Suchergebnisse

Of over 7,000 known rare diseases, only 5% currently have an available treatment option worldwide. Moreover, the vast majority of rare disease patients in China have no access to treatment due to limited availability and the lack of appropriate infrastructure in China's healthcare system. Despite increased interest in orphan drug development, drug companies in China with active programs on drugs to treat rare diseases are still limited. Hence, there is a huge unmet need in China, with over 10 million patients suffering from rare diseases. Nonetheless, this has created unprecedented opportunities for the Chinese drug development market. Life science innovation in China has recently received a healthy boost from the 13th National Five-Year Plan and from on-going reform of the China Food and Drug Administration (CFDA). Rare diseases are now recognized as a national priority with increasing governmental support, creating tremendous opportunities for both domestic and multinational drug companies. China is anticipated to play an increasingly important role in the global fight against rare diseases. To ensure future success, Chinese drug companies should leverage the valuable knowledge assembled over the past three decades by Western countries in the area of orphan drug development.

Recognized as the most common inherited from of intellectual disability (ID) and the most common known monogenic cause of autism spectrum disorders (ASD), Fragile X syndrome (FXS) is identified as an unmet medical need for the development of personalized medicine and targeted therapeutics for neurodevelopment disorders as a result of improved understanding of the genetic and cellular mechanisms. Consequently promising pharmacological targets have emerged from basic and translational research, are now being pursued by global pharmaceutical and biotech companies in early proof-of-concept clinical trials. With the world's largest rare disease population, China potentially has a large number of FXS patients, many of whom are under-diagnosed or even misdiagnosed, barely with any treatment. In spite of improved awareness of FXS in recent years, big gaps still exist between China and developed countries in multiple aspects. With increased public awareness, strong government support and investment, coupled with an increasingly large number of Western-trained experienced researchers engaging in new drug discovery and development, China has the potential to become an important player in the discovery of effective diagnostics and treatments for a rare disease like FXS.

Abstract
Background
Risks of adverse ecological effects of copper (Cu) consider of water quality parameters were not fully understood in China. Here, a national-scale exposure of Cu in Chinese surface water was investigated, and the first report using multiple linear regression approach to predict and correct toxicity data based on water chemistries in China. Risk of Cu was overestimated without considering water quality parameters in the previous studies.

Results
Under prevalent water quality conditions of hardness = 150.0 mg/L, pH = 7.8, and dissolved organic carbon (DOC) = 3.0 mg/L, across China, the predicted no effect concentration for total, dissolved Cu was 9.71 μg/L. Based on results of the preliminary risk quotients method, 1.19% (a total of 43 in 3610 sites) were classified as "high risk", only one sixth of the percentage of sites with "high risk" than the proportion predicted when not considering water quality parameters, which was 7.51%. Similar results were obtained by application of both the margin of safety method (0.71% compared to 2.81%) and joint probability curve method (3.34% compared to 16.29%), both of which overestimated risks posed by Cu to aquatic organisms in China.

Conclusion
After correcting for bioavailability based on water quality parameters, consider both concentrations and frequencies during ecological risk assessment, regions of China at greatest risk from adverse effects of Cu were the Hai River (Haihe), Huai Rivers (Huaihe) and Chao Lake. These findings provide a comprehensive method for a more accurate assessment of risks of adverse effects of Cu to aquatic life in surface waters.

Abstract
Background
Management of pharmaceuticals and personal care products (PPCPs) in the environment has become a social issue. In the present study, concentrations of 140 PPCPs at 20 sites in Baiyangdian Lake and Tai Lake from 2016 to 2017 were analyzed by ultra performance liquid chromatography mass spectrometer (UPLC–MS). Risk quotients (RQ) were calculated for each detected chemical at all sites and prioritization indices (PI), based on maximum RQ, were calculated. To assess the risk of chemicals that identified high priority (PI > 1), a more accurate method of joint probability curves (JPCs) was applied.

Results
A total of 42 PPCPs were identified and quantified detected in the two lakes, with maximum concentrations ranging from 0.04 to 889 ng/L. Among these, seven PPCPs were identified as high or moderate-risk pollutants for at least one site, 3 in Tai Lake and 5 in Baiyangdian Lake. Carbamazepine posed significant ecological risk at all 20 sites, such that more attention should be paid to that drug. Based on results of the JPCs, sulfamethoxazole, caffeine, diethyltoluamide, and carbamazepine were categorized as high or intermediate risks.

Conclusion
Occurrences and distributions of PPCPs were different in the two lakes. Multiple-level risk assessment from simple to more complex was appropriate in chemical risk management.

Abstract
Background
As a triazole fungicide, triadimefon is widely used around the world. The ubiquitous occurrence of triadimefon in aquatic environments and potential adverse effects on aquatic organisms have resulted in global concerns. In this review, the current state of knowledge on occurrence, environmental behavior, and toxic effects are presented and used to conduct an assessment of risks posed by current concentrations of triadimefon in aquatic environments.

Results
The key findings from this review are that: (1) triadimefon occurred widely in surface waters, with high rates of detection; (2) abiotic degradation of triadimefon was affected by many factors. Stereoselectivity was found during biotic degradation and metabolism of triadimefon. Different enantiomers can cause various adverse effects, which complicates the assessment and requires enantiomers-specific considerations; (3) triadimefon exposure can affect organisms by causing multiple toxic effects on the thyroid, reproductive system, liver, nervous system as well as carcinogenicity and teratogenicity, and it can also act synergistically with other pesticides. Long-term, low-dose effects were considered to be the main characteristics of toxic effects of triadimefon; (4) results of the risk assessment based on probabilistic relationships represented by joint probability curves (JPCs) indicated that risk of triadimefon was classified as low risk.

Conclusion
Triadimefon occurred widely in surface waters, with high rates of detection, while the concentration data of triadimefon in surface water is insufficient. Researches about toxic effects and mechanisms of triadimefon on invertebrate are needed. Meanwhile, researches about toxic effects and environmental exposure of chiral monomers are also required. Due to its reproductive toxicity, triadimefon might result in adverse effects on the population level or even on the ecosystem level. Risk assessments for pesticides that cause long-term and low-dose effects on aquatic organisms such as triadimefon need to consider higher-level ecological risk.