Rare diseases, also known as "orphan diseases", refer to diseases with very low incidence. Countries and regions define rare diseases according to epidemiological standards, economic standards of rare drugs and disease severity. The World Health Organization (WHO) has suggested the prevalence rate of less than 6.5 to 10 per 10 000 people to define rare diseases. In May 2018, "China's First List of Rare Diseases" was released, including 121 rare diseases. Most rare diseases are hereditary diseases with early onset, severe disease, and poor prognosis. About 75% of rare genetic diseases occur in the neonatal period or childhood, which are important part of human birth defects and brings a huge burden to society and families. The effective prevention and treatment of rare diseases is one of the important goals of building a "Healthy China". With the development of molecular biology technology and the continuous research and development of advanced medical products in the field of gene therapy, the level of clinical diagnosis and treatment of rare diseases has risen to a new level, which provides a possibility for the cure of some rare diseases. In China, most rare diseases rely on imported drugs, which cost a lot and bring heavy economic burden to patients. Improving the medical insurance system for rare diseases has become a difficult point in the current medical reform. This paper mainly discusses the definition of rare diseases, the research status, efforts and future development direction of rare diseases in China, in order to deepen the understanding and response of medical workers and the whole society to rare diseases.

AIM: To explore the effects of axial stress regulation on healing of lengthened ca llus. METHODS: Tibiofibulars of 30 rabbits were lengthened 2 cm with t wice plane sreminobicular crib external fixator. Experimental group continues to lengthen 3 mm, and then were drawn and shortened 0.5mm once every 24 h separate ly for 10 days. Ten days later, tibiofibulars were axial short-stressed 1 mm wee kly with three times. Animals were killed 58 days after operation and X-ray, bon e density and histology tests were performed with lengthened bone. RESULTS: X-ray examination had no significant difference between two group animal when le ngthen ended, but X-ray showed lengthened callus was different on day 58. In con trol group, lengthened center had a serial callus and cortex had no formed, in experimental group, lengthened center had serial cortex and transfixial medullar y cavity expect serial callus. Bone density tests with two-energetic X-ray bone density measuring device showed bone density was higher in experimental group th an control group (P

Objective:To establish a specialized detection method for quinolone drugs illegally added in health foods and Chinese traditional patent medicines. Methods: LC-MS/MS was used to simultaneously screen pipemidic acid, norfloxacin, ciprofloxacin, lomefloxacin, enoxacin, fleroxacin, pefloxacin, sparfloxacin, gatifloxacin and ofloxacinan in health foods and Chinese traditional patent medicines. Qualitative and quantitative analysis and methodology validation were studied as well. Results:Under the conditions of the analysis method, the 10 quinolone drugs added illegally obtained a good separation on a chromatographic column. With the two grade mass spectrum for the qualitative analysis and the peak area of multiple reactions monitoring mode for the quantitative calculation, the method was specific and sophisticated. The recovery and linear relationship met the demand of screening. Conclusion:The method is simple and accurate in the detection of quinolone drugs in health food and Chinese traditional patent medicines.

Objective To observe the effects of different concertrations of calcifying nanoparticles (CNP) on growth and proliferation of human renal tubular epithelial cells (HK-2),and to explore the effects of autophagy of human renal tubular epithelial cells induced by CNP. MethodsNormal growth HK-2 cells were cultured in vitro and the culture medium was changed to serum-free medium after cell growth to confluence,CNP with different concentrations were then added and the cell proliferation inhibition was measured by MTT assay after 12,24,48 and 72 h co-incubation.EGFP-LC3 express plasmid was transfected into HK-2 cells,CNP with certain concentration was then added after 24h incubation.The formation of autophagosomes and their adherence to cells were observed by electron microscopy,and EGFP-LC3 staining was used to detect the formation of autophagosome by flourescence microscopy after 3,6,24 and 48 h co-incubation. ResultsCNP presented a concentration-dependent cell proliferation inhibition on HK-2 cells,the inhibitory ratio in cell proliferation was 14.5 ％ after 48 h co-incubation when CNP density was 0.05 mg/ml,and the inhibitory ratio was 21.5％ after 72 h co-incubation when CNP density was 0.1 mg/ml.Autophagosome formation and CNP adherence to cell surface could be observed by electron microscopy 6 h after CNP was added to the DMEM medium.The LC3-positive dots were observed in HK-2 cells incubated with CNP.Conclusions Autophagy of HK-2 could be activated by co-incubation with CNP,which may play an important role in the formation of nephrolithiasis.

Tumor vaccine is one of the most promising therapeutic strategies in tumor immunotherapy. It promotes the antigen presentation process by delivering tumor antigen and then activates the anti-tumor immune response. As a new class of vaccines, messenger RNA (mRNA) vaccines can activate the immune system to achieve the purpose of immunotherapy by delivering the mRNA sequence of a specific antigen into the body and expressing the corresponding antigen protein. Compared with traditional vaccines, mRNA vaccines have the advantages of a short production cycle, high effectiveness, and strong immunogenicity. In recent years, the application of mRNA vaccines in tumor immunotherapy has attracted widespread attention, but the instability and low delivery efficiency of mRNA limit its application. Nano delivery system can effectively solve the problem of mRNA vaccine delivery, greatly promote the research process and clinical application of mRNA tumor vaccines, and has become a hot spot in the research of mRNA vaccines. In this review, we introduced the mRNA tumor vaccines, focusing on the application of nano delivery system in mRNA tumor vaccines, in order to provide new ideas and new methods for the efficient delivery of mRNA tumor vaccines and tumor immunotherapy.

