Rare diseases are characterized by extremely low incidence rate and small number of patients in total. The drugs used to treat rare diseases are called orphan drugs. Currently, 450 kinds of rare skin diseases have been identified, most of which lack in effective treatments. Supported by the policy-making from the country and pushed by all sectors of the society, drugs for rare skin diseases have been emerging continuously recently in China. This paper reviews the current accessibility of the orphan drugs for skin rare diseases that have been approved in China and in other countries and regions for a better understanding of rare dermatosis and orphan drugs for the diseases.

Authenticity verification is a very important aspect of medical device registration quality management system verification of medical device. How to verify the authenticity of samples is a problem worth discussing. This study analyzes the methods of authenticity verification from the aspects of product retention sample, registration inspection report, traceability of records, hardware facilities and equipment. In order to provide reference for relevant supervisors and inspectors in the verification of registration quality management system.

Objective: To investigate direct and indirect economic burden, psychological impact, and quality of life in patients with psoriasis. Methods: Patients with psoriasis were recruited nationwide from "the psoriasis patient mutual assistance network" , a WeChat official account of "psoriasis patient mutual assistance platform" , and WeChat groups of psoriasis patients in different regions between July and September in 2018. An internet-based online questionnaire survey was carried out on these patients by using a self-designed questionnaire and Dermatology Life Quality Index (DLQI) scale. Comparison of enumeration data was carried out by using chi-square test, and comparison of measurement data by using Mann-Whitney U test. Results: A total of 497 valid questionnaires were collected, and 497 patients with psoriasis were enrolled into this survey, including 190 patients with mild to moderate psoriasis and 307 patients with severe psoriasis. These patients were from 8 geographic regions of China, and mainly in east China and north China. The total annual expenditure for psoriasis per patient accounted for 20% (8%, 50%) (M[P25, P75]) of the total annual income, the annual hospitalization rate was 21.3%, the annual sick leave or absence duration was 15.0 (1.0, 40.0) days, and the unemployment rate due to psoriasis was 37.0%. Of the 497 patients, 443 (89.1%) suffered from mental stress due to psoriasis, 169 (34.0%) had suicide intention, and 23 (4.6%) had ever attempted suicide. The DLQI score for all the patients was 14 (8, 19) , 307 (61.8%) patients reported a severe or extremely severe impact on the quality of life (DLQI > 10, severe psoriasis group) , and 190 (38.2%) patients reported a mild or moderate impact on the quality of life (0 ≤ DLQI ≤ 10, mild to moderate psoriasis group) . Compared with the mild to moderate psoriasis group, the severe psoriasis group showed a significantly higher ratio of total annual expenditure to total annual income (30% vs. 10.0%, P < 0.01) , hospitalization rate (26.4% vs. 13.2%, P < 0.01) , annual sick leave or absence duration (20.0 days vs. 5.5 days, P < 0.01) , unemployment rate (47.9% vs. 19.5%, P < 0.01) , proportion of patients with mental stress (99.0% vs. 73.2%, P < 0.01) , proportion of patients with suicide intention (46.3% vs. 14.2%, P < 0.01) and proportion of patients who had suicide behavior (6.8% vs. 1.1%, P < 0.01) . Conclusions Psoriasis imposes heavy economic and psychological burden on patients, and decreases their quality of life. Meanwhile, patients with severely or extremely severely affected quality of life have higher disease burden compared with those with mildly to moderately affected quality of life.

Objective: To explore the application value of interferon gamma release assay (IGRA) combined with tuberculin skin test (TST) in diagnosis of intraocular tuberculosis and latent tuberculosis infection. Methods: One hundred and ten patients with pulmonary tuberculosis (observation group) and 80 healthy persons (control group) in Hebei Chest Hospital from January 2016 to December 2018 were selected. Among the 110 patients with pulmonary tuberculosis, intraocular tuberculosis was in 35 cases, and latent tuberculosis infection was in 75 cases. All the patients were examined by ocular secretions IGRA and TST. Results: The positive rates of IGRA and TST in observation group were significantly higher than those in control group: 88.18% (97/110) vs. 11.25% (9/80) and 83.64% (92/110) vs. 41.25% (33/80), and there were statistical differences (χ² = 113.138 and 36.971, P<0.01). The positive rate of IGRA in patients with intraocular tuberculosis was significantly higher than that in latent tuberculosis infection: 97.14% (34/35) vs. 84.00% (63/75), and there was statistical difference (χ² = 3.955, P<0.05). There was no statistical difference in the positive rate of TST between the patients with intraocular tuberculosis and patients with latent tuberculosis infection: 91.43% (32/35) vs. 80.00% (60/75), χ² = 2.277, P>0.05. The consistency rate of IGRA and TST was 89.90% (Kappa = 0.867, P>0.05). The sensitivity of IGRA combined with TST was significantly higher than the single detection of IGRA and TST (97.83% vs. 88.18% and 83.64%), while the specificity of IGRA combined with TST was significantly lower than the single detection of IGRA and TST (61.11% vs. 92.31% and 83.33%), and there were statistical differences (P<0.05). The receiver operating characteristic curve analysis result showed that the area under curve of IGRA in diagnosis of intraocular tuberculosis and latent tuberculosis infection was 0.781, area under curve of TST was 0.604, and area under curve of IGRA combined with TST was 0.679. Conclusions IGRA has high value in the diagnosis of intraocular tuberculosis and latent tuberculosis infection, and can be used as a diagnostic means of intraocular tuberculosis.

To provide reference for further improve the level of medical devices clinical trial, to ensure the medical devices quality combing with the problems found in the medical devices clinical trial in Shandong province, the problems and countermeasures of medical devices (II) clinical trial were explored. Four countermeasures were put forward to solve the problems of medical devices (II) clinical trial from different angles including sponsors, clinical trials institutions and the important part of clinical trials: raising the threshold of entry, consummating relevant laws and regulations,establishing quality management system, strengthening personnel training, attaching great importance to CRA and CRC.

Aspergillus niger, as an important industrial fermentation strain, is widely applied in the production of organic acids and industrial enzymes. With the development of diverse omics technologies, the data of genome, transcriptome, proteome and metabolome of A. niger are increasing continuously, which declared the coming era of big data for the research in fermentation process of A. niger. The data analysis from single omics and the comparison of multi-omics, to the integrations of multi-omics based on the genome-scale metabolic network model largely extends the intensive and systematic understanding of the efficient production mechanism of A. niger. It also provides possibilities for the reasonable global optimization of strain performance by genetic modification and process regulation. We reviewed and summarized progress in omics research of A. niger, and proposed the development direction of omics research on this cell factory.
Aspergillus niger ; genetics ; Fermentation ; Genome, Fungal ; Metabolic Networks and Pathways ; Metabolome ; Proteome ; Transcriptome

Objective To report a pedigree with X?linked dominant protoporphyria(XLDPP), and to detect 5?aminolevulinic acid synthetase 2(ALAS2)gene mutations in this pedigree. Methods A clinical investigation was performed in a pedigree with XLDPP, and relevant data were collected from family members. A next?generation sequencing method was applied to screen possible mutation sites, and Sanger sequencing was performed to determine pathogenic gene mutations. Dermoscopy was conducted to observe skin lesions in the patients with XLDPP, and the Fotofinder system and very high frequency (VHF) ultrasound system were utilized to assess the severity of photodamage. Liver and gallbladder ultrasonography as well as blood examination were performed for all the family members. Results A deletion mutation, c.1706?1709ΔAGTG, was detected in the ALAS2 gene on the X chromosomes of all the patients in this family, which led to replacement or loss of 19-20 C?terminal residues through transcriptional frameshifting, and eventually caused an increase in ALAS2 activity. In the patients with XLDPP, skin photodamage was relatively severe;protoporphyrin?induced hepatobiliary damage was observed and aggravated with age;anemia and iron deficiency occurred sometimes. Conclusion The deletion mutation c.1706?1709ΔAGTG of the ALAS2 gene may be the underlying cause of XLDPP in this pedigree.

Carbon-limited continuous culture was used to study the relationship between the growth of Aspergillus niger and the production of glucoamylase. The result showed that when the specific growth rate was lower than 0.068 h(-1), the production of glucoamylase was growth-associated, when the specific growth rate was higher than 0.068 h(-1), the production of glucoamylase was not growth-associated. Based on the result of continuous culture, the Monod dynamics model of glucose consumption of A. niger was constructed, Combining Herbert-Pirt equation of glucose and oxygen consumption with Luedeking-Piret equation of enzyme production, the black-box model of Aspergillus niger for enzyme production was established. The exponential fed-batch culture was designed to control the specific growth rate at 0.05 h(-1) by using this model and the highest yield for glucoamylase production by A. niger reached 0.127 g glucoamylase/g glucose. The black-box model constructed in this study successfully described the glucoamylase production by A. niger and the result of the model fitted the measured value well. The black-box model could guide the design and optimization of glucoamylase production by A. niger.
Aspergillus niger ; metabolism ; Batch Cell Culture Techniques ; Carbon ; Culture Media ; Glucan 1,4-alpha-Glucosidase ; biosynthesis ; Glucose ; Industrial Microbiology ; methods ; Oxygen

Objective To investigate the relationship between serum homocysteine ( Hcy ) and cognitive impairment in patients with cerebral infarction combined chronic obstructive pulmonary disease (COPD) after stroke, and observe the plasma Hcy levels and cognitive function improvement when treated with folic acid and vitamin B12 .Methods 87 acute cerebral infarction combined with COPD patients as the research object, then the general clinical data were recorded, hematology indexes ( Hcy, folic acid, vitamin B12 ) were determined, and their cognitive function with a simple mental state scale (MMSE) was assayed.According to the plasma Hcy levels, the subjects were divided into Hcy-normal group (n =21) and Hcy-increased group (n=66), then compare the cognitive function between the two groups.Hcy-increased subjects were randomly divided into intervention group (conventional treatment +folic acid 2.5 mg +VitB12 0.5 mg) and control group (conventional treatment).After six months follow-up, we retested plasma Hcy levels and MMSE assessment, comparison of plasma Hcy concentration change and cognitive function improvement between two groups.Results Compared with Hcy-normal group, plasma folic acid, VitB12 levels significantly decreased in Hcy-increased group (P<0.05).And Hcy concentration was negatively correlated with folic acid(r=-0.351,P =0.000)and VitB12(r=-0.242,P=0.015)levels.In addition, the MMSE, directional force and delayed recall score decreased in Hcy-increased group compared with the Hcy-normal group ( P<0.05 ).Hcy levels were significantly lower than the baseline level (P<0.05), MMSE and the sub-project of cognitive function score increased after treated with folic acid and VitB12 for six months, although there was no statistically significant difference.Conclusion Plasma Hcy level is associated with cognitive impairment in patients with cerebral infarction combined chronic obstructive pulmonary disease (COPD), patients treated with folic acid and VitB12 may help slow the recent cognitive dysfunction after stroke in the near future.