The image characteristics of spectral-domain optical coherence tomography on retinal tuft / 中华眼底病杂志

Objective:To describe the spectral-domain optical coherence tomography (SD-OCT) features of retinal tuft.Methods:A retrospective clinical study. From May 2019 to April 2020, 22 patients (22 eyes) diagnosed as retinal tuft by clinical fundus examination in Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. There were 9 eyes in 9 males and 13 eyes in 13 females. All patients underwent ultra-widefield laser scanning fundus photography and SD-OCT examination. SD-OCT was performed with a 55° wide-angle lens to observe the morphology, color, size and location of the lesions.Results:Twenty-six retinal tuft lesions were found in 22 eyes, all of which were solitary, gray, thylakoid and protrusion. SD-OCT images showed that all the lesions of retinal tuft showed a local protuberant appearance with moderate and hyperreflectivity, which was higher than the surrounding retina plane. In 22 lesions (84.62%, 22/26), there were one or more irregular hyporeflective cavities between the retinal neuroepithelial layers, and the other 4 lesions (15.38%,4/26) contained no hyporeflective cavities. In addition, 23 cases (88.46%, 23/26) with hyperreflective condensed cortical vitreous attached to the retina at the top of lesions, 8 cases (30.77%, 8/26) with retinal tear, and 6 cases (23.08%, 6/26) with shallow retinal detachment.Conclusions:In SD-OCT, the retinal tufts show moderate and strong local protrusion, which are higher than the surrounding retinal plane. In most of the lesions, there are multiple or single irregular weak reflex cavities, and there are hyperreflective condensed cortical vitreous attached to the retina at the top of lesions. Local retinal tears or shallow retinal detachment are present in some lesions.

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome / 基因组蛋白质组与生物信息学报·英文版

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Advances of long-acting recombinant protein therapeutics / 生物工程学报

Some of the recombinant protein therapeutics with short half-life requires high frequent dose or injection, which results in poor patient compliance. This challenge has prompted the development of long-acting recombinant proteins in recent years. Four strategies and methods, including chemical modification, protein engineering, fusion proteins and protein glycosylation are used to modify protein molecule and finally obtain improved pharmacokinetics (PK) properties. This article reviews the four strategies of half-life extension and presents a detailed list of long-acting therapeutics on US, EU and China markets.

Effect of adenylate cyclase antagonists andagonist in acute lung injury induced by lipopolysaccharide / 中国药理学通报

Aim To explore the effect of adenylate cyclase(AC) antagonists SQ22536 and agonist forskolin on acute lung injury induced by lipopolysaccharide.Methods ICR mice were randomly divided into normal saline control group(N group), model group(group L), dexamethasone group(group D),AC antagonists s(group SQ) and AC agonist group(group F).The ALI mouse model was induced by instilling intratracheally with LPS(2 mg·kg-1), and 6 h later, the lung tissue and alveolar lavage fluid(BALF) were harvested, pathological changes in lung were observed, white blood cell and neutrophil, albumin content in BALF and myeloperoxidase(MPO) activity of lung tissue homogenate were determined, and tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β), interleukin 6(IL-6) and cAMP content in lung homogenates were detected by ELISA.Results Compared with normal saline group, a large number of neutrophils infiltrated around the pulmonary vessel and airway 6 h after LPS intratracheal instillation in model group.White blood cells and neutrophils and protein content increased in BALF;MPO activity and cAMP levels increased in lung tissues.In the lung tissue TNF-α and IL-6, IL-1β content increased, compared with model group.Forskolin could improve the pathological changes of lung tissue, reduce the total number of leukocytes, number of neutrophils and protein content in BALF, and reduce MPO activity and TNF-α content in lung tissue, at the same time it increased the cAMP content;SQ22536 had no significant effect when compared with model group.Conclusion AC agonists have protective effects on LPS-induced acute lung injury in mice, and the mechanism may be related to elevating cAMP levels, inhibiting neutrophil adhesion and chemotaxis and reducing inflammatory factor levels.

Advances of the effects of antibody heterogeneity on the function and metabolism of monoclonal antibody drugs / 中国药科大学学报

Antibody drugs often show "heterogeneity",including the related isomers differing from one another in glycosylation,charge or molecular size.Most of these isomers come from post-translational modifications,such as aggregation,degradation,glycosylation,oxidation,deamidation or disulfide misfolding,of the recombinant protein in the "cell factories".These modifications not only influence the quality,safety and efficacy of the antibodies,but also serve as an important indication of product quality throughout the whole process of antibody production.This paper reviews the relationship between glycoslation,charge and size heterogeneities of monoclonal antibodies and drug efficacy,safety,pharmacokinetics as well as immunogenicity,contributing to a better understanding of the relationship between antibody structure and function.It will provide some support and guidance for the research and development of antibody drugs,especially biosimilars.