Objective:To investigate the prenatal MRI diagnosis of fetal intracranial hemorrhage (ICH) and the pregnancy outcomes.Methods:This retrospective study included 49 cases of fetal ICH diagnosed by MRI in Obstetrics and Gynecology Hospital of Fudan University from July 2011 to November 2019. Two experts with more than five years of experience in obstetric radiology determined the location, number, area, stage and grade of the hemorrhage based on the MRI findings. Maternal age, gestational age at MRI, and the site, number, stage and grade of hemorrhage as well as other intracranial and extracranial abnormalities of the fetuses were compared between women with fetal germinal matrix-intraventricular hemorrhage (GM-IVH; GM-IVH group, n=39) and those without (non-GM-IVH group, n=10). MRI and ultrasound examination results of 37 cases who had MRI within three days after the ultrasound examination were compared. Postnatal and follow-up outcomes were summarized. Statistical analysis was performed using the independent sample t-test, Mann-Whitney U test and Chi-square test. Results:There was no significant difference in the maternal age, gestational age at MRI, or the site, number or stage of hemorrhage between the GM-IVH group and non-GM-IVH group (all P>0.05). The incidence of ventriculomegaly was higher in the GM-IVH group than that in the non-GM-IVH group [87% (34/39) vs 0/10, t=24.522, P<0.001]. There were 51% (19/37) of the lesions that were missed by ultrasound found by MRI, including GM-IVH in 17 cases, right cerebellar hemisphere hemorrhage in one case and corpus callosum hemorrhage in one case. Among the 49 cases, seven were lost to follow-up, 29 terminated the pregnancy (six in non-GM-IVH group and 23 in GM-IVH group), two experienced intrauterine fetal death in late pregnancy and 11 gave live birth. Ten live births had GM-IVH, among them a relatively good prognosis was noted in fetuses with grade Ⅰ (two cases), grade Ⅱ (four cases), and grade Ⅲ (three cases) GM-IVH, while one case with grade Ⅳ GM-IVH had mental retardation at eight years old; one non-GM-IVH infant had hearing loss at birth and a cochlear was implanted with no other anomalies reported during a three-year follow-up. Conclusions:MRI can provide a more direct view of the location and grade of fetal ICH and is more accurate than prenatal ultrasound in diagnosing fetal ICH, which is a beneficial supplement to ultrasound. The prognosis of cases with grade Ⅳ GM-IVH is not good.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

The detection and molecular characterization of circulating tumor cells(CTCs) is one of the most important tool for liquid biopsy, which has the potential to enable non-invasive diagnostic tests for personalized medicine. Commercial platforms represented by CellSearch, the first FDA approved assay, have been considered to be valid for CTCs detection. However, special equipment and consumptive materials are required in the techniques listed above. Besides, most of them can not differentiate between apoptotic and viable cells, which indicates the portion of active and functional CTCs. Therefore, how to develop novel method for CTCs enrichment with metastatic potential has great significance in clinical routine. Telomerase-specific replication-selective oncolytic viruses expressing green fluorescent protein(GFP), including herpes simplex virus and adenovirus, allow the detection for human CTCs in the peripheral blood. After 24 h of transfection with recombinant virus, the tumor cells stably express GFP, and it could be used for CTCs counting by fluorescent microscopy or flow cytometry. Moreover, downstream analysis would be achieved by combination with PCR or DNA sequencing. Recombinant virus enables early detection of metastatic tumor cells, because the fluorescent signal is amplified only in viable, infected CTCs, by viral replication. This GFP-expressing virus-based method is remarkably sensitive, simple, and feasible, and it offers a new opportunity to detect and characterize CTCs in clinical routine.