using nationally representative data in China METHODS: This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002-2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China's annual consumer price index. RESULTS: The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage. CONCLUSION: The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs.

Mechanism of tumor­derived extracellular vesicles in regulating renal cell carcinoma progression by the delivery of MALAT1.

Renal cell carcinoma (RCC) is a major healthcare burden globally. Tumor­derived extracellular vesicles (EVs) contribute to the formation of a pro­metastatic microenvironment. In the present study, we explored the role and mechanism of RCC cell 786­O­derived EVs (786­O­EVs) in RCC. First, 786­O­EVs were extracted and identified, and EV internalization of RCC cells was observed. RCC cell malignant behaviors and long noncoding RNA (lncRNA) metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) expression patterns were detected before and after 786­O­EV treatment. MALAT1 was intervened to evaluate RCC cell behaviors. The downstream mechanism involving MALAT1 was predicted. In addition, the relationship among MALAT1, transcription factor CP2 like 1 (TFCP2L1) and ETS proto­oncogene 1, transcription factor (ETS1) was analyzed. TFCP2L1 expression patterns were measured after 786­O­EV exposure. Tumor xenograft formation assay and lung metastasis model were adopted to verify the role of 786­O­EVs in vivo in RCC. It was found that 786­O­EVs could be internalized by RCC cells. 786­O­EVs promoted RCC cell malignant behaviors, accompanied by elevated MALAT1 expression levels. The 786­O­EVs with MALAT1 knockdown attenuated the promotive effect of sole 786­O­EVs on RCC cells. MALAT1 located ETS1 in the TFCP2L1 promoter and negatively regulated TFCP2L1, and ETS1 protein could specifically bind to MALAT1. 786­O­EVs enhanced the binding of ETS1 and the TFCP2L1 promoter and decreased TFCP2L1 expression. In vivo, 786­O­EVs promoted tumor growth and RCC lung metastasis, which was suppressed following inhibition of MALAT1. Our findings indicated that 786­O­EVs promoted RCC invasion and metastasis by transporting MALAT1 to promote the binding of transcription factor ETS1 and TFCP2L1 promoter.

Streptomyces albogriseolus SY67903 Produces Eunicellin Diterpenoids Structurally Similar to Terpenes of the Gorgonian Muricella sibogae, the Bacterial Source.

Microeunicellols A (1) and B (2), two undescribed eunicellin diterpenoids, were isolated from the culture of a bacterial symbiont, Streptomyces albogriseolus SY67903. Their structures, including absolute configurations revealed by spectroscopic data and single-crystal X-ray diffraction analysis, are closely related with the diterpenoids from its host, a South China Sea gorgonian, Muricella sibogae. This is the first report of eunicellin diterpenoids, commonly coral-derived, from a bacterial symbiont of coral. The chemical metabolic relationship between the bacterium and its host is discussed. Biological evaluation revealed that compound 1 possessed cytotoxicities against several human cancer cell lines.

Circ_0039569 promotes renal cell carcinoma growth and metastasis by regulating miR-34a-5p/CCL22.

Circular RNAs (circRNAs) belong to non-coding RNAs and are known as key regulators in gene regulation. CircRNAs involve in the various biological processes of cancer. However, the functions of circRNAs in renal cell carcinoma (RCC) are still not clear. In this study, the circRNA expression profile was performed in the RCC tissues by microarray. There were 35 significantly expressed circRNAs with more than 5 folds from microarray analysis. Hsa_circ_0039569 (circ_0039569) was verified to be up-regulated in RCC and cells compared with the controls by real time RT-PCR. The assays of cellular functions showed that circ_0039569 down-regulation suppressed the proliferation and metastasis of RCC cells. The molecular mechanism of circ_0039569 in RCC cells showed that circ_0039569 promoted RCC progression by up-regulating CCL22 expression via down-regulating miR-34a-5p. Taken together, the study indicated that circ_0039569 played an important role in RCC cell survival and metastasis, which suggested that an oncogenic role of circ_0039569 in RCC progression.

Cytotoxic Spliceostatin Analogs from Pseudomonas sp.

Two new spliceostatin analogs, designed as spliceostatins J and K (1 and 2), were isolated and identified from the culture of Pseudomonas sp., along with two known ones, FR901464 (3) and spliceostatin E (4). Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS. Spliceostatin J (1) represented the first example of spliceostatins bearing an unusual hexahydrofuro[3,4-b]furan moiety. Biological assay showed all the isolated compounds except 1 displayed potent cytotoxic activities against two cancer cell lines (MDA-MB-231 and A-549). Structure-activity-relationship studies revealed that the tetrahydropyran ring in spliceostatin analogs was necessary for their bioactive retention.

Health utility scores of family caregivers for leukemia patients measured by EQ-5D-3L: a cross-sectional survey in China.

BACKGROUND: This study assessed the health related quality of life of family caregivers (FCs) of leukemia patients by using the health utility scores derived from the EuroQol five-dimensional (EQ-5D) questionnaire. METHODS: A cross-sectional survey was undertaken on 306 family caregivers of leukemia patients to assess their health utility using the EQ-5D-3L. Participants were recruited from three hospitals in China's Heilongjiang province. The health utility scores of the participants were estimated based on the Chinese EQ-5D-3L value set and compared with those of the local general population. Factors predicting the health utility scores were identified through the Kruskal-Wallis analysis of variance and median regression analyses. RESULTS: FCs had lower health utility scores than the general population (p < 0.001). The participants with a lower socioeconomic status had lower utility scores and reported more problems than those with a higher socio-economic status. Better family function and higher social support were associated with higher health utility scores. The type of leukemia, household income, and social support are significant predictors of health utility scores of the FCs. Chronic lymphocytic leukemia, low socio-economic status, and low social support are associated with lower health utility scores of the FCs. CONCLUSIONS: FCs for leukemia patients have lower health utility scores than the local general population, as measured by the EQ-5D-3L. There is an immediate need to address the health concerns of FCs, who play an important role in the Chinese health care system.

Assessing Health-Related Quality of Life of Chinese Adults in Heilongjiang Using EQ-5D-3L.

This study aimed to assess health-related quality of life (HRQOL) of Heilongjiang adult populations by using the EuroQol five-dimension three-level (EQ-5D-3L) questionnaire and to identify factors associated with HRQOL. Data from the National Health Services Survey (NHSS) 2008 in Heilongjiang province were obtained. Results of EQ-5D-3L questionnaires completed by 11,523 adult respondents (18 years or older) were converted to health index scores using a recently developed Chinese value set. Multivariate linear regression and logistic regression models were established to determine demographic, socioeconomic, health, and lifestyle factors that were associated with HRQOL and reported problems in the five dimensions of EQ-5D-3L. The Heilongjiang population had a mean EQ-5D-3L index score of 0.959. Lower EQ-5D-3L index scores were associated with older age, lower levels of education, chronic conditions, temporary accommodation, poverty, unemployment, and lack of regular physical activities. Older respondents and those who were unemployed, had chronic conditions, and lived in poverty were more likely to report problems in all of the five health dimensions. Higher educational attainment was associated with lower odds of reporting health problems in mobility, pain/discomfort, and anxiety/depression. Low socioeconomic status is associated with poor HRQOL. Regional population norms for EQ-5D-3L are needed for health economic studies due to great socioeconomic disparities across regions in China. Overall, the Heilongjiang population has a similar level of HRQOL compared with the national average.

GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve.

Bicuspid aortic valve (BAV) is the most common form of congenital cardiovascular defect in humans worldwide and is responsible for substantial morbidity and mortality. Accumulating evidence has demonstated that genetic risk factors are involved in the pathogenesis of BAV. However, BAV is genetically heterogeneous and the genetic basis underlying BAV in a large number of patients remains unknown. In the present study, the coding regions and splice junction sites of the GATA5 gene, which codes for a zinc-finger transcription factor crucial for the normal development of the aortic valve, was sequenced initially in 110 unrelated patients with BAV. The available relatives of the mutation carriers and 200 unrelated healthy individuals used as controls were subsequently genotyped for GATA5. The functional effect of the mutations was characterized by using a luciferase reporter assay system. As a result, two novel heterozygous GATA5 mutations, p.Y16D and p.T252P, were identified in two families with autosomal dominant inheritance of BAV, respectively. The variations were absent in 400 control chromosomes and the altered amino acids were completely conserved evolutionarily. Functional assays revealed that the two GATA5 mutants were associated with significantly reduced transcriptional activity compared with their wild-type counterpart. To the best of our knowledge, this is the first study on the association of GATA5 loss-of-function mutations with enhanced susceptibility to BAV, providing novel insight into the molecular mechanism involved in human BAV and suggesting a potential role for the early prophylaxis and personalized treatment of this common congenital heart disease.

High-level expression, purification, and in vitro refolding of soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a new member of the TNF superfamily. In this paper, we report the expression, purification, and preparation of a recombinant form of the extracelluar domain of the TRAIL (sTRAIL) without posttranslational modifications, which may selectively induce apoptosis of tumor cells in vitro. To obtain recombinant nonfusion sTRAIL protein, the encoding region for sTRAIL was cloned between KpnI and BamHI in pET32a. The Trx (thioredoxin)/sTRAIL fusion proteins were expressed in the form of inclusion bodies in Escherichia coli host strain BL21 (DE3). The expression level was more than 35% of total cell lysate. Inclusion bodies were disrupted, washed, and isolated at pH 9.0, and were completely dissolved in a buffer containing 2 M urea at pH 9.0. After nickel ion metal affinity chromatography, gel filtration chromatography, and renaturation, the refolded fusion proteins with a purity of >98% were obtained. Trx/sTRAIL L proteins were digested by enterokinase to both Trx and sTRAIL fragments, which then were separated by cation exchange chromatography. Cell proliferation experiments proved that the rsTRAIL (98% purity) retains its cancer-selective apoptosis-inducing properties. This result suggested that the recombinant sTRAIL may have cancer therapeutic applications.

Efficient expression and purification of human interferon alpha2b in the methylotrophic yeast, Pichia pastoris.

The human interferon alpha2b (hIFN-alpha2b) is the most widely used member of IFNalpha family, and it exerts many biological actions including broad-spectrum antiviral effects, inhibition of tumor cell proliferation and enhancement of immune functions. Herein, the cDNA coding for hIFN-alpha2b has been cloned into the secreting expression organism Pichia pastoris, and the high level expression of hIFN-alpha2b has been achieved. SDS-PAGE and Western blotting assays of culture broth from a methanol-induced expression strain demonstrated that recombinant hIFN-alpha2b, a 18.8 kDa protein, was secreted into the culture medium. The recombinant protein was purified to greater than 95% using Source Q ion exchange and Superdex 75 size-exclusion chromatography steps. Finally, 298 mg of the protein was obtained in high purity from 1l of the supernatant and its identity to hIFN-alpha2b was confirmed by NH(2)-terminal amino acid sequence analysis. The bioassay of the recombinant protein gave a specific activity of 1.9 x 10(9)IU/mg. Our results suggest that the P. pastoris expression system can be used to produce large quantities of fully functional hIFN-alpha2b for both research and industrial purpose.