BackgroundOrphan drugs are intended to treat, prevent or diagnose rare diseases. In recent years, China healthcare policy makers and patients have become increasingly concerned about orphan drug issues. However, very few studies have assessed the availability and affordability of orphan drugs for rare diseases in China. The aim of this study was to provide an overview of the availability and affordability of orphan drugs in China and to make suggestions to improve patient access to orphan drugs.MethodsTwo components of the availability of orphan drugs were examined. Market availability was assessed by the extent to which orphan drugs were marketed in China with a comparison to orphan drugs in international markets, such as the U.S., EU and Japan. We conducted surveys and collected data from 24 tertiary public hospitals in China to measure hospital-level availability of orphan drugs. The affordability of orphan drugs was calculated using hospital dispensary prices and was expressed as days of average daily income required for the cost of a course of treatment. Affordability was also analyzed under the Chinese basic medical insurance system.ResultsOrphan drugs approved in the U.S., EU and Japan had 37.8 %, 24.6 % and 52.4 % market availability in China, respectively. Median availability of 31 orphan drugs surveyed at the 24 tertiary public hospitals was 20.8 % (very low). Within a periodic treatment course, the average treatment cost of 23 orphan drugs is approximately 4, 843. 5 USD, which equates to 505.6 days of per capita net income for an urban resident with a middle income (187.4 days for a high-income urban resident) or 1,582.8 days’s income for a rural resident with a middle income (657.2 days for a high-income rural resident). Except for homoharringtonine, 22 orphan drugs for 14 rare diseases were unaffordable for the most of residents in China. With 5 % out-of-pocket expenses, only three generics could be afforded by middle-income residents, whereas seven drugs for high-income urban residents.ConclusionsThe Chinese government can take more responsibility for improving the availability and affordability of orphan drugs through setting up incentive policies and public platforms for sharing of orphan drug information. Control of the high price of orphan drugs, combined with a joint funding model from both government and private enterprise can efficiently reduce the economic burden of affected patients in China.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0392-4) contains supplementary material, which is available to authorized users.

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In the present study, we investigated the effects of tetramethylpyrazine (TMP) on hydrogen peroxide (H2O2)-induced apoptosis in PC12 cells. The apoptosis in H2O2-induced PC12 cells was accompanied by a decrease in Bcl-2/Bax protein ratio, release of cytochrome c to cytosol and the activation of caspase-3. TMP not only suppressed the down-regulation of Bcl-2, up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol, but also attenuated caspase-3 activation and eventually protected against H2O2-induced apoptosis. These results indicated that TMP blocked H2O2-induced apoptosis by the regulation of Bcl-2 family members, suppression of cytochrome c release, and caspase cascade activation in PC12 cells.

BackgroundLittle is known regarding the role of the microbiome of the paranasal sinuses and its contribution to sinus mucosal health and disease. Consequently, we examined the microbiome of chronic rhinosinusitis patients with polyps (CRSwNP) and a control population to provide new insights into the microbiota associated with the pathogenesis of CRSwNP.MethodsFifty‐nine CRSwNP patients and 27 controls were enrolled in the study. The bacterial communities of the middle meatus were detected using 16S ribosomal RNA (rRNA)‒targeted Illumina MiSeq sequencing after microbial DNA was extracted from swabs.ResultsAlthough there was no difference in diversity between the 2 groups, richness was lower in the CRSwNP group than in the control group (p = 0.03). At the phylum level, Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were predominant in both groups; however, the relative abundance was different, with the proportions of Actinobacteria (predominantly Corynebacterium) and Dolosigranulum being significantly higher in the control group than in the CRSwNP group.ConclusionThese results support the theory of microbial dysbiosis as the pathogenesis of CRSwNP. The reduction in the proportions of potentially protective bacteria may decrease the overall stability of the sinonasal bacterial community.

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Hypoxia is one of the characteristics of human and animal tumors. To investigate the association between hypoxia and the immune evasion of cancer cells, the present study examined paraffin sections of pancreatic tissues from patients with pancreatic carcinoma, chronic pancreatitis and normal pancreatic tissue and established a series of PANC‑1 cell lines, which were cultured under various hypoxic and normoxic conditions. The results demonstrated that the expression of hypoxia‑inducible 1α (HIF‑1α) in pancreatic carcinoma was significantly higher compared with that in the chronic pancreatitis and normal pancreatic tissues, which revealed that a hypoxic microenvironment existed in pancreatic carcinoma. HIF‑1α was inversely correlated with major histocompatibility complex class I chain‑related (MIC) genes, which indicated that hypoxia was involved in tumor immune evasion. The cell experiments demonstrated that the mechanism involved shedding of the MIC from the membrane of the pancreatic carcinoma cells, which then formed soluble (s)MIC. The sMIC genes downregulated natural killer (NK) group 2, member D and the cytotoxic activity of NK cells. Depending on its activity, the nitric oxide‑cyclic guanosine monophosphate‑protein kinase G signaling pathway can either increase or inhibit immune evasion of pancreatic cancer cells.