Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary cornification disorder presented with abnormal skin scaling. In this paper, we used next-generation sequencing to determine the variants in a Chinese ARCI patient. We used sanger sequencing to verify bidirectionally the DNA from the proband and her parents. Results showes that two compound heterozygous variants (c.235G > T and c.641delG) in CYP4F22 gene, and both of the mutations are novel. The parents were heterozygous carriers. The two variants are classified as pathogenic variants based on interpretation guidelines. The compound heterozygous mutations in CYP4F22 gene were the causative mutations responsible for ARCI in proband.

This article teases out the main regulatory incentives for innovative drugs in China and US, including optimizing the processes, setting time limits for registration, expedited programs, R&D and evaluation communication and receiving clinical data from overseas. Meanwhile, case study method is used to analyze the impact of these regulatory incentives on BeiGene's zanubrutinib, which is the first drug from Chinese Innovation Company simultaneously developed in US and China. The results show that regulatory incentives are key factors to realize simultaneous development of zanubrutinib by shortening the time of registration in both countries and reducing the costs and risks of drug development. Other domestic companies can learn from the experience of zanubrutinib, to target unmet clinical needs, to rationally use domestic and foreign regulatory policies, and to enhance communication with regulators. Domestic regulator also can provide more suggestion to companies who have the intention to develop products abroad, so that more innovative drugs developed by local companies can be on the world stage.

Objective:To evaluate the impact of sample pooling strategy on 2019-nCoV RNA detection results.Methods:Ten negative swabs were stored in 6 ml virus transport medium, mixed thoroughly and diluted 1∶2 and 1∶10. Inactivated 2019-nCoV culture medium was added to simulate pooling samples: 10 pooling samples, 5 pooling samples and 1 swab sample. Extraction and amplification were made using three nucleic acid extraction reagents a, b, and c with different extraction methods and systems, as well as five 2019-nCoV detection reagents A-E with various template loading volumes and sensitivities respectively.Results:For the same sample, the Ct values of extracted templates a were 2.10±0.47 and 3.46±0.62 earlier than extracted templates b and c. For samples with identical amplifying, the Ct valves of N and ORF1ab gene of A reagent were 1.16±0.48 and 2.36±0.54 earlier than that of reagent B. Adding nucleic acid of 10 negative swabs to the amplification system lagged the Ct values of reagent A by about 1.36±0.32 Ct, while Ct values of reagent B were not affected. Extracted by regent a, a lag of 1.66±0.39 Ct on average was observed in C, D, and E reagents in detecting pooling samples of ten swabs as compared with one swab sample. When extracting 400 copies/ml pooling samples of ten swabs by reagent a, N gene could be detected by reagents C and E, but not by reagent D.Conclusion:Large amount of extraneous DNA is introduced by sample pooling, which could interfere the effiency of extraction and amplification. Strategies of using extraction reagents with large loading volume and high effiency, together with amplification reagents with large template volume and low limit of detection are helpful for ensuring detection sensitivity of pooling samples, and greatly reducing the risk of false negative results.

Objective To evaluate the effect and cost-benefit of influenza vaccination for patients with chronic diseases in Wujin district of Changzhou City. Methods An epidemiological quasi-experiment was employed in this study. A total of 441 patients with chronic diseases were recruited as the vaccine group and inoculated with trivalent influenza virus vaccine, while 467 patients with chronic diseases matched with the age, gender and health status of the vaccine group were selected as the control group for both baseline and follow-up investigations. Results A total of 431 subjects in the vaccine group and 460 subjects in the control group completed baseline and 1-year follow-up investigations. The incidence of influenza-like illness was 7.42% (32/431) and 14.13% (65/460) in the vaccine group and the control group, respectively, with a statistically significant difference (χ²=9.634, P=0.002). The protective rate was 47.46%, and the effect index was 1.90. The incidence of common cold was 16.94% (73/431) and 25.43% (117/460), respectively, and the difference was statistically significant (χ²=9.077, P=0.003), with a protective rate of 33.41%, and an effect index of 1.50. The incidence of chronic disease was 5.57% (24/431) and 9.35% (43/460), respectively. The difference was statistically significant (χ²=4.043, P=0.044), with a protective rate of 40.43% and an effect index of 1.68. The per capita benefit of inoculation was 675.86 yuan, and the benefit-cost ratio was 10.09:1. Conclusion Influenza vaccination for patients with chronic diseases effectively prevented the occurrence of influenza-like illness and reduced the incidence of related chronic diseases.

Objective To assess the rate achieving the target vancomycin trough level (VTL) and its influencing factors in critically ill patients.Methods The retrospective observational study recruited adult patients treated with intravenous vancomycin in the intensive care unit (ICU) at Zhongda Hospital from January 2015 to December 2017.Serum VTL was tested at steady state.Patients' demographics,the sites of infection,microbial culture results,the severity of illness,laboratory data and vancomycin regimen were obtained at the baseline.The rate achieving target VTL (15-20 mg/L) was analyzed based on renal function.Linear regression was performed to determine the influencing factors of VTL.Results A total of 85 patients were enrolled,among whom only 23.5％ (20/85) achieved the target VTL.In patients with normal renal function,the achieving rate was only 11.4％ (4/35),and 80.0％ (28/35) was lower than the target trough level multiple linear regression analysis showed that procalcitonin (PCT),estimated glomerular filtration rate (eGFR) and acute physiology and chronic health disease classification system Ⅱ (APACHE Ⅱ) score were independent factors associated with VTL.Conclusion Achieving target VTL in critically ill patients is not satisfactory.Further study to optimize the administration is needed to facilitate prompt attainment of target VTL.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Ebola virus (EBOV) harbors an RNA genome encapsidated by nucleoprotein (NP) along with other viral proteins to form a nucleocapsid complex. Previous Cryo-eletron tomography and biochemical studies have shown the helical structure of EBOV nucleocapsid at nanometer resolution and the first 450 amino-acid of NP (NPΔ451-739) alone is capable of forming a helical nucleocapsid-like complex (NLC). However, the structural basis for NP-NP interaction and the dynamic procedure of the nucleocapsid assembly is yet poorly understood. In this work, we, by using an E. coli expression system, captured a series of images of NPΔ451-739 conformers at different stages of NLC assembly by negative-stain electron microscopy, which allowed us to picture the dynamic procedure of EBOV nucleocapsid assembly. Along with further biochemical studies, we showed the assembly of NLC is salt-sensitive, and also established an indispensible role of RNA in this process. We propose the diverse modes of NLC elongation might be the key determinants shaping the plasticity of EBOV virions. Our findings provide a new model for characterizing the self-oligomerization of viral nucleoproteins and studying the dynamic assembly process of viral nucleocapsid in vitro.
Ebolavirus ; chemistry ; genetics ; metabolism ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Nucleocapsid ; chemistry ; genetics ; metabolism ; RNA, Viral ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Virus Assembly

OBJECTIVETo optimize the extraction condtions in the modification of Rhizoma Cyperi, which had been extracted by the technique of supercritical CO2 extraction.

METHODThe semi-bionic extraction (SBE) conditions were optimized through homogeneous design while the extracts (< or = 1 000), the total area of HPLC and dry extracts were adopted as markers.

RESULTThe optimized SBE extraction conditions are the following: pH in first extraction was adjusted to 2.005 3. And then pH in second and third extraction adjusted to 6.508 2 and 8.945 6, time of the whole extracted process was 3.912 7 h.

CONCLUSIONCombine the faction of production,we make sure the conclusion is pH in first extraction was 2.00, pH in second and third extraction adjusted to 6.50 and 9.00, duration of run was 2.0 h, 1.0 h and 1.0 h, respectively.

Carbon Dioxide ; chemistry ; Chromatography, Supercritical Fluid ; methods ; Cyperus ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Hydrogen-Ion Concentration ; Rhizome ; chemistry