Aim To prepare sterically stabilized liposomes modified with chimeric TNT-3 monoclonal antibody (chTNT-3) and investigate their immunoreactivity and in vitro targeting. Methods An endgroup functionalized polyethylene glycol-lipid derivative (pyridylthiopropionoylamino-polyethylene glycolhydrogenated soy phosphatidylethanolamine, PDP-PEG-HSPE ) was synthesized and incorporated to sterically stabilized liposomes. After mild thiolysis of the PDP groups by dithiothreitol, liposomes were covalently linked with maleimide-derivatized chTNT-3 and formed sterically stabilized immunoliposomes.Coupling efficiency, antibody density, size distribution, immunoreactivity of chTNT-3-modified sterically stabilized liposomes (chTNT-3-SLs) and specific binding properties of the chTNT-3-SLs to fixed Raji cells were determined, separately. Results Higher initial Ab/PDP-PEG-HSPE molar ratios resulted in higher antibody density on the surface of liposomes but lower coupling efficiency. The optimal coupling efficiency of 71% was obtained while antibody density in liposome was 106 μg antibody/μmol phospholipids (as initial antibody/PDP-PEG-HSPE = 1: 10). The chTNT-3-SLs had a narrow size distribution after extrusion and the mean size of this immunoliposomes was (115 ± 33) nm. The immunoreactivity of chTNT-3 can be preserved after efficient attachment of maleimide-derivatized chTNT-3 to the surface of liposomes. But calculated per antibody concentration, the immunoreactivity of chTNT-3-SLs would obviously decrease compared to that of chTNT-3 or chTNT-3 derivatives. Significantly higher binding of chTNT-3-SLs to fixed Raji cells directed by chTNT-3 was obtained compared to other preparations in serial dilutions (P＜0.01). Conclusion chTNT-3-SLs prepared by PDP-PEG-HSPE method remained most immunoreactivity of chTNT-3 and was able to bind nuclear antigens in vitro.

Animals ; Bibenzyls ; chemical synthesis ; therapeutic use ; Imidazoles ; chemical synthesis ; therapeutic use ; Mice ; Pyrimidines ; chemical synthesis ; therapeutic use ; Sarcoma 180 ; drug therapy

Objective To compare three ways of transplanting neural stem cells(NSCs) to treat hypoxia-ischemic encephalopathy (HIE) ,such as through axillary vein,internal carotid artery and lumbar puncture. Methods Newborn piglets were divided into three groups randomly,and transplanted NSCs through axillary vein,through internal carotid artery or through lumbar puncture after hypoxic-ischemic damage operations. Each group had five piglets. Two hours after hypoxic ischemic damage,2 × 106 NSCs with green fluorescent protein were injected through axillary vein,internal carotid artery or lumbar puncture. Piglets were sacrificed 24 hours after operations. Slices were gotten at hippocarnpus, anterior horn of lateral ventricle and posterior horn of lateral ventricle. NSCs were counted at four visual fields of each four slices of each lays through fluorescence microscope with 400 amplification factor len. Results The positive cells of axillary vein group,internal carotid artery group and lumbar puncture group were 53. 80 ± 8. 78,69. 80 ± 11.90,265.00 ± 29.65respectively. The positive cells of lumbar puncture group were more than the other groups, and there was statistic significance(P < 0. 01). Conclusion The study proved NSCs injected through lumbar puncture could enter brain tissue. It is feasible to transplant NSCs through lumbar puncture to treat newborn with HIE.

Molecular imprinting technique (MIT) involves the synthesis of polymer in the presence of a template to produce complementary binding sites in terms of its size, shape, and functional group orientation. Such kind of polymer possesses specific recognition ability towards its template molecule. Despite the rapid development of MIT over the years, the majority of the template molecules that have been studied are small molecules, while molecular imprinting of proteins remains a significant yet challenging task due to their large size, structural flexibility and complex conformation. In this review, we summarize the research findings over the past five years, and discuss the characteristics of the technique, the most recent progress and the perspective in the field of molecular imprinting of proteins.

ObjectiveTo investigate the flora distribution and drug resistance status of nosocomial fungal infection in cancer hospitals for providing the scientific basis for clinical prevention and control.Methods The related clinical data and results of drug sensitivity tests of fungal infection in hospitalized patients from April 2006 to November 2010 were analyzed retrospectively.ResultsA total of 1011 strains of candida were isolated in five years, in which, Candida albicans (41.6％ on average) were the highest detection rate strains.The proportion of Candida albicans declined from 53.8％ in 2006 to 31.7％ in 2010, while the other non-Candida albicans increased from 46.2％ in 2006 to 68.3％ in 2010.In the General surgery, the Internal medicine,the Hepatobiliary surgery, and the Chinese and Western medicine, the number of candida were more than the other departments.The specimens were mainly isolated from sputum and swab, followed by blood specimens.In vitro susceptibility test results showed that: voriconazole, amphotericin B and 5-fluorocytosine showed high sensitivity and itraconazole, fluconazole showed high drug resistance to albicans.Conclusion Distribution of pathogens causing nosocomial fungal infection has changed, and the rates of fungal resistance were rising,so this situation should arouse the clinician's attention